Infusion Pumps

Number: 0161

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

Policy

Scope of Policy

This Clinical Policy Bulletin addresses infusion pumps.

Medical Necessity

Aetna considers the following interventions medically necessary:
1. Aetna considers implanted infusion pumps medically necessary durable medical equipment (DME) when all of the following criteria are met:
  1. The drug is medically necessary for the treatment of the member (see medical necessity criteria for various types of infusion pumps below); and
  2. It is medically necessary that the drug be administered by an implanted infusion pump; and
  3. The infusion pump has been approved by the U.S. Food and Drug Administration (FDA) for infusion of the particular drug that is to be administered;
2. Intrathecal pump for baclofen (e.g. Gablofen, Lioresal) therapy
  
  An intrathecal pump for baclofen therapy is considered medically necessary for the treatment of intractable spasticity when the following criteria are met:
  1. Member has severe spasticity of cerebral or spinal origin (e.g., spinal cord disease, spinal cord injury, stiff person syndrome, stroke, traumatic brain injury (TBI), multiple sclerosis) (Note: per the U.S. Food and Drug Administration [FDA], persons with spasticity due to TBI should wait at least one year after the injury before consideration of long-term intrathecal baclofen therapy); and
  2. Member requires therapy in order to sustain upright posture, balance in locomotion, or increased function; and
  3. There is documentation that member's spasticity was unresponsive to other treatment methods (e.g., maximum doses of oral baclofen, tizanidine, and/or dantrolene); or oral therapy was contraindicated, not tolerated, or ineffective in controlling spasticity. A trial of oral baclofen is not a required prerequisite to intrathecal baclofen therapy in children ages 12 years or less due to the increased risk of adverse effects from oral baclofen in children; and
  4. There is documentation of a favorable response to the trial intrathecal dosage of the baclofen before subsequent dosages are considered medically necessary. An implanted pump for continuous fusion of baclofen is considered not medically necessary for members who do not respond to a 100 mcg intrathecal bolus;
3. Anti-spasmodic drugs
  
  Aetna considers an implantable infusion pump medically necessary when used to intrathecally administer anti-spasmodic drugs (e.g., baclofen) to treat chronic intractable spasticity in persons who have proven unresponsive to less invasive medical therapy as determined by the following criteria:
  1. Member has failed a six-week trial of non-invasive methods of spasticity control, such as oral anti-spasmodic drugs, either because these methods fail to adequately control the spasticity or produce intolerable side effects; and
  2. Member has a favorable response to a trial intrathecal dosage of the anti-spasmodic drug prior to pump implantation;
4. Drugs for the treatment of chronic intractable pain
  1. A preliminary trial of intraspinal (epidural or intrathecal) administration of opioid drugs (e.g., morphine), ziconotide (Prialt), and/or clonidine is considered medically necessary when both of the following criteria are met:
    1. The member has severe chronic intractable pain of malignant or non-malignant origin that is unresponsive to less invasive medical therapy; and
    2. The member's history must indicate that he or she has not responded adequately to non-invasive methods of pain control, such as systemic opioids (including attempts to eliminate physical and behavioral abnormalities which may cause an exaggerated reaction to pain).
    Note: A 1 to 2 day inpatient stay is considered medically necessary for a preliminary trial of intraspinal opioid drug administration.
  2. An implantable infusion pump is considered medically necessary when used to administer opioid drugs (e.g., morphine), ziconotide (Prialt), and/or clonidine intrathecally or epidurally for treatment of severe chronic intractable pain of malignant or non-malignant origin in persons who meet criteria above and where the following criteria are met:
    1. A preliminary trial of intraspinal opioid drug administration with a temporary intrathecal/epidural catheter has substantiated adequately acceptable pain relief with a 50 percent reduction in pain, the degree of side effects (including effects on the activities of daily living), and acceptance; and
    2. For nonmalignant pain only, a psychological evaluation has been obtained and indicates that the individual is a favorable candidate for permanent intrathecal pump implantation;
5. Intrahepatic chemotherapy infusion for liver metastases from colorectal cancer
  
  Implantable infusion pumps are considered medically necessary for administration of intrahepatic chemotherapy (e.g., floxuridine) to members with primary hepatocellular carcinoma and for metastatic colorectal cancer where metastases are limited to the liver;
  
  Note: An average 3 to 5 days inpatient hospitalization is considered medically necessary for intrahepatic chemotherapy. Hospital discharge is dependent on resolution of pain, nausea and vomiting which complicate the procedure.
6. Contraindications to implantable infusion pumps
  
  Implantable infusion pumps are considered not medically necessary for persons with any of the following contraindications to implantable infusion pumps:
  1. Members who have an active infection that may increase the risk of the implantable infusion pump; or
  2. Members whose body size is insufficient to support the weight and bulk of the device; or
  3. Members with known allergy or hypersensitivity to the drug being used (e.g., oral baclofen, morphine, etc.); or
  4. Members with other implanted programmable devices where the crosstalk between devices may inadvertently change the prescription;
7. External infusion pumps
  
  Aetna considers external infusion pumps medically necessary DME for administration of any of the following medications:
  1. Certain parenteral anticancer chemotherapy drugs (e.g., cladribine, fluorouracil, cytarabine, bleomycin, floxuridine, doxorubicin, vincristine, vinblastine, cisplatin, paclitaxel) if the drug is part of an evidence-based chemotherapy regimen and parenteral infusion of the drug at a strictly controlled rate is necessary to avoid systemic toxicity or adverse effects, and the drug is administered either:
    1. By continuous infusion over 8 hours; or
    2. By intermittent infusions lasting less than 8 hours that do not require the person to return to the physician's office prior to the beginning of each infusion; or
  2. Certain parenteral antifungal or antiviral drugs (e.g., acyclovir, foscarnet, amphotericin B, or ganciclovir); or
  3. Chemotherapy for primary hepatocellular carcinoma or colorectal cancer where the tumor is unresectable or the member refuses surgical excision of the tumor; or
  4. Deferoxamine for the treatment of acute iron poisoning and iron overload (only external infusion pumps); or
  5. Heparin for the treatment of thromboembolic disease and/or pulmonary embolism (only external infusion pumps used in an institutional setting are considered medically necessary for this indication); or
  6. Heparin to adequately anticoagulate women throughout pregnancy (warfarin compounds are not routinely used for this indication); or
  7. Insulin for persons with diabetes mellitus who meet the selection criteria for external insulin infusion pumps for diabetes set forth below; or
  8. Morphine or other narcotic analgesics (except meperidine) for intractable pain caused by cancer; or
  9. Parenteral epoprostenol or treprostinil for persons with pulmonary hypertension; or
  10. Parenteral inotropic therapy with dobutamine, milrinone, and/or dopamine; or
  11. Post-operative nerve blocks; or
  12. Other parenterally administered drugs where an infusion pump is necessary to safely administer the drug at home;
8. External insulin infusion pumps for diabetes
  
  Aetna considers external insulin infusion pumps medically necessary DME for the persons with diabetes who meet the criteria in section 1 or in section 2 below:
  1. The member is not currently established on therapy with an insulin pump and all of the following criteria are met:
    1. The member is managing their diabetes with multiple daily insulin injections (i.e., at least 3 injections per day), with frequent self-adjustments of the insulin dose; and
    2. The member has completed a comprehensive diabetes education program; and
    3. The member has documented frequency of glucose self-testing an average of at least 4 times per day for the past 2 months or has been using a continuous glucose monitor (CGM) for the past 2 months; and
    4. The member has experienced an elevated glycosylated hemoglobin level (e.g., HbA1c greater than 7 percent) while on multiple daily injections of insulin (i.e., at least 3 injections per day) for at least 6 monthsFootnote1* or the member has experienced any of the following while on multiple daily injections of insulin (i.e., at least 3 injections per day) for at least 3 months:
      1. History of recurrent hypoglycemia (e.g., blood glucose levels less than 70 mg/dL); or
      2. Wide fluctuations in blood glucose before mealtime (e.g., pre-prandial blood glucose levels commonly exceed 140 mg/dL); or
      3. Dawn phenomenon with fasting blood sugars frequently exceeding 200 mg/dL; or
      4. History of severe glycemic excursions; or
      Footnote1* It may be considered medically necessary to initiate the use of insulin infusion pumps during pregnancy earlier than the criteria stated above to avoid fetal and maternal complications of diabetes and pregnancy. It may be considered medically necessary for poorly controlled women with diabetes to sometimes get started on the pump pre-pregnancy or in the first trimester.
  2. The member is currently established on therapy with an insulin pump and has documented frequency of glucose self-testing an average of at least 4 times per day, or the member is using a continuous glucose monitor (CGM);
    
    Notes on External Insulin Infusion Pumps:
    1. Aetna considers a disposable external insulin infusion pump (e.g., Omnipod DASH, Omnipod 5, or V-Go disposable insulin delivery device) an acceptable alternative to a standard insulin infusion pump for members who meet medical necessity criteria for external insulin infusion pumps. Omnipod GO is a basal-only insulin device (provides a fixed rate of continuous rapid-acting insulin for 72 hours) which will be considered medically necessary for member who has type 2 diabetes, does not require bolus or mealtime insulin, has a hypersensitivity to an ingredient in all available basal insulin (e.g., long-acting insulin, intermediate-acting insulin), has completed a comprehensive diabetes education program, and has documented frequency of glucose self-testing at least once daily or has been using a continuous glucose monitor (CGM).
    2. Aetna's medical necessity criteria for external infusion pumps for diabetes have been adapted, in part, from Medicare national policy on external insulin infusion pumps, as outlined in CMS's Coverage Issues Manual Section 60-14.
    3. Documentation of continued medical necessity of the external insulin infusion pump requires that the member be seen and evaluated by the treating physician at least once every 6 months.
    4. External subcutaneous insulin infusion pumps are only considered medically necessary for persons who have demonstrated ability and commitment to comply with a regimen of pump care, frequent self-monitoring of blood glucose, and careful attention to diet and exercise.
    5. Some external insulin infusion pumps (e.g., Paradigm Real-Time Insulin Pump and Continuous Glucose Monitoring System, Animas OneTouch PING, Animas VIBE) are able to take results of the blood glucose reading, calculate the appropriate insulin infusion rate, wirelessly transmit the results from the blood glucose monitor to the pump, and automatically adjust the insulin infusion rate, saving the member some extra steps. These insulin pump features, when present, are considered integral to the external insulin infusion pump and blood glucose monitor.
    6. The pump must be ordered by and follow-up care of the member must be managed by a physician with experience managing persons with insulin infusion pumps and who works closely with a team including nurses, diabetic educators, and dieticians who are knowledgeable in the use of insulin infusion pumps.
    See also CPB 0070 - Diabetes Tests, Programs and Supplies.
9. Supplies and drugs used with implantable or external infusion pumps
  
  Aetna considers supplies that are needed for the effective use of the DME medically necessary. Such supplies include those drugs and biologicals that must be put directly into the equipment in order to achieve the therapeutic benefit of the DME or to assure the proper functioning of the equipment;
10. Replacement pumps
  1. Replacement of an external insulin pump is considered medically necessary for children who require a larger insulin reservoir;
  2. The replacement of infusion pumps that are out of warranty, are malfunctioning, and cannot be refurbished is considered medically necessary;
  3. The replacement of Personal Diabetes Monitors (PDMs) for Omnipod Systems that are out of warranty, are malfunctioning, and cannot be refurbished is considered medically necessary;
  4. Replacement of a functioning insulin pump with an insulin pump with wireless communication to a glucose monitor is considered not medically necessary as such wireless communication has not been shown to improve clinical outcomes.
11. Artificial pancreas devices / Automated insulin delivery system
  1. Open-loop system (fully user controlled)
    
    An FDA-approved continuous glucose monitor (CGM) and insulin pump with a low glucose suspend feature where system needs input from the user (e.g., Medtronic MiniMed 530G, MiniMed 630G) is considered as an equally acceptable alternative to a standard insulin pump and CGM for members who meet medical necessity criteria for external insulin infusion pumps for diabetes;
  2. Closed-loop system (mostly hands-off; automated)
    
    An FDA-approved continuous glucose monitor (CGM) and insulin pump with closed loop system (programmed to automatically adjust delivery of basal insulin based on CGM sensor glucose values) (e.g. Beta Bionics iLet Bionic Pancreas) is considered as an equally acceptable alternative to a standard insulin pump and CGM for members who meet medical necessity criteria for external insulin infusion pumps for diabetes;
  3. Hybrid closed-loop system (semiautomated, requires some user input)
    
    An FDA-approved continuous glucose monitor (CGM) and insulin pump hybrid closed-loop system (e.g., Insulet's Omnipod 5; Metronic's MiniMed 670G, 770G, 780G; Tandem's t:slim X2 insulin pump with Basal-IQ Technology, Tandem Mobi) is considered as an equally acceptable alternative to a standard insulin pump and CGM for members who meet medical necessity criteria for external insulin infusion pumps for diabetes.
  For diabetes tests (including glucose monitoring devices), programs, and supplies, see CPB 0070 - Diabetes Tests, Programs and Supplies.
  
  For Trina Health artificial pancreas treatment, see CPB 0742 - Intermittent Intravenous Insulin Therapy.
Experimental, Investigational, or Unproven

The following interventions are considered experimental, investigational, or unproven because the effectiveness of these approaches has not been established:
1. Intrathecal baclofen:
  1. As a treatment for cancer-related pain, hydrocephalus, neuromyotonia (Isaac's syndrome), and rheumatoid arthritis;
  2. When combined with other agents (clonidine, hydromorphone, morphine, and ziconotide), because the safety of these combinations has not been established;
2. Implantable infusion pumps for intrathecal or epidural infusion of opioids, ziconotide, and clonidine as a treatment for gastroparesis and for all other indications because their effectiveness for indications other than the one listed above has not been established. Note: Currently, morphine and ziconotide are the only FDA-approved analgesics for long-term intrathecal infusion;
3. "One-shot" arterial chemotherapy for persons with liver metastases from colorectal cancer;
4. Implanted infusion pumps for all other indications, including any of the following:
  1. Implantable infusion pumps for intrahepatic administration of chemotherapy for indications other than noted above, including treatment of hepatic metastases from cancers other than colorectal cancer; or
  2. Implantable pumps for the infusion of heparin for recurrent thromboembolic disease; or
  3. Implantable pumps for the infusion of insulin to treat diabetes; or
  4. Implantable pumps for the infusion of baclofen for chronic neuropathic pain (e.g., complex regional pain syndrome/reflex sympathetic dystrophy).>
  See also CPB 0607 - Anesthetic and Antiemetic Infusion Pumps.
5. External infusion pumps for all other indications (e.g., subacromial pain pump for pain management following shoulder surgery). See also CPB 0468 - Magnesium Sulfate Injections and Terbutaline Pump for Preterm Labor;
6. External infusion pumps for diabetes where the above-listed criteria are not met.
Related Policies

Table:
CPT Codes / HCPCS Codes / ICD-10 Codes
Code	Code Description
*Implantable Infusion Pumps*:
CPT codes covered if selection criteria are met:
36563	Insertion of tunneled centrally inserted central venous access device with subcutaneous pump
36576	Repair of central venous access device, with subcutaneous port or pump, central or peripheral insertion site
36578	Replacement, catheter only, of central venous access device, with subcutaneous port or pump, central or peripheral insertion site
36583	Replacement, complete, of a tunneled centrally inserted central venous access device, with subcutaneous pump, through same venous access
36590	Removal of tunneled central venous access device, with subcutaneous port or pump, central or peripheral insertion
62350 - 62351	Implantation, revision or repositioning of tunneled intrathecal or epidural catheter, for long-term medication administration via an external pump or implantable reservoir/infusion pump
62355	Removal of previously implanted intrathecal or epidural catheter
62360 - 62362	Implantation or replacement of device for intrathecal or epidural drug infusion
62365	Removal of subcutaneous reservoir or pump, previously implanted for intrathecal or epidural infusion
62367 - 62370	Electronic analysis of programmable, implanted pump for intrathecal or epidural drug infusion (includes evaluation of reservoir status, alarm status, drug prescription status)
95990 - 95991	Refilling and maintenance of implantable pump or reservoir for drug delivery, spinal (intrathecal, epidural) or brain (intraventricular)
96365 - 96368	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug)
96374 - 96376	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); intravenous push
96409 - 96411	Chemotherapy administration, intravenous push technique
96413 - 96417	Chemotherapy administration, intravenous infusion technique
96422 - 96425	Chemotherapy administration, intra-arterial, infusion technique
96522	Refilling and maintenance of implantable pump or reservoir for drug delivery, systemic (e.g., intravenous, intra-arterial)
96523	Irrigation of implanted venous access device for drug delivery systems
99601 - 99602	Home infusion/specialty drug administration
HCPCS codes covered if selection criteria are met:
A4220	Refill kit for implantable infusion pump
A4221	Supplies for maintenance of drug infusion catheter, per week (list drug separately)
A4223	Infusion supplies not used with external infusion pump, per cassette or bag (list drugs separately)
A4224	Supplies for maintenance of insulin infusion catheter, per week
A4225	Supplies for external insulin infusion pump, syringe type cartridge, sterile, each
A4300	Implantable access catheter, (e.g., venous, arterial, epidural subarachnoid, or peritoneal, etc) external access
A4301	Implantable access total catheter, port/reservoir (e.g., venous, arterial, epidural, subarachnoid, peritoneal, etc.)
A4305	Disposable drug delivery system, flow rate of 50 ml or greater per hour [not covered for intralesional administration of narcotic analgesics and anesthetics]
A4306	Disposable drug delivery system, flow rate of less than 50 ml per hour [not covered for intralesional administration of narcotic analgesics and anesthetics]
C1772	Infusion pump, programmable (implantable)
C1891	Infusion pump, nonprogrammable, permanent (implantable)
C2626	Infusion pump, nonprogrammable, temporary (implantable)
C8957	Intravenous infusion for therapy/diagnosis; initiation of prolonged infusion (more than 8 hours), requiring use of portable or implantable pump
E0782	Infusion pump, implantable, nonprogrammable (includes all components, e.g., pump, catheter, connectors, etc.)
E0783	Infusion pump system, implantable, programmable (includes all components, e.g., pump, catheter, connectors, etc.)
E0785	Implantable intraspinal (epidural/intrathecal) catheter used with implantable infusion pump, replacement
E0786	Implantable programmable infusion pump, replacement (excludes implantable intraspinal catheter)
J0475	Injection baclofen, 10 mg
J0476	Injection, baclofen, 50 mcg for intrathecal trial
J0735	Injection, clonidine HCl, 1 mg
J1643	Injection, heparin sodium (pfizer), not therapeutically equivalent to J1644, per 1000 units
J2270	Injection, morphine sulfate, up to 10 mg
J2272	Injection, morphine sulfate (fresenius kabi) not therapeutically equivalent to J2270, up to 10 mg
J2278	Injection, ziconotide, 1 microgram
J9000 - J9999	Chemotherapy drugs
Q0081	Infusion therapy, using other than chemotherapeutic drugs, per visit
Q0084	Chemotherapy administration by infusion technique only, per visit
S0093	Injection, morphine sulphate, 500 mg (loading dose for infusion pump)
S5035	Home infusion therapy, routine service of infusion device (e.g., pump maintenance)
S5036	Home infusion therapy, repair of infusion device (e.g., pump repair)
S5497	Home infusion therapy, catheter care/maintenance, not otherwise classified; includes administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S5502	Home infusion therapy, catheter care/maintenance, implanted access device, includes administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment, (drugs and nursing visits coded separately), per diem (use this code for interim maintenance of vascular access not currently in use)
S5517	Home infusion therapy, all supplies necessary for restoration of catheter patency or declotting
S5518	Home infusion therapy, all supplies necessary for catheter repair
S9325	Home infusion therapy, pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem (do not use this code with S9326, S9327 or S9328)
S9326	Home infusion therapy, continuous (24 hours or more) pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9327	Home infusion therapy, intermittent (less than 24 hours) pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9328	Home infusion therapy, implanted pump pain management infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9329	Home infusion therapy, chemotherapy infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem (do not use this code with S9330 or S9331)
S9330	Home infusion therapy, continuous (24 hours or more) chemotherapy infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9331	Home infusion therapy, intermittent (less than 24 hours) chemotherapy infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9363	Home infusion therapy, antispasmodic therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
HCPCS codes not covered for indications listed in the CPB:
J1811	Insulin (fiasp) for administration through dme (i.e., insulin pump) per 50 units
J1813	Insulin (lyumjev) for administration through dme (i.e., insulin pump) per 50 units
J1817	Insulin for administration through DME (i.e., insulin pump) per 50 units
S9336	Home infusion therapy, continuous anticoagulant infusion therapy (e.g., Heparin), administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9353	Home infusion therapy, continuous insulin infusion therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
ICD-10 codes covered if selection criteria are met (not all inclusive):
C18.0 - C21.8	Malignant neoplasm of colon, rectosigmoid junction, rectum, anus and anal canal
C22.0	Liver cell carcinoma
C78.7	Secondary malignant neoplasm of liver and intrahepatic bile duct
G25.82	Stiff-man syndrome
G35	Multiple sclerosis
G80.0 - G80.9	Cerebral palsy
G81.10 - G81.14	Spastic hemiplegia
G82.20 - G82.22	Paraplegia
G82.50 - G82.54	Quadriplegia
G89.0	Central pain syndrome
G89.21 - G89.29	Chronic pain, not elsewhere classified
G89.4	Chronic pain syndrome
G95.11 - G95.19	Vascular myelopathies
I69.831 - I69.898	Monoplegia, hemiplegia and hemiparesis and other paralytic syndrome following other cerebrovascular disease
M62.40 - M62.49 M62.830 - M62.838	Spasm of muscle
R25.0 - R25.9	Abnormal involuntary movements
R26.0 - R26.1, R26.81 - R26.9	Abnormalities of gait and mobility
S06.0X0A - S06.A1XS	Intracranial injury [traumatic brain injury]
S12.000+ - S12.001+ S12.100+ - S12.101+ S12.200+ - S12.201+ S12.300+ - S12.301+ S12.400+ - S12.401+ S12.500+ - S12.501+ S12.600+ - S12.601+ S14.101+ - S14.107+ S14.111+ - S14.117+ S14.121+ - S14.127+ S14.131+ - S14.137+ S14.151+ - S14.157+	Fracture of vertebral column with spinal cord injury
S14.101+ - S14.139+ S14.151+ - S14.159+	Injury of nerves and spinal cord at neck level
ICD-10 codes not covered for indications listed in the CPB:
A00.0 - A32.9 A35 - A48.0 A48.2 - B99.9 D86.0 - D86.9 J02.0 J03.00 - J03.01 K90.81, L08.1, L44.4 L94.6 M02.30 - M02.39 M35.2 M60.000 - M60.09 N34.1	Certain infectious and parasitic diseases
E08.00 - E13.9	Diabetes mellitus
G89.3	Neoplasm related pain (acute) (chronic)
G91.0 - G91.9	Hydrocephalus
I26.90 - I26.99	Pulmonary embolism without acute acute cor pulmonale
I74.01 - I75.89	Arterial embolism and thrombosis and atheroembolism
I80.00 - I82.91	Phlebitis and thrombophlebitis, portal vein thrombosis and other venous embolism and thrombosis
K31.84	Gastroparesis
M05.00 - M14.89	Inflammatory polyarthropathies
M54.10 - M54.18	Radiculopathy
M79.2	Neuralgia and neuritis, unspecified
O24.011 - O24.93	Diabetes mellitus complicating pregnancy, childbirth, and the puerperium [range includes gestational diabetes]
O35.0xx0 - O35.3xx9	Maternal care for (suspected) central nervous system malformation in fetus [hydrocephalus]
O99.810 - O99.815	Abnormal glucose complicating pregnancy, childbirth and the puerperium
Q03.0 - Q03.9	Congenital hydrocephalus
Q05.0 - Q05.4	Spina bifida with hydrocephalus
R63.6	Underweight
Z79.4	Long-term (current) use of insulin
Z86.711 - Z86.718	Personal history of venous thrombosis and embolism
Z86.72	Personal history of thrombophlebitis
Z88.5	Allergy status to narcotic agent status
Z88.6	Allergy status to analgesic agent status
Z95.0 Z95.810 Z95.818 Z95.9	Presence of cardiac device
Z96.41	Presence of insulin pump (external) (internal)
*External Infusion Pumps*:
CPT codes covered if selection criteria are met:
64400 - 64530	Introduction/injection of anesthetic agent (nerve block), diagnostic or therapeutic
96365 - 96368	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug)
96374 - 96376	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); intravenous push
96409 - 96411	Chemotherapy administration, intravenous push technique
96413 - 96417	Chemotherapy administration, intravenous infusion technique
96422 - 96425	Chemotherapy administration; intra-arterial, infusion technique
96521	Refilling and maintenance of portable pump
99601 - 99602	Home infusion/specialty drug administration
Other CPT codes related to the CPB:
23000 – 23921	Surgery / Musculoskeletal System Shoulder [subacromial pain pump not covered following shoulder surgery]
95249	Ambulatory continuous glucose monitoring of interstitial tissue fluid via a subcutaneous sensor for a minimum of 72 hours; patient-provided equipment, sensor placement, hook-up, calibration of monitor, patient training, and printout of recording
95250	Ambulatory continuous glucose monitoring of interstitial tissue fluid via a subcutaneous sensor for a minimum of 72 hours; physician or other qualified health care professional (office) provided equipment, sensor placement, hook-up, calibration of monitor, patient training, removal of sensor, and printout of recording
95251	Ambulatory continuous glucose monitoring of interstitial tissue fluid via a subcutaneous sensor for a minimum of 72 hours; analysis, interpretation and report
HCPCS codes covered if selection criteria are met:
A4221	Supplies for maintenance of drug infusion catheter, per week (list drugs separately)
A4222	Infusion supplies for external drug infusion pump, per cassette or bag (list drugs separately)
A4226	Supplies for maintenance of insulin infusion pump with dosage rate adjustment using therapeutic continuous glucose sensing, per week
A4230	Infusion set for external insulin pump, non needle cannula type
A4231	Infusion set for external insulin pump, needle type
A4232	Syringe with needle for external insulin pump, sterile, 3cc
A4300	Implantable access catheter, (e.g., venous, arterial, epidural subarachnoid, or peritoneal, etc) external access
A4301	Implantable access total catheter, port/reservoir (e.g., venous, arterial, epidural, subarachnoid, peritoneal, etc.)
A4305	Disposable drug delivery system, flow rate of 50 ml or greater per hour [not covered for intralesional administration of narcotic analgesics and anesthetics]
A4306	Disposable drug delivery system, flow rate of less than 50 ml per hour [not covered for intralesional administration of narcotic analgesics and anesthetics]
A4602	Replacement battery for external infusion pump owned by patient, lithium, 1.5 volt, each
A9274	External ambulatory insulin delivery system, disposable, each, includes all supplies and accessories
C8957	Intravenous infusion for therapy/diagnosis; initiation of prolonged infusion (more than 8 hours), requiring use of portable or implantable pump
E0607	Home blood glucose monitor
E0779	Ambulatory infusion pump, mechanical, reusable, for infusion 8 hours or greater
E0780	Ambulatory infusion pump, mechanical, reusable, for infusion less than 8 hours
E0781	Ambulatory infusion pump, single or multiple channels, electric or battery operated, with administrative equipment, worn by patient
E0784	External ambulatory infusion pump, insulin
E0787	External ambulatory infusion pump, insulin, dosage rate adjustment using therapeutic continuous glucose sensing
E1520	Heparin infusion pump for hemodialysis
G0068	Professional services for the administration of anti-infective, pain management, chelation, pulmonary hypertension, and/or inotropic infusion drug(s) for each infusion drug administration calendar day in the individual's home, each 15 minutes
G0070	Professional services for the administration of intravenous chemotherapy or other intravenous highly complex drug or biological infusion for each infusion drug administration calendar day in the individual's home, each 15 minutes
G0090	Professional services, initial visit, for the administration of intravenous chemotherapy or other highly complex infusion drug or biological for each infusion drug administration calendar day in the individual's home, each 15 minutes
J0475	Injection baclofen, 10 mg
J0476	Injection baclofen, 50 mcg for intrathecal trial
J0895	Injection, defoxamine mesylate [Desferal], 500 mg
J1250	Injection, Dobutamine HCL, per 250 mg
J1644	Injection, Heparin sodium, per 1,000 units
J1811	Insulin (fiasp) for administration through dme (i.e., insulin pump) per 50 units
J1812	Insulin (fiasp), per 5 units
J1813	Insulin (lyumjev) for administration through dme (i.e., insulin pump) per 50 units
J1814	Insulin (lyumjev), per 5 units
J1815	Injection insulin, per 5 units
J1817	Insulin for administration through DME (i.e., insulin pump) per 50 units
J2260	Injection, milrinone lactate, 5 mg
J9000 - J9999	Chemotherapy drugs
K0601 - K0605	Replacement battery for external infusion pump owned by patient
Q0081	Infusion therapy, using other than chemotherapeutic drugs, per visit
Q0084	Chemotherapy administration by infusion technique only, per visit
S1034	Artificial pancreas device system (e.g., low glucose suspend (lgs) feature) including continuous glucose monitor, blood glucose device, insulin pump and computer algorithm that communicates with all of the devices
S1035	Sensor; invasive (e.g., subcutaneous), disposable, for use with artificial pancreas device system
S1036	Sensor; invasive (e.g., subcutaneous), disposable, for use with artificial pancreas device system
S1037	Receiver (Monitor); External, For Use With Artificial Pancreas Device System
S9140	Diabetic management program, follow-up visit to non-MD provider
S9141	Diabetic management program, follow-up visit to MD provider
S9145	Insulin pump initiation, instruction in initial use of pump (pump not included)
S9336	Home infusion therapy, continuous anticoagulant infusion therapy (e.g., Heparin), administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9345	Home infusion therapy, anti-hemophilic agent infusion therapy (e.g., factor VIII); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits codes separately), per diem
S9346	Home infusion therapy, alpha-1-proteinase inhibitor (e.g., Prolastin); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9347	Home infusion therapy, uninterrupted, long-term, controlled rate intravenous or subcutaneous infusion therapy (e.g., epoprostenol); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9348	Home infusion therapy, sympathomimetic/inotropic agent infusion therapy (e.g., Dobutamine); administrative services, professional pharmacy services, care coordination, all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9353	Home infusion therapy, continuous insulin infusion therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9355	Home infusion therapy, chelation therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9357	Home infusion therapy, enzyme replacement intravenous therapy; (e.g., Imiglucerase); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9359	Home infusion therapy, antitumor necrosis factor intravenous therapy; (e.g., Infliximab); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9363	Home infusion therapy, anti-spasmodic therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9373	Home infusion therapy, hydration therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem (do not use with hydration therapy codes S9374-S9377 using daily volume scales)
S9374	Home infusion therapy, hydration therapy; 1 liter per day, administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9375	Home infusion therapy, hydration therapy; more than 1 liter but no more than 2 liters per day, administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9376	Home infusion therapy, hydration therapy; more than 2 liters but no more than 3 liters per day, administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9377	Home infusion therapy, hydration therapy; more than 3 liters per day, administrative services, professional pharmacy services, care coordination, and all necessary supplies (drugs and nursing visits coded separately), per diem
S9455	Diabetic management program, group session
S9460	Diabetic management program, nurse visit
S9490	Home infusion therapy, corticosteroid infusion; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9494	Home infusion therapy, antibiotic, antiviral, or antifungal therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately, per diem) (do not use with home infusion codes for hourly dosing schedules S9497 - S9504)
S9497	Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 3 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9500	Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 24 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9501	Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 12 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9502	Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 8 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9503	Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 6 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
S9504	Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 4 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
HCPCS codes not covered for indications listed in the CPB:
Disposable insulin delivery systems [e.g., V-G™] - no specific code:
J0735	Injection, clonidine hydrochloride, 1 mg [not covered in combination with baclofen]
J1171	Injection, hydromorphone, 0.1 mg
J2270	Injection, morphine sulfate, up to 10 mg [not covered in combination with baclofen]
J2272	Injection, morphine sulfate (fresenius kabi) not therapeutically equivalent to J2270, up to 10 mg
J2278	Injection, ziconotide, 1 microgram [not covered in combination with baclofen]
Other HCPCS codes related to the CPB:
A4238	Supply allowance for adjunctive, non-implanted continuous glucose monitor (cgm), includes all supplies and accessories, 1 month supply = 1 unit of service
A4239	Supply allowance for non-adjunctive, non-implanted continuous glucose monitor (cgm), includes all supplies and accessories, 1 month supply = 1 unit of service
A9276	Sensor; invasive (e.g., subcutaneous), disposable, for use with non-durable medical equipment interstitial continuous glucose monitoring system, one unit = 1 day supply
A9277	Transmitter; external, for use with non-durable medical equipment interstitial continuous glucose monitoring system
A9278	Receiver (monitor); external, for use with non-durable medical equipment interstitial continuous glucose monitoring system
E2102	Adjunctive, non-implanted continuous glucose monitor or receiver
E2103	Non-adjunctive, non-implanted continuous glucose monitor or receiver
J1642	Injection, heparin sodium, (heparin lock flush), per 10 units
ICD-10 codes covered if selection criteria are met (not all-inclusive):
A00.0 - A32.9 A35 - A48.0 A48.2 - B99.9 D86.0 - D86.9 J02.0 J03.00 - J03.01 K90.81, L08.1, L44.4 L94.6 M02.30 - M02.39 M35.2 M60.000 - M60.09 N34.1	Certain infectious and parasitic diseases
C18.0 - C21.8	Malignant neoplasm of colon, rectosigmoid junction, rectum, anus and anal canal
C22.0 - C22.9	Malignant neoplasm of liver and intrahepatic bile ducts
E08.00 - E13.9	Diabetes mellitus
E83.10 - E83.19	Disorders of iron metabolism
G89.3	Neoplasm related pain (acute) (chronic)
I26.90 - I26.99	Pulmonary embolism without acute acute cor pulmonale
I27.0	Primary pulmonary hypertension
I27.20 - I27.29	Other secondary pulmonary hypertension
I74.01 - I75.89	Arterial embolism and thrombosis and atheroembolism
I80.00 - I82.91	Phlebitis and thrombophlebitis, portal vein thrombosis and other venous embolism and thrombosis
O22.00 - O22.93 O87.0 - O87.9	Venous complications in pregnancy and the puerperium
O24.011 - O24.93	Diabetes mellitus complicating pregnancy, childbirth, and the puerperium [range includes gestational diabetes]
O88.011 - O88.83	Obstetric embolism
O99.810 - O99.815	Abnormal glucose complicating pregnancy, childbirth and the puerperium
T45.4X1+ - T45.4X4+	Poisoning by iron and its compounds
Z79.4	Long-term (current) use of insulin

Background

Implantable infusion pumps are subcutaneously inserted devices that deliver drugs through central venous, intra-arterial, intrathecal or intraperitoneal catheters. Implantable infusion pumps allow drug delivery directly to specific sites and can be programmed for continuous or variable rates of infusion. Examples of implantable infusion pumps include Codman 3000, InfusAid Pump. MedStream Programmable Infusion System, Prometra Programmable Infusion Pump System, SynchroMed Infusion System, and SynchroMed II.

Baclofen (Lioresal) is a derivative of gamma aminobutyric acid (GABA) that acts specifically at the spinal end of the upper motor neurons to cause muscle relaxation. Intrathecal baclofen may be indicated for patients with severe chronic spasticity of spinal cord origin. An implantable infusion pump is required for the administration of intrathecal baclofen. Intrathecal baclofen therapy is indicated for persons with severe chronic spasticity of spinal cord origin (including multiple sclerosis) that is refractory to oral baclofen or where there are unacceptable side effects from oral baclofen at the effective dose. The patient should be shown to respond to a single intrathecal bolus dose of up to 100 mcgs of baclofen. A positive response is defined as an average two-point drop on an objective muscle tone or spasm screening system (e.g., The Ashworth and Spasm scale). According to available guidelines, intrathecal baclofen therapy is not considered appropriate if the patient has a history of hypersensitivity to Lioresal, is pregnant or has inadequate birth control, has severely impaired renal function, has severe hepatic or gastrointestinal disease, or has cerebral lesions as the source of spasticity.

Brennan and Whittle (2008) stated that continuous infusion of intrathecal baclofen (ITB) via a subcutaneously implanted pump has developed over the past 2 decades as a powerful tool in the management of spasticity in various adult and pediatric neurological conditions. Acting more focally on spinal GABA receptors, ITB causes fewer systemic side effects than orally administered baclofen. The result is facilitation of daily caring, and symptomatic relief from painful spasm. With increasing experience of ITB use, novel applications and indications are emerging. These include the management of dystonia and chronic neuropathic pain. However, despite some recent authoritative reviews, there is still uncertainty about optimal use and evaluation of this therapy.

Shilt et al (2008) stated that ITB is an effective treatment of spasticity in patients with cerebral palsy (CP). However, several recent reports have raised concerns that the treatment may be associated with a rapid progression of scoliosis. The objective of this study was to further examine the effect of ITB treatment on the progression of scoliosis in patients with CP. Spastic CP patients who were ITB candidates were followed radiographically. Baseline Cobb angles of the primary curve were measured during the period of ITB pump insertion and at the most recent follow-up visit. Each patient was matched with a control patient by the diagnosis of CP, age, sex, topographical involvement, and initial Cobb angle. The mean rate of change in Cobb angle was compared between ITB and control patients using paired-t test. A multiple linear regression model was used to examine the difference, controlling for age, sex, topographical involvement, and initial Cobb angle. A total of 50 ITB patients and 50 controls were included in the analysis. There was no statistically significant difference between the mean change in Cobb angle in ITB patients (6.6 degrees per year) compared with the matched control patients (5.0 degrees per year, p = 0.39). The results from the multiple regression analysis also failed to show a statistically significant difference (0.92 degrees per year difference between ITB patients and controls, p = 0.56). The authors concluded that the progression of scoliosis in CP patients with ITB treatment is not significantly different from those without ITB treatment. The findings suggest that patients receiving ITB experience a natural progression of scoliosis similar to the natural history reported in the literature.

The discovery of spinal opiate receptors, and that the binding of morphine at relatively low concentrations to these receptors produced effective analgesia have led to the development of intraspinal analgesia for the management of pain. This mode of opioid administration has become an attractive alternative for cancer patients whose pain is not relieved by conventional drugs and/or routes; and for others who cannot tolerate the side effects of systemic administration of opioids in the dose needed for adequate analgesia as the disease progresses. A popular procedure for intraspinal administration of opioids analgesics is the implantation of an infusion pump which allows the direct delivery of opioids to the receptors in the spinal cord continuously and/or in an intermittent manner.

Available evidence indicates that chronic intrathecal opioids administration via implantable pumps can provide satisfactory pain relief for patients who suffer from intractable cancer pain. In addition, it allows the patients to be less dependent on hospital services, thus improving the quality of their lives. Studies have also shown that the same method of treatment was successful in providing quality analgesia to carefully selected patients who experienced chronic pain from nononcologic origins, although reductions in pain and improvements in function is observed less consistently in noncancer pain. Some investigators have reported untoward side effects of intrathecal opioid administration, including development of a fibrous mass around the tip of the catheter, resulting in compression of the intrathecal space with displacement of the spinal cord.

To be considered for spinal analgesia, a patient must have a normal platelet count and no coagulation disorder, infection, or other problems that might preclude the use of spinal drugs. Before the implantation of a permanent infusion system, an efficacy test is usually performed to assess the patient's response and dose. One or several trial doses of 5 to 10 mg of epidural morphine, or 0.5 to 1.0 mg intrathecal morphine is/are administered while all other analgesic medications are stopped. Subjective pain ratings and undesirable side effects are evaluated for several days. A decision to implant the pump is made only if pain is markedly reduced and other opioid analgesics are not needed by the patient.

University of California-San Francisco’s webpage on “Intrathecal Drug Delivery” (2015) states that “Before a permanent pain pump is implanted, most patients have a trial procedure to determine if they are a good candidate for a permanent pump. This usually involves using a needle to place a temporary spinal catheter, followed by an inpatient stay of several days while pain medication is infused through it. In other cases, a single or series of pain medication injections around the spine are given on an outpatient basis”.

TouchStone Interventional Pain Center states that “Although pump placement is an inpatient procedure, most patients spend only 1 night in the hospital for observation”.

Furthermore, Wilkes (2014) stated that “The Polyanalgesic Consensus Conference (PACC) guidelines strongly recommend at least 24-hour inpatient observation for trialing”.

Insulin Pumps

Insulin pumps are devices used to deliver insulin in a programmed and controlled manner to diabetic individuals. These devices work with a separate glucometer through manual or remote functions. The goals of insulin pump therapy are to achieve near-normal control of blood glucose levels. Insulin pumps are categorized as follows:

External insulin pumps deliver insulin via subcutaneous or intraperitoneal routes. External insulin pumps may be either disposable or have disposable components. The following are examples of U.S/.. Food and Drug Administration (FDA) cleared external insulin pumps:
- ACCU-CHEK Spirit Insulin Pump: Non disposable insulin pump with programmable reminders for basal and bolus delivery of insulin. Bluetooth capable for 2-way wireless communication with meter to deliver insulin and adjust pump settings remotely.
- OmniPod System is a disposable insulin pump that consolidates the pump, tubing and subcutaneous needle into one compact unit. The unit is worn up to three days before requiring replacement.
- One-Touch Ping is a non-disposable insulin pump with programmable basal and bolus insulin delivery that uses a meter with remote capability.
- t:slim and t:flex Insulin Delivery System is a battery operated infusion pump capable of both basal and bolus delivery of insulin. It utilizes a motor-driven mechanism to deliver insulin from a disposable cartridge. Unlike other pumps which deliver the insulin by applying pressure from behind the full contents of the syringe/reservoir, this pump withdraws small amounts of insulin from its reservoir and transfers it into the micro-delivery chamber before being delivered into the subcutaneous tissue at the correct increment and rate.
- V-Go Disposable Insulin Delivery Device is a fully disposable, non-electronic device for the delivery of basal-bolus insulin therapy for adults with diabetes. It provides a continuous preset basal rate of insulin and allows for on-demand bolus dosing around mealtimes. It is a delivery option for diabetics and is applied to the skin daily for one 24-hour period.
Implantable insulin pumps deliver insulin via intraperitoneal or intravenous routes. Currently there are not any devices that have received FDA approval for use outside of a clinical trial.

Aetna's medical necessity criteria for external infusion pumps for diabetes have been adapted from Medicare national policy on external insulin infusion pumps, as outlined in CMS's Coverage Issues Manual Section 60-14.

There are some limited evidence that external insulin infusion pumps improve glycemic control over multiple daily injections in persons with type 2 diabetes (Hammond, 2004; Pickup & Renard, 2008; Fatourechi, et al., 2009), although not all studies have been consistent (see, e.g., Raskin, et al., 2003; Herman, et al., 2005; Berthe, et al., 2007; Parkner, et al., 2008).

Fatourechi et al (2009) reported on a meta-analysis of randomized controlled clinical trials of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) in persons with diabetes. The investigators identified 15 eligible randomized trials of moderate quality, with elevated baseline and end-of-study hemoglobin A1c (HbA1c) levels. The investigators reported that patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects weighted mean difference, -0.2 %; 95 % confidence interval (CI): -0.3 to -0.1, compared with MDI], with no significant difference in severe (pooled odds ratio, 0.48; 95 % CI: 0.23 to 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95 % CI: 0.33 to 2.03). Adolescents and adults with type 1 diabetes enrolled in cross-over trials had no-nsignificantly fewer minor hypoglycemia episodes per patient per week (-0.08; 95 % CI: -0.21 to 0.06) with CSII than MDI; children enrolled in parallel trials had significantly more episodes (0.68; 95 % CI: 0.16 to 1.20; p (interaction) = 0.03). The investigators reported that outcomes were not different in patients with type 2 diabetes. The investigators concluded that "[c]ontemporary evidence indicates that compared to MDI, CSII slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on hypoglycemia. In type 2 diabetes, CSII and MDI had similar outcomes. The effect in patients with hypoglycemia unawareness or recurrent severe hypoglycemia remains unclear because of lack of data."

Guidelines from the American Association of Clinical Endocrinologists (Robard, et al., 2007) provide a grade C recommendation for patients with type 2 diabetes, "[c]onsider use of continuous subcutaneous insulin infusion in insulin-treated patients." Guidelines from the National Institute for Health and Clinical Excellence (2008) do not recommend use of CSII in persons with type 2 diabetes.

An American Association of Clinical Endocrinologists (2010) consensus statement on insulin pumps in diabetes included a recommendation for use of insulin pumps in persons with type 2 diabetes. The consensus stated that the ideal continuous subcutaneous insulin infusion (CSII) candidate would be a patient with type 1 diabetes mellitus or absolutely insulin-deficient type 2 diabetes mellitus who currently performs 4 or more insulin injections and 4 or more self-monitored blood glucose measurements daily, is motivated to achieve tighter blood glucose control, and is willing and intellectually and physically able to undergo the rigors of insulin pump therapy initiation and maintenance. The consensus statement also included a recommendation for use of insulin infusion pumps in selected patients with insulin-requiring type 2 diabetes mellitus who satisfy any or all of the following:

C-peptide positive but with suboptimal control on a maximal program of basal/bolus injections;
substantial “dawn phenomenon”;
erratic lifestyle (eg, frequent long distance travel, shift-work, unpredictable schedules leading to difficulty maintaining timing of meals); and
severe insulin resistance, candidate for U500 insulin by continuous subcutaneous insulin infusion (CSII).

The consensus statement said that current literature on insulin pump use has focused primarily on the benefits of CSII in patients with type 1 diabetes mellitus, with some attention to the role of CSII in patients with severely insulin-deficient type 2 diabetes mellitus. The consensus statement indicated that "few clinical investigations have examined CSII use in patients with type 2 DM." The consensus statement noted that one analysis of 4 randomized controlled trials in patients with type 2 diabetes mellitus (citing Monami, et al.) found no significant HbA1c improvements and no significant differences in hypoglycemic risk with CSII versus multiple daily injection therapy over 12 weeks. The consensus statement noted, however, that there was a nonsignificant trend toward decreased insulin requirements was observed among CSII patients. The statement also cited other recent meta-analysis of insulin pump therapy in type 2 diabetes, one by Jeitler, et al. (2008) which they interpreted as finding "no conclusive CSII benefits for patients with type 2 DM", and a meta-analysis by Fatourechi, et al. (2009), which they interpreted as finding "CSII and MDI outcomes were similar among patients with type 2 DM." The consensus statement also referenced a nested case-control study of the use of insulin infusion pumps versus non-pump therapy in pregnant women with type 2 diabetes or gestational diabetes (Simmons, et al., 2001).

A systematic evidence review by Mukhopadhyay et al (2007) found no advantage of using continuous subcutaneous insulin infusion (CSII) over multiple daily injections in pregnant women with diabetes. The investigators identified randomized controlled clinical trials of the effects of CSII versus multiple daily insulin injections on glycemic control and pregnancy outcome in women with diabetes. Studies were rated for quality independently by 2 reviewers. Summary weighted mean differences and odds ratios were estimated for insulin dose, birthweight, gestational age, mode of delivery, hypoglycemic/ketotic episodes, worsening retinopathy, neonatal hypoglycemia, and rates of intrauterine fetal death. Six randomized clinical trials met the inclusion criteria. The investigators found that pregnancy outcomes and glycemic control were not significantly different among treatment groups. The investigators found higher numbers of ketoacidotic episodes and diabetic retinopathy in the CSII group, but these differences did not reach statistical significance. The investigators found that this systematic review did not find any advantage or disadvantage of using CSII over multiple daily injections in pregnant diabetic women.

Cummins et al (2010) examined the clinical effectiveness and cost-effectiveness of using CSII to treat diabetes. These investigators updated the previous assessment report by reviewing evidence that has emerged since the last appraisal, and took account of developments in alternative therapies, in particular the long-acting analog insulins, which cause fewer problems with hypoglycaemia. The primary focus for type 1 diabetes mellitus (T1DM) was the comparison of CSII with MDI, based on the newer insulin analogs, but trials of neutral protamine Hagedorn (NPH)-based MDI that had been published since the last assessment were identified and described in brief. For type 2 diabetes mellitus (T2DM), all trials of MDI versus CSII were included, whether the long-acting insulin was analog or not, because there was no evidence that analog-based MDI was better than NPH-based MDI. Trials that were shorter than 12 weeks were excluded. Information on the patients' perspectives was obtained from 4 sources:

the submission from the pump users group -- Insulin Pump Therapy (INPUT);
interviews with parents of young children who were members of INPUT;
some recent studies; and
from a summary of findings from the previous assessment report.

Economic modeling used the Center for Outcomes Research (CORE) model, through an arrangement with the NICE and the pump manufacturers, whose submission also used the CORE model. The 74 studies used for analysis included 8 randomized controlled trials (RCTs) of CSII versus analog-based MDI in either T1DM or T2DM, 8 new (since the last NICE appraisal) RCTs of CSII versus NPH-based MDI in T1DM, 48 observational studies of CSII, 6 studies of CSII in pregnancy, and 4 systematic reviews. The following benefits of CSII were highlighted: better control of blood glucose levels, as reflected by HbA1c levels, with the size of improvement depending on the level before starting CSII; reduction in swings in blood glucose levels, and in problems due to the dawn phenomenon; fewer problems with hypoglycemic episodes; reduction in insulin dose per day, thereby partly off-setting the cost of CSII; improved quality of life, including a reduction in the chronic fear of severe hypoglycemia; more flexibility of lifestyle -- no need to eat at fixed intervals, more freedom of lifestyle and easier participation in social and physical activity; and benefits for the patients' family. The submission from INPUT emphasised the quality of life gains from CSII, as well as improved control and fewer hypoglycemic episodes. Also, there was a marked discrepancy between the improvement in social quality of life reported by successful pump users, and the lack of convincing health-related quality of life gains reported in the trials. With regard to economic evaluation, the main cost of CSII is for consumables, such as tubing and cannulae, and is about 1800 to 2000 pounds per year. The cost of the pump, assuming 4-year life, adds another 430 to 720 pounds per year. The extra cost compared with analog-based MDI averages 1700 pounds. Most studies, assuming a reduction in HbA1c level of 1.2 %, found CSII to be cost-effective. The authors concluded that based on the totality of evidence, using observational studies to supplement the limited data from RCTs against best MDI, CSII provides some advantages over MDI in T1DM for both children and adults. However, there was no evidence that CSII is better than analog-based MDI in T2DM or in pregnancy. They stated that further trials with larger numbers and longer durations comparing CSII and optimized MDI in adults, adolescents and children are needed. In addition, there should be a trial of CSII versus MDI with similar provision of structured education in both arms. A trial is also needed for pregnant women with pre-existing diabetes, to investigate using CSII to the best effect.

Zu et al (2011) described the preparation and characterization of chitosan (CS)-polyvinyl alcohol (PVA) blend hydrogels for the controlled release of nano-insulin; CS- PVA blend hydrogels were prepared using glutaraldehyde as the cross-linking agent. The obtained hydrogels, which have the advantages of both PVA and CS, can be used as a material for the transdermal drug delivery (TDD) of insulin. The nano-insulin-loaded hydrogels were prepared under the following conditions: 1.2g of polyethylene glycol, 1.5 g of CS, 1.2 g of PVA, 1.2 ml of 1 % glutaraldehyde solution, 16 ml of water, and 40 mg of nano-insulin with 12 mins of mixing time and 3 mins of cross-linking time. The nano-insulin-loaded hydrogels were characterized using scanning electron microscopy, energy dispersive spectrometry, Fourier-transform infrared spectroscopy, differential scanning calorimetry, thermo-gravimetric analysis, X-ray diffraction, and its mechanical properties were analyzed. The results showed that all molecules in the hydrogel have good compatibility and they formed a honeycomb-like structure. The hydrogel also showed good mechanical and thermal properties. The in-vitro drug release of the hydrogel showed that the nano-insulin accorded with Fick's first law of diffusion and it has a high permeation rate (4.421 μg/(cm(2)hr)). The authors concluded that these results suggested that the nano-insulin-loaded hydrogels are a promising non-invasive TDD system for diabetes chemotherapy.

Ito et al (2012) developed a dissolving microneedle (DM) application system, where 225 to 300 insulin-loaded DMs were formed on a chip. After the heat-sealed sheet is removed, the system covered with the press-through package layer is put on the skin. By pressing with the hand, insulin DMs were inserted into the skin. Factors affecting the penetration depth of DM were studied using applicator in-vitro and in-vivo experiments. The penetration depth was determined for rat and human skin. Two-layered DM array chips were prepared to obtain complete absorption of insulin and administered to the rat abdominal skin. Plasma glucose levels were measured for 6 hrs. By comparing the hypoglycemic effect with that obtained after subcutaneous injection, relative pharmacological availability was determined. The penetration depth increased from 21 +/- 3 μm to 63 +/- 2 μm in proportion to application speed to isolated rat skin, at 0.8 to 2.2 m/s. Human skin showed similar results in the penetration depth. The in-vivo penetration depth was dependent on the force (0.5 to 2.5 N) and duration (1 to 10 mins), as the secondary application force. The penetration depth was 211 +/- 3 μm with 3-min duration in the in-vivo rat experiment. Dissolving microneedle array chips having an insulin-loaded space of 181.2 +/- 4.2 and 209 +/- 3.9 μm were evaluated in the rat. Relative pharmacological availability values of insulin from DMs were 98.1 +/- 0.8 % and 98.1 +/- 3.1 %, respectively. The authors concluded that these findings suggested the usefulness of the 2-layered DM application system for the transdermal delivery of insulin.

Jahn et al (2013) noted that as all major insulin pump manufacturers comply with the international infusion pump standard EN 60601-2-24:1998, there may be a general assumption that all pumps are equal in insulin-delivery accuracy. These researchers investigated single-dose and averaged-dose accuracy of incremental basal deliveries for 1 patch model and 3 durable models of insulin pumps. For each pump model, discrete single doses delivered during 0.5 U/hr basal rate infusion over a 20-hr period were measured using a time-stamped micro-gravimetric system. Dose accuracy was analyzed by comparing single doses and time-averaged doses to specific accuracy thresholds (± 5 % to ± 30 %). The percentage of single doses delivered outside accuracy thresholds of ± 5 %, ± 10 %, and ± 20 % were as follows: Animas OneTouch® Ping® (43.2 %, 14.3 %, and 1.8 %, respectively), Roche Accu-Chek® Combo (50.6 %, 24.4 %, and 5.5 %), Medtronic Paradigm® Revel™/Veo™ (54.2 %, 26.7 %, and 6.6 %), and Insulet OmniPod® (79.1 %, 60.5 %, and 34.9 %). For 30 mins, 1 hr, and 2 hrs averaging windows, the percentage of doses delivered outside a ± 15 % accuracy were as follows: OneTouch Ping (1.0 %, 0.4 %, and 0 %, respectively), Accu-Chek Combo (4.2 %, 3.5 %, and 3.1 %), Paradigm Revel/Veo (3.9 %, 3.1 %, and 2.2 %), and OmniPod (33.9 %, 19.9 %, and 10.3 %). The authors concluded that this technical evaluation demonstrated significant differences in single-dose and averaged-dose accuracy among the insulin pumps tested. Differences in dose accuracy were most evident between the patch pump model and the group of durable pump models. Of the pumps studied, the Animas OneTouch Ping demonstrated the best single-dose and averaged-dose accuracy.

Omnipod GO Insulin Delivery Device

In March 2023, the FDA cleared for marketing the Omnipod GO Insulin Delivery Device (Insulet Corporation), a basal-only insulin pod for use in adults with type 2 diabetes. The Omnipod GO is a tubeless, wearable subcutaneous infusion device intended to provide a fixed rate of continuous rapid-acting insulin in one 24-hour time period for 3 days (72 hours). Typically, patients initiating insulin for type 2 diabetes start with a "basal" insulin, taking intermediate-acting or long-acting forms of insulin, which is usually administered once daily. The Omnipod GO device was developed to serve this patient population by alleviating the need for daily injections. However, the Omnipod GO does not offer the ability to deliver a bolus. Thus, if a patient requires both basal and bolus dosing, then the patient would need to transition to another insulin delivery device. In addition, the Omnipod GO does not check blood glucose levels. The Omnipod GO is contraindicated for persons who are unable to monitor glucose as recommended by their healthcare provider. The Omnipod GO is programmed with seven different daily rates, ranging from 10 to 40 units per day. Each strength is available as a kit with 5 pods per kit. Omnipod GO should be changed once every 3 days. The Omnipod GO Pod is compatible with the following U-100 insulins: NovoLog®, Fiasp®, Humalog®, Admelog®, and Lyumjev®. The device is expected to be commercially available in the United States in 2024.

V-Go Disposable Insulin Delivery Device

A non-programmable insulin delivery system using a transdermal microneedle has been advocated as a needle-free alternative to subcutaneous injection conventionally used to treat type 2 diabetes (Johns et al, 2014; Rosenfeld et al, 2012; Kapitza et al, 2008). The V-Go is a newly developed insulin delivery system. The push of a button inserts a needle into the patient once daily and remains attached for 24 hours. The V-Go is designed to release a set basal rate throughout the day, while allowing patients to provide up to 36 units of on-demand bolus insulin with the manual click of 2 buttons. It is a spring-loaded device filled daily with rapid-acting insulin that runs without the use of batteries or computer software. However, the effectiveness of a non-programmable transdermal microneedle insulin delivery in the management of diabetic patients has not been established.

Winter et al (2015) reported on a prospective active comparator study to observe the A1C lowering effects of multiple daily insulin injections (MDII) versus the use of the V-Go insulin delivery system for patients with uncontrolled type 2 diabetes mellitus over a 3-month period. The investigators also assessed the effect on insulin requirement for these patients with secondary comparisons of weight, blood pressure, prevalence of hypoglycemic events, and quality of life before and after 3 months of intensified insulin therapy with regular monitoring by a clinical pharmacist at an internal medicine clinic. The average A1C lowering experienced by the 3 patients in the V-Go group was 1.5 %, while the average A1C change in the 3 patients in the MDII group was an increase of 0.2 %. All patients in the V-Go group experienced a decrease in insulin total daily dose (TDD), with an average decrease of 26.3 units. All patients in the MDII group experienced an increase in insulin TDD with an average of 15 units daily to achieve therapeutic goals individualized for each patient. All patients who underwent intensification of insulin therapy experienced an increase in subjective quality of life (QOL) as determined using the Diabetes-39 (D-39) questionnaire, though QOL results lacked statistical significance. Limitations of this study include its observational nature, small size, and limited duration of followup.

Kapitza et al (2008) reported on a proof-of-concept study to evaluate the clinical functionality, safety, and pharmacodynamics of the V-Go delivering insulin aspart and redistributing a single basal dose of insulin glargine as a constant basal infusion supplemented with prandial insulin in subjects with type 2 diabetes mellitus. In 6 subjects receiving once-daily subcutaneous (SC) injections of insulin glargine (> or = 15 U/day) with or without concomitant oral antidiabetic drugs, glargine was discontinued following a 3-day baseline phase. The V-Go was then applied to the lower abdomen of the subjects once daily for 7 days (days 1 to 3 inpatient, days 4 to 7 outpatient). Each V-Go provided a continuous 24-hour preset basal infusion rate of insulin aspart (0.6 U/h) and up to 3 daily prandial doses at mealtimes. Capillary blood glucose concentrations were measured at 11 time points per day during the baseline and inpatient phases and at 4 time points per day during the outpatient phase. Additionally, glucose profiles were measured continuously on all days. The V-Go was well tolerated and operated as anticipated. The mean +/- SEM prestudy daily dose of SC insulin glargine was 33.3 +/- 13.8 U; the mean daily total insulin aspart dose infused with the V-Go was 31.5 +/- 7.5 and 32.3 +/- 7.8 U for the inpatient and outpatient periods, respectively. Fasting blood glucose values were similar to those observed at baseline throughout the study, with nonsignificant (NS) reductions in readings collected during the outpatient phase before lunch (-35 +/- 27 mg/dl) and before dinner (-38 +/- 25 mg/dl). The 2-hour post-prandial glucose trended lower from 231 to 195 mg/dl (NS) at breakfast, 234 to 166 mg/dl (NS) at lunch, and 222 to 171 mg/dl (NS) at dinner. Bedtime blood glucose decreased (mean change from baseline -52 +/- 21 mg/dl; p = 0.0313), as did nighttime (3:00 AM) measurements (-20 +/- 9 mg/dl; P = 0.0313). Overall glycemic control tended to improve, as shown by continuous glucose monitoring changing from 173 to 157 mg/dl (p = 0.063, NS) and 156 mg/dl (p = 0.219) during inpatient and outpatient periods, respectively. Glycemic variability assessed by the M value similarly tended to decrease from 33 +/- 9 to 25 +/- 4 (NS) and 21 +/- 4 (NS) for inpatient and outpatient periods, respectively. The authors concluded that these first data suggested that use of the V-Go is an attractive alternative to SC insulin injection therapy because metabolic control appears to be maintained or even improved without increasing daily insulin doses.

Rosenfeld et al (2012) described patient perceptions regarding their experience and reported findings in a retrospective analysis of glycemic control in a cohort of patients who used the V-Go, a mechanical, 24-hr disposable, subcutaneous continuous insulin delivery device that delivers a preset basal infusion rate and on-demand insulin. Patients used the V-Go and answered telephone surveys about their perception of device use. Corresponding clinical data were retrospectively collected before V-Go initiation, after 12 weeks of use, at the end of treatment, and 12 weeks after discontinuation. Analyses were performed with non-parametric statistical tests. A total of 23 patients participated in this study. Mean values of the following characteristics were documented: patient age, 61 years; body mass index, 30 kg/m2; diabetes duration, 16 years; duration of insulin therapy, 7 years; average duration of V-Go use, 194 days; and mean total daily insulin dose, 50 U at baseline, 46 U while on V-Go, and 51 U after stopping V-Go treatment. Mean patient rating of the overall experience was 9.1 at 12 weeks on a scale from 1 to 10 (10 being most positive). Mean hemoglobin A1c value decreased from baseline (8.8 % to 7.6 %; [p = 0.005]) while using the V-Go, and it increased to 8.2 % after treatment. Fasting plasma glucose trended from 205 mg/dL at baseline to 135 mg/dL while using V-Go and increased to 164 mg/dL after V-Go was stopped. Weight was essentially unchanged. No differences in hypoglycemic events were found; site reactions were minor. The authors concluded that glycemic control improved when patients were switched to the V-Go for insulin delivery, and it deteriorated when the V-Go was discontinued. The main drawbacks of this study were its retrospective nature, small sample size, and short-term follow-up. These preliminary findings need to be validated by well-designed studies.

Much of the other data on V-Go are in abstract form. Furthermore, current guidelines from the American Diabetes Association and the American College of Clinical Endocrinology do not mention the use of a non-programmable disposable insulin delivery systems.

Lajara et al (2016) compared 2 methods of delivering intensified insulin therapy (IIT) in patients with type 2 diabetes inadequately controlled on basal insulin ± concomitant anti-hyperglycemic agents in a real-world clinical setting. Data for this retrospective study were obtained using electronic medical records from a large multi-center diabetes system. Records were queried to identify patients transitioned to V-Go disposable insulin delivery device (V-Go) or MDI using an insulin pen to add prandial insulin when A1C was greater than 7 % on basal insulin therapy. The primary end-point was the difference in A1C change using follow-up A1C results. A total of 116 patients were evaluated (56 V-Go, 60 MDI). Both groups experienced significant glycemic improvement from similar mean baselines. By 27 weeks, A1C least squares mean change from baseline was -1.98 % (-21.6 mmol/mol) with V-Go and -1.34 % (-14.6 mmol/mol) with MDI, for a treatment difference of -0.64 % (-7.0 mmol/mol; p = 0.020). Patients using V-Go administered less mean ± SD insulin compared to patients using MDI, 56 ± 17 units/day versus 78 ± 40 units/day (p < 0.001), respectively. Diabetes-related direct pharmacy costs were lower with V-Go, and the cost inferential from baseline per 1 % reduction in A1C was significantly less with V-Go ($118.84 ± $158.55 per patient/month compared to $217.16 ± $251.66 per patient/month with MDI; p = 0.013). The authors concluded that progression to IIT resulted in significant glycemic improvement. Insulin delivery with V-Go was associated with a greater reduction in A1C, required less insulin, and proved more cost-effective than administering IIT with MDI.

The main drawbacks of this study included:

findings were based on retrospective data, and although careful review was performed to identify patients, a selection bias was possible concerning which intensified insulin regimen was prescribed,
better outcomes in patients prescribed V-Go may be due to a higher level of motivation to control diabetes, as demonstrated by their willingness to try a new method of insulin delivery. For all patients, diabetes management was provided with no expected frequency of patient contact or mandatory titration, which when enforced may impact A1C reductions. Prescribed insulin dosing and bolus frequency were based on information obtained from medical records; actual insulin dosing and frequency may have differed across both delivery methods,
patients using MDI were prescribed fewer boluses per day compared to patients using V-Go. Although the ratio of basal to bolus insulin was similar between groups and patients in the MDI group were prescribed significantly more insulin, the difference in bolus frequency may have impacted glycemic control for the MDI group,
insulin adjustments based on meal content and daily glucose profiles were not analyzed due to incomplete data, which limits the ability to fully evaluate daily glycemic control and insulin coverage between groups, and
the reporting of hypoglycemic events was based primarily on patient-reported events documented in progress notes and therefore may not accurately depict the risk or severity of hypoglycemia associated with either delivery method.

Artificial Pancreas Devices / Automated Insulin Delivery System / Bionic Endocrine Pancreas

Standard insulin pumps have a fixed rate of insulin delivery and do not communicate with a continuous glucose monitor (CGM) for insulin adjustments based on a persons blood glucose levels. The insulin pump and CGM have demonstrated to be beneficial as standalone devices; however, newer technology allows for connecting the the two devices in an integrated system.

The artificial pancreas device is a system of devices that closely mimics the glucose regulating function of a healthy pancreas. These systems include a CGM, insulin infusion pump, and computer-controlled algorithm that facilitates continuous communication between the CGM and insulin pump. Sometimes artificial pancreas device systems are referred to as a "closed-loop" system, an "automated insulin delivery" system, or an "autonomous system for glycemic control". The system monitors glucose levels in the body and automatically adjusts the delivery of insulin to reduce hyperglycemia and minimize the incidence of hypoglycemia with little or no input from the patient (FDA, 2018).

In other words, an automated insulin delivery (AID) system integrates data from a CGM system, a control algorithm, and an insulin pump to automate subcutaneous insulin delivery. The CGM communicates with the insulin pump, and the pump adjusts insulin delivery based on the information it receives. Over the years, this technology has been referred to as an "artificial pancreas" or "bionic pump". All describe the same fundamental approach; however, the term “AID” is becoming standard language and is now used by regulatory agencies like the U.S. Food and Drug Administration (FDA) (Sherr et al, 2023).

There are three types of AID systems, open-loop, closed-loop, and hybrid.

An open-loop insulin delivery system (e.g., Medtronic's MiniMed 530G, 630G with low glucose suspend feature) includes a CGM (via a subcutaneous sensor) and a wearable insulin infusion pump; however, the system does not use an algorithm to automate the insulin response to a changing glucose level. Thus, requires full user input.
A closed-loop system also includes use of a CGM with an insulin pump; however, it incorporates an algorithm-based software to automatically adjust insulin delivery based on person's glucose level. The iLet Bionic Pancreas from Beta Bionics was FDA-approved in 2023 as the first closed-loop system (for ages 6 and older) that determines 100% of all insulin doses. This closed-loop system automatically delivers insulin which is calibrated by a person's body weight, requiring no manual input or adjustments to the doses. When it comes to mealtimes, iLET uses a 'meal announcement' feature, with no need for precise carb counting. However, the user will need to remain carb aware (Beta Bionics, 2023; Doskica, 2024; FDA, 2023).
A hybrid closed-loop system also includes use of a CGM, algorithm-based software, and an insulin pump; however, individuals still need to count carbs and provide the system with bolus information when they eat, as well as input adjustments for exercise. The CGM picks up on the glucose changes ( via the subcutaneous sensor) and communicates the information with the insulin pump. It does this 24 hours a day. There are several FDA-approved hybrid closed-loop AID systems available in the U.S. (e.g., Insulet's Omnipod 5, Medtronic's MiniMed 670G, 770G, 780G; Tandem's t:slim X2 insulin pump with control-IQ technology).

Artificial Pancreas Device Systems with a Low Glucose Suspend Feature

Threshold suspend is the first step towards an artificial pancreas device system (APDS). This technology integrates CGMs with an insulin pump which allows the user to set a low blood sugar threshold value. When the CGM sensor detects the preset low glucose threshold, insulin delivery is suspended.

The MiniMed 530G System is intended for continuous delivery of basal insulin (at user selectable rates) and administration of insulin boluses (in user selectable amounts) for the management of diabetes mellitus in persons, sixteen years of age and older, requiring insulin as well as for the continuous monitoring and trending of glucose levels in the fluid under the skin. This device automatically stops insulin delivery (for up to two hours) when sensor glucose values reach a preset level and when the individual does not respond to the threshold suspend alarm.

MiniMed Connect (compatible with MiniMed 530G with Enlite and MiniMed Paradigm Revel insulin pump) is an optional wireless device used to access continuous glucose monitor sensor data. Information can be viewed using an internet application through a smart device or via a browser accessible website and can be shared as needed.

A Blue Cross Blue Shield TEC Assessment was published in May 2014 which evaluated the use of artificial pancreas device systems that included a low glucose suspend feature. The low glucose suspend feature uses a combination of an insulin pump, an continuous glucose monitor, a transmitter, and a computer algorithm to connect the insulin pump and continuous glucose monitor (e.g. the Medtronic MiniMed 530G System). In contrast to a continuous glucose monitor, a low glucose suspend feature does not require verification of the interstitial glucose level (e.g. by fingerstick), but rather sounds an alarm when the continuous glucose monitor registers that glucose level has fallen to a predetermined level. If the alarm is not turned off, the device will suspend insulin delivery for up to 2 hours. The TEC Assessment based findings primarily on the in-home-arm of the ASPIRE trial, as they concluded that there is a dearth of comparative studies with a sample size of 15 or more subjects. The TEC Assessment concluded that further research is needed beyond the single ASPIRE study that met their criteria for inclusion in their assessment. Therefore, they concluded that the evidence is insufficient to permit conclusion on the impact of the artificial pancreas device system with low glucose suspend feature on health outcomes.

Bergenstal et al (2013) noted that the threshold-suspend feature of sensor-augmented insulin pumps is designed to minimize the risk of hypoglycemia by interrupting insulin delivery at a preset sensor glucose value. Therefore, the authors conducted a study in patients with nocturnal hypoglycemia to evaluate the efficacy and safety of sensor-augmented insulin-pump therapy with and without the threshold-suspend feature. Patients with type 1 diabetes and documented nocturnal hypoglycemia were randomly assigned to receive sensor-augmented insulin-pump therapy with or without the threshold-suspend feature for 3 months. Of a total of 247 patients, 127 patients were randomly assigned to receive sensor-augmented insulin-pump therapy with the threshold-suspend and 126 patients served as controls, receiving standard sensor-augmented insulin-pump therapy. The changes in glycated hemoglobin values were similar in the two groups with a mean AUC for nocturnal hypoglycemic events that was 37.5% lower in the threshold-suspend group than in the control group (980 ± 1200 mg per deciliter [54.4 ± 66.6 mmol per liter] × minutes vs. 1568 ± 1995 mg per deciliter [87.0 ± 110.7 mmol per liter] × minutes, P<0.001). Thus, hypoglycemic events occurred 31.8% less frequently in the threshold-suspend group than in the control group (1.5 ± 1.0 vs. 2.2 ± 1.3 per patient-week, P<0.001). During the study 1438 instances at night in which the pump was stopped for 2 hours were noted and the mean sensor glucose value was 92.6 ± 40.7 mg per deciliter (5.1 ± 2.3 mmol per liter). Four control patients had a severe hypoglycemic event and no patients in either study group had diabetic ketoacidosis. The authors concluded that over a 3-month period the use of sensor-augmented insulin-pump therapy with the threshold-suspend feature reduced nocturnal hypoglycemia without increasing glycated hemoglobin values.

Additional studies supporting the conclusions drawn by Bergenstal et al (2013) are needed to support an evidence base for use of the artificial pancreas device system with a low-glucose suspense feature. It should be noted that Medtronic, Inc. received Premarket Approval for the MiniMed 530G System, which is a threshold suspend artificial pancreas device system, on September 26, 2013 (FDA, 2013).

In September 2013, the FDA granted premarket approval (PMA) to Medtronic's MiniMed 530G System. The MiniMed 530G is intended for continuous delivery of basal insulin (at user selectable rates) and administration of insulin boluses (in user selectable amounts) for the management of diabetes mellitus in persons, 16 years of age and older, requiring insulin as well as for the continuous monitoring and trending of glucose levels in the fluid under the skin. The MiniMed 530G System can be programmed to automatically suspend delivery of insulin when the sensor glucose value falls below a predefined threshold value.

Closed-Loop Systems (Including Hybrid)

Closed-loop glucose systems includes the use of a continuous glucose monitor (CGM), via a subcutaneous sensor, and an insulin pump that uses software-based algorithm to automatically deliver insulin dosages. A closed-loop system is considered a mostly automated (hands off) system (e.g.,Beta Bionics iLet Bionic Pancreas); or semiautomated automated (hybrid) -- requiring user to input adjustments for meals or exercise.

Closed-loop hybrid systems are characterized by automated algorithm-based insulin delivery and patient-initiated insulin delivery (e.g., post-meal boluses). There are several systems using hybrid closed loop technology currently offered in the U.S. (e.g., Insulet's Omnipod 5, Medtronic's MiniMed 670G, 770G, 780G; Tandem's t:slim X2 insulin pump with control-IQ technology).

The Medtronic MiniMed 770G System was the 1st FDA-approved hybrid closed loop system that monitors glucose and automatically adjusts the delivery of long acting or basal insulin based on the user’s glucose reading in users 2 years and up. An earlier version of this device (MiniMed 670G System, without the Bluetooth capability) was approved only for users aged 7 years and up.

Brown et al (2019) noted that closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with T1DM. In a 6-month randomized, multi-center study, patients with T1DM were assigned in a 2:1 ratio to receive treatment with a closed-loop system (closed-loop group) or a sensor-augmented pump (control group). The primary outcome was the percentage of time that the blood glucose level was within the target range of 70 to 180 mg/dL (3.9 to 10.0 mmol/L), as measured by continuous glucose monitoring (CGM). A total of 168 patients underwent randomization; 112 were assigned to the closed-loop group, and 56 were assigned to the control group. The age range of the patients was 14 to 71 years, and the HbA1c level ranged from 5.4 % to 10.6 %. All 168 patients completed the trial. The mean (± SD) percentage of time that the glucose level was within the target range increased in the closed-loop group from 61 ± 17 % at baseline to 71 ± 12 % during the 6 months and remained unchanged at 59 ± 14 % in the control group (mean adjusted difference, 11 percentage points; 95 % confidence interval [CI]: 9 to 14; p < 0.001). The results with regard to the main secondary outcomes (percentage of time that the glucose level was greater than 180 mg/dL, mean glucose level, glycated hemoglobin level, and percentage of time that the glucose level was less than 70 mg/dL or less than 54 mg/dL [3.0 mmol/L]) all met the pre-specified hierarchical criterion for significance, favoring the closed-loop system. The mean difference (closed loop minus control) in the percentage of time that the blood glucose level was lower than 70 mg/dL was -0.88 percentage points (95 % CI: -1.19 to -0.57; p < 0.001). The mean adjusted difference in glycated hemoglobin level after 6 months was -0.33 percentage points (95 % CI: -0.53 to -0.13; p = 0.001). In the closed-loop group, the median percentage of time that the system was in closed-loop mode was 90 % over 6 months. No serious hypoglycemic events occurred in either group; 1 episode of diabetic ketoacidosis occurred in the closed-loop group. The authors concluded that in this 6-month trial involving patients with T1DM, the use of a closed-loop system was associated with a greater percentage of time spent in a target glycemic range than the use of a sensor-augmented insulin pump.

In an editorial on the afore-mentioned study by Brown et al (2019), Bruttomesso (2019) stated that the closed-loop system is becoming a mature technology ready for practical use; however, there are a variety of barriers to a fully automated closed-loop system, including slow subcutaneous absorption of insulin, low stability of present glucagon formulations, insufficient sensor accuracy, and algorithms that are not yet flexible enough for everyday needs. Whether closed-loop systems can be used in higher-risk patients, such as those with impaired awareness of hypoglycemia, also remains a pressing issue. Cost-effectiveness, user acceptance, as well as training of both patients and healthcare professionals also need to be addressed. It is clear that patients would appreciate wearing devices that require minimal interaction, resulting in a more care-free lifestyle. The editorialist noted that “We are not there yet, but the trial by Brown et al offers an almost fingerstick-free option, providing a big step toward a brighter future for patients”.

In a randomized, controlled trial, McAuley et al (2020) examined glycemic and psychosocial outcomes with hybrid closed-loop (HCL) versus user-determined insulin dosing with multiple daily injections (MDI) or insulin pump (i.e., standard therapy for most adults with T1DM). Adults with T1DM using MDI or insulin pump without CGM were randomized to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was masked CGM time in range (TIR; 70 to 180 mg/dL) during the final 3 weeks. Subjects were randomized to HCL (n = 561) or control (n= 559). Baseline mean (SD) age was 44.2 (11.7) years, HbA1c was 7.4 % (0.9 %) (57 [10] mmol/mol), 53 % were women, and 51 % used MDI. HCL TIR increased from (baseline) 55 % (13 %) to (26 weeks) 70 % (10 %) with the control group unchanged: (baseline) 55 % (12 %) and (26 weeks) 55 % (13 %) (difference 15 % [95 % CI: 11 to 19]; p < 0.0001). For HCL, HbA1c was lower (median [95 % CI] difference 20.4 % [20.6 to 20.2]; 24 mmol/mol [27, 22]; p < 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 [95 % CI: 0.4 to 1.9]; p < 0.0048) without a deterioration in diabetes distress, perceived sleep quality, or cognition. A total of 17 (9 device-related) versus 13 serious AEs occurred in the HCL and control groups, respectively. The authors concluded that in adults with T1DM, 26 weeks of HCL improved TIR, HbA1c, and their sense of satisfaction from managing their diabetes compared with those continuing with user-determined insulin dosing and self-monitoring of blood glucose. For most patients living with T1DM globally, this study showed that HCL was feasible, acceptable, and advantageous.

Alvarenga et al (2022) noted that among the treatments for T1DM, CSII is a device that infuses insulin via the subcutaneous tissue in an uninterrupted manner, and that comes closest to the physiological secretion of insulin. The use of CSII could provide the family with greater security; and children and adolescents have more autonomy in relation to the treatment of T1DM. There is a lack of reviews that systematically gather the mounting evidence regarding the use of CSII in children and adolescents with T1DM. The objective of this review was to group and describe primary and secondary studies on the use of CSII in children and adolescents with T1DM. These investigators carried out a systematic mapping review based on searches in the following databases: PubMed, Embase, CINAHL, Lilacs and PsycINFO, using a combination of descriptors and keywords. The screening of the studies was carried out with the aid of the Rayyan software and reading in full was conducted independently by 2 reviewers. The data extraction of the studies was carried out using an extraction tool adapted and validated by researchers specialized in diabetes. The data were analyzed according to the content analysis technique. The map from geocoding of the studies was produced using the ArcGis 10.5 software. A total of 113 studies were included in the review, including primary studies, literature reviews and gray literature publications. The content analysis of the results of the studies allowed for the identification of 4 categories: metabolic control; support networks; benefits of using CSII; and challenges of using CSII; with each category having its respective sub-categories. The review also made it possible to perform a rigorous mapping of the literature on the use of CSII considering the location of development and the design of the studies. The authors concluded that the use of CSII should be indicated by healthcare professionals able to prepare children, adolescents, and their families for the treatment of T1DM, and, despite being a technological device, it may not be suitable for the entire pediatric population.

In a retrospective, cross-sectional study, Guo et al (2022) compared the effectiveness of CSII therapy with MDI therapy on glycemic metrics examined by retrospective continuous glucose monitoring (CGM) in Chinese patients with T1DM. A total of 362 patients with T1DM from the outpatient department of the Second Xiangya Hospital, Central South University, who underwent intensive insulin therapy and used a retrospective CGM system were included in this trial. Comprehensive analysis of clinical and biological features and retrospective CGM derived-metrics was carried out on the 362 enrolled T1DM patients who underwent CSII (n = 61) or MDI (n = 301) therapy (defined as 4 or more insulin injections per day). The results revealed that patients who underwent CSII therapy, compared with those who received MDI therapy, had lower levels of HbA1c and fasting blood glucose. Moreover, CSII therapy was associated with better glycemic outcomes in terms of increasing time in range (TIR), decreasing time above range (TAR), and achieving CGM-associated targets of TIR 70 % or higher and TAR of less than 25 %. However, patients who underwent CSII therapy did not experience decreasing time below range (TBR), achieving CGM-associated targets of TBR of less than 4 %, and reduction of the risk of hypoglycemia as evidenced by comparing TBR and low blood glucose index (LBGI) between the 2 treatment regimens. The parameters of glycemic variability, such as standard deviation of glucose (SD), mean amplitude glycemic excursion (MAGE), and large amplitude glycemic excursion (LAGE) in T1DM patients who underwent CSII therapy outperformed. The authors concluded that the findings of this study provided further evidence that CSII therapy was safe and effective for management of Chinese T1DM patients, which was confirmed by a lower HbA1c level and better CGM-derived metric; but no demonstration of improvement in the risk of hypoglycemia. To achieve more satisfactory glycemic outcomes via the use of CSII therapy for Chinese T1DM patients, a strong physician-patient relationship is essential.

On July 11, 2023, the FDA cleared for the Tandem Mobi insulin pump for home use in patients with type 1 diabetes aged 6 years and up. The Tandem Mobi is fully controllable from a mobile app and is the world’s smallest durable automated insulin delivery system. The Tandem Mobi features a 200-unit insulin cartridge and an on-pump button that provides an alternative option to phone control for administering bolus insulin.

On May 23, 2023, the FDA cleared the first fully closed-loop device, the Beta Bionics iLet ACE Pump and Dosing Decision Software for people 6 years of age and older with type 1 diabetes. These two devices, along with a compatible FDA-cleared integrated continuous glucose monitor (iCGM), will form a new system called the iLet Bionic Pancreas. This new automated insulin dosing (AID) system uses an algorithm to determine and command insulin delivery. The iLet Bionic Pancreas uses an adaptive closed-loop algorithm that is initialized only with a user’s body weight and requires no additional insulin dosing parameters. This adaptive algorithm removes the need to manually adjust insulin pump therapy settings and variables as is needed with conventional pump therapy and is easier to initiate than other available AID systems. The iLet device also simplifies use at mealtime by replacing conventional carb counting with a new meal announcement feature. With the new feature, users can estimate the amount of carbs in their meal as small, medium or large and the algorithm learns over time to respond to users’ individual insulin needs.

Combined Intrathecal Baclofen and Other Agents

Gatscher and associates (2002) stated that complex pain syndromes due to spasticity and central deafferentation often fail to respond to medical therapy and create challenging problems in the pain management. So far, only spasticity associated musculoskeletal pain has been reported to respond to intrathecal baclofen application. These investigators reported the treatment of severe neuropathic pain in a patient with erectile dysfunction (ED) and the combined intrathecal application of baclofen and morphine in 5 patients with severe spasticity related pain. Continuous intrathecal baclofen infusion resulted in a pain-free period of 20 months in the patient with ED. Patients with spasticity treated with intrathecal application of baclofen and morphine were pain-free for a mean period of 2 years. The authors concluded that intrathecal baclofen and morphine application was effective in spasticity-related and central deafferentation pain and should therefore be considered in the management of these patients. The major drawback of this study was its small sample size (n = 5 for patients with spasticity treated with intrathecal baclofen and morphine).

Wallace and colleagues (2010) noted that ziconotide is a non-opioid intrathecal analgesic used to manage moderate to severe chronic pain. Although ziconotide is approved for intrathecal monotherapy only, the need exists for a critical assessment of the currently available published literature on ziconotide combination therapy. These investigators evaluated the publications from pre-clinical and clinical peer-reviewed experiments that examined the safety and effectiveness of ziconotide in combination with a variety of other drugs. A total of 11 relevant publications were identified through a systematic search of multiple databases. In pre-clinical studies, additive or synergistic anti-nociceptive effects were discovered when ziconotide was used in combination with morphine, clonidine, or baclofen; however, no additional anti-nociceptive effects were observed when bupivacaine was added to ziconotide therapy. Safety data from animal studies revealed that ziconotide did not exacerbate morphine-induced respiratory depression, or clonidine-induced hypotension or bradycardia; however, ziconotide did potentiate morphine-induced hypotension and inhibition of gastro-intestinal (GI) tract motility. Results from 2 open-label trials indicated that combination ziconotide and morphine therapy produced greater analgesia than was produced by the use of either drug alone. Preliminary support for the use of ziconotide in combination with morphine, baclofen, or hydromorphone was provided by case studies. The authors concluded that although pre-clinical and clinical studies provided some support for the use of ziconotide in combination with morphine, hydromorphone, clonidine, or baclofen, strong evidence-based data are limited. They stated that controlled, long-term clinical trials are needed.

Saulino (2012) noted that intrathecal therapy has separate indications for refractory pain and spasticity. Both entities have a relatively high prevalence in neurologic diseases. This study examined the potential effectiveness of utilizing additive intrathecal morphine (ITM) therapy to a group of patients who had previously stabilized on intrathecal baclofen (ITB) therapy. Pain intensity was assessed via VASPI; 183 individuals participated in ITB therapy from January 1998 to December 2007; 47 individuals elected to add ITM to their intrathecal therapy regimen; 3 patients were intolerant to ITM/ITB combination therapy. No significant demographic differences between the 2 groups existed with respect to gender and race. Non-traumatic and traumatic spinal cord injury (SCI) patients were more likely to participate in combination therapy compared to other diagnoses. The average stabilized ITB dose for the monotherapy group was not statistically different for the combination therapy group. The average stabilized ITM for the combination therapy group was 1,730 μg/day (range of 27 to 10,500, SD = 2,350). The average decrement in VASPI was 35 %; 30 out of 47 patients experienced a decrease greater than 30 % in visual analog scale of pain intensity (VASPI) while 13 of the 47 patients experienced a decrease greater than 50 % in VASPI. There was no significant relationship between percent improvement in VASPI and morphine dosing; 8 of 47 combination patients experienced adverse events (AEs) attributable to intrathecal morphine but were capable to utilize the combination therapy for a least 1 year. The author concluded that reduction in pain intensity with combined therapy was variable; intrathecal morphine can be a safe and effective adjunct pain therapy to patients utilizing intrathecal baclofen for spasticity. The major drawbacks of this study were the lack of a control group and its relative small sample size (n = 47).

Intrathecal Baclofen for Cancer-Related Pain

Xing and colleagues (2018) evaluated the evidence in support of intrathecal drug delivery systems and spinal cord stimulation (SCS) for the treatment of cancer-related pain. In the past 3 years, a number of prospective studies have been published supporting intrathecal drug delivery systems for cancer pain. Additional investigation with adjuvants to morphine-based analgesia including dexmedetomidine and ziconotide support drug-induced benefits of patient-controlled intrathecal analgesia. A study has also been recently published regarding cost-savings for intrathecal drug delivery system compared to pharmacologic management, but an analysis in the Ontario, Canada healthcare system projects additional financial costs. Finally, the Polyanalgesic Consensus Committee has updated its recommendations regarding clinical guidelines for intrathecal drug delivery systems to include new information on dosing, trialing, safety, and systemic opioid reduction. There is still a paucity of clinical evidence for SCS in the treatment of cancer-related pain. There are new intrathecal drugs under investigation including various conopeptides and AYX1. The authors concluded that large, prospective, modern, randomized controlled studies are needed to support the use of both intrathecal drug delivery systems as well as SCS for cancer pain populations. There are multiple prospective and small RCTs that highlight a potential promising future for these interventional modalities. Related to the challenge and urgency of cancer-related pain, the pain practitioner community is moving toward a multi-modal approach that includes discussions regarding the role of intrathecal therapies and SCS to the individualized treatment of patients.

Furthermore, National Comprehensive Cancer Network’s clinical practice guideline on “Adult cancer pain” (Version 1.2018) does not mention baclofen as a therapeutic option.

Intrathecal Baclofen for Dyskinetic Cerebral Palsy

In a Cochrane review, Hasnat and Rice (2015) examined if ITB is an effective treatment for spasticity in children with CP. These investigators searched the CENTRAL, Medline, Embase and CINAHL databases, hand-searched recent conference proceedings, and communicated with researchers in the field and pharmaceutical and drug delivery system companies. They included studies which compared the effect of ITB treatment on spasticity, gross motor function or other areas of function with controls. Two authors selected studies, 2 authors extracted data and 2 authors assessed the methodological quality of included studies. A total of 6 studies met the inclusion criteria. The data obtained were unsuitable for the conduct of a meta-analysis; these researchers have completed a qualitative summary. All studies were found to have high or unclear risk of bias in some aspects of their methodology; 5 of the 6 studies reported data collected in the randomized controlled phase of the study. A 6th study did not report sufficient results to determine the effect of ITB versus placebo. Of these 5 studies, 4 were conducted using lumbar puncture or other short-term means of delivering ITB; 1 study assessed the effectiveness of implantable ITB pumps over 6 months. The 4 short-term studies demonstrated that ITB therapy reduced spasticity in children with CP. However, 2 of these studies utilized inappropriate techniques for statistical analysis of results. The single longer-term study demonstrated minimal reduction in spasticity with the use of ITB therapy. One of the short-term studies and the longer term study showed improvement in comfort and ease of care. The longer term study found a small improvement in gross motor function and also in some domains of health-related QOL. These investigators noted that some caution is needed in interpreting the findings of the all the studies in the review due to methodological issues. In particular, there was a high risk of bias in the methodology of the longer term study due to the lack of placebo use in the control group and the absence of blinding to the intervention after randomization for both participants and investigators. The authors concluded that there was some limited short-term evidence that ITB was an effective therapy for reducing spasticity in children with CP. The effect of ITB on long-term spasticity outcomes was less certain. The validity of the evidence for the effectiveness of ITB in treating spasticity in children with CP from the studies in the review was constrained by the small sample sizes of the studies and methodological issues in some studies. Spasticity is an impairment in the domain of body structure and function. Consideration must also be given to the broader context in determining whether ITB therapy was effective. The aim of therapy may be, for example, to improve gross motor function, to increase participation at a social role level, to improve comfort, to improve the ease of care by others or to improve the overall QOL of the individual. The authors stated that ITB may improve gross motor function in children with CP, but more reliable evidence is needed to determine this. There is some evidence that ITB improves ease of care and the comfort and QOL of the individuals receiving it, but again small sample sizes and methodological issues in the studies meant that these results should be interpreted with caution; and further evidence of the effectiveness of ITB for treating spasticity, increasing gross motor function and improving comfort, ease of care and QOL is needed from other investigators in order to validate these findings. The short duration of the controlled studies included in this review did not allow for the exploration of questions regarding whether the subsequent need for orthopedic surgery in children ITB therapy is altered, or the safety and the economic implications of ITB treatment when long-term therapy is administered via an implanted device. These researchers stated that controlled studies are not the most appropriate study design to address these questions, cohort studies may be more appropriate.

In a retrospective cohort study, Eek and associates (2018) examined the effect of ITB on function and activity in dyskinetic CP. This trial entailed 25 children (15 males, 10 females; mean age of 10 years 11 months , SD 4 years 9 months); 5 were classified in Gross Motor Function Classification level IV and 20 in level V. Parents were interviewed about activities in daily life (ADL), sitting, communication, pain, sleep, and gross and fine motor function. Differences before and 1 year after ITB were graded as positive, no change, or negative. Assessments of dystonia (using the Barry-Albright Dystonia Scale) and muscle tone (Ashworth Scale) were made; joint ROM was measured. Both dystonia and increased muscle tone, present in all participants before ITB, decreased after (p < 0.001). Passive ROM was restricted, with no difference after. Parents reported improvements in ADL (p < 0.001), sitting (p < 0.001), communication (p < 0.001), and fine motor function (p = 0.013), but no change in gross motor function. Before ITB, pain and disturbed sleep were reported. There was a reduction in pain (p = 0.002) and sleep improved (p = 0.004) after ITB. The authors concluded that ITB may have the potential to improve everyday life for children and young people with dyskinetic CP. However, it is important to evaluate the effects of ITB in dyskinetic CP in a RCT. One such study is underway, which will hopefully shed light on the effects of ITB and their magnitude in dyskinetic CP.

The authors stated that this study had several limitations. This was a small study (n = 25) without a comparison group, which limited the generalizability of the results and the conclusions that could be drawn from the data. As in other studies evaluating the effect of ITB, the results in this study were mostly based on interviews with parents. It was difficult to cover all aspects of everyday life both for the child and for their family through interviews, but using these was partly because of the lack of objective methods and instruments for assessing children with severe impairments. They noted that there is a need for more objective tools to measure effects of interventions on activity, and there is also a lack of instruments for assessing sitting function in this group. The presence of pain may have been under-estimated in this study, compared with the data from a multi-center European study. It is difficult to evaluate pain in children with impaired communication, and some parents stated after ITB that the children probably had pain before, although the parents had not realized this at the time. A similar inconsistency was illustrated by the fact that parents reported disturbed sleep in 7 cases before ITB, and improved sleep in 9 cases at follow‐up.

In a systematic review, Buizer and colleagues (2019) examined the effects of continuous ITB therapy in children with CP and other neurological conditions. This review was conducted using standardized methodology, searching 4 electronic databases (PubMed, Embase, CINAHL, Cochrane Library) for relevant literature published between inception and September 2017. Included studies involved continuous ITB as an intervention and outcome measures relating to all International Classification of Functioning, Disability and Health: Children and Youth (ICF-CY) components. A total of 33 studies were identified, of which one, including 17 children with spastic CP, produced level II evidence, and the others, mainly non-controlled cohort studies, level IV and V. Outcomes at body function level were most frequently reported. Results suggested continuous ITB may be effective in reducing spasticity and dystonia in CP, as well as other neurological conditions, and may improve the ease of care and QOL of children with CP, but the level of evidence was low. The authors concluded that despite 30 years of applying ITB in children and a relatively large number of studies investigating the treatment effects, a direct link has not yet been demonstrated because of the low scientific quality of the primary studies. They stated that further investigation into the effects of continuous ITB at all levels of the ICF-CY is needed. Although large, controlled trials may be difficult to realize, national and international collaborations may provide opportunities. Furthermore, prospective, multi-center, cohort studies with long-term follow-up, employing harmonized outcome measures, can offer prospects to expand knowledge of the effects of continuous ITB therapy in children.

Furthermore, an UpToDate review on “Management and prognosis of cerebral palsy” (Patterson, 2018) states that “Intrathecal baclofen (administered via a pump) achieves higher cerebrospinal fluid (CSF) drug levels as compared with oral administration, which results in low CSF drug levels because of poor lipid solubility. Intrathecal baclofen may be effective in reducing spasticity in severely affected patients, but its use is also associated with substantial complications. Therefore, this treatment is generally restricted to patients with severe spasticity that is not responsive to other measures. Guidelines for determining patient selection and the optimal dose and placement of the catheter tip have not been established. Evidence for the advantages or otherwise of intrathecal baclofen over selective dorsal rhizotomy is lacking. Both procedures carry significantly more risk than less invasive interventions … Side effects of intrathecal baclofen include lethargy, confusion, and hypotonia, which appear to be dose-related and occur in up to 50 % of patients. Catheter-related complications include infection, seroma, and cerebrospinal fluid leak”. Intrathecal baclofen is not listed in the “Summary and Recommendations” section of this review.

Intrathecal Baclofen for Gaucher Disease

Hori and associates (2017) noted that Gaucher disease (GD) is the most common type of lysosomal storage disease, with type 2 being the most severe subtype. Type 2 GD patients suffer significant progressive neurological impairment, including spasticity, opisthotonus, seizure, and apnea. The recently developed enzyme replacement therapy (ERT) has shown therapeutic benefit for GD. However, as the enzymes do not cross the blood-brain barrier, ERT does not ameliorate neurological impairment in GD. Intrathecal baclofen therapy (IBT) has been reported to be beneficial in improving several manifestations of GD, such as scoliosis caused by muscle spasticity and respiratory function. To-date, the potential benefits of IBT for treating lysosomal storage diseases such as GD have not been examined. The authors provided the first report of a patient with type 2 GD treated with IBT, and demonstrated its therapeutic benefit in ameliorating the neurological aspects of this disease.

Intrathecal Baclofen for Rett Syndrome

Kadyan and colleagues (2003) noted that ITB infusions have proven to be effective for management of spasticity in the past 20 years. Efficacy of ITB for spasticity of spinal origin has been well-established and has shown promise in treatment of spasticity that is not spinal in origin. Rett syndrome is a neurodevelopmental disorder primarily affecting girls and women. Manifested in the advanced stages of this syndrome is increased spasticity leading to functional decline. These researchers presented a case report of a 32-year old white woman with Rett syndrome, diagnosed before the age of 2 years, and significant spasticity that was successfully managed with ITB. After placement of an ITB pump, the dose was increased slowly during 1 year to 800 ug/day with good clinical response. There was observed a significant decrease in upper and lower limb Ashworth scores, from an average of 3-4 to 2-3, during this 1-year period. The decrease in spasticity in this patient eventually led to improved range of motion (ROM), positioning, skin care, hygiene, and QOL. The authors concluded that ITB was an effective option in managing severe spasticity from Rett syndrome.

Intrathecal Baclofen for Post-Stroke Spasticity

Olvey et al (2010) stated that muscle spasticity after stroke may be painful and severe and may restrict the patient's ability to perform routine daily tasks, particularly when the affected muscles are in the ULs. Treatments targeted at reducing this spasticity have evolved over time. In a systematic review, these researchers examined recent studies focusing on contemporary pharmacologic therapies for UL spasticity after stroke. Medline, Embase, and the Cochrane Controlled Trials Register were searched for clinical trials published in English from January 1995 to July 2010 using search terms that included spasticity, stroke, hemiplegia, phenol, baclofen, tizanidine, dantrolene, benzodiazepine, and BTX. The level of evidence of the identified publications was assessed using the Oxford Centre for Evidence-Based Medicine criteria. A total of 113 potentially relevant articles were identified by the search; of these, 54 studies were included in the review (23 randomized controlled trials [RCTs] and 31 open-label, non-randomized, or observational studies). Of these, 51 involved treatment with BTX. All studies assessed spasticity; some also assessed additional outcomes, such as pain, disability, and functional status; 38 clinical trials reported a significant reduction in spasticity with BTX, either compared with baseline or with placebo (p < 0.05). A head-to-head comparison found a significant reduction in spasticity with BTX injections compared with oral tizanidine (TZD) (p < 0.001); 2 studies of intrathecal baclofen (ITB) reported significant reductions in UL spasticity after 12 months of treatment, and 1 study of tizanidine reported significant reductions in UL spasticity after 16 weeks of treatment (all, p < 0.001). General or local weakness, injection-site pain, and fatigue were the most frequently reported AEs with BTX type A, and dry mouth was the most frequently reported AE with BTX type B. No serious or life-threatening AEs were reported in any trial of BTX. The authors concluded that the 54 studies included in this systematic review of treatments for UL spasticity after stroke measured multiple outcomes using a variety of instruments; 51 studies focused on treatment with a BTX formulation; BTX appeared to be an effective and well-tolerated focal treatment for reducing tonicity in patients with UL spasticity after stroke, supporting current guideline recommendations.

Dvorak et al (2011) stated that stroke is one of the leading causes of adult disability in the United States, with a reported prevalence of 6.4 million people. Spasticity is one of the clinical features of the upper motor neuron syndrome observed following a stroke. The prevalence of spasticity after a stroke ranges from 17 % to 42.6 %, and an average of 2/3 of people with spasticity have upper and lower extremity (UL and LE) involvement. Oral medications and BTX injections are current treatments for problematic spasticity. However, these treatments are often limited by side effects or dose ceilings; ITB is a proven method for the management of disabling spasticity from multiple etiologies. Studies have demonstrated improved mobility, activities of daily living (ADL), and quality of life (QoL) in spastic post-stroke patients. Despite the benefits of ITB, fewer than 1 % of stroke patients with severe disabling spasticity are being treated with ITB. The authors reviewed the prevalence of severe post-stroke spasticity (PSS) and the rate of ITB use and discussed reasons for its limited use in stroke survivors.

In a prospective, observational study, Schiess et al (2011) examined the effects of ITB therapy for the treatment of post-stroke spastic hemiparesis on QOL , functional independence, and UE / LE motor functions. Subjects included adult men and women with a minimum 6-month stroke-related spastic hemiparesis graded as greater than or equal to 2 in UE and LE on Modified Ashworth Scale (MAS). Patients served as their own controls with measures compared pre-implant with 12 months post ITB including: MAS, manual muscle test (MMT), gait distance/velocity, Functional Independence Measures (FIM), stroke-specific QOL scale (SSQL), and UE manual activity log. After 12-month ITB therapy, 26 patients (post-stroke = 6.4 ± 9 years) demonstrated reduced MAS/increased MMT for most LE muscle groups (p ≤ 0.0001); reduced MAS/increased MMT most UE muscle groups (p ≤ 0.01); FIM scores improved (p ≤ 0.05) except bed mobility and lower body dressing; gait distance and velocity improved (p ≤ 0.05); SSQL domains of family roles, mobility, personality, self-care, social roles, thinking, UE function, and work/productivity improved (p ≤ 0.05); and amount of use and quality of movement of the spastic UE in performing common ADL increased (p<0.0001). The authors concluded that regardless of duration of spastic hemiparesis, a reduction in tone with ITB therapy facilitated motor strength improvement and was associated with clinically significant improvements in functional independence and QOL.

Maneyapanda et al (2017) noted that ITB often is used to treat severe spasticity of cerebral origin. Although literature exists regarding the efficacy of ITB, there has been minimal investigation related to dosing in the adult-acquired brain injury population, particularly at long-term duration. In a retrospective cohort study, these investigators examined long-term dosing of ITB in adult patients with spasticity of cerebral origin due traumatic brain injury (TBI), stroke, and hypoxic-ischemic encephalopathy (HIE). A total of 42 adult patients with spasticity secondary to TBI, stroke, or HIE treated with ITB for greater than 3 years. Medical records and device manufacturer records of included patients were reviewed to obtain demographic data, dosing information, dates of pump and catheter placements, and revisions. Main outcome measures included average daily ITB doses and mean change in ITB dose over 1, 2, and 3 years. Goal of ITB treatment (active function versus comfort/care/positioning) also was compared. Of 42 total patients, spasticity was attributed to either TBI (n = 19), stroke (n = 11), or HIE (n = 12). The mean (standard deviation) age was 35.21 (10.17), 56.7 (13.1), and 35.1 (12.4) years for the TBI, stroke, and HIE groups, respectively (p < 0.001). There was a significant difference in the goal of therapy with "improving functional independence," accounting for 27.8 %, 72.8 %, and 0 % in the TBI, stroke, and HIE groups, respectively (p = 0.002). The mean duration of ITB therapy was 8.5 (5.0), 7.8 (3.4), and 9.1 (4.6) years in the TBI, stroke, and HIE groups, respectively (p = 0.79). The mean daily ITB dose was 596.9 (322.8) μg/d, 513.2 (405.7) μg/d, and 705.2 (271.7) μg/d for the TBI, stroke, and HIE groups, respectively (p = 0.39). In the subset of the cohort with ITB therapy for more than 5 years, the mean percent change in daily ITB dose between time of chart review and 1, 2, and 3 years previously was 7.3 % (13.6), 12.7 % (16), and 24.7 % (50.3), respectively. A complex dosing pattern was used more frequently in those with stroke (36.4 %) compared with the TBI and HIE (9.7 %) groups (p = 0.04). The authors concluded that despite the long-term use of ITB therapy in this cohort, the mean daily dose of ITB continued to require adjustments. There was no significant difference in the mean daily dose between patients with a diagnosis of TBI, stroke, or HIE. A complex dosing pattern was used more frequently in patients with stroke.

Creamer et al (2018) noted that ITB is an effective treatment for managing patients with severe PSS, who can experience continued pain and decline in their QoL. SISTERS (Spasticity In Stroke-Randomized Study) was a randomized, controlled, open-label, multi-center, phase-IV study to evaluate ITB therapy versus conventional medical management (CMM) with oral antispastic medications for treatment of post-stroke spasticity. Post-stroke patients with spasticity in greater than or equal to 2 extremities and an Ashworth Scale score of greater than or equal to 3 in greater than or equal to 2 affected lower extremity (LE) muscle groups were randomized (1:1) to ITB (n = 31) or CMM (n = 29). Both treatment arms received physiotherapy throughout. The primary outcome was the change in average Ashworth Scale score in the LEs of the affected side from baseline to month 6. These researchers reported results for secondary outcomes: pain via the Numeric Pain Rating Scale, health-related QoL by the EuroQol-5 dimensional 3 level utility score and health status visual analog scale score, stroke-specific QoL, and patient satisfaction. Analyses were performed on an intention-to-treat (ITT) basis. They observed significant treatment effects in favor of ITB over CMM for changes from baseline to month 6 in Numeric Pain Rating Scale scores for actual pain (ITB versus CMM: mean of -1.17 [SD, 3.17] versus 0.00 [3.29]; median, -1.00 versus 0.00; p = 0.0380) and least pain (mean of -1.61 [2.29] versus 0.24 [3.07]; median of -1.00 versus 0.00; p = 0.0136), and EuroQol-5 dimensional 3 level utility scores (mean of +0.09 [0.26] versus +0.01 [0.16]; median of +0.07 versus 0.00; p = 0.0197). Between-group differences were not statistically significant for EuroQol-5 dimensional 3 level visual analog scale (VAS), stroke-specific QoL summary, or Numeric Pain Rating Scale worst pain scores, although ITB patients showed greater numeric improvements from baseline during follow-up. More ITB patients than CMM patients (73 % versus 48 %) were satisfied with the spasticity reduction at month 6. The authors concluded that these findings supported that ITB therapy was associated with improvements in pain and QoL in post-stroke patients.

Intrathecal Baclofen for Traumatic Brain Injury (TBI) Spasticity

The use of intrathecal baclofen for traumatic brain injury (TBI) spasticity resistant to oral drugs and/or their adverse severe effects is supported in several small observational case studies/series (Pérez-Arredondo et al, 2016). Enslin and colleagues (2020) state that intrathecal baclofen is promising as it causes fewer systemic side effects, and that a consensus panel has stated that intrathecal baclofen is safe for children with TBI induced spasticity. The efficacy of intrathecal baclofen was investigated in three controlled clinical trials; two enrolled patients with cerebral palsy and one enrolled patients with spasticity due to previous brain injury. The first study, a randomized controlled cross-over trial of 51 patients with cerebral palsy, provided strong, statistically significant results; intrathecal baclofen was superior to placebo in reducing spasticity as measured by the Ashworth Scale. A second cross-over study was conducted in 11 patients with spasticity arising from brain injury. Despite the small sample size, the study yielded a nearly significant test statistic (p=0.066) and provided directionally favorable results. The last study, however, did not provide data that could be reliably analyzed.

The FDA has approved intrathecal baclofen therapy for the management of severe spasticity of cerebral or spinal origin in adult and pediatric patients age 4 years and above. FDA-approved labeling for intrathecal baclofen therapy (Gablofen [Piramal Critical Care, Inc]; Lioresal [Saol Therapeutics, Inc.]), state persons with spasticity due to TBI should wait at least one year after the injury before consideration of long-term intrathecal baclofen therapy.

Gablofen and Lioresal are gamma-aminobutyric acid (GABA) ergic agonist indicated for use in the management of severe spasticity of cerebral or spinal origin in adult and pediatric patients age 4 years and above. It should be reserved for patients unresponsive to oral baclofen therapy, or those who experience intolerable central nervous system side effects at effective doses. Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump. Patients who do not respond to a 100 mcg intrathecal bolus should not be considered for an implanted pump for chronic infusion. The labels carry a boxed warning regarding abrupt discontinuation. Regardless of the cause, abrupt discontinuation has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure and death.

Subacromial Pain Pump use Following Shoulder Surgery

Schwartzberg and co-workers (2013) stated that arthroscopic rotator cuff repair can be a painful out-patient procedure. These researchers examined the efficacy of continuous subacromial bupivacaine infusion to relieve pain following arthroscopic rotator cuff repair. They hypothesized that patients receiving continuous subacromial bupivacaine infusions following arthroscopic rotator cuff repair will have less post-operative pain in the early post-operative period than placebo and control groups. A total of 88 patients undergoing arthroscopic rotator cuff repair were randomized in a blinded fashion into 1 of 3 groups: Group 1 received no post-operative subacromial infusion catheter; group 2 received a post-operative subacromial infusion catheter filled with saline solution; and group 3 received a post-operative subacromial infusion catheter filled with 0.5 % bupivacaine without epinephrine. Infusion catheters were scheduled to infuse at 4 ml/hour for 50 hours. Post-operative pain levels were evaluated with VAS scores hourly for the first 6 post-operative hours, every 6 hours for the next 2 days, and then every 12 hours for the next 3 days. Patients recorded daily oxycodone consumption for the first 5 post-operative days. Immediately post-operative, the group with no catheter had significantly lower VAS scores (p = 0.04). There were no significant differences in VAS scores among the groups at any other time-point. There were no differences found among the groups regarding mean daily oxycodone consumption. The authors concluded that the use of continuous bupivacaine subacromial infusion catheters resulted in no detectable pain reduction following arthroscopic rotator cuff repair based on VAS scores and narcotic medication consumption. Level of Evidence = I.

Busfield and colleagues (2014) noted that intra-articular pain pumps with local anesthetics have been implicated as a potential cause of post-arthroscopic glenohumeral chondrolysis (PAGCL) of the shoulder. Patients with full thickness rotator cuff tears may be at high risk of PAGCL given disruption of the tendinous integrity which may allow intra-articular infusion of local anesthetics. These researchers hypothesized that subacromial pain pump use following arthroscopic rotator cuff repair would not result in PAGCL. They analyzed a consecutive series of 34 patients treated with subacromial pain pump placement following arthroscopic rotator cuff repair and subacromial decompression for full thickness rotator cuff tears. A total of 30 patients met inclusion criteria of greater than 12-month follow-up with an average age of 51 (28 to 68) years. All patients had the subacromial pain pumps placed under arthroscopic visualization and infused 0.25 % bupivacaine without epinephrine at 2 cc/hour for 48 hours. All patients had clinical examinations and radiographic studies performed more than 1 year after surgery. Patients had an average rotator cuff size of 1.6 cm and fixation was carried out with bioabsorbable suture anchors. All patients had at least 150° of abduction and forward flexion at latest follow-up without palpable crepitus and no patients had any evidence of joint space narrowing on post-operative radiographs. The authors concluded that subacromial pain pump use following arthroscopic rotator cuff repair was safe. Despite probable lack of a water-tight seal from repair, there were no cases of PAGCL. Moreover, these researchers stated that it was important to note that this study used a low flow-rate of 2 cc/hour, and conclusions regarding higher flow rates were uncertain. Level of Evidence = IV.

Toma and co-workers (2019) noted that rotator cuff repair can be associated with significant and difficult-to-treat post-operative pain. These investigators examined the available literature and developed recommendations for optimal pain management following rotator cuff repair. They carried out a systematic review using procedure-specific postoperative pain management (PROSPECT) methodology; RCTs published in English from January 1, 2006 to April 15, 2019 evaluating post-operative pain following rotator cuff repair using analgesic, anesthetic or surgical interventions were identified from Medline, Embase and Cochrane Databases. Of 322 eligible studies identified, 59 RCTs and 1 systematic review met the inclusion criteria. Pre-operative and intra-operative interventions that improved post-operative pain were paracetamol, cyclo-oxygenase-2 inhibitors, intravenous dexamethasone, regional analgesia techniques including interscalene block or suprascapular nerve block (with or without axillary nerve block) and arthroscopic surgical technique. Limited evidence was found for pre-operative gabapentin, perineural adjuncts (opioids, glucocorticoids, or α-2-adrenoceptor agonists added to the local anesthetic solution) or post-operative transcutaneous electrical nerve stimulation (TENS). Inconsistent evidence was found for subacromial/intra-articular injection, and for surgical technique-linked interventions, such as platelet-rich plasma (PRP). No evidence was found for stellate ganglion block, cervical epidural block, specific post-operative rehabilitation protocols or post-operative compressive cryotherapy. The analgesic regimen for rotator cuff repair should include an arthroscopic approach, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), dexamethasone and a regional analgesic technique (either interscalene block or suprascapular nerve block with or without axillary nerve block), with opioids as rescue analgesics. The authors concluded that further RCTs are needed to confirm the influence of the recommended analgesic regimen on post-operative pain relief. Subacromial pain pump is not mentioned as a management tool.

An and associates (2020) stated that subacromial analgesia (SAA) is hypothesized to reduce pain following arthroscopic shoulder surgery by delivering a continuous infusion of local anesthetic directly to the surgical site. In a systematic review and meta-analysis, these investigators examined the efficacy of SAA versus placebo for pain relief following arthroscopic subacromial shoulder procedures. Medline, Embase, PubMed, and the Cochrane Central Register of Controlled Trials were searched for RCTs comparing SAA with placebo following arthroscopic shoulder surgery. Outcomes collected included pain scores (converted to equivalent ordinal VAS; minimal clinically important difference 1.4 cm), oral morphine equivalents used post-operatively, and catheter-related complications. Meta-analysis was carried out via a random-effects model. Included trials underwent a risk of bias and quality of evidence assessment. A total of 9 studies involving 459 subjects were included. There were no clinically significant changes for pain scores in SAA at 6-, 12-, 24-, and 48-hour post-operative time-points. Patients receiving SAA used less morphine equivalents of pain medication at 12 hours only (-0.37 mg, 95 % CI: -0.63 to -0.11); however, there was no significant difference at 24 and 48 hours. There were no major complications (infection or re-operation). Included trials demonstrated a moderate risk-of-bias, and low-to-very low quality of evidence for primary outcomes. The authors concluded that subacromial continuous infusion of local anesthetic did not provide a clinically significant benefit compared with placebo as part of a multi-modal analgesia regimen following arthroscopic subacromial surgical procedures. Moreover, these researchers stated that future, high-quality trials are needed to further examine the efficacy of SAA against placebo. Level of Evidence = II.

References

The above policy is based on the following references:

Agency for Health Care Policy and Research (AHCPR). Reassessment of external insulin infusion pumps. AHCPR Assessment No. 9. Rockville, MD: AHCPR; July 1991.
Albright AL. Intrathecal baclofen in cerebral palsy movement disorders. J Child Neurol. 1996;11 Suppl 1:S29-S35.
Alsaleh FM, Smith FJ, Taylor KM. Experiences of children/young people and their parents, using insulin pump therapy for the management of type 1 diabetes: Qualitative review. J Clin Pharm Ther. 2012;37(2):140-147.
Alvarenga CS, La Banca RO, Neris RR, et al. Use of continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes mellitus: A systematic mapping review. BMC Endocr Disord. 2022;22(1):43.
American Diabetes Association. Continuous subcutaneous insulin infusion. Diabetes Care. 2003;26 Suppl 1:S125.
American Diabetes Association: Clinical practice recommendations 1995. Diabetes Care. 1995;18(Supp 1):1-96.
American Medical Association (AMA). Continuous subcutaneous insulin infusion. Diagnostic and Therapeutic Technology Assessment. Chicago, IL: AMA; 1989.
An VVG, Farey JE, Karunaratne S, et al. Subacromial analgesia via continuous infusion catheter vs. placebo following arthroscopic shoulder surgery: A systematic review and meta-analysis of randomized trials. J Shoulder Elbow Surg. 2020;29(3):471-482.
Andersen J, Hartling L, Tjosvold L, Watt J. Oral baclofen for the management of spasticity in children with cerebral palsy (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2005;(3):CD005357.
Angel IF, Gould HJ Jr, Carey ME. Intrathecal morphine pump as a treatment option in chronic pain of nonmalignant origin. Surg Neurol. 1998;49(1):92-98; discussion 98-99.
Armstrong RW, Steinbok P, Cochrane DD, et al. Intrathecally administered baclofen for treatment of children with spasticity of cerebral origin. J Neurosurg. 1997;87(3):409-414.
Bayram N, van Wely M, van der Veen F. Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility associated with polycystic ovary syndrome. Cochrane Database Syst Rev. 2004;(1):CD000412.
Belicar P, Lassmann-Vague V. Local adverse events associated with long-term treatment by implantable insulin pumps. The French EVADIAC Study Group experience. Evaluation dans le Diabete du Traitement par Implants Actifs. Diabetes Care. 1998;21(2):325-326.
Berthe E, Lireux B, Coffin C, et al. Effectiveness of intensive insulin therapy by multiple daily injections and continuous subcutaneous infusion: A comparison study in type 2 diabetes with conventional insulin regimen failure. Horm Metab Res. 2007;39(3):224-229.
Beta Bionics. Beta Bionics announces FDA clearance and commercialization of the iLet Bionic Pancreas. Press Release. Concord, MA: Beta Bionics; May 22, 2023.
Bode B, Steed RD, Davidson PC. Reduction in severe hypoglycemia with long-term continuous subcutaneous insulin infusion in type I diabetes. Diabetes Care. 1996;19(4):324-327.
Boswell G, Bekersky I, Mekki Q, Eisenach J. Plasma concentrations and disposition of clonidine following a constant 14-day epidural infusion in cancer patients. Clin Ther. 1997;19(5):1024-1030.
Brennan PM, Whittle IR. Intrathecal baclofen therapy for neurological disorders: A sound knowledge base but many challenges remain. Br J Neurosurg. 2008;22(4):508-519.
Brown SA, Kovatchev BP, Raghinaru D, et al; iDCL Trial Research Group. Six-month randomized, multicenter trial of closed-loop control in type 1 diabetes. N Engl J Med. 2019;381(18):1707-1717.
Bruttomesso D. Toward automated insulin delivery. N Engl J Med. 2019;381(18):1774-1775.
Buizer AI, Martens BHM, Grandbois van Ravenhorst C, et al. Effect of continuous intrathecal baclofen therapy in children: A systematic review. Dev Med Child Neurol. 2019;61(2):128-134.
Busfield BT, Romero DM, Korshad D, Kharrazi FD. Subacromial pain pump use is safe after arthroscopic rotator cuff repair. J Orthop. 2014;11(2):64-67.
Caird MS, Palanca AA, Garton H, et al. Outcomes of posterior spinal fusion and instrumentation in patients with continuous intrathecal baclofen infusion pumps. Spine. 2008;33(4):E94-E99.
Centers for Medicare & Medicaid Services (CMS). Decision memo for insulin pump: C-peptide levels as a criterion for use (CAG-00092R). Baltimore, MD: CMS; December 17, 2004.
Colquitt JL, Green C, Sidhu MK, et al. Clinical and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes. Health Technol Assess. 2004;8(43):iii, 1-171.
Coombs DW, Saunders RL, Gaylor MS, et al. Relief of continuous chronic pain by intraspinal narcotics infusion via an implanted reservoir. JAMA. 1983;250(17):2336-2339.
Cote B, St-Hilaire C. Comparison of the insulin pump and multiple daily insulin injections in intensive therapy for type 1 diabetes. Montreal, QC: Agence d'Evaluation des Technologies et des Modes d'Intervention en Sante (AETMIS); 2004.
Creamer M, Cloud G, Kossmehl P, et al. Effect of intrathecal baclofen on pain and quality of life in poststroke spasticity. Stroke. 2018;49(9):2129-2137.
Cummins E, Royle P, Snaith A, et al. Clinical effectiveness and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes: Systematic review and economic evaluation. Health Technol Assess. 2010;14(11):iii-iv, xi-xvi, 1-181.
Doci R, Bignami P, Bozzetti F, et al. Intrahepatic chemotherapy for unresectable hepatocellular carcinoma. Cancer. 1988;61(10):1983-1987.
Dos Santos TJ, de Mata Donado Campos J, Argente J, Rodriguez-Artalejo F. Effectiveness and equity of continuous subcutaneous insulin infusions in pediatric type 1 diabetes: A systematic review and meta-analysis of the literature. Diabetes Res Clin Pract. 2021;172:108643.
Doskicz J. What's the difference between insulin pumps and automated insulin delivery (AID) systems? GoodRx Health [online]. Santa Monica, CA: GoodRx: updated February 13, 2024. Available at: https://www.goodrx.com/conditions/diabetes/closed-loop-insulin-pump. Accessed May 20, 2024.
Durand-Zaleski I, Roche B, Buyse M, et al. Economic implications of hepatic arterial infusion chemotherapy in treatment of nonresectable colorectal liver metastases. Meta-analysis Group in Cancer. J Natl Cancer Inst. 1997;89(11):790-795.
Dvorak EM, Ketchum NC, McGuire JR. The underutilization of intrathecal baclofen in poststroke spasticity. Top Stroke Rehabil. 2011;18(3):195-202.
Ebel H, Buschmann D, Conzen M, et al. Initial experiences with implantable pump systems for intrathecal therapy of chronic pain conditions. Nervenarzt.1993;64(7):468-473.
Eek MN, Olsson K, Lindh K, et al. Intrathecal baclofen in dyskinetic cerebral palsy: Effects on function and activity. Dev Med Child Neurol. 2018;60(1):94-99.
Eichner HL, Selam J, Holleman CB, et al. Reduction of severe hypoglycemic events in type I (insulin dependent) diabetic patients using continuous subcutaneous insulin infusion. Diabetes Res. 1988;8(4):189-193.
Eisenach JC, DuPen S, Dubois M, et al. Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group. Pain. 1995;61(3):391-399.
Enslin JMN, Rohlwink UK, Figaji A. Management of spasticity after traumatic brain injury in children. Front Neurol. 2020;11:126.
Exner HJ, Peters J, Eikermann M. Epidural analgesia at end of life: Facing empirical contraindications. Anesth Analg. 2003;97(6):1740-1742.
Farkas-Hirsch R, Hirsch IB. The question is answered. Now what?. Diabetes Care. 1994;17(3):237-238.
Farrar D, Tuffnell DJ, West J, West HM. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. Cochrane Database Syst Rev. 2016;(6):CD005542.
Farrar D, Tuffnell DJ, West J. Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. Cochrane Database Syst Rev. 2007;(3):CD005542.
Fatourechi MM, Kudva YC, Murad MH, et al. Clinical review: Hypoglycemia with intensive insulin therapy: A systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections. J Clin Endocrinol Metab. 2009;94(3):729-740.
Gatscher S, Becker R, Uhle E, Bertalanffy H. Combined intrathecal baclofen and morphine infusion for the treatment of spasticity related pain and central deafferentiation pain. Acta Neurochir Suppl. 2002;79:75-76.
Gianino JM, York MM, Paice JA, et al. Quality of life: Effect of reduced spasticity from intrathecal baclofen. J Neurosci Nurs. 1998;30(1):47-54.
Grunberger G, Bailey TS, Cohen AJ, et al.; AACE Insulin Pump Management Task Force. Statement by the American Association of Clinical Endocrinologists Consensus Panel on insulin pump management. Endocr Pract. 2010;16(5):746-762.
Guo K, Li J, Zhang L, et al. Comparing the effectiveness of continuous subcutaneous insulin infusion with multiple daily insulin injection for patients with type 1 diabetes mellitus evaluated by retrospective continuous glucose monitoring: A real-world data analysis. Front Public Health. 2022:10:990281.
Hammond P. Continuous subcutaneous insulin infusion: Short-term benefits apparent, long-term benefits speculative. Br J Diabetes Vasc Dis. 2004;4(2):104-108.
Hansel DE, Hansel CR, Shindle MK, et al. Oral baclofen in cerebral palsy: Possible seizure potentiation? Pediatr Neurol. 2003;29(3):203-206.
Harvey SC, O'Neil MG, Pope CA, et al. Continuous intrathecal meperidine via an implantable infusion pump for chronic, nonmalignant pain. Ann Pharmacother. 1997;31(11):1306-1308.
Hasnat MJ, Rice JE. Intrathecal baclofen for treating spasticity in children with cerebral palsy. Cochrane Database Syst Rev. 2015;(11):CD004552.
Hassenbusch SJ, Pillay PK, Magdinec M, et al. Constant infusion of morphine for intractable cancer pain using an implanted pump. J Neurosurg. 1990;73(3):405-409.
Hassenbusch SJ, Stanton-Hicks MD, Soukup J, et al. Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural infusions for intractable non-cancer pain. Neurosurgery. 1991;29(1):76-82.
Herman WH, Ilag LL, Johnson SL, Martin CL, et al. A clinical trial of continuous subcutaneous insulin infusion versus multiple daily injections in older adults with type 2 diabetes. Diabetes Care. 2005;28(7):1568-1573.
Hori YS, Fukuhara T, Aoi M, et al. Intrathecal baclofen pump implantation for type 2 Gaucher disease. Pediatr Neurosurg. 2017;52(5):331-335.
Hoving MA, van Raak EP, Spincemaille GH, et al. Efficacy of intrathecal baclofen therapy in children with intractable spastic cerebral palsy: A randomised controlled trial. Eur J Paediatr Neurol. 2009;13(3):240-246.
Hughes D. Gaucher disease: Treatment. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed October 2018.
Hundal R, Kowalyk S, Wakim A, et al. Multicenter real-world assessment of the effectiveness of V-Go wearable insulin delivery device in adult patients with type 2 diabetes (ENABLE Study): A retrospective analysis. Med Devices (Auckl). 2020;13:283-291.
Institute for Clinical Systems Improvement (ICSI). Dorsal rhizotomy and intrathecal baclofen for lower extremity spasticity associated with cerebral palsy. Technology Assessment Report. Bloomington, MN: ICSI; 2000.
Insulet Corporation. Omnipod GO User Guide. Acton, MA: Insulet: May 2023. Available at: https://www.omnipod.com/sites/default/files/Omnipod-GO_User_Guide_US_English.pdf. Accessed October 31, 2023.
Ito Y, Nakahigashi T, Yoshimoto N, et al. Transdermal insulin application system with dissolving microneedles. Diabetes Technol Ther. 2012;14(10):891-899.
Jahn LG, Capurro JJ, Levy BL. Comparative dose accuracy of durable and patch insulin infusion pumps. J Diabetes Sci Technol. 2013;7(4):1011-1020.
Jaremko J, Rorstad O. Advances toward the implantable artificial pancreas for treatment of diabetes. Diabetes Care. 1998;21(3):444-450.
Johns BR, Jones TC, Sink JH 2nd, Cooke CE. Real-world assessment of glycemic control after V-Go® initiation in an endocrine practice in the southeastern United States [letter]. J Diabetes Sci Technol. 2014;8(5):1060-1061.
Kadyan V, Clairmont AC, George RJ, Johnson EW. Intrathecal baclofen for spasticity management in Rett syndrome. Am J Phys Med Rehabil. 2003;82(7):560-562.
Kapitza C, Fein S, Heinemann L, et al. Basal-prandial insulin delivery in type 2 diabetes mellitus via the V-Go: A novel continuous subcutaneous infusion device. J Diabetes Sci Technol. 2008;2(1):40-46.
Kitzmiller JL, Gavin LA, Gin GD, et al. Preconception care of diabetes: Glycemic control prevents congenital anomalies. JAMA. 1991;265(6):731-736.
Koivisto VA, Yki-Järvinen H, Helve E, et al. Pathogenesis and prevention of the dawn phenomenon in diabetic patients treated with CSII. Diabetes. 1986;35:78-82.
Krames ES. Intrathecal infusional therapies for intractable pain: Patient management guidelines. J Pain Symptom Manage. 1993;8(1):36-46.
Krames, E. Intraspinal opioid therapy for chronic non-malignant pain: Current practice and clinical guidelines. J Pain Symptom Manage. 1996;11(6):333-352.
Lajara R, Davidson JA, Nikkel CC, Morris TL. Clinical and cost-effectiveness of insulin delivery with V-Go (®) disposable insulin delivery device versus multiple daily injections in patients with type 2 diabetes inadequately controlled on basal insulin. Endocr Pract. 2016;22(6):726-735.
Lajara R, Fetchick DA, Morris TL, Nikkel C. Use of V-Go® insulin delivery device in patients with sub-optimally controlled diabetes mellitus: A retrospective analysis from a large specialized diabetes system. Diabetes Ther. 2015;6(4):531-545.
Lassmann-Vague V, Clavel S, Guerci B, et al; Société francophone du diabète (ex ALFEDIAM). When to treat a diabetic patient using an external insulin pump. Expert consensus. Société francophone du diabète (ex ALFEDIAM) 2009. Diabetes Metab. 2010;36(1):79-85.
Lassmann-Vague V, Guerci B, Hanaire-Broutin H, et al. Use of implantable insulin pumps: The EVADIAC position. Recommendations of ALFEDIAM (French Language Association for the Study of Diabetes and Metabolic Diseases). Evaluation dans le Diabete du Traitement par Implants Actifs. Diabetes Metab. 1997;23(3):234-250.
Levy R, Leiphart J, Dills C. Analgesic action of acute and chronic intraspinally administered opiate and alpha 2-adrenergic agonists in chronic neuropathic pain. Stereotact Funct Neurosurg. 1994;62(1-4):279-289.
Logtenberg SJ, Kleefstra N, Houweling ST, et al. Improved glycemic control with intraperitoneal versus subcutaneous insulin in type 1 diabetes: A randomized controlled trial. Diabetes Care. 2009;32(8):1372-1377.
Lorenz M, Staib-Sebler E, Koch B, et al. The value of postoperative hepatic arterial infusion following curative liver resection. Anticancer Res. 1997;17(5B):3825-3833.
Maneyapanda MB, McCormick ZL, Marciniak C, Reger C. Long-term dosing of intrathecal baclofen in the treatment of spasticity after acquired brain injury. PM R. 2017;9(6):556-562.
Marcus AO, Fernandez MP. Insulin pump therapy. Acceptable alternative to injection therapy. Postgrad Med. 1996;99(3):1-7.
Martin JK, O'Connell MJ, Wieand HS, et al. Intra-arterial floxuridine vs systemic fluorouracil for hepatic metastases from colorectal cancer. Arch Surg. 1990;125(8):1022-1027.
McAuley SA, Lee MH, Paldus B, et al for the Australian JDRF Closed-Loop Research Group. Six months of hybrid closed-loop versus manual insulin delivery with fingerprick blood glucose monitoring in adults with type 1 diabetes: A randomized, controlled trial. Diabetes Care 2020;43:3024-3033.
McCulloch DK. General principles of insulin therapy in diabetes mellitus. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2012a.
McCulloch DK. Insulin therapy in adults with type 1 diabetes mellitus. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed December 2012b.
McCulloch DK. Insulin therapy in type 2 diabetes mellitus. UpToDate [online serial]. Waltham, MA: UpToDate; December 2012c.
Medtronic MiniMed. The Paradigm Wireless Diabetes Management System. Northridge, CA: Medtronic MiniMed; 2004. Available at: http://www.minimed.com/patientfam/pf_ipt_paradigm_pump_overview.shtml. Accessed February 24, 2004.
Mercadante S, Portenoy RK. Opioid poorly-responsive cancer pain. Part 3. Clinical strategies to improve opioid responsiveness. J Pain Symptom Manage. 2001;21(4):338-354.
Mercadante S. Neuraxial techniques for cancer pain: An opinion about unresolved therapeutic dilemmas. Reg Anesth Pain Med. 1999;24(1):74-83.
Misso ML, O'Connor DA, Egberts KJ, Shaw J. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2005;(1):CD005103.
Mukhopadhyay A, Farrell T, Fraser RB, Ola B. Continuous subcutaneous insulin infusion vs intensive conventional insulin therapy in pregnant diabetic women: A systematic review and metaanalysis of randomized, controlled trials. Am J Obstet Gynecol. 2007;197(5):447-456.
National Comprehensive Cancer Network (NCCN). Adult cancer pain. NCCN Clinical Practice Guidelines in Oncology, Version 1.2018. NCCN: Fort Washington, PA: NCCN; 2018.
National Heritage Insurance Company (NHIC). External infusion pumps. Local Coverage Determination No. L5044. Durable Medical Equipment Medicare Administrative Contractor (DME MAC) Jurisdiction A. Chico, CA: NHIC; revised March 1, 2008.
National Institute for Clinical Excellence (NICE). Guidance on the use of continuous subcutaneous insulin infusion for diabetes. Technology Appraisal Guidance No. 57. London, UK: NICE; February 2003.
National Institute for Health and Clinical Excellence (NICE). Continuous subcutaneous insulin infusion for the treatment of diabetes mellitus. Review of technology appraisal guidance 57. NICE Technology Appraisal Guidance 151. London, UK: NICE; July 2008.
No authors listed. Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. Meta-analysis Group in Cancer. J Natl Cancer Inst. 1996;88(5):252-258.
Oduneye F. Insulin pumps, conventional and intensive multiple injection insulin therapy for type 1 diabetes mellitus. Bazian Ltd., eds. London, UK: Wessex Institute for Health Research and Development, University of Southampton; 2002.
Okada S. Chemotherapy in hepatocellular carcinoma. Hepatogastroenterology. 1998;45 (Suppl 3):1259-1263.
Olvey EL, Armstrong EP, Grizzle AJ. Contemporary pharmacologic treatments for spasticity of the upper limb after stroke: A systematic review. Clin Ther. 2010;32(14):2282-303.
Ontario Ministry of Health and Long-Term Care, Medical Advisory Secretariat. Intrathecal baclofen pump for spasticity. Health Technology Review. Toronto, ON: Ontario Ministry of Health and Long-Term Care; May 2005.
Parkner T, Laursen T, Vestergaard ET, et al. Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long-acting insulin in Type 2 diabetes. Diabet Med. 2008;25(5):585-591.
Patterson MC. Management and prognosis of cerebral palsy. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed October 2018.
Pérez-Arredondo A, Cázares-Ramírez E, Carrillo-Mora P, et al. Baclofen in the therapeutic of sequele of traumatic brain injury: Spasticity. Clin Neuropharmacol. 2016;39(6):311-319.
Pickup JC, Renard E. Long-acting insulin analogs versus insulin pump therapy for the treatment of type 1 and type 2 diabetes. Diabetes Care. 2008;31 Suppl 2:S140-145.
Pickup JC. Management of diabetes mellitus: Is the pump mightier than the pen? Nat Rev Endocrinol. 2012;8(7):425-433.
Piramal Critical Care, Inc. Gablofen (baclofen injection), for intrathecal use. Prescribing Information. Bethlehem, PA: Piramal Critical Care; revised October 2020.
Portas M, Marty JY, Buttin C, et al. Refractory pain in children with cancer: Role of peridural analgesia. Arch Pediatr. 1998;5(8):851-860.
Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: Report of 38 cases. Pain. 1986;25:171-186.
Raskin P, Bode BW, Marks JB, et al. Continuous subcutaneous insulin infusion and multiple daily injection therapy are equally effective in type 2 diabetes: A randomized, parallel-group, 24-week study. Diabetes Care. 2003;26(9):2598-2603.
Reichard P. Are there any glycemic thresholds for the serious microvascular diabetic complications? J Diab Comp. 1995;9:25-30.
Rice JE, O'Donnell ME. Intrathecal baclofen for treating spasticity in children with cerebral palsy (Protocol for Cochrane Review). Cochrane Database Syst Rev. 2004;(1):CD004552.
Robert G. Implantable infusion devices (IIPs) for long-term pain management. DEC Report 55. Southampton, UK: Wessex Institute for Health Research and Development (WIHRD); 1996.
Roberts DJ, Rees D, Howard J, et al. Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia. Cochrane Database Syst Rev. 2005;(4):CD004450.
Rodbard HW, Blonde L, Braithwaite SS, et al.; AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13 Suppl 1:1-68.
Rodriguez Lopez MJ, de la Torre Liebanas M, Sanchez-Guijo Bernal JJ, et al. Treatment of chronic pain of oncologic origin with epidural or intrathecal morphine administered by continuous or programmable flow implanted pumps. Rev Esp Anestesiol Reanim. 1990;37(6):339-345.
Rosenfeld CR, Bohannon NJ, Bode B, et al. TheV-Go insulin delivery device used in clinical practice: Patient perception and retrospective analysis of glycemic control. Endocr Pract. 2012;18(5):660-667.
Rougier P, Laplanche A, Huguier M, et al. Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: Long term results of a prospective randomized trial. J Clin Oncol. 1992;10(7):1112-1118.
Rougier P. Are there indications for intraarterial hepatic chemotherapy or isolated liver perfusion? The case of liver metastases from colorectal cancer. Recent Results Cancer Res. 1998;147:3-12.
Sakai Y, Izumi N, Tazawa J, et al. Treatment for advanced hepatocellular carcinoma by transarterial chemotherapy using reservoirs or one-shot arterial chemotherapy. J Chemother. 1997;9(5):347-351.
Sampson FC, Hayward A, Evans G, et al. The effectiveness of intrathecal baclofen in the management of patients with severe spasticity. InterTASC Report No. 06/2000. Sheffield, UK: Trent Institute for Health Services Research, Universities of Leicester, Nottingham and Sheffield; 2000.
Saol Therapeutics, Inc. Lioresal intrathecal (baclofen injection). Prescribing Information. Roswell, GA: Saol Therapeutics; revised January 2019.
Saudek CD, Duckworth WC, Giobbie-Hurder A, et al. Implantable insulin pump vs multiple-dose insulin for non-insulin-dependent diabetes mellitus: A randomized clinical trial. Department of Veterans Affairs Implantable Insulin Pump Study Group. JAMA. 1996;276(16):1322-1327.
Saulino M. Simultaneous treatment of intractable pain and spasticity: Observations of combined intrathecal baclofen-morphine therapy over a 10-year clinical experience. Eur J Phys Rehabil Med. 2012;48(1):39-45.
Schiess MC, Oh IJ, Stimming EF, et al. Prospective 12-month study of intrathecal baclofen therapy for poststroke spastic upper and lower extremity motor control and functional improvement. Neuromodulation. 2011;14(1):38-45; discussion 45.
Schultz RJ, Glaze DG. Rett syndrome: Treatment and prognosis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed October 2018.
Schwartzberg RS, Reuss BL, Rust R, et al. Efficacy of continuous subacromial bupivacaine infusion for pain control after arthroscopic rotator cuff repair. J Shoulder Elbow Surg. 2013;22(10):1320-1324.
Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev. 2003;(4):CD001332.
Sherr JL, Heinemann L, Fleming GA, et al. Automated insulin delivery: Benefits, challenges, and recommendations. A Consensus Report of the Joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association. Diabetologia. 2023;66(1):3-22.
Shilt JS, Lai LP, Cabrera MN, et al. The impact of intrathecal baclofen on the natural history of scoliosis in cerebral palsy. J Pediatr Orthop. 2008;28(6):684-687.
Simpson B, Middleton P, Maddern G. Implantable spinal infusion devices for chronic pain and spasticity: A accelerated systematic review. ASERNIP-S Report No. 42. North Adelaide, SA: Royal Australasian College of Surgeons, Australian Safety and Efficacy Register of New Interventional Procedures (ASERNIP) - Surgical; 2003.
Soga K, Nomoto M, Ichida T, et al. Clinical evaluation of transcatheter arterial embolization and one-shot chemotherapy in hepatocellular carcinoma. Hepatogastroenterology. 1988;35(3):116-120.
Taricco M, Adone R, Pagliacci C, Telaro E. Pharmacological interventions for spasticity following spinal cord injury. Cochrane Database Syst Rev. 2000;(2):CD001131.
The Diabetes Control and Complications Trial Research Group. Implementation of treatment protocols in the Diabetes Control and Complications Trial. Diabetes Care. 1995;18(3):361-376.
The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986.
Toma O, Persoons B, Pogatzki-Zahn E, et al; PROSPECT Working Group collaborators. PROSPECT guideline for rotator cuff repair surgery: Systematic review and procedure-specific postoperative pain management recommendations. Anaesthesia. 2019;74(10):1320-1331.
Turk DC, Wilson HD, Cahana A, et al. Treatment of chronic non-cancer pain. Lancet. 2011;377(9784):2226-2235.
U.S. Department of Health and Human Services, Health Care Financing Administration (HCFA). Infusion pumps. Medicare Coverage Issues Manual §60-14. HCFA Pub. 6. Baltimore, MD: HCFA; 2000.
U.S. Department of Health and Human Services, Health Care Financing Administration (HCFA). Continuous subcutaneous insulin infusion pump. Decision Memorandum. Issue # CAG-00041. Baltimore, MD: HCFA; August 26, 1999.
U.S. Department of Health and Human Services, Health Care Financing Administration (HCFA). Medicare will cover insulin pumps for beneficiaries. Press Release. Baltimore, MD: HCFA; September 24, 1999. Available at: http://www.hcfa.gov/news/pr1999/pr990924.htm. Accessed September 28, 1999.
U.S. Food and Drug Administration (FDA). Center for Devices and Radiological Health (CDRH). Omnipod GO Insulin Delivery Device. 510(k) no. K223372. Silver Spring, MD: FDA; March 10, 2023.
U.S. Food and Drug Administration (FDA). FDA clears new insulin pump and algorithm-based software to support enhanced automatic insulin delivery. FDA News Release. Silver Spring, MD: FDA; May 19, 2023.
U.S. Food and Drug Administration (FDA). What is the pancreas? What is an artificial pancreas device system? Silver Spring, MD: FDA; August 30, 2018.
Urabe T, Kaneko S, Matsushita E, et al. Clinical pilot study of an intrahepatic arterial chemotherapy with methotrexate, 5-fluorouracil, cisplatin and subcutaneous interferon-alpha-2b for patients with locally advanced hepatocellular carcinoma. Oncology. 1998;55(1):39-47.
Vague P, Lassmann-Vague V, Belicar P, Alessis C. The implantable insulin pump in the treatment of diabetes. Hopes and reality? Bull Acad Natl Med. 1996 ;180(4):831-841; discussion 841-843.
Valentino L, Pillay KV, Walker J. Managing chronic nonmalignant pain with continuous intrathecal morphine. J Neurosci Nurs. 1998;30(4):233-239, 243-244.
Villanueva E, Anderson J. Intrathecal baclofen for spasticity. Evidence Centre Report. Clayton, VIC: Monash Institute of Public Health & Health Services Research, Centre for Clinical Effectiveness (CCE); 2000.
Wallace MS, Rauck RL, Deer T. Ziconotide combination intrathecal therapy: Rationale and evidence. Clin J Pain. 2010;26(7):635-644.
Wasiak J. Can clonidine be used in effectively in epidural and intrathecal catheters? Evidence Centre Report. Clayton, VIC: Monash Institute of Public Health & Health Services Research, Centre for Clinical Effectiveness; March 10, 2000.
Wilkes D. Programmable intrathecal pumps for the management of chronic pain: Recommendations for improved efficiency. J Pain Res. 2014;7:571-577.
Williams JE, Louw G, Towlerton G. Intrathecal pumps for giving opioids in chronic pain: A systematic review. Health Technol Assess. 2000;4(32):1-65.
Winkelmuller M, Winkelmuller W. Long-term effects of continuous intrathecal opioid treatment in chronic pain of nonmalignant etiology. J Neurosurg. 1996;85(3):458-467.
Winter A, Lintner M, Knezevich E. V-Go Insulin Delivery System versus multiple daily insulin injections for patients with uncontrolled type 2 diabetes mellitus. J Diabetes Sci Technol. 2015;9(5):1111-1116.
Xing F, Yong RJ, Kaye AD, Urman RD. Intrathecal drug delivery and spinal cord stimulation for the treatment of cancer pain. Curr Pain Headache Rep. 2018;22(2):11.
Yoshida GM, Nelson RW, Capen DA, et al. Evaluation of continuous intraspinal narcotic analgesia for chronic pain from benign causes. Am J Orthop. 1996;25(10):693-694.
Zu Y, Zhang Y, Zhao X, et al. Preparation and characterization of chitosan-polyvinyl alcohol blend hydrogels for the controlled release of nano-insulin. Int J Biol Macromol. 2012;50(1):82-87.

Last Review 11/12/2024

Effective: 05/28/1997

Next Review: 05/22/2025
Review History
Definitions

Infusion Pumps

Table Of Contents

Policy

Scope of Policy

Medical Necessity

Intrathecal pump for baclofen (e.g. Gablofen, Lioresal) therapy

Anti-spasmodic drugs

Drugs for the treatment of chronic intractable pain

Intrahepatic chemotherapy infusion for liver metastases from colorectal cancer

Contraindications to implantable infusion pumps

External infusion pumps

External insulin infusion pumps for diabetes

Supplies and drugs used with implantable or external infusion pumps

Replacement pumps

Artificial pancreas devices / Automated insulin delivery system

Experimental, Investigational, or Unproven

Related Policies

CPT Codes / HCPCS Codes / ICD-10 Codes

Implantable Infusion Pumps:

CPT codes covered if selection criteria are met:

HCPCS codes covered if selection criteria are met:

HCPCS codes not covered for indications listed in the CPB:

ICD-10 codes covered if selection criteria are met (not all inclusive):

ICD-10 codes not covered for indications listed in the CPB:

External Infusion Pumps: