Rapid-acting insulin may be given via intravenous, subcutaneous, and insulin pump.
Individualize dose based on route of administration, patient’s metabolic needs, blood glucose monitoring results, and glycemic control goal. It is imperative that dosing is individualized and adjusted based on blood glucose determinations; see Precautions. Several protocols have been published. Review institution-specific protocol if available.
Glycemic control in hospitalized patient (unlabeled):
Rapid-acting insulins have been used for glycemic control via infusion as an alternative to human regular insulin, although subcutaneous use is more common.
Diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) (unlabeled):
A fixed rate of insulin infusion (0.05-0.1 unit/kg/h) is suggested with hourly glucose and every 2 to 4 hours electrolyte monitoring and systematic fluid resuscitation per hospital protocol. Fluid resuscitation (500-1000 mL/h with a crystalloid solution) will also lower blood glucose. An insulin bolus dose is optional 0.1 unit/kg but does not improve time to goal and is generally not advised unless there is a delay to insulin infusion initiation. The goal in DKA is to close the anion gap and raise bicarbonate/normalize pH while reducing glucose (initially decline 50-70 mg/dL/h) and preventing hypoglycemia. Targeting normoglycemia is not necessary in the first 24 to 48 hours, rather target 150 to 200 mg/dL to avoid relative hypoglycemia. The goal in HHS is to replace fluid and normalize electrolytes. Insulin is added when glucose stops declining with those therapies. A fixed rate of insulin 0.1 unit/kg/h is used, and dextrose is initiated when blood glucose is <250 mg/dL.
Potassium should be monitored and replaced as needed to maintain a level of 4 to 5.5 mmol/L. Delay insulin until potassium replacement is initiated if initial potassium is <3.3 mmol/L in DKA/HHS. Long-acting insulin may be continued per home dose.
For DKA a dextrose (5%-10%) infusion is initiated at 100 to 125 mL/h when the blood glucose is <250 mg/dL as a single infusion (one bag) or a two-bag method or when glucose is <300 mg/dL in HHS. The insulin rate may be reduced to 0.05 unit/kg/h if dextrose is unable to prevent glucose from falling.
Insulin is continued in DKA until the anion gap has closed and pH >7.3 and the patient is able to eat or drink. At that point, insulin may be transitioned to a subcutaneous regimen (basal/prandial/correction) with infusion continued for 2 to 4 hours after basal insulin dose (or resumed on insulin pump). If unable to eat/drink, a titrated dose insulin infusion may be used per hospital protocol.
Euglycemic DKA (e.g. with sodium-glucose cotransporter [SGLT] inhibitors) is treated the same as DKA with hyperglycemia, except that 10% glucose infusion is initiated immediately with insulin. If glucose falls despite 10% dextrose infusion, lower insulin infusion rate to 0.05 unit/kg/hr.
Insulin/fluids/dextrose is continued in HHS to maintain glucose 250 to 300 mg/dL until the patient is fluid resuscitated/hyperosmolarity is resolved and can eat or drink.
Mild to moderate DKA may be managed with frequent doses of rapid-acting insulin in some settings.
Hyperkalemia (unlabeled):
Insulin may be used in patients with or without diabetes mellitus to treat hyperkalemia in conjunction with 25 to 50 g dextrose. Insulin effect may persist longer than dextrose bolus and hypoglycemia is a risk with this regimen. Frequent blood glucose monitoring (every 1–2 hours for 4–6 hours) should be initiated. Weight <50 kg, renal insufficiency, female gender, age >60 years, or glucose <150 mg/dL before treatment are associated with increased risk of hypoglycemia. An insulin dose of 5 units with 25 to 50 g dextrose is associated with less hypoglycemia than 10 units with comparable effect on potassium.
Management of DKA follows the same pattern as adults with weight-based fluid replacement (initial bolus average 70 mL/kg, range 30–100 mL/kg) followed by ongoing replacement over the next 24 to 48 hours. Insulin infusion starts at 0.1 unit/kg/h after 1 hour of fluid resuscitation, although 0.05 unit/kg/h may be preferred in children <6 years or others with greater insulin sensitivity until resolution of ketoacidosis. An insulin bolus is not used at start of therapy. Dextrose is added when glucose is <250 mg/dL like adults using a one- or two-bag method with 10% dextrose. The process for electrolyte monitoring and replacement is comparable to adults. Transition to a basal/prandial/correction subcutaneous insulin regimen is also similar to adults when DKA is resolved, and child is eating/drinking normally.
Hyperosmolar hyperglycemic state (unlabeled):
The frequency of HHS related to uncontrolled diabetes in children is increasing. Fluid resuscitation is initiated, and insulin is added once glucose is declining by <50 mg/dL/hr with fluid alone. Insulin is administered at 0.025 to 0.05 unit/kg/hr initially and may be titrated to maintain a decline in glucose of 50 to 75 mg/dL/hr. An insulin bolus is not recommended.
Administer 0.1 unit/kg of insulin with 400 mg/kg of glucose; usual ratio of combination therapy of insulin to glucose is 1 unit of insulin for every 4 g of glucose.
Insulin infusion doses should be adjusted based on local protocol with frequent (every 1–2 hour) glucose checks. Changes in metabolic stress levels, nutrition, and medications such as catecholamines or corticosteroids are important variables.
See comments under Usual Dose. Dose requirements may be reduced in patients with renal or hepatic impairment. Dose adjustment may be indicated if it is necessary to change from one insulin product to another. Dose adjustment may be needed when coadministered with certain drugs; see Drug/Lab Interactions.
Insulin aspart 0.5 to 1 unit/mL using polypropylene bags, stable in 0.9% NaCl; Lispro 0.1 to 1 unit/mL in 0.9% NaCl; Lispro-aabc 1 unit/mL in normal saline (NS) or dextrose 5% in water (D5W; using 100 unit/mL solution); Glulisine 0.05–1 unit/mL in 0.9% NaCl using polyvinyl chloride bags.
Use only if insulin solution is clear.
100 units of insulin (1 mL) to 100 mL of NS will yield a solution with a final concentration of 1 unit/mL.
Store unopened vials in refrigerator. Vials may be stored at room temperature up to 25° C (77° F) for up to 30 days in original carton. Do not place vial back in refrigerator. Discard after 30 days if stored at room temperature. Do not freeze and do not use if it has been frozen. Do not shake. Discard any unused portion. Protect from sunlight and freezing.
Insulin is adsorbed to the material of the infusion bag and IV tubing. Prime new tubing and flush an additional 20 mL. The actual amount of insulin delivered is substantially less than apparent. If Y-sited into another solution, chose a site closest to the patient.
Prepared as indicated in dilution are stable for: Aspart 24 hours at room temperature; Lispro-Humalog 48 hours under refrigeration (36°F-46° F) and then may be used at room temperature for another 48 hours; Lispro-Admelog stable for 24 hours under refrigeration or up to 4 hours at room temperature; Lispro-aabc-Lyumjev 100 unit/mL solution stable for up to 4 days under refrigeration or for up to 12 hours at room temperature; Glulisine stable for 48 hours at room temperature.
Do not shake. Discard any unused portion.
Do not add supplementary medication or additives.
Other sources suggest specific compatibilities for insulin dependence on concentration and manufacturer; consult a pharmacist.
Administer insulin infusion in conjunction with close monitoring of glucose (every 1–2 hours) and a validated protocol.
A hormone produced by the pancreas that controls the storage and metabolism of carbohydrates, proteins, and fat. Responsible for regulation of glucose metabolism. Binds to insulin receptors on muscle and fat cells and lowers blood glucose by facilitating cellular uptake of glucose and inhibiting hepatic glucose production. Also inhibits lipolysis, proteolysis, and gluconeogenesis and enhances protein synthesis and conversion of excess glucose into fat. Rapidly and widely distributed. The glucose-lowering activities of regular insulin, insulin aspart, insulin glulisine, and insulin lispro are equipotent when administered by the IV route. The average elimination half-life is dose dependent and ranges from 0.25 to 1 hour, depending on dose and product.
Treatment of patients with diabetes mellitus to improve glycemic control as an alternative to human regular insulin via infusion or for subcutaneous correction/prandial doses or in a continuous subcutaneous pump. Proper medical supervision is required to prevent hypoglycemia and hypokalemia.
Contraindicated during episodes of hypoglycemia and in patients hypersensitive to regular human insulin, insulin aspart, insulin glulisine, insulin lispro, or one of the excipients of any of these products.
Rapid-acting insulin: Concomitant oral antidiabetic treatment may need to be adjusted. Hypoglycemia and hypokalemia are potential side effects of insulin therapy. Use caution in patients in whom these side effects may be clinically relevant (e.g., patients who are fasting, have autonomic neuropathy, are using potassium-lowering drugs [e.g., diuretics], or are taking drugs sensitive to serum potassium levels [e.g., digoxin]). Severe hypoglycemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or death. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions such as long-standing diabetes, diabetic nerve disease, and the use of medications such as beta-blockers. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Use with caution in patients with renal or hepatic impairment; may be at a higher risk of hypoglycemia; see Dose Adjustments. Frequent monitoring may be required. Insulin requirements may be altered during illness or stress. Anti-insulin antibodies have been reported. Clinical significance of anti-insulin antibodies is unknown. Systemic hypersensitivity reactions have been reported. May include hypotension, pruritus, rash, shortness of breath, sweating, tachycardia, and/or wheezing.
Anaphylaxis has occurred. See Drug/Lab Interactions.
Insulin potency may be reduced by ≥20% and possibly ≥80% via the glass or plastic infusion container and plastic IV tubing before reaching the venous system when given by infusion. Use of a syringe pump (instead of infusion containers) reduces surface area for adsorption.
Depending on indication for use, response to insulin may be measured by blood glucose, blood pH, ketones, blood urea nitrogen, serum creatinine, fluid status, sodium, potassium, chloride, osmolality, anion gap, and mental status. Monitor patient carefully in all situations. Glucose and potassium levels must be monitored closely during IV administration of insulin to avoid potentially fatal hypoglycemia and hypokalemia. See Drug/Lab Interactions.
Monitor blood glucose as directed. Adhere to consistent diet and exercise programs. Avoid alcohol. Review medications or changes in medication regimen with a health care professional. Review signs and symptoms of hypoglycemia and hyperglycemia with a health care professional. Be familiar with the treatment for each. Insulin requirements may change with onset of illness. Monitor glucose carefully and adjust insulin therapy as required.
Insulin therapy is the preferred treatment of type 1 and 2 diabetes during pregnancy.
Poorly controlled diabetes in pregnancy increases maternal risk for DKA, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Monitor carefully; insulin requirements may change at different stages of pregnancy and may drop immediately postpartum. Use caution in breastfeeding. Breast-feeding may decrease insulin requirements. Inadequately controlled maternal blood glucose late in pregnancy may cause increased insulin production in the fetus. Monitor and treat neonatal hypoglycemia postpartum.
No overall differences in safety or effectiveness were observed between elderly and younger patients. Elderly patients may be at increased risk of hypoglycemia due to comorbid conditions and concomitantly administered medications; see Dose Adjustments and Drug/Lab Interactions. Initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia.
Hypoglycemic effect may be potentiated by angiotention-converting enzyme inhibitors, anabolic steroids, angiotensin II receptor-blocking agents, disopyramide, fluoxetine, fibrates, guanethidine, monoamine oxidase inhibitors, oral antidiabetic agents, pentoxifylline, salicylates, sulfonamides, and many others. Dose adjustment and increased frequency of glucose monitoring may be required with concomitant use. Drugs that may reduce blood glucose-lowering effects include atypical antipsychotic medications, corticosteroids, danazol, diuretics, estrogen, glucagon, isoniazid (INH), niacin, oral contraceptives, phenothiazine derivatives, protease inhibitors, somatropin, sympathomimetic agents, and thyroid preparations. Dose adjustment and increased frequency of glucose monitoring may be required with concomitant use. Alcohol, beta-adrenergic blockers including via ophthalmic route, clonidine, and lithium may either potentiate or inhibit the blood glucose-lowering effect of insulin. Dose adjustment and increased frequency of glucose monitoring may be required with concomitant use. Will affect serum potassium levels; use caution in patients taking digoxin. Octreotide may alter insulin, glucagon, and growth hormone secretion, resulting in hypoglycemia or hyperglycemia. Monitor serum glucose and adjust insulin dose as indicated. Pentamidine is toxic to the beta cells of the pancreas. Patients may develop hypoglycemia initially as insulin is released. This may be followed by hypoinsulinemia and hyperglycemia with continued pentamidine therapy. Signs and symptoms of hypoglycemia may be masked in the presence of beta-blockers, clonidine, guanethidine, and reserpine. Increased frequency of glucose monitoring may be required with concomitant use. Thiazolidinediones (TZDs) can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients receiving concomitant therapy should be monitored for signs and symptoms of heart failure. Dose reduction or discontinuation of the TZD may be indicated if heart failure develops.
The most common adverse reactions with IV administration of insulin include hypoglycemia (<70 mg/dL), hypokalemia, and rare hypersensitivity reactions, pruritus, and rash. Other commonly reported reactions are injection site reactions, peripheral edema, and weight gain. Additional side effects reported in studies include abdominal pain, arthralgia, asthenia, back pain, chest pain, diarrhea, dysmenorrhea, fever, headache, hypertension, hyporeflexia, influenza, myalgia, nasopharyngitis, nausea, onychomycosis, pain, sensory disturbances, sinusitis, skin disorders, upper respiratory infections, and urinary tract infections. Severe hypersensitivity reactions may include anaphylaxis, angioedema, bronchospasm, generalized skin reactions, rash, hypotension, and shock.
Severe hypoglycemia and hypokalemia. Severe hypoglycemia may result in coma, seizures, or neurologic impairment. Severe, untreated hypokalemia may lead to respiratory paralysis, ventricular arrhythmia, and death.
Discontinue insulin immediately and notify physician of adverse reactions or hypoglycemia. Follow the hospital hypoglycemia management protocol. Glucagon 1 to 2 mg intramuscularly or subcutaneously is the specific antidote for insulin overdose. It may be supplemented by 15 to 20 g dextrose IV and recheck glucose in 5 to 15 minutes. Oral carbohydrates such as glucose tablets or gel or orange juice may be sufficient to combat early symptoms of mild hypoglycemia. A titrated dextrose dose may be calculated to avoid overcorrection during insulin infusion [dextrose g = (100-glucose mg/dL) x 0.2]. Replace potassium as indicated. Resume insulin at a modified dose. Hypersensitivity reactions usually respond to symptomatic treatment.