Bedside Snapshot

Use It For
DKA and HHS; severe hyperkalemia (with dextrose); beta-blocker or calcium channel blocker shock (high-dose insulin); persistent ICU hyperglycemia ≥180 mg/dL
Adult Dose
  • DKA: 0.1 units/kg/hr IV; HHS: 0.05 units/kg/hr IV
  • Hyperkalemia: 10 units IV with dextrose 25 g (D10 50 mL/hr for 5 hr if glucose <126 mg/dL); arrest 10 units with D50 50 g
  • BB/CCB shock: 1 unit/kg IV, then 1–10 units/kg/hr
Pediatric Dose
DKA: 0.05–0.1 units/kg/hr IV, no bolus, from 1 hr after fluids. Hyperkalemia arrest: 0.1 units/kg IV over 15–30 min (max 10 units) with D10 5 mL/kg; non-arrest: none established. BB/CCB shock: adult per-kg dose
Onset / Duration
IV bolus: 10–15 min / 2–6 hr (T½ about 20 min). K⁺ shift: within 15 min, peak 30–60 min, about 2 hr. Subcut regular: about 30 min / about 8 hr
Do Not Give / Hold If
Glucose <70 mg/dL (treat first); DKA/HHS with K⁺ <3.5 mEq/L (replace K⁺ first); insulin hypersensitivity
Watch For
Hypoglycemia (glucose every 1–2 hr on drips; every 20 min in the first HIET hour; 30–360 min after a hyperkalemia dose, at least 6 hr); hypokalemia (K⁺ every 4 hr in DKA)
Reversal / Rescue
No antidote: stop or reduce insulin. Hypoglycemia: dextrose 10–25 g IV (child 0.5–1 g/kg, max 25 g) or glucagon 1 mg IM (0.5 mg if <25 kg); recheck in 15 min
Must Remember
Units, not mL: draw from a U-100 vial with an insulin syringe, never write “U”, and double-check every bolus, bag and rate. In DKA, add dextrose rather than stopping insulin

Indications

ED / ICU / Transport

  • Diabetic ketoacidosis (DKA): Use an IV regular insulin infusion for moderate or severe DKA in adults and children. Subcut rapid-acting insulin is only for uncomplicated mild or moderate adult DKA.
  • Euglycemic DKA: DKA with glucose <200 mg/dL, seen with SGLT2 inhibitors, pregnancy, poor intake, alcohol or liver failure. Give dextrose with the insulin from the start.
  • Hyperosmolar hyperglycemic state (HHS) and mixed DKA/HHS: Run a lower-rate IV infusion once fluid resuscitation has started.
  • Severe hyperkalemia: A temporary K⁺ shift into cells, given with dextrose. IV calcium comes first for ECG changes, and K⁺ removal runs alongside (off-label).
  • Beta-blocker or calcium channel blocker poisoning with shock: Use high-dose insulin euglycemia therapy (HIET) as an inotrope, with or after vasopressors (off-label).
  • Persistent hyperglycemia in critical illness: Start an IV infusion when glucose stays at or above 180 mg/dL. Aim for 140–180 mg/dL.

Other Uses

  • Hospital glycemic management: Scheduled subcut basal-bolus insulin, including the switch off an IV infusion.

Dosing & Administration

These are the E3 house doses. Where a regimen differs from the FDA label, the row says so.

Available Forms

  • Regular insulin U-100 vials: 100 units/mL (Humulin R 10 mL and 3 mL; Novolin R 10 mL). IV boluses and compounded infusions use this form and no other.
  • Premixed bag: 100 units in 100 mL 0.9% sodium chloride (1 unit/mL; Myxredlin), single-dose. Often already running at transfer.
  • Compounded infusions: Humulin R 0.1–1 unit/mL in 0.9% sodium chloride; Novolin R 0.05–1 unit/mL in polypropylene bags
  • Subcut only: Rapid-acting analogs, basal insulins, pens and U-500. Never draw an IV dose from any of them.
High-Alert Medication: Four ways this goes wrong: “U” gets misread as 0. mL gets confused with units. U-500 or a pen gets drawn up. The bag concentration is wrong. Draw from a U-100 vial with an insulin syringe. Write “units” in full. Have a second clinician check the dose, the bag and the pump rate.

Adult Dosing

IndicationDose & RouteRepeat / MaxNotes
DKA (moderate or severe)
0.1 units/kg/hr IV infusion; 0.1 units/kg IV or IM (off-label) bolus only if IV access is delayed
Glucose <250 mg/dL: add D5–D10 and reduce to 0.05 units/kg/hr; hold glucose about 200 mg/dL: no fixed max
High-alert Do not start until K⁺ is above 3.5 mEq/L. Continue until ketoacidosis resolves, not until glucose normalizes
DKA (mild or moderate, uncomplicated)
Subcut rapid-acting analog every 1–2 hr per protocol
Per protocol: no fixed max
High-alert Not for severe DKA, HHS or poor perfusion
Euglycemic DKA (glucose <200 mg/dL)
0.1 units/kg/hr IV with D5–D10 started with 0.9% saline
Titrate dextrose to keep insulin running: no fixed max
High-alert Stop SGLT2 inhibitors on admission
HHS
0.05 units/kg/hr IV; 0.1 units/kg/hr for mixed DKA/HHS (BHB ≥3 mmol/L, pH <7.30 or HCO₃⁻ <18 mEq/L)
Glucose fall ≤90–120 mg/dL/hr; osmolality fall 3–8 mOsm/kg/hr: no fixed max
High-alert Fluids first; some protocols hold insulin until glucose falls with fluids alone
Transition to subcut insulin
Basal insulin subcut 1–2 hr before stopping the infusion; insulin-naive estimate 0.5–0.6 units/kg/day
About 0.3 units/kg/day with kidney failure or frailty
High-alert Basal 0.15–0.3 units/kg may start during the infusion
Hyperkalemia (K⁺ ≥6.5 mEq/L recommended; 6–6.4 suggested)
Regular insulin 10 units IV mixed with dextrose 25 g (50 mL D50), over 5–15 min into a large vein. Arrest: 10 units IV over 15–30 min with D50 50 g (AHA 2025 COR 2b; UKKA 2026 gives 25 g)
10 units per dose. Repeat at 2 hr if K⁺ is still 6 mEq/L or higher (consider); if still uncontrolled, call nephrology or critical care
High-alert Pre-dose glucose under 126 mg/dL: add D10 50 mL/hr for 5 hr. Always give dextrose with insulin; glucose alone is not recommended. Not for DKA/HHS. Checks: see Monitoring
Beta-blocker or CCB poisoning with shock (HIET)
1 unit/kg IV bolus, then 1 unit/kg/hr IV infusion
Increase by 1 unit/kg/hr every 20–30 min if no response; max 10 units/kg/hr
High-alert AHA 2025 COR 1 (C-LD) for beta-blocker poisoning with vasopressor-refractory hypotension; COR 1 (B-NR) for CCB. Poison center consult; see HIET Protocol
Persistent ICU hyperglycemia
IV infusion per a validated institutional protocol once glucose is ≥180 mg/dL twice in 24 hr
Target 140–180 mg/dL (110–140 mg/dL in selected patients without hypoglycemia): no fixed max
High-alert Sliding-scale-only regimens are discouraged

Pediatric Dosing

IndicationDose (per kg) & RouteMax Single / Max TotalNotes
DKA
0.05–0.1 units/kg/hr IV infusion, started at least 1 hr after IV fluids; no IV bolus
Until DKA resolves; 0.05 units/kg/hr if pH >7.15 (0.03 under 5 yr, mild DKA): no fixed max
High-alert Add D5 at glucose 250–300 mg/dL (D10–D12.5 if needed). K⁺ <3.5 mEq/L: hold insulin and give IV potassium chloride as an infusion (never IV push), no faster than 0.5 mEq/kg/hr, on a cardiac monitor. If K⁺ is above 5.5 mEq/L, hold K⁺ until urine output is documented
DKA (mild or moderate, no infusion)
Rapid-acting analog 0.15 units/kg subcut every 2 hr, starting 1 hr after fluids
Reduce to 0.1 units/kg every 2 hr if glucose falls >90 mg/dL/hr despite dextrose
High-alert Only with good peripheral circulation
HHS
0.025–0.05 units/kg/hr IV once glucose falls by less than 50 mg/dL/hr with fluids alone
Titrate to a glucose fall of 50–75 mg/dL/hr: no fixed max
High-alert Start earlier in mixed DKA/HHS
Cardiac arrest from suspected hyperkalemia
0.1 units/kg IV over 15–30 min with dextrose 0.5 g/kg (D10 5 mL/kg IV)
Max 10 units per dose
High-alert AHA 2025 Part 10 Table 3. Glucose before the dose, then per pediatric protocol
Beta-blocker or CCB poisoning with shock (HIET)
1 unit/kg IV bolus, then 1 unit/kg/hr (same per-kg dosing as adults)
Increase by 1 unit/kg/hr every 20–30 min; max 10 units/kg/hr
High-alert Glucose under 200 mg/dL first: dextrose 0.5–1 g/kg (D25 2–4 mL/kg)
Non-arrest hyperkalemia: there is no established pediatric dose here.

See weight-based dosing. For pediatric DKA, ISPAD 2022 defines resolution as pH >7.30, HCO₃⁻ >18 mEq/L and BHB <1 mmol/L. The full DKA and HHS pathway is on the Diabetic Ketoacidosis condition page.

HIET Protocol

High-dose insulin euglycemia therapy (HIET) for beta-blocker or calcium channel blocker shock
StepActionTarget / Notes
Before insulin
Glucose under 200 mg/dL: consider D50 50 mL (adult) or D25 2–4 mL/kg (child). Replace K⁺ if under 3 mEq/L
Hypoglycemia and severe hypokalemia corrected first
Infusion
Prepare 1 unit/mL; concentrate (for example 10 units/mL) only as needed to avoid fluid overload, pharmacy-prepared and labeled
Differs from FDA label: Novolin R is labeled for IV infusion at 0.05–1 unit/mL. Dedicated line and pump
Dextrose
Adult: D10 in 0.45% NaCl at 100 mL/hr (age-appropriate rate in children); add D25 or D50 boluses as needed
Target 100–200 mg/dL; beta-blocker poisoning often needs more glucose
Titrate
No hemodynamic response: +1 unit/kg/hr every 20–30 min
Max 10 units/kg/hr. Goal SBP >90, MAP >65 mmHg, HR >50
Monitor
Glucose every 20 min in the first hour and during titration, then hourly. K⁺ hourly during titration, then every 2 hr once stable
Glucose under 100 mg/dL: dextrose bolus or faster infusion. Replace K⁺ if under 3 mEq/L
Wean
Vasopressors usually weaned first, then insulin by 1 unit/kg/hr steps
Dextrose may be needed up to 24 hr after insulin stops; CCB needs can rise as toxicity clears

Continuous Infusion

SettingExample ConcentrationStartTitrateUsual Range / Max
Adult DKA
1 unit/mL (100 units in 100 mL 0.9% NaCl), example (institution-specific)
0.1 units/kg/hr
0.05 units/kg/hr plus dextrose once glucose <250 mg/dL
To resolution of ketoacidosis
Adult HHS
1 unit/mL, example (institution-specific)
0.05 units/kg/hr
Keep glucose fall ≤90–120 mg/dL/hr
Until osmolality <300 mOsm/kg and glucose <250 mg/dL
Pediatric DKA
1 unit/mL (50 units in 50 mL 0.9% NaCl), example (institution-specific)
0.05–0.1 units/kg/hr
Adjust dextrose, not insulin, to hold glucose
To resolution of DKA
ICU hyperglycemia
1 unit/mL, example (institution-specific)
Per protocol
Per protocol; glucose every 1–2 hr
Target 140–180 mg/dL
HIET
1 unit/mL; concentrate (for example 10 units/mL) only as needed to avoid fluid overload, pharmacy-prepared. Differs from FDA label (0.05–1 unit/mL)
1 unit/kg/hr after a 1 unit/kg bolus
+1 unit/kg/hr every 20–30 min
Max 10 units/kg/hr

Preparation & Administration

  • Dilution: Regular insulin only, within the labeled range. Use premixed bags as supplied, with nothing added.
  • Rate: The hyperkalemia dose runs over 5–15 min per UKKA 2026, or 15–30 min in arrest per AHA 2025. Some US protocols push the dextrose rapidly IV. The house rates above apply.
  • Flush / prime: Flush the tubing with insulin solution before starting. Reprime every new set.
  • Line and pump: A peripheral line is adequate for insulin. Put D50 into a large vein. Use a smart pump in units/hr or units/kg/hr from the drug library. Verify concentration at every bag change.
  • IM route (off-label): The U-100 label covers subcut and IV use only. IM is used only for the initial adult DKA bolus, and only when IV access is delayed.
Dosing Notes:
  • Lower dose (5 units): Some US protocols use 5 units or 0.1 units/kg. The meta-analysis of 10 retrospective studies found less hypoglycemia at lower doses and no difference in the K⁺ fall. One single-center retrospective study found 10 units lowered K⁺ further, 0.9 vs 0.63 mmol/L. UKKA 2026 says more study is needed before 5 units can be recommended. This page uses 10 units.
  • Practical: Every adult dose is 10 units. When pre-dose glucose is under 126 mg/dL, manage hypoglycemia with extra dextrose. Add scheduled glucose checks.
  • Arrest dextrose: This differs from UKKA 2026, which gives 25 g. AHA 2025 Table 3 gives 50 g. AHA rates insulin-glucose in hyperkalemic arrest COR 2b and calls its effectiveness not well established.
  • No dextrose omission: There is no sourced glucose cutoff for skipping dextrose. Give the standard 25 g and check glucose closely.

Contraindications & Precautions

Contraindications

  • During an episode of hypoglycemia (treat it first)
  • Hypersensitivity to insulin human or an excipient
  • No other absolute contraindication when insulin is indicated for DKA, HHS, hyperkalemia or BB/CCB shock

Precautions

  • Hypokalemia: every dose pulls K⁺ into cells. Untreated hypokalemia can cause respiratory paralysis, ventricular arrhythmia and death.
  • Kidney or liver impairment, adrenal insufficiency: Slower clearance, less glucose production and a weaker counterregulatory response all raise hypoglycemia risk.
  • Beta-blockers and autonomic neuropathy: The adrenergic warning signs of hypoglycemia may be missing.
  • SGLT2 inhibitors: DKA can show up with a near-normal glucose.
  • Thiazolidinediones: Fluid retention and heart failure, with insulin on board.
  • Older adults, heart failure, dialysis: Use smaller fluid boluses during DKA/HHS. Dextrose loads add volume too.

Hold / Reassess If

  • Glucose <70 mg/dL: stop or reduce insulin and treat
  • DKA/HHS with K⁺ <3.5 mEq/L: hold insulin until K⁺ is above 3.5 mEq/L
  • DKA glucose <250 mg/dL: add dextrose and reduce the rate; do not stop
  • HHS glucose falling faster than 90–120 mg/dL/hr or osmolality faster than 8 mOsm/kg/hr
  • Hyperkalemia in DKA/HHS: follow the DKA/HHS protocol rather than a separate insulin-dextrose dose; IV calcium gluconate for ECG changes
  • HIET K⁺ <3 mEq/L: replace per protocol without stopping insulin; rising oxygen needs or crackles: concentrate insulin and dextrose rather than stopping
Never stop the drip because glucose is normal: In DKA the drip treats the ketosis, not the glucose. When glucose falls, add dextrose and lower the rate. Stop early and the ketoacidosis comes back.

Adverse Effects & Toxicity

Common

  • Hypoglycemia: about 6–20% after insulin for hyperkalemia across the studies UKKA 2026 reviewed (5 or 10 units alike)
  • Hypokalemia during DKA and HHS treatment; hypophosphatemia and hypomagnesemia (DKA, HIET)
  • Subcut use: injection-site reactions, lipodystrophy, localized cutaneous amyloidosis; edema and weight gain with intensified therapy

Serious / Life-Threatening

EffectRecognitionManagement
Clinically significant or severe hypoglycemia
Level 2: glucose <54 mg/dL. Level 3: altered mental or physical status needing assistance, at any glucose value; beta-blockers blunt signs
Stop insulin, give IV dextrose, recheck every 15 min
Severe hypokalemia
K⁺ ≤2.5 mEq/L; weakness, U waves, ventricular ectopy
Hold insulin if K⁺ <3.5 mEq/L in DKA/HHS; IV K⁺ with cardiac monitoring
Cerebral edema
DKA, mostly children: new headache or vomiting after treatment starts, slowing heart rate, falling GCS
Hyperosmolar therapy per protocol, airway support, imaging without delay
Recurrent ketoacidosis
Rising BHB or glucose after the infusion stops
Restart IV insulin; basal insulin at least 1–2 hr before the next stop
Anaphylaxis
Rash, bronchospasm, hypotension
Stop insulin; IM epinephrine; supportive care
Volume overload (HIET)
Crackles, falling SpO₂ with large dextrose volumes
Concentrate insulin and dextrose; central access

Overdose & Toxicity Management

  • Signs: sweating, tremor, confusion, seizure, coma; hypokalemia
  • Immediate: point-of-care glucose; alert patients take oral glucose; others get dextrose 10–25 g IV (child 0.5–1 g/kg, max 25 g)
  • No IV access: glucagon 1 mg IM or subcut (0.5 mg if <25 kg)
  • After recovery: hypoglycemia can recur: start a dextrose infusion plus food, monitor glucose and K⁺, and observe

Monitoring
ParameterWhen / How OftenTarget / Act If
Clinical: glucose (DKA/HHS, ICU infusion)
Every 1–2 hr; more often after rate changes
Glucose <70 mg/dL: stop or reduce and treat; DKA <250 mg/dL: add dextrose, reduce the rate
Laboratory: potassium
Before insulin; 2 hr after starting, then every 4 hr until DKA resolves
K⁺ <3.5 mEq/L: hold insulin and replace; keep 4–5 mEq/L
Laboratory: BHB, pH, HCO₃⁻
Every 4 hr in DKA
Resolved: BHB <0.6 mmol/L and pH ≥7.3 or HCO₃⁻ ≥18 mEq/L. Do not use urine ketones
Laboratory: osmolality, Na⁺, creatinine (HHS)
Every 4 hr
Osmolality falling faster than 8 mOsm/kg/hr or Na⁺ falling more than 10 mEq/L in 24 hr: slow correction. Rising creatinine: reassess fluids and K⁺
Laboratory: phosphate
Every 4 hr until DKA resolves
Replace only for severe hypophosphatemia with weakness or cardiac or respiratory compromise (20–30 mmol potassium phosphate in fluids)
Clinical: neuro checks (DKA)
Hourly, closer in children
Headache, vomiting or falling GCS after treatment starts: treat as cerebral edema
Clinical: hyperkalemia dose
Glucose before the dose, then at 30, 60, 90, 120, 180, 240, 300 and 360 min (at least 6 hr); K⁺ at 1, 2, 4, 6 and 24 hr
Glucose <70 mg/dL: treat and recheck in 15 min. K⁺ still 6 mEq/L or higher at 2 hr, or rebound: repeat per the dosing table; plan K⁺ removal or dialysis
Clinical: high-risk patients after hyperkalemia dose
Continue glucose checks beyond 6 hr at a protocol-set interval
High risk: repeat doses, kidney failure, low body weight, no diabetes, low pre-dose glucose. Lows reported up to about 7.5 hr
Clinical: HIET
Continuous ECG, BP, HR; volume status
Goal SBP >90, MAP >65 mmHg, HR >50; glucose and K⁺ per the HIET table
Infusion safety: pump and bag
Start, bag change, rate change, handoff
Concentration, units/hr and units/kg/hr match the order

Hypoglycemia after insulin for hyperkalemia is most likely when pre-dose glucose is low, kidney function is impaired, body weight is low, the patient is older, the patient has no diabetes, and the dose is 10 units with only 25 g of glucose. Most of it lands in the first 2–3 hr.

Interactions & Compatibility

Clinically Significant Interactions

Drug / ClassEffectWhat To Do
Other K⁺-lowering therapy (albuterol, sodium bicarbonate, furosemide, binders, dialysis)
Additive K⁺ fall (about 1.2 mmol/L with nebulized beta-agonist plus insulin, vs 0.65–1 mEq/L with insulin alone)
Recheck K⁺ at 1–2 hr; avoid overshoot
Beta-blockers, clonidine
Mask tremor and tachycardia of hypoglycemia
Rely on scheduled glucose checks
SGLT2 inhibitors
Euglycemic DKA
Stop on admission; start dextrose with insulin
Sulfonylureas, other antidiabetics, ACE inhibitors, ARBs, octreotide, salicylates, sulfonamides
Increase hypoglycemia risk
Lower doses and more frequent glucose checks
Corticosteroids, sympathomimetics, atypical antipsychotics, diuretics
Raise glucose and insulin needs
Expect higher infusion rates; high-dose steroids can drive refractory ketonemia
Thiazolidinediones (pioglitazone)
Fluid retention, heart failure
Watch for edema and dyspnea

IV Compatibility

  • Humulin R: 0.9% sodium chloride only (0.1–1 unit/mL)
  • Novolin R: 0.9% sodium chloride, 5% dextrose, or 10% dextrose with 40 mmol/L potassium chloride (0.05–1 unit/mL, polypropylene bags)
  • Premixed bags: add no other drugs and do not connect in series
  • Verify with an institutional compatibility resource.

Special Populations
  • Pediatrics: Labeled for children with diabetes. Start DKA infusions at least 1 hr after fluids, with no bolus. Children carry the highest cerebral edema risk. See the Pediatric Dosing table.
  • Pregnancy: Published data have not linked human insulin to birth defects or miscarriage. Uncontrolled diabetes, on the other hand, harms mother and fetus. DKA can happen at glucose <200 mg/dL, so bring in obstetrics early.
  • Lactation: Human insulin passes into milk. No infant effects have been reported. Continue as needed.
  • Older Adults: Frailty raises both hypoglycemia risk (transition estimate about 0.3 units/kg/day) and fluid-overload risk at 250 mL boluses.
  • Renal Impairment: Slower clearance means higher hypoglycemia risk, so check glucose more often. Dialysis patients have the highest hypoglycemia rates after insulin for hyperkalemia. Extend the glucose checks.
  • Hepatic Impairment: The liver is the main clearance organ. Liver failure can cause euglycemic DKA.
  • Obesity / Dosing Weight: Infusions are weight-based. Whether actual or adjusted weight is used varies by protocol. In obese subjects, the subcut peak stretched to about 3 hr and the half-life to about 3.6 hr (Humulin R label).
  • SGLT2 Inhibitor Users: Suspect DKA even with near-normal glucose. Restarting after DKA is not routinely recommended.

Field & Transport Considerations
  • Scope: RN and critical-care transport crews (Paramedic/RN/CCT) manage insulin infusions and HIET on interfacility transfers. This varies by state and agency protocol.
  • Storage & Stability: refrigerate unopened vials at 2–8°C. At room temperature a Humulin R vial lasts 31 days (up to 30°C) and a Novolin R vial 42 days (up to 25°C). Premixed bags: refrigerated, or up to 30 days at ≤25°C, never back in the fridge. Diluted Humulin R: 28 days refrigerated or 14 days at 30°C. Novolin R infusion bags: 24 hr at room temperature. Do not freeze; keep out of vehicle heat.
  • Carried Concentration: confirm bag concentration (usually 1 unit/mL; HIET may be 10 units/mL) and program units/hr, not mL/hr alone.
  • Infusions in Transport: pump with drug library, dedicated line, glucose meter, and enough insulin and dextrose fluid for the trip; check glucose before departure and at least hourly en route. HIET: every 20 min for the first hour and after each rate change, then hourly.
  • Handoff Essentials: weight, current rate (units/hr and units/kg/hr), bag concentration, last glucose, K⁺, BHB and pH with times, dextrose and K⁺ infusions, basal insulin given, SGLT2 inhibitor use; HIET bolus, titration steps and vasopressors.

Clinical Pearls
Potassium before insulin (CCRN/FP-C): Total-body K⁺ is depleted in DKA, even when serum K⁺ reads normal or high. Insulin pulls K⁺ into cells within hours. So check K⁺ first, and hold insulin until it is above 3.5 mEq/L.
Judge DKA resolution by ketones, not the gap: Use BHB with pH or bicarbonate. The trap: large saline volumes can keep bicarbonate low after the ketosis clears, and urine ketones lag behind.
Euglycemic DKA: An SGLT2 inhibitor patient with vomiting, Kussmaul breathing and glucose under 200 mg/dL? That may still be DKA. Check ketones and a blood gas. Give dextrose with the insulin from the start.
DKA vs HHS insulin:
  • DKA: Insulin stops the ketogenesis. Full rate. Add dextrose early.
  • HHS: Fluids do most of the work. Half the rate. Slow the osmolality fall.
  • Mixed DKA/HHS: Treat the ketoacidosis at the DKA rate.
Insulin moves potassium but does not remove it: Pair it with K⁺ removal: a binder, a diuretic or dialysis. Then recheck for rebound.
HIET is an inotrope: High-dose insulin improves contractility in beta-blocker and calcium channel blocker shock. The glucose need can outlast the drip by a day.

Pharmacology

Mechanism of Action

  • Insulin receptor activation sends glucose into muscle and fat and cuts hepatic glucose output, so glucose falls.
  • Lipolysis and ketogenesis are suppressed. Ketoacid production stops, and the DKA resolves.
  • Na⁺/K⁺-ATPase activation pulls K⁺ into cells. Serum K⁺ falls within 15 min, regardless of the glucose effect.
  • High-dose myocardial uptake of glucose and lactate gives positive inotropy in beta-blocker and calcium channel blocker poisoning.

Pharmacokinetics

RouteOnsetPeakDuration
IV bolus (regular)
10–15 min
—
2–6 hr (median about 4 hr) after 0.1–0.2 units/kg
K⁺ shift (IV)
Within 15 min
30–60 min (fall about 0.65–1 mEq/L)
Up to about 2 hr, then rebound
Subcut (regular)
About 30 min
About 2 hr (label range 20 min–6 hr)
About 8 hr (3–14 hr)
  • Half-life: IV about 20 min at 0.1 units/kg and 1 hr at 0.2 units/kg; subcut apparent about 1.5 hr (Humulin R label)
  • Metabolism and elimination: Most uptake and breakdown happens in the liver, with some in kidney, muscle and fat. Kidney and liver failure cut clearance, which prolongs the effect.
  • Distribution: volume 0.32–0.67 L/kg after IV doses (Humulin R label)
  • Rapid-acting analogs (subcut): insulin aspart peaks in 40–50 min (regular 80–120 min), peak effect 1–3 hr, duration 3–5 hr (NovoLog label)

Names & Classification
Generic Name
Insulin human (regular insulin), U-100
Brand Names
Humulin R U-100, Novolin R; Myxredlin (premixed 100 units/100 mL in 0.9% sodium chloride); Humulin R U-500 is concentrated and subcut only
Pharmacologic Class
Short-acting human insulin (peptide hormone)
Therapeutic Class
Antihyperglycemic; potassium-shifting agent; high-dose inotrope in beta-blocker and calcium channel blocker poisoning (HIET)
Controlled Substance
Not controlled
ISMP High-Alert
Yes: ISMP high-alert medication (insulin, subcutaneous and IV)
Look-Alike / Sound-Alike
HumuLIN / HumaLOG; NovoLIN / NovoLOG; U-100 / U-500 regular insulin; insulin / heparin (both dosed in units)
Error-Prone Abbreviations to Avoid
“U” or “IU” for units (misread as 0, 4 or IV); “SS” for sliding scale; “SC” or “SQ” (write subcut)

Related

References
  1. Eli Lilly and Company. (2023). Humulin R (insulin human) injection, for subcutaneous or intravenous use: Prescribing information (revised June 2023; DailyMed SPL version 35, September 2026). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b519bd83-038c-4ec5-a231-a51ec5cc291f
  2. Baxter Healthcare Corporation. (2025). Myxredlin (insulin human) in sodium chloride injection, for intravenous use: Prescribing information (DailyMed SPL version 12, July 2026). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=afca6e80-a802-49fb-a978-5fe28a173001
  3. Novo Nordisk. (2022). Novolin R (human insulin injection) prescribing information (revised November 2022). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aee7f1f3-612c-4027-8ce9-4fd1f41eed71
  4. Novo Nordisk. (2023). NovoLog (insulin aspart injection) prescribing information (revised February 2023). DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3a1e73a2-3009-40d0-876c-b4cb2be56fc5
  5. Umpierrez, G. E., Davis, G. M., ElSayed, N. A., Fadini, G. P., Galindo, R. J., Hirsch, I. B., Klonoff, D. C., McCoy, R. G., Misra, S., Gabbay, R. A., Bannuru, R. R., & Dhatariya, K. K. (2024). Hyperglycemic crises in adults with diabetes: A consensus report. Diabetes Care, 47(8), 1257–1275. https://doi.org/10.2337/dci24-0032
  6. American Diabetes Association Professional Practice Committee for Diabetes. (2026). 16. Diabetes care in the hospital: Standards of Care in Diabetes—2026. Diabetes Care, 49(Suppl 1), S339–S355. https://doi.org/10.2337/dc26-S016
  7. Glaser, N., Fritsch, M., Priyambada, L., Rewers, A., Cherubini, V., Estrada, S., Wolfsdorf, J. I., & Codner, E. (2022). ISPAD clinical practice consensus guidelines 2022: Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatric Diabetes, 23(7), 835–856. https://doi.org/10.1111/pedi.13406
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  9. Ontario Poison Centre. (2024). High-dose insulin euglycemia therapy (HDIE) / hyperinsulinemia-euglycemia therapy (HIE) (revised February 2024). Hospital for Sick Children. https://www.ontariopoisoncentre.ca/siteassets/pdfs/english/highdoseinsulin2024.pdf
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  11. Moussavi, K., Garcia, J., Tellez-Corrales, E., & Fitter, S. (2021). Reduced alternative insulin dosing in hyperkalemia: A meta-analysis of effects on hypoglycemia and potassium reduction. Pharmacotherapy, 41(7), 598–607. https://doi.org/10.1002/phar.2596
  12. Finder, S. N., McLaughlin, L. B., & Dillon, R. C. (2022). 5 versus 10 units of intravenous insulin for hyperkalemia in patients with moderate renal dysfunction. The Journal of Emergency Medicine, 62(3), 298–305. https://doi.org/10.1016/j.jemermed.2021.10.027

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