# Insulin Therapy and Electrolyte Management in DKA and HHS — ADA 2024

## Insulin Therapy for DKA

### Intravenous Insulin (Preferred for Moderate-Severe DKA)

- **Fixed-rate infusion:** 0.1 units/kg per hour of regular insulin.
- **Optional initial bolus:** 0.1 units/kg IV bolus before starting infusion, particularly if infusion delay is anticipated.
- **Variable-rate alternative:** Nurse-driven, titratable insulin infusion protocol (institution-specific).

### Dose Reduction When Glucose < 250 mg/dL

- Reduce infusion rate to **0.05 units/kg per hour**.
- Titrate to maintain blood glucose around **200 mg/dL**.
- Add **5-10% dextrose** to IV fluids to prevent hypoglycemia while continuing insulin to resolve ketonemia.

**Key principle:** Continue insulin infusion until ketonemia resolves (beta-hydroxybutyrate < 0.6 mmol/L and pH >= 7.3), even if glucose has normalized. Premature discontinuation of insulin leads to recurrent ketoacidosis.

### Concurrent Basal Insulin During IV Infusion

- Administering subcutaneous basal insulin at **0.15-0.3 units/kg** during IV insulin infusion has been shown to:
  - Reduce time to DKA resolution
  - Reduce ICU length of stay
  - Reduce rebound hyperglycemia after IV insulin discontinuation
  - No increased risk of hypoglycemia

### Subcutaneous Insulin (Mild-Moderate Uncomplicated DKA Only)

- **Rapid-acting insulin analogs** (lispro, aspart) administered every **1-2 hours** are an effective alternative for mild-to-moderate, uncomplicated DKA.
- **Not recommended** for severe DKA, hemodynamic instability, or complicated cases.
- Requires appropriate monitoring infrastructure and nursing availability.

## Insulin Therapy for HHS

| Clinical Scenario | Insulin Regimen |
|---|---|
| **HHS without significant ketonemia** (beta-hydroxybutyrate < 3.0 mmol/L) | Fixed-rate IV infusion at **0.05 units/kg per hour** |
| **HHS with significant ketonemia** (beta-hydroxybutyrate >= 3.0 mmol/L) — mixed DKA/HHS | Fixed-rate IV infusion at **0.1 units/kg per hour** |

**Important:** In HHS, aggressive early insulin administration before adequate fluid resuscitation may cause a precipitous drop in glucose and osmolality, increasing the risk of cerebral edema. Fluid resuscitation takes priority.

## Potassium Replacement

Potassium is the most critical electrolyte to monitor during DKA and HHS management. Serum potassium levels typically decline by 1-2 mmol/L within 48 hours of initiating treatment due to insulin-mediated cellular uptake and correction of acidosis.

### Potassium Management Algorithm

```
Check serum potassium on admission
  --> K+ < 3.5 mmol/L (hypokalemia)?
      --> Replace at 10 mmol/hour IV
      --> DELAY insulin until K+ > 3.5 mmol/L
      --> Recheck K+ every 1-2 hours until > 3.5 mmol/L
  --> K+ 3.5-5.0 mmol/L?
      --> Add 20-30 mmol potassium per liter of IV fluid
      --> Start insulin therapy
      --> Recheck K+ at 2 hours after starting insulin, then every 4 hours
  --> K+ > 5.0 mmol/L?
      --> Do NOT replace potassium
      --> Start insulin therapy
      --> Recheck K+ at 2 hours after starting insulin, then every 4 hours
      --> Begin replacement when K+ falls below 5.0 mmol/L

Target range: 4.0-5.0 mmol/L
```

### Critical Warning

- **Severe hypokalemia (<= 2.5 mmol/L) is associated with a threefold increase in mortality.**
- Insulin drives potassium into cells; administering insulin to a hypokalemic patient can precipitate fatal cardiac arrhythmias.
- Potassium should be given as a combination of **KCl and KPhos** to prevent hyperchloremia and address concurrent phosphate depletion.

## Bicarbonate Administration

- **Not routinely recommended** in DKA.
- Consider **only** if venous pH < 7.0.
- If administered: **100 mmol sodium bicarbonate in 400 mL sterile water**, infused every 2 hours until pH > 7.0.
- Routine bicarbonate administration has not been shown to improve outcomes in DKA with pH >= 7.0 and may:
  - Worsen hypokalemia
  - Delay ketone clearance
  - Paradoxically worsen intracellular acidosis
  - Increase the risk of cerebral edema

## Phosphate Replacement

- **Not routinely indicated** in DKA or HHS.
- Consider replacement only if serum phosphate < 1.0 mmol/L (3.1 mg/dL) **with** clinical manifestations:
  - Muscle weakness
  - Respiratory depression
  - Cardiac dysfunction
- If replacing: **20-30 mmol potassium phosphate** added to IV fluids.
- No demonstrated clinical benefit of routine phosphate replacement in DKA.

## Monitoring During Insulin and Electrolyte Therapy

| Parameter | Frequency | Target |
|---|---|---|
| **Capillary glucose** | Every 1-2 hours | Decline of 50-75 mg/dL per hour; maintain ~200 mg/dL after reaching < 250 mg/dL |
| **Serum potassium** | 2 hours after insulin start, then every 4 hours | 4.0-5.0 mmol/L |
| **Beta-hydroxybutyrate** | Every 4 hours | Decline by >= 0.5 mmol/L per hour; target < 0.6 mmol/L for resolution |
| **Venous pH and bicarbonate** | Every 4 hours | pH >= 7.3 and bicarbonate >= 18 mmol/L for resolution |
| **Serum creatinine** | Every 4 hours | Monitor renal function and guide fluid management |
| **Osmolality (HHS)** | Every 4 hours | Decline 3.0-8.0 mOsm/kg per hour; target < 300 mOsm/kg |

## Special Populations

### Pregnancy

- Euglycemic DKA may occur in pregnancy due to physiologic changes in glucose metabolism.
- Requires **immediate expert senior medical and obstetric intervention**.
- Should be managed in **delivery suites or high-dependency units**.
- Lower thresholds for diagnosis and more aggressive treatment are warranted.

### SGLT2 Inhibitor-Associated DKA

- **Discontinue SGLT2 inhibitor on admission** to hospital with DKA.
- Presents with euglycemic DKA (glucose often < 200 mg/dL).
- SGLT2 inhibitors are **not routinely recommended** for reinitiation after DKA resolution in T2D.
- SGLT2 inhibitors are **not recommended** for use in T1D.

### Patients on Insulin Pumps

- **Disconnect or remove the insulin pump** upon admission for DKA.
- Transition to IV insulin for the duration of DKA management.
- Pump malfunction (occlusion, infusion set failure) is a recognized precipitant of DKA.

## Limitations

- Insulin dosing recommendations are based on body weight and may not account for insulin resistance in all patients.
- The role of concurrent basal insulin during IV insulin infusion, while supported by evidence showing reduced resolution time, requires further validation in diverse populations.
- Potassium monitoring frequency (every 4 hours) may be insufficient in patients with severe hypokalemia or renal impairment.
- Subcutaneous insulin protocols for mild DKA require adequate nursing support and monitoring infrastructure, which may not be available in all settings.
