Diabetic Ketoacidosis Insulin Therapy

Diabetic ketoacidosis is insulin deficiency causing hyperglycaemia, ketone production and metabolic acidosis. It is confirmed by glucose over 11 mmol/L or known diabetes, blood ketones of 3.0 mmol/L or more, and venous pH under 7.3 or bicarbonate under 15 mmol/L. Severe disease is pH under 7.0, bicarbonate under 5 mmol/L, ketones over 6 mmol/L, or reduced consciousness. Treatment is fluids first, then fixed-rate intravenous insulin with potassium.

Precipitants. Infection (including malaria and typhoid in endemic areas), omitted insulin, new-onset type 1 diabetes, pancreatitis, myocardial infarction, steroids, and SGLT2 inhibitors (which can cause ketoacidosis with near-normal glucose).

Order of treatment. Fluids, potassium check, then insulin. Do not give insulin if potassium is under 3.3 mmol/L until it has been corrected.

Insulin. Soluble human insulin by intravenous infusion, 50 units in 50 mL of 0.9% sodium chloride.

Fluids. 0.9% sodium chloride as the main resuscitation fluid, with 10% glucose added once glucose is under 14 mmol/L.

Long-acting insulin. Continue the usual basal insulin alongside, or start it on day 1 at 0.2 units/kg if newly diagnosed.

Fluids (adults). Give 0.9% sodium chloride 1 litre over 1 hour (if systolic blood pressure is under 90 mmHg, give 500 mL over 10 to 15 minutes and repeat), then 1 litre with potassium over 2 hours, 1 litre over 2 hours, 1 litre over 4 hours, 1 litre over 4 hours, and 1 litre over 6 hours, adjusted to volume status. Use smaller volumes in older adults, heart failure and kidney disease.

Insulin. Start fixed-rate insulin 0.1 units/kg/hour (maximum 15 units/hour initially unless local practice differs) when potassium is 3.3 mmol/L or more and fluids are running. Do not give an insulin bolus.

Potassium. - Over 5.5 mmol/L: no potassium; recheck in 2 hours. - 3.5 to 5.5 mmol/L: add 40 mmol of potassium chloride to each litre of fluid. - Under 3.5 mmol/L: senior review, give 20 to 30 mmol/hour of potassium and delay insulin if under 3.3 mmol/L.

Glucose. When glucose falls under 14 mmol/L, start 10% glucose at 125 mL/hour in addition to the sodium chloride, and continue the insulin infusion.

Bicarbonate. Not advised unless pH is under 6.9, when 100 mmol of sodium bicarbonate in 400 mL of water with 20 mmol of potassium chloride over 2 hours may be given.

Targets for the first hours. Ketones should fall by at least 0.5 mmol/L/hour, bicarbonate should rise by at least 3 mmol/L/hour, and glucose should fall by at least 3 mmol/L/hour. If targets are missed, increase the insulin rate by 1 unit/hour and check the line and fluids.

Thromboprophylaxis. Enoxaparin 40 mg subcutaneously once daily, with 20 mg once daily if creatinine clearance is under 30 mL/min.

Resolution. Venous pH over 7.3 and ketones under 0.6 mmol/L. Then convert to subcutaneous insulin when the patient is eating, giving the first rapid-acting dose with a meal and continuing the infusion for 30 to 60 minutes afterwards.

Special groups.

• Children and adolescents: give 10 mL/kg of 0.9% sodium chloride over 30 to 60 minutes, then replace the deficit over 48 hours at a rate set by degree of dehydration, and start insulin 0.05 to 0.1 units/kg/hour 1 hour after fluids begin. Watch closely for cerebral oedema.
• Pregnancy: manage as an emergency with obstetric and critical care input.
• SGLT2 inhibitor associated ketoacidosis: stop the drug; give glucose-containing fluid early because glucose may be near normal.
• Kidney impairment: smaller fluid volumes and closer potassium checks.

Monitoring. Glucose and ketones hourly; venous gas, potassium and bicarbonate at 1 hour, 2 hours, then every 2 hours; sodium, urea and creatinine at 1 hour, then every 4 to 6 hours. Fluid balance and cardiac monitoring in severe disease.

Complications. Hypokalaemia, hypoglycaemia, cerebral oedema (headache, falling consciousness, bradycardia), pulmonary oedema, and acute kidney injury.

Stopping the infusion. Continue until ketones are under 0.6 mmol/L and pH is over 7.3, and keep it running for 30 to 60 minutes after the first subcutaneous rapid-acting dose.

Referral and escalation. Escalate to critical care for pH under 7.0, ketones over 6 mmol/L, bicarbonate under 5 mmol/L, potassium under 3.5 mmol/L on admission, Glasgow Coma Scale under 12, systolic blood pressure under 90 mmHg, oxygen saturation under 92%, or pregnancy.