Prescribing in Critical Illness

Critical illness changes both what the body does to a drug and what the drug does to the body. Volume of distribution rises with resuscitation and capillary leak, albumin falls, organ function shifts from hour to hour, and enteral absorption becomes unreliable, so doses chosen for stable patients often fail.

Distribution. Hydrophilic drugs (beta-lactams, aminoglycosides, vancomycin) have an enlarged volume of distribution, so loading doses are given in full and are never reduced for organ failure.

Clearance. Early sepsis, trauma and burns can produce augmented renal clearance (creatinine clearance over 130 mL/min), which lowers beta-lactam levels. Later, acute kidney injury, liver dysfunction, continuous renal replacement therapy and extracorporeal support change clearance in the opposite direction.

Route and delivery. The intravenous route is used for all urgent drugs. Enteral feeding reduces absorption of phenytoin, ciprofloxacin and levothyroxine. Modified-release tablets must not be crushed.

Antimicrobials. In septic shock the first dose of an effective antimicrobial is given within 1 hour of recognition, at full dose, whatever the kidney function. Extended or continuous infusion of beta-lactams is used for severe infection.

Continue. Beta blockers (unless in shock), antiepileptic drugs, levodopa, long-term corticosteroids (with stress dosing), and antiarrhythmics where still indicated.

Hold or stop. ACE inhibitors, angiotensin receptor blockers, diuretics, metformin, SGLT2 inhibitors, sulphonylureas and non-essential sedatives. Switch oral anticoagulants to heparin.

Special groups.

• Obesity: use actual weight for loading doses of vancomycin and aminoglycoside, and adjusted weight for maintenance of hydrophilic drugs.

• Children: dose by weight with doses checked by a second clinician.

• Pregnancy: avoid teratogenic drugs unless life saving, and use left lateral tilt after 20 weeks.

• East Africa: when severe malaria is possible, give artesunate 2.4 mg/kg intravenously at 0, 12 and 24 hours, then daily, together with antibacterial cover, and note that drug level monitoring is often unavailable, so rely on conservative nephrotoxin use and clinical review.

• Vancomycin: loading 25 mg/kg intravenously (maximum 3 g), then by level aiming for a pre-dose level of 15 to 20 mg/L.

• Piperacillin with tazobactam: 4.5 g intravenously loading, then 4.5 g every 6 to 8 hours, given as an extended infusion over 3 to 4 hours after the first dose.

• Meropenem: 1 g intravenously every 8 hours, given over 3 hours after the first bolus dose. Reduce by creatinine clearance after 48 hours.

• Paracetamol: 1 g every 6 hours, maximum 4 g daily (15 mg/kg, maximum 60 mg/kg daily if under 50 kg).

Monitoring. Review the full chart daily for indication, dose, route, duration, interactions, QT interval, and renal and hepatic function. Measure drug levels for vancomycin, aminoglycosides, phenytoin and antifungals where available. Document stop dates for every antimicrobial.

Stop rules. Stop any drug without a current indication, and reassess antimicrobials at 48 to 72 hours with culture results.

Referral and escalation. Involve the critical care pharmacist and microbiologist for augmented renal clearance, renal replacement therapy, extracorporeal support, drug-resistant organisms, and interacting regimens.

Common errors. Reducing the first antimicrobial dose for kidney injury, crushing modified-release tablets, ignoring enteral feed interactions, and continuing drugs after the indication has resolved.