9.6 Trauma, Burns, Supportive Care, and End-of-Life Pharmacotherapy
Key Takeaways
Severe burns require the Parkland formula (4 mL x kg x %BSA lactated Ringer's in first 24h, half in first 8h) and aggressive pain control, with subsequent high-volume crystalloid needs driving renally-cleared antibiotic dosing (augmented renal clearance is common).
Trauma patients frequently develop augmented renal clearance (ARC), requiring higher doses of beta-lactams, vancomycin, and anticoagulants; massive transfusion mandates calcium replacement due to citrate-induced hypocalcemia.
Supportive ICU care includes DVT prophylaxis (LMWH preferred over UFH in trauma per EAST guidelines), stress ulcer prophylaxis in mechanically ventilated patients, and bowel regimen for opioid-induced constipation.
End-of-life pharmacotherapy prioritizes symptom control: opioid and benzodiazepine infusions for dyspnea and anxiety, anticholinergics for secretions, and palliative sedation with midazolam/propofol for refractory symptoms.
Trauma, Burns, Supportive Care, and End-of-Life Pharmacotherapy
Severe Burn Pharmacotherapy
Initial Resuscitation (Parkland Formula)
- 4 mL x kg x %BSA of lactated Ringer's in first 24 hours (from time of burn, not admission).
- Half in first 8 hours post-burn; remainder over 16 hours.
- Titrate to urine output 0.5-1.0 mL/kg/hour.
- Brooke and modified Brooke formulas are alternatives; Parkland is most common in US practice.
Pharmacotherapy Considerations in Burns
| Issue | Implication |
|---|---|
| Augmented renal clearance (ARC) | Burn hypermetabolism produces CrCl >130 mL/min; need higher doses of vancomycin (target AUC 400-600), beta-lactams (extended or continuous infusion), anticoagulants |
| Volume of distribution | Massive fluid shifts increase Vd; initial loading doses often need to be 1.5-2x standard |
| Protein binding | Hypoalbuminemia increases free fraction of highly-bound drugs; titrate to clinical effect |
| Escharotomy | Compartment syndrome may require fasciotomy; analgesia with ketamine preferred |
| Inhalation injury | High-dose heparin/N-acetylcysteine/bronchodilators nebulized; monitor for ARDS |
| Infection | Burn wound sepsis: empiric antipseudomonal + anti-MRSA; topical silver sulfadiazine for partial-thickness (avoid if sulfonamide allergy) |
| Nutrition | Early enteral feeding within 24h reduces infection; high protein (1.5-2 g/kg/day), high calorie needs |
Trauma Pharmacotherapy
Massive Transfusion Protocol
- 1:1:1 ratio (PRBC:FFP:platelets) for trauma-induced coagulopathy.
- Calcium replacement critical: each unit PRBC contains ~3 g citrate; ionized calcium drops precipitating hypotension, prolonged QT, coagulopathy. Replace with calcium gluconate 1-2 g IV q1-2h or calcium chloride 1 g IV (central line preferred) guided by ionized calcium.
- TXA within 3 hours of injury (CRASH-2): 1 g IV bolus over 10 min, then 1 g IV over 8 hours. Beyond 3 hours, may increase mortality.
- Reversal of anticoagulants per agent (see 9.3).
Trauma-Specific Pharmacotherapy
- Pain: multimodal — acetaminophen, ketamine (sub-dissociative 0.1-0.3 mg/kg/hour for opioid-sparing), regional anesthesia, opioid sparing.
- DVT prophylaxis: LMWH (enoxaparin 30 mg SC q12h or 40 mg daily) preferred over UFH in trauma (EAST practice guidelines); start within 24-72h if no contraindication. Considerate IVC filter only if anticoagulation contraindicated.
- Stress ulcer prophylaxis: indicated if mechanical ventilation >48h or coagulopathy; pantoprazole 40 mg IV daily.
- Antibiotic prophylaxis: not routine; single dose pre-operative for open fractures.
Traumatic Brain Injury Pharmacotherapy
- Avoid hypotension (SBP <100 or MAP <65) and hypoxia.
- Hyperosmolar therapy: mannitol 0.25-1 g/kg IV or 3% hypertonic saline 250 mL bolus for elevated ICP.
- Propofol for sedation (preserves neuro exam, lowers ICP, but watch for PRIS).
- Seizure prophylaxis (levetiracetam 1 g IV) for 7 days post-severe TBI with intracranial hemorrhage.
- Avoid corticosteroids (worsen mortality in TBI per CRASH trial).
Supportive Care in the ICU
DVT Prophylaxis
Per PADIS and CHEST guidelines:
- Medical ICU: enoxaparin 40 mg SC daily or UFH 5000 units SC q8-12h.
- Surgical/trauma ICU: enoxaparin 30 mg SC q12h (start 24-72h post-op once hemostasis).
- Renal dysfunction (CrCl <30): enoxaparin 30 mg SC daily or UFH, dalteparin 5000 IU daily; avoid fondaparinux; DOACs contraindicated.
- Mechanical prophylaxis (SCDs) as adjunct; not monotherapy.
Stress Ulcer Prophylaxis
Indicated for: mechanical ventilation >48h, coagulopathy, major burns (>35% BSA), traumatic brain injury, major trauma with spinal cord injury, history of GI bleed within 1 year.
- Pantoprazole 40 mg IV daily preferred; H2 blockers alternative.
- Discontinue when ICU risk factors resolve.
Bowel Regimen
Opioid-induced constipation is universal:
- Stool softener + stimulant (docusate + senna).
- Osmotic laxative (PEG, lactulose) for constipation.
- Methylnaltrexone 8-12 mg SC q48h for refractory opioid-induced constipation (does not cross blood-brain barrier, no analgesia reversal).
- Naloxegol 12.5-25 mg PO daily alternative.
End-of-Life Pharmacotherapy (Palliative Care in ICU)
Symptom-Based Approach
| Symptom | First-Line |
|---|---|
| Pain | Morphine 1-5 mg IV q1h or continuous infusion 0.5-2 mg/hour; hydromorphone 0.2-1 mg q2h if renal dysfunction |
| Dyspnea | Low-dose opioid (morphine 2-5 mg IV PRN or infusion); benzodiazepines for anxiety |
| Anxiety/agitation | Lorazepam 0.5-2 mg IV q1h PRN; midazolam infusion 1-5 mg/hour for palliative sedation |
| Delirium | Haloperidol 0.5-2 mg IV q1h PRN; avoid benzodiazepines unless alcohol withdrawal |
| Secretions (death rattle) | Glycopyrrolate 0.2 mg IV q4-6h or scopolamine patch 1 mg/72h; hyoscine butylbromide alternative |
| Nausea | Haloperidol 0.5-2 mg IV q8h; ondansetron 4 mg IV q8h; metoclopramide 5-10 mg IV q6h (avoid if bowel obstruction) |
Palliative Sedation
For refractory symptoms in actively dying patients:
- Midazolam infusion 1-10 mg/hour titrated to comfort.
- Propofol infusion 10-50 mcg/kg/min as alternative.
- Ethical principles: proportional sedation, informed consent, team agreement, family discussion.
Goals of Care and Caregiver Education
- Family meetings within 72h of ICU admission improve outcomes and reduce non-beneficial treatment.
- Pharmacist role: deprescribe unnecessary medications (statins, antihypertensives, antibiotics) when prognosis <2 weeks.
- Caregiver education for terminal discharge includes home opioid administration, sublingual routes, anticipatory prescribing.
Clinical Scenario
A 25-year-old with 50% BSA burns develops febrile septic shock on day 4. He has CrCl 175 mL/min by 8-hour measured urine creatinine. Vancomycin and piperacillin-tazobactam are ordered. How should dosing be adjusted, and what is the monitoring strategy?
Answer: This patient has augmented renal clearance (ARC) from burn hypermetabolism. Standard vancomycin and beta-lactam doses will fail PD targets. Use extended-infusion piperacillin-tazobactam 4.5 g q6h over 4 hours and vancomycin 25-30 mg/kg load then 1.5-2 g q8-12h targeting AUC 400-600 with Bayesian or peak-trough monitoring. Consider continuous infusion beta-lactam in severe ARC. Re-dose after CRRT if initiated, accounting for circuit clearance.
A trauma patient receiving massive transfusion develops hypotension and a prolonged QT interval. Which derangement is most likely responsible, and what is the appropriate treatment?
Hypomagnesemia treated with magnesium sulfate 2 g IV
Citrate-induced hypocalcemia treated with calcium gluconate 1-2 g IV
Hyperkalemia treated with insulin/dextrose and calcium chloride
Hyponatremia treated with 3% hypertonic saline
Which pharmacotherapy is most appropriate for terminal secretions ("death rattle") in an actively dying ICU patient?
Ondansetron 4 mg IV
Glycopyrrolate 0.2 mg IV q4-6h
Furosemide 20 mg IV
Naloxone 0.04 mg IV
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