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?
Which pharmacotherapy is most appropriate for terminal secretions ("death rattle") in an actively dying ICU patient?