Table 2.
Pharmacokinetic parameters in healthy volunteers versus critical illness
| Medication | MW (Daltons) | Protein binding (%) | Vd (L/kg) | t1/2 (h) | PK/PD characteristic | Excretion | Recommended adjustments in critical illness and CRRT |
|---|---|---|---|---|---|---|---|
| Analgesicsa | |||||||
| Oxycodone70 | 315 | 38 | 2.6 | 3.7 | Relatively hydrophilic, evaluate efficacy using NRS/CPOT | Urine | 2.5–5 mg p.o./p.f.t. q. 4–6 h p.r.n. |
| Hydromorphone71 | 285 | 8 | 4 | 2 | Context-sensitive half-life, lipophilic, evaluate efficacy using NRS/CPOT | Urine, Feces | 1–2 mg p.o./p.f.t. q. 4–6 h p.r.n. 0.2–0.5 mg i.v. q. 2–4 h p.r.n. |
| Morphine72,73 | 285 | 31 | 1 | 2 | Relatively hydrophilic, evaluate efficacy using NRS/CPOT | Urine, Feces | 5 mg p.o./p.f.t. q. 4–6 h p.r.n. 0.5–2 mg i.v. q. 2–6 h p.r.n. |
| Fentanyl74 | 336 | 87 | 4 | 2 | Context-sensitive half-life, lipophilic, evaluate efficacy using NRS/CPOT | Urine 75%, Feces 9% | 12.5–50 μg i.v. q. 15–60 min p.r.n. |
| Methadone75 | 309 | 85 | 1 | 8 | Context-sensitive half-life, lipophilic, evaluate efficacy using NRS/CPOT | Urine | 5–10 mg p.o./p.f.t. q. 6–12 h p.r.n. 2.5–5 mg i.v. q. 6–12 h p.r.n. |
| Anticonvulsants | |||||||
| Valproic acid76, 77, 78 | 144 | 90 | 0.14 | 6 | Lipophilic; evaluate free valproic acid concentrations (Note: total valproic acid concentrations may be misleading) | Urine | Seizures: 10–15 mg/kg per day Status epilepticus: 20–40 mg/kg (max. 3 g) (Divided dosing: i.v. q. 6 h, p.o./p.f.t. q. 6–8 h) |
| Carbamazepine79, 80, 81 | 236 | 27 | 0.6 | 12 | Lipophilic | Urine 72%, feces 28% | Seizures: 2–3 mg/kg per day p.o./p.f.t. q. 6–12 h |
| Levetiracetam82, 83, 84, 85 | 170 | <10 | 0.5 | 6 | Lipophilic | Urine | Seizures: 750–1000 mg q 12 h |
| Phenytoin86,87 | 252 | 90 | 0.5 | 12 | Lipophilic; evaluate free phenytoin concentrations | Urine | Seizures: 15 mg/kg (max. 2 g) i.v. loading dose divided q. 8–12 h, 4–7 mg/kg per day divided q. 6–12 h |
| Lacosamide88, 89, 90 | 250 | <15 | 0.6 | 13 | Lipophilic | Urine 95%, feces <0.5% | Seizures: 100 mg i.v./p.o./p.f.t. q. 12 h Status epilepticus: 400 mg i.v. loading dose, followed by 200 mg i.v. q. 12 h |
| Topiramate91,92b | 339 | 15 | 0.6 | 19 | Lipophilic | Urine | Seizures: 50 mg p.o./p.f.t. q. 24 h Status epilepticus: 200 mg p.o./p.f.t. Q12 h |
| Lorazepam93,94 | 321 | 85 | 1.3 | 12 | Context-sensitive half-life, lipophilic, evaluate RASS | Urine 88%, feces 7% | Anxiety: 0.5–2 mg i.v./p.o. q. 4–6 h p.r.n. Seizures: 2–4 mg i.v. q. 3–4 min p.r.n. |
| Midazolam94,95 | 326 | 97 | 1 | 3 | Context-sensitive half-life, lipophilic, evaluate RASS | Urine 90%, feces 10% | Anxiety/sedation: 0.5–5mg i.v. Q15 min p.r.n.; avoid continuous sedation, if needed for mechanical ventilation start 0.01 mg/kg per hour Status epilepticus: 0.2 mg/kg i.v. q. 3–5 min, 0.05–2 mg/kg per hour continuous i.v. infusion |
| Clonazepam96 | 316 | 85 | 1.5 | 17 | Context-sensitive half–life, lipophilic, evaluate RASS | Urine | 0.25 mg p.o./p.f.t. q. 12–24 h |
| Diazepam97 | 285 | 96 | 1 | 60 | Context-sensitive half-life, lipophilic, evaluate RASS | Urine | Anxiety/sedation: 2–10 mg i.v./p.o./p.f.t. q. 4–6 h p.r.n. Status epilepticus: 5–10 mg i.v. q. 3–5 min p.r.n. |
| Pentobarbital98, 99, 100 | 226 | 20 | 1 | 22 | Context-sensitive half-life, lipophilic, pentobarbital concentrations | Urine | Sedation: 100 mg i.v. q. 3–5 min Seizures: 5–13 mg/kg bolus, followed by 0.5–5 mg continuous infusion |
| Phenobarbital100, 101, 102, 103 | 232 | 48 | 0.6 | 79 | Lipophilic, monitor RASS, phenobarbal concentrations | Urine 25% | Sedation: 30–120 mg/d i.v./p.o. in 2–3 divided doses Seizures: 2 mg/kg per day i.v./p.o. in 2–3 divided doses Status epilepticus: 15–20 mg/kg i.v. |
| Gabapentin104,105 | 171 | <3 | 0.8c | 5 | Lipophilic, monitor RASS | Urine | 100–300 mg p.o./p.f.t. q. 12 h |
| Pregabalin106 | 159 | 0 | 0.5 | 6.3 | Lipophilic, monitor RASS | Urine 90% | 25–50 mg IR p.o./p.f.t. q. 8 h |
| Additional Sedatives and Psychotropic Medicationsd | |||||||
| Propofol107 | 178 | 97 | 2 | 4 | Context-sensitive half-life, lipophilic, monitor RASS | Urine 88%, feces <2% | 5–75 μg/kg/min continuous infusion |
| Dexmedetomidine108 | 200 | 94 | 1.7c | 2 | Context-sensitive half-life, lipophilic, monitor RASS | Urine 95%, feces 4% | 0.2–1.5 μg/kg continuous infusion |
| Ketamine109 | 238 | 27 | 2.4 | 0.25 | Context-sensitive half-life, lipophilic, monitor RASS | Urine 91%, feces 3% | Sedation: 0.5–2 mg/kg bolus, 0.2–2.5 mg/kg per hour continuous infusion |
| Acetaminophen110,111 | 151 | 10 | 1 | 2 | Hydrophilic, monitor NRS/CPOT | Urine <5% | 325–1000 mg i.v./p.o./p.f.t. q. 6 h |
| Tramadol112 | 263 | 20 | 2.6 | 6.3 | Hydrophilic, monitor NRS, CPOT | Urine 30% | 50 mg p.o./p.f.t. q. 6 h |
| Clonidine113 | 230 | 20 | 2.9 | 12 | Lipophilic, monitor RASS | Urine 40 % | 0.1–0.5 mg p.o./p.f.t. q. 6–12 h |
| Buproprion114 | 240 | 84 | 20 | 3 | Lipophilic | Urine 87 %, feces 10% | 100 mg IR p.o./p.f.t. b.i.d. |
| Trazodone115 | 372 | 89 | 0.5 | 7 | Lipophilic, monitor RASS | Urine 70%, feces 21% | 12.5–50 mg p.o./p.f.t. q.d. at bedtime |
| Venlafaxine116 | 277 | 27 | 7.5 | 5 | Hydrophilic | Urine 87%, | 37.5 mg p.o./p.f.t. q.d. |
| Fluoxetine117 | 309 | 95 | 12 | 24–96 | Lipophilic | Urine | 10–20 mg p.o./p.f.t. q.d. |
| Paroxetine118 | 329 | 93 | 8.7 | 21 | Lipophilic | Urine 64%, feces 36% | 10–20 mg p.o./p.f.t. q.d. |
| Sertraline119 | 306 | 98 | 20 | 26 | Lipophilic | Urine 40%, feces 40% | 25–50 mg p.o./p.f.t. q.d. |
| Amitriptyline120 | 277 | >90 | 18–22 | 13–36 | Lipophilic | Urine | 10–25 mg p.o./p.f.t. q.d. |
| Nortriptyline121 | 263 | 86 | 21 | 26 | Lipophilic | Urine | 10–25 mg p.o./p.f.t. q.d. |
| Quetiapine122 | 384 | 83 | 10 | 6 | Lipophilic, monitor RASS | Urine 73 %, feces 20% | Sedation: 25 mg p.o./p.f.t. q.d. – q. 12 h Bipolar: 100–200 mg p.o./p.f.t. q evening |
| Risperidone123 | 410 | 90 | 1–2 | 20 | Lipophilic, monitor RASS | Urine 70%, feces 14% | 1–2 mg p.o./p.f.t. q.d. |
| Aripiprazole124 | 448 | >99 | 4.9 | 75 | Lipophilic, monitor RASS | Feces 55%, Urine 25% | 10–15 mg p.o./p.f.t. q.d. |
| Olanzapine125 | 312 | 93 | 14 | 30 | Lipophilic, monitor RASS | Urine 57%, feces 30% | 2.5–5 mg p.o./p.f.t. q.d. 2.5–5 mg i.v./i.m. q. 2–4 h p.r.n. |
Pharmacokinetic parameters of protein binding, volume of distribution, and half-life summarized in this table were obtained from product insert information, largely derived from healthy adults. CCRT, continuous renal replacement therapy; CPOT, Critical Care Pain Observation Tool; i.m., intramuscularly; IR, immediate release; i.v., intravenously; MW, molecular weight; NRS, numeric rating scale; PK/PD, pharmacokinetic/pharmacodynamic; p.f.t., per feeding tube; p.r.n., as needed; q., every; q.d., every day; RASS, Richmond Agitation−Sedation Scale.
a
Suggestion based on opioid-naive patient. Lowest effective dose should be used.
b
Feeding tube administration varies by manufacturer. Please check manufacturer information prior to trialing.
c
Assuming a 70-kg patient.
d
Suggestion for psychotropic medication based on starting doses for intensive care unit sedation purposes only. Higher doses may be indicated based on past medical history, concomitant underlying conditions, or concomitant use of inducer.