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.

^aSuggestion based on opioid-naive patient. Lowest effective dose should be used.

^bFeeding tube administration varies by manufacturer. Please check manufacturer information prior to trialing.

^cAssuming a 70-kg patient.

^dSuggestion 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.