Pain, Agitation/Sedation, Delirium, Immobility, Sleep Disruption, and Neuromuscular Blockade

Lipid formulation considerations: Standard propofol is a 1% (10 mg/mL) lipid emulsion containing 1.1

kcal/mL (0.1 g of fat per 1 mL of propofol); this should be accounted for when calculating nutritional

intake (e.g., propofol at 50 mcg/kg/minute in a 70-kg patient would provide around 500 calories per

day contributed by fat). Propofol contains 0.005% disodium edetate (EDTA) to decrease the rate of

microorganism growth, which is known to chelate trace metals, including zinc. Zinc supplementation

should be considered in patients at high risk of zinc deficiency (sepsis, burns, large-volume diarrhea)

if propofol is used for more than 5 days. Strict aseptic technique must be followed when handling

propofol; manufacturers recommend discarding propofol bottles and changing intravenous tubing

every 12 hours to decrease the risk of contamination. Propofol is not contraindicated in patients with

egg or soybean allergies as historically thought. Propofol contains egg yolks, and most patients are

allergic to egg whites. Propofol contains soybean oil not soybean-derived proteins, which have been

linked to allergic reactions.

Dosing range for ICU sedation: Usual starting dose 5–10 mcg/kg/minute, titrated every 5–10 minutes

to goal sedative effect. Abrupt discontinuation of propofol is not recommended because of its rapid

clearance (5–10 minutes).

Data: In a multicenter European trial (PRODEX), Jakob et al. compared propofol (n=249) with

dexmedetomidine (n=251) for sedation in prolonged mechanical ventilation. Patients in both groups

were treated with daily sedation interruption trials and spontaneous breathing trials (SBTs), and pain

was treated with fentanyl boluses. Proportion of time in target RASS (0, −3) without rescue therapy

was the same in the propofol group (65%) as in the dexmedetomidine group (65%). There was no

difference in median time on mechanical ventilation in propofol (5 days) versus dexmedetomidine

(4 days), p=0.24. Patients’ ability to communicate discomfort was better in the dexmedetomidine

group. Rates of hypotension and bradycardia were similar between the two groups. Critical illness

polyneuropathy was more common in the propofol group (n=11) than in the dexmedetomidine group

(n=2), p<0.02. The composite outcome of agitation, anxiety, and delirium occurred in propofol (29%)

Adverse effects: Bradycardia and hypotension (may be more common or severe in patients with

cardiac dysfunction, intravascular volume depletion, or low systemic vascular resistance); respiratory

depression, hypertriglyceridemia (most institutions use a threshold of 800–1000 as a cutoff of when to

stop propofol), pancreatitis with or without hypertriglyceridemia, PRIS

PRIS: This is a rare but life-threatening complication of propofol, usually occurring at doses greater

than 50 mcg/kg/minute for 48 hours or more. The mechanism of PRIS may include alterations in

hepatic metabolism of the lipid emulsion, leading to an accumulation of ketone bodies and lactate

and/or disruptions in the mitochondrial respiratory chain and inhibition of oxidative phosphorylation.

Patients with urea cycle disorders may experience alterations in propofol metabolism within 24–48

hours of propofol use. Consider avoiding in patients with acute liver failure, or pancreatitis, because

the symptoms of PRIS may be difficult to distinguish from the underlying disease state abnormalities.

PRIS carries a high mortality rate, and propofol should be discontinued immediately if symptoms are

present.

Clinical characteristics of PRIS: Metabolic acidosis, acute renal failure, cardiovascular collapse,

cardiac arrhythmias including Brugada-like syndrome, rhabdomyolysis, myoglobinemia,

myoglobinuria, hyperkalemia, hypertriglyceridemia, elevated creatine kinase concentrations

Risk factors for PRIS or other adverse effects of propofol: Neurologic injury, sepsis, use of

vasoactive medications, high-dose propofol, acute liver failure

Dexmedetomidine

SCCM suggests that in adult ICU patients with delirium unrelated to alcohol or benzodiazepine

withdrawal, dexmedetomidine infusions rather than benzodiazepine infusions should be administered

for sedation to reduce the duration of delirium.