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

iv.

Significant adverse effects: Decreased respiratory drive: This may be a desired effect in

some ICU scenarios; however, a depressed respiratory drive is a critical negative implication

during the ventilator weaning process; decreased blood pressure and heart rate, constipation,

gastrointestinal (GI) intolerance, altered sensorium.

GI intolerance and constipation: A bowel regimen should be initiated on day 1 unless

contraindicated, with assessment for efficacy every 24–48 hours. GI intolerance in the ICU

can result in increased time on mechanical ventilation, delayed time to attaining nutritional

goals, and prolonged ICU stay. Constipation may also contribute to agitation.

vi.

Altered mental status: Opiates may induce a sedative effect as well as an altered sensorium in

some patients. Unless contraindicated, clinicians should consider tapering the opiate dose in

an altered patient who has adequate pain control.

vii.

Patient-controlled analgesia: In alert and clinically stable patients, use of patient-controlled

analgesia may be considered to titrate to the patient’s perceived level of pain. Patient-controlled

analgesia may also be useful on discontinuation of continuous infusion opiates.

Fentanyl

Pharmacokinetics: Hepatic metabolism, cytochrome P450 (CYP) 3A4 substrate. Quick onset

and short duration of action; lacks a pharmacologically active metabolite. Highly lipophilic,

high volume of distribution and protein binding; maintains a three-compartment model;

continuous infusion dosing may lead to prolonged and unpredictable clearance (prolonged

context-sensitive half-time).

ii.

Many dosage forms: Injectable (intravenous, intramuscular, intrathecal, epidural), transdermal,

transmucosal, nasal spray. Different dosage forms should not be converted on a 1:1 mcg basis;

use specific manufacturer recommendations if converting. Injectable form of fentanyl is most

commonly used in the ICU setting. The fentanyl patch is not generally appropriate for use in

the ICU because of its latent onset (about 12 hours) and erratic/increased absorption in a febrile

patient.

iii.

Adverse effects: Respiratory depression, bradycardia, hypotension, CNS depression,

constipation, ileus, risk of serotonin syndrome when used with other serotonergic agents

Morphine

Pharmacokinetics: Hepatic metabolism by glucuronidation to two major active metabolites,

morphine-3-glucuronide

(45%–55%)

and

morphine-6-glucuronide

(10%–15%).

The

glucuronide metabolites of morphine are both renally eliminated; accumulation can occur

with the chronic use of morphine or in patients with decreased renal function. Morphine-3-

glucuronide does not have analgesic activity, but adverse effects may include seizure activity

or agitation. Morphine-6-glucuronide does have analgesic activity by the mu-receptor and

may cause additive sedation and respiratory depression if accumulation occurs. Continuous

morphine infusions are rarely used for analgesia in the ICU setting because of the concerns

with the active metabolites.

ii.

Dosage forms: Injectable (intravenous, subcutaneous, intrathecal, epidural) and oral.

Intravenous-to-oral conversion is not a 1:1 mg ratio.

iii.

Adverse effects: Histamine release may cause significant hypotension; bradycardia, respiratory

depression, CNS depression, constipation, ileus.

Pharmacokinetics: Hepatic metabolism by glucuronidation to an inactive but potentially

neurotoxic metabolite. Low volume of distribution, highly water soluble, and relatively low

protein binding.