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

Nonpharmacologic therapy for pain

The PADIS guidelines suggest offering cold therapy for procedural pain management in critically

ill adults.

The PADIS guidelines suggest offering relaxation techniques for procedural pain management

in critically ill adults. Music therapy is suggested for both nonprocedural and procedural pain in

critically ill adults.

Intravenous opioids on an as-needed, scheduled, or continuous infusion basis are recommended

to treat pain in the ICU. The pharmacokinetics of different opioids may vary; thus, opioids should

be chosen according to patient comorbidities and individual needs (Table 3). Fentanyl is the most

commonly used intravenous opioids in U.S. adult ICUs.

Drug

Metabolic/Drug

Interaction

Considerations

Usual CI Starting

Dosea

Drug-Specific

Adverse Effectsb

Drug Accumulation Factors

Fentanyl

3A4 major

substrate

12.5–25 mcg/hr;

0.35–0.5 mcg/

kg loading dose

follwed by 12.5–25

mcg/hr

Muscle rigidity

Hepatic failure; high volume of

distribution; high lipophilicity;

unpredictable clearance (long

context-sensitive half-time)

with prolonged infusion

Morphine

Glucuronidation

1–2 mg/hr

Hypotension,

bradycardia from

histamine release

Hepatic failure; active

metabolite (3- and 6-morphine

glucuronide) accumulates in

renal failure

Hydromorphone

Glucuronidation

0.25–0.5 mg/hr

Overdose

effects 
from

dosing errors

(high-potency

opiate)

Hepatic failure

Methadone

3A4 and 2B6

major substrates

N/A

QTc prolongation,

serotonin

syndrome

Long half-life; hepatic and

renal failure will delay

clearance

Remifentanil

Blood and tissue

esterases

Loading dose: 1.5

mcg/kg

CI: 0.5–15 mcg/

kg/hr

Chest wall rigidity;

rebound pain on

discontinuation

aUsual starting dose in the ICU for pain management in an opiate-naive patient.

bOther common significant adverse effects for all opiates to be considered: Constipation, respiratory depression, bradycardia, hypotension, altered mental status.

CI = continuous infusion.

General mechanism of action of opiates: Bind to mu-opioid receptors in the central nervous

system (CNS)

ii.

Commonly used intravenous opioids in the ICU: Fentanyl, morphine, hydromorphone,

remifentanil, and methadone

iii.

Tolerance: May quickly develop to all opiates, particularly when given as a continuous infusion.

If switching to a different intravenous or oral opiate, equianalgesic dosing may be difficult to

estimate, and low starting doses should be considered.