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.