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Invasive procedure: intravenous line placement, scoping procedures, chest tube placement or removal, paracentesis, lumbar puncture, biopsies, and fracture reductions.
Several scenarios in the ICU make the self-reporting of pain challenging for clinicians (e.g., mechanical ventilation, presence of sedation and/or delirium). a study found that higher-intensity pain and pain distress before the procedure were associated with a high risk of increased pain during the procedure. A recent study by Kanji et al. found that the CPOT is a valid pain assessment in noncomatose, delirious adult ICU patients who are not able to reliably self-report the absence or presence of pain
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. 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. 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.
Different dosage forms should not be converted on a 1:1 mcg basis Patch is not commonly used in ICU bc of its latent onset (12 h) & erratic/ increased absorption in a febrile pt.
Rebound pain: Quick offset (5–10 minutes) may lead to rebound pain and withdrawal symptoms, and additional pain medication may be needed if remifentanil is interrupted or discontinued
the d-isomer of methadone works as both a partial mu-agonist and an N-methyl-d-aspartate receptor antagonist (the l-isomer is a full mu-agonist). These properties of the d-isomer are thought to decrease the tolerance effect to other opioids. Methadone is currently marketed as the racemic mixture. On initiating oral methadone, steady state and peak analgesic effect may not be reached for 3–5 days; oversedation and respiratory depression may occur if titrated too quickly.
It is a schedule III controlled substance Ketamine is void of the constipation, respiratory depression, and hypotensive effects that plague the opiate class.
Other uses include rapid sequence intubation, refractory pain syndromes, cancer pain, neuropathic pain, asthma (bronchodilatory effects), refractory seizure activity, and depression.
S.E of Benzodiazepines: respiratory depression, altered mental status, GI slowing
Pain in the ICU
Pain in the ICU
>50% of ICU survivors report severe pain as the most thing
they remember from their ICU stay.
Short & long term negative consequences are related to
uncontrolled pain in the ICU.
Assessing pain is challenging (esp. if pt is unable to
Exacerbation of chronic pain
Acute/chronic underlying dz (cancer pain)
Common causes of pain in the ICU:
Routine nursing care
Provision of life-sustaining measures
Presence of endotracheal tube & endotracheal tube suctioning
Tube or Foley insertion
Physical/ occupational therapy
Other invasive procedures
Less noticeable causes:
Acute pain -> stress response -> hypercatabolic state ->
decrease tissue perfusion & impaired wound healing.
Uncontrolled pain-> suppress natural killer cell activity &
neutrophil fcn -> decrease in pts immune response to
Short-term consequences of pain in
Health-related quality of life decreased in up to 20% of
Chronic pain in up to 4% of pts
Posttraumatic stress d/o in 5-20% of pts.
Long-term consequences of pain in
ICU (12 months):
Gold standard for assessing pain: Pts self-report of pain.
The Behavioral Pain Scale (BPS)
The Critical-Care Pain Observation Tool (CPOT)
Should be used routinely in all ICU patients
Most protocols assess pain q4-6h (while pt is awake)
It’s important to re-asses w/in 30-60min after a PRN
PAD guidelines rcd trx w/in 30 mins of a “sig. pain” score.
BPS > 5 or CPOT ≥3 indicate pain.
Vital signs not rcd for pain assessement
Assessment of pain:
IV opioids are 1st line for nonneuropathic pain
Non-opioids for mild-moderate pain or w/ opioids to
reduce opioid dose.
Treatment of pain in ICU:
Preprocedural pain management with both non-phar & phar
Examples of nonpharmacologic:
Preemptive analgesia for chest tube removal.
Postoperative thoracic epidural anesthesia/analgesia
is recommended for patients undergoing abdominal
aortic aneurysm treatment
IV opioids on an as-needed, scheduled, or continuous
infusion basis are recommended to treat pain in the
Fentanyl is the most commonly used amongst others.
MOA: Bind to mu-opioid receptors in CNS
Pharmacotherapy for PAIN:
Tolerance: May quickly develop to all opiates,
particularly when given as a continuous infusion.
there is an equianalgesic dosing for switching
between IV & PO opiate, but may be difficult to
estimate, and low starting doses should be
Significant adverse effects:
o Decreased respiratory drive
o Decreased BP and HR.
o GI intolerance
Drug Drug intx Dose Adverse effects
Fentanyl 3A4 major substrate 12.5–25 mcg/hr;
CNS depression, constipation,
ileus, risk of serotonin
syndrome when used with
other serotonergic agents,
Morphine Glucuronidation 1–2 mg/hr Hypotension, bradycardia
from histamine release,
respiratory depression, CNS
Glucuronidation 0.25–0.5 mg/hr CNS alterations (e.g.,
abnormal dreams, aggressive
behavior, altered thinking),
HIGH potency opiate.
Drug Drug intx Dose Adverse effects
Methadone 3A4 and 2B6 major
syndrome, altered mental
status, respiratory depression,
arrhythmias, constipation, risk
of serotonin syndrome when
used with other serotonergic
Remifentanil Blood and tissue
1.5 mcg/kg CI:
Chest wall rigidity; rebound
pain on discontinuation,
o Hepatic metabolism
o CYP450 3A4 substrate
o Quick onset and short duration of action
o No active metabolites
o Highly lipophilic
o High Vd and protien binding
o 3-compartment model
o Continuous infusion -> prolonged & unpredictable clearance
Dosage forms: injectable, transdermal, transmucosal and
o Two active metabolites: morphine-3-glucuronide (no
analgesic effect) & morphine-6-glucuronide
o Renally eliminated
Dosage forms: injectable and oral.
o Inactive but neurotoxic metabolite
o Low Vd
o Highly water soluble
o Low protein binding
Dosage forms: injectable and oral
Pharmacokinetics: Clearance by blood and tissue esterase
clearance not dependent on organ function.
o Fast onset and duration of action
o High Vd
o High protien binding
Benefit in adult ICUs: decreased time on mechanical
ventilation with short-term use.
Dosage forms: injectable only.
o Inactive metabolites
o Many drug interactions
o Variable duration of action (12-48hr)
o Marketed as a racemic mixture
Dosage forms: injectable and oral
Clinically stable patients may tolerate a conversion
from opiates to non-opiate medications.
Local and regional anesthetics such as bupivacaine
Non-opioid adjunctive meds:
Maximum daily dose: 4g
Decreased total daily dose in liver dysfcn pt
IV acetaminophen: dose should be reduced if CrCl ≤
30ml/min/1.73m2 OR w/ continuous renal replacement
C/I in severe hepatic dz.
PO or rectal is cheaper than IV.
For critically ill pts. w/ renal or hepatic dysfcn.
May increase risk of AKI, bleeding, or GI SE.
IV or PO NSAID meds:
Used for analgesia and sedation in the ICU, primarily in the
N-methyl-d-aspartate receptor antagonist.
A “dissociative anesthetic,” providing analgesic activity at
S.E: Mild - severe emergence reactions (e.g., confusion,
excitement, irrational behavior, hallucinations, delirium),
enhanced skeletal muscle tone, tachycardia, hypertension,
Dose analgesia or sedation initial: 0.1mg/kg/hr.
for adult ICU pts: 0.1-2.5mg/kg/hour.
Gabapentin: 300-600mg/d divided 2-3/d & requires renal
S.E: CNS depression, paresthesias, and asthenias
Carbamazepine: 50-100mg BID
Use w/caution in pt w/ hepatic impairment and adjust for CrCl
<10ml/min/1.73m2 or hemodialysis
PK: strong CYP inducer, monitor intx.
S.E : Somnolence, severe skin reactions (e.g., Stevens-Johnson
syndrome, toxic epidermal necrolysis), pancytopenia, syndrome
of inappropriate antidiuretic hormone
Anticonvulsants: rcd w/opioids for
confirmed neuropathic pain.
It advices the use of opiate medications before prescribing an
anxiolytic/hypnotic medication to provide patient comfort in
the ICU unless anxiolytics are otherwise indicated.
Early pain relief in ICU -> decrease agitation &/or general
Minimize the use of alternative meds (for agitation) like
Analgosedation Method in the ICU