Pain and Sedation

Pain
 Assessment:
o In an awake patient - 0–10 NRS Visual (NRS-V) preferred
o Pediatric patients: Wong-Baker FACES scale
 Resulted in higher reported pain in adults
o Nonverbal/unresponsive patients:
 Behavioral Pain Scale in intubated (BPS) and nonintubated (BPS-NI) patients
 Critical-Care Pain Observation Tool (CPOT)

o Family reporting – potentially helpful, particularly in pediatrics

 Tendency to over-estimate pain
 Procedures with high pain reported: arterial catheter insertion, chest tube removal (CTR),
wound drain removal, turning and repositioning, and tracheal suctioning
 Non-Opioids
o Multi-modal pain management
o Suggested per guidelines for opioid-sparing
 Acetaminophen
 NSAIDs – NOT recommended by guidelines for use in ICU
 Concerns: Bleed risk, AKI
 Gabapentin/Pregabalin – neuropathic pain

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  Ketamine – based on a single RCT that only included post-op patients
 low-dose ketamine (0.5 mg/kg IVP x 1 followed by 1-2 μg/kg/min
infusion)
 Concerns: hallucinations/psychological disturbances
 Not widely adopted
 Lidocaine
 IV lidocaine in some surgery patients, high dose with risk of side effects
(also not widely adopted)
 Opioids
o Guidelines recommend fentanyl, hydromorphone, morphine, and remifentanil for ICU
patients
o Why do we want to avoid opioids in general?
 Tolerance, physical dependence, opioid-withdrawal symptoms during weaning
 Strategies to minimize tolerance:
o Intermittent dosing vs continuous
o Opioid rotating
o Tapering of opioid dose when pain score is reached
 10-20% reduction every 1-4 days
o Conversion to PCA when possible
 Methadone use in adults when weaning? I’ve seen it used more
commonly in PICU
o MOA: Full mu-opioid receptor agonist, NMDA receptor blocker
and serotonin-reuptake activity and blocking adenylate cyclase
overactivity, which is partly responsible for the withdrawal
symptoms
o Variable metabolism, risk of QT prolongation – use cautiously in
ICU
 Contribute to delirium
 Contributes to the development of chronic pain later and opioid-induced
hyperalgesia (a paradoxical hypersensitivity to pain) (NEJM Opioid Tolerance in
Critical Illness)
o Side Effects
 constipation, urinary retention, and bronchospasm
 respiratory depression
 hypotension
 nausea
o Comparison - see comparison chart in NEJM article appendix
 100 mcg fentanyl = 10 mg morphine = 100 mg hydromorphone
 Fentanyl
 Duration of effect is very short with push dose (relative to morphine,
dilaudid), ~30 minutes as pain relied
 Very lipophilic
 Fentanyl oxidized by CYP3A4
 AE: serotonin syndrome?, stiff lung syndrome @ high doses

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  Morphine
 NOT renally cleared – undergoes glucuronidation to active metabolite
for renal excretion
 More hypotension, itching due to antihistamine
 Hydromorphone
 Similar half-life to morphine
 Cleared via glucuronidation, but not an active metabolite so analgesia
not affected by renal dysfunction

Sedation
 Guidelines suggest using light sedation (vs deep sedation) in critically ill, mechanically ventilated
adults
o Daily sedative interruption and nursing driven protocols *may* help achieve this, but
low level of evidence and not a true recommendation in guidelines
o Bispectral index (BIS) monitoring – typical target is 40-60 in unstimulated patients
o RASS to assess degree of sedation

 Sedative Selection:
o Propofol or dexmedetomidine are preferable to benzodiazepine sedatives (either
midazolam or lorazepam) in critically ill, mechanically ventilated adults because of
improved short term outcomes such as ICU LOS, duration of mechanical ventilation, and
delirium
 No difference in outcomes between propofol and precedex – only difference
was precedex causing less delirium at 48 hours post-cessation of sedation

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 Medication Comparison:
o See chart in 2020 Intensive Care Medicine article
o Precedex
 MOA: centrally-acting alpha-2 adrenergic agonist – alpha 2 binding causes
negative feedback for NE, which decreases sympathetic outflow
 Vastly more selective for alpha-2 compared to clonidine
 Eliminated via glucuronidation
 Does NOT suppress respiratory drive
 Max RASS score of -3 with precede (need to aim for -4 to -5 when paralyzed)
 Bradycardia
o Propofol
 MOA: GABA activation
 Very lipophilic – drug could be stored in adipose tissue and redistributed over
time (may result in delayed awakening)
 Hypertriglyceridemia > 1000  “for real” risk of pancreatitis
 > 500  risk of pancreatitis
 Provides 1.1 kcal/mL
 Suppresses respiratory drive
 Non-renal elimination
 Hypotension
o Benzos
 GABA activation
 Cause retrograde amnesia
 Lorazepam is technically preferred
 Propylene glycol is in the formulation  risk of propylene glycol toxicity
 Hepatically metabolized by glucuronidation (No CYP)
 Longer duration than midazolam
 Diazepam – really long half life. NOT continuous infusion
 Midazolam – shortest half-life as a single dose (increases with longer
infusion/administration  eventually just as long as lorazepam)
 Most lipophilic
 Renally eliminated active metabolite
 Metabolized by CYP3A4
o Ketamine
 Not a lot of good data for continuous infusion
 Lighter sedation like precedex

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  Analgesia-first sedation results in improved outcomes, including fewer days on a ventilator, as
compared with combined analgesic–sedative regimens (NEJM Opioid Tolerance in Critical
Illness)
o Reduced risk of delirium

Delirium
 Delirium: disturbance in mental abilities that results in confused thinking and reduced
awareness of the environment
o Impaired thinking/cognitive dysfunction, disorganized thinking
 Risk Factors:
o BZDs
o Transfusion administration
o Age
o Dementia
o prior coma
o pre-ICU emergency surgery or trauma
 Assessment:
o CAM-ICU

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 o Only validated if RASS 0 to -2
 Long Term Effects: longer hospital stay, increased incidence in cognitive impairment
 Prevention:
o Mobilization
o Sleep-wake cycles (lights on during the day, off at night)
o Audio and visual help – glasses, hearing aids
o Presence of familiar people
 Treatment:
o Wean sedation, preference for precedex
o Antipsychotic use not recommended by guidelines, but data is mixed

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