Pain, Sedation, and Delirium

Pain

Pain – “an unpleasant sensory and emotional experience associated with actual or potential tissue
damage, or described in terms of such damage”

Types Sources
Acute Somatic
Chronic Visceral
Acute-on-Chronic Neuropathic

Pain should be treated before a sedative agent is considered

Two approaches to analgosedation

o Analgesia-first sedation  analgesic is used before a sedative to reach the sedative goal
o Analgesia-based sedation  analgesic is used instead of a sedative to reach goal

How can severe pain impact patient status?

 _______________________________________________

Pain at rest is common in critically ill patients

 Younger age and prior surgery both predicted greater pain at rest among 301 mechanically
ventilated patients
 Cohort of > 5,000 ICU patients with self-reported pain  younger age, need for support with
ADLs, number of comorbidities, depression/anxiety, and an expectation of a future poor QOL
were all predictors of higher self-reported pain

What is the most reliable and valid pain assessment methods?

 In patients who can communicate reliably, a patient’s self-report of pain is the reference
standard
 Patients who cannot communicate reliability
o CPOT, BPS, BPS-NI
o Can consider involving family in the patient’s pain assessment
 Vital signs are not valid indicators for pain and should only be cues to initiate further assessment
Multi-Modal Pain Approach

Opioids

Remains the mainstay of pain management in most ICUs

Use the lowest effective dose
Fentanyl, dilaudid, morphine, and remifentanil are recommended for procedural pain

Acetaminophen

Should be utilized to decrease pain intensity and opioid consumption

Ketamine

_______________________--> blocks glutamate

Can utilize low dose ketamine in combo w/ opioids

Gabapentin, Pregabalin, Carbamazepine

Recommended as combination therapy for neuropathic pain

Can consider utilizing after CV surgery for pain management

IV Lidocaine

Blocks Na channels and reduces duration of action potential

Should not routinely be used as an opioid adjunct

COX-1 Selective NSAIDs

____________________________________________
Should not routinely be used as an opioid adjunct

More On Opioids….

 ADRs: _______________________________________________
  Caution in combination with ______________________________________
 Morphine is commonly utilized for comfort measures  ____________________________
 Morphine causes the most histamine release
 Fentanyl is serotonergic and lipophilic
 What should all patients on scheduled opioids have on their med list?
o ______________________________________________________________

Table 1: Opioid Equivalent Analgesic Dosing

Opioid IV PO
Fentanyl 0.1 --
Hydrocodone -- 30
Hydromorphone 1.5 7.5
Morphine 10 30
Oxycodone -- 20
Oxymorphone -- 10

Non-pharm pain management strategies

 Recommend NOT offering cybertherapy or hypnosis

 Music and massage have been shown to reduce opioid use
 Suggest offering cold therapy for procedural pain management in critically ill adults
o Cold ice packs applied for 10 minutes and wrapped in dressing gauze on the area around
a chest tube prior to removal

Agitation/Sedation

Utilized to relieve anxiety, reduce the stress of being mechanically ventilated, and prevent agitation-
related harm

Recommend targeting a light level of sedation (vs. deep sedation)

 No universal definition of light sedation

 Goal must be defined – most frequently within the order itself
o Typically RASS 0 to -2
 Appropriateness of the goal should be re-assessed frequently

Recommended agents

 Non-benzo sedatives (propofol or precedex) > benzos (midazolam or lorazepam)

o Specifically recommend propofol for patients mechanically ventilated after cardiac
surgery
 Ketamine is also an option for sedation  higher doses than when utilized for pain

Dexmedetomidine

 MOA: selective alpha 2 agonist with anesthetic and sedative properties

 ICU sedation dosing:
 o 0.2 – 1.5 mcg/kg/hr; titrate by 0.2 mcg/kg/hr every 30 minutes to sedation goal
 Can induce hyperthermia or pyrexia, which may be resistant to traditional cooling methods
 May exacerbate underlying cardiac myocardial dysfunction
o Associated with hypotension and/or bradycardia. May also cause hypertension (less
common)
o Risk factors for hypotension and/or bradycardia
 Low baseline arterial BP, increased age, increased severity of illness, loading
dose, inotrope use (cardiac ICU patients), CAD, lack of adjuvant sedatives,
titration < 30 mins, infusion > 6 hrs
o Risk factors for hypertension
 LD and higher peak plasma concentrations (effect on alpha 2B)
 SL formulation recently approved for agitation associated with schizophrenia or bipolar disorder

Propofol

 MOA: short-acting, lipophilic general anesthetic  causes CNS depression presumably through
agonism of GABAA receptors
 Usual ICU sedation maintenance dosing
o 5-50 mcg/kg/min
 Avoid in ____________________________
o American Academy of Allergy, Asthma, and Immunology statement suggest that
propofol may be used safely in soy or egg allergic patients
 May cause bradyarrhythmias and convert tachyarrhythmias to sinus rhythm
o May also be associated rarely with prolonged QT or shortening of the QT interval
 May rarely cause anaphylaxis, angioedema, and bronchoconstriction
o May be due to the presence of the diisopropyl side chain or phenol group

 Hypertriglyceridemia
o Can cause __________________________
o Formulated as ~10% lipid emulsion
o Risk factors
  Doses > 50 mcg/kg/min for > 2 days
 Higher severity of illness
 Longer ICU stay
 COVID +
 Younger patients
 Hypotension
o 30% decrease or higher in MAP
o Risk factors
 Bolus dosing
 Hypovolemia
 Older, debilitated, or ASA Physical Class 3 or 4
 Baseline MAP 60-70
 Changes in infusion rate
 Need for renal replacement therapy during treatment with propofol
 RSI with trauma
 Sepsis
 Severe aortic stenosis
 Propofol-Related Infusion Syndrome (PRIS)
o High mortality rate
o Dysrhythmia (bradycardia or tachycardia), widening of the QRS complex, HF,
hypotension, asystole, lipemia and hypertriglyceridemia, metabolic acidosis, and/or
rhabdo or myoglobinuria with AKI and hyperkalemia

Delirium

Modifiable Risk Factors

 _________________________________________________

Unmodifiable Risk Factors

 _________________________________________________

Critically ill adults should be regularly assessed for delirium using a valid tool

 CAM-ICU, ICDSC
 Level of arousal may influence delirium assessments with a validated screening tool
 Rapidly reversible delirium is associated with outcomes that are similar to patients who never
experience delirium
 Positive delirium screening in critically ill adults is strongly associated with cognitive impairment
at 3 and 12 months after ICU discharge and may be associated with a longer hospital stay
Delirium in critically ill adults is NOT associated with PTSD or post-ICU distress

 NOT consistently shown to be associated with ICU LOS discharge disposition to a place other
than home, depression, functionality/dependence, or mortality

Pharmacologic Therapy

 Recommend not using Haldol, an atypical antipsychotic, dexmed, statins, or ketamine to prevent
delirium in all critically ill adults
 Recommend not using Haldol or an atypical antipsychotic to treat subsyndromal delirium in
critically ill adults
o Subsyndromal Delirium = intermediate stage between delirium and normal cognition
 Recommend dexmed for delirium in mechanically ventilated adults where agitation is precluding
weaning/extubation

Haldol

 MOA: typical antipsychotic – blocks D2 receptors in the brain

 Associated with QTc prolongation, Extrapyramidal symptoms, temperature dysregulation,
increased mortality in older adults with dementia.
 Can be given PO, IM, or IV
o QT prolongation risk greatest with IV

Quetiapine

 MOA: atypical antipsychotic – blocks D2 and serotonin receptors

o Also hits histamine and alpha receptors
 High incidence of _____________________________
  Associated with QTc prolongation, Extrapyramidal symptoms, temperature dysregulation,
orthostatic hypotension, increased mortality in older adults with dementia

Non-Pharmacologic Therapy

 Recommend against bright light therapy to reduce delirium

 Suggest using a multicomponent, nonpharm interventions that are focused on reducing
modifiable risk factors for delirium, improving cognition, and optimizing sleep, mobility, hearing,
and vision in critically ill adults

2018 PADIS Guidelines:

Devlin JW, Skrobik Y, Gelinas C, et al. Clinical Practice Guidelines for the Prevention and Management of
Pain, Agitation/Sedation, Delirium, Immobolity, and Sleep Disruption in Adult Patients in the ICU. Crit
Care Med. 2018;46(9):e825-e873. Doi:10.1097/CCM.0000000000003299