Prevention and Management of Pain,

Agitation/Sedation, Delirium,
Immobility, and Sleep Disruption in
Adult Patients in the ICU
John W.Davlin,et al.Crit care med.2018
Society of Critical Care Medicine
ABCDE Bundle elements
A Assess, Prevent and manage pain
B Both SAT and SBT
C Choice of anesthesia and sedation
D Delirium ; assess, prevent and manage
E Early mobility and exercise
F Family engagement and empowerment
G Good sleep
Eduard E Vasilevskis,et al.Chest.2010
Judy E Davinson,et al.Am nurse Today.2013
Pain
• An unpleasant sensory and emotional experience associated with
actual or potential tissue damage, or described in term of such
damage.
• Complex and influenced by psychological ( anxiety, depression, etc)
and demographic (young age, co-morbidities, surgery) variables.
• Gold standard to pain assessment is self-report
Pain
• Pain assessment in ICU
• Numeric rating scale (0-10) ; for communicable patient
Pain
• Pain assessment in ICU

Start analgesia when score ≥ 6

Gerald Chanques,et al.Intensive Care Med.2009

Payen j,et al.Crit Care Med.2001
Pain
• Pain assessment in ICU

Critical care pain observation tool (CPOT)

Start analgesia when score ≥ 3

Pain
• Multi-modal analgesia
• Pharmacological treatments
• Opioids ; mainstay…
• First line for non-neuropathic pain in ICU  IV opioids.
• ADR : Respiratory depression, over sedation, constipation, ileus, nausea/vomit, pruitus.
Withdraw
• Produce sedating effects but not diminish awareness.
• Adjunct analgesia
• Acetaminophen
• Nefopam
• Ketamine
• Lidocaine and COX-1 selective NSAIDs not recommendation for routine use
 Accumulation with hepatic/renal impairment
Histamine release

Less hypotension
Less accumulation with hepatic impairment

Normeperidine  neuroexcitation
Acetaminophen
- Prefer iv route
- 1 g IV/PO/PR q 6 hr for 24 to 72 hr
- Lower dose in liver impairment

Nefopam
- Inhibit dopamine, noradrenaline, serotonin
- 20 mg dose effect comparable to 6 mg of iv mm
- Least side effect ; gastric, renal/hepatic, ventilation
- Tachycardia, glaucoma, seizure and delirium

Ketamine
- NMDA receptor
- Low dose 0.5 mg/kg followed by 1-2 ug/kg/min
- Reduce risk for opioid hyperalgesia
Pain
• Neuropathic pain medication
• Recommended for neuropathic pain management in critically ill adults
• Gabapentin
• Carbamazepine
• Pregabalin
Pain
• Non-pharmacologic treatment
• Suggested
• Massage
• Music
• Not-suggested
• Hypnosis
• Cyber therapy (virtual reality)
Sedation-agitation
• Analgesia before sedation
• Reduce anxiety and agitation
• Facilitate mechanical ventilation
• Induce sleep
• Reduce delirium
• Facilitate patient’s communication
• Improve comfort and safety
• Decrease PTSD
Sedation-agitation
• Richmond agitation sedation scale (RASS) Light sedation
• 90-day mortality
• Time to extubation
• Delirium
• Tracheostomy
• Cognitive and physical
functional decline
• Depression
• PTSD

Curtis N,et al. Am J Respir Crit Care Med.2002

 Sedation-agitation
Adventage Disadventage
Propofol Ultrashort acting
Antiemetic
Hypotension
Respiratory depression
anxiolytic Rhabdomyolysis/propofol infusion
syndrome
Contamination/sepsis
No analgesia

Loading ; 0.25-1 mg/kg maintenance ; 25-75 mcg/kg/min onset of action <1 min
PRIS ; incidence 1.1%
metabolic acidosis + cardiac dysfunction and at least one of
…rhabdomyolysis, hypertriglyceridemia
Risk ; dose > 4mg/kg/hr and duration > 48 hrs
Olaf L Cremer,et al. Crit Care.2009
 Sedation-agitation
Adventage Disadventage
Benzodiazepine Palliative Respiratory depression
Hypotension (MAP decrease 10-25%
(midazolam*, No analgesia
lorazepam. Diazepam) Paradoxical agitation
Risk of delirium
Sedation-agitation
Adventage Disadventage
Dexmedetomidine Cooperative sedation
Mimics natural sleep
Bradycardia if bolus
Vasoconstriction then vasodilatation
hydrochloride Anxiolytic and analgesia Expensive
(DXMD) Reduces shivering
No respiratory depression
…selective α2 agonist Predictable cardiovascular response

No bolus
Loading : 1 mcg/kg over mins maintenance : 0.2-0.7 mcg/kg/hr
Metabolized in liver, elimination renal excretion
Sedation-agitation
• Propofol vs benzodiazepine
• Shorter time to light sedation
• Shorter time to extubation
• Dexmedetomidine vs
benzodiazepine
• Reduce delirium
• Shorter duration of mechanical
ventilation
• More incidence of bradycardia
Devlin JW,et al. Crit Care med.2018
Sedation-agitation

Richard R. Riker,et al. JAMA.2009

Sedation-agitation

Dexmedetomidine pt
had higher actual RASS scores
in both studies

Stephan M. Jakob,et al. JAMA.2012

Sedation-agitation

Duration of Mechanical Ventilation and ICU stay was not significantly different

Stephan M. Jakob,et al. JAMA.2012

 Result ;
- A rate of death at 90 days similar
- Bradycardia and hypotension more
common in the dexmedetomidine group.

NEJM.May 19,2019.

- Randomized trial, critically ill adults

- Undergoing ventilation for less than 12 hours in the ICU
- Receive dexmedetomidine (1-1.5 mcg/kg/hr) as the sole vs receive usual care (propofol, midazolam, or other sedatives)
- The target range of sedation-scores … RASS -2 to +1
The median of 63.7 years, with lower mortality in older patients and higher mortality in younger patients.
It could be due to age-related changes in the pharmacokinetics of sedatives.

Y. Shehabi,et al.NEJM.May 19,2019.

Sedation-agitation

128 adult patients, mechanical ventilation, continuous infusions of sedative drugs in ICU.
In the intervention group, the sedative infusions were interrupted until the patients were awake, on a daily basis.
In the control group, the infusions were interrupted only at the discretion of the clinicians.

JOHN P,et al. N Engl J Med. 2000.

Neuromuscular blocking agents
• Indication
• Intubation
• Ventilator dysynchrony, PF ratio < 150
• Shivering during TTM
• Depolarizing muscle relaxant
• Succinylcholine ;
• 1 mg/kg, intubation within 1-1.5 mins, resume respiration in 5-6 mins
• SE ; bradycardia, fasciculation, hyperkalemia, increase ICP/IOP
Neuromuscular blocking agents
• Non-depolarizing muscle relaxant
• Benzylisoquinolines
Cisatracurium Atracurium
Initial bolus 0.15 mg/kg or 15 mg 0.4-0.5 mg/kg
Starting rate 3 mg/kg/min 11-13 mg/kg/min
Metabolism Hoffman elimination Hoffman elimination
Side effects Histamine release, Skin flushing, histamine
bronchospasm, release with doses > 0.6
hypotension mg/kg
Neuromuscular blocking agents
• Non-depolarizing muscle relaxant
• Aminosteroids
Rocuronium Vecuronium
Initial bolus 0.6mg/kg or 1.2 mg for rapid 0.8 mg/kg
sequence intubation
Starting rate 10-12 mg/kg/min 1 mg/kg/min
Metabolism Tissue redistribution, renal Urinary excretion
Side effects Transient anaphylaxis
hypotension/hypertension,
anaphylaxiz

Sugammandex 16 mg/kg iv reverse rocuronium

Sedation-agitation
• Monitoring
• Bispectral index (BIS) ; target 40-60
Delirium
• Acute onset of cerebral dysfunction with a change or fluctuation in
baseline mental status, inattention and either disorganized thinking or
an altered level of consciousness
• Incidence of ICU delirium
• 60 – 80% of mechanically ventilated patients
• 20 – 40% of non-ventilated patients
• Subtypes
• Hyperactive ; agitated, hallucinations and delusions
• Hypoactive ; calm or lethargic, confusion and sedation
• Combination of both Barr J,et al. Crit Care Med.2013
Brummel, et al.Crit Care Med.2014
Delirium
• Risk factors
• Age
• Hx of dementia/hypertension
• Emergency Sx, trauma Dexmedetomidine associated with
• APACHE II score a lower prevalence of delirium
• Mechanical ventilation
• Metabolic acidosis
• Coma
• Multi organ failure

Barr J et al.Crit Care Med.2013

Zaal et al.Crit Care Med.2015.
Delirium
• Regular assessment with a validated assessment tool
• 5 Monitoring tools evaluated
• Intensive Care Delirium Screening Checklist (ICDSC)
…The most valid and reliable
• Confusion Assessment Method for the ICU (CAM-ICU)
• Cognitive Test for Delirium (CTD)
• Delirium Detection Score (DDS)
• Nursing Delirium Screening Scale (Nu-DESC)

Barr J et al.Crit Care Med.2013

Neto AS et al. Crit Care Med 2012
Delirium

Copyright © 2002, E. Wesley Ely, MD, MPH and Vanderbilt University.

Devlin JW,et al.Crit Care.2008
Delirium
• Associated with ;
• Cognitive impairment at 3 and 12 months post discharge
• Associated with longer hospital stay
• Not associated ;
• PTSD, ICU length of stay, depression, functional dependence, mortality, discharge
disposition to place other then home
• Prevention
• Early mobilization of adult ICU patients whenever feasible to reduce the incidence and
duration of delirium
• No recommendation ;
• Haloperidol or atypical antipsychotics
• Dexmedetomidine to prevent delirium
Adler J and Malone D. Cardiopulm Phys Ther J. 2012
Delirium
• Treatment
• Multi-component ; non-pharmacologic intervention on risk reduction
• Improve sleep
• Improve wakefulnee
• Reduce immobility
• Reduce visual/hearing impairment

• Adult ICU patients with delirium, IV infusions of dexmedetomidine

rather than benzodiazepine infusions for sedation in order to reduce
delirium
Delirium
• Haloperidol : starting dose: 1-2mg q 4-6hrs PRN, Metabolic pathway:
Glucuronidation and CYP 3A4/2D6 substrate.
• Adverse effects: sedation, EPS, QTc prolongation (IV route)

Current evidence does not show

a reduction in shorterm mortality despite
a reduction in delirium duration

Al-Qadheeb NS, et al. Crit Care Med . 2014;

Delirium
• Evidence is lacking to support the best agent of antipsychotics
• Small studies available with limited results
• The MIND Trial (Girard 2010)
• Devlin JW et al, 2010 (Devlin 2010)
• Michaud CJ et al, 2015 (Michaud 2015)
• Current ongoing research
• The Modifying the Impact of ICU-Associated Neurological Dysfunction –USA
Study (MIND-USA)
Delirium
• Recommended ;
• Either daily sedation interruption or a light target of level of sedation be
routinely used in mechanically ventilated patients.
• Analgesia-first sedation be used in mechanically ventilated adult ICU patients.
• Promoting sleep in adult ICU patients by optimizing patients’ environments,
using strategies to control light and noise, clustering patient care activities,
and decreasing stimuli at night to protect patients’ sleep cycles
• Interdisciplinary ICU team approach.
Immobility : rehabilitation/mobilization
• Recommended for critically ill adults
• Begin if stability even if with vasoactive infusion or mechanical
ventilation
• HR 60-13-/min
• BP 90-18-/60-100 mmHg
• RR 5-40/min
• SpO2 >= 88%
• FiO2< 0.6 and PEEP < 10
• Airway is secured
Sleep
• Potentially modifiable risk factor influencing recovery in critically ill
adults
• Sleep intervention lessen delirium occurrence

Flannery, et al.Crit Care Med.2016

Sleep
• Pharmacologic intervention
• No recommendation ; melatonin, dexmedetomidine
• Recommend against ; propofol
• No data ; antidepressants, antipsychotics
• non-pharmacologic intervention
• ACV > PSV
• Reduce noise and light

Sairam Parthasarathy,et al. Am J Respir Crit Care Med . 2002.

John W.Davlin,et al.Crit care med.2018.
Caring for Critically Ill Patients with the ABCDEF
Bundle: Results of the ICU Liberation Collaborative in
Over 15,000 Adults

Brenda T. Pun,et al.Crit Care Med.2019.

Caring for Critically Ill Patients with the ABCDEF
Bundle: Results of the ICU Liberation Collaborative in
Over 15,000 Adults
Symptom-related outcomes

Brenda T. Pun,et al.Crit Care Med.2019.

Conclusion
• Pain control before sedative agent
• Assess with validated tools, manage with opioids as needed but consider pharmacologic and non-pharmacologic adjuncts
• Protocols work.
• Agitation
• Light better than deep sedation
• If infusion, either daily interruption or nurse-driven targeted protocol.
• Delirium
• Assess regularly
• Pharmacologic prevention not recommended.
• Prevention best.
• Imobility
• Rehab/mobilization is safely done and recommended for most ICU patients
• Sleep
• ICU patients sleep poorly.
• Non-pharmacologic intervention recommended, no pharmacologic intervention is proven.