This document discusses sedation and paralysis practices in the ICU. It notes that agitation occurs in 50% of ICU patients with stays over 24 hours and is often due to pain, delirium, anxiety or sleep deprivation. Sedation goals are listed as providing patient comfort while allowing interaction. Ideal sedation agents lack respiratory depression and provide analgesia, easy titration and arousability. Common sedation scales are described. Evidence supports lighter sedation over deep sedation. Propofol may allow faster extubation than benzodiazepines. Dexmedetomidine is beneficial but can cause bradycardia. Haloperidol is not routinely recommended for delirium. Neuromuscular blockade is described along

1. SEDATION AND PARALYSIS IN ICU
BY DR.ABHINOB ROY
SENIOR RESIDENT
CRITICAL CARE MEDICINE

2. ICU Triad
Pain
Agitation
Delirium

3. What do we know about agitation/discomfort?
•Prevelance
- 50% incidence in those with length of stay >24 hours
• Primary cause
• Unrelieved pain
• Delirium
• Anxiety
• Sleep deprivation

4. ICU Agitation/discomfort sequelae
Immediate
• Patient-ventilator
dyssynchrony
• Increased oxygen
consumption
• Self (and health care
provider) injury
• Family anxiety
Long term
• Chronic anxiety disorders
• Post-traumatic stress
disorder.

5. Goals of sedation in ICU
• Patient comfort
• Control of Pain
• Anxiolysis and amnesia
• Blunting adverse autonomic and hemodynamic responses
• Facilitate nursing management
• Facilitate mechanical ventilation
• Avoid self-extubation
• Reduce oxygen consumption

6. Characteristics of an ideal sedation agent for
the ICU
• Lack of respiratory depression
• Analgesia, especially for surgical patients.
• Rapid onset, titrable, with short elimination half-time
• Sedation with ease of orientation and arousability
• Anxiolytic
• Haemodynamic stability
• The optimal level of sedation for most patients is what offers comfort
while allowing for interaction with the environment

7. Validated sedation assessment tools
• Richmond Agitation-sedation Scale[RASS]
• Ramsay sedation scale [RSS]
• Riker sedation- agitation Scale [SAS]
• Observer assessment of Alertness/Sedation scale
[OAASS]
• Motor activity assessment scale [MAAS]

9. Riker sedation-agitation scale

10. Daily goal is arousable, comfortable
sedation
Sedation needs to be protocolised and
titrated to goal:
• Ideal sedation goal : patient to be awake and
comfortable with minimal to no distress (eg 0
on RASS scale

11. Effect of this strategy on outcomes:
• 15% reduction in overall mortality,
• 1.73-day reduction in ICU length of stay
• 3.55-day reduction in hospital length of stay
• 31% reduction in tracheostomy

12. Administration
• Current practice favours intermittent bolus dose, daily interruption or
dose minimization titrated to lighter levels of sedation (RASS -2 to 0)
of continuous infusion

13. Sedativeoptions
How to sedate?
• Benzodiazepines
• Propofol
• Alpha 2 agonists

14. Sedation options: Benzodiazepines
(Midazolam and Lorazepam)
Features Midazolam Lorazepam
Onset of action 2-5 minutes 15-20 minutes
Elimination half-time 1-4 hours (Reves Et al 1985) 10-20 hours
Duration of action (after bolus) 1-2 hours 6-10 hours
Metabolism In liver by P450 enzymes In liver by glucoronidation
Active metabolite 1 hydroxymidazolam None
Loading dose 0.01-0.05 mg/kg 0.02-0.04 mg/kg (</= 2 mg)
Continuous infusion 0.02-0.1 mg/kg/hr 0.01-0.1 mg/kg/hr (</= 10 mg/hr)

15. Benefits
• Anxiolytic
• Amnestic
• Sedating
• Anticonvulsant
Risks
• Delirium
• No analgesia
• Excessive sedation : especially after long term sustained use
• Propylene glycol toxicity after parentral lorezepam
• Unexplained metabolic acidosis during prolonged (> 24 hours) infusion

16. Sedation option : Propofol
• Mechanism of action- GABA agonist
• Pharmacokinetics/ pharmacodynamics-
• Onset- 1-2 minutes
• Duration of action- 10 minutes
• Context sensitive half-time for infusion lasitng upto 8 hrs : < 40 minutes.
( Hughes Et al 1992)
• Metabolism-Hepatic ( glucoronidation)
• Elimination – renal

17. • Dose -25-75 mcg/kg/min
• Benefits
• Rapid onset and offset and easily titrated
• Hypnotic and anti emetic
• Anticonvulsant action
• Risks
• No analgesia
• Hypotension
• Hypertriglyceridemia
• Respiratory depression
• Propofol infusion syndrome
• Prolonged high dose infusion >75mcg/kg/min for >24 hrs ( Badr Et al 2001)
• Rhobdomyolysis
• Severe metabolic acidosis
• Cardiac failure

18. Sedation option : Dexmedetomedine
• Mechanism of action – alpha 2 receptor agonist( alpha 2:alpha 1
selectivity :: 1620:1)
• Pharmacokinetics and pharmacodynamics-
• Onset of action -5-10 minutes
• Elimination half time- Approx. 2 hrs
• Metabolism- in liver ( glucuronidation,hydroxylation,n-methylation)
• Dose
• loading –1mcg/kg over 10 minutes
• Maintainance- 0.2-0.7 mcg/kg/hr

19. • Benefits
• Doesn’t cause respiratory depression
• Arousal is maintained despite deep levels of sedation
• Risks
• Life threatening bradycardia

20. Other modality for sedation
• AnaConDa system- Inhalational anesthesia system designed in
Sweden.
• For use with ventlators in ICU.
• Better pharmacokinetic profile than than many i.v sedatives.

21. Significance of ICU delirium
• Prevelance –
The prevalence of delirium reported in medical and surgical ICU cohort
studies has varied from 20% to 80%, depending upon severity of illness
observed and diagnostic methods used. (Thomason JW Et al, 2008)
• Definition –
Disturbance of consciousness (ie, reduced clarity of awareness of the
environment) occurs, with reduced ability to focus, sustain, or shift attention.
(DSM-5 diagnostic criteria for delirium)

22. Types of delirium
• decreased responsiveness
• withdrawal
• apathy
Hypoactive
delirium
• agitation
• restlessness
• emotional lability
hyperactive
delirium

24. Validated tools for delirium assessment
•CAM ICU (Confusion Assessment method for the
intensive care unit)
•ICDSC (Intensive Care delirium screening
Checklist)

25. CAM -ICU
Content of consciousness is assessed (delirium is diagnosed) using the Confusion Assessment Method for the ICU
(CAM-ICU) [50,53]. When three of four diagnostic features are present (either features 1, 2, and 3, or features 1, 2,
and 4), delirium is diagnosed .

26. Pharmacological intervention : Haloperidol
• Mechanism of action : Dopamine receptor blocker
• Onset of action : 10-20 minutes
• Duration of action : 10-20 minutes
• Dose
• Mild anxiety 0.5 -2 mg
• Moderate anxiety 5-10 mg
• Severe anxiety 10-20 mg
• REDUCE trial conducted across 21 ICU in Netherland showed Prophylactic
treatment with 2 mg Haloperidol 8 hourly did not prevent the onset of
delirium (33% 2 mg Haloperidol vs. 33% Placebo, difference 0.4%, 95% CI,
−4.6% to 5.4%) and did not alter delirium/coma-free days (median
difference, 0 days, IQR 0 to 0 days)

27. BENEFITS
• Hemodynamic neutrality
• No respiratory depression
Adverse effects
• QTc prolongation and torsades pointes
• Extrapyramidal side effects : less common when given intravenously

28. Atypical antipsychotics : Quetiapine,
Olanzepine,Risperidone, Ziprasidone
One prospective randomized study showing equal efficacy of
olanzapine to haloperidol with less extra pyramidal symptoms.

29. 2018 Pain ,Agitaion/sedation, Delirium, Immobility
and Sleep disruption (PADIS) guideline
-SCCM
• Focus – on improving post- ICU outcomes.
• Investigating –
sedation delivery paradigm ( light vs deep)
specific sedative medications

30. Sedation delivery paradigm
- light vs deep sedation
•Evidence – 8 RCTs and 3 Observational studies

31. • 90 days mortality ( 2RCTs, 324 patients)
• Not significant. RR 1.01 (95%CI, 0.80 to 1.27; low quality)
• Self extubation (4 RCTs, 546pts)
• Not significant RR 1.29 (95% CI , 0.58 to 2.88;low quality)
• Light sedation was not associated with reduction in
• PTSD (2 RCTs, 62 pts) RR 0.67 (95% CI, 0.12 to3.79)
• Depression (2 RCTs, 128 pts) , RR 0.76 (95% CI ,0.10 to 5.58)
• Delirium ( 2 RCTs , 140 pts) RR 0.96 ( (%% CI, 0.80 to 1.16)

32. • Tracheostomy rate (1 RCT & 1 Observational , 452 pts)
• Reduced RR 0.57 (95 % CI , 0.41 to 0.80)
• Time to extubation ( 3 RCTs 453 pts ;low quality)
• Associated with shorter time , MD – 0.77 days ( 95% CI , -0.24to 0.50)
• Time to extubation ( 3 observation, 1524 pts ; low quality)
• Associated with shorter time MD- 3.46 days (95% CL, -5.70 to -1.23)

33. Recommendation
• Light sedation ( vs deep sedation ) is recommended in critically ill ,
mechanically ventilated adults ( low quality of evidence)..

34. Choice of sedative: medical and surgical
patients ( non cardiac surgery)
• For sedation in critically ill and mechanically ventilated adults
comparison of the following drugs have been done-
Propofol vs benzodiazepines
Dexmed vs benzodiazepines
Dexmed vs propofol

35. • Propofol vs benzodiazepines
• Time to extubation ( 10 RCTs, 423 pts )
• Reduced by 11.6 hr ( 95%CI , -15.6 to 7.6 ; low quality)
• Time to light sedation (10 RCTs, 357 pts)
• Reduced by 7.2 hr ( 95 % CI , -8.9to -5.5 ;low quality )
• Dexmed vs Benzodiazepines
• No significant benefit of Dexmed ovr BZD infusion for-
• Duration of mechanical ventilation
• ICU length of stay
• Risk of delirium
• Dexmed vs Propofol
• No significant difference in time to extubation (3 RCTs , 850 pts)

36. Recommendation
• Either Profopol or Dexmed is suggested over benzodiazepines for
sedation in critically ill, mechanically ventilated adults
In the existing studies for this recommendation –
Bzodiazepines mostly given as infusion rather than bolus.

37. Recommendation
•Routinely using Haloperidol and antipsychotic to
treat delirium not suggested (low quality
evidence)

38. Neuromuscular Blockade (NMB) (Paralytics) in the
Adult ICU
• Used most often acutely (single dose) to facilitate intubation or
selected procedures
• Issues
NO ANALGESIC or SEDATIVE properties
If administering for prolonged period (> 6 - 12 hours), use an objective monitor
to assess degree of paralysis.

39. Indications
• Facilitate mechanical ventilation, especially with abdominal
compartment syndrome, high airway pressures, and dyssynchrony
• Assist in control of elevated intracranial pressures
• Reduce oxygen consumption
• Prevent muscle spasm in neuroleptic malignant syndrome, tetanus, etc.

40. Two classes of NMBS
Depolarizers
-Succhinylcholine
- Prolonged binding to acetylcholine receptor to produce
depolarization (fasciculations) and subsequent desensitization so that the
motor endplate cannot respond to further stimulation right away
Nondepolarizers
- Blocks acetylcholine from postsynaptic receptor competitively
- Benzylisoquinoliniums - Curare, atracurium, cisatracurium, mivacurium,
doxacuronium
- - Aminosteroids - Pancuronium, vecuronium, rococuronium

41. Quick Onset Muscle Relaxants for Intubation
Patients with aspiration risk need rapid onset paralysis for intubation.
• Rocuronium
Duration 60 minutes
Dose is 1.2 mg/kg to have intubating conditions in 45 seconds
Succinylcholine
Duration - 10 minutes
Dose is 1 - 2 mg/kg to have intubating conditions in 30 seconds

42. Potential Contraindications of Succinylcholine
• Increases serum potassium by 0.5 to 1 meq/liter in all patients
• Can cause bradycardia, anaphylaxis, and muscle pain
• Potentially increases intragastric, intraocular, and intracranial pressure
• Severely elevates potassium due to proliferation of extrajunctional
receptors in patients with denervation injury, stroke, trauma, or burns
of more than 24 hours

43. Nondepolarizing muscle relaxants
Pancuronium, vecuronium,atra/cisatracurium
All rapid onset (2 - 3 minutes)
• Differ in duration (pancuronium >50 minutes, vecuronium,atra/
cisatracurium 20 to 50 minutes)
• Differ in route of elimination (pancuronium = renal/liver, vecuronium
= renal/bile, atra/cisatracurium = Hoffman degradation)

44. Infusion doses
• Pancuronium 0.048 - 0.1 mg/kg/h (Greenberg 2013)
• Vecuronium 0.048 - 0.72 mg/kg/h
• Atracurium 0.24 – 1.2 mg/kg/h (Murray 2002)
• Cisatracurium 0.06- 0.18 mg/kg/hr (Greenberg 2013)
Other distinguishing features
• Pancuronium causes tachycardia
• Vecuronium has neutral effects on hemodynamics but has several renally
excreted active metabolites
• Elimination of atra/cisatracurium is not affected by organ dysfunction

45. Monitoring NMBAs
• Goal - To prevent prolonged weakness associated with excessive NMBA
administration.
• Methods
Peripheral nerve stimulation
• Train of four response consists of four stimulae of 2 Hz, 0.2 msec in duration,
and 500 msec apart.
• 4 twitches seen 0-75% receptors are blocked
• 3 twitches seen at least 75% receptors are blocked
• 2 twitches seen 80% of receptors are blocked
• 1 twitch 90% receptors are blocked
For monitoring sedation during paralysis BIS (Bispectral index) is used.

46. THANK YOU