Sedation, Analgesia and Paralysis in ICU
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Transcript of Sedation, Analgesia and Paralysis in ICU
Sedation, Analgesia and Paralysis in ICU
Mazen Kherallah, MD, FCCP
ICU Sedation
• ICU sedation is a complex clinical problem
• Current therapeutic approaches all have potential adverse side effects
• Agitated patients are often hypertensive, increase stress hormones, and require more intensive nursing care
The Need for Sedation
• Anxiety• Pain• Acute confusional status• Mechanical ventilation• Treatment or diagnostic procedures• Psychological response to stress
• Patient comfort and • Control of pain• Anxiolysis and amnesia• Blunting adverse autonomic and
hemodynamic responses• Facilitate nursing management• Facilitate mechanical ventilation• Avoid self-extubation• Reduce oxygen consumption
Goals of sedation in the ICU
Characteristics of an ideal sedation agents for the ICU
• Lack of respiratory depression• Analgesia, especially for surgical patients• Rapid onset, titratable, with a short
elimination half-time• Sedation with ease of orientation and
arousability• Anxiolytic• Hemodynamic stability
The Challenges of ICU Sedation
• Assessment of sedation• Altered pharmacology• Tolerance• Delayed emergence• Withdrawal• Drug interaction
Sedation
SedativesCauses for Agitation
Undersedation
Sedatives
Causes for AgitationAgitation & anxietyPain and discomfortCatheter displacementInadequate ventilationHypertensionTachycardiaArrhythmiasMyocardial ischemiaWound disruptionPatient injury
Oversedation
Sedatives
Causes for Agitation
Prolonged sedationDelayed emergenceRespiratory depressionHypotensionBradycardiaIncreased protein breakdownMuscle atrophyVenous stasisPressure injuryLoss of patient-staff interactionIncreased cost
Correctable Causes of Agitation• Full bladder• Uncomfortable bed position• Inadequate ventilator flow rates• Mental illness• Uremia• Drug side effects• Disorientation• Sleep deprivation• Noise• Inability to communicate
Causes of Agitation Not to be Overlooked
• Hypoxia• Hypercarbia• Hypoglycemia• Endotracheal tube malposition• Pneumothorax• Myocardial ischemia• Abdominal pain• Drug and alcohol withdrawal
Altered PharmacologyMidazolam and Age
00.5
11.5
22.5
33.5
44.5
5
10 20 30 40 50 60 70 80
Age (y)
T 1 / 2
hou
rs
Harper et al. Br J Anesth, 1985;57:866-871
Delayed Emergence
• Overdose (prolonged infusion)– pK derived from healthy patients– Drug interaction– Individual variation
• Delayed elimination– Liver (Cp450)– Kidney dysfunction– Active metabolites
Morphine Metobolism
M orp h in e-3 -GA n tian a lg es ic
N orm orp h in eN eu ro toxic ity
M orp h in e-6 -GA n a lg es ic (4 0 X )
M orp h in eTyp e t it le h e re
80% 10%
Withdrawal
• Withdrawal from preoperative drugs• Sudden cessation of sedation
– Return of underlying agitation• Hyperadrenergic syndrome
– Hypertension, tachycardia,sweating• Opioid withdrawal
– Salivation, yawning, diarrhea
Drug InteractionsDiazepam-Morphine Interaction
Synergism
Antagonism
Morphine
Diazepam
ED50 isobologramRighting reflexIn rats
Kissin et al. Anesthesiology. 1989, 70:689-694
Strategies for Patient Comfort
• Set treatment goal• Quantitate sedation and pain• Choose the right medication• Use combined infusion• Reevaluate need• Treat withdrawal
Set Treatment Goal
Sedation Analgesia
Amnesia AnxiolysisHypnosis
Patient Comfort
Quantitate Sedation & Analgesia
• Subjective measure• Objective measures
Sedation Scoring Scales
• Ramsay Sedation Scale (RSS)• Sedation-agitation Scale (SAS)• Observers Assessment of
Alertness/Sedation Scale (OAASS)• Motor Activity Assessment Scale (MAAS)
BMJ 1974;2:656-659Crit Care Med 1999;27:1325-1329J Clin Psychopharmacol 1990;10:244-251Crit Care Med 1999;27:1271-1275
The Ramsay Scale
Scale Description1 Anxious and agitated or restless, or both
2 Cooperative, oriented, and tranquil
3 Response to commands only
4 Brisk response to light glabellar tap or loud auditory stimulus
5 Sluggish response to light glabellar tap or loud auditory stimulus
6 No response to light glabellar tap or loud auditory stimulus
The Riker Sedation-Agitation ScaleScore Description Definition
7 Dangerous agitation Pulling at endotracheal tube, trying to strike at staff, thrashing side to side
6 Very agitated Does not calm despite frequent verbal commands, biting ETT
5 Agitated Anxious or mildly agitated, attempting to sit
4 Calm and cooperative
Calm, awakens easily, follows commands
3 Sedated Difficult to arouse, awakens to verbal stimuli, follows simple commands
2 Very sedated Arouse to physical stimuli, but does not communicate spontaneously
1 Unarousable Minimal or no response to noxious stimuli
The Motor Activity Assessment Scale
Score Description Definition6 Dangerous agitation Pulling at endotracheal tube, trying to strike
at staff, thrashing side to side
5 Agitated Does not calm despite frequent verbal commands, biting ETT
4 Restless and cooperative
Anxious or mildly agitated, attempting to sit
3 Calm and cooperative
Calm, awakens easily, follows commands
2 Responsive to touch or name
Opens eyes or raises eyebrows or turns head when touched or name is loudly spoken
1 Responsive only to noxious stimuli
Opens eyes or raises eyebrows or turns head with noxious stimuli
0 Unresponsive Does not move with noxious stimuli
What Sedation Scales Do
• Provide a semiquantitative “score”• Standardize treatment endpoints• Allow review of efficacy of sedation• Facilitate sedation studies• Help to avoid oversedation
What Sedation Scales Don’t Do
• Assess anxiety• Assess pain• Assess sedation in paralyzed patients• Predict outcome• Agree with each other
BIS Monitoring
BIS Monitoring
BIS Range GuidelinesAwake
Responds to loud commands or mild prodding/shaking
Low probability to explicit recallsUnresponsive to verbal stimuli
Burst suppression
Flat line EEG
Responds to normal voice Axiolysis
Moderatesedation
Deep Sedation
100
80
60
40
20
0
BIS
Pain
Assess Pain Separately
Visual Pain Scales
0 1 2 3 4 5 6 7 8 9 10
No pain Worst possible pain
Signs of Pain
• Hypertension• Tachycardia• Lacrimation• Sweating• Pupillary dilation
Principles of Pain Management• Anticipate pain• Recognize pain
– Ask the patient– Look for signs– Find the source
• Quantify pain • Treat:
– Quantify the patient’s perception of pain– Correct the cause where possible– Give appropriate analgesics regularly as required
• Remember, most sedative agents do not provide analgesia• Reassess
Nonpharmacologic Interventions
• Proper position of the patient• Stabilization of fractures• Elimination of irritating stimulation• Proper positioning of the ventilator tubing
to avoid traction on endotracheal tube
Choose the Right Drug
• Benzodiazepines• Propofol• Opioids-2 agonists
Choose the Right Drug
Sedation Analgesia
Amnesia AnxiolysisHypnosis
Benzodiazepines
Benzodiazepines
Onset Peaks Duration
Diazepam 2-5 min 5-30 min >20 hr
Midazolam 2-3 min 5-10 min 30-120 min
Lorazepam 5-20 min 30 min 10-20 hr
Choose the Right Drug
Sedation Analgesia
Amnesia AnxiolysisHypnosis
Propofol
Propofol
Onset Peaks Duration
Propofol 30-60 sec 2-5 min short
Propofol Dosing
• 3-5 g/kg/min antiemetic• 5-20 g/kg/min anxiolytic• 20-50 g/kg/min sedative hypnotic• >100 g/kg/min anesthetic
Choose the Right Drug
Sedation Analgesia
Amnesia AnxiolysisHypnosis
Opioids
Pharmacology of Selected Analgesics
Agent Dose (iv) Half-life Metabolic pathway Active metabolites
Fentanyl 200 g 1.5-6 hr Oxidation NoneHydromorphone 1.5 mg 2-3 hr Glucuronidation None
Morphine 10 mg 3-7 hr Glucuronidation Yes (Sedation in RF)
Meperidine 75-100 mg
3-4 hr Demethylation & hydroxylation
Yes (neuroexcitation in RF)
Codeine 120 mg 3 hr Demethylation & Glucuronidation
Yes ( analgesia, sedation)
Remifentanil 3-10 min Plasma esterase NoneKeterolac 2.4-8.6 hr Renal None
Opioids
Lipid Solubility
Histamine Release
Potency
Morphine +/- +++ 1
Hydromorphone + + 5
Fentanyl +++ - 50
Opioids
Onset Peaks Duration
Morphine 2 min 20 min 2-7 hr
Fentanyl 30 sec 5-15 min 30-60 min
Problems with Current Sedative Agents
Midazolam Propofol OpioidsProlonged weaning X - XRespiratory depression X - XSevere hypotension X X -Tolerance X - XHyperlipidemia - X -Increased infection - X -Constipation - - XLack of orientation and cooperation
X X X
Choose the Right Drug
Sedation Analgesia
Amnesia AnxiolysisHypnosis
-2 agonists
Alpha-2 Receptors
Brain(locus ceruleus)
Spinal Cord
Peripheral vasculature
SedationAnxiolysis
Sympatholysis
Analgesia
Vasoconstriction
DEX: Dosing
Loading infusion0.25-1 g/kg(10-20 min)
Maintenance infusion0.2-0.7 g/kg/hr
Use Continuous and Combined Infusion
Plasma Level
Load
Maintenance
Repeated Bolus
Plasma levels
Opioid + Hypnotic Infusion
Fentanyl + Midazolam or Propofol
Analgesia AmnesiaAnxiolysisHypnosis
Continuous Infusion Regimens
Fentanyl 25-250 g/h
Midazolam 0.5-5 mg/hr
Propofol 15-50 g/kg/min
Choose the Right Drug
Sedation Analgesia
Amnesia AnxiolysisHypnosis
-2 agonistsPrimary
Adjunct sedation Propofol
Choose the Right Drug
Sedation Analgesia
Amnesia AnxiolysisHypnosis
-2 agonistsPrimary
Adjunct sedation Midazolam
Choose the Right Drug
Sedation Analgesia
Amnesia AnxiolysisHypnosis
-2 agonistsPrimary
Adjunct analgesia Morphine
Choose the Right Drug
Sedation Analgesia
Amnesia AnxiolysisHypnosis
-2 agonistsPrimary
Adjunct analgesia Fentanyl
Reassess Need
• Use sedation score as endpoint• Initiate sedation incrementally to desired
level• Periodically (q day) titrate infusion rate
down until the patient begins to emerge• Gradually increase infusion rate again to
desired level of sedation
Barr, Donner. Crit Care Clin. 1995;11827
Treat Withdrawal
• Acute management– Resume sedation– Beta-blockade, dexmedetomidine
• Prolonged management– Methadone 5-10 mg VT bid– Clonidine 0.1-0.2 mg VT q8h– Lorazepam 1-2 mg IV q8h