Transcript Sedation, Analgesia, and Neuromuscular Blockade in the

SEDATION IN THE ICUSHIFTS & STRATEGIES
DR. RAKESH K. CHAWLA
MD,FCCP(USA)
SR. CONSULTANT RESPIRATORY MEDICINE, CRITICAL CARE
AND SLEEP DISORDERS
JAIPUR GOLDEN HOSPITAL,SAROJ HOSPITAL & RAJIV GANDHI
CANCER INSTITUTE
MOBILE-09810072860

NISO FINANCIAL GRANT FOR THIS
LECTURE.PURE ACADEMIC
Sedation in the ICU
The ICU is a hostile environment and
while pain is often the root cause of
distress experienced by the patient in
the unit , anxiety, dyspnoea, delirium
and sleep deprivation may be additive
or synergistic.
Everyone who works in Intensive
Care Unit(I.C.U) has already faced an
anxious and agitated patient
requiring sedation for different goals
such as management of difficult
airway, improvement of mechanical
ventilation or just as adjuvant
therapy to commonly procedures
done in Intensive Care Medicine.

Majority of critically ill patients
experience significant distress, anxiety,
and agitation during their intensive care
unit stays. Numerous factors, including
sleep deprivation, unfamiliar
environment, delirium, adverse
medication effect, pain, and extreme
anxiety can contribute to ICU patient
distress.

Intensivists often employ various
sedative agents to relieve ICU
associated distress and prevent
secondary complications of such
distress. There are a variety of
pharmacologic agents used for this
purpose, including benzodiazepines,
propofol, antipsychotic agents, and
alpha agonists.

Important patho-physiologic
mechanisms affected by ICU –
associated distress include significant
increases in catecholamines, cortisol,
growth hormone, vasopressin, prolactin,
glucagon, fatty acids, and protein
catabolism. Clinically significant
sequelae of this physiologic
dysregulation include fluid and
electrolyte imbalances, altered wound
healing , and disturbances of the sleep
wake cycles.
ICU sedation is aimed at keeping the
patient
comfortable
but
easily
arousable. Deep
sedation with or
without muscle relaxants is rarely
indicated and is associated with a higher
incidence of delirium and death. Analgo
– sedation is administered to relieve
pain, anxiety and discomfort and to
facilitate treatment and nursing. .
Providing analgesia first, and adding
sedation as required (“analgo sedation”).
What We Know About ICU
Agitation/Discomfort
Prevalence
• 50% incidence in those with length of stay > 24 hours
Primary causes: unrelieved pain, delirium,
anxiety, sleep deprivation, etc.
Immediate sequelae:
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Patient-ventilator dyssynchrony
Increased oxygen consumption
Self (and health care provider) injury
Family anxiety
Long-term sequelae: chronic anxiety disorders
and post-traumatic stress disorder (PTSD)
Causes of Agitation Not to be
Overlooked
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Hypoxia
Hypercarbia
Hypoglycemia
Endotracheal tube malposition
Pneumothorax
Myocardial ischemia
Abdominal pain
Drug and alcohol withdrawal
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

Medications Associated With Agitation in ICU Patients
Antibiotics
Acyclovir
Amphotericin B
Cephalosporins
Ciprofloxacin
Imipenem – cilastatin (Primaxin , Merck)
Ketoconazole
Metronidazole
Penicillin
Rifampin
Trimethoprim – Sulfamethoxazole
Anticonvulsants
Phenobarbital
Phenytoin
Cardiac Drugs
Captopril
Clonidine
Digoxin
Dopamine
Labetalol
Lidocaine
Nifedipine
Nitroprusside
Propranolol
Quinidine Sulfate
Corticosteroids
Dexamethasone
Methylprednisolone
Opiold Analgesics
Codeine
Meperidine
Morphine Sulfate
Miscellaneous Drugs
Anticholinergics
Benzodiazepines
Hydroxyzine
Ketamine
Metoclopramide
Nonsteroidal anti –
inflammatory drugs
Theophylline
Recall in the ICU
Some degree of recall occurs in up to 70% of
ICU patients.
• Anxiety, fear, pain, panic, agony, or nightmares reported in
90% of those who did have recall.
Potentially cruel:
• Up to 36% recalled some aspect of paralysis.
Associated with PTSD in ARDS?
• 41% risk of recall of two or more traumatic experiences.
Associated with PTSD in cardiac surgery
Goals of Sedation in ICU
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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
Treatment or Diagnostic procedures
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
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The Challenges of ICU
Sedation
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Assessment of sedation
Altered pharmacology
Tolerance
Delayed emergence
Withdrawal
Drug interaction
Sedation
Causes for Agitation
Sedatives
Incidence of Inadequate Sedation
Kaplan L, et al. Crit Care 2000;4(suppl 1):S110.
Sedation: Background
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Significant issues with some current agents
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Opiate/benzodiazepine – tolerance, efficacy
Chloral hydrate - predictability
Pentobarbital – agitation, duration
Propofol – limited access in some jurisdictions
Ketamine – emergence reactions, tolerance
2-adrenoreceptor agonists
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Prototype agent is clonidine
Recent applications in clinical practice- Sedation,
Behavior disorders , Drug withdrawal , Hypertension
Complications of Under/Over Sedation
Under sedation
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Patient recall (PTSD)
Device removal
Ineffectual mechanical
ventilation
Initiation of
neuromuscular
blocker therapy
Myocardial or cerebral
ischemia
Decreased family
satisfaction with care
Over sedation
Prolonged mechanical
ventilation
 Need for additional
diagnostic testing
 Increased length of
ICU and hospital stay
 Increased risk of
complications
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◦ Ventilator-associated
pneumonia
◦ Thrombo-embolic events
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Drug withdrawal
Undersedation
Sedatives
Causes for Agitation
Agitation & anxiety
Pain and discomfort
Catheter displacement
Inadequate ventilation
Hypertension
Tachycardia
Arrhythmias
Myocardial ischemia
Wound disruption
Patient injury
AGITATED PATIENT
Oversedation
Causes for Agitation
Prolonged sedation
Delayed emergence
Respiratory depression
Hypotension
Bradycardia
Increased protein breakdown
Muscle atrophy
Venous stasis
Pressure injury
Loss of patient-staff interaction
Increased cost
Sedatives
DEEPLY SEDATED
Daily Goal is Arousable,
Comfortable Sedation
Sedation needs to be protocolized and titrated to
goal:
• Lighten sedation to appropriate wakefulness daily.
Effect of this strategy on outcomes:
• One- to seven-day reduction in length of sedation and mechanical
ventilation needs
• 50% reduction in tracheostomies
• Three-fold reduction in the need for diagnostic evaluation of CNS
Protocols and Assessment
Tools
SCCM practice guidelines can be used as a
template for institution-specific protocols.
Titration of sedatives and analgesics guided by
assessment tools:
• Validated sedation assessment tools (Ramsay Sedation Scale
[RSS], Sedation-Agitation Scale [SAS], Richmond Sedationagitation Scale [RSAS], etc.)
- No evidence that one is preferred over another
• Pain assessment tools - none validated in ICU (numeric rating
scale [NRS], visual analogue scale [VAS], etc.)
Strategies for Patient Comfort
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Set treatment goal
Quantitate sedation and pain
Choose the right medication
Use combined infusion
Reevaluate need
Treat withdrawal
How do we assess sedation?
Sedation Scales : Very useful
, very underused.
What Sedation Scales Do
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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
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Assess anxiety
Assess pain
Assess sedation in paralyzed patients
Predict outcome
Agree with each other
Ramsay Sedation Scale (RSS)
 Sedation-agitation Scale (SAS)
 Observers Assessment of Alertness/Sedation
Scale (OAASS)
 Motor Activity Assessment Scale (MAAS)

BMJ 1974;2:656-659
Crit Care Med 1999;27:1325-1329
J Clin Psychopharmacol 1990;10:244-251
Crit Care Med 1999;27:1271-1275
Sedation Scoring Scales
Sedation should be targeted to a
Ramsay score of 2 to 3.
The Riker Sedation-Agitation Scale
Score 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
MASS (Motor Assessment Scale )
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The MASS is scored from 0 (patient
unresponsive) to 6 (dangerously agitated,
uncooperative patient).
The Motor Activity Assessment Scale
Score
Description
Definition
6
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
VICS (Vancouver Interaction and
Calmness Scale)
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The VICS consists of two separate scores,
the interaction score and the calmness
score. Each score is composed of five
categories , with each category graded on
a scale .
SAS (Sedation – Agitation Scale)
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The SAS is scored from 1 (unarousable )
to 7 (dangerous agitation).
Level
Behaviors
7
Dangerous agitation pulls at endotracheal tube, tries to
remove catheter climbs over bed rail , strikes at staff,
thrashes side - to – side.
6
Very agitated . Does not calm , despite frequent verbal
reminders; requires verbal reminding of limits, physical
restraints; bites endotracheal tube.
5
Agitated , Anxious or mildly agitated , attempts to sit up,
calms down to verbal instructions.
4
Calm and cooperative. Calm , awakens easily, follow
commands
3
Sedated. Difficult to arouse, awakens to verbal stimuli or
gentle shaking but drifts off again, follows simple
commands
2
Very sedated. Arouses to physical stimuli but does not
communicate or follow commands, may move
spontaneously
1
Unarousable. Minimal or no response to noxious stimuli,
does not communicate or follow commands.
AVRIPAS
This scale consists of four components :
(a) agitation; (b) alertness; (c) heart rate;
(d) respiration.
 Agitation, alertness , and respiration are
measured on a 5 point scoring system.
Heart rate is measured on a 4 point scale .
The overall sedation score for this system
is a sum of each component , with scores
ranging from 1 (sedated) to 19 (need for
more sedation).
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Bloomsbury
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Also known as the University College
London Hospitals sedation protocol, this
scale spans from -3 (unarousable) to +3
(agitated and restless). There is also
categorization for natural sleep. The
bloomsbury scale appears to have a high
association with the Ramsay Sedation
Scale.
Choose the Right Drug
Sedation
Amnesia
Analgesia
Hypnosis
Anxiolysis
Propofol
Benzodiazepines
Patient Comfort
-2 agonists
Opioids
Sedation Options: Benzodiazepines
(Midazolam and Lorazepam)
Pharmacokinetics/dynamics
• Lorazepam: onset 5 - 10 minutes, half-life 10 hours, glucuronidated
• Midazolam: onset 1 - 2 minutes, half-life 3 hours, metabolized by
cytochrome P450, active metabolite (1-OH) accumulates in renal disease
Benefits
• Anxiolytic
• Amnestic
• Sedating
Risks
•
•
•
•
Delirium
NO analgesia
Excessive sedation: especially after long-term sustained use
Propylene glycol toxicity (parenteral lorazepam): significance uncertain
- Evaluate when a patient has unexplained acidosis
- Particularly problematic in alcoholics (due to doses used) and renal failure
• Respiratory failure (especially with concurrent opiate use)
• Withdrawal
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
Sedation Options: Propofol
Pharmacology: GABA agonist
Pharmacokinetics/dynamics: onset 1 - 2 minutes,
terminal half-life 6 hours, duration 10 minutes,
hepatic metabolism
Benefits
• Rapid onset and offset and easily titrated
• Hypnotic and antiemetic
• Can be used for intractable seizures and elevated intracranial
pressure
Risks
•
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•
•
•
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Not reliably amnestic, especially at low doses
NO analgesia!
Hypotension
Hypertriglyceridemia; lipid source (1.1 kcal/ml)
Respiratory depression
Propofol Infusion Syndrome
- Cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal failure
- Caution should be exercised at doses > 80 mcg/kg/min for more than 48
hours
- Particularly problematic when used simultaneously in patient receiving
catecholamines and/or steroids
Propofol
Propofol
Onset
Peaks
Duration
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
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Problems with Current Sedative Agents
Midazolam
Propofol
Opioids
Prolonged weaning
X
-
X
Respiratory depression
X
-
X
Severe hypotension
X
X
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Tolerance
X
-
X
Hyperlipidemia
-
X
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Increased infection
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X
-
Constipation
-
-
X
Lack of orientation and
cooperation
X
X
X
Opiate and Benzodiazepine
Withdrawal
Frequency related to dose and duration
• 32% if receiving high doses for longer than a week
Onset depends on the half-lives of the parent drug and
its active metabolites
Clinical signs and symptoms are common among agents
• CNS activation: seizures, hallucinations,
• GI disturbances: nausea, vomiting, diarrhea
• Sympathetic hyperactivity: tachycardia, hypertension, tachypnea,
sweating, fever
No prospectively evaluated weaning protocols available
• 10 - 20% daily decrease in dose
• 20 - 40% initial decrease in dose with additional daily reductions of
10 - 20%
Consider conversion to longer acting agent or
transdermal delivery form
Withdrawal
Withdrawal from preoperative drugs
 Sudden cessation of sedation
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◦ Return of underlying agitation
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Hyperadrenergic syndrome
◦ Hypertension, tachycardia,sweating
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Opioid withdrawal
◦ Salivation, yawning, diarrhea
Treat Withdrawal
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Acute management
◦ Resume sedation
◦ Beta-blockade, dexmedetomidine
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Prolonged management
◦ Methadone 5-10 mg VT bid
◦ Clonidine 0.1-0.2 mg VT q8h
◦ Lorazepam 1-2 mg IV q8h
Sedation Options: Dexmedetomidine
Alpha-2-adrenergic agonist like clonidine but with much
less imidazole activity
Has been shown to decrease the need for other sedation
in postoperative ICU patients
Potentially useful while decreasing other sedatives to
prevent withdrawal
Benefits
• Does not cause respiratory depression
• Short-acting
• Produces sympatholysis which may be advantageous in certain patients
such as postop cardiac surgery
Risks
• No amnesia
• Small number of patients reported distress upon recollection of ICU
period despite good sedation scores due to excessive awareness
• Bradycardia and hypotension can be excessive, necessitating drug
cessation and other intervention
Dosage
Route of Administration and Dosage
 IV infusion parenteral injection, 100 mcg/mL in a 2 mL vial Sodium Chloride 0.9%
Administration
 Diluted in 0.9% sodium chloride solution to achieve required concentration (4 mcg
/mL) prior to administration. To prepare the infusion, withdraw 2 mL of
Dexmedetomidine and add to 48 mL of 0.9% sodium chloride injection to a total of
50 mL.
Intensive Care Unit Sedation
 Initiation- Loading infusion of up to 1 mcg/kg over 10 to 20 minutes, if needed.
 Maintenance- Adults generally require a maintenance infusion of 0.2-0.7 mcg/kg/hr.
Conscious Sedation
 Clinically effective onset of sedation 10 to 15 minutes after start of infusion
 Initiation- Loading infusion of 1 mcg/kg over 10 minutes. For patients over 65 years
of age or those undergoing less invasive procedures, a loading infusion of 0.5
mcg/kg over 10 minutes may be suitable
 Maintenance- Generally initiated at 0.6 mcg /kg/hr and titrated from 0.2 to 1
mcg/kg/hr
 Following the load in AFI, a fixed maintenance dose of 0.7 mcg/kg/hr is
recommended until the ETT is secured.
Indications
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Intensive Care Unit Sedation
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Sedation of initially intubated and mechanically ventilated
postsurgical patients during treatment in an intensive care
setting by continuous intravenous infusion.
It has been continuously infused in mechanically ventilated
patients prior to extubation, during extubation, and postextubation. It is not necessary to discontinue the drug prior
to extubation.
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Conscious Sedation
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Sedation of non-intubated patients prior to and/or during
surgical and other procedures by continuous intravenous
infusion for the following procedures:
Monitored Anaesthesia Care (MAC)
Awake Fibreoptic Intubation (AFI)
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Clinical Effects
RESPIRATORY EFFECTS
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Minimal respiratory depressing effects
◦ 0.17% incidence on monogram
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Most data suggests SaO2 and PaCO2 unaffected , Numerous reports during
spont vent
NON-CNS EFFECTS
◦ Hypertension: peripheral 1-agonism
 Bradycardia/hypotension: Sympathetic inhibition - medullary VMC
  shivering, Diuresis:  renin, vasopressin;  ANP
PERIOPERATIVE OBSERVATIONS
hypotension vs propofol
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Blunted tachycardia during controlled hypotension
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Blunted catecholamine response: Potential importance with vascular procedures
PACU analgesia requirements
Clinical Uses of Dex .
Sedation in CT and MRI imaging studies
Mason K, Ped Anesth 2008
Koroglu A, Anesth Analg 2006
Outpatient third molar surgery
Ustin Y, J Oral Maxilfac Surg 2006
Cheung C, Anaesthesia 2007
Cataract surgery
Alhashemi J, Br J Anaest 2006
Cardiac catheterization
Tosun Z, J Card Vasc Anesth 2006
Mester R, Am J Therap 2008
GI Procedures
Demiraran Y, Can J Gastroenter 2007
Dex may be a good alternative to midazolam for
upper endoscopy
Dex: Use in Sleep Apnea, Gastric Bypass
Sleep Apnea Patients
Anesthesia considerations
 Morbid obesity, at risk for aspiration
 Difficult IV access
 Systemic + pulm HTN, cor pulmonale
 Postop airway obstruction + ventilatory arrest with
anesthetic drugs
Dex: Anesthetic adjunct to minimize opioid + sedative use
Ogan OU, Plevak DJ: Mayo Clinic; www.sleepapnea.org
Gastric Bypass Surgery Patients
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Morbidly obese patients, Prone to hypoxemia
Sleep apnea is common, Respiratory depression w opioids
Dexmedetomidine, 0.1 to 0.7 ug/kg/hr, prospectively studied
in 32 pts
  opioid use in dex group, pts more normotensive
Craig MG et al: IARS abstract, 2002. Baylor
Drug interactions
Anesthetics, sedatives, hypnotics, opioids
 Co-administration of Dexmedetomidine with anesthetics, sedatives,
hypnotics, and opioids is likely to lead to an enhancement of effects.
Specific studies have confirmed these effects with sevoflurane, isoflurane,
propofol, alfentanil, and midazolam.
 No pharmacokinetic interactions with isoflurane, propofol, alfentanil and
midazolam have been demonstrated. However, a reduction in dosage of
Dex or the concomitant anesthetic, sedative, hypnotic or opioid may be
required.
Neuromuscular Blockers- no clinically meaningful increases in the
magnitude
 Cytochrome P-450- No evidence of cytochrome P450 mediated drug
interactions
 Vagal effects- can be counteracted by atropine / glyco

Contraindications
 Patients who are hypersensitive to drug or to any ingredient
◦ Caution in pts with advanced heart block, severe ventricular dysfunction,
shock
Adverse Reactions
Adverse Drug Reaction Overview
 Serious adverse reactions: Hypotension, bradycardia and sinus arrest,
Transient hypertension
 Most common treatment-emergent adverse reactions, occurring in greater
than 2% of patients include hypotension, bradycardia and dry mouth.
Clinical Trial Adverse Drug Reactions
Intensive Care Unit Sedation: Hypotension, Hypertension, Nausea,
Bradycardia, Fever, Vomiting, Atrial Fibrillation, Hypoxia, Tachycardia,
Hemorrhage, Anemia, Dry Mouth, Rigors, Agitation, Hyperpyrexia, Pain,
Hyperglycemia , Acidosis , Pleural Effusion, Oliguria , Thirst
 Conscious Sedation: Hypotension , Hypertension , Respiratory
depression, Hypoxia, Bradypnea, Bradycardia , Tachycardia , Nausea , Dry
mouth
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Post-Market Adverse Drug Reactions
 Hypotension and bradycardia were the most common adverse
reactions associated with the use during post approval use of the drug.
Patient Focused Sedation:
Key Points
Non-pharmacological measures
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Minimize:
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Dimming lights at night (sleep-wake cycle)
Massage, therapeutic touch and music therapy
◦ Blood draws, X-rays
◦ Blood pressure measurements, Blood glucose measurements
Selection of Sedatives
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Benzodiazepines- Diazepam, Lorazepam, Midazolam
Propofol
Dexmedetomidine
Haloperidol, other neuroleptics
Patient Focused Sedation:
Key Points
Choose medications best suited to the patient’s characteristics
 Organ function and Drug metabolism
 Risk of side effects
 Sedation needs differ among patients and vary over time

Tips to minimize sedation
◦ Use a sedation protocol
◦ Incorporate Daily Interruption of Sedation (DIS)
◦ Provide Analgesia Management First
◦ Use Newer Medications With Different Properties
◦ Use Other Non pharmacologic Interventions
Overview of SCCM Algorithm
ALGORITHM FOR SEDATION AND ANALGESIA OF M ECHANICALLY VENTILATED PATIENTS
Is the Patient Comf ortable & at Goal?
Yes
No
Reassess goal daily ,
Titrate and taper therapy to maintain goal,
Consider daily wake-up,
Taper if > 1 week high-dose therapy & monitor
f or withdrawal
Rule out and Correct Rev ersible Causes
1
2
3
Use Non-pharmacologic Treament,
Optimize the Env ironment
*
Use Pain Scale to
Assess f or Pain
Use Sedation Scale**
to Assess f or
Agitation/Anxiety
Hemody namically Unstable
Fentanyl 25 - 100 mcg IVP Q 5-15 min, or
Hydromorphone0.25 - 0.75 mg IVP Q 5 - 15 min
Hemody namically stable
Morphine2 - 5 mg IVP Q 5 - 15 min
Set Goal
f or
Analgesia
(except neuro pt.)
Use Delirium Scale*** to
Assess f or Delirium
Consider continuous
inf usion opiate or
sedativ e
Lorazepam via
infusion?
Use a low rate and IVP
loading doses
Acute Agitation #
Midazolam 2 - 5 mg IVP Q 5 - 15 min until
acute ev ent controlled
Ongoing Sedation #
Lorazepam1 - 4 mg IVP Q 10-20 min until
at goal then Q 2 - 6 hr scheduled prn,
+
or
Propofol start 5 mcg/kg/min, titrate Q 5 min
until at goal
> 3 Day s Propof ol?
4
Yes
Repeat until pain controlled, then scheduled doses
+ prn
Set Goal
f or
Sedation
Yes
IVP Doses
more of ten thanQ
2hr?
Benzodiazepine or Opioid:
Taper Inf usion Rate by
10-25% Per Day
Conv ert to
Lorazepam
Set Goal
f or Control
of Delirium
Haloperidol2 - 10 mg IVP Q 20 - 30 min,
then 25% of loading dose Q 6hr x 2-3 day s,
then taper
Jacobi J, Fraser GL, Coursin D, et al. Crit Care Med. 2002;30:119-141.
Doses
approximate for
70kg adult
Delirium
1. Acute onset of mental status changes or
a fluctuating course
&
2. Inattention
&
3. Disorganized
Thinking
or
Courtesy of W Ely, MD
4. Altered level of
consciousness
Risk Factors for Delirium
Primary CNS Dx
Infection
Metabolic derangement
Pain
Sleep deprivation
Age
Substances including tobacco (withdrawal as well
as direct effect)
Significance of ICU Delirium
Seen in > 50% of ICU patients
Three times higher risk of death by six months
Five fewer ventilator free days (days alive and
off vent.), adjusted P = 0.03
Four times greater frequency of medical device
removal
Nine times higher incidence of cognitive
impairment at hospital discharge
Treatment of Delirium
Correct inciting factor, but as for pain…relief need
not be delayed while identifying causative factor
Control symptoms?
• No evidence that treatment reduces duration and
severity of symptoms
• Typical and atypical antipsychotic agents
• Sedatives?
- Particularly in combination with antipsychotic and for drug/alcohol
withdrawal delirium
No treatment FDA approved
Case Scenario #1
22-year-old male with isolated closed head injury who
was intubated for GCS of 7
He received 5 mg of morphine, 40 mg of etomidate,
and 100 mg of succinylcholine for his intubation.
He is covered in blood spurting from an arterial
catheter that was just removed, and he appears to be
reaching for his endotracheal tube.
What sedative would you use and why?
What are the particular advantages in this situation?
How could you avoid the disadvantages of this drug?
Case Scenario #1 - Answer
Propofol will rapidly calm a patient who is displaying
dangerous behavior without need for paralysis.
Titratable and can be weaned quickly to allow for
neurologic exam
Can treat seizures and elevated ICP which may be
present in a head trauma with GCS of eight or less
Minimizing dose and duration will avoid side effects.
Case Scenario #2
54-year-old alcoholic who has been admitted for
Staph sepsis
Intubated in the ICU for seven days and is currently
on midazolam at 10 mg/hour
His nurse was told in report that he was a “madman”
on the evening shift.
Currently, he opens his eyes occasionally to voice but
does not follow commands nor does he move his
extremities to deep painful stimulation.
Is this appropriate sedation?
What would you like to do?
How would you institute your plan of action?
Case Scenario #3
62-year-old, 65-kg woman with ARDS from aspiration
pneumonia
Her ventilator settings are PRVC 400, RR 18, PEEP 8,
and FIO2 100%. She is dyssynchronous with the
ventilator and her plateau pressure is 37 mm Hg.
She is on propofol at 50 mcg/kg/min, which has been
ongoing since admit four days ago.
She is also on norepinephrine 0.1 mcg/kg/min and she
was just started on steroids.
What do you want to do next?
Do you want to continue the propofol?
Why or why not?
What two iatrogenic problems is she likely at risk for?
Case Scenario #3 - Answer
This patient needs optimization of her sedatives, and
potentially chemical paralysis to avoid complications
of ventilator dyssynchrony and high airway pressures.
If you continue to use propofol, higher doses are
required and the patient is already on norepinephrine.
In addition, if paralysis is used, you do not have
reliable amnesia.
She is at risk for propofol infusion syndrome and
critical illness polyneuropathy.