controlling icu agitation; context determines strategy ways to facilitate knowledge transfer
DESCRIPTION
TRANSCRIPT
Controlling ICU Agitation; Context Determines Strategy
Ways to Facilitate Knowledge Transfer
Gil Fraser, PharmD, FCCM
Critical Care, MMC
Professor
UVM College of Medicine
Some Things Are Easy
• Job(s) 1 = Patient comfort, patient and care-giver safety, maintenance of oxygenation and perfusion
• Assume accumulation of parent drug (lorazepam and midazolam) and active metabolite (midazolam) with prolonged use
• Don’t complicate things• Don’t complicate things– Avoid deliriogenic drugs
– Avoid propofol and dex with high dose vasoactive therapy
• Initiate home medications when appropriate
It’s Gotten a Bit Complicated
ICU Sedation
Literature Citations vs Time
1576
1838
1400
1600
1800
2000
880 85
197
613
991
0
200
400
600
800
1000
1200
1400
1960-9 1970-9 1980-4 1985-9 1990-4 1995-9 2000-4 2005-9
Cit
ati
on
s
Managing ICU Agitation Is NOT Easy
Maldonado. Crit Care Clin 2008;24:789
Facilitating Rapid Knowledge
Transfer to the Bedside
• Options
– Use clinical practice guideline as a model
– Create “bundles” for implementing essential
components of practice guidelines
– Develop protocols for managing pain/agitation/delirium– Develop protocols for managing pain/agitation/delirium
– Offer real time clinical decision support
• ADAPT then ADOPT previously developed tools
New Sedation Guidelines!
Will be published in
2010
Recommendations Recommendations
per GRADE
methodology
Clinical Practice Guidelines (CPG)
The Temptation of SimplicityAppreciating the Thinness of Ice
• Temptation:– Defer to identified experts for objective evaluation of
issues and controversies
– Use their simplified algorithms for management strategies
• Management decisions should be• Management decisions should be– Individualized within the context of the treated patient
• Problem:– Rush to incorporate vulnerable data into CPGs and quality
improvement efforts
What to Do??No desire to cast aspersions on CPGs or bundles
Understand their limitations
Do not blindly accept all recommendationsDo not blindly accept all recommendations
Base clinical decisions on individual patient context
Use most recent rigorous data to assess risk:benefit
Your Job for Today
• Value protocolized pain/agitation/delirium management
• Understand new data that redefine risks and benefits of drug management strategies
• Evaluate various strategies for beside • Evaluate various strategies for beside implementation of best practice
• Become completely confused about ICU delirium—defer to Dr. Devlin
Importance of Protocolization
• Helps bring “best practice” to the bedside
• Limits practice variation
• Reduces delays in management
– Encourages regular assessment of pain, – Encourages regular assessment of pain,
agitation, delirium
– Facilitates pharmacologic interventions: drug
choice, dosing, titration
Surveys of ICU Sedation Practices
• In the US, 64% use protocol, with 40%
using daily interruption.
• In Canada, 29% use protocol, 40% use daily • In Canada, 29% use protocol, 40% use daily
interruption.
• Adherence to protocols ~50%
Why Are Protocols Not Used?
ICU patients and protocols are too complex
Sedation/Analgesia Algorithm for Ventilated Patients
Intermittent
Sustained
Preprocedural Anxiety Delirium
SAS 3 or 4 SAS 1 or 2
•Mechanically Ventilated •Frequent Neurologic Evaluation•Mechanically Ventilated
•High Dose Vasopressors and Mechanically Ventilated
•Not Mechanically Ventilated
•High Dose Vasopressors andNot Mechanically Ventilated
•Frequent Neurologic Evaluationis Necessary
•Frequent Neurologic EvaluationNot Necessary
•GABA Agonist Withdrawal•Delirium•Renal Disease•Liver Disease•Refractory Agitation
Over 150
possible
clinical scenarios
Why Are Protocols Not Used?
• Too complex
• Determination of adequacy of sedation
remains subjectiveremains subjective
– How deep is too deep?
– Is deep just right?
• Greater than 40% patients are more deeply sedated than desired
• Drug-induced coma present during 32% of patient evaluations
Deep Sedation
32% of patient evaluations– Yet only 2.6% rated as “oversedated”
Weinert. CCM 2007:35:393
Payen. Anesthesiology 2007:106:687
Martin. ICM 2006; 32:1137
Does This
Matter?
Factors Supporting Deep
Sedation = Humane Treatment
• Lying in a sleep-like state without motor activity = comfortable patient
• The ICU experience is inhumane
– The ability to form factual memories is cruel• Could even lead to PTSD
Non-
evidence
based
• Could even lead to PTSD
– Amnesia of the ICU experience is desired
Avoiding Coma Impacts Outcomes
Fraser and Riker. CCM 2007; 35:635
What about long-term
outcomes?
Periscope depth
Depth of Sedation?
“PTSD was highest in
the middle level of
To the ocean floor
the middle level of
wakefulness and lowest
when least aroused or
the most awake.’
Griffiths. CCM 2008; 36:945
ICU Pain and Discomfort
Pain and/or Discomfort Should ALWAYS
Be Considered a Cause of ICU Agitation
• “Mundane/routine” aspects of ICU care are the most troublesome for patients
1990
63% remembered moderate to severe painPuntillo. Heart Lung 1990; 19:526Puntillo. Heart Lung 1990; 19:526
2007
50% remembered unmet analgesic needsGelinas. Intensive Crit Care Nurs 2007; 23:298
There has been little progress despite 17 years of focused
attention on pain as an important clinical issue
New Paradigm: Analgesia-based “Sedation”
Crit Care 2005; 9: R200 , Crit Care 2004; 8:R1, Anesthesiology 2004; 101:640, Br J Anaesth 2007; 98:76, ICM 2009; 35:291
• Also known as analgosedation or analgesia-
first (A-1) sedation
• Acknowledges that discomfort is a common
cause of agitationcause of agitation
• Continuous infusion remifentanil or
fentanyl
– Rapid onset and offset
• ~ 50% will require additional sedation
Redefining the Roles of
Available Sedative Agents
• A very selective review of data
– Dexmedetomidine
– Benzodiazepines– Benzodiazepines
– Propofol
Dex Dose, Duration, and Downsides
61% required more than 0.7mcg/kg/h
Duration up to 15 days
Riker. JAMA. 2009; 301:489-99.
Time to Successful Extubation ≠
Shorter ICU Stay
Time to
Extubation
Dexmedetomidine
(n=244)
Midazolam
(n=122)
Absolute
Reduction
(%, days)
P
value
Median
(95%CI)
3.7 days
(3.1 – 4.0)
5.6 days
(4.6-5.9)
32.2%
1.9 days0.01
Riker. JAMA. 2009; 301:489-99.
ICU LOS
daysDexmedetomidine
(N=244)
Midazolam(N=122)
Absolute
Reduction
(%), days
P
value
Median
(95%CI)
5.9 days
(5.7 - 7.0)
7.6 days
(6.7 – 8.6)
22.3%
1.7 d0.24
Pearls For The Use of Dex
• Do not use loading dose
• Expand dosing range to 0.1-1.4mcg/kg/hr
• Expand permissible treatment duration >24h>24h
• Anticipate dex-induced hemodynamic instability and bradycardia
• Combine with other sedative or analgesic agents as needed
• Transition to clonidine
30 Minute Dexmedetomidine Dose
Adjustments Reduce HypotensionGerlach. J Crit Care 2009; 24:568
ICU Costs Comparing
Dexmedetomidine vs Midazolam
It’s a Matter of Time and Ability to Discharge
• % time at target sedation range: midazolam = dexmedetomidine (JAMA 2009; 30:489)
• Blinded evaluation of costs of care– ICU length of stay, time on vent, drug costs, and cost – ICU length of stay, time on vent, drug costs, and cost
of adverse reactions using cost minimization analysis
• Median savings: dex vs midazolam – Median drug costs: Dex = $1826, Midazolam = $60
– Primary drivers of cost savings = ICU stay and time on the ventilator; ~ $6K and $3K respectively
– $9,679 (95% CI = $2,314-17,045, p = .01)
Dasta. CCM 2010 epub ahead of print
Benzodiazepines
Sedative Infusions:
Propofol >> BenzodiazepinesWunsch. CCM 2009 (Project IMPACT)
50% receive continuous
infusion sedation; most
propofol, 30% = benzo
Propofol infusion use
increasing, not lorazepam
Benzodiazepine Concerns: Delirium
Benzodiazepines• Independent risk
factor for development
of delirium
• Especially if used to • Especially if used to
induce even brief
periods of coma
Pandharipande. Anesthesiology 2006; 104:21 and J Trauma 2008; 65:34
Ouimet. ICM 2007; 33:66
Lorazepam as a Source of Propylene Glycol (PG)
• PG toxicity
– Metabolic acidosis,
hyperosmolality, acute
kidney injury
– Osmol gap of >10-12 – Osmol gap of >10-12
may serve as surrogate
for propylene glycol
accumulation in
patients receiving >
1mg/kg/d lorazepam 80% of a vial of lorazepam is PG
Yahwak. Pharmacotherapy 2008: 28:984
Propofol
Propofol: Concerns• NO analgesia!
– 25% receive opiate infusion while on propofol vs 66% with benzo infusions Wunsch 2009 CCM
• Hypotension• Hypertriglyceridemia; lipid source (1.1 kcal/ml)
– Monitor triglycerides twice weekly– Monitor triglycerides twice weekly
• Respiratory depression
• Propofol Infusion Syndrome (PRIS)--rare, but often fatal• Asystole/bradycardia, cardiovascular collapse, rhabdomyolysis, and
severe metabolic acidosis
• Caution should be exercised at doses >80mcg/kg/min for more than 48 hours—also seen at lower doses within a few hours of initiation
• Most commonly reported in patients also receiving catecholamines and/or steroids
• Discontinue propofol in the setting of unexplained bradycardia or metabolic acidosis
PRIS: More Common Than Thought?Iyer. CCM 2009; 37 epub
• 11 year review of refractory status epilepticus pts
• Outcomes in the propofol treated group (N = 31)
– PRIS features occurred in 39%
• 20% of this cohort (N= 3) developed life-threatening cardiac
arrest ----2 died. arrest ----2 died.
– Peak propofol dose in these patients = 141 vs 60mcg/kg/min in
noncardiac arrest PRIS patients.
• None of the PRIS features occurred in patients
who did not receive propofol
ICU Agitation Management
• Homemade or canned?– Doesn’t matter as long as the essential ingredients are
included
• Management strategies are context/patient specific– Probable reason for agitation
• Pain• Pain
• Withdrawal
• Anxiety
• Delirium
– Other modifiers • Intubated vs not
• Short vs long-term sedation
• Organ dysfunction: heart, brain, liver, and kidney
• Deep vs light
Tools to Facilitate Bedside
Application
• Order sets based on agreed-upon institution
specific protocols
• Real-time clinical decision support • Real-time clinical decision support
• Bundles imbedded with data feedback
Real-Time Clinical Decision
Support Tools
Once modifiers are selected, all orders appropriate for this
patient become available
Sedation, Analgesia, Delirium (SAD) Bundle
Make your own “bundle” with elements and metrics1. Screen for the presence of pain, agitation, and delirium and
accurately document on a consistent basis• How often is this documented each day?
2. Insure that measures to prevent and treat pain, agitation, and delirium are a part of routine ICU care
• Adhere to institution-specific protocols
• Provide analgesia prior to procedure associated with pain• Provide analgesia prior to procedure associated with pain
• Provide management < 0.5 h of discomfort or agitation
• Achieve sedation goal without coma or dangerous agitation
• Document strategies to prevent delirium each day
3. Monitor the effectiveness of these strategies • % time spent in drug induced coma (SAS 1-2)
• % patients reporting moderate to severe pain
• % SBT stalled due to under and over-sedation
• ICU ventilator time (or ventilator-free time)
• % patients developing delirium during the ICU stay
Adapted from VISICU
Managing ICU Agitation
• Complexity is daunting
• Tempting to use guidelines/bundles blindly– Adapt before you adopt
• Caregiver responsibilities– Understand that short AND long-term ICU patient – Understand that short AND long-term ICU patient
outcomes are affected by therapeutic choice and method of administration
• Institution responsibilities– Provide adequate resources to implement systems that
guide “best practice” and allow for feedback to caregivers
Time to leave….. thanks for your attention
They Do Things Differently Down UnderProtocolization of ICU Sedation
• NA and European trials = outcomes
improve with protocolized sedation
• But NOT in Australia!
– Why? Is the strategy not beneficial?– Why? Is the strategy not beneficial?
– Do unique aspects of care impact results?
• 1:1 RN to patient ratio
• RNs manage ventilator
• ICUs are “closed”
• Twice daily multidisciplinary rounding
• ANZ care model may impact outcomes
more than sedation protocolization
Bucknall. Crit Care Med 2008; 36:1444
Elliott. Intensive Care Med 2006; 32:1506
Fraser. Crit Care Med 2007; 35:635
How Are Clinical Practice
Guidelines Used?
Purpose: GUIDE management of complex clinical issues
Reality: PRESCRIBE management of complex clinical issues
And what’s wrong with that?
Intellectual Whiplash
Intensive
Glucose Control
Factor VIIa for
ICH
Drotrecogin for
Sepsis
ACTH stim
testing
Developing “Fad-Free” Guidelines
Steroids for
Septic Shock
Benzo InfusionsFor Long-term
Sedation
PPI Use for
SUP
They Do Things Differently Down UnderProtocolization of ICU Sedation
• NA and European trials = improved
outcomes with protocolized sedation
• But NOT in Australia!
– Why? Is the strategy not beneficial?– Why? Is the strategy not beneficial?
– Do unique aspects of care impact results?
• 1:1 RN to patient ratio
• RNs manage ventilator
• ICUs are “closed”
• Twice daily multidisciplinary rounding
• ANZ care model may impact outcomes
more than sedation protocolization
Bucknall. Crit Care Med 2008; 36:1444
Elliott. Intensive Care Med 2006; 32:1506
Fraser. Crit Care Med 2007; 35:635
Often Boils Down to Competing Concerns
• Breathing vs comfort
• Hemodynamic stability vs comfort
• Amnesia vs memory formation
• Short-term control vs long-term sequelae• Short-term control vs long-term sequelae
• Coma vs interactive and comfortable
• Side effect profiles: can we accept the risks
– Unusual, but deadly (propofol, remi) vs
common and manageable (dex) vs easily
monitored for and identifiable (opiates)
Unique Aspects of ICU Pain
• Pain relief usually involves some evasive action
– Avoidance response not possible in the ICU
• Incredibly common: 71% frequency
• Physiologic consequences
– Initiates stress response, hemodynamic derangement,
hyperglycemia, altered immune function and increases
oxygen consumption
• Psychological consequences
– Anxiety
– Delirium
– PTSD
Discomfort from Typical ICU Procedures
Mean Pain Intensity (0-10)
N = 6000 Adults
22.5
33.5
44.5
5
Puntillo. Am J Crit Care. 2001;10:238
00.5
11.5
2
Mean intensity 4.93 4.67 4.42 3.94 2.72 2.65
TurningDrain
removal
Wound
careTrach sx
Central
line
Femoral
sheath
Less than 25% receive procedural pain
management
Puntillo. Am J Crit Care 2002;11:415, Payen. Anesthesiology 2007;
106:687
Screeningup to 96 h
Double-Blind Treatment (X - 30 d)
Follow-Up
48 h
DEX (Optional load; 0.2-1.4 µg/kg/h)
Randomized 2:1 DEX:MDZ
ETT
Day 0
DEX (Optional load; 0.2-1.4 µg/kg/h)
MDZ (Optional load; 0.02-0.1 mg/kg/h)
Daily Arousal & CAM-ICUQ 4 hr RASS -2 to +1
Nurse Assessment Q Shift
Riker. JAMA. 2009; 301:489-99.
Dexmedetomidine: Indications and
Pharmacology
• Alpha-2-adrenergic agonist
– Has sedating, anxiolytic, and opiate sparing properties
– Permits patient awareness and responsiveness upon
stimulation
– Not indicated when deep sedation or amnesia is required– Not indicated when deep sedation or amnesia is required
• Benefits
– Does not cause respiratory depression
– Decreases sympathetic activity
– Reduces shivering
– Shorter time on the ventilator and in the ICU with a lower
incidence of delirium when compared to benzodiazepine-
based sedation Pandharipande. JAMA. 2007;298:2644,
Riker. JAMA 2009; 301:489
Dexmedetomidine: Concerns
• Hypotension and bradycardia
– Avoid in patients dependent on sympathetic
tone for hemodynamic stability
• Excessive sedation
• Withdrawal tachycardia/hypertension
(theoretical risk)
Disadvantages of Benzodiazepines
• Oversedation and prolonged duration of
mechanical ventilation
– Titrate carefully and use daily wake ups
Propofol: Indications and
Pharmacodynamics
• Pharmacology: GABA agonist
• Pharmacokinetics/dynamics: onset 1-2 min, duration 10 min
• Benefits– Rapid onset & offset– Rapid onset & offset
• Allows easy dose titration to goal and facilitates daily sedation evaluation
• When compared to benzodiazepines, results in shorter time on mechanical ventilation and in the ICU Carson. CCM 2006; 34:1326
– Hypnotic and antiemetic
– Can be used for intractable seizures and elevated intracranial pressures
Use of Sedative InfusionsProject IMPACT database
Wunsch. CCM 2009
• 174 U.S. ICUs during 2001-2007
• 50% of >100K mechanically ventilated
adult patients received sedative infusions
– Most patients received propofol
– Pure analgosedation = 10%
• A1 still has a long way to go for acceptance
– Benzodiazepine infusions still widely used
Bundles, Guidelines, and Marginal Data
• Sepsis bundle based on “Surviving Sepsis Campaign”
(the CPG with the strongest recommendations =
abandon futile therapy)
– Single center trials
• Early goal directed therapy and intensive glucose control
– Trials with limited scope
• Drotrecogin
– Trials that lacked meaningful endpoints
• Corticosteroids
Not endorsed by IDSA, ATS, ANZICS in part because of the
fear that components of the CPG will morph into performance
or quality measures. Hicks. Crit Care Resuscitation 2008; 10: 6
Dexmedetomidine: ICU Roles
• Consider using– When respiratory function is tenuous
– When tachycardia and hypertension are present
– In conjunction with benzodiazepines for ethanol withdrawalwithdrawal
• When is dex probably not indicated– Severe vasodilatory or cardiac shock
– If you wouldn’t use beta blockade, you shouldn’t use dex