Drugs, Delirium and Daily Interruptions of Sedation

1
Drugs, Delirium and Daily Interruptions of
Sedation

• Noel Baldwin BSN, RN
• University of Michigan
• Critical Care Medicine Unit

2
Points of Discussion

• Review of sedatives commonly used in the ICU
• Describe the need to identify and assess for
  delirium in the ICU
• Describe current recommendations to improve
  outcomes

3
Common ICU sedatives analgesia

• Benzodiazepines ativan, versed, valium
• Hypnotic propofol
• Alpha 2 agonist dexmedetomidine (Precedex)
• Analgesia morphine, fentanyl, dilaudid

4
Benzodiazepines enhance the effect of the GABA
neurotransmitter thereby decreasing neuron
excitability

• Versed short acting with 1.5 to 5 minute onset
  of action, effects last an average of 2 hours,
  half life of 2.5 hours
• Ativan intermediate acting with 15 to 30 minute
  onset, effects last an average of 6-8 hours, half
  life is 9.5-19 hours
• Valium long acting with rapid IV onset of 1-5
  minutes, half life is 20-50 hours
• Wake up time after continuous infusions
  unpredictable

5
Propofol several mechanisms of action both
through potientiation of GABA receptors and also
acts as a sodium channel blocker

• A short acting hypnotic agent with rapid onset of
  less than 1 minute. Wake up time is usually
  minutes, but if used for prolonged period, build
  up in tissues will lead to longer wake up.
• Artificial airway required due to apnea (unless
  MD with deep sedation privelages)
• Monitor for hypotension
• Lipid based solution, monitor triglycerides

6
Dexmedetomidine agonist of the a2 adrenergic
receptor. It produces sedative, analgesic and
anxiolytic effects

• Bolus dose followed by continuous infusion.
  Onset of action is 30-60 minutes with a duration
  of 4 hours. Half life is 2-3 hours.
• NO RESPIRATORY SUPPRESSION
• Bradycardia is most common side effect
• Expensive. Still under patent.

7
More alert, cooperative patients PT ready?
Jakob et al. JAMA 2012 307(11) 1151-1160
8
Analgesia

• Morphine gold standard for treating pain.
• Fentanyl potent, synthetic narcotic with rapid
  onset and short acting. 100 times more potent
  than morphine.
• Dilaudid semi-synthetic narcotic. 6-8 times
  more powerful than morphine but with a lower risk
  of dependency.

9
Sedation Scales

• Richmond Agitation Sedation Scale

• Ramsay Scale

• 4 Combative, violent, danger to staff
• 3 Aggressive, pulls or removes tubes
• 2 Frequent nonpurposeful movements
• 1 Anxious, apprehensive
• 0 Alert and calm
• -1 Verbal stimulation, eye contact gt10sec
• -2 Verbal stimulation, eye contact lt 10sec
• -3 Verbal stimulation, no eye contact
• -4 Physical stimulation, responds
• -5 Physical stimulation, no response

• 1 anxious, agitated or restless
• 2 cooperative, oriented, tranquil
• 3 Responding only to verbal commands
• 4 brisk response to light glabella tap or loud
  auditory stimulus
• 5 sluggish response to light glabella tap or loud
  auditory stimulus
• 6 no response to light glabella tap or loud
  auditory stimulus

10
What is Delirium?
11
di-lir-E-m

• a disturbance of consciousness that is
  accompanied by a change in cognition that cannot
  be better accounted for by a preexisting
  dementia
• in contrast to dementia which develops slowly
  and persists over time, delirium symptoms develop
  rapidly and often fluctuate over a period of
  hours to days
• American Psychiatric Association

12
Perception v. Reality

• Perception delirium in the ICU is part of the
  scenery, or an expected and inconsequential
  outcome of mechanical ventilation and other
  therapies necessary to save lives.
• Reality delirium is an acute organ dysfunction
  that needs to be treated with medical urgency.

13
Estimated delirium rates

• Mechanically ventilated ICU patients
• 26-50
• Non-ventilated ICU patients
• 10-25

14
Looking Deeper.
15
Subtypes of Delirium

• Hyperactive agitation, restlessness, and
  hyper-vigilance patient often displays frequent
  non-purposeful movement or makes attempts to
  discontinue treatment
• Hypoactive withdrawal, flat affect and
  decreased responsiveness
• Mixed a fluctuation between both subtypes

16
Delirium Prevalence

• 614 critically ill medical ICU patients at a
  tertiary care center
• Hyperactive 1.6
• Mixed 55
• Hypoactive 43.5
• Peterson JF et al. J Am Geriatr Soc 2006 54
  479-84

17
Quiet is not always good.

• Hypoactive delirium patients seem to be the ideal
  patient quiet and peaceful. However, hypoactive
  delirium carries with it a worse prognosis than
  hyperactive delirium. Their delirium is often
  not recognized.
• Hyperactive delirium may lead to more sedatives.
  More sedatives may lead to prolonged, worsening
  of delirium. Sedatives should be reserved for
  utilization only if patient is at risk of harm to
  self.

18
How do I know if my patient is delirious?
19
Commonly Utilized Delirium Assessment Tools

• Intensive Care Delirium Screening Checklist
  (ICDSC)
• Confusion Assessment Method for the ICU (CAM-ICU
• Both proven sensitive and reliable

20
ICDSC

• Completed throughout the day/shift
• 4 delirium

21
CAM-ICU

• Approximately 2 minutes to complete
• Objective
• Patient must be able to open eyes to voice

for
22
CAM-ICU content
23
Why do we care?
24
It is expensive!
ICU delirium is associated with costs ranging
from 4 to 16 billion annually in the US alone,
not including added cost of lost workdays,
caregiver burden or cognitive rehabilitation
Pun et al 2007. CHEST 132(2) 624-636
25
2X Longer LOS
Ely et al JAMA 2004 291(14) 1753-1762
26
5X Self-Extubation

• Dubois, MJ et al. Intensive Care Med 2001 27
  1297-1304

27
More Cognitive Impairment

• Jackson and coworkers reviewed nine prospective
  studies, nearly 1900 patients, and found delirium
  was associated with long term cognitive decline
  over 1-3 years after discharge
• The relationship between long term cognitive
  impairment and delirium is still being studied
  but preliminary data suggests the association is
  significant.
• Jackson et al. Neuropsychol Review 2004 14
  87-98

28
Cognitive outcomes for delirious
patients

• 126 patients, 99 survived 3 months
• At 3 mos
• 21 (16/76) with no impairment
• 17 (13/76) with mild/moderate impairment
• 62 (47/76) with severe impairment
• At 12 mos
• 29 (15/52) with no impairment
• 35 (18/52) with mild/moderate impairment
• 36 (19/52) with severe impairment
• Duration of delirium was an independent predictor
  of worse cognitive performance
• Girard et al, Crit Care Med 2010 38
  1513-1520

29
People Die! 3X more likely to be dead in 6 months

Ely et al. JAMA 2004 291 1753-1762
30
Delirium duration and mortality 1 day 10
higher risk

Pisani et al. Am J Respir Crit Care Med 2009
180 1092-1097
31
What to think if your patient is delirious!

• Toxic situations CHF, shock, dehydration,
  deliriogenic medicines, new organ failure
• Hypoxemia
• Infection or Immobility
• Non-pharmacologic efforts hearing aids,
  eyeglasses, reorientation, noise reduction,
  sleep, ambulation
• K or Electrolyte problems

32
Predisposing Risk Factors

• Age gt 70yrs
• Depression
• Polypharmacy
• Anemia
• CHF
• Renal Failure
• HTN
• Tobacco use
• Pain
• Visual/hearing impairment
• Malnutrition
• Dementia
• Evaluate risk factors on admit!

33
Are the restraints necessary?
34
The problem with benzos
35
What can I do to help my delirious patient?
36
Prevention

• Use of eyeglasses and hearing aides
• Blinds open and lights on during daytime hours
• Allow for sleep at night (is that 2 a.m. bath
  really necessary?)
• Cognitive stimulation
• Familiar objects in the room (picture of family)
• Monitor hydration
• Early mobility
• Treat pain
• Limit deliriogenic drugs (benzos)

37
Pharmacological Approach

• Zero approved agents for delirium
• Common treatment protocols include haloperidol,
  resperidone, olanzapine and quetiapine
• Delirium protocols not well validated
• STOP deliriogenic medications!

38
MIND Trial
Outcomes Haldol N35 Ziprasidone N30 Placebo N36 p
Delirium/coma free days 14 (16-18) 15 (9.1-18) 12.5 (1.2-17.2) .66
Delirium days 4 (2-7) 4 (2-8) 4 (2-6) .93
Res of delirium on study drug, n () 24 (69) 23 (77) 21 (56) .28
21-day mortality, N () 4 (11) 4 (13) 6 (17) .81
Girard TD, et al. Crit Care Med 2010 38428-437
39
What about Dexmedetomidine?

• SEDCOM Trial

• MENDS Trial

Pandharipande PP, et al. JAMA 2007 298 2644-2653
Riker RR, et al. JAMA 2009 301489-499
40
Quetiapine (Seroquel)- Resolution of delirium
Devlin et al. Crit Care Med 2010 38 419-427
41
ABCDE Approach Modifying Risk Factors in the ICU
Combine awakening with breathing trials
42
Daily Awakening Trials

• Decreased days on ventilator
• Decreased ICU LOS
• Decreased hospital LOS
• Less diagnostic testing

Kress et al. NEJM 2000 342(20) 1471-1477
43
Daily awakening trial paired with breathing trials

• Duplicated daily awakening trial data
• PLUS, demonstrated a mortality benefit. For
  every seven patients treated, one life saved

Girard et al. Lancet 2008 371 126-134
44
Daily Awakening and Delirium
45
Stop Sedation?! What about the Emotional Trauma?

• Kress et al. AJRCCM(2003)168 1457-1461

46
Early Mobility
47
Best Patient Care

• Is the sedated patient stable?

48
The Lasting Legacy of ICU SurvivorshipEvidence
for Practice Change

• Physical Impairments
• Cognitive Decline
• Mental Health Issues
• Caregiver/Family Strain
• More to come on these issues later today

49
It is no longer a matter how we keep them alive,
but rather how well we keep them alive.--Wes
Ely, M.D, M.P.H