Transcript Barr J, et al. Crit Care Med. 2013

Pain, Agitation and Delirium (PAD):
An Overview of Recent Guidelines
Brenda Pun, RN, MSN, ACNP
Vanderbilt University Medical Center
Barr J, et al. Crit Care Med. 2013;41:263–306.
Pain, Agitation, and Delirium
Are Interrelated
Delirium
Barr J, et al. Crit Care Med. 2013;41:263-306.
5 Key Themes
1. Goal = Light sedation
2. Sedative titration method =
– Daily Sedative Interruption or
– Targeted sedation
3. Avoid/Minimize Benzodiazepines
4. Early Mobility
5. No Med Recommendation for Delirium
#1: Light Sedation
(rather than deep)
PAD Depth of Sedation Recommendations
We recommend that sedative medications be
titrated to maintain a light rather than a deep level
of sedation in adult ICU patients, unless clinically
contraindicated (+1B).
Light Sedation: patient is arousable and able
to purposefully follow simple commands
Barr J, et al. Crit Care Med 2013; 41:263–306
Early Deep Sedation:
Longer Ventilation, Reduced Survival
• Early deep sedation was also an
independent predictor of hospital
• Deep sedation (RASS -3 to death and 180-day mortality
5)
– 76% within 4 hours of MV
– 68% at 48 hours
• Multicenter study (N=251)
• Early deep sedation was
independent predictor of time
to extubation (P<0.001)
– Deeply sedated, 7.7 days
– Not deeply sedated, 2.4
days
Survival
Days
Probability of death at 180 days
Shehabi Y, et al. Am J Respir Crit
Care Med. 2012;186:724-731. 9
Mental Health and Light vs Deep Sedation
• Sedation with midazolam
– Light: Ramsay 1-2, intermittent injection
– Deep: Ramsay 3-4, continuous infusion
• Results
4 weeks after ICU discharge the deep group:
• Higher PTSD Scores
• Trouble remembering the ICU
• Disturbing memories
Treggiari MM, et al. Crit Care Med. 2009 Sep;37(9):2527-2534.
#2: Sedative Titration Method
Daily Sedative
Interruption
Light Targeted
Titration
PAD Titration Recommendations
We recommend either daily sedation interruption
or a light target level of sedation be routinely
used in mechanically ventilated adult ICU
patients (+1B).
Barr J, et al. Crit Care Med 2013; 41:263–306
Daily Sedation Interruption
Methods:
Hold sedation infusion until patient awake and then restart
at 50% of the prior dose
Results:
•Shorter time on the ventilatory
•Shorter stay in the ICU
•Fewer diagnostic tests to assess changes in mental
status
• No increase in rate of agitated-related complications or
episodes of patient-initiated device removal
• No increase in PTSD or cardiac ischemia
Kress JP, et al. N Engl J Med. 2000;342:1471-1477.
Kress, JP, et al. AJRCCM 2003; 168: 1457-1461
Wake up and Breathe
(ABC) Study
The ABC protocol reduced….
A: Spontaneous
Awakening Trials
• Duration of mechanical
ventilation by ~3 days
• ICU and hospital length of stay
by ~4 days
B: Spontaneous
Breathing Trials
• Duration of coma by ~1 day
• 32% lower likelihood of dying
and a number needed to treat
(NNT) of 7 to save a life at 1
year
Girard TD, et al. Lancet. 2008;371:126-134.
Nursing-Implemented Sedation Protocol:
Barnes Jewish Pilot
25
P < 0.001
Protocol n = 162
Routine n = 159
Significant patient characteristics/metrics/outcomes
Protocol
Routine
P value
CIVS†
66 (40)
66 (42)
0.9
Duration CIVS, hrs*
3.5 ± 4
5.6 ± 6.4
0.003
Bolus†
118 (72)
127 (80)
0.14
Reintubated†
14 (8.6)
21 (13)
0.2
Trached†
10 (6.2)
21 (13.2)
0.04
20
Median Time (days)
20
14
15
P = 0.13
10
P = 0.003
4.8
5
7.5
5.7
*Data presented in median; †Data presented as n (%)
CIVS: continuous intravenous infusion sedation
2.3
0
Duration of MV
ICU LOS
Hospital LOS
Single center, prospective, trial of 332 consecutive ICU patients requiring mechanical ventilation randomized
to protocolized sedation (n = 162) or routine care (n = 159) at Barnes Jewish Hospital from 8/97 to 7/98.
Protocol used goal orientated sedation to target Ramsey with bolus requirements before initiation of
continuous infusion and uptitration of opioids and benzodiazepines.
Brook AD, et al. Crit Care Med. 1999;27(12):2609-2615.
Pharmacist Enforced Adherence to an ICU
Sedation Guideline
25
RPh intervention n = 78
P = 0.001
Significant patient characteristics/metrics/outcomes
Control n = 78
19.8
Median Time (days)
20
RPh
Control
P value
15 (19.2)
6 (7.7)
0.03
Lorazepam
equivalents/vent
day, mg*
65.2 ±
114.1
74.8 ±
76.1
0.54
Fentanyl
equivalents/vent
day, mcg*
102.5 ±
328
400 ±
1026
0.02
Alcohol/drug
overdose†
P = 0.002
15
P = 0.0004
11.8
10.6
8.9
10
7
5.3
*Data presented in mean ; †Data presented as n (%)
5
0
Duration of MV
ICU LOS
Hospital LOS
Single center trial of 156 adult MICU patients requiring mechanical ventilation before (n = 78)
and after (n = 78) implementation of RPh enforced guideline sedation management at Boston
Medical Center. Guideline addressed use of agent selection, goal oriented therapy, and dose
limitation strategies.
Marshall J, et al. Crit Care Med. 2008;36(2):427-433.
#3: Avoid/Minimize
Benzodiazepine use
PAD Choice of Sedative
Recommendations
• We suggest that analgesia-first sedation be used in
mechanically ventilated adult ICU patients (+2B).
• We suggest that sedation strategies using
nonbenzodiazepine sedatives (either propofol or
dexmedetomidine) may be preferred over sedation with
benzodiazepines (either midazolam or lorazepam) to
improve clinical outcomes in mechanically ventilated
adult ICU patients (+2B).
• We suggest that in adult ICU patients with delirium
unrelated to alcohol or benzodiazepine withdrawal,
continuous IV infusions of dexmedetomidine rather than
benzodiazepine infusions be administered for sedation to
reduce the duration of delirium in these patients (+2B).
Barr J, et al. Crit Care Med 2013; 41:263–306
Analgosedation
• Analgesia Sedation vs. Hypnotic Sedation
• Analgesic first sedation + supplement with
hypnotic sedative
• Treats pain + provides sedation
– Remifentanil
– Fentanyl
– Morphine
• Not appropriate for drug or alcohol withdrawal
Park G, et al. Br J Anaesth. 2007;98:76-82.
Rozendaal FW, et al. Intensive Care Med. 2009;35:291-298.
Analgosedation Study
Results
• Patients receiving analgosedation had
–
–
–
–
More days without ventilation (13.8 vs 9.6 days, P = 0.02)
Shorter stay in ICU (HR 1.86, P = 0.03)
Shorter stay in hospital (HR 3.57, P = 0.004)
More agitated delirium (N = 11, 20% vs N = 4, 7%, P = 0.04)
• No differences found in
– Accidental extubations
– Need for CT or MRI
– Ventilator-associated
pneumonia
Strøm T, et al. Lancet. 2010;375:475-480.
PAD Choice of Sedative
Recommendations
• We suggest that analgesia-first sedation be used in
mechanically ventilated adult ICU patients (+2B).
• We suggest that sedation strategies using
nonbenzodiazepine sedatives (either propofol or
dexmedetomidine) may be preferred over sedation with
benzodiazepines (either midazolam or lorazepam) to
improve clinical outcomes in mechanically ventilated
adult ICU patients (+2B).
• We suggest that in adult ICU patients with delirium
unrelated to alcohol or benzodiazepine withdrawal,
continuous IV infusions of dexmedetomidine rather than
benzodiazepine infusions be administered for sedation to
reduce the duration of delirium in these patients (+2B).
Barr J, et al. Crit Care Med 2013; 41:263–306
Propofol vs. Benzodiazepines
Randomized Trial
ICU
Comparator
Superior
Ronan et al.1995
Surgical
Midazolam
Propofol
Chamorro et al. 1996
General
Midazolam
Propofol
Hsiao et al. 1996
Surgical
Midazolam
Equivalent
Kress et al. 1996
Medical
Midazolam
Propofol
Barrientos-Vega et al. 1997
General
Midazolam
Propofol
Searle et al. 1997
Cardiac
Midazolam
Equivalent
Weinbroum et al. 1997
General
Midazolam
Both
Sanchez-Izquierdo-Riera JA, et al. 1998
Trauma
Midazolam
Propofol
Mixed
Midazolam
Propofol
Medical
Lorazepam
Propofol
Hall et al. 2001
Carson et al. 2006
Outcomes improved by propofol: sedation quality, ventilator synchrony, time to
awakening, variability of awakening, time to extubation from discontinuation of
sedation, overall time to extubation, ventilator days, ICU LOS among survivors,
costs of sedation
Dexmedetomidine vs Benzodiazepines
Trials with better outcomes
with Dex
Population
Outcome Improved
Pandharipande et al/2007
Mixed ICU
Riker et al/2009
Mixed ICU
Ruokonen et al/2009
Mixed ICU
Maldonado et al/2009
Cardiac surgery
Esmaoglu et al/2009
Eclampsia
More accurate sedation, more
delirium/coma-free days
Lower prevalence of delirium,
earlier extubation
Shorter duration of mechanical
ventilation
Lower incidence and duration of
delirium
Shorter ICU length of stay
Dasta et al/2010
Mixed ICU
Lower ICU costs
Jakob et al/2012
General ICU
Lighter sedation, fewer
ventilation days
• Trials with better outcomes with Benzo’s = None
Ely EW, et al. Chest. 2012;142(2);287-289.
#4: Early Mobility
Early Mobility in the ICU
• Early exercise = progressive mobility
• Study design: paired SAT/SBT protocol with PT/OT
from earliest days of mechanical ventilation
Wake Up, Breathe, and
Move
Schweickert WD, et al. Lancet. 2009;373:1874-1882.
Early Mobility Study
Results:
• Return to
independent
functional
status at d/c
(59% vs 35%)
• Decrease in
ICU and Hosp
Delirium (2 vs 4
days)
• Decrease in
time on Vent
Schweickert WD, et al. Lancet. 2009;373:1874-1882.
#5: No medication
recommendation for the treatment
of delirium
Delirium Risks
During the
ICU/Hospital Stay
After Hospital
Discharge
• Increased mortality
• Longer intubation time
• Average 10 additional days in hospital
• Higher costs of care
• Increased mortality
• Development of dementia
• Long-term cognitive impairment
• Requirement for care in chronic care facility
• Decreased functional status at 6 months
PAD Treatment of Delirium
Recommendations
• There is no published evidence that treatment
with haloperidol reduces the duration of
delirium in adult ICU patients (No Evidence).
• Atypical antipsychotics may reduce the duration
of delirium in adult ICU patients (C).
• We do not recommend administering
rivastigmine to reduce the duration of delirium in
ICU patients (–1B).
Barr J, et al. Crit Care Med 2013; 41:263–306
The MIND Study
Haloperidol
n = 35
Ziprasidone
n = 32
Placebo
n = 36
Design:
• Randomized and double-blind
• Multisite (6 centers), 103 MV patients
• PO/IM delivery of study drug
Results:
• No difference in any outcome
• No difference in any side effect
Girard TD, et al. Crit Care Med. 2010;38(2):428-437.
PAD Treatment of Delirium
Recommendations
• There is no published evidence that treatment
with haloperidol reduces the duration of
delirium in adult ICU patients (No Evidence).
• Atypical antipsychotics may reduce the duration
of delirium in adult ICU patients (C).
• We do not recommend administering
rivastigmine to reduce the duration of delirium in
ICU patients (–1B).
Barr J, et al. Crit Care Med 2013; 41:263–306
Quetiapine vs. Placebo
Delirium +
Haloperidol PRN
Quetiapine (n = 18)
Placebo (n = 18)
Design:
• Randomized, double-blind, placebo-controlled
• Multisite (3 centers), 36 ICU patients
• PO delivery of study drug
Results:
• Faster delirium resolution & Less agitation
• Greater rate of transfer to home or rehabilitation
Devlin JW, et al. Crit Care Med. 2010;38(2):419-427.
PAD Treatment of Delirium
Recommendations
• There is no published evidence that treatment
with haloperidol reduces the duration of
delirium in adult ICU patients (No Evidence).
• Atypical antipsychotics may reduce the duration
of delirium in adult ICU patients (C).
• We do not recommend administering
rivastigmine to reduce the duration of delirium in
ICU patients (–1B).
Barr J, et al. Crit Care Med 2013; 41:263–306
Rivastigmine for Delirium?
Survival (%)
• FDA approved for dementia of Alzheimer’s or
Parkinson’s
• Cholinesterase inhibitor
• Result
− Mortality (vs placebo): 22% vs 8%, P = 0.07
− Delirium (vs placebo): 5 vs 3 days, P = 0.06
• Conclusion:
Time (days after inclusion)
− Need RCTs for delirium as endpoint
− Don’t use rivastigmine for ICU delirium
http://www.accessdata.fda.gov. Accessed March 2012.
Van Eijk MM, et al. Lancet . 2010;376(9755):1829-1837.
Helpful Approach to Delirium
Management
• Stop
• THINK
• Lastly Medicate
What to THINK if positive for delirium
Toxic Situations
– CHF, shock, dehydration
– Deliriogenic meds (tight titration)
– New organ failure (liver, kidney, etc)
Hypoxemia;
Infection/sepsis (nosocomial), Immobilization
Nonpharmacological interventions
K+ or Electrolyte problems
Pain, Agitation, and Delirium
Are Interrelated
Delirium
Barr J, et al. Crit Care Med. 2013;41:263-306.
PAD Interdisciplinary Team
Pharmacy
Champion
Physical
Therapy
Champion
RT
Champion
Hospital
Administrators
RN
Champion
MD
Champion
Family
Integrated
Approach to
PAD
Patient
Courtesy J Barr, MD
Teach your team how to
Communicate and Think!
If you give a man a fish,
he will eat for a day.
If you teach a man to fish,
he will eat for a lifetime.
Chinese Proverb
Start with the Foundation:
Assessment
Pain
– CPOT
– BPS
Agitation
– SAS
– RASS
Delirium
– CAM-ICU
– ICDSC
Barr J, et al. Crit Care Med. 2013;41:263-306.
Brain Road Map
1. Where is the patient going?
(Target Sedation Level)
2. Where is the patient now?
(Current PAD Assessnent)
© Brian Sloan via Flickr
3. How did they get there?
Drug exposures
Brain Road Map
Script for Rounds
Investigate
(Ask these questions)
Where is the patient
going?
Report
(only takes 10 seconds)
Target level of consciousness
(RASS/SAS)
Actual level of consciousness
(RASS/SAS)
Delirium assessment
Where is the patient now?
(CAM-ICU/ICDSC)
Pain Assessment Scale
(BPS/CPOT)
How did they get there?
Drug exposures
Brain Road Map
Example
Investigate
(Ask these questions)
Where is the patient
going?
Report
(only takes 10 seconds)
Target/Goal is RASS -1/0
Currently:
RASS is -3 (-3 and -4 for past 6 hrs)
Where is the patient now?
CAM-ICU positive
CPOT of 4
How did they get there?
Propofol infusion 40 mcg/kg/min &
intermittent fentanyl for pain
5 Key Themes
1. Goal = Light sedation
2. Sedative titration method =
– Daily Sedative Interruption or
– Targeted sedation
3. Avoid/Minimize Benzodiazepines
4. Early Mobility
5. No Med Recommendation for Delirium
Questions?
www.ICUdelirium.org
[email protected]