Whats New in the Patient Safety World
April 2016
Dexmedetomidine and Delirium
Pharmacologic interventions to prevent or treat delirium have been elusive. Antipsychotic drugs have sometimes been touted to be successful but the evidence has not been very convincing. A meta-analysis of antipsychotic treatment in patients with delirium (Kishi 2015) suggested that second generation antipsychotics have a benefit for the treatment of delirium with regard to efficacy and safety compared with haloperidol but emphasized that further study using larger samples is required. But another recent systematic review and meta-analysis found that current evidence does not support the use of antipsychotics for prevention or treatment of delirium (Neufeld 2016). Those authors found antipsychotic use was not associated with reduction in delirium incidence, change in delirium duration, severity, or hospital or ICU length of stay.
For several years
now there has been interest in the use of dexmedetomidine, an
α2-adrenoreceptor agonist, as a sedation agent in the ICU because it might
be associated with less delirium. In our February 10, 2009 Patient Safety Tip
of the Week Sedation
in the ICU: The Dexmedetomidine Study we discussed the SEDCOM (Safety and
Efficacy of Dexmedetomidine Compared With Midazolam) Study, which concluded that
dexmedetomidine was as effective as midazolam at keeping patients in the
desired sedation range and was associated with a reduced prevalence of delirium
and reduced time to extubation (Riker 2009).
However, we urged caution in interpreting the conclusions of that study because
of several methodological and other concerns outlined in our column. We again
discussed dexmedetomidine in our June
16, 2015 Patient Safety Tip of the Week Updates
on Delirium.
Now another study has addressed the use of dexmedetomidine in intubated ICU patients with delirium (Reade 2016). The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial in 15 ICUs in Australia and New Zealand. Subjects were ICU patients who were deemed to be ready for extubation except that they had delirium. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively). Among several secondary outcome measures they also found that dexmedetomidine reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo), and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours).
Again, this sounds
encouraging, particularly since our pharmacologic armamentarium for managing
delirium is so limited. Yet there are again some red flags that urge us to be
cautious in recommending widespread use of dexmedetomidine. First of all, this
study applies only to a very select group of patients those who were already
well enough to be being considered for extubation except for their delirium.
The authors note that they screened 21,500 patients to recruit just the 74
patients randomized in the study! That small sample size (actually only 71
patients after 3 withdrawals for various reasons). Even more importantly, the
study was terminated before its planned recruitment of 96 patients. Studies
with early termination typically show more exaggerated effect sizes. Early
termination was apparently done because the funding source ceased funding
beyond the originally defined period. The authors note that the funding source
had no role in the design of the study and had no access to study data during
the study, and the authors performed sensitivity analyses suggesting the abbreviated
sample size was unlikely to alter the primary conclusion. Nevertheless, such
occurrences always raise our hype radar or spin radar (see our February 16,
2010 Patient Safety Tip of the Week Spin/Hype
Knowing
It When You See It).
So while we are
somewhat encouraged by the results of the DahLIA study, were not yet ready to
jump on the dexmedetomidine bandwagon for more widespread use. Remember, this
was a very narrow patient population and it would be premature to extrapolate
the results to patients with delirium earlier in their ICU course (i.e. before
they were deemed otherwise ready for extubation). The good news, though, is that
the dexmedetomidine seemed to be well tolerated in this study and adverse
events were rare. We therefore look forward to further studies on the use of
dexmedetomidine for either prevention or treatment of delirium.
Some of our prior
columns on delirium assessment and management:
·
October
21, 2008 Preventing
Delirium
·
October
14, 2008 Managing
Delirium
·
February
10, 2009 Sedation
in the ICU: The Dexmedetomidine Study
·
March
31, 2009 Screening
Patients for Risk of Delirium
·
June 23,
2009 More
on Delirium in the ICU
·
January
26, 2010 Preventing
Postoperative Delirium
·
August
31, 2010 Postoperative
Delirium
·
September
2011 Modified
HELP Helps Outcomes in Elderly Undergoing Abdominal Surgery
· December 2010 The ABCDE Bundle
·
February
28, 2012 AACN
Practice Alert on Delirium in Critical Care
·
April 3, 2012 New
Risk for Postoperative Delirium: Obstructive Sleep Apnea
·
August
7, 2012 Cognition,
Post-Op Delirium, and Post-Op Outcomes
·
September
2013 Disappointing
Results in Delirium
·
October
29, 2013 PAD:
The Pain, Agitation, and Delirium Care Bundle
·
February
2014 New
Studies on Delirium
·
March
25, 2014 Melatonin
and Delirium
·
May 2014
New
Delirium Severity Score
·
August
2014 A
New Rapid Screen for Delirium in the Elderly
·
August
2014 Delirium
in Pediatrics
·
November
2014 The
3D-CAM for Delirium
·
December
2014 American
Geriatrics Society Guideline on Postoperative Delirium in Older Adults
·
June 16,
2015 Updates
on Delirium
·
October
2015 Predicting
Delirium
·
April
2016 Can
Antibiotics Lead to Delirium?
References:
Kishi T, Hirota T, Matsunaga S, Iwata N. Antipsychotic medications for the treatment of delirium: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry 2015; Published online first September 4, 2015
http://jnnp.bmj.com/content/early/2015/09/04/jnnp-2015-311049.abstract
Neufeld KJ, Yue J, Robinson TN, et al. Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis. Journal of the American Geriatrics Society 2016; published online 23 March 2016
http://onlinelibrary.wiley.com/doi/10.1111/jgs.14076/abstract
Riker RR, Shehabi Y, Bokesch PM, et al for the SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients. A Randomized Trial. JAMA. 2009; 301(5):489-499. Published online February 2, 2009
http://jama.jamanetwork.com/article.aspx?articleid=183300
Reade MC, Eastwood GM, Bellomo R, et al. Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium: A Randomized Clinical Trial. JAMA 2016; Published online March 15, 2016
http://jama.jamanetwork.com/article.aspx?articleid=2503421
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