Patient Safety Tip of the Week
June 16, 2015 Updates on Delirium
A recent systematic review and meta-analysis of 42 studies
on delirium in ICU patients (Salluh 2015) reinforces
much of which we have already discussed about delirium. The authors found that
about a third (31.8%) of ICU patients develop delirium, most studies using the
CAM-ICU tool for diagnosis of delirium. The overall risk of death in patients
with delirium was about double that of patients without delirium, and remained
high even after adjustment for age and severity of illness (as measured by
APACHE II scores). Patients with delirium had longer mean length of stay in the
ICU (1.38 days longer), mean hospital length of stay (0.97 days longer), and
mean duration of mechanical ventilation (1.79 days longer). Studies on longer
term mortality (6 months to 1 year) were conflicting, with some showing
considerable relationship between delirium and mortality but at least one sizable
study showing no relationship after adjustment for multiple variables. Delirium
was associated with worse function on a variety of cognitive outcome measures
in multiple studies.
The incidence of postoperative
delirium in the elderly tends to be even higher, particularly in certain
types of surgery. A new study (Zywiel
2015) looked at hip fracture patients aged 65 and older in Canada over a 2
year period. They found that 48% developed delirium before, during or after
surgery. Those with delirium were older and had higher ASA scores but even
after adjustment for these factors they had an average 7.4 day longer hospital
stay and costs that were 50% higher than those without delirium.
A recent systematic review of risk factors for delirium in
the ICU found somewhat surprising results (Zaal
2015). The authors looked only for those risk factors having high or
moderate strength of evidence. They identified 33 studies of acceptable quality
to review. They found that only 11 putative risk factors for delirium are
supported by either strong or moderate level of evidence. There was strong
evidence that age, dementia, hypertension, pre-ICU emergency surgery or trauma,
APACHE II score, mechanical ventilation, metabolic acidosis, delirium on the
prior day, and coma are risk factors for delirium and moderate evidence that
multiple organ failure is a risk factor for delirium. Evidence was strong that
gender is not associated with delirium. They found strong evidence that use of
dexmedetomidine is associated with a lower delirium prevalence.
Most striking in the Zaal review is that they found the
evidence inconclusive for benzodiazepines, analgosedatives, and opiates as risk
factors for delirium. That is disturbing, since those are among the few truly
modifiable risk factors traditionally noted for preventing delirium. Multiple
previous studies have demonstrated benzodiazepines, sedatives and opioids as
factors contributing to the development of delirium. Another recent study found
a strong association between infusion of benzodiazepines and/or opioids and
transition to delirium in mechanically ventilated ICU patients (Kamdar
2015).
However, we concur with the view of the editorial
accompanying the Zaal study that the considerable heterogeneity of the studies
makes it very difficult to truly assess risk factors. Brown and Dowdy (Brown
2015) point out that even those studies in the Zaal review using the same
tool (the CAM-ICU) found the incidence of delirium in the ICU ranged from 22%
to 78%. So the original intent of Zaal and colleagues to use pooled data to
assess delirium risk factors was largely precluded by the heterogeneity. Brown
and Dowdy conclude that the Zaal results likely reflect preferential collection
of certain data as much as any underlying causal link.
The systematic review by Zaal and colleagues (Zaal
2015) found strong evidence that use of dexmedetomidine is associated with
a lower delirium prevalence. We dont concur with that conclusion. Two of the
studies they note as showing strong evidence of this beneficial association we
discussed in our February 10, 2009 Patient Safety Tip of the Week Sedation
in the ICU: The Dexmedetomidine Study. We pointed out several
methodological and other problems with those studies. We think that the jury is
still out on whether use of dexmedetomidine is associated with a lower delirium
prevalence.
There are no proven
pharmacologic agents for preventing or treating delirium. One that has had
some mixed results in past studies is haloperidol. Now a new study even
questions whether haloperidol may actually increase the risk of delirium (Pisani
2015). Among nonintubated patients, and after adjustment for time-dependent
confounding and important covariates, each additional cumulative milligram of
haloperidol was associated with 5% higher odds of next-day delirium.
Another recent systematic review and meta-analysis looked at
pharmacologic agents for the prevention and treatment of delirium in patients
undergoing cardiac surgery (Mu
2015). It somewhat surprisingly concluded that moderate to high-quality
evidence supports the use of pharmacologic agents for the prevention of
delirium but those results are based largely on one randomized controlled
trial. That trial showed a beneficial effect of intraoperative dexamethasone (Dieleman
2012). They also note their funnel plot indicated that there is likely
publication bias. They go on to state that the evidence for treating post-cardiac
surgery delirium is inconclusive. The accompanying editorial concurs that there
is no magic bullet at this time (Bruder
2015). Well also note that a substudy of the above mentioned large study
showing less delirium with dexamethasone showed no beneficial effect of
dexamethasone on postoperative cognitive dysfunction at one or twelve months
after cardiac surgery (Ottens
2014).
Of the nonpharmacologic means of preventing and treating
delirium, promoting more normal
sleep-waking and day-night cycles has been a focus. One study done in a
medical ICU employed multifaceted sleep-promoting interventions implemented
with the aid of daily reminder checklists for ICU staff (Kamdar
2013). Though improvements in overall sleep quality ratings did not reach
statistical significance, there were significant improvements in the incidence
of delirium/coma (odds ratio: 0.46) and daily delirium/coma-free status (odds
ratio: 1.64). In a subsequent secondary analysis from that study Kamdar and
colleagues (Kamdar
2015) found that there was no association between daily perceived sleep
quality ratings (by patients or their nurses) and transition to delirium.
However, as mentioned above, that study showed a strong association between infusion
of benzodiazepines and/or opioids and transition to delirium in mechanically
ventilated patients. Interestingly, it also showed that patients reporting use
of sleep aids at home were less likely to transition to delirium.
Speaking of the relationship between sleep and delirium we
had previously noted it was only a matter of time until someone looked at
manipulation of melatonin in patients with delirium (see our March 25, 2014 Patient Safety Tip of the Week
Melatonin
and Delirium). In that column we noted 3 studies that had shown a
beneficial effect of melatonin or the melatonin agonist ramelteon in preventing
or treating delirium. But we expressed our skepticism about these studies
because of small numbers, methodological concerns, and too good to be true
results. A more recent randomized controlled study of almost 400 patients age
65 and older who were scheduled for acute hip surgery found that melatonin
treatment did not reduce the risk of delirium (de
Jonghe 2014).
The mainstay of delirium prevention has been multicomponent nonpharmacological
interventions such as HELP, the
Hospital Elder Life Program (see our October 21, 2008 Patient Safety Tip of the
Week Preventing
Delirium). Inouye et al (Inouye
1999) showed in a landmark
study of 852 medical patients aged 70 and older that management of 6 risk
factors was able to reduce the incidence of delirium from 15% to 9.9%. The
number of days with delirium and the number of episodes of delirium was also
reduced by the intervention. The intervention targeted cognitive impairment,
sleep deprivation, immobility, visual impairment, hearing impairment, and
dehydration. This was strong evidence that a multicomponent intervention could
be of benefit in reducing delirium.
A meta-analysis of multicomponent nonpharmacological
interventions for delirium prevention was recently published (Hshieh
2015). It confirmed that multicomponent nonpharmacological interventions
are effective in decreasing delirium incidence and preventing falls. It
estimates that potential savings in the US from such programs might be more
than $16 billion annually. The meta-analysis included over 4000 patients from
14 studies. Most used HELP or a modified HELP program. Some used volunteers,
family, or nurses in their interventions. Overall, the odds of delirium were 53% lower in patients receiving these
interventions and the NNT (number needed to treat) was 14.3. In addition,
the odds of falling were 62% lower
among patients with such interventions (delirium is a risk factor for falls).
While there were trends favoring those in the intervention group for length of
stay, rate of institutionalization, and changes in functional or cognitive
status, these trends did not reach statistical significance.
Multicomponent nonpharmacological interventions may also be
used for management of patients who already have delirium. A good example of
team-delivered multicomponent nonpharmacological interventions for delirium was
recently presented at the American Association of Critical-Care Nurses (AACN)
2015 National Teaching Institute and Critical Care Exposition (Haseeb 2015). A
nurse-led team consisted of a critical care nurse, physician, pharmacist, and
an exercise physiologist. Patients in a med/surg ICU were randomized in a 2:1
fashion after screening positive for delirium with the CAM-ICU tool. Patients
managed by the team had a statistically significant reduction in mean duration
of delirium (4.96 vs 9.00 days). There were also statistically significant
reductions in duration of therapy for benzodiazepines and opiates.
With the evidence now accumulating for the effectiveness and
cost-effectiveness of multicomponent nonpharmacological interventions for
delirium prevention and treatment it makes sense for any hospital with a
sizable ICU population or significant surgical volume to consider putting
together a team to deliver such interventions.
We also refer you
back to our December 2014 Whats New in the Patient Safety World column American
Geriatrics Society Guideline on Postoperative Delirium in Older Adults. The
American Geriatrics Society has just published a best practice statement for
Postoperative Delirium in Older Adults (AGS
Expert Panel 2014). Its a guideline that really only recommends
evidence-based best practices. Though it is for patients with postoperative
delirium most of the principle recommendations also apply to delirium in
general. And we also refer you back to our many previous columns on delirium
prevention and management noted below.
Some of our prior
columns on delirium assessment and management:
·
October
21, 2008 Preventing
Delirium
·
October
14, 2009 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
References:
Salluh JIF, Wang H, Schneider EB, et al. Outcome of delirium
in critically ill patients: systematic review and meta-analysis. BMJ 2015; 350:
h2538 (published online June 3, 2015)
http://www.bmj.com/content/350/bmj.h2538
Zywiel MG, Hurley R, Perruccio A, et al. The Health Economic
Implications of Perioperative Delirium in Older Patients with Low-energy Hip
Fractures.
American Academy of Orthopaedic Surgeons 2015 Annual
Meeting. Paper 038 (abstract).
Zaal IJ, Devlin JW, Peelen LM, Slooter AJC. A Systematic
Review of Risk Factors for Delirium in the ICU. Critical Care Medicine 2015; 43(1):
40-47
Kamdar BB, Niessen T, Colantuoni E, et al. Delirium
Transitions in the Medical ICU: Exploring the Role of Sleep Quality and Other
Factors. Critical Care Medicine 2015; 43(1): 135-141
Brown CH, Dowdy D. Risk Factors for Delirium: Are Systematic
Reviews Enough? Critical Care Medicine 2015; 43(1): 232-233
Pisani MA, Araujo KLB, Murphy TE. Association of Cumulative
Dose of Haloperidol with Next-Day Delirium in Older Medical ICU Patients. Crit Care Med 2015; 43(5): 996-1002
Mu JL, Lee A, Joynt G. Pharmacologic Agents for the
Prevention and Treatment of Delirium in Patients Undergoing Cardiac Surgery:
Systematic Review and Metaanalysis. Critical Care Medicine 2015; 43(1): 194-204
Dieleman JM, Nierich AP, Rosseel PM, et al. for the
Dexamethasone for Cardiac Surgery (DECS) Study Group. Intraoperative High-Dose
Dexamethasone for Cardiac SurgeryA Randomized Controlled Trial. JAMA 2012;
308(17): 1761-1767
http://jama.jamanetwork.com/article.aspx?articleid=1389612&resultClick=3
Bruder NJ, Velly L. Pharmacologic Approach for Delirium
after Cardiac Surgery: There Is No Magic Bullet. Critical Care Medicine 2015;
43(1): 256-257
Ottens TH, Dieleman JM, Sauλr AC, et al. Effects of
Dexamethasone on Cognitive Decline after Cardiac Surgery: A Randomized Clinical
Trial. Anesthesiology 2014; 121: 492-500
http://anesthesiology.pubs.asahq.org/Article.aspx?articleid=1921499
Kamdar BB, King LM, Collop NA, et al. The Effect of a
Quality Improvement Intervention on Perceived Sleep Quality and Cognition in a
Medical ICU. Critical Care Medicine 2013; 41(3): 800-809
de Jonghe A, van Munster BC, Goslings JC, et al.on behalf of
the Amsterdam Delirium Study Group. Effect of melatonin on incidence of
delirium among patients with hip fracture: a multicentre, double-blind
randomized controlled trial. CMAJ
2014; published ahead of print September 2, 2014
Inouye SK, Bogardus ST, Charpentier PA, Leo-Summers L,
Acampora D, Holford TR, Cooney LM. A Multicomponent Intervention to Prevent
Delirium in Hospitalized Older Patients. N Engl J Med 1999; 340: 669-676
http://content.nejm.org/cgi/reprint/340/9/669.pdf
Hshieh TT, Yue J, Oh E, et al. Effectiveness of Multicomponent
Nonpharmacological Delirium Interventions: A Meta-analysis. JAMA Intern Med
2015; 175(4): 512-520
http://archinte.jamanetwork.com/article.aspx?articleid=2107611&resultClick=3
Haseeb C, Prado I, Moscoso-Stafford G, Grami P. Delirium
Causing Havoc in Health Care: A Multidisciplinary Approach to Delirium
Assessment and Management in the Intensive Care Unit. American Association of
Critical-Care Nurses (AACN) 2015 National Teaching Institute and Critical Care
Exposition. Abstract RS2. Presented May 19, 2015
http://ajcc.aacnjournals.org/content/24/3/e28.short
The American Geriatrics Society Expert Panel on
Postoperative Delirium in Older Adults. Postoperative Delirium in Older Adults:
Best Practice Statement from the American Geriatrics Society. Journal of the
American College of Surgeons 2014; Published Online: November 14, 2014
http://www.journalacs.org/article/S1072-7515%2814%2901793-1/fulltext
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