Do benzos, opioids, or strong anticholinergics cause · PDF fileDo benzos, opioids, or strong...
Transcript of Do benzos, opioids, or strong anticholinergics cause · PDF fileDo benzos, opioids, or strong...
Delirium in the ICU
Occurs in up to 85% of MICU/SICU MV patients
20-50% of lower severity ICU patients develop delirium
Hypoactive or mixed forms most common
65-70% undiagnosed if routine monitoring not implemented
<5% of Canadian ICUs routinely monitor for delirium
Ely ICM 2001; 27:1892-1900Pandharipande J Trauma 2008;65:34-41Ouimet ICM 2007;33:66-73.Lat CCM 2009;37:1898-1905
Sequelae of Delirium
During the ICU or Hospital stay
Post hospital discharge
5 fewer ventilator free days
3x greater re-intubation rate
~10 additional days in hospital
$15-25K higher hospital costs
Mortality
Mortality
9x higher incidence of cognitive impairment
Transfer to chronic care facility
Functional status @ 6 months
Milbrandt CCM 2004;32:955-62 Lin CCM 2004;32:2254-59Ely JAMA 2004;291:1753-62
Delirium Treatment
Am Psychiatric Association (1999) Antipsychotic medications are often the pharmacologic treatment
of choice (grade I = recommended with substantial clinical confidence)
Some clinicians choose to use atypical antipsychotics
SCCM (2002) Haloperidol is the preferred agent for the treatment of delirium in
critically ill patients (grade C recommendations)
Use of antipsychotics is common practice in ICUs (25-40%)
Lack of substantial evidence treatment improves clinical outcomes plus significant adverse effects associated with antipsychotics, energies should focus on prevention
Trzepacz APA 1999Jacobi CCM 2002;30:119-141Patel CCM 2009;37:825-832Wang NEJM 2005
• 18767 studies reporting on medications and delirium
• 136 medications listed as potential causes
• Estimated 40% of delirium cases are caused by medications
•Numerous limitations in study design (e.g. size, definition of drug exposure).
Opioids – Conflicting data!
Evidence from 2 moderate quality multivariate analyses support association of increased delirium risk in medical-surgical patients Dubois et al: Morphine all doses OR 6.0 -9.2
& Epidural OR 3.5 (1.20-10.39)
Recent ‘no sedation’ study (opioid offered without sedation) found this strategy to be associated with increased agitated delirium (n = 140 pt; 20% vs. 7%; p=0·0400)
Inverse dose-response relationship in patients recovering from hip fracture < 10 mg morphine RR 25.2, 95% CI 1.3-493.3
10-30 mg morphine RR 4.4, 95% CI 0.3 – 68.6
Clegg Age and Ageing 2010;0:1-7 Gaudreau Psychosomatics 2005;46:302-316Dubois Int Care Med 2001;27:1297-1304 Strom Lancet 2010;375:475-480
Opioids - Surgical & Trauma ICU patients
N = 100; 70% had delirium
Figure illustrates the proportion of time that pts were delirious while receiving the drug vs. those not exposed
Exposed to fentanyl: SICU [OR 3.99 (1.47,10.85)] vs TICU [OR 1.03 (0.47, 2.25)]
Exposed to morphine: SICU [OR 0.37(0.13-1.08)] vs TICU [OR 0.22(0.06-0.82)]
caution – low # of patients included
Benzodiazepines
In a mixed ICU Dubois et al (n = 216) found lorazepam doses > 1.8 mg/day was linked to delirium OR 3.3 (1.31-8.04) by univariate analysis; multivariate not significant
In mixed ICUs Van Rompaey et al (n = 523) found OR 2.89 (1.44-5.69)
Higher doses during a 24 hr period associated with increased risk compared to lower doses
OR 3.3 (1.0-11.0) vs. 2.6 (0.8-9.1)
In a MICU Pisani et al (n = 304 > 60 years) found exposure to benzodiazepine or opioid to be associated with increased duration of delirium [RR 1.64 (1.27-2.10)]
Clegg Age and Ageing 2010;0:1-7Dubois Int Care Med 2001;27:1297-1304Pisani Crit Care Med 2009;37:177-183
Midazolam - Surgical-Trauma ICU patients
100 surgical-trauma ICU patients
Exposed to midazolam:
SICU [OR ( 3.22 (1.27-8.20, p0.007)]
TICU [OR (2.45 (1.09,5.52, p0.936]
Most consistent & significant predictor of transitioning into delirium
Agents with significant anticholinergic effects
Atropine
Antidepressants – amitriptyline, clomipramine, doxepin, phenelzineparoxetine
Antipsychotics – chlorpromazine, clozapine, olanzapine, thioridazine
Anti-allergy – diphenhydramine, hydroxyzine
Antiemetics – dimenhydrinate, promethazine, scopolamine
Belladona alkaloids
Parkinsonism – amatadine, benztropine, biperidine, trihexyphenidyl
Strong Anticholinergics
Pisani et al: N = 304 MICU; > 60 years
Evaluated impact of drugs on the duration of delirium
Administration of anticholinergic to 32% of patients
Anticholinergics were not associated with increased duration of delirium
Pandharipande et al: N = 198 MICU patients
32% (63) were administered anticholinergics; 83% (n = 52) experienced delirium
Administration of anticholinergic was not associated in univariate or multivariable analysis with delirium
Pandharipande Anesthesiology 2006;104(1):21-26Han Arch Intern Med 2001;161:1099-1105
Work in progress…
A prospective evaluation of the association between psychoactive medications and delirium in critically ill adults
535 mixed ICU patients from 6 sites admitted at least 24 hr
Daily delirium assessment with ICDSC until discharge
Pre-enrollment drug exposure, cigarettes, illicit drugs and ethanol use
Captured daily drug exposure, use of sedation strategies, physical restraint use, catheters, lab values, environmental factors, mobilization, clinical outcomes
Enrollment closed June 27, 2012
Summary
Delirium is common in the ICU & associated with poor outcomes
Medications are an important consideration for patients with or at risk of delirium
Whether or not sufficient evidence that these medications cause delirium there are significant other benefits from reducing sedative doses (e.g. duration of MV)
Further clarification of the risk of delirium following exposure to medications is important for changing prescribing practices
including further evaluation of dose relationships, impact of drug titration strategies (e.g. DSI), & polypharmacy