Delirium in Older Persons
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In her review article about delirium in older persons (March 16 issue),1 Inouye mentions anticholinergic drugs, which are associated with an increased risk of delirium. Many commonly prescribed drugs have anticholinergic effects.2 Ophthalmic medications containing anticholinergic agents are frequently overlooked as a cause of delirium.3,4 Cycloplegic and mydriatic agents (including eyedrops containing anticholinergic drugs, such as atropine and cyclopentolate) are frequently prescribed for elderly persons. Systemic side effects (which are mainly cerebellar or cerebral and include visual and tactile hallucinations, incoherent speech, agitation, disorientation, memory loss, and acute psychotic reactions) have been described after topical administration of ocular cyclopentolate.5 Systemic reactions caused by absorption of such drugs transconjunctivally or through the nasolacrimal duct must be taken into account in the prevention and management of delirium in elderly patients in the hospital.4
Enrique Anton, M.D., Ph.D.
Juan Marti, M.D., Ph.D.
Hospital of Zumarraga
20700 Zumarraga, Guipuzcoa, Spain
ejaaranda@hotmail.com
References
Inouye SK. Delirium in older persons. N Engl J Med 2006;354:1157-1165.
Tune L, Carr S, Hoag E, Cooper T. Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatry 1992;149:1393-1394.
Wütrich B, Anit MB, Kuhn M, Matter BZ, Priske S. Systemic anticholinergic side-effects. Allergy 2000;55:788-789.
Han L, McCusker J, Cole M, Abrahamowicz M, Primeau F, Elie M. Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. Arch Intern Med 2001;161:1099-1105.
Burns A, Gallagley A, Byrne J. Delirium. J Neurol Neurosurg Psychiatry 2004;75:362-367.
To the Editor: Inouye rightly stresses that the prevention of delirium is the best strategy. However, the inclusion of several atypical antipsychotic agents under pharmacologic treatment of delirium in Table 4 of her article is troubling. The data on the use of atypical antipsychotic agents to treat delirium are limited and conflicting, especially in regard to lorazepam, which has actually been shown to cause delirium.1 A recent meta-analysis of studies of the use of atypical antipsychotic drugs in elderly persons showed a high risk of death associated with the use of these agents.2 Gill et al. even suggest that deaths associated with delirium may be caused by antipsychotic drugs that are used to treat delirium.3 Until we reach an informed consensus on the use of atypical antipsychotic drugs in patients with delirium, these agents should not be considered as treatment options.
Madan M. Kwatra, Ph.D.
Duke University Medical Center
Durham, NC 27710
kwatr001@mc.duke.edu
References
Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006;104:21-26.
Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934-1943.
Gill SS, Seitz D, Rochon PA. Atypical antipsychotic drugs, dementia, and risk of death. JAMA 2006;295:495-496.
To the Editor: Inouye focuses on causes of delirium in older persons, risk factors, and pathogenesis. However, delirium after surgery is an important problem in surgical departments that treat older patients. It has now been shown that delirium after surgery has procedure-related and patient-related risk factors1,2,3 that differ from those identified in geriatric studies.4 However, it remains to be proved that early prediction of the risk in particular patients can lead to effective prevention of postoperative delirium.
Hinrich B?hner, M.D.
Lukaskrankenhaus Neuss
41456 Neuss, Germany
hboehner@lukasneuss.de
Frank Schneider, M.D., Ph.D.
Rheinisch-Westf?lische Technische Hochschule
Aachen University
52074 Aachen, Germany
References
Wang SG, Lee UJ, Goh EK, Chon KM. Factors associated with postoperative delirium after major head and neck surgery. Ann Otol Rhinol Laryngol 2004;113:48-51.
Yildizeli B, Ozyurtkan MO, Batirel HF, Kuscu K, Bekiroglu N, Yuksel M. Factors associated with postoperative delirium after thoracic surgery. Ann Thorac Surg 2005;79:1004-1009.
Rudolph JL, Babikian VL, Birjiniuk V, et al. Atherosclerosis is associated with delirium after coronary artery bypass graft surgery. J Am Geriatr Soc 2005;53:462-466.
Bohner H, Hummel TC, Habel U, et al. Predicting delirium after vascular surgery: a model based on pre- and intraoperative data. Ann Surg 2003;238:149-156.
Dr. Inouye replies: Anticholinergic drugs that are administered by any route pose a substantial risk of delirium in older persons. The emphasis that Drs. Anton and Marti place on ophthalmic medications as a frequently overlooked cause of delirium is an important clinical reminder.
Dr. Kwatra's cautionary notes are well advised and were highlighted in the Comments section of Table 4 of my article, which listed the drugs that are currently in wide use for the treatment of delirium. It should be stressed that haloperidol remains the only recommended agent for the treatment of delirium in older persons. All other drugs should be reserved for use in the patient subgroups indicated. The use of atypical antipsychotic drugs is not recommended, since the efficacy of these drugs remains unclear in light of inadequate evaluation, and the increased mortality among patients with dementia arouses substantial concern. As mentioned in Table 4, lorazepam may prolong and worsen symptoms of delirium. Please note that a correction has been published (April 13 issue) regarding the recommended dosage of quetiapine in Table 4, which should have listed a starting dose of 25 to 50 mg twice daily.
Postoperative delirium is a frequent and important problem for older persons. A previous clinical trial by Marcantonio et al.1 that involved proactive geriatric consultation demonstrated successful prevention of delirium in patients with hip fracture. The consultation intervention did not apply a targeted risk-factor approach to delirium, but it did address well-known risk factors. However, as Drs. B?hner and Schneider indicate, studies will be needed to evaluate whether strategies targeting specific risk factors will prevent postoperative delirium.
Sharon K. Inouye, M.D., M.P.H.
Harvard Medical School
Boston, MA 02115
References
Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc 2001;49:516-522.
Enrique Anton, M.D., Ph.D.
Juan Marti, M.D., Ph.D.
Hospital of Zumarraga
20700 Zumarraga, Guipuzcoa, Spain
ejaaranda@hotmail.com
References
Inouye SK. Delirium in older persons. N Engl J Med 2006;354:1157-1165.
Tune L, Carr S, Hoag E, Cooper T. Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatry 1992;149:1393-1394.
Wütrich B, Anit MB, Kuhn M, Matter BZ, Priske S. Systemic anticholinergic side-effects. Allergy 2000;55:788-789.
Han L, McCusker J, Cole M, Abrahamowicz M, Primeau F, Elie M. Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. Arch Intern Med 2001;161:1099-1105.
Burns A, Gallagley A, Byrne J. Delirium. J Neurol Neurosurg Psychiatry 2004;75:362-367.
To the Editor: Inouye rightly stresses that the prevention of delirium is the best strategy. However, the inclusion of several atypical antipsychotic agents under pharmacologic treatment of delirium in Table 4 of her article is troubling. The data on the use of atypical antipsychotic agents to treat delirium are limited and conflicting, especially in regard to lorazepam, which has actually been shown to cause delirium.1 A recent meta-analysis of studies of the use of atypical antipsychotic drugs in elderly persons showed a high risk of death associated with the use of these agents.2 Gill et al. even suggest that deaths associated with delirium may be caused by antipsychotic drugs that are used to treat delirium.3 Until we reach an informed consensus on the use of atypical antipsychotic drugs in patients with delirium, these agents should not be considered as treatment options.
Madan M. Kwatra, Ph.D.
Duke University Medical Center
Durham, NC 27710
kwatr001@mc.duke.edu
References
Pandharipande P, Shintani A, Peterson J, et al. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology 2006;104:21-26.
Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934-1943.
Gill SS, Seitz D, Rochon PA. Atypical antipsychotic drugs, dementia, and risk of death. JAMA 2006;295:495-496.
To the Editor: Inouye focuses on causes of delirium in older persons, risk factors, and pathogenesis. However, delirium after surgery is an important problem in surgical departments that treat older patients. It has now been shown that delirium after surgery has procedure-related and patient-related risk factors1,2,3 that differ from those identified in geriatric studies.4 However, it remains to be proved that early prediction of the risk in particular patients can lead to effective prevention of postoperative delirium.
Hinrich B?hner, M.D.
Lukaskrankenhaus Neuss
41456 Neuss, Germany
hboehner@lukasneuss.de
Frank Schneider, M.D., Ph.D.
Rheinisch-Westf?lische Technische Hochschule
Aachen University
52074 Aachen, Germany
References
Wang SG, Lee UJ, Goh EK, Chon KM. Factors associated with postoperative delirium after major head and neck surgery. Ann Otol Rhinol Laryngol 2004;113:48-51.
Yildizeli B, Ozyurtkan MO, Batirel HF, Kuscu K, Bekiroglu N, Yuksel M. Factors associated with postoperative delirium after thoracic surgery. Ann Thorac Surg 2005;79:1004-1009.
Rudolph JL, Babikian VL, Birjiniuk V, et al. Atherosclerosis is associated with delirium after coronary artery bypass graft surgery. J Am Geriatr Soc 2005;53:462-466.
Bohner H, Hummel TC, Habel U, et al. Predicting delirium after vascular surgery: a model based on pre- and intraoperative data. Ann Surg 2003;238:149-156.
Dr. Inouye replies: Anticholinergic drugs that are administered by any route pose a substantial risk of delirium in older persons. The emphasis that Drs. Anton and Marti place on ophthalmic medications as a frequently overlooked cause of delirium is an important clinical reminder.
Dr. Kwatra's cautionary notes are well advised and were highlighted in the Comments section of Table 4 of my article, which listed the drugs that are currently in wide use for the treatment of delirium. It should be stressed that haloperidol remains the only recommended agent for the treatment of delirium in older persons. All other drugs should be reserved for use in the patient subgroups indicated. The use of atypical antipsychotic drugs is not recommended, since the efficacy of these drugs remains unclear in light of inadequate evaluation, and the increased mortality among patients with dementia arouses substantial concern. As mentioned in Table 4, lorazepam may prolong and worsen symptoms of delirium. Please note that a correction has been published (April 13 issue) regarding the recommended dosage of quetiapine in Table 4, which should have listed a starting dose of 25 to 50 mg twice daily.
Postoperative delirium is a frequent and important problem for older persons. A previous clinical trial by Marcantonio et al.1 that involved proactive geriatric consultation demonstrated successful prevention of delirium in patients with hip fracture. The consultation intervention did not apply a targeted risk-factor approach to delirium, but it did address well-known risk factors. However, as Drs. B?hner and Schneider indicate, studies will be needed to evaluate whether strategies targeting specific risk factors will prevent postoperative delirium.
Sharon K. Inouye, M.D., M.P.H.
Harvard Medical School
Boston, MA 02115
References
Marcantonio ER, Flacker JM, Wright RJ, Resnick NM. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc 2001;49:516-522.