An official website of the United States government
Here's how you know
Official websites use .gov
A
.gov website belongs to an official
government organization in the United States.
Secure .gov websites use HTTPS
A lock (
) or https:// means you've safely
connected to the .gov website. Share sensitive
information only on official, secure websites.
As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with,
the contents by NLM or the National Institutes of Health.
Learn more:
PMC Disclaimer
|
PMC Copyright Notice
. 2001 Jun 30;322(7302):1602.
Optimising management of delirium
Placebo controlled trials of pharmacological treatments are needed
Editor—In reviewing the management of delirium, Meagher asserts that antipsychotic drugs are effective in patients with delirium.1 There is, however, little evidence to support this assertion. There are no placebo controlled trials of antipsychotic drugs in patients with delirium. One trial compared antipsychotic drugs with benzodiazepines and found that antipsychotic drugs were superior, but, given that it is widely acknowledged that benzodiazepines may worsen delirium, this result hardly constitutes evidence of efficacy.2 Most clinicians have gained the impression that antipsychotic drugs speed recovery in delirium, but their anecdotal observations must be doubted. Most episodes of delirium last only several days and will improve when the patient's underlying medical condition resolves. In practice, medical management is always instituted simultaneously with prescription of antipsychotic drugs. As a consequence, it would be very difficult for clinicians to isolate the relative effect of an antipsychotic drug on the resolution of delirium. Uncontrolled trials suggesting efficacy will present the same problems.
Delirium often manifests with hallucinations, delusions, or thought disorder. In other psychiatric disorders, such as schizophrenia, these symptoms are improved by antipsychotic drugs, so it is reasonable to postulate that these drugs may also help in cases of delirium. But this hypothesis may be invalid. Treatments for asthma will not necessarily help pneumonia, although both illnesses cause shortness of breath. With so little evidence to support the use of antipsychotic drugs in patients with delirium, management strategies invoking them must be extremely cautious. Meagher proposes a strategy for the management of severe behavioural disturbance in patients with delirium that could quickly lead to doses of haloperidol of up to 100 mg per day. Doses this high may be associated with anticholinergic toxicity and akathisia—a sense of inner restlessness—that may worsen agitation rather than quell it. Such doses also entail an increased risk of torsades de pointes and the neuroleptic malignant syndrome.3,4
Moreover, if the analogy with schizophrenia is valid, it is unlikely that patients would benefit from more than 12 mg of haloperidol per day.5 Antipsychotic drugs should be avoided until all non-pharmacological management options are exhausted. If they are to be used, haloperidol is the drug of choice, but doses should not exceed 12 mg per day. If pharmacological management of behavioural disturbance is required after this, then benzodiazepines should be used, with the understanding that gaining control of the behavioural disturbance may involve an unavoidable perpetuation of the delirium that is driving disturbance. Obviously, there is an urgent need for placebo controlled trials.
2.Breitbart W, Marotta R, Platt MM, Weisman H, Derevenco M, Grau C, et al. A double blind trial of haloperidol, chlorpromazine and lorazepam in the treatment of delirium in hospitalised AIDS patients. Am J Psychiatry. 1996;153:231–237. doi: 10.1176/ajp.153.2.231. [DOI] [PubMed] [Google Scholar]
3.Hunt N, Stern TA. The association between intravenous haloperidol and torsades de pointes. Three cases and a literature review. Psychosomatics. 1995;36:541–549. doi: 10.1016/S0033-3182(95)71609-7. [DOI] [PubMed] [Google Scholar]
4.Carnoff SN, Mann SC. Neuroleptic malignant syndrome. Med Clin North America. 1993;77:185–201. doi: 10.1016/s0025-7125(16)30278-4. [DOI] [PubMed] [Google Scholar]
5.American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Washington, DC: American Psychiatric Association; 1997. [Google Scholar]
BMJ. 2001 Jun 30;322(7302):1602.
Patients with delirium should be treated with care
Editor—With respect to Meagher's review of delirium and its management we would like to raise a cautionary note.1-1 Measures that protect vulnerable (often elderly) people from the appearance of delirium, such as good nursing care and the provision of an appropriate ward environment, are always preferable to sedation with psychotropic medication of those who have developed the condition. Every medical and nursing student is taught the basic strategies to be used in managing a delirious individual that Meagher reviews, yet a visit to any busy medical ward shows that such principles are often forgotten in the face of shortages of skilled nurses, rapid discharge of patients, and harassed junior medical staff.
Chemical restraint of delirious patients should never be used as a substitute for simple nursing care. When medication has to be used, because of the hazards associated with psychotropic drugs, doses should be kept to an absolute minimum. Traditionally, haloperidol has been the mainstay of such treatment, and in our experience doses at the absolute lower end of those suggested by Meagher—for example, haloperidol 0.5-1.0 mg—are sufficient for effective control of agitated behaviour in delirium. As old age psychiatrists, we are surprised and disturbed by the high doses of haloperidol suggested in the article for the pharmacological treatment of severe disturbance in delirium, since most of those who will be treated are elderly. If one followed the treatment plan suggested, then this could involve giving up to 30 mg haloperidol intravenously within 30 minutes and repeating this in the following 30 minutes, with the worryingly reassuring message that up to 100 mg intravenous haloperidol every 24 hours is generally safe.
These doses may be suitable for the acute management of young patients with functional psychoses who exhibit disturbed or violent behaviour to which one of the references cited in support of this regimen pertains,1-2 but should not be taken as a guide in elderly medically ill or cognitively impaired individuals. Two thirds of patients with delirium have an underlying dementia and 20% of dementia patients have dementia with Lewy bodies.1-3 Hence, at least 10% of all cases of delirium will have dementia with Lewy bodies, and since this is characterised by exquisite sensitivity to neuroleptics,1-4 this represents a further need for extreme caution in management.
1-2.Kerr IB, Taylor D. Acute disturbed or violent behaviour: principles of treatment. J Psychopharmacol. 1997;11:271–279. doi: 10.1177/026988119701100311. [DOI] [PubMed] [Google Scholar]
1-3.Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med. 1999;106:565–573. doi: 10.1016/s0002-9343(99)00070-4. [DOI] [PubMed] [Google Scholar]
1-4.McKeith IG, Fairbairn AF, Perry RH, Thompson P, Perry EK. Neuroleptic sensitivity in patients with senile dementia of Lewy body type. BMJ. 1992;305:673–678. doi: 10.1136/bmj.305.6855.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
Editor—These letters highlight the difficulties in attempting to control for the many factors that influence outcome in treatment studies of a complex neuropsychiatric disorder of multifactorial aetiology. The situation in patients with delirium is further complicated by the issue of consent. In the absence of controlled studies, the best available evidence supports the contention that the use of typical antipsychotic drugs is associated with rapid resolution of delirium in most patients that is evident before the impact of medical interventions, is independent of sedative actions, and correlates with alterations in measures of monoamine metabolism.2-1 Although Ryan thinks that most cases of delirium will rapidly resolve regardless of whether antipsychotic agents are used, accumulating evidence indicates that this is a misconception and thus provides support for more aggressive treatment of these patients.2-2 Nevertheless, controlled studies would help clarify the impact of antipsychotic agents in the management of delirium.
The theoretical basis for the use of antipsychotic agents extends beyond the observation of symptomatic overlap with functional psychoses and derives from preclinical and clinical observations regarding the neurochemical disturbances that relate to delirium.2-3 Direct extrapolation from observations that relate to patients with schizophrenia, for example, should be made with caution.
The letters also draw attention to some of the risks of using haloperidol. Partly as a consequence of the inactivity that has characterised the field of delirium, drug treatment of delirious patients typically involves non-licensed use of psychotropic drugs. Appropriate doses for delirium management have not been established, but caution is required in prescribing for patients with concomitant problems that confer a greater susceptibility to adverse effects from antipsychotic agents. The review emphasises the importance of non-pharmacological approaches to treatment and advocates haloperidol at low doses as the most appropriate treatment where pharmacotherapy is deemed necessary. In addition, the problem of management of highly disturbed patients in intensive treatment settings with potentially life threatening levels of behavioural disturbance is addressed. The management of elderly patients with suspected Lewy body dementia, a condition characterised by neuroleptic intolerance, would be expected to differ considerably, and, according to preliminary evidence, procholinergic agents may be a useful option in these cases.2-4 Clinicians should consider the relative benefits and risks of treatment with haloperidol at high doses versus the not inconsiderable risks of uncontrolled disturbance in severely ill delirious patients, which include death. The available literature indicates that high doses of haloperidol have been used with therapeutic success in such situations.2-5 The management of this small number of extremely challenging cases should not be confused with the routine management of patients with delirium.
Footnotes
Competing interests: None declared.
References
2-1.Nakamura J, Uchimura N, Yamada S, Nakaawa Y. Does plasma free-3-methoxy-4-hydroxyphenyl(ethylene)glycol increase in the delirious state? A comparison of the effects of mianserin and haloperidol on delirium. Int Clin Psychopharmacol. 1997;12:147–152. doi: 10.1097/00004850-199705000-00005. [DOI] [PubMed] [Google Scholar]
2-2.Levkoff SE, Evans DA, Liptzin B, Cleary PD, Lipsitz LA, Wetle TT, et al. Progression and resolution of delirium in elderly patients hospitalised for acute care. Am J Ger Psych. 1994;2:230–238. doi: 10.1097/00019442-199400230-00007. [DOI] [PubMed] [Google Scholar]
2-3.Trzepacz PT. Is there a final common neural pathway in delirium? Focus on acetylcholine and dopamine. Seminars Clin Neuropsychiatry. 2000;5:132–149. doi: 10.153/SCNP00500132. [DOI] [PubMed] [Google Scholar]
2-4.Kaufer DI, Catt KE, Lopez OL, DeKosky ST. Dementia with Lewy bodies: response of delirium-like features to donepezil. Neurology. 1998;51:1512. doi: 10.1212/wnl.51.5.1512. [DOI] [PubMed] [Google Scholar]
2-5.Hassan E, Fontaine DK, Nearman HS. Therapeutic considerations in the management of agitated or delirious critically ill patients. Pharmacotherapy. 1998;18:113–129. [PubMed] [Google Scholar]
Editor—Droperidol is a drug used by psychiatrists for its sedative and antipsychotic effects. It is also, however, a widely used and highly effective antiemetic when used at low doses for both the prevention and treatment of postoperative nausea and vomiting.3-1–3-3 It has a very good side effect profile at these doses.3-2 It is also a drug that is commonly used in combination with morphine for patient controlled analgesia, where it has consistently been shown to reduce the incidence of opiate induced nausea and vomiting.3-4 A recent review suggests that it is the only antiemetic with any evidence of efficacy in those circumstances.3-5
It surprised us therefore to learn that Janssen-Cilag withdrew this useful drug on 31 March 2001. We appreciate that there may be a problem with the chronic usage of this drug in a psychiatric setting, the concerns being about the potential effect of droperidol on the cardiac QT interval. We find it hard to believe that this makes it unviable for Janssen-Cilag to continue to produce the injectable preparation for its perioperative uses, given its presence in most anaesthesia rooms. In this setting, the small doses used and the short term administration of the drug make it unlikely that the same problems would occur as in continuous treatment with high doses.
We understand that an assessment of the risks and benefits assessment has been carried out, which led Janssen-Cilag to withdraw droperidol voluntarily, but we seriously doubt whether its short term, low dose use was included in this. Janssen-Cilag is the sole manufacturer of branded droperidol, and we are unaware of any generic alternative. It is likely that when supplies become exhausted soon after the withdrawal date we will have to turn to more expensive alternatives with its consequences for the national drug bill.
Footnotes
Competing interests: None declared.
References
3-1.Pueyo FJ, Carrascosa F, Lopez L, et al. Combination of ondansetron and droperidol in the prophylaxis of post operative nausea and vomiting. Anesth Analg. 1996;83:117–122. doi: 10.1097/00000539-199607000-00021. [DOI] [PubMed] [Google Scholar]
3-2.Sniadach MS, Alberts MS. A comparison of the prophylactic anti-emetic effect of ondansetron and droperidol on patients undergoing gynaecologic laparoscopy. Anesth Analg. 1997;85:797–800. doi: 10.1097/00000539-199710000-00015. [DOI] [PubMed] [Google Scholar]
3-3.Korttila K, Kauste A, Tuominen M, Salo H. Droperidol prevents and treats nausea and vomiting after enflurane anaesthesia. Eur J Anaesthesiol. 1985;2:379–385. [PubMed] [Google Scholar]
3-4.Sharma SK, Davies MW. Patient-controlled analgesia with a mixture of morphine and droperidol. Br J Anaesth. 1993;71:435–436. doi: 10.1093/bja/71.3.435. [DOI] [PubMed] [Google Scholar]
3-5.Tramer MR, Walder B. Efficacy and adverse effects of prophylactic antiemetics during patient-controlled analgesia therapy: a quantitative systematic review. Anesth Analg. 1999;88:1354–1361. doi: 10.1097/00000539-199906000-00030. [DOI] [PubMed] [Google Scholar]
