Miriam Friedlander, Yana Brayman, and William Breitbart have produced an excellent review of delirium in the palliative care setting. Their paper is thorough, readable, and thoughtful, and will be helpful to oncologists caring for patients with advanced illness. I particularly like the fact that the authors make it clear that delirium is not only a very common complication of advanced cancer, but that it is also a major source of suffering and distress for both patients and families. In view of the problems delirium presents and the frequency with which delirium arises as death approaches, this complication of advanced and terminal illness has received inadequate attention. My thanks and congratulations go to the authors for providing such a clear and helpful review of this challenging clinical problem.
Delirium is of particular importance in palliative care because impairments of cognition interfere with meaningful communication and connection between patients and professional caregivers, and more importantly between patients and loved ones. The end of one's life is much more than an opportunity to receive aggressive symptom control. For many, it is an opportunity to find and celebrate meaning, to pass on blessings, to heal broken relationships and strengthen intact ones, to express and receive loving concern, and to say goodbyes. These critical goals of good palliative care cannot be achieved in the setting of a significant cognitive impairment. Friedlander, Brayman, and Breitbart are right to say "the desired and frequently achievable outcome is a patient who is awake, alert, calm, cognitively intact, not psychotic, and able to communicate coherently with family and staff." Any reasonable effort that has potential to help achieve this outcome is worth considering. For patients and families, this time of life is precious.
For this reason, it is worth addressing the therapeutic pessimism that readers of any review on delirium in palliative care must confront. True, delirium arising in the setting of advanced and terminal illness is less likely to resolve than delirium in an acute medical setting (where the precipitating underlying illness itself may more often be reversible). True, decisions about invasive or uncomfortable evaluations or interventions must be informed by the goals of care. And true, the better part of valor in managing an end-of-life delirium is often having the discretion to recommend symptomatic and supportive treatment only. All that said, however, an episode of delirium is often-or at least sometimes-reversible, even in the palliative care setting (as is clear from the studies included in this review).
Earlier Detection and Intervention
Though there is little evidence at this time to support such an approach, a strategy such as Inouye and colleagues[ 2] undertook in hospitalized older patients would seem to have merit in the palliative care setting. Because delirium is so common in hospice and palliative care populations, serial screening and monitoring for early or subtle cognitive decline and predictors of such decline might allow earlier and more effective intervention with antipsychotics, reversal of underlying infectious or metabolic problems, discontinuation of offending medications, and initiation of nonpharmacologic interventions before the proverbial horse is out of the barn (ie, before an obvious, florid, and likely irreversible delirium has developed). Though such a strategy is not likely to eliminate or even substantially reduce the overall incidence of delirium as death approaches, it might be expected to contribute to improved preservation of cognitive clarity (with delirium concentrated in the days just prior to death) and to reduction in the frequency with which difficult decisions to initiate intentional heavy sedation might have to be entertained.
Patient and Family Education
Another point worth emphasizing is the importance of patient and family education. Delirium is distressing to families and sometimes to patients (when patients are able to recall the experience of being delirious). Families need to have confused and agitated behaviors and apparent changes in personality explained to them. They may wonder, "Does this mean my loved one has developed a concurrent mental illness (eg, schizophrenia)?" "Does this mean my loved one is dying now?" Additionally, families should be advised about what to do to be helpful and what to expect. Questions need to be proactively addressed, such as, "What can I do to help my loved one get better or calm down?" "Is this delirium likely to resolve?" "What is the likely course of symptom resolution or progression?"
Finally, patients who emerge from a delirium should be debriefed and given a chance to ask questions about their recollection of being delirious, though many are mercifully amnesic for the experience of delirium.
Treatment With Antipsychotics
As described in the review, antipsychotics are the mainstay of pharmacologic treatment of delirium. Intravenous haloperidol is a commonly used treatment. While generally safe, well tolerated, and effective, there have been some reports of hypotension (usually in the setting of hypovolemia) and ventricular tachycardia (torsades de pointes) associated with intravenous administration of haloperidol.[4,5] Slower infusion (as opposed to bolus infusion) of haloperidol, volume correction, and recognition of conditions that predispose to arrhythmias (eg, hypokalemia, hypomagnesemia, prolonged Q-T interval, concurrently administered proarrhythmic drugs) may help minimize the risk. Cassem and Murray have published a protocol for intravenous administration of haloperidol.
Limitations of Benzodiazepine Therapy
The authors rightly emphasize that the goal of benzodiazepine therapy in palliative care delirium/terminal delirium should be sedation. This drug class does not contribute to restoration of a delirious patient to a state of being "awake, alert, calm, cognitively intact" and "able to communicate coherently with family and staff." Antipsychotics, drug discontinuations, and nonpharmacologic interventions are much more likely than benzodiazepines to restore and preserve cognitive "connectedness" for delirious patients.
Treatment Initiation Threshold
Finally, I agree with the need to shape care to the individual patient's situation, but I would not endorse a "wait and see" approach for nonagitated terminal delirium as a matter of routine, as suggested in the section on controversies. Certainly, if a patient is actively or imminently dying and seems comfortable, intervention other than close monitoring ("wait and see") is not generally necessary. Otherwise, the evidence that antipsychotic treatment is as effective for quiet delirium as for agitated delirium, combined with evidence of undertreatment of delirious cancer patients with these drugs,[7,8] would suggest that a lower threshold for initiating a treatment trial is reasonable.
Acknowledgments: The author would like to acknowledge the support of Research and Development at the Veterans Affairs Medical Center, Tuscaloosa, Alabama, in preparing this commentary.
Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
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2. Inouye SK, Bogardus ST Jr, Charpentier PA, et al: A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med 340(9):669-676, 1999.
3. Breitbart W, Gibson C, Tremblay A: The delirium experience: Delirium recall and delirium- related distress in hospitalized patients with cancer, their spouses/caregivers, and their nurses. Psychosomatics 43(3):183-194, 2002.
4. Cassem NH, Murray GB: Delirious patients, in Cassem NH, Stern TA, Rosenbaum JF, et al (eds): Massachusetts General Hospital Handbook of General Hospital Psychiatry, 4th ed, pp 101-122. Saint Louis, Mosby, 1997.
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8. Stiefel FC, Kornblith AB, Holland JC: Changes in the prescription patterns of psychotropic drugs for cancer patients during a 10- year period. Cancer 65(4):1048-1053, 1990.