By David Nowels, MD, MSPH, University of Colorado Health Sciences Center
I saw Ms. H during a palliative care consult last week. The consult request indicated that she had been obtunded for a few days before I saw her, probably as a result of her multiple problems – CO2 retention with encephalopathy, hypoxia, infection, and chronic opioid and benzodiazepine use. However, when I visited the next day she had awakened and become very agitated. Her family was extremely upset and indicated that “nothing” was being done for her despite their being told that she would be kept comfortable. I learned that she had not received any opioids or benzodiazepines for about 24 hours due to her poor mentation.
Ms H. was lying down when I first saw her and immediately asked if I could help her sit up. Her family indicated that she had been asking to sit up or get out of bed, then whenever she did get up within 30 seconds she was asking to go back to bed and lay down. I did try to help her up – but she began to slip off the edge of the bed as I gave her a hand. Due to her immense size (over 450 lbs) I was concerned about her safety and encouraged her to lie back down until we could get adequate help. Ms. H. became very upset with this plan, insisting on getting up, as she was “uncomfortable.” She could not tell me more about how she was feeling, but agreed that she was not having pain. She could not answer any other questions I asked – she simply could not focus on the question. Her speech was pressured and she was mildly confused when telling me about events of the last few hours.
Ms. H. was severely agitated, however, that was only part of the picture. She met DSM-IV criteria for an agitated delirium: 1) acute onset and fluctuating course, 2) reduced clarity of awareness of the environment, 3) perceptual disturbance, disorientation, or memory disturbance, and 4) underlying general medical condition. When this occurs in patients who have a very limited lifespan it often is best referred to as an agitated terminal delirium, though terminal agitation or terminal restlessness are terms frequently used. These latter terms focus on the behavioral component of the clinical syndrome. Severely agitated patient can be very challenging. Clinicians are concerned that their patient will not be safe, that families will “burn out” in trying to provide care for these patients, and that they will be unsuccessful in trying to relieve, or even evaluate, the other problems of the patient. As distressing as the behavioral disturbance can be, usually the root problem is a cognitive one. Recognizing and addressing the cognitive impairment in agitated delirium is usually a more effective way of helping the patient and family.
Delirium is present in 50% of hospice patients at any time and probably occurs in 80-90% overall. Up to 1/2 of patients with delirium are misidentified because of a focus on the neurobehavioral components of the syndrome. Delirium is associated with worse outcomes for the patient and their loved ones. Overall 80% of episodes of confusion in hospice are thought to cause problems for the patient, their loved ones, or the care team.
Delirious patients experience worse pain management, more skin problems, more falls, and a shortened lifespan. Moreover, they can neither participate in their care nor address the tasks and issues around dying. Families are often upset by the patients’ behaviors and loss of function, and there is a widespread belief that the experience carries a higher risk for complicated grief, especially if the deceased displayed an agitated form of delirium.
The first step in helping these individuals is to accurately identify the syndrome. Agitated delirium is often difficult to distinguish from other syndromes in which agitation is evident – delirium, dementia, depression, grief, primary anxiety disorders and psychotic illness. Delirium with somnolent behaviors may even be more difficult to identify. Simple diagnostic tools such as the mini-mental status exam and the Confusion Assessment Method are important to use to correctly identify delirium.
After the “diagnosis” of delirium is made an evaluation of some of potentially reversible causes of the episode should be undertaken. This evaluation should especially focus on pain, minor infections, constipation, incomplete emptying of the bladder, drug toxicities (most commonly opioids and benzodiazepines), drug withdrawal, dehydration, elevated calcium, hypoxemia, and accumulation of CO2 (in patients who hypoventilate). Several published series of patients with advanced cancer who became acutely confused while receiving care in palliative situations have reported reversal of up to 50% of episodes of delirium with a change in medications (opioid reduction or rotation and benzodiazepine reduction or removal) or with hydration.
Non-pharmacologic interventions should be performed next. These include educating and supporting the family, creating a calm, safe environment that supports re-orienting the patient (calendar, clock, etc), and providing the patient with needed aids such as eyeglasses and hearing aids.
Clinicians frequently give benzodiazepines to patients with agitated delirium. This approach may temporarily address the behavioral aspect to the presentation by sedating the patient. Unfortunately benzodiazepines do nothing to clear the patient sensorium; they typically cloud thinking even more, sometimes leading to paradoxical worsening. Because short acting preparations are frequently used, the cycle of confusion, agitation, treatment, sedation, worse confusion, agitation, etc is created. Typically it is better to use a neuroleptic first, when the decision to medicate is made. This class of drugs calms patients without interfering with cognition. A randomized trial comparing haloperidol with lorazepam revealed the benefit of using the neuroloptic. Serious side effects associated with using major tranquilizers are uncommon. Dose escalation similar to that seen in pain management is often useful, as sometimes are more sedating major tranquilizers such as chlorpromazine (Thorazine).
Some patients who are very agitated and actively dying might have their delirium better managed by sedation rather than by trying to improve their cognition. When the goal of treatment is shifted to sedation, benzodiazepines given regularly and routinely may be used. A midazolam infusion is usually very effective. I view the management goal of sedation for agitated terminal delirium as one for which I obtain special informed consent since the treatment may lead to shortened lifespan.
Ms. H. had multiple potential reasons for her acute, agitated confusion. Her infection was being treated with appropriate antibiotics, treatment of her CO2 retention was addressed, and her opioids and intermediate acting benzodiazepines were re-started at a lower dose. We felt that the major cause of her delirium was her opioid withdrawal. Within 12 hours of restarting her medication her agitation resolved and her cognition had cleared considerably. Because she has experienced delirium once, she has a higher chance of again developing confusion, though both the cause and the treatment plan will probably differ from this episode. An important aspect to her hospice care will be to monitor her medication and cognition carefully and educate the patient and family about possible recurrence.
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