A 34-year-old woman with unknown medical history presented to the emergency department (ED) with "emotional disturbance." The patient was brought in by police, who noticed her "wandering and confused" in a local shopping mall. The police reported to the triage nurse that the patient was not making sense when they attempted to question her. The police became even more concerned when she told them, "My angel has dropped me here, but now he has returned to salvation."
In the ED, she struggled to find words, frequently stopping in mid sentence. The only truly coherent complaints that could be elicited on review of systems were that she was nauseated, had a headache, and felt "fuzzy." She was unable to provide any medical or psychiatric history because of her confusion.
On presentation to the ED's triage nurse, her vital signs were temperature, 36.1°C (97.0°F); pulse rate, 97 beats per minute; and blood pressure, 165/95 mm Hg. Her blood glucose level was 98 mg/dL on finger stick. Pulse oximetry revealed a normal oxygen saturation of 98% on room air. Her weight was 300 lb and height was 64 in. She was disorientated to day, date, and name of hospital and appeared disheveled, confused, and lethargic. The patient was then taken to an ED bed and told to wait with police for the doctor.
Shortly after admission to the ED and before further evaluation could commence, she experienced a generalized tonic-clonic seizure. Intravenous diazepam was given and the seizure quickly remitted. While the laboratory evaluation was under way, a physical examination revealed a gravid uterus and moderate bilateral lower extremity edema.
An initial laboratory test for urine b-human chorionic gonadotropin was positive, indicating that she was pregnant. Furthermore, the results of her hepatic panel were abnormal, with an alanine aminotransferase level of 340 IU/L, an aspartate aminotransferase level of 320 IU/L, and an albumin level of 2.6 g/dL. Other findings of a comprehensive metabolic panel were normal. Results of a urinalysis showed a protein finding of 2+. Complete blood cell count revealed an abnormal platelet count of 80,000/mL. Results of a urine drug screen were negative.
The patient was subsequently transferred to the labor and delivery unit of a nearby tertiary care center.
Differential diagnosis. The ED staff was working under the assumption that the patient had a chronic psychiatric disorder and her symptom presentation most probably represented a psychotic decompensation of her chronic condition. She received routine supportive care on presentation and was triaged to a bed in the ED. Unfortunately, her problem turned out to be much more medically acute.
In the evaluation of patients presenting with altered mental status, it is prudent to consider delirium before relegating the symptoms and signs to a psychiatric condition such as schizophrenia. When this case is more closely examined, there are several signs and symptoms present that would help differentiate delirium from psychosis, despite the aspects of the patient's history that are suggestive of a chronic psychiatric disorder. She was delusional, her thinking was disorganized, she was wandering in a public place, and she made bizarre statements to police. However, she also had an altered level of consciousness (lethargy), trouble sustaining attention (could not give a medical history), and cognitive changes (language disturbance).
An altered level of consciousness is not seen in chronic psychiatric disorders, such as schizophrenia, unless there is superimposed toxicity from medications or substances of abuse. Cognitive deficits and decreased attention are sometimes symptoms of psychosis but are hallmarks of delirium. Her relatively unremarkable findings during the review of symptoms and vital signs are somewhat reassuring but certainly do not rule out all of the causes of delirium or even all of the imminently dangerous ones.
To definitively establish the diagnosis of delirium, the symptoms must develop quickly and be the result of a medical condition. Collateral information to establish this and the patient's baseline mental status would be helpful. Initially, however, time is often better spent searching for possible medical conditions that may explain the patient's symptoms. By quickly recognizing her presentation as delirium, or at least proceeding as if this were the case, staff could have ensured that she was seen immediately by the physician so that all of the potentially life-threatening causes of delirium could be quickly ruled out.
Etiology. A reminder of 7 of the most dangerous causes of delirium is the acronym WHHHHIMP--Wernicke encephalopathy or withdrawal, hypoxemia, hypertensive encephalopathy, hypoperfusion, hypoglycemia, intracranial bleed or infection, meningitis or encephalitis, and poisons or medications.1 Many of them are effectively ruled out in ED triage, but not all of them. For example, Wernicke encephalopathy may not be associated with abnormal vital signs or obvious intoxication with alcohol. Intracerebral hemorrhage may not present with obvious neurologic signs, and poisoning may not be easily recognized. One could think that a relatively modest elevation in blood pressure would not be associated with encephalopathy. However, this patient had preeclampsia that subsequently evolved into eclampsia.
Preeclampsia is not an uncommon cause of mental status changes in pregnant women who are nearing term.2 It would have been an easy diagnosis to make had it been known that the patient was pregnant. Because of her obesity, this was not obvious but could have been discovered by an earlier physical examination or an immediate urine pregnancy test on admission. In addition to confusion, women with preeclampsia can present with right upper quadrant pain and lower extremity edema. Laboratory findings include elevated transaminase levels, proteinuria, and thrombocytopenia.
Convulsions are a late development and define the transition into full-blown eclampsia. Eclampsia is a medical emergency that is life-threatening to the fetus as well as the mother.
Treatment. The definitive treatment of eclampsia is delivery of the fetus. Other interventions can help prevent additional seizures and further complications until this can be achieved.3 Once the patient was medically stabilized, transfer to a center with a fully equipped labor and delivery unit for delivery and specialized care by an obstetric team was the appropriate way to proceed.
A 74-year-old man was brought to the ED by ambulance from his assisted living facility (ALF). Staff at the ALF reported that for the past 12 hours the patient was increasingly anxious, agitated, and confused. He woke up early on the morning of presentation in a cold sweat, complaining that red spiders were crawling all over the floor.
According to the limited ALF records that accompanied the patient, he had "mild dementia, hypertension, and gastroesophageal reflux disease." While he was at the ALF, the following medications were prescribed: propranolol, 20 mg tid; hydrochlorothiazide, 25 mg/d; and pantoprazole, 40 mg/d. The patient had moved to the ALF 2 days before presenting in the ED, because his wife had become ill and was no longer able to care for him at home.
Attempts to gather a history and review of systems from the patient were limited because of the patient's cognitive impairment. He did complain of continued visual hallucinations, anxiety, nausea, and a mild headache. The patient's vital signs were temperature, 36.4°C (97.5°F); blood pressure, 135/95 mm Hg; pulse rate, 85 beats per minute; respiration rate, 18 breaths per minute; and oxygen saturation rate, 95% on 2 L of oxygen via nasal canula. His blood glucose level was 80 mg/dL.
Physical examination revealed a thin man who appeared older than his stated age. The patient was noticeably flushed, anxious, and irritable. He would frequently get out of his bed and walk around the ED making loud and threatening demands of the staff to get him cigarettes and send him back to his "real home." He was oriented to self only; he believed he was in jail and was off by several months when giving the date. The patient exhibited a mild coarse tremor in the bilateral upper extremities, and his skin was damp to the touch. Other physical examination findings were unremarkable.
As a result of the patient's behavioral problems and staff concerns about dangerousness, the patient was given 20 mg of intramuscular ziprasidone to allow for completion of the medical evaluation. Benzodiazepines were considered but not given because of a concern that these medications would worsen his confusional state, considering the documented history of dementia.
Laboratory evaluation revealed normal urinalysis findings and mild macrocytic anemia; a hepatic panel was remarkable only for decreased albumin and total protein levels. A CT scan of the head showed generalized cerebral atrophy but no bleeding or mass. His symptoms failed to improve with ziprasidone therapy.
When the ED physician was able to talk to the patient's son, the son reported that he had found dozens of empty liquor bottles at his father's house when he was cleaning it out. As a consequence of this new information, the ED physician began a more focused workup and initiated treatment with intravenous thiamine and benzodiazepines. After this workup, the patient received a diagnosis of alcohol withdrawal delirium and was transferred to a medical floor for detoxification.
Differential diagnosis. In this case, the ED physician quickly recognized that the patient was delirious and appropriately began a workup to discover the cause.
Etiology. Because there initially was a low index of suspicion for alcohol withdrawal in this patient, the diagnosis of alcohol withdrawal delirium was missed and treatment was delayed. The low suspicion was a result of several factors: difficulty obtaining pertinent medical and psychiatric history in the ED setting, the patient's age, the patient's residence in a supervised setting, and his relatively unremarkable autonomic symptoms. Although alcohol abuse among the elderly is not uncommon, it often is not diagnosed.4 In addition, spouses are frequently quiet enablers of the problem. It is likely that the patient's transfer to the ALF was the event that precipitated his withdrawal, since alcohol would be harder to obtain there and he was therefore probably abstinent from alcohol since admission 2 days before presentation.
Delirium tremens, or alcohol withdrawal delirium, usually has its onset within 48 to 72 hours following cessation of alcohol use.5 Although the patient's relatively unremarkable autonomic symptoms also argued against the diagnosis of alcohol withdrawal, he was taking propranolol for blood pressure control, and b-blockers can mask (or blunt) the tachycardia and elevation in blood pressure that is usually seen with this condition. Nonetheless, his tremor, visual hallucinations, flushing, nausea, and headache were all suggestive of alcohol withdrawal. The same symptoms in a younger patient would probably have led to an earlier consideration of alcohol withdrawal delirium as the source of this patient's altered mental status.
The more focused workup that the ED physician began at the end of the case history included evaluation of serum cyanocobalamin (vitamin B12), folate, and ammonia levels. Deficiencies in vitamin B12 and folate represent potentially reversible causes of dementia and delirium and may be found in long-term alcohol users who have poor nutrition. Hepatic encephalopathy represents another potential cause of altered mental status in patients with liver disease; this patient's normal transaminase levels do not rule out liver disease, especially if it is advanced.
Another concern in patients who abuse alcohol is Wernicke encephalopathy. This patient should be carefully assessed for symptoms of this potentially disabling condition with the classic findings of altered mental status, ataxia, and ophthalmoplegia.6 Thiamine deficiency is the cause of Wernicke encephalopathy, and thiamine was appropriately given, after determination of glucose level, to prevent this very serious complication of alcohol abuse.
Treatment. Benzodiazepines are the treatment of choice for managing alcohol withdrawal delirium. There are many different protocols for their administration that can broadly be divided into 2 categories. One approach is to give benzodiazepines on a fixed schedule that tapers off over the course of a few days. Another approach is to give them on a symptom-triggered basis. The symptom-triggered approach results in less medication being given and shorter hospital stays.7
All benzodiazepines are effective in the management of alcohol withdrawal. Longer-acting agents such as diazepam are favored because of their long half-life, which allows for fewer doses to be given and less risk of benzodiazepine withdrawal. On the other hand, shorter-acting agents, such as lorazepam, that do not depend on the cytochrome P-450 system for metabolism may be safer for patients with severe liver failure. Regardless of the approach, this patient requires an inpatient setting for detoxification because of his inability to comply with a complex outpatient regimen of medication and because of the severity of his symptoms.
A 54-year-old man presented to the ED with his wife. She reported that for the past week, her husband had been spending most of his time in bed. He would sleep off and on during the day and then remain awake for most of the night, flipping through the television channels. Her husband had been struggling with depression, and she initially attributed his behavior to this and hoped that things would improve over time because he was getting treatment. The psychiatrist had told them not to expect much improvement for the first few weeks of antidepressant treatment.
The patient's wife became very concerned when his symptoms became progressively worse over the 3 days before ED presentation. His sleep became nearly continuous; when he woke up, he seemed confused. On the morning of the day that he presented to the ED, the patient briefly opened his eyes and called his wife "mother"; the patient's mother had been dead for several years. He also told his wife that someone had stolen the remote control for the television and was using it to "control the news." He then fell asleep again. He had not showered or eaten in 2 days.
One month before presentation, the patient was treated by a psychiatrist, who diagnosed major depression. The psychiatrist presribed paroxetine and titrated the dosage to 40 mg/d. The patient's symptoms, which included sadness, hopelessness, restlessness, insomnia, and ruminations about poor performance at work, remained unchanged. One week before his arrival in the ED, he called his primary care physician and complained of continued terrible insomnia. His primary care physician prescribed amitriptyline, 25 mg at bedtime, to help him sleep at night.
The patient was able to provide very little history, and his responses to questions were consistently off topic. He kept perseverating on asking for water, regardless of the question posed. Coherent responses to review of systems were difficult to obtain but seemed negative except for a complaint of constipation. His wife, who was a very good historian, clearly stated that the patient had no significant medical history and that he had never abused alcohol or illicit substances. His only medications were amitriptyline and paroxetine. His wife had the pill bottles with her, and they both had the proper amount of medication in them.
Vital signs were all within normal limits. On physical examination, the patient was very lethargic and slow to arouse from apparent sleep. His hygiene was poor, and he was malodorous. His skin was dry. Other findings of his physical examination were unremarkable.
The patient was disorientated to place and time. He believed he was in "the basement" and that the year was 1967 (more than 20 years earlier than the actual date.) When asked to do serial 7s in an attempt to gauge his attention, he responded very slowly, "100 . . . 97 . . . 7 . . . 7 . . . 7 . . . ." The patient failed to recall any of 3 objects after 5 minutes, instead stating, "1967, 7, and I forget the other one."
Results of routine laboratory studies, including electrolyte levels, complete blood cell count, urinalysis, and a urine drug screen, were unremarkable. Serum was negative for acetaminophen and salicylates but positive for tricyclic antidepressants. A CT scan of the head was unremarkable as well. An ECG revealed normal sinus rhythm. The patient was subsequently admitted to the ICU with telemetry.
The patient's paroxetine and amitriptyline were withheld, and a psychiatric consultation was sought. An electroencephalogram (EEG) showed diffuse slowing. Treatment with haloperidol was started by the psychiatry team, and his symptoms improved somewhat. The treatment team continued to withhold his other medications. Over the course of 2 days, his confusion, lethargy, and disorientation resolved. He and his wife agreed that he was "back to his usual self," except for ongoing complaints of depression, hopelessness, and insomnia. As a result, the psychiatrist started antidepressant treatment with mirtazapine and carefully assessed him for suicidality. The assessment was reassuring, and the treatment team discharged him home.
Differential diagnosis. In this case, the main question was whether the patient's symptoms were a result of his depression or new-onset delirium. Many symptoms of hypoactive delirium are the same as those of depression. This patient was sleeping erratically and had low energy, poor appetite, and little motivation to do anything. He also had delusional thinking.
The correct diagnosis was made in this case because a good mental status examination was performed. A decreased level of consciousness is rare in depression, although it can be confused with profound lack of motivation. Although depressed patients may lose track of the exact day and date, disorientation as severe as this patient's is not seen in pure depression. Depressed patients can become delusional, but the delusions are usually mood-congruent. This patient's delusions were disorganized and loose and not necessarily depressive in their content.
Cognitive testing may be abnormal in depression, but this is usually because of poor effort and not cognitive failure. For example, patients will either not answer or say they do not know the answer without ever really trying. This patient was slow to respond, but he did try to answer the questions. Despite his attempts, the responses he gave were incorrect and preservative.
The timing of the patient's symptoms is also suggestive of delirium. His profound lethargy began shortly after beginning a new medication and evolved over a course of just a few days. Based on these findings, the ED physician correctly diagnosed delirium. Diffuse slowing on an EEG obtained after admission to the ICU confirmed the diagnosis.
Etiology. In a young and healthy patient, drug effects are a common cause of mental status changes, whether the drugs are illicit or prescribed by a physician. This patient's wife denied that he had any problem with illicit drugs. Because of his history of depression, the physician considered an intentional overdose and checked for aspirin and acetaminophen in the blood. An overdose of tricyclic antidepressants was a real possibility, but there were no missing pills.
Perhaps there was an interaction between his medications to explain his symptoms. Amitriptyline and paroxetine can interact in 2 different ways: pharmacodynamically and pharmacokinetically. First, pharmacodynamically, multiple serotonergic agents can produce serotonin syndrome, which is characterized by confusion, mydriasis, myoclonus, and autonomic instability.8 This patient lacked some of the features of this disorder. Second, paroxetine pharmacokinetically increases levels of amitriptyline by strongly inhibiting the P-450 enzyme 2D6.9,10 Both amitriptyline and paroxetine have anticholinergic activity, and the addition of amitriptyline probably precipitated anticholinergic delirium because the patient's liver was unable to metabolize it quickly enough to prevent it from building to toxic levels.
Treatment. Several important and appropriate decisions were made regarding this patient's treatment. Admission to the ICU was appropriate because he needed close monitoring for possibly toxic levels of amitriptyline. It was very important that this patient was not admitted to a general psychiatric inpatient unit with an incorrect diagnosis of depression based on the history of the patient recently being treated for major depression. Tricyclic antidepressant toxicity can produce life-threatening cardiac arrhythmias and profound hypotension; either event is a potential catastrophe on a mental health unit.
The most important intervention after transferring the patient to the appropriate treatment setting was to address the underlying cause of the patient's delirium. In this case, it was a simple matter of withholding the offending medications. The patient's symptoms then were managed while waiting for his medications to clear.
Haloperidol is an effective therapy for the symptoms of delirium.11 It has little if any anticholinergic activity and thus was a good choice for this patient with suspected anticholinergic delirium. Also, it is available for intravenous administration, an important consideration when a patient is too lethargic or confused to swallow pills. Treatment of his symptoms was appropriate because delirium is terrifying for patients and families both, and prolonged delirium is associated with poor outcomes. After the delirium cleared, mirtazapine was a good choice for a new antidepressant because it is helpful for decreased appetite and insomnia and has very little anticholinergic activity.12 *
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