Catatonia is a neuropsychiatric syndrome of altered mental status and characteristic psychomotor findings, which occurs in response to a wide variety of psychiatric, neurological, and medical conditions. A common misconception is that catatonia is exclusive to schizophrenia. In fact, catatonia occurs more frequently in patients with medical illness or affective disorders (e.g., depression, bipolar illness, and anxiety) (1, 2). Catatonia secondary to medical illness ranges from 7% to 45% in various clinical settings; however, its exact prevalence within the ICU is unknown, with one report on a small number of patients suggesting it may affect up to 4% of critically ill patients (3–5).
The underlying pathophysiologic mechanism for catatonia is likely heterogeneous. It has been proposed that basal ganglia-thalamo-cortical circuit dysregulation with resulting changes in neurotransmitter function is a potential precipitant factor (6, 7).
Clinically, catatonia is often divided into withdrawn and excited subtypes, although catatonic patients frequently display features of both subtypes. Withdrawn features include stupor, mutism, posturing, and rigidity. Excited features include hyperactivity, disorganized overproductive speech, disorientation, strange mannerisms, and combativeness (8).
Autonomic instability including tachycardia and fever may also be present. Stupor and immobility result in a higher prevalence of morbidity due to the development of malnutrition, pressure ulcers, metabolic derangements, urinary retention, constipation, contractures, aspiration pneumonia, various other infectious processes, deep venous thromboses, and pulmonary emboli (9).
The differential diagnosis of altered mental status in the critically ill patient is broad and includes many commonly encountered conditions that cause delirium, including oversedation, metabolic derangements, systemic inflammatory response syndrome, and neurological insult. Catatonia is rarely entertained in this differential despite the fact that catatonia is more likely to be common in ICUs than in other care settings given catatonia’s association with acute illness and common ICU practices (e.g., administration of dopamine antagonists and withholding benzodiazepines). Furthermore, timely recognition and treatment of catatonia in the critically ill patient with altered mental status is essential, given the substantial morbidity and mortality associated with the condition (10). Complications of catatonia may include myocardial infarction, respiratory compromise or arrest, deep venous thrombosis, pulmonary embolism, metabolic derangements, disseminated intravascular coagulation, muscle contractures, rhabdomyolysis, renal failure, and pressure ulcers, with a contemporary mortality rate approaching 10% (5, 11).
To increase awareness of the diagnosis and treatment of catatonia in the critically ill population, we report on five critically ill patients with diverse medical and surgical presentations who developed catatonia while in the ICU, along with a discussion of the clinical features, diagnosis, management, and treatment of patients with catatonia in the ICU setting.
MATERIALS AND METHODS
Five patients who developed catatonia in varied critical care units at the Massachusetts General Hospital were identified. Their clinical courses were reviewed, and information regarding their past medical history, comorbid disease, physical examination, laboratory investigation, and imaging results were recorded. Additionally, electroencephalogram (EEG) results were reviewed when available. The institutional review board waived the need for informed consent.
There are currently no accepted standard criteria for diagnosing catatonia in critically ill patients. For the purposes of this review, catatonia diagnosis was made when all three of the following were present: exclusion of likely alternative diagnoses, presence of pathognomic examination features, and temporally associated response to treatment for catatonia (i.e., benzodiazepines and/or electroconvulsive therapy [ECT]).
A 78-year-old woman was admitted to a surgical ICU for management of hypertensive crisis with systolic blood pressure of 250 mm Hg and altered mental status 1 week after sigmoid colectomy for diverticulitis. Her past medical history was notable for coronary artery disease and peripheral vascular disease, along with depression and anxiety treated with alprazolam 0.5 mg three times daily for 40 years. Her initial head CT was unrevealing, and given her altered mental status, all sedatives, including the benzodiazepines she had been receiving on the general care floor, were withheld. Despite initial moderate improvement in her mental status with blood pressure control, on ICU day 4, she experienced an acute worsening of her mental status, becoming mute and staring with limited blink and tracking. On ICU day 5, there was a strong clinical concern of pneumonia, and she was intubated for increased work of breathing and inability to clear secretions. Her mental status did not improve despite appropriate infection control. Richmond Agitation-Sedation Scale (RASS) scores of –5 to –3 prompted discontinuation of a low-dose propofol infusion. Despite 3 days without sedatives and subsequent extubation, her mental status remained altered. On ICU days 9 and 10, an MRI was performed which revealed no signs of acute hemorrhage or infarction, and an EEG was negative for epileptiform activity. On ICU day 11, a consultant psychiatrist noted several classic catatonic features including akinetic mutism, catalepsy, waxy flexibility, and negativity. A diagnosis of catatonia secondary to benzodiazepine withdrawal was made. Upon empiric trial of IV lorazepam, the patient became mobile and communicative within 15 minutes. Her home alprazolam was reinstituted along with an as needed IV lorazepam order. After substantial improvement of her catatonia, she was discharged to a step-down unit on ICU day 14. She was discharged from the hospital 1 week later at her baseline mental status.
A 77-year-old woman was admitted to the cardiac surgery ICU after urgent coronary artery bypass grafting and mitral valve replacement. Her past medical history was otherwise notable for depression, anxiety, and panic disorder for which she had been treated with chlordiazepoxide for more than 15 years. This had been discontinued at an outside hospital prior to transfer, and it was not reinstituted upon her arrival to the unit. On ICU day 3, she became confused and examination was notable for verbigeration (continuously repeating a phrase) with perseveration on her husband’s name, stereotypies (repetitive movements and behaviors), upper and lower extremity rigidity, posturing, negativism, and a glassy fixed gaze. A primary neurological injury was suspected, but the findings from MRI were negative for acute pathology. Psychiatry was consulted for altered mental status and abnormal behavior. The aforementioned catatonic signs were connected, and a trial of IV lorazepam was undertaken with resultant decreased limb rigidity. A trial of standing IV lorazepam (three times daily) was instituted. Within 1 day, her affect and mental status had returned to baseline, and she was discharged within 1 week. On follow-up 4 months later, she remained stable on her home dose of chlordiazepoxide.
A 48-year-old man underwent emergent fasciotomy for a right forearm compartment syndrome that he sustained after a fall and burn injury. On postoperative day 2, he was admitted to a surgical ICU for respiratory failure and hypotension secondary to an aspiration event. His postoperative course was further complicated by altered mental status, rhabdomyolysis with acute renal failure, witnessed seizure, and fever. His initial head CT was unrevealing. His medical history was notable for chronic lymphocytic leukemia and schizoaffective disorder with anxiety for which he was taking clozapine, escitalopram, and quetiapine. All psychotropic medications were withheld at admission to the ICU. An MRI, obtained on ICU day 3 to evaluate for persistent altered mental status, demonstrated a shower of embolic strokes that were widely scattered throughout both cerebral hemispheres in the territories of the bilateral middle cerebral arteries and the left posterior cerebral artery. An EEG was also obtained, which demonstrated epileptiform activity consistent with the infarction sites. Lumbar puncture was negative for infection, and no embolic source was identified. The patient was started on levetiracetam. This was transitioned to valproic acid for seizure prophylaxis and mood stabilization given his underlying schizoaffective disorder. His mental status continued to worsen, and on ICU day 7, he was no longer initiating any purposeful movements and was only responding intermittently to voice with eye opening. Physical examination revealed minimal upper extremity rigidity. Repeat EEG showed no further epileptiform activity. On ICU day 12, he was transferred to a respiratory step-down unit for pulmonary toilet and management of secretions.
On step-down unit day 8 (hospital day 22), his examination became notable for verbigeration, delayed blink, and negativism. The psychiatry consultation service had been following for his underlying psychiatric disorder, and upon noting these catatonic features recommended initiation of IV lorazepam. Response was minimal but suspicion for catatonia remained given his physical examination, and on step-down unit day 14 (hospital day 28), ECT was commenced. After three treatments, the patient became increasingly appropriate, interactive, and less rigid, with notable stepwise improvement after each subsequent treatment. After a total of eight treatments over 2 weeks, the patient had returned to his baseline, and he was transferred to a rehabilitation facility.
A 52-year-old man was admitted to a surgical ICU for pancreatitis. His course was complicated by abdominal compartment syndrome requiring emergent decompressive exploratory laparotomy, respiratory failure ultimately requiring tracheostomy, acute renal failure requiring dialysis, and sepsis. Over the first 2 weeks of his ICU stay, he was intermittently agitated and managed with the use of dopamine antagonists, including haloperidol (up to 10 mg every 4 hr) and quetiapine (up to 300 mg every 6 hr) with reported favorable effect. After a 3-week ICU stay, he was transferred to a respiratory step-down unit for weaning from ventilatory support. One day following his transfer, he displayed mutism, rigidity, and waxy flexibility, and the psychiatry consultation service was consulted for these symptoms in the presence of altered mental status. He concomitantly remained febrile and tachycardiac. Catatonia in the setting of medical illness (infection, metabolic derangements) was suspected, but his vital signs and the recent use of high-dose dopamine antagonist medications also raised concern for malignant catatonia secondary to neuroleptic medication (i.e., neuroleptic malignant syndrome [NMS]). Creatine kinase levels were normal, and an MRI was unrevealing. Dopamine antagonist medications (including dopamine-blocking antiemetics) were discontinued. Immediate improvement in his symptoms were noted with administration of lorazepam, and within 2 weeks of continued therapy with lorazepam and amantadine, the patient’s catatonia resolved and his mental status returned to baseline.
A 17-year-old boy initially presented to an outside hospital for an acute psychotic break with visual hallucinations and paranoid delusions. His medical history was notable for Asperger syndrome, depression, and anxiety. He was initially started on chlorpromazine, however, and subsequently developed intermittent agitation, hypertension, and tachycardia, followed by eventual nonresponsiveness to commands. Creatine kinase was elevated (peak at 3,660 IU/L) and concern was raised for NMS by the outside hospital primary pediatric team. All dopamine antagonists were promptly discontinued and treatment with bromocriptine and IV benzodiazepines was commenced. After 2 weeks of treatment, there was no improvement in the catatonic symptoms of presumed NMS. His interim course was complicated by development of pneumonia and transfer to the PICU to manage intermittent desaturations and inability to manage secretions. As he continued to display catatonic features despite the cessation of dopamine antagonists, he was transferred to our institution for ECT. Upon arrival, his examination was notable for catalepsy, rigidity, waxy flexibility, mutism, and stupor. He was treated with ECT for refractory catatonia. He experienced stepwise improvement in his psychomotor symptoms with return to his baseline after a total of 25 rounds of ECT treatments.
Our report suggests that catatonia may manifest in a variety of intensive care settings and patient populations, including in patients with no underlying psychiatric history (Table 1). Our report further illustrates that catatonia may be difficult to differentiate from other common causes of altered mental status in critically ill patients.
The pathophysiology of catatonia is not completely understood, though prevailing theory involves neurotransmitter dysregulation. Catatonic patients have lower gamma-aminobutric acid (GABA)-A activity in the orbitofrontal cortex than do healthy and psychiatric control patients (21). Benzodiazepines, which are GABA-A agonists, are first-line therapy for catatonia. Other effective pharmacologic therapies modulate the glutamate and dopamine systems (22, 23).
Clinically, catatonia is characterized by excited or withdrawn features, though patients often manifest some of both types during the course of their illness (Table 2). Catatonic withdrawal, with posturing, rigidity, mutism, and repetitive behaviors, is the most commonly recognized form, and in severe states may present as stupor or even with decreased Glasgow Coma Scale scores. Catatonic states presenting with hyperactivity, pressured speech, restlessness, agitated behavior accompanied by bizarre stereotypies, mannerisms, grimacings, echophenomena, and perseverations are also reported, though less commonly. Malignant catatonia, a particularly severe form, is further characterized by fever and increasing autonomic instability and is associated with mortality rates as high as 75–100% in some studies (12). NMS, which was considered in cases 4 and 5, is a form of malignant catatonia with “lead-pipe” muscle rigidity and creatine kinase levels generally greater than 1,000 IU/L occurring exclusively after treatment with antipsychotic medication or other dopamine antagonists (13, 14).
Catatonic complications are secondary to stupor and prolonged bed rest and include aspiration pneumonia (as seen in cases 1 and 5), other infectious processes, malnutrition, deep venous thromboses, pulmonary emboli, and pressure ulcers. If unrecognized, catatonia leads to significant cost, morbidity, and, although the mortality rate has been reduced by means of increased recognition and better management, a 10% risk of mortality remains (15, 16).
Diagnosis of catatonia in critically ill patients is challenging. The Modified Bush-Francis Catatonia Rating Scale (BFCRS) is a 23-item rating scale that operationally defines each catatonic sign, rates its severity, and provides a standardized schema for clinical examination (1). Catatonia may be diagnosed when two of 14 motor signs are present for greater than 24 hours, but the presence of multiple confounding factors and the broad differential of altered mental status in the ICU limit the value of this definition. To address the poor specificity of conventional definitions when applied to critically ill patients, we propose a novel algorithmic approach to the diagnosis and management of catatonia in the ICU (Fig. 1).
When catatonia is suspected, a trial of 1–2 mg of IV lorazepam can produce immediate, impressive reversal of catatonic features. This maneuver, known as the “lorazepam test,” is associated with reduced catatonia scores on the BFCRS by 60% within 10 minutes and response rates of 60–80% within hours or days (17, 18). It is often useful to differentiate catatonia from other causes of altered mental status, as illustrated in cases 1, 2, and 4 (14).
Despite the lack of prospective randomized evidence in nonschizophrenic catatonic patients, benzodiazepines are the gold standard form of treatment in catatonia based on numerous retrospective reports (13, 24). IV lorazepam is commonly used starting with doses of 2 mg daily, and titrating as needed, occasionally to total doses of 20–30 mg daily (11). Other treatment options with reported success include amantadine, zolpidem, memantine, valproate, and phenobarbital (25–28); all these act on GABA, glutamate, or dopamine receptors and may be reasonable adjuncts to benzodiazepines or alternatives to them if side effects, particularly sedation and respiratory compromise, limit benzodiazepine use. Antipsychotic medication and dopamine antagonists should almost always be withheld. In cases where these medications may be beneficial for an underlying psychosis or the development of an agitated delirium, psychiatry consultation should be considered. Importantly, catatonia is a secondary syndrome, not a primary illness, and workup should be aimed at identifying and treating precipitant conditions.
ECT, the most successful treatment for catatonia, is usually reserved for patients with benzodiazepine-resistant catatonia, as in cases 4 and 5. ECT is also useful in patients with malignant catatonia (including NMS), in which acute resolution of symptoms not affected by IV benzodiazepines is necessary (29–34). Most ECT centers have protocols that serve as a guide for pre-ECT evaluation and often for both a dedicated psychiatrist and an anesthesiologist who perform the procedure. Although there are no absolute contraindications to ECT, a few conditions do confer an increased risk of complications from ECT and warrant greater evaluation and communication among providers (19). Many centers do not offer ECT, and in these situations, psychiatry consultation and communication with another institution that performs the procedure may be necessary.
The differential for common ICU conditions that may look like catatonia includes delirium, metabolic disturbances, critical illness myopathy or polyneuropathy, cerebrovascular events, neurodegenerative disorders, CNS infections, vegetative states, NMS, serotonin syndrome, autoimmune encephalopathy, and seizures. Table 3 offers specific distinguishing features for the common differential diagnoses. Distinguishing these conditions requires attention to the clinical course, psychomotor findings on physical examination, and response to empiric treatment (Fig. 1). Catatonic patients with hypoarousal may appear sedated. Commonly used tools such as the RASS are not specific enough to differentiate catatonia from sedation. Differentiating catatonia from delirium is especially important, as catatonia is treated with benzodiazepines whereas delirium may be exacerbated by benzodiazepine administration. Conversely, dopamine antagonists, such as IV haloperidol, while generally safe, effective, first-line agents for the delirious agitated patient in the ICU, may induce catatonia or convert a simple catatonia to a more severe form. Both syndromes can have waxing and waning presentations, and both can be characterized by fluctuating periods of hypoarousal and agitation (20). Given the opposed treatment strategies of these two conditions, psychomotor examination is of particular importance to distinguish the two conditions. Some degree of symptom overlap between delirium and catatonia can make this difficult. For example, states of encephalopathy, including anticipated inflammatory responses following operations or certain trauma, in addition to the administration of dopamine antagonists, may be associated with increased upper and lower extremity tone. Although this may initially be perceived as a symptom of catatonia, the clinician must take into account the patient’s overall clinical course, recent medication administration, and other high yield signs of catatonia that help in more accurate diagnosis (Fig. 1). For example, finding negativism, as reflected in active resistance to mouth and eye opening, is suggestive of catatonia if present. With either syndrome, treatment of precipitant illness is imperative. While delirium typically resolves with treatment of the precipitant condition, medical catatonia may not and often requires pharmacological intervention for timely resolution of symptoms and prevention of associated morbidity and mortality. Importantly, delirium and catatonia may and often do occur together. In these cases, lysing the catatonia with benzodiazepines with minimization of strong dopamine blockade remains the priority.
Intensivists should be aware that the presence of catatonia does not exclude concomitant causes of altered mental status. This is illustrated in case 3, where the patient had embolic stroke, seizure activity, and catatonia during the same admission. The clinical reality is that most patients with catatonia have underlying psychosis or delirium symptoms, which become particularly evident once the motoric symptoms of catatonia are resolved.
Notably, common critical care practices may induce or exacerbate catatonia. Abrupt discontinuation of benzodiazepines upon ICU admission has become increasingly popular given the association between benzodiazepines and delirium (21). This should be performed cautiously in patients who have been administered benzodiazepines routinely prior to their ICU or hospital admission. Catatonia is a well-described, albeit uncommon, benzodiazepine withdrawal syndrome (22–25). Review of the literature suggests that this withdrawal syndrome may be more typical in older individuals (range of ages in retrieved reports is 51–88) and in individuals who have taken benzodiazepines for more than 6 months (22–25). This is consistent with the two patients (cases 1 and 2) whose catatonia was likely attributable, in part, to abrupt benzodiazepine discontinuation. Furthermore, given the high prevalence of nausea and agitated delirium within the intensive care setting, many patients receive dopamine antagonists for the treatment of these conditions. The resulting dopamine blockade may either induce or worsen an emerging catatonia, as was likely with cases 4 and 5.
The current report illustrates the need for intensivists to be aware of catatonia as a syndrome of critical illness and include it in their working differential for altered mental status. Catatonia can occur in a wide variety of intensive care settings and can complicate a range of clinical presentations. Catatonia may occur with or without precedent history of mood disorder or psychosis, and it may be exacerbated or induced by common intensive care practices including withholding benzodiazepines and administering dopamine antagonists. Psychomotor findings must be included in examination of critically ill patients with altered mentation in order to differentiate other commonly found intensive care syndromes from catatonia.
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