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What's Causing the Dyspnea, Choking Feeling in Woman With Schizophrenia?

<ѻý class="mpt-content-deck">— Initial misdiagnosis of panic attack led to a potentially fatal treatment delay
MedpageToday
A woman with chest pain.

A 27-year-old woman presents to an emergency department (ED) in Riyadh, Saudi Arabia, due to a choking sensation and extreme shortness of breath. She states that her symptoms have varied in intensity since starting about 4 hours previously and that she is not aware of anything that might have triggered the symptoms.

She tells clinicians that she has not felt faint or passed out, or had chest pain, cough, fever, or gastrointestinal symptoms. She says she has no prior history of allergies, and is not aware of any family history of allergic sensitivities. She says she has not taken any new medications, nor been exposed to any chemicals or insect bites that might have triggered the symptoms.

Her medical history is unremarkable, except for a past diagnosis of schizophrenia, which is being treated with a second-generation antipsychotic and benztropine daily.

Clinicians note that she is alert and conscious, although moving restlessly on the bed. She is speaking but not completing her sentences. She has no cough, is not drooling or salivating heavily, and has no evident stridor or cyanosis.

The team detects no angioedema, and auscultation shows a clear chest with equal breath sounds bilaterally.

Physical examination findings:

  • Heart rate: 120 beats/minute
  • Blood pressure: 136/85 mm Hg
  • Respiratory rate: 24 breaths/minute
  • Oxygen saturation: 97% on room air
  • Oral temperature: 36.7°C
  • Blood glucose: 144 mg/dL

Neurological Exam

The patient has normal muscle tone, and there is no evidence of weakness or loss of sensation in the upper and lower limbs. She walks normally with normal coordination, with no sign of dysmetria. Her pupils are the same size and reactive, and the extraocular muscles show full range of motion with no evidence of nystagmus. Examination of the cranial nerves is unremarkable.

Clinicians consider a diagnosis of anaphylaxis, but ultimately rule it out since there is no probable initial trigger, and the patient has a clear chest with no evidence of gastrointestinal symptoms or skin or mucous membrane involvement.

Epiglottis is also considered and determined to be unlikely given the absence of upper respiratory tract infection symptoms and the intermittent nature of the symptoms.

Clinicians make a presumed diagnosis of panic attack, and due to the patient's ongoing tachycardia and mild tachypnea, keep the patient on a monitored bed. The clinicians also alert the emergency team that invasive airway management may be needed should the patient's condition continue to decline.

About 15 minutes after undergoing the initial assessment, the patient develops extension of the neck and upper and lower limbs bilaterally, along with arching of her back, and transient rolling up of the eyes.

Clinicians diagnose the patient with an acute dystonic reaction and administer 50 mg of intravenous diphenhydramine. The symptoms quickly improve, and the patient returns to her baseline status. Interestingly, a venous blood gas taken shortly after assessment showed a pH of 7.26, CO2 level of 58 mmHg, and bicarbonate/HCO3 of 26 mmol/L.

Records show that the patient has been receiving both 3 mg of risperidone and 2 mg of benztropine once daily. Review of the patient's file reveals that she had presented to the ED a week earlier with similar, although less severe, symptoms.

Laboratory test results at that time identify only mild leukocytosis, presumably due to acute stress (17.00×109/L), with a slightly elevated lactic acid (2.43 mmol/L, reference 0.5-2.20 mmol/L). At that visit, she is treated with 1 mg of lorazepam intravenously and discharged.

Clinicians note that during both episodes, the patient's venous blood gas shows acute respiratory acidosis. When questioned further regarding her medical history, the patient notes that she had not been taking her benztropine as prescribed. It also emerges that 2 weeks prior to her first visit to the ED, her psychiatrist had increased the risperidone dosage from 2 mg to 3 mg.

After consulting with the psychiatry service on-call, clinicians continue the patient's risperidone dose as usual to prevent a relapse of her schizophrenia, and advise her to maintain strict compliance to benztropine.

Given the normal findings of the neurological assessment, the lack of focality in symptoms, and the fact that the timing of symptoms coincides with the change in antipsychotic dosage, as well as the improvement with anticholinergic therapy, clinicians determine that no central nervous system imaging is required to make a diagnosis of acute laryngeal dystonia (ALD). They again advise her to continue taking the benztropine daily, and she is discharged to home.

Follow-Up

During the months that follow, the patient returns to the ED on several occasions with the same symptoms. On her last visit, she required emergency airway attention, but treatment with intravenous anticholinergics resolves the symptoms, thus averting the need for invasive air­way management.

Psychiatry on-call consults with the patient, and eventually her risperidone dosage is lowered to 2 mg, while the dose of benztropine is increased to 2 mg twice daily. Quetiapine is also prescribed to augment her antipsychotic regimen, in order to prevent a relapse of the schizophrenia and with the longer-term goal of slowly increasing the dose while tapering risperidone.

Discussion

Clinicians presenting this of a patient with risperidone-induced ALD note that it may be the first case re­port of ALD in the Middle East. The patient's presentation with acute-onset shortness of breath was initially misdiagnosed as a panic attack, resulting in a delay in management. Prompt identification is key to management and prevention of these life-threatening episodes.

Other occasional initial misdiagnoses include anaphylaxis, acute anxiety, and epiglottis. Other case reports of ALD all involved various signs of upper-airway obstruction, including cyanosis, stridor, gasping, and inability to manage secretions. Many cases of ALD are diagnosed only retrospectively after the patient's death or after establishing a definitive airway.

An estimated 3-20% of patients on antipsychotic medication are affected by acute dystonic reactions, the clinician authors note. These reactions can involve any groups of muscles, such as oculogyric crisis, torticollis, trismus, and opisthotonos. Thus, the clinical presentation of ALD varies considerably, and most dystonic reactions occur during the first 3 days of therapy.

Risk factors for acute dystonic reaction include male sex, young age, history of previous dystonic reaction, and a recent increase in dosage.

ALD was first described in 1958, and the first ALD-associated fatality was reported in 1981. Multiple case reports followed describing the relationship between ALD and use of multiple typical and atypical antipsychotics, including some reactions that were fatal.

Most ALD case reports have been associated with use of typical antipsychotics. Although second-generation or atypical antipsychotics have been thought to be less likely to be associated with extrapyramidal symptoms, there is significant variation in incidence among these medications. For example, one large in 2012 found that risperidone had the highest association with extrapyramidal symptoms among atypical agents.

While the mechanism behind ALD is not fully understood, theoretically it may result from paradoxical adduction of the vocal cords during inspiration that leads to upper-airway obstruction. Confirming a diagnosis involves performing direct laryngoscopy without a paralyzing agent, which is typically not feasible in normal clinical practice.

Response to anticholinergics has been reported in the majority of patients diagnosed clinically with ALD, which supports acute dystonia as the underlying pathophysiological mechanism, the case authors note.

In contrast to this case, three previously reported cases of ALD in patients taking risperidone all presented with stridor. Treatment with intramuscular benztropine resolved the symptoms in two patients within 15 minutes. The third patient was placed under observation for 48 hours after developing on-and-off stridor, and ALD was diagnosed retrospectively when the symptoms resolved spontaneously.

Two cases were associated with concomitant use of several antipsychotics: one involving use of haloperidol, chlorpromazine, and risperidone during a 3-day period, in which there were no recurrences when the patients were subsequently challenged with risperidone. The other patient had received haloperidol in addition to risperidone. Thus, antipsychotic polypharmacy rather than risperidone alone was the most the probable cause of the symptoms in two of these four cases.

There are also reports linking use of both typical and atypical antipsychotics with sudden cardiac death in comparison with nonusers -- presumably due to cardiac toxicity. Furthermore, overall life expectancy has been reported to be 11 to 20 years shorter among individuals with bipolar disorder or schizophrenia compared with the general population, according to a 2013 of life expectancy and death by diseases of the circulatory system in patients with bipolar disorder or schizophrenia in Nordic countries.

The increased mortality seen in this group of patients may also reflect death by asphyxiation, the authors note, pointing to two case reports of ALD-associated death. The recommendation is that once the diagnosis is made, clinicians should establish a clear plan to decrease the antipsychotic dose or replace the offending drug promptly to prevent recurrent episodes, as occurred with this patient.

Conclusions

The case authors conclude that this rare, reversible complication of anti­psychotics should be considered in any psychiatric patient presenting with undifferentiated acute-onset shortness of breath, particularly in the presence of other features of extrapyramidal symptoms or a recent increase in anti­psychotic dosage. If a high index of suspicion exists, parenteral administration of anticholinergics may help avoid the need for invasive airway management.

Clinicians should also allow for recent sedation and ongoing antipsychotic use in patients at risk of developing ALD. Awareness of this condition and prompt treatment with parenteral anticholinergic medication can be lifesaving.

  • author['full_name']

    Kate Kneisel is a freelance medical journalist based in Belleville, Ontario.

Disclosures

The authors reported no conflicts of interest.

Primary Source

American Journal of Case Reports

Alkharboush GA, Alsalamah MA "Risperidone-induced acute laryngeal dystonia: A case report" Am J Case Rep 2020; 21:e922393.