Antipsychotic drugs and the acute respiratory distress syndrome
Norwich, UK
* E-mail: hughcatherinewilson{at}btinternet.com
Editor—Neuroleptic malignant syndrome can be triggered by antipsychotic drugs and may also precipitate the acute respiratory distress syndrome (ARDS).1 2 However, there are only a few case reports directly linking antipsychotics drugs with ARDS,3 4 but none of these patients required prolonged intensive care support. Given the increased prescription of antipsychotic and anti-depressant drugs,5–7 it is important that intensivists are aware of this association. Our recent experience provides an excellent example.
A 75-yr-old lady was admitted from a residential home for elective reversal of an ileostomy. She had a past medical history of severe depression and bipolar affective disorder. She had no known drug allergies. She had undergone an emergency laparotomy 18 months previously for a caecal volvulus with ileo-caecal resection and an ileostomy. After her emergency surgery, she spent 6 days in the intensive care unit (ICU). She developed hypotension requiring a norepinephrine infusion for the first 24 h after operation. She subsequently developed a left lower lobe pneumonia for which she received antibiotics and chest physiotherapy. She also had non-cardiogenic pulmonary oedema and required non-invasive positive pressure ventilation (NIPPV) for 2 days. After this, she made a good recovery and was discharged. At this time, her anti-depressant medication was venlafaxine 37.5 mg b.d. and olanzepine 25 mg o.d.
During the intervening period, her antipsychotic medication was changed to carbamazepine 200 mg b.d., sertraline 50 mg b.d., and pericyazine 5 mg t.d.s. (a phenothiazine derivative).
An end ileo-colic anastomosis was performed without any major adverse cardiorespiratory events. However, on the third postoperative day, she became hypoxic with signs and symptoms consistent with pneumonia and acute lung injury. Although her CXR showed pulmonary oedema, she did not have evidence of heart failure, ECG and echocardiogram were both normal. She received vancomycin 1 g b.d. and ciprofloxacin 400 mg b.d. for presumed hospital-acquired pneumonia. Her hypoxia was treated at first with CPAP, then BiPAP, and finally tracheal intubation, mechanical ventilation with high PEEP, and tidal volumes between 4 and 6 ml kg–1. I.V. furosemide was started to achieve a negative fluid balance. Norepinephrine 0.32 mg h–1 was added to support her arterial pressure. The patient's ARDS failed to resolve, she had severe respiratory failure. She then developed multiple organ failure and died. She remained on her regular medications including pericyazine throughout her intensive care treatment.
Treatment after her first surgery involved treating hypotension, left lower lobe pneumonia, and non-cardiogenic pulmonary oedema. This combination occurred after the second surgery and ICU admission, but was resistant to treatment. We suggest that continuing her phenothiazine therapy during the second ICU admission may have influenced the outcome by triggering acute lung injury which developed into prolonged and intractable ARDS.
Case studies and series have previously reported a link between ARDS, neuroleptic malignant syndrome, and anti-depressant drugs, including antipsychotic drugs. Although there is not sufficient evidence to accurately describe the pathophysiological mechanism from these observations, they may be classified as: a dose-related effect,4 part of the neuroleptic malignant syndrome,1 2 a cause of neurogenic pulmonary oedema,3 and an allergic reaction involving general activation of neutrophils in many tissues including the lung.8 9
It is not possible to say with complete confidence whether or not our patient's antipsychotic medication predisposed her to developing fulminant ARDS. Although ARDS is common in critically ill patients, it does not often follow such an intractable and relentless course if the triggering event is effectively treated. If antipsychotic medication played a role, its mechanism of action remains uncertain. However, we think that neurogenic pulmonary oedema is the most likely mechanism. Stopping long-term psychotropic medication can be dangerous and lead to acute deterioration in the patient's state which may compound any other acute problems and treatment. Generally, such medication ought to be continued in the critical care setting, but intensivists should be aware of the association between antipsychotic medication and ARDS so that this general principle can be reviewed in light of the clinical situation, especially if ARDS develops.
References
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4 Dahlin KL, Lastbom L, Blomgren B, et al. Acute lung failure induced by tricyclic antidepressants. Toxicol Appl Pharmacol (1997) 146:209–16.
5 Briesacher BA, Limcangco MR, Simoni-Wastila L, et al. The quality of antipsychotic drug prescribing in nursing homes. Arch Intern Med (2005) 165:1280–5.
6 Rapoport M, Mamdani M, Shulman KL, et al. Antipsychotic use in the elderly: shifting trends and increasing costs. Int J Geriatr Psychiatry (2005) 20:749–53.[CrossRef][Web of Science][Medline]
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8 Savici D, Katzenstein A-L. Diffuse alveolar damage and recurrent respiratory failure report of 6 cases. Hum Pathol (2001) 32:1398–402.[CrossRef][Web of Science][Medline]
9 Mecca P, Tobin E, Carlson JA. Photo-distributed neutrophilic drug eruption and adult respiratory distress syndrome associated with antidepressant therapy. J Cutan Pathol (2004) 31:189–94.[CrossRef][Web of Science][Medline]
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