Presentations

Abstract

Introduction:

Antipsychotic agents have been the primary treatment modality for schizophrenia, particularly demonstrating efficacy in the management of psychosis. Olanzapine belongs to the class of atypical antipsychotics and has demonstrated an enhanced efficacy and safety profile. It works via antagonism of different classes of receptors - dopamine (D1-4), serotonin (5HT1A, 2A, 2C, 3, 6,7) and α1, α2. However, it does have the propensity to induce weight gain, increase insulin resistance and alter lipid metabolism. In this case, we would like to highlight a rare side effect of central neurogenic hyperventilation in a patient receiving Olanzapine for the management of agitation while on mechanical ventilation.

Case description:

We present a 59-year-old male patient with a medical history significant for heart failure with a reduced ejection fraction (HFrEF) who underwent aortic root replacement and transaortic valve replacement for severe aortic stenosis and an ascending aortic aneurysm. His postoperative course was complicated by cardiogenic shock requiring impella and inotropic support. He was transferred to the ICU for further hemodynamic monitoring via a Swan-Ganz catheter. During his ICU stay, he continued to have a complicated course of acute hypoxic respiratory failure, resulting in multiple reintubations and eventually resulting in him getting a tracheostomy. The Impella was later switched to LVAD to manage his cardiogenic shock. In the interim, he was started on Olanzapine in addition to dexmedetomidine drip for multiple episodes of agitation and desynchrony with mechanical ventilation. Over the course of the next five days, his ventilation requirements increased from 6.6 to 9.6 L/min (reaching max 20 L/min), with Vt of 550 ml and respiratory rate up to 40/min. An arterial blood gas revealed a pH of 7.62, PCO2 of 24.4, PO2 of 125 and bicarbonate of 25, indicating acute respiratory alkalosis. Chest x-ray and CTA chest demonstrated mild pulmonary edema and small bilateral effusions, treated with intermittent hemodialysis. Imaging studies were negative for a pulmonary embolism.

A complete evaluation and review were conducted to determine the culprit responsible for the increased respiratory drive, including an extensive review of his medications, clinical history and examination. However, no definitive cause could be identified. A decision was made to stop Olanzapine (why). Over the next 48 hours, the patient's hyperventilation resolved, indicated by a drop in his ventilation requirements to 7 L/min, tidal volume of 350 ml and respiratory rate of 20/min. ABG showed resolved respiratory alkalosis with a pH of 7.44, PCO2 of 36.9, PO2 of 112 and bicarb of 26.

Discussion:

Olanzapine has been known to cause side effects of dystonia, tardive dyskinesia, insulin resistance and, less commonly, seizures and neuroleptic malignant syndrome. However, only a handful of case reports have demonstrated a relationship between Olanzapine and hyperventilation. Although proving causality is difficult, an increased minute ventilation on the ventilator while on olanzapine therapy, lack of other causes of increased respiratory drive, and improvement after discontinuation suggest a causal association. Several medications, including adenosine, salicylates, progestin and quetiapine, have also increased minute ventilation. However, the mechanism is still unclear. It is postulated due to its direct action on the respiratory center and indirect action, through serotonergic involvement, in central and peripheral chemoreceptors. Another explanation is respiratory dyskinesia, an akathisia-like extrapyramidal side effect involving respiratory muscles causing forceful breathing and hyperventilation. This association has also been reported in patients not on mechanical ventilation. Moreover, hyperventilation appears to be dose-dependent; hence, patients tolerate lower doses of Olanzapine without experiencing respiratory symptoms.

Conclusion:

Olanzapine is a commonly used medication for patients with agitation and delirium in the ICU. Compared to typical antipsychotics, atypical antipsychotics, like Olanzapine, are known for their better-tolerated side effect profile and decreased risk of extrapyramidal effects. This case report highlights that physicians should be cautious when using atypical antipsychotics - specifically Olanzapine- which can cause increased respiratory drive without other explainable causes.