Unsuspected serotonin toxicity in the ICU

Abstract

Background: Delirium is a frequently occurring syndrome in patients admitted to the intensive care unit (ICU) or medium care unit (MCU), yet the pathophysiology remains poorly understood. An excess of central serotonin can lead to an altered mental status, associated with autonomic hyperactivity, and neuromuscular excitation. Drugs with serotonergic properties are frequently and for prolonged periods administered to ICU/MCU patients. Therefore, central serotonergic toxicity may constitute a predisposing, contributing or precipitating factor in the emergence of delirium. The purpose of the present study is to determine the number of patients admitted to the ICU or MCU who are diagnosed with delirium and who show characteristics of serotonin toxicity in association with the administration of serotonergic drugs.Methods: During a 10-week prospective observational cohort study in the ICU and MCU, patients aged 18 or older, diagnosed with delirium in the ICU or MCU, were included. Patients were considered as delirious in case of a positive CAM-ICU and/or at the start of haloperidol prescription on suspicion of delirium. Once included, patients were screened for recent administered serotonergic drugs and screened for physical signs associated with serotonin toxicity by a standardized physical examination by a specifically trained physician.Results: A total of 61 patients diagnosed with delirium were enrolled. In 44 out of 61 patients (72 %), the use of drugs potentially contributing to serotonergic toxicity was recorded. Out of 44 patients, seven (16 %) patients showed physical signs of serotonin toxicity and in addition met the Hunter serotonin toxicity criteria, suggesting the presence of serotonergic toxicity. None of these patients were recognized as such by the treating physicians.Conclusions: A significant proportion of delirious patients in the ICU might in fact be classified as suffering from central serotonin toxicity. The awareness of potential serotonin toxicity is low among physicians.

Knowledge, attitude, and practice (KAP) Study on Serotonin Syndrome Among Neuro Physicians

“…observations, 72% patients with delirium in ICU were on serotonergic drugs, and 16% fulfilled the Hunter serotonin toxicity criteria. [ 13 ] It highlights the need of examination for clonus in ICU patients. Cases of SS have been described in all clinical settings.…”

Interventions of a clinical pharmacist in a medical intensive care unit – a retrospective analysis

“…For the daily review of the prescribed therapy for drugdrug interactions (DDIs), the CP used mainly Lexicomp ® interaction database and considered only clinically relevant interaction of type D (consider therapy modification) and type X (avoid combinations). For specific interactions, the CP studied in detail case-report and case-series reviews (e.g., fentanyl -linezolid interaction [18][19][20], esomeprazoleclopidogrel interaction [21][22][23][24][25], and carbapenem -valproate interaction [26][27][28][29][30]).…”

Postoperative Serotonin Syndrome Following Administration of Preoperative Intrapulmonary Methylene Blue and Intraoperative Granisetron: A Case Report

“…They work on the neural pathways involved with vomiting by blocking serotonin from entering nerve cells. It is unlikely that even high doses of 5-HT3 antagonist, alone, would cause severe serotonin toxicity [ 8 , 9 ]. However, previous reports showed that when used concomitantly with other serotonergic medicines, 5-HT3 antagonists could be linked with a potential risk of serotonin syndrome [ 5 , 8 – 11 ].…”

“…It is unlikely that even high doses of 5-HT3 antagonist, alone, would cause severe serotonin toxicity [ 8 , 9 ]. However, previous reports showed that when used concomitantly with other serotonergic medicines, 5-HT3 antagonists could be linked with a potential risk of serotonin syndrome [ 5 , 8 – 11 ]. In 2012, the World Health Organization (WHO) concluded that 5-HT3 antagonists can contribute to the development of serotonin syndrome in susceptible patients who are concomitantly receiving other drugs affecting the serotonin system [ 12 ].…”