title: 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.
authors: Department of Intensive Care 7D16, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors: Catharina E
authors: CE
authors: van Ewijk
authors: Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.|Centre for Human Drug Research, Leiden, The Netherlands.
authors: Gabriel E
authors: GE
authors: Jacobs
authors: Department of Intensive Care 7D16, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. a.girbes@planet.nl.
authors: Armand R J
authors: http://orcid.org/0000-0002-0711-0494
authors: ARJ
authors: Girbes
keywords: Delirium; Intensive care; Medication; Opioids; Serotonin syndrome; Serotonin toxicity