title: Interventions to decrease the risk of adverse cardiac events for patients receiving chemotherapy and serotonin (5-HT3) receptor antagonists: a systematic review.
abstract: BACKGROUND
  Patients may experience nausea and vomiting when undergoing chemotherapy or surgery requiring anesthesia. Serotonin 5-hydroxytryptamine 3 (5-HT3) receptor antagonists are effective antiemetics, yet may cause adverse cardiac events, such as arrhythmia. We aimed to identify interventions that mitigate the cardiac risk of 5-HT3 receptor antagonists.
  
  
  METHODS
  Electronic databases, trial registries, and references were searched. Studies on patients undergoing chemotherapy or surgery examining interventions to monitor cardiac risk of 5-HT3 receptor antagonists were included. Search results were screened and data from relevant studies were abstracted in duplicate. Risk of bias of included studies was assessed using the Cochrane Effective Practice and Organisation of Care (EPOC) group's risk-of-bias tool. Due to a dearth of included studies, meta-analysis was not conducted.
  
  
  RESULTS
  Two randomized clinical trials (RCT) and 1 non-randomized clinical trial (NRCT) were included after screening 7,637 titles and abstracts and 1,554 full-text articles. Intravenous administration of different dolasetron doses was examined in the NRCT, while dolasetron versus ondansetron and palonosetron versus ondansetron were examined in the RCT. Electrocardiogram (ECG) was the only intervention examined to mitigate cardiac harm. No differences in ECG evaluations were observed between dolasetron or palonosetron versus ondansetron after 15 minutes, 24 hours, and 1 week post-administration in the 2 RCTs. Four deaths were observed in one RCT, which were deemed unrelated to palonosetron or ondansetron administration. Minor increases in PR and QT intervals were observed in the NRCT for dolasetron dosages greater than 1.2 mg/kg 1-2 hours post-administration, but were deemed not clinically relevant.
  
  
  CONCLUSIONS
  ECG monitoring of chemotherapy patients administered with 5-HT3 receptor antagonists did not reveal clinically significant differences in arrhythmia between the medications at the examined time periods. The usefulness of ECG to monitor chemotherapy patients administered with 5-HT3 receptor antagonists remains unclear, as all patients received ECG monitoring.
  
  
  BACKGROUND
  PROSPERO registry number: CRD42013003565.
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1 W8, Canada. TriccoA@smh.ca.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Tricco
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1 W8, Canada. SoobiahC@smh.ca.
authors.forename: Charlene
authors.initials: C
authors.lastname: Soobiah
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1 W8, Canada. HuiW@smh.ca.
authors.forename: Wing
authors.initials: W
authors.lastname: Hui
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1 W8, Canada. AntonyJ@smh.ca.
authors.forename: Jesmin
authors.initials: J
authors.lastname: Antony
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1 W8, Canada. v.struchkov@utoronto.ca.
authors.forename: Vladi
authors.initials: V
authors.lastname: Struchkov
authors.affiliation: Clinical Epidemiology Program, Centre for Practice-Changing Research, Ottawa Hospital Research Institute, 725 Parkdale Ave., Ottawa, Ontario, K1Y 4E9, Canada. bhutton@ohri.ca.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutton
authors.affiliation: Departments of Medicine and Community Health Sciences, University of Calgary, TRW Building, 3rd Floor, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6, Canada. Brenda.Hemmelgarn@albertahealthservices.ca.
authors.forename: Brenda
authors.initials: B
authors.lastname: Hemmelgarn
authors.affiliation: Clinical Epidemiology Program, Centre for Practice-Changing Research, Ottawa Hospital Research Institute, 725 Parkdale Ave., Ottawa, Ontario, K1Y 4E9, Canada. dmoher@ohri.ca.
authors.forename: David
authors.initials: D
authors.lastname: Moher
authors.affiliation: Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, East Building, Toronto, Ontario, M5B 1 W8, Canada. sharon.straus@utoronto.ca.|Department of Geriatric Medicine, Faculty of Medicine, University of Toronto, 27 Kings College Circle, Toronto, Ontario, M5S 1A1, Canada. sharon.straus@utoronto.ca.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Straus
mesh_terms: D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000517:prevention & control*; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D004562:Electrocardiography / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000009:adverse effects; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects; D017294:Ondansetron / Q000008:administration & dosage / Q000009:adverse effects; D000077924:Palonosetron; D011807:Quinolizines / Q000009:adverse effects; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D007211:Indoles; D007546:Isoquinolines; D011807:Quinolizines; D011812:Quinuclidines; D058831:Serotonin 5-HT3 Receptor Antagonists; D017294:Ondansetron; D000077924:Palonosetron; C060344:dolasetron