Article

QT prolongation in the intensive care unit: commonly used medications and the impact of drug-drug interactions.

University of Pittsburgh School of Pharmacy, Critical Care Pharmacist, Medical Intensive Care Unit, University of Pittsburgh Medical Center, 200 Lothrop Street, PFG 01-01-01, Pittsburgh, PA 15213, USA.
Expert Opinion on Drug Safety (Impact Factor: 2.62). 04/2010; 9(5):699-712. DOI: 10.1517/14740331003739188
Source: PubMed

ABSTRACT Critically ill patients are at an increased risk to develop drug-drug interactions (DDIs). DDIs that increase the risk of QT prolongation, and ultimately torsades de pointes, can result in a medical emergency. Many clinicians are unaware of the risk of certain drug combinations that may precipitate QT prolongation in the intensive care unit (ICU). Additional DDI education and a review of management strategies could assist with prevention of future adverse outcomes.
This review focuses on some commonly used medications in the ICU that may be involved in pharmacokinetic and/or pharmacodynamic DDIs leading to the development of QT prolongation and possibly torsades de pointes. Also, appropriate management strategies are discussed.
The ICU clinician will gain a better understanding of common medications used in the ICU and DDIs that put patients at risk for the development of QT prolongation and torsades de pointes.
Medications that may cause QT prolongation are common in the ICU and DDIs need to be identified and prevented by the clinician to avoid a potentially life-threatening dysrrhythmia.

1 Bookmark
 · 
156 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To test the primary hypothesis that ondansetron or dolasetron extends the rate-corrected QT electrocardiographic interval (QTc) greater than 60 milliseconds or increases the fraction of patients with QTc greater than 500 milliseconds in patients having noncardiac surgery, and the secondary hypothesis that QTc prolongation is worse in diabetic patients. Patients and Methods We extracted data from the Cleveland Clinic's Perioperative Health Documentation System between March 25, 2006, and September 30, 2010, and additional perioperative medications from Cleveland Clinic pharmacy's Epic Cost of Goods Sold (COGS) system. We searched for patients who had a preoperative electrocardiogram within 1 month of surgery and postoperatively within 2 hours. We excluded patients given an antiemetic drug other than ondansetron or dolasetron perioperatively, and those given amiodarone. Results A total of 1429 patients given serotonin-3 receptor (5HT3R) antagonists and 1022 controls met the enrollment criteria. Seventeen percent of patients given 5HT3R antagonists (n=242) and 22% of controls (n=220) had postoperative QTc exceeding 500 milliseconds. Mean ± SD presurgical and postsurgical QTc, respectively, were 438±37 milliseconds and 464±41 milliseconds for 5HT3R antagonist patients and 443±40 milliseconds and 469±47 milliseconds for control patients. Univariable mean ± SD perioperative increases in QTc were 26±39 and 26±48 milliseconds in the 2 groups. After adjusting for confounding variables, there were no differences in the mean increase in QTc in patients who were and were not given 5HT3R antagonists: –0.1 milliseconds (97.5% CI, –5.2 to 5.0 milliseconds; multivariable P=.97). The QTc was prolonged, but not significantly, in diabetic patients given 5HT3R antagonists (P=.16). Conclusions The average QTc prolongation from baseline was only 6%. Perioperative use of ondansetron or dolasetron was not associated with extended QT prolongation, and these results did not vary by diabetic status. Perioperative use of 5HT3R antagonists does not produce potentially dangerous perioperative electrocardiographic changes and does not seem to warrant a drug safety warning from the Food and Drug Administration.
    Mayo Clinic Proceedings 01/2014; 89(1):69–80. · 5.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: To determine the most common drug-drug interaction (DDI) pairs contributing to QTc prolongation in cardiac intensive care units (ICUs). MATERIALS AND METHODS: This retrospective evaluation included patients who were admitted to the cardiac ICUs between January 2009 and July 2009 aged ≥18 years with electrocardiographic evidence of a QTc ≥500 ms. Patients receiving at least two concomitant drugs known to prolong the QT interval were considered to experience a pharmacodynamic DDI. Drugs causing CYP450 inhibition of the metabolism of QT prolonging medications were considered to cause pharmacokinetic DDIs. The causality between drug and QTc prolongation was evaluated with an objective scale. RESULTS: One hundred eighty-seven patients experienced QT prolongation out of a total of 501 patients (37%) admitted during the study period. Forty-three percent and 47% of patients experienced 133 and 179 temporally-related pharmacodynamic and pharmacokinetic interactions, respectively. The most common medications related to these DDIs were ondansetron, amiodarone, metronidazole, and haloperidol. CONCLUSION: DDIs may be a significant cause of QT prolongation in cardiac ICUs. These data can be used to educate clinicians on safe medication use. Computerized clinical decision support could be applied to aid in the detection of these events.
    Journal of critical care 01/2013; · 2.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: STUDY OBJECTIVES: To measure concordance between different intensive care unit (ICU) clinicians and a consensus group of electrophysiology (EP) cardiologists for use of a common rate-corrected QT interval (QTc)-prolonging medication in cases containing different potential risk factor(s) for torsade de pointes (TdP). DESIGN: Prospective case-based evaluation. SETTING: Academic medical center with 320 beds. SUBJECTS: Medical house staff (MDs) and ICU nurses (RNs) from one center and select critical care pharmacists (PHs). INTERVENTION: Completion of a survey containing 10 hypothetical ICU cases in which patients had agitated delirium for which a psychiatrist recommended intravenous haloperidol 5 mg every 6 hours. Each case contained different potential risk factor(s) for TdP in specific combinations. A group of five EP cardiologists agreed that haloperidol use was safe in five cases and not safe in five cases. MEASUREMENTS AND MAIN RESULTS: For each case, participants were asked to document whether they would administer haloperidol, to provide a rationale for their decision, and to state their level of confidence in that decision. Most clinicians (92 of 115 [80%]) invited to participate completed the cases. Among the five cases where EP cardiologists agreed that haloperidol was not safe, 29% of respondents felt that haloperidol was safe. Conversely, in the five cases where EP cardiologists felt haloperidol was safe, 21% of respondents believed that it was not safe. Overall respondent-EP cardiologist agreement for haloperidol use across the 10 cases was moderate (κ = 0.51). MDs and PHs were in agreement with the EP cardiologists more than RNs (p=0.03). Interprofessional variability existed for the TdP risk factors each best identified. Clinician confidence correlated with EP cardiologist concordance for MDs (p=0.002) and PHs (p=0.0002), but not for RNs (p=0.69). CONCLUSION: When evaluating use of a QTc interval-prolonging medication, ICU clinicians often fail to identify the TdP risk factors that EP cardiologists feel should prevent its use. Clinician-EP cardiologist concordance varies by the specific risk factor(s) for TdP and the ICU professional conducting the assessment.
    Pharmacotherapy 03/2013; · 2.31 Impact Factor