12473
2014
AOPXXX10.1177/1060028013512473Annals of PharmacotherapyPersonett et al
Research Report
Intravenous Metoprolol Versus Diltiazem for Rate Control in Noncardiac, Nonthoracic Postoperative Atrial Fibrillation
Annals of Pharmacotherapy 2014, Vol. 48(3) 314–319 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013512473 aop.sagepub.com
Heather A. Personett, PharmD1, Dustin L. Smoot, MD2, Joanna L. Stollings, PharmD3, Mark Sawyer, MD4, and Lance J. Oyen, PharmD4
Abstract Background: Little guidance exists on effective management of postoperative atrial fibrillation (POAF) following noncardiac, nonthoracic (NCNT) surgery. Objectives: The purpose of this study was to identify whether a difference exists between intravenous (IV) metoprolol and diltiazem when used to achieve hemodynamically stable rate control in POAF following NCNT surgery. Methods: This retrospective cohort study examined critically ill adult surgical patients experiencing POAF with rapid ventricular response. Inclusion in the metoprolol or diltiazem treatment group was determined by the initial rate control agent chosen by the prescriber. The primary end point was hemodynamically stable rate control, defined by heart rate (HR) 90 mm Hg, maintained for 6 hours. Main Results: Patients on metoprolol (n = 66) and diltiazem (n = 55) were similar in age, comorbidities, surgical procedure distribution, acuity of illness, and home rate and rhythm control medications continued during hospitalization; 76% of diltiazem-treated patients achieved hemodynamically stable rate control, compared with only 53% of those receiving metoprolol (P = .005). Safety end points were similar between groups, including the portion requiring a new vasopressor or fluid bolus for hemodynamic support. Conclusions: In NCNT surgery, patients with POAF, IV diltiazem more effectively controlled HR and hemodynamics compared with metoprolol. Results warrant further research into optimal medical management of POAF in this population using these 2 agents. Keywords surgery, critical care, arrhythmia
Introduction The frequency of atrial fibrillation (AF) with rapid ventricular response (RVR) following noncardiac, nonthoracic (NCNT) surgical intervention underpins the importance of defining effective management strategies for the 3% to 8% of patients affected.1 Independent of baseline risk factors, surgery introduces a multitude of mechanisms potentially leading to development of AF. These include sympathetic stimulation, oxidative stress, and activation of the inflammatory cascade.2 Heart rate (HR) control has been established as a safe and effective alternative to potentially toxic antiarrhythmic medications in some non–critically ill patients with AF.3-5 Similar outcomes may also be desirable in select intensive care unit (ICU) patients. Lowering of HR may prolong cardiac filling time, increase stroke volume, and prevent tachycardia-induced cardiomyopathy.5,6 Although frequently used in the clinical setting, research has scarcely evaluated
this concept in the ICU7-10 and focuses little on NCNT surgery patients. Absence of effective treatment subjects these individuals to increases in mortality, morbidity, hospital cost, and length of stay.1,11-13 Current investigations of rate control medications in postoperative atrial fibrillation (POAF) put little emphasis on achievement of rate control or hemodynamic stability.7-9 Research comparing esmolol and diltiazem in cardiac 1
Mayo Clinic–Rochester Methodist Hospital, Rochester, MN, USA Iowa Methodist Medical Center, Des Moines, IA, USA 3 Vanderbilt University Medical Center, Nashville, TN, USA 4 Mayo Clinic–Saint Mary’s Hospital, Rochester, MN, USA 2
Corresponding Author: Heather A. Personett, PharmD, Department of Pharmacy Services, Mayo Clinic–Rochester Methodist Hospital, 201 West Center Street, Rochester, MN 55902, USA. Email: [email protected]
Downloaded from aop.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 15, 2015
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Personett et al surgery patients portrays esmolol as being superior with respect to conversion to normal sinus rhythm.9 In these studies, rate control is described only as a secondary end point.8,9 An analysis of a noncardiac surgery population randomizing patients to receive esmolol or diltiazem provides minimal information regarding ventricular rate control and hemodynamic stability.7 To determine if a superior management strategy exists for rate control of POAF in NCNT surgery patients, we must evaluate the abilities of a β-receptor antagonist and a calcium channel blocker to achieve hemodynamically stable rate control. The purpose of this study was to compare intravenous (IV) metoprolol and diltiazem for rate control in NCNT surgical patients with POAF.
Methods Patients This was a retrospective cohort study of adult patients developing POAF with RVR while in the ICU following trauma, vascular, orthopedic, or general surgery. Authors obtained study approval from the Mayo Clinic Institutional Review Board, ID 10-008595. Patients were evaluated for inclusion from January 1, 2008, to December 31, 2009; were at least 18 years old; and received initial treatment with a single agent, either IV metoprolol or diltiazem, for their arrhythmia. Patients were excluded if the procedure was cardiac or thoracic in nature or involved transplantation. Other exclusion criteria consisted of the presence of a pacemaker, direct current cardioversion, and simultaneous new rate or rhythm control interventions following the onset of AF. Simultaneous new rate or rhythm control interventions include concomitant metoprolol and diltiazem or the addition of any other HR or rhythm control therapy to either metoprolol or diltiazem within a single hour of drug initiation. Patients were also excluded if the dose of a preexisting home medication for rate or rhythm control was increased from the strength reported prior to hospitalization. Inclusion in the metoprolol or diltiazem treatment group was determined by the initial rate control agent chosen by the prescriber. No standardized approach to management of POAF existed at the institution, and decisions regarding drug and dosing strategy were at the discretion of the treating physician.
Data Elements Baseline demographics recorded were age, gender, APACHE (Acute Physiology and Chronic Health Evaluations) III score, type of surgical procedure, blood pressure (BP), and HR. Data were gathered on past medical history pertinent to the prevalence of AF,11,14 including structural heart disease, lung disease, or a preexisting diagnosis of AF. Home
medication regimens at the time of hospitalization were recorded if they pertained to HR or rhythm control. When available, electrolytes, pH, fluid status, and use of vasopressor agents were recorded at the onset of POAF and at the time the primary end point was reached. The primary end point was achievement of hemodynamically stable rate control, defined as HR 90 mm Hg, maintained for a minimum of 6 hours. HR and BP were recorded at least every 15 minutes using automated monitoring and documentation systems in each ICU. Patients were evaluated for this outcome during the first 24 hours of therapy with the single chosen agent (monotherapy). Those not achieving hemodynamically stable rate control at any point within this period were considered nonresponders. Failure of monotherapy was defined by drug discontinuation or the addition of another HR or rhythm control agent between hours 2 and 24, with hour 0 being the start of monotherapy. Secondary clinical outcomes included ICU length of stay and readmission to the ICU for POAF. Hemodynamic tolerance of therapy was assessed by recording new vasopressor requirements and fluid boluses of 250 mL or more. Data were collected only for a patient’s first episode of POAF during the study time period.
Statistical Analysis Given the lack of published data in a NCNT patient population with which to perform a power analysis a priori and the rigidity of exclusion criteria, authors included as many patients as met criteria during the study time frame. Categorical variables were assessed using the χ2 test. In the case of analysis of secondary end points, this test was not adjusted for multiple comparisons. Normally distributed continuous data were evaluated using the unpaired Student’s t test and described using means and standard deviations. Continuous data that were not normally distributed were analyzed using the Mann-Whitney U test and described using medians and interquartile ranges. The Wilcoxon signed rank test was used for nonnormally distributed paired data. A P value
2014
AOPXXX10.1177/1060028013512473Annals of PharmacotherapyPersonett et al
Research Report
Intravenous Metoprolol Versus Diltiazem for Rate Control in Noncardiac, Nonthoracic Postoperative Atrial Fibrillation
Annals of Pharmacotherapy 2014, Vol. 48(3) 314–319 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028013512473 aop.sagepub.com
Heather A. Personett, PharmD1, Dustin L. Smoot, MD2, Joanna L. Stollings, PharmD3, Mark Sawyer, MD4, and Lance J. Oyen, PharmD4
Abstract Background: Little guidance exists on effective management of postoperative atrial fibrillation (POAF) following noncardiac, nonthoracic (NCNT) surgery. Objectives: The purpose of this study was to identify whether a difference exists between intravenous (IV) metoprolol and diltiazem when used to achieve hemodynamically stable rate control in POAF following NCNT surgery. Methods: This retrospective cohort study examined critically ill adult surgical patients experiencing POAF with rapid ventricular response. Inclusion in the metoprolol or diltiazem treatment group was determined by the initial rate control agent chosen by the prescriber. The primary end point was hemodynamically stable rate control, defined by heart rate (HR) 90 mm Hg, maintained for 6 hours. Main Results: Patients on metoprolol (n = 66) and diltiazem (n = 55) were similar in age, comorbidities, surgical procedure distribution, acuity of illness, and home rate and rhythm control medications continued during hospitalization; 76% of diltiazem-treated patients achieved hemodynamically stable rate control, compared with only 53% of those receiving metoprolol (P = .005). Safety end points were similar between groups, including the portion requiring a new vasopressor or fluid bolus for hemodynamic support. Conclusions: In NCNT surgery, patients with POAF, IV diltiazem more effectively controlled HR and hemodynamics compared with metoprolol. Results warrant further research into optimal medical management of POAF in this population using these 2 agents. Keywords surgery, critical care, arrhythmia
Introduction The frequency of atrial fibrillation (AF) with rapid ventricular response (RVR) following noncardiac, nonthoracic (NCNT) surgical intervention underpins the importance of defining effective management strategies for the 3% to 8% of patients affected.1 Independent of baseline risk factors, surgery introduces a multitude of mechanisms potentially leading to development of AF. These include sympathetic stimulation, oxidative stress, and activation of the inflammatory cascade.2 Heart rate (HR) control has been established as a safe and effective alternative to potentially toxic antiarrhythmic medications in some non–critically ill patients with AF.3-5 Similar outcomes may also be desirable in select intensive care unit (ICU) patients. Lowering of HR may prolong cardiac filling time, increase stroke volume, and prevent tachycardia-induced cardiomyopathy.5,6 Although frequently used in the clinical setting, research has scarcely evaluated
this concept in the ICU7-10 and focuses little on NCNT surgery patients. Absence of effective treatment subjects these individuals to increases in mortality, morbidity, hospital cost, and length of stay.1,11-13 Current investigations of rate control medications in postoperative atrial fibrillation (POAF) put little emphasis on achievement of rate control or hemodynamic stability.7-9 Research comparing esmolol and diltiazem in cardiac 1
Mayo Clinic–Rochester Methodist Hospital, Rochester, MN, USA Iowa Methodist Medical Center, Des Moines, IA, USA 3 Vanderbilt University Medical Center, Nashville, TN, USA 4 Mayo Clinic–Saint Mary’s Hospital, Rochester, MN, USA 2
Corresponding Author: Heather A. Personett, PharmD, Department of Pharmacy Services, Mayo Clinic–Rochester Methodist Hospital, 201 West Center Street, Rochester, MN 55902, USA. Email: [email protected]
Downloaded from aop.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 15, 2015
315
Personett et al surgery patients portrays esmolol as being superior with respect to conversion to normal sinus rhythm.9 In these studies, rate control is described only as a secondary end point.8,9 An analysis of a noncardiac surgery population randomizing patients to receive esmolol or diltiazem provides minimal information regarding ventricular rate control and hemodynamic stability.7 To determine if a superior management strategy exists for rate control of POAF in NCNT surgery patients, we must evaluate the abilities of a β-receptor antagonist and a calcium channel blocker to achieve hemodynamically stable rate control. The purpose of this study was to compare intravenous (IV) metoprolol and diltiazem for rate control in NCNT surgical patients with POAF.
Methods Patients This was a retrospective cohort study of adult patients developing POAF with RVR while in the ICU following trauma, vascular, orthopedic, or general surgery. Authors obtained study approval from the Mayo Clinic Institutional Review Board, ID 10-008595. Patients were evaluated for inclusion from January 1, 2008, to December 31, 2009; were at least 18 years old; and received initial treatment with a single agent, either IV metoprolol or diltiazem, for their arrhythmia. Patients were excluded if the procedure was cardiac or thoracic in nature or involved transplantation. Other exclusion criteria consisted of the presence of a pacemaker, direct current cardioversion, and simultaneous new rate or rhythm control interventions following the onset of AF. Simultaneous new rate or rhythm control interventions include concomitant metoprolol and diltiazem or the addition of any other HR or rhythm control therapy to either metoprolol or diltiazem within a single hour of drug initiation. Patients were also excluded if the dose of a preexisting home medication for rate or rhythm control was increased from the strength reported prior to hospitalization. Inclusion in the metoprolol or diltiazem treatment group was determined by the initial rate control agent chosen by the prescriber. No standardized approach to management of POAF existed at the institution, and decisions regarding drug and dosing strategy were at the discretion of the treating physician.
Data Elements Baseline demographics recorded were age, gender, APACHE (Acute Physiology and Chronic Health Evaluations) III score, type of surgical procedure, blood pressure (BP), and HR. Data were gathered on past medical history pertinent to the prevalence of AF,11,14 including structural heart disease, lung disease, or a preexisting diagnosis of AF. Home
medication regimens at the time of hospitalization were recorded if they pertained to HR or rhythm control. When available, electrolytes, pH, fluid status, and use of vasopressor agents were recorded at the onset of POAF and at the time the primary end point was reached. The primary end point was achievement of hemodynamically stable rate control, defined as HR 90 mm Hg, maintained for a minimum of 6 hours. HR and BP were recorded at least every 15 minutes using automated monitoring and documentation systems in each ICU. Patients were evaluated for this outcome during the first 24 hours of therapy with the single chosen agent (monotherapy). Those not achieving hemodynamically stable rate control at any point within this period were considered nonresponders. Failure of monotherapy was defined by drug discontinuation or the addition of another HR or rhythm control agent between hours 2 and 24, with hour 0 being the start of monotherapy. Secondary clinical outcomes included ICU length of stay and readmission to the ICU for POAF. Hemodynamic tolerance of therapy was assessed by recording new vasopressor requirements and fluid boluses of 250 mL or more. Data were collected only for a patient’s first episode of POAF during the study time period.
Statistical Analysis Given the lack of published data in a NCNT patient population with which to perform a power analysis a priori and the rigidity of exclusion criteria, authors included as many patients as met criteria during the study time frame. Categorical variables were assessed using the χ2 test. In the case of analysis of secondary end points, this test was not adjusted for multiple comparisons. Normally distributed continuous data were evaluated using the unpaired Student’s t test and described using means and standard deviations. Continuous data that were not normally distributed were analyzed using the Mann-Whitney U test and described using medians and interquartile ranges. The Wilcoxon signed rank test was used for nonnormally distributed paired data. A P value
