Anxiolytic medication is an independent risk factor for 30-day morbidity or mortality after surgery Nicholas Ward, BSc,a J. Scott Roth, MD,b Clark C. Lester, MD,c Lori Mutiso, PhD,d Karen M. Lommel, DO,c and Daniel L. Davenport, PhD,b Lexington, KY
Background. This study examined the effects of the use of anxiolytic medications (AXM) and antidepressant medications (ADMs) on outcomes after noncardiac surgery. Study design. A single-center review of prospectively obtained, perioperative and 30-day outcome data, including AXM and ADM use at admission, as part of the National Surgery Quality Improvement Program. Results. Of the 1846 patients undergoing surgery, 380 (20.6%) were taking an ADM, 288 (15.6%) AXM, 124 (6.7%) were taking both, and 545 (29.5%) were taking either at the time of admission. Both ADM and AXM patients more often were female than nonusers, had a greater American Society of Anesthesiologists class and suffered more from hypertension, COPD, and dyspnea (all P < .005). AXM patients also were more often smokers. ADM patients had a greater mortality and a greater risk of an infective complication, but these effects did not remain after adjustment for procedure and comorbid risks. Patients taking AXM had greater duration of stay, as well as an increased incidence of return to the operating room, infections, wound occurrences, and cardiovascular or cerebrovascular events (all P < .005). After adjustment, AXM was associated with greater combined major morbidity or mortality (odds ratio 1.72, 95% confidence interval 1.08–2.73, P = .023). Conclusion. AXM was used by 16% of patients in our institution undergoing a noncardiac operation and was an independent risk factor for poorer short-term outcome after surgery. ADM was found to be used by 21% of patients but was not an independent risk factor for poor outcome. (Surgery 2015;158:420-7.) From the College of Medicine,a Department of Surgery,b Department of Psychiatry, c and College of Nursing,d University of Kentucky, Lexington, KY
THE
INCIDENCE OF PSYCHIATRIC ILLNESS IS INCREASING IN
UNITED STATES, with an estimated 9.6 million adult individuals (4.1% of all adults in the United States) suffering from serious mental illness as defined by the National Survey on Drug Use and Health.1,2 The lifetime morbid risk of any mood disorder, including major depression, is estimated to be 31%, and of any anxiety disorder to be as great as 41.7%.3 In addition to this increasing national incidence, the prevalence of depression and anxiety
THE
Presented at the 10th Annual Academic Surgical Congress in Las Vegas, NV, February 3–5, 2015. Accepted for publication March 16, 2015. Reprint requests: Daniel L. Davenport, PhD, Associate Professor, University of Kentucky, Department of Surgery, 800 Rose Street, Room MN278, Lexington, KY 40536-0298. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2015.03.050
420 SURGERY
has been shown to be substantially greater among cardiac surgery candidates than the general population. Indeed, after cardiac surgery, depression and anxiety are associated with greater durations of stay, greater rates of hospital readmission, reoperation, and short- and long-term mortality.4-9 Studies of the relationship between depression or anxiety and outcomes after noncardiac surgery are, as yet, rare. Therefore, the goal of this study was to assess the relationships between medically treated anxiety or depression and short-term outcomes after noncardiac surgery. METHODS The University of Kentucky Medical Institutional Review Board reviewed and approved this study and allowed a waiver of informed consent. This study was a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) data gathered prospectively at the University of Kentucky A. B. Chandler Medical Center (UKMC) between
Surgery Volume 158, Number 2
Ward et al 421
Fig. The percentage of patients admitted for surgery using antidepressants or anxiolytics; stratified by the procedure performed. *‘‘Other’’ cases include a systematic sample of a broad range of general and vascular surgery cases performed under general anesthetic.
October 1, 2011, and September 30, 2012. All of the adult NSQIP procedures tracked at UKMC were included in the study and encompassed a broad range of general, vascular, urologic, and plastic surgery procedures (see the Fig).
Cardiothoracic, orthopedic, and neurosurgical cases were not included in the NSQIP protocol at the UKMC during this period. Two custom variables were added to the NSQIP protocol during that period at the time of
422 Ward et al
Surgery August 2015
Table I. List of antidepressant and anxiolytic drugs used to classify patients at admission Antidepressants, generic
Antidepressants, brand name
Anxiolytics, generic
Citalopram Escitalopram Paroxetine Fluoxetine Fluvoxamine Sertraline
Celexa Lexapro Paxil Prozac Luvox Zoloft
Duloxetine Venlafaxine Desvenlafaxine Buproprion Mirtazepine Trazodone Amitriptyline Imipramine Nortriptyline Protriptyline Perphenazine/Amitryptyline Tranylcypromine Phenelzine Selegiline Isocarbozxazid
Cymbalta Effexor XR Pristiq Wellbutrin/Zyban Remeron Desyrel Elavil Tofranil Pamelor Vivactil Triavil Parnate Nardil Emsam, Elderpyl, Zelapar Marplan
admission: antidepressant medications (ADMs) and anxiolytic medications (AXMs). The list of drugs used for each psychotropic designation is shown in Table I and was generated by a practicing clinical psychiatrist (K.L.). The data on medication usage were obtained from the UKMC medication review list, which indicated last dosage taken or ‘‘noncompliant’’ per the patient. The patients categorized as using the drugs in this study indicated they were taking these medications actively at the time of admission. At the UKMC, the NSQIP data are obtained prospectively and systematically by nurses with operative or intensive care unit experience who follow precise clinical definitions. The data include demographics, more than 30 preoperative clinical risk variables, perioperative processes, and 22 specific outcomes, including death up to 30 days after the operation. The validity of the data and the protocol have been described elsewhere.10,11 The procedures analyzed included all those included in the adult NSQIP program at the UKMC during the study period and are listed in the Fig. Each procedure had 100% sampling during the study period except for the ‘‘other’’ group, which included a broader systematic sample of other major general and vascular operations performed under general anesthetic.
Anxiolytics, brand name
Alprazolam Diazepam Clonazepam Lorazepam Chlordiazepoxide
Xanax Valium Klonopin Ativan Librium
Hydroxyzine
Atarax/Vistaril
Specific outcomes analyzed included duration of hospital stay, death, and major morbidity occurring up to 30-day after the operation including: return to the operating room for any reason, surgical-site infection (superficial, deep, or organ/ space) or wound dehiscence, sepsis or septic shock, urinary tract infection, renal insufficiency or failure, deep venous thrombosis or pulmonary embolism, stroke with deficit, cardiac arrest, and acute myocardial infarction. Univariate comparisons of all preoperative, intraoperative and outcome variables were performed between patients using AXM or ADM and nonusers using t-tests, Mann-Whiney U, v2, or Fisher exact tests as appropriate. Given the number of comparisons performed, we increased the threshold for significance to P < .005 for the univariate analyses. Two multivariable logistic regressions were performed. The first analyzed the effects of AXM or ADM use (with their interaction term) on combined mortality or major morbidity with adjustment for only the procedure performed. The second regression had 4 stages that started with the comorbid conditions that differed significantly in the univariate analyses fixed in the model; then other comorbid risks were added in a forward fashion with P for entry .10; third, intraoperative variables were added in a similar forward manner; and finally AXM use, ADM use and
Ward et al 423
Surgery Volume 158, Number 2
Table II. Patient characteristics that differed in antidepressant or anxiolytic groups Patient characteristic No. patients Preoperative characteristics Female, % ASA class I or II III IV or V Smoker, % Severe COPD, % Dyspnea, % Treated hypertension, % Intraoperative characteristics Duration of operation, min, mean ± SD
No antidepressant use 1,466
Antidepressant use 380 (20.6%)
52.2 44.1 49.2 6.6 32.7 5.9 14.1 49.7 169 ± 133
P value
1,557
Background. This study examined the effects of the use of anxiolytic medications (AXM) and antidepressant medications (ADMs) on outcomes after noncardiac surgery. Study design. A single-center review of prospectively obtained, perioperative and 30-day outcome data, including AXM and ADM use at admission, as part of the National Surgery Quality Improvement Program. Results. Of the 1846 patients undergoing surgery, 380 (20.6%) were taking an ADM, 288 (15.6%) AXM, 124 (6.7%) were taking both, and 545 (29.5%) were taking either at the time of admission. Both ADM and AXM patients more often were female than nonusers, had a greater American Society of Anesthesiologists class and suffered more from hypertension, COPD, and dyspnea (all P < .005). AXM patients also were more often smokers. ADM patients had a greater mortality and a greater risk of an infective complication, but these effects did not remain after adjustment for procedure and comorbid risks. Patients taking AXM had greater duration of stay, as well as an increased incidence of return to the operating room, infections, wound occurrences, and cardiovascular or cerebrovascular events (all P < .005). After adjustment, AXM was associated with greater combined major morbidity or mortality (odds ratio 1.72, 95% confidence interval 1.08–2.73, P = .023). Conclusion. AXM was used by 16% of patients in our institution undergoing a noncardiac operation and was an independent risk factor for poorer short-term outcome after surgery. ADM was found to be used by 21% of patients but was not an independent risk factor for poor outcome. (Surgery 2015;158:420-7.) From the College of Medicine,a Department of Surgery,b Department of Psychiatry, c and College of Nursing,d University of Kentucky, Lexington, KY
THE
INCIDENCE OF PSYCHIATRIC ILLNESS IS INCREASING IN
UNITED STATES, with an estimated 9.6 million adult individuals (4.1% of all adults in the United States) suffering from serious mental illness as defined by the National Survey on Drug Use and Health.1,2 The lifetime morbid risk of any mood disorder, including major depression, is estimated to be 31%, and of any anxiety disorder to be as great as 41.7%.3 In addition to this increasing national incidence, the prevalence of depression and anxiety
THE
Presented at the 10th Annual Academic Surgical Congress in Las Vegas, NV, February 3–5, 2015. Accepted for publication March 16, 2015. Reprint requests: Daniel L. Davenport, PhD, Associate Professor, University of Kentucky, Department of Surgery, 800 Rose Street, Room MN278, Lexington, KY 40536-0298. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2015.03.050
420 SURGERY
has been shown to be substantially greater among cardiac surgery candidates than the general population. Indeed, after cardiac surgery, depression and anxiety are associated with greater durations of stay, greater rates of hospital readmission, reoperation, and short- and long-term mortality.4-9 Studies of the relationship between depression or anxiety and outcomes after noncardiac surgery are, as yet, rare. Therefore, the goal of this study was to assess the relationships between medically treated anxiety or depression and short-term outcomes after noncardiac surgery. METHODS The University of Kentucky Medical Institutional Review Board reviewed and approved this study and allowed a waiver of informed consent. This study was a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) data gathered prospectively at the University of Kentucky A. B. Chandler Medical Center (UKMC) between
Surgery Volume 158, Number 2
Ward et al 421
Fig. The percentage of patients admitted for surgery using antidepressants or anxiolytics; stratified by the procedure performed. *‘‘Other’’ cases include a systematic sample of a broad range of general and vascular surgery cases performed under general anesthetic.
October 1, 2011, and September 30, 2012. All of the adult NSQIP procedures tracked at UKMC were included in the study and encompassed a broad range of general, vascular, urologic, and plastic surgery procedures (see the Fig).
Cardiothoracic, orthopedic, and neurosurgical cases were not included in the NSQIP protocol at the UKMC during this period. Two custom variables were added to the NSQIP protocol during that period at the time of
422 Ward et al
Surgery August 2015
Table I. List of antidepressant and anxiolytic drugs used to classify patients at admission Antidepressants, generic
Antidepressants, brand name
Anxiolytics, generic
Citalopram Escitalopram Paroxetine Fluoxetine Fluvoxamine Sertraline
Celexa Lexapro Paxil Prozac Luvox Zoloft
Duloxetine Venlafaxine Desvenlafaxine Buproprion Mirtazepine Trazodone Amitriptyline Imipramine Nortriptyline Protriptyline Perphenazine/Amitryptyline Tranylcypromine Phenelzine Selegiline Isocarbozxazid
Cymbalta Effexor XR Pristiq Wellbutrin/Zyban Remeron Desyrel Elavil Tofranil Pamelor Vivactil Triavil Parnate Nardil Emsam, Elderpyl, Zelapar Marplan
admission: antidepressant medications (ADMs) and anxiolytic medications (AXMs). The list of drugs used for each psychotropic designation is shown in Table I and was generated by a practicing clinical psychiatrist (K.L.). The data on medication usage were obtained from the UKMC medication review list, which indicated last dosage taken or ‘‘noncompliant’’ per the patient. The patients categorized as using the drugs in this study indicated they were taking these medications actively at the time of admission. At the UKMC, the NSQIP data are obtained prospectively and systematically by nurses with operative or intensive care unit experience who follow precise clinical definitions. The data include demographics, more than 30 preoperative clinical risk variables, perioperative processes, and 22 specific outcomes, including death up to 30 days after the operation. The validity of the data and the protocol have been described elsewhere.10,11 The procedures analyzed included all those included in the adult NSQIP program at the UKMC during the study period and are listed in the Fig. Each procedure had 100% sampling during the study period except for the ‘‘other’’ group, which included a broader systematic sample of other major general and vascular operations performed under general anesthetic.
Anxiolytics, brand name
Alprazolam Diazepam Clonazepam Lorazepam Chlordiazepoxide
Xanax Valium Klonopin Ativan Librium
Hydroxyzine
Atarax/Vistaril
Specific outcomes analyzed included duration of hospital stay, death, and major morbidity occurring up to 30-day after the operation including: return to the operating room for any reason, surgical-site infection (superficial, deep, or organ/ space) or wound dehiscence, sepsis or septic shock, urinary tract infection, renal insufficiency or failure, deep venous thrombosis or pulmonary embolism, stroke with deficit, cardiac arrest, and acute myocardial infarction. Univariate comparisons of all preoperative, intraoperative and outcome variables were performed between patients using AXM or ADM and nonusers using t-tests, Mann-Whiney U, v2, or Fisher exact tests as appropriate. Given the number of comparisons performed, we increased the threshold for significance to P < .005 for the univariate analyses. Two multivariable logistic regressions were performed. The first analyzed the effects of AXM or ADM use (with their interaction term) on combined mortality or major morbidity with adjustment for only the procedure performed. The second regression had 4 stages that started with the comorbid conditions that differed significantly in the univariate analyses fixed in the model; then other comorbid risks were added in a forward fashion with P for entry .10; third, intraoperative variables were added in a similar forward manner; and finally AXM use, ADM use and
Ward et al 423
Surgery Volume 158, Number 2
Table II. Patient characteristics that differed in antidepressant or anxiolytic groups Patient characteristic No. patients Preoperative characteristics Female, % ASA class I or II III IV or V Smoker, % Severe COPD, % Dyspnea, % Treated hypertension, % Intraoperative characteristics Duration of operation, min, mean ± SD
No antidepressant use 1,466
Antidepressant use 380 (20.6%)
52.2 44.1 49.2 6.6 32.7 5.9 14.1 49.7 169 ± 133
P value
1,557
