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Ann Thorac Surg 2001;71:110-116
© 2001 The Society of Thoracic Surgeons

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Original article: cardiovascular

Temperature during coronary artery bypass surgery affects quality of life

^a Departments of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina USA
^b Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA
^c Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA

Accepted for publication August 21, 2000.

Address reprint requests to Dr Blumenthal, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3119, Durham, NC 27710
e-mail: blume003{at}mc.duke.edu

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Background. The objective of this study was to examine the effects of temperature on a variety of indices of psychologic adjustment and quality of life.

Methods. A total of 209 patients randomly received normothermic (warm) or hypothermic (cold) conditions during coronary artery bypass surgery (CABS), and a number of physical, social, and psychologic measures were assessed before as well as 6 weeks and 6 months after CABS.

Results. Repeated measures analyses of covariance revealed significant temperature group main effects for anxiety (p = 0.008) and depression (p = 0.039), with the normothermic group obtaining lower anxiety and depression levels than the hypothermic group at both 6 weeks and 6 months after surgery. Additionally, among patients who entered the study with higher depression levels, those in the hypothermic group tended to have higher depression scores at follow-up compared with patients in the normothermic condition (p = 0.012). No temperature group differences were observed on other quality of life indices.

Conclusions. The results of the present study indicate that hypothermic conditions during CABS are associated with higher levels of emotional distress after CABS than normothermic conditions, particularly for patients with greater stress to begin with.

	Introduction

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Coronary artery bypass surgery (CABS) has become one of the most established interventions for intractable angina and life-threatening ischemic heart disease [1]. Because improvements in surgical techniques have resulted in marked reduction in mortality [2], interest in alternative endpoints of CABS is growing [3, 4]. Psychosocial adjustment and quality of life have gained considerable attention because improvement in physical, psychologic, and social functioning as well as overall sense of well-being can be related to the relief of angina and improvement of physical functioning that typically follow CABS [1, 5]. Although there is no consensus on what "quality of life" means and how it should be measured, there is general agreement that quality of life is a multidimensional construct [6] that includes biological, psychologic and social components [3].

Despite evidence for poor outcome for some patients after successful CABS (eg, increase in depression, anxiety, or cognitive dysfunction) [7, 8], most studies have demonstrated that CABS has beneficial effects on psychological functioning and quality of life for the majority of patients [1]. Within 6 months after surgery, most patients report a reduction in depressive and anxiety symptoms [9]. Patients also experience marked improvements in physical (eg, fewer restrictions on activity; decreased fatigue and sleep problems), sexual (eg, reduction in pain and worry; increased desire and energy), social (eg, increased participation in social activities and hobbies), and work activity (return to work, improved job performance) [9–11]. Furthermore, 1 year after surgery, patients report increased life satisfaction and improvements in emotional well-being and family life [12].

A number of studies have examined predictors of quality of life after CABS using a range of measures including preoperative factors such as psychologic maladjustment, personality characteristics, and social activity [1, 5]. Low levels of depression and anxiety and high levels of social support before surgery have been found to predict satisfactory rehabilitation, positive social adjustment, and relief from symptoms [9, 13, 14]. Conversely, high levels of preoperative depression and anxiety predict high levels of depression and anxiety and low life satisfaction after surgery [15, 16]. However, as the interest in quality of life after CABS has increased, researchers have noted the need for prospective studies that examine a wider range of quality of life measures with attention to other potential factors such as disease severity and demographic variables.

Investigation of the psychologic adjustment and quality of life after CABS has become particularly important since the advent of warm heart surgery and the subsequent scrutiny of the neuroprotective role of hypothermic CABS [17]. Although some studies suggest that normothermic ("warm") conditions during CABS have been associated with improved myocardial outcome [18], others indicate that hypothermic ("cold") conditions may be related to decreased risk for neurologic dysfunction [19]. Preliminary comparisons of normothermic conditions versus hypothermic conditions on neurologic outcomes during CABS have yielded mixed results. Several studies have found no differences between normothermic and hypothermic conditions in neurologic outcome [17], whereas others report that normothermic conditions are associated with increased risk for poor neurologic outcome [19]. Assessing other outcomes of CABS as a function of temperature may be important given the current debate on normothermic versus hypothermic conditions during bypass. Research evaluating psychologic functioning and quality of life in patients exposed to normothermic versus hypothermic conditions during CABS is lacking. Therefore, the purpose of the present study was to examine the effects of temperature on mood, physical functioning, and related aspects of quality of life. The present study is a prospective analysis of ancillary quality of life endpoints in a randomized clinical trial in which patients were randomly assigned to either normothermic or hypothermic conditions during CABS. In the present study, a number of physical, social, and psychologic indices of adjustment were systematically assessed before as well as 6 weeks and 6 months after CABS.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Subjects
A total of 227 consecutive patients undergoing elective CABS between April 1994 and August 1997 were recruited for participation. Patients who could not read, had a major psychiatric illness, suffered a stroke, had known cerebrovascular disease, or were involved in competing research protocols were excluded. Emergent cases were also excluded from the study. In addition 18 (8%) patients were randomized (10 normothermia; 8 hypothermia) but did not complete the psychologic assessments, yielding a final sample of 209 patients for whom complete pre- and post-CABS data were available.

Procedure
After obtaining informed consent, patients scheduled for CABS completed a battery of quality of life measures the day before surgery (baseline) as well as 6 weeks and 6 months after surgery. The two treatments were randomly assigned before surgery by means of computer-generated random numbers to a normothermic (35.5°C to 36.5°C) cardiopulmonary bypass (CPB) or to a hypothermic (28°C to 30°C) CPB with hypothermic cardioplegia group. Patients in the hypothermic CPB group were cooled to a nasopharyngeal temperature of 28°C to 30°C through management of arterial inflow temperature. Patients in the normothermic group were maintained at temperatures of 35.5°C to 36.5°C by maintenance of inflow temperatures. The hypothermic group was rewarmed to 37°C before separation from CPB. Arterial inflow temperature did not exceed 38°C in any patient. Investigators performing the pre- and postoperative assessments were blinded to the temperature group assignment of each patient. Only the physicians involved in intraoperative care of these patients were aware of the temperature group, but they were unaware of the psychologic test results.

Anesthetic management with midazolam, fentanyl, and vecuronium has previously been described [20]. The perfusion apparatus consisted of a Cobe CML oxygenator (Cobe Laboratories; Lakewood, CO), a Sarns 7000 max pump (Sarns Inc, Ann Arbor, MI), and a Pall SP 3840 arterial line filter (Pall Biomedical Products, East Hills, NY). Nonpulsatile perfusion of 2 to 2.4 L · min^-1 · m^-2 was maintained throughout the study periods. The pump was primed with crystalloid solution designed to achieve a hematocrit of 0.18 or greater during extracorporeal circulation. Packed red blood cells were added when necessary to achieve the desired hematocrit. All patients underwent CPB through an ascending aortic cannula. Arterial CO₂ tension was maintained throughout CPB at 35 to 40 mm Hg (uncorrected for temperature), and PaO₂ was maintained at 150 to 250 mm Hg. Preoperative hemodynamic status was not different between groups.

Psychometric instruments were administered individually in a private hospital room by a trained psychometrician who was blinded to temperature group assignment. Follow-up assessments were conducted in a laboratory at the hospital by the same examiner who performed the baseline assessment without knowledge of the subject’s treatment group assignment. Most of the questionnaires were self-administered; however, the measures were read to patients if they were feeling ill and unable to read, did not have their reading glasses with them, or if they had such a low level of education that they had trouble reading. The following psychometric measures were used:

1. Center for Epidemiological Studies Depression Scale (CES-D) [21]. The CES-D is a 20-item self-report measure designed to measure symptoms of depression. Subjects rate the degree to which they have experienced a range of symptoms of depression on items such as "I had crying spells" and "I felt lonely." Scores range from 0 to 60, with higher scores indicating greater depressive symptoms. Scores greater than 16 are typically considered indicative of clinically significant depression.
   
2. Spielberger Anxiety Inventory—State [22]. The STAI State consists of a 20-item scale that measures state (current) anxiety. Representative items include statements such as "I feel nervous" and "I feel worried." These items are rated on a four-point scale of how well they describe the patient’s current mood from "not at all" to "very much so." Scores range from 20 to 80, with higher scores indicating greater anxiety.
   
3. The Medical Outcomes Study (MOS) Social Support Survey [23]. The MOS Social Support Survey is a 19-item measure of functional social support that includes multiple dimensions of support: emotional/informational, tangible, affectionate, and positive social interaction. Items are rated on a five-point scale from "none of the time" to "all of the time" and scores range from 19 to 95, with higher scores indicating greater perceived social support. Items include how often there is "someone you can count on to listen to you when you need to talk" and "someone to help with daily chores if you were sick."
   
4. The Duke Activity Status Index (DASI) [24]. The DASI is a 12-item scale of functional capacity that has been found to correlate well with objective measures of maximal exercise capacity. Items reflect activities of personal care, ambulation, household tasks, sexual function, and recreational activities. Scores range from 12 to 48, with higher scores generally reflecting increased physical limitations.
   
5. The Duke Older Americans Resources and Services Procedures—Instrumental Activities of Daily Living (OARS-IADL) [25]. This measure contains the six IADL items from the OARS that assess the ability to perform important tasks for daily living (eg, "Could you prepare your own meals?" "Could you drive a car?"). Scores range from 6 to 30, with higher scores indicating increasing difficulty in engaging in daily activities.
   
6. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) Role limitations due to physical health scale [26]. This measure includes a modified version of the role limitations due to physical health scale of the SF-36. The eight items assess problems with work as a result of physical health, and were scored on a 4-point Likert scale ranging from 1 ("rarely or none of the time") to 4 ("most or all of the time"). Sample items include symptoms such as "heart pain/angina, arthritis, and lack of energy/fatigue." Higher scores indicate greater role limitations due to physical health. Patients also answered a single item from the SF-36 regarding the extent to which their physical health interfered with their normal social activities on a scale ranging from 1 ("not at all") to 5 ("extremely").
   
7. Subjective perception of health. Participants answered a four-point, single item regarding perception of health ("During the past month, would you say your health was ...") on a scale ranging from "poor" to "excellent."
   

Statistical analysis
The primary analytic approach was a 2 x 2 x 2 repeated measures analysis of covariance (ANCOVA), in which temperature group (normothermia vs hypothermia) and gender (male vs female) served as between-subjects factors, and time (6 weeks and 6 months) served as the within-subjects (repeated measures) factor. Each model included the corresponding baseline level of the outcome variable and age as covariates.

Separate models were estimated for each outcome measure. Analyses were carried out using SAS PROC MIXED (SAS, Cary, NC) with restricted maximum likelihood estimation. In these models, we allowed heterogeneous variances (diagonals of the r matrix) across sex [27]. All models were checked for violations of assumptions of heterogeneity of slopes with respect to the covariates, and for appropriate error distributions and influential cases. All models met the above assumptions with the exception of the model for depression. In this case we observed significant heterogeneity of slopes across treatment groups with respect to baseline depression levels, indicating that the effect of temperature group depended on the initial level of depression. Accordingly we included a Baseline by Group interaction term in the model. Covariates were centered at the sample mean. For descriptive purposes, we also calculated within-groups change scores from baseline to 6 weeks and from baseline to 6 months on each of the outcome variables. Group differences on baseline characteristics were evaluated using t tests for continuously measured data and ² tests for categorical data. Following Benjamini and Hochberg [28] we also applied a sequential correction procedure to control for multiple tests within domains, eg, psychological outcomes (depression and anxiety) and functional quality of life outcomes. Specifically, p values were ranked by size and assessed sequentially at 0.05/k, 0.05/k-1, 0.05/k-2 ... , where k is the number of tests of interest in the domain. Application of this procedure did not change any outcome.

	Results

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Baseline characteristics
The groups were comparable with regard to demographic and clinical characteristics including age, gender, education level, and medical history, as well as left ventricular ejection fraction (Table 1). In addition, there were no group differences in intraoperative measures such as pump time, clamp time, and the number of bypassed vessels. The mean peak temperature was slightly higher for the hypothermic group compared to the normothermic group (p < 0.001), however (Table 2). The groups also had similar levels of depression, anxiety, and quality of life-related variables before surgery (Table 3). Overall, the study cohort had moderate preoperative levels of anxiety and depression. In all, 32 patients (30%) in the normothermic group and 32 patients (31%) in the hypothermic group had CES-D scores of less than 16, suggesting the presence of clinical depression on the CES-D. On the STAI 35 patients (34%) in the hypothermic group had a score of 45 or greater, whereas 42 patients (40%) demonstrated high scores in the normothermic group, suggesting the presence of comparably high levels of anxiety in a significant subgroup of patients. After surgery 35 patients (30%) undergoing normothermia and 38 patients (34%) undergoing hypothermia had at least one significant complication (p = 0.51).

Follow-up analysis of the treatment group by baseline level depression interaction revealed that for patients who entered the study with low depression scores, the rate of improvement in depression was similar across temperature conditions. However, for patients who entered the study with higher depression levels, those in the hypothermic group tended to have higher depression scores at follow-up compared with patients in the normothermic condition (Fig 1). Adjusting for maximum rewarming temperature did not change the substantive or statistical significance of the group by baseline depression interaction (p = 0.006). Maximum rewarming temperature itself was unrelated to post-CABS depression (p = 0.90). At 6 weeks, 47 (25%) of patients exhibited CES-D scores greater than 16, and at 6 months follow-up only 39 patients (22%) were clinically depressed. However, the percentage of patients with scores in this range did not differ by temperature group at 6 weeks of follow-up (24% of normothermic vs 27% of hypothermic patients; p = 0.64) or at 6 months of follow-up (20% of normothermic vs 24% of hypothermic patients; p = 0.51).

View larger version (18K): [in this window] [in a new window]   Fig 1. Fitted postsurgical depression scores for patients entering trial with (high, CESD = 20) and without (low, CESD = 5) clinically significant levels of depression. Values are predicted from mixed statistical model adjusting for age, gender, left ventricular ejection fraction, and presurgical depression levels. Error bars represent standard errors. Among patients entering the trial with clinically significant depression, those in the hypothermia condition exhibited higher depression scores at 6 weeks and 6 months after surgery compared with patients in the normothermia group. No treatment differences were seen among patients entering the trial without clinically significant depression.

View larger version (14K): [in this window] [in a new window]   Fig 2. Fitted postsurgical values for anxiety. Values are predicted from mixed statistical model adjusting for age, gender, left ventricular ejection fraction, and presurgical anxiety levels. Error bars represent standard errors. Patients in the hypothermic group had significantly higher levels of anxiety at 6 weeks and 6 months compared with patients in the normothermic group.

Subjective Perception of health as well as Health interference with social and work activity followed a pattern similar to the Activity status and daily function scores, with both groups worse at 6 weeks compared with baseline but improving to above baseline levels at 6 months. Neither main effects for temperature (p = 0.87) nor for gender (p = 0.14) were significant. For Perception of health the change from 6 weeks to 6 months was significant (p = 0.0001), with patients reporting improved health over this period. For Health interference with social activity the change from 6 weeks to 6 months was also significant (p = 0.0001), with patients reporting less interference with social activities over time. There was no effect of temperature condition (p = 0.64) or of gender (p = 0.55). Finally, for Health interference with work activity, the change from 6 weeks to 6 months was significant (p = 0.0001), again with patients showing less interference with work activities over time. There was no effect of temperature condition (p = 0.99) or of gender (p = 0.48).

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Data from the current study generally indicate improved overall quality of life by 6 months after CABS. Although there was some worsening of symptoms acutely, by 6 months most patients were generally improved over their baseline levels on such measures as physical activity, perceived health, and interference with social and work activity. Examination of gender differences suggested that women exhibit more impairment in quality of life than do men after CABS. This observation is consistent with other reports [1]. For example, women have been shown to have poorer rehabilitative results and greater illness symptoms after CABS as compared with men [29]. As few studies have examined gender differences in psychosocial outcomes after bypass, further investigation of the possible factors involved in this differential pattern of recovery is needed [1].

The results of the present study indicate that normothermia during CABS was associated with better psychologic outcomes than was hypothermia, particularly for patients who had greater depression before CABS. Although neither temperature condition was associated with clinically significant increased levels of depression and anxiety, patients in the hypothermic group were more likely to report more symptoms of anxiety and depression than were patients in the normothermic group 6 weeks and 6 months after CABS. Among patients who had greater depression before CABS, hypothermia was associated with higher depression scores as compared to normothermia. It should be noted that the mechanisms responsible for this observation could be due to brief hyperthermia during the rewarming and not necessarily to the hypothermia during CABS. However, these group differences remained significant even when maximum rewarming temperature was added as a covariate in the model. In addition, despite these temperature group differences, there were no group differences on other quality of life indices, suggesting that heightened anxiety and depression were not necessarily associated with impairment in functioning.

The pattern of findings for temperature group differences is interesting given the evidence that normothermia may be associated with increased risk for neurologic deficits [17]. Data supporting the neuroprotective role of hypothermia are limited, however [19]. Methodologic differences have been cited in explaining these mixed findings. Mora and Murkin [29] have suggested that because even small increases in temperature may affect neurologic outcome, temperature variations between studies may in fact not reflect the neuroprotective role of hypothermia but, rather, the risk of hyperthermia. The present design was not designed to examine the mechanisms by which temperature during CABS affected quality of life. The finding that patients who underwent hypothermic CABS had higher distress at follow-up could be due either to hypothermia during CPB or to hyperthermia during rewarming. Moreover, it is possible that the mechanisms by which temperature during CABS affects neurologic and psychologic functioning may be different. Although differences in cerebral blood flow between the two temperature conditions may play a role, the possible mechanisms of the effect of temperature on anxiety and depression are unknown and suggest an avenue for future research. If mild hypothermic CPB allows the safe conduct of CPB while avoiding the hyperthermia associated with rapid rewarming from profound or moderate hypothermia, then this temperature management strategy may allow the optimization of outcome in a population at high risk for neurologic deterioration and reduced quality of life. The interaction of preoperative depression and temperature group suggests that hypothermia may be particularly deleterious for patients reporting high levels of depression before CABS. The lack of temperature group differences on other quality of life indices are consistent with several studies that have failed to find differences between normothermic and hypothermic conditions during CABS in neurologic functioning. We also plan to examine changes in neuropsychologic functioning in future analyses. In addition the anticipation of CABS actually may have increased state anxiety levels. However because the primary analyses involved between group comparisons after CABS, the stressful preoperative period is unlikely to have affected the results.

In summary, patients who experienced hypothermic conditions during CABS reported higher levels of depression and anxiety than did patients in the normothermic conditions. A significant subgroup of patients (30% to 40%) exhibited clinically significant levels of depression and anxiety that were generally reduced at 6 weeks and 6 months of follow-up. There were no temperature group differences on reports of physical functioning, social or work activity, or perceived health. However normothermic conditions during CABS were associated with reduced risk for depression after surgery for patients who reported high levels of preoperative depression. These findings suggest that preoperative psychologic functioning may be an important consideration in assessing postoperative psychosocial outcomes after CABS.

	Acknowledgments

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The preparation of this article was supported, in part, by National Institutes of Health grants HL49572, 49678, AG09663, MH49679, and HL59672.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Mark F. Newman Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khatri, P. Articles by Blumenthal, J. A. Search for Related Content PubMed PubMed Citation Articles by Khatri, P. Articles by Blumenthal, J. A. Related Collections Cerebral protection Coronary disease