Early extubation after cardiac surgery: Emotional status in the early postoperative period

Early Extubation After Cardiac Surgery: Emotional Status in the Early Postoperative Period Brendan S. Silbert, FANZCA, John D. Santamaria, MD, FRACP, William J. Kelly, MD, FRACP, Jennifer L. O’Brien, RN, BN, Carolyn M. Blyth, RN, Maggie Y. Wong, MB, BS, Nicholas B. Allen, PhD, and The Fast Track Cardiac Care Team* Objective: To compare the emotional state during the first 3 days after coronary artery surgery of patients who had undergone early versus conventional extubation. Design: A prospective, randomized, controlled trial. Setting: University hospital, single center. Participants: Eligible patients (n ⴝ 100) presenting for elective coronary artery surgery, randomized to an early extubation group or a conventional extubation group. Interventions: Emotional status was measured by the Hospital Anxiety and Depression Scale (HAD), the Self Assessment Manikin (SAM), and the Multiple Affect Adjective Check List–Revised (MAACL-R). Tests were administered preoperatively and on the 1st and 3rd days postoperatively. Measurements and Main Results: Of patients in the conventional extubation group, 30% showed moderate-to-severe depressive symptoms (HAD score >10) on day 3 post-

operatively compared with 8% of patients in the early extubation group (p ⴝ 0.02). There was a clinically insignificant increase in MAACL-R depression score on the 1st postoperative day within both groups but no other differences within or between groups in SAM or MAACL-R scores. Conclusion: Early extubation results in fewer patients displaying depressive symptoms on the 3rd postoperative day but appears to have little effect on other measurements of emotional status. Anesthetic management during coronary artery bypass graft surgery may play an important role in the overall well-being of the patient by decreasing the incidence of postoperative depression. Copyright © 2001 by W.B. Saunders Company

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conclusion of CPB. Additional fentanyl or a propofol infusion was administered if anesthesia was considered inadequate at any stage, and vecuronium was administered for further muscle relaxation. The EE group was given a reduced dose of fentanyl, 15 ␮g/kg, and anesthesia was augmented with propofol, 6 to 8 mg/kg/hr for induction and 3 to 4 mg/kg/hr for maintenance. Additional propofol (but not fentanyl) was administered if indicated. At the conclusion of surgery, muscle relaxation in both groups was reversed using neostigmine, 2.5 mg, and glycopyrrolate, 0.4mg. Five surgeons were involved in the study. CPB was performed for all patients using a Cobe membrane oxygenator (Cobe Cardiovascular, Inc, Arvado, CO) with continuous flow of 2.0 to 2.4 L/min/m2. For all but one of the surgeons, arrest of the heart was managed using a combination of antegrade and retrograde warm blood cardioplegia without active cooling. The remaining surgeon used cold crystalloid antegrade cardioplegia with active cooling. All patients were actively rewarmed to 37°C before discontinuation of CPB. Cross-clamp time, CPB time, duration of surgery, and number of grafts were recorded.

HE ROUTINE USE of mechanical ventilation postoperatively after cardiac surgery has been a long tradition because of the potential advantages offered by this approach.1 There has been a tendency to change anesthetic and postoperative intensive care management to permit early extubation. Reports have focused on morbidity outcomes2,3 and economic advantages4 of this approach. Hickey and Cason5 stated that early extubation may influence patient satisfaction and suggested that quantification of patient experience, although difficult to measure, is important. Early extubation offers patients the opportunity to respond to questions at a time when they previously would have been sedated and ventilated. To investigate this area, the authors undertook a prospective, randomized, controlled study to compare the emotional state of patients selected for early extubation with patients managed conventionally during the early postoperative period. METHODS

After Institutional Ethics Committee approval and informed consent, 100 patients scheduled for first-time elective coronary artery bypass graft surgery were entered into the study. Patients with concurrent valve disease, poor myocardial function, associated systemic illness, contraindications to early extubation (eg, respiratory disease), communication problems, language difficulties, or psychiatric illness (including depression) were excluded. Eligible patients were randomized by computer-generated random numbers (in blocks of 4) to the conventional extubation (CE) group or early extubation (EE) group. Anesthesia was administered by 5 anesthesiologists according to the following protocols. All patients were premedicated with intramuscular papaverutum, 0.3 mg/kg, and scopolamine, 0.006 mg/kg, and received midazolam (maximum of 0.1 mg/kg) during insertion of arterial and pulmonary artery catheters. The CE group was induced with fentanyl, 50 ␮g/kg; given pancuronium, 0.1 mg/ kg; intubated and ventilated with 100% oxygen. Midazolam, 0.1 mg/kg, was administered at the start of cardiopulmonary bypass (CPB), and morphine, 0.1 mg/kg, was given at the

KEY WORDS: cardiac surgery, emotional status, fast-track anaesthesia

* Rowan Molnar, FANZCA, Sue Portelli, RN, Patricia Mooney, RN, David Scott, FANZCA, Michael Davies, FANZCA, Charles Domaingue, FANZCA, Roman Kluger, Damon Sutton, FANZCA, and Russell Cook, FANZCA. From the Departments of Anaesthesia and Intensive Care, St. Vincent’s Hospital, and Department of Psychiatry, University of Melbourne, Victoria, Australia. Supported in part by a research grant provided by the Australian Society of Anaesthetists and Abbott Australasia and by a grant-in-aid provided by ICI Pharmaceuticals. Address reprint requests to Brendan Silbert, FANZCA, Department of Anaesthesia, St. Vincent’s Hospital, Victoria Parade, Melbourne, 3065, Victoria, Australia. E-mail: [email protected] Copyright © 2001 by W.B. Saunders Company 1053-0770/01/1504-0007$35.00/0 doi:10.1053/jcan.2001.24978

Journal of Cardiothoracic and Vascular Anesthesia, Vol 15, No 4 (August), 2001: pp 439-444

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For both groups, intraoperative hemodynamic management was standardized. Hypotension was treated with volume replacement, ephedrine or metaraminol as indicated. Hypertension was treated by deepening anesthesia or with nitroglycerin. Tachycardia was treated by deepening anesthesia with ␤-blocker, and bradycardia was treated with atropine or ephedrine. All patients were returned to the intensive care unit (ICU) intubated. No attempt was made to blind ICU staff to treatment group because a pilot study had previously shown that patients in the EE group became readily apparent. In the ICU, all patients were treated with warm air heaters (Bair Hugger, Model 500/OR Warming Unit, Augustine Medical Inc, Eden Prairie, MN) to ensure normothermia. Cardioactive drugs were continued, and analgesia was given by intravenous morphine infusion as indicated. To support standardization of care in ICU, process flow maps were used to provide guidelines for postoperative management. The key elements of management minimized sedation and encouraged early extubation in both groups. Liberalized extubation criteria were introduced that permitted extubation if certain criteria were satisfied after a trial of continuous positive airway pressure and pressure support. The protocol allowed for a bail-out mechanism in the EE group at any time should the anesthetic, surgical, or ICU course prove difficult. The EE protocol could be abandoned and changed to a high-dose fentanyl technique in the operating room or sedating and maintaining intubation and ventilation should problems occur in the ICU. Patients qualifying for bail-out included patients with hemodynamic instability, with abnormal arterial blood gases or electrolytes, with prolonged CPB (⬎2 hours), or with poor-quality grafts as judged by the surgeon, or patients judged unsuitable for EE for any reason by the anesthesiologist. Within the ICU, sedative and analgesic medications were recorded using a clinical information system (Care Vue 9000, Hewlett-Packard Inc, Andover, MA). The medical management of this trial is the subject of a prior study,6 whereas this focuses on comparison of emotional status between groups. The authors administered a series of psychologic tests to measure emotional status. The Hospital Anxiety and Depression Scale (HAD)7 is a 14-item questionnaire that measures anxious and depressive symptoms on 2 subscales. Scores ⬎10 on either scale indicate moderate-to-severe anxious or depressive symptoms. The HAD is specifically designed to screen physically ill patients and does not require the presence of somatic symptoms to determine the likely presence of a psychiatric disorder. The Self-Assessment Manikin,8,9 which has been used effectively to measure emotional responses in a variety of situations, was used to quantify mood because of ease of administration. Although a computer-driven version is available, the paperand-pencil version was considered more appropriate to the postoperative setting. Ratings were measured on 3 independent affective dimensions of valence (eg, happy/sad), arousal (eg, aroused/calm), and dominance (eg, in control/controlled). The ratings were quantified on a 5-point scale by asking the patient to mark which picture best represented their current state (a 9-point scale was impractical because many patients found it difficult to mark between figures).9 Higher scores indicated

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more positive valence, higher arousal, and greater dominance (ie, feeling in control). The Multiple Affect Adjective Check List–Revised (MAACL-R)10 is a questionnaire that measures anxiety (A), depression (D), hostility (H), positive affect (PA), and sensation seeking (SS). There are 2 summary scores: dysphoria (Dy ⫽ A ⫹ D ⫹ H) and positive affect/sensation seeking (PASS ⫽ PA ⫹ SS). The check list consists of 132 adjectives, and the STATE version, which asks how the patient feels now, was used. Although normative data can be obtained, the authors used raw scores for comparison between groups.10 All tests were administered the day before, the 1st day after, and the 3rd day after surgery by investigators blinded to group allocation under the supervision of a trained psychologist. (The SAM was administered in the ICU on the day of surgery, but because response rates were poor, the data were not analyzed.) The results are expressed as mean and SD for normally distributed variables and as median and range for nonnormally distributed variables. For comparisons between groups, unpaired t-tests, Mann-Whitney U-test, Wilcoxon matched pairs signed-rank test, and chi-squared analysis were used. Analyses were performed with the STATA (Version 5.0, STATA Corp, College Station, TX,) statistical package. RESULTS

Of the 100 consenting randomized patients, 20 were withdrawn from the study. Eight patients were withdrawn before anesthesia was administered. Within each group 2 patients withdrew consent after randomization, 1 patient was withdrawn because documentation did not arrive in the operating room, and another patient was excluded because at the last minute the surgeon decided to use bilateral radial artery grafts (it was thought inappropriate to include the patients in a clinical trial because the surgical technique was relatively new). Of the 12

Table 1. Reasons for Withdrawal From Study Conventional extubation group Returned to operating room for surgical exploration after cardiac tamponade Electively ventilated because of aortic repair at proximal graft site* Electively ventilated because of poor myocardial and respiratory function Electively ventilated because of poor myocardial function and high inotrope requirement Early extubation group Patient hemodynamically unstable post-CPB Protamine reaction Difficulty in hemostasis and low SVR post-CPB Perioperative coagulopathy and cardiogenic shock post-CPB* Hypokalemic VF arrest on return to ICU Prolonged ST depression and high epinephrine requirements post-CPB Surgical difficulties with kinking of grafts Difficulty ventilating during transport to ICU, requiring anesthesia and muscle relaxtion Abbreviations: CPB, cardiopulmonary bypass; SVR, systemic vascular resistance; VF, ventricular fibrillation; ICU, intensive care unit. *Patient subsequently died.

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Table 2. Demographic and surgical data

Age (y) Female/male Weight (kg) Height (cm) Body mass index Duration of surgery (min) CPB time (min) Cross-clamp time (min) Minimum temperature (°C) No. grafts

Conventional Extubation (n ⫽ 42)

Early Extubation (n ⫽ 38)

62 ⫾ 8 10/32 82 ⫾ 16 170 ⫾ 9 28.3 ⫾ 4.0 234 ⫾ 48.7 86.2 ⫾ 28.7 63.6 ⫾ 26.6

62 ⫾ 7 8/30 82 ⫾ 13 170 ⫾ 10 28.5 ⫾ 4.0 230.7 ⫾ 54.1 87.9 ⫾ 21.5 66.3 ⫾ 24.8

35.9 ⫾ 1.3 3.0 ⫾ 1.1

35.9 ⫾ 0.70 3.1 ⫾ 0.9

NOTE. All values expressed as mean ⫾ SD except female-to-male ratio. Abbreviation: CPB, cardiopulmonary bypass.

patients withdrawn after the start of anesthesia, 4 were in the CE group and 8 were in the EE group. The reasons for withdrawal are listed in Table 1. Data from the remaining 38 patients in the EE group and 42 patients in the CE group were analyzed. The demographic data were similar for both groups (Table 2). There were no significant differences between groups in duration of surgery, CPB time, aortic cross-clamp time, minimum temperature, or number of grafts placed. The median time to extubation in group EE was 240 minutes, (range, 30 to 930 minutes; mean, 308 minutes). This time was significantly less than for group CE (p ⫽ 0.001), which had a median time to extubation of 420 minutes (range, 125 to 1140 minutes; mean, 474 minutes). The median length of stay for group EE was 8 days (range, 6 to 32 days) and for group CE was 7 days (range, 6 to 21 days), and there was no significant difference between groups. No comparison was made for length of stay in the ICU because all patients routinely stayed in the ICU until the day after surgery. The total doses of sedatives and analgesics administered in the ICU are shown in Table 3. There was no difference between groups in the use of these drugs. Testing of HAD was completed in 37 patients in group EE and 40 patients in group CE. Testing of SAM and MACL-R was completed in 33 patients in group EE and 36 patients in group CE. The number of patients completing the tests is less than the total analyzed for extubation time because several patients in each group experienced medical complications that made testing difficult, and the remainder were not tested because of logistic difficulties.

Fig 1. The percentage of patients in each group with moderateto-severe depressive symptoms as measured by the Hospital Anxiety and Depression Scale. * p ⴝ 0.02 for between-group comparison on ,, day 3. ■, conventional extubation; ,, ,, , early extubation.

The results of the HAD for depression are shown in Fig 1, and the results for anxiety are shown in Fig 2. There was no difference between groups in the incidence of moderate-tosevere depressive symptoms preoperatively and on day 1 postoperatively. In group CE, 30% (12 patients) displayed moderate-to-severe depressive symptoms on day 3 compared with 8.1% (3 patients) in group EE (p ⫽ 0.02). The 95% confidence interval for the difference in proportion between patients displaying depressive symptoms in each group on day 3 is 0.053 to 0.378. There was no significant difference between or within groups in the incidence of anxiety (p ⬎ 0.05). The results of SAM are represented by median and range because the 5-point scale was not distributed normally (Table 4). No significant differences (p ⬎ 0.05) were observed for group (Mann-Whitney U-test) or for the day of measurement (Wilcoxon matched pairs) for valence, arousal, or dominance.

Table 3. Sedatives and Analgesics Administered in Intensive Care Unit

Morphine (mg) Midazolam (mg) Indomethacin (mg)

Conventional Extubation (n ⫽ 42)

Early Extubation (n ⫽ 38)

0.32 ⫾ 0.1.7 1.19 ⫾ 7.23 16.6 ⫾ 37.7

0.15 ⫾ 0.36 0 36.8 ⫾ 58.9

NOTE. All values expressed as mean ⫾ SD.

Fig 2. The percentage of patients in each group with moderateto-severe anxiety symptoms as measured by the Hospital Anxiety ,, , early extubaand Depression Scale. ■, conventional extubation; ,, ,, tion.

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The MAACL-R state scores are shown in Table 5. The median depression score increased significantly from a preoperative value of 0 to 1 on the 1st postoperative day (Wilcoxon matched pairs; p ⬍ 0.05). No other significant difference was seen either between or within groups. DISCUSSION

Testing of emotional status after cardiac surgery has previously been undertaken in relation to 2 areas. First, tests for depression and anxiety have been performed as an accompaniment of neuropsychologic testing after cardiac surgery because these emotions may influence postoperative cognitive changes.11 Second, emotional changes after cardiac surgery may be a component of adjustment disorders.12 In both cases, postoperative testing has been undertaken no earlier than 5 days after surgery and often many months after the procedure. The testing of emotional status has been of secondary importance to the main investigation of cognitive changes or adjustment disorders. Little attention has been paid to emotional status as an important entity in its own right. The details of the anesthetic technique associated with these studies have not been described, and it is assumed that anesthesia was based on the conventional approach of high-dose opioids and prolonged postoperative ventilation. The introduction of anesthetic and postoperative management techniques aimed at early extubation4,13 has allowed the successful extubation of patients after coronary artery bypass graft surgery with minimal postoperative ventilation. Prompted by the apparent alertness of such patients in pilot studies, the authors undertook a comparison of emotional status with a group of patients undergoing conventional management. Because this was an efficacy study, only the results of patients remaining in the study were compared. A potential source of bias may have arisen because the nursing staff in the ICU were not blinded to treatment allocation because it had been found in pilot studies that patient group became obvious soon after admission. In an attempt to overcome this bias, the assessments were carried out by an investigator blinded to group allocation. Applying psychologic tests after major surgery is a challenge. Patients may not have the concentration or ability to perform tests that are administered in the ambulatory setting. As a result, tests were chosen that made minimal demands on patients. The authors previously used SAM and HAD after major surgery.14 The MAACL-R has been used to examine postoperative mood alterations following anesthesia after minor surgery.15 In the present study, the MAACL-R score showed a small (0 to 1) but significant increase in depression score on the 1st postoperative day within both groups. The

small magnitude of this change renders it unlikely to reflect clinically significant phenomena. Apart from this, the SAM and the MAACL-R were unable to detect any changes in valence or mood within or between groups. In contrast, the HAD scores showed a strong tendancy for fewer patients to be depressed on day 3 within the EE group. The difference from the CE group is large enough to suggest that early extubation may be associated with fewer depressive symptoms than conventional anesthesia. One important matter to address is the different pattern of results obtained for ratings of mood, using the SAM and the MACCL-R, and the ratings of depressive symptoms obtained by the HAD. Usually ratings of depressed mood (as indicated by low valence on the SAM and the dysphoria or depression scales of the MACCL-R) would be expected to covary with ratings of depressive symptom severity as measured by the HAD.16 In this case, however, the 2 forms of measurement may be tapping into fundamentally different components of the depression construct. Research has asserted that there are 2 independent components of mood known as negative affect and positive affect.17 Negative affect includes such moods as sadness, anger, guilt, and fear; whereas positive affect includes pleasurable moods such as excitement, interest, joy, and pride.16 Although negative affect, or emotional distress, can be elevated in a wide range of psychopathologic conditions (including depression), low levels of positive affect are a distinctive feature of depressed states.18,19 Examination of the depression items on the HAD reveals that they exclusively deal with the low positive affect, or anhedonic, aspect of depression (eg, “I still enjoy things the way I used to”; “I look forward with enjoyment to things”). Previous research has revealed the HAD depression scale to be distinctively associated with measures of anhedonic depression,20 whereas the MAACL-R depression scale includes items that load on both positive affect and negative affect.21 This analysis suggests that it is chiefly anhedonia, or the loss of positive affect, that is greater in the CE group. It has been asserted that mood disorders of this type are more likely to be biologic in origin,7 and may result from the lingering effects of anesthetic agents. The absence of depressive symptoms in both groups on the 1st postoperative day contrasts with the observations on day 3 and may be related to continued drug effects, especially opioids and sedatives. Elevated scores on a depression symptom rating scale such as the HAD are not synonymous with case-level clinical depression. A study by Coyne and Schwenk22 showed that selfreported distress and case-level depression are not identical constructs, especially in nonpsychiatric populations. The 30% incidence of moderate-to-severe depression in the CE group compares with 28% in chronic pain clinic patients

Table 4. Self-Assessment Manikin Scores Conventional Extubation Group (n ⫽ 36)

Valence Arousal Dominance

Early Extubation Group (n ⫽ 33)

Preoperative

Day 1

Day 3

Preoperative

Day 1

Day 3

2(1-5) 3(1-5) 4(1-5)

2(1-5) 4(1-5) 4(1-5)

2(1-4) 4(2-5) 4(1-5)

2(1-3) 3(1-5) 4(2-5)

3(1-4) 4(0-5) 4(1-5)

3(1-5) 4(1-5) 4(1-5)

NOTE. All values expressed as median (range).

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Table 5. Multiple-Affect Adjective Check List–Revised Conventional Extubation Group (n ⫽ 36)

Anxiety Depression Hostility Positive affect Sensation seeking Dysphoria Positive affect/sensation seeking

Preoperative

Day 1

Day 3

0(1-9) 0(0-20) 0(0-6) 8(1-21) 2(0-9) 1.5(0-16) 10(1-29)

1(0-9) 1(0-9)* 0(0-8) 10(0-21) 3(0-9) 3(0-25) 11(0-30)

1(0-9) 0(0-8) 0(0-12) 6(0-21) 1(0-8) 1(0-29) 7(0-29)

Early Extubation Group (n ⫽ 33) Preoperative

1(0-9) 0(0-3) 0(0-5) 8(0-21) 1(0-9) 1(0-16) 10(0-30)

Day 1

Day 3

1(0-9) 1(0-6)* 0(0-7) 12(0-21) 2(0-9) 1(0-22) 15(0-28)

0(0-9) 0(0-9) 0(0-4) 9(0-21) 1(0-9) 1(0-20) 10(0-29)

NOTE. All values expressed as median (range). *p ⬍ 0.05 compared with preoperative value within each group.

and 31% of cancer patients,23 and is ⬎13% reported by Zigmond and Snaith24 for medical outpatients. Underwood et al25 previously reported a preoperative anxiety rate of 28% and depression rate of 47% in patients awaiting cardiac surgery and correlated such findings with a series of influencing factors. The preoperative scores in the present series indicate a different patient population. The preoperative scores show similarity between patients in each group, highlighting the difference in the rate of depressive symptoms in the CE group on the 3rd postoperative day. It is interesting to speculate on the cause for the difference in the rate of depression between groups. It is unlikely that fentanyl is still present in the plasma 3 days after a dose of 50 ␮g/kg. The high concentration of fentanyl may have in some way altered opioid receptor sensitivity or regulation, however, resulting in a prolonged effect on mood. Alternatively, propofol has been reported to alter mood15 and may be responsible for decreasing the incidence of depression. (One way to verify this theory would be to use isoflurane as the anesthetic agent for early extubation). A further expla-

nation may involve the more rapid mobilization and return to activity of the EE group. The sedative and analgesics administered in the ICU are unlikely to play a part because doses were small and did not differ between groups. Accurate data on drugs administered during the first 3 postoperative days were not collected prospectively, but there is no reason to believe these data differed between groups or influenced the rates of depression. In conclusion, a range of tests to explore the early postoperative mood of patients after early extubation indicates that there is little difference in most measurements of affect when compared with conventional anesthesia. There is some evidence, however, that depressive symptoms may be decreased on the 3rd postoperative day. This observation warrants further exploration. It suggests that there may be more benefit to the application of an early extubation approach than safety4 or theoretic physiology.26 The relationship of anesthetic technique to long-term effects on mood requires further study.

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22. Coyne J, Schwenk T: The relationship of distress to mood disturbance in primary care and pychiatric populations. J Consult Clin Psychol 65:161-168, 1997 23. Jack TM, Walker VA, Moreley SJ, et al: Depression, anxiety and chronic pain. Anesthesia 42:1235, 1987 24. Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Scand 67:361-370, 1983 25. Underwood MJ, Firmin RK, Jehu D: Aspects of psychological and social morbidity in patients awaiting coronary artery bypass. Br Heart J 69:382-384, 1993 26. Higgins T: Early endotracheal extubation is preferable to late extubation in patients following coronary artery surgery. Cardiothorac Vasc Anesth 6:488-493, 1992