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J Thorac Cardiovasc Surg 2004;127:57-64
© 2004 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

Predictors of delirium after cardiac surgery delirium: Effect of beating-heart (off-pump) surgery

^a Department of Cardiac Surgery, Heart Center, University of Leipzig, Leipzig, Germany

Received for publication December 31, 2002; revisions received June 10, 2003; accepted for publication July 14, 2003.

^* Address for reprints: Jan Bucerius, MD, University of Leipzig, Heart Center, Department of Cardiac Surgery, Strümpellstr. 39, D-04289 Leipzig, Germany
bucerj{at}medizin.uni-leipzig.de

	Abstract

Top Abstract Methods Results Discussion Conclusions Appendix 1 References

 
BACKGROUND: Despite improved outcomes after cardiac operations, postoperative delirium remains a common complication that is associated with increased morbidity and prolonged hospital stay.

METHODS: Univariate and multivariate predictors of postoperative delirium were determined from prospectively gathered data on 16,184 patients undergoing cardiac operations with cardiopulmonary bypass (conventional, n = 14,342) and without cardiopulmonary bypass (beating-heart surgery, n = 1847) between April 1996 and August 2001. Delirium was defined as a transient mental syndrome of acute onset characterized by global impairment of cognitive functions, a reduced level of consciousness, attentional abnormalities, increased or decreased psychomotor activity, and a disordered sleep-wake cycle.

RESULTS: The overall prevalence of postoperative delirium was 8.4%. Of 49 selected patient-related risk factors and treatment variables, 35 were highly associated with postoperative delirium by univariate analysis. Stepwise logistic regression revealed the following variables as independent predictors of delirium: history of cerebrovascular disease, peripheral vascular disease, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction of 30% or less, preoperative cardiogenic shock, urgent operation, intraoperative hemofiltration, operation time of 3 hours or more, and a high perioperative transfusion requirement. Two variables were identified as having a significant protective effect against postoperative delirium: beating-heart surgery and younger patient age.

CONCLUSIONS: Postoperative delirium is a common complication in cardiac operations. The increased use of beating-heart surgery without cardiopulmonary bypass may lead to a lower prevalence of this complication and thus improve patient outcomes.

Neuropsychological and psychiatric disorders after cardiac operations have been well described since the 1950s and continue to be a subject of active research.³ In contrast to relatively uncommon major neurologic complications, such as stroke, neuropsychological impairment is a common problem after cardiac operations; most studies report a prevalence of approximately 30%.^2,4,5,6 However, the etiology and pathogenesis of cognitive impairment and delirium remain unknown. Many preoperative, intraoperative, and postoperative variables have been described as risk factors for these complications, but their exact etiologic roles have yet to be determined.

Many investigators have focused on the deleterious effects of cardiopulmonary bypass (CPB) on postoperative cognitive function. A recent development in cardiac surgery is the ability to perform operations, particularly coronary bypass surgery, without the use of CPB (so-called beating-heart [BH] surgery). Several studies have compared postoperative cognitive outcomes in patients undergoing BH surgery with those in patients undergoing conventional procedures with CPB, but results have been inconclusive.^7-13 Differences in the definition of neuropsychological impairment between studies may explain some of the discrepant results.¹⁴

The purpose of this study was to identify risk factors for post–cardiac surgery delirium in a large number of patients from a single institution. In addition, we attempted to evaluate the effect of BH surgery without CPB on postoperative delirium.

	Methods

Top Abstract Methods Results Discussion Conclusions Appendix 1 References

 
Study population
A total of 16,184 consecutive adult patients underwent heart operations between April 1996 and August 2001 at the Leipzig Heart Center. To assess the effects of CPB on postoperative delirium, patients were divided into groups on the basis of the type of operation performed. Coronary artery bypass grafting (CABG) with CPB was performed in 8917 patients (CABG-CPB). For the purposes of this study, patients undergoing coronary bypass grafting with CPB support, but without cardioplegic arrest, were still considered part of the CABG-CPB group. CABG without CPB (BH), either through a median sternotomy (n = 765) or through a left lateral minithoracotomy (n = 1077), was performed in 1842 patients. Although most of these BH procedures were performed by 4 of our surgeons, all surgeons performed at least some of these operations. A third group of patients consisted of those undergoing cardiac valvular operations or combined CABG plus valvular operations (n = 5425). Patients undergoing replacement of the ascending aorta (n = 255) were also included in this group. All operations for this third group of patients were performed by using CPB and involved the opening of cardiac chambers (VALVE-CPB).

CPB was performed according to a standard protocol. The systemic body temperature was cooled to 32°C, mean arterial pressure was kept >60 mm Hg, and blood flow was maintained at 2.4 L · min-1 · m^-2 body surface area during CPB. Proximal coronary bypass anastomoses were performed with a single aortic crossclamp technique (since 1999) in the CABG-CPB group and with a side-clamp technique in the BH group. Cardiotomy suction and administration of aprotinin were routinely used in all patients. We did not use coated oxygenators or tubing.

Definition of postoperative delirium
In accordance with the American Psychiatric Association guidelines, postoperative delirium was defined as a transient mental syndrome of acute onset characterized by global impairment of cognitive functions, a reduced level of consciousness, attentional abnormalities, increased or decreased psychomotor activity, and a disordered sleep-wake cycle.^15,16 The diagnosis of delirium was made by physicians involved in the daily clinical care of patients and was most frequently made while patients were in the intensive care unit. Patients with prolonged delirium or focal neurologic signs underwent computed tomography of the brain to look for evidence of stroke.¹⁷ Stroke patients with delirium were included in the study cohort.

Data collection
Perioperative data were recorded prospectively by using an online database system as previously described (Medwork database software; Lenz + Partner GmbH, Dortmund, Germany).¹⁸ All variables analyzed were entered by clinicians in a prospective fashion to accomplish a complete data set for each patient. Data quality was routinely assessed and verified by the generation of text documents that became the patient's chart during the hospital stay. Preoperative and intraoperative variables that were assessed as possible predictors of delirium are listed in Appendix 1. Postoperative variables were not analyzed as possible risk factors of delirium.

Statistical analysis
Continuous variables are expressed as mean ± SD, and categorical data are expressed as proportions throughout the article. Comparisons of continuous variables between patients with and without postoperative delirium were performed with the Student unpaired t test or analysis of variance, with the appropriate correction for multiple comparisons. Categorical variables were compared by ² analysis. Univariate analyses of risk factors for delirium were performed by calculating odds ratios (OR) with 95% confidence intervals. All P values were 2 tailed. Variables with a P value < .05 were subjected to a multivariate logistic regression model to determine the risk-adjusted predictors of delirium by using a backward (Wald) stepwise procedure. A P value of <.05 was used to enter and eliminate variables.¹⁹ All statistical analyses were performed with the SPSS statistical package version 9.0 (SPSS Inc, Chicago, Ill).

	Results

Top Abstract Methods Results Discussion Conclusions Appendix 1 References

 
Baseline preoperative patient characteristics for the different surgical groups are shown in Table 1. Patients older than 70 years constituted 32.5% of the population, and 3.6% were 80 years of age or older. Most patients were male, and 3.6% of the study population had a history of cerebrovascular disease.

Patients in the CABG-CPB group had a higher prevalence of Canadian Cardiovascular Society classification 3 or greater and received more coronary bypass grafts than patients in the BH group (P < .0001 and P = .01, respectively). The prevalence of New York Heart Association (NYHA) class III or greater symptomatology was highest in the CABG-CPB group (P < .0001 compared with the other groups) and was higher in the VALVE-CPB group than in the BH group (P < .0001; Table 1).

The overall prevalence of postoperative delirium was 8.4% (n = 1354). Of these patients, 219 (16.2%) also had a diagnosis of perioperative stroke. The prevalence of delirium varied among the 3 surgical groups as shown in Figure 1. Postoperative delirium was significantly (P < .0001) less likely to occur in BH patients compared with the other 2 surgical groups. The prevalence of postoperative delirium in all patients 70 years of age was 12.9%, with significant differences among the 3 surgical groups (CABG-CPB, 11.9%; BH, 5.1%; VALVE-CPB, 16.4%; P < .001).

View larger version (16K): [in this window] [in a new window]   Figure 1. Prevalence of postoperative delirium according to the type of cardiac surgical procedure. CABG-CPB, Coronary artery bypass grafting with cardiopulmonary bypass; BH, beating heart surgery; VALVE-CPB, valvular surgery with or without coronary artery bypass grafting with cardiopulmonary bypass. #P < .0001 versus CABG-CPB and VALVE-CPB. P < .0001 versus CABG-CPB.

Univariate analysis revealed that 35 of 49 recorded preoperative and intraoperative variables had a significant association with postoperative delirium (Appendix 1, bold). Significant variables were consecutively subjected to a stepwise logistic regression analysis. Ten variables were identified as independent predictors of postoperative delirium, and 2 variables were associated with a significantly lower prevalence of delirium (Table 2). Of particular note was that operation without CPB had a protective effect against delirium in this risk-adjusted analysis. The prevalence of perioperative independent predictors of delirium and statistically significant differences regarding these predictors among the 3 groups are shown in Table 3.

	Discussion

Top Abstract Methods Results Discussion Conclusions Appendix 1 References

The diagnosis of delirium is currently made with clinical assessment,^15,16 in contrast to postoperative neuropsychological impairment, which is diagnosed with neuropsychological tests and usually is part of a research protocol.^4,14,20 The definition of delirium chosen in this series is the same as that recommended by the American Psychiatric Association and is readily applicable by clinicians involved in the daily postoperative care of cardiac surgery patients. The symptoms of delirium—in particular, confusion—make neuropsychological testing impractical in this patient population. Postoperative delirium may represent a more severe form of neurologic injury than neuropsychological impairment, a complication that is known to be very common after cardiac surgery.^4,7,14,20

The prevalence of postoperative delirium in our study varied among the different surgical procedures. Patients undergoing valve or combined valve and CABG operations had postoperative delirium more often than patients undergoing isolated CABG operations, a finding that has been previously described.²¹ The reason for this observation is unknown but may be related to embolization of air that is trapped within cardiac chambers during VALVE procedures.²²

The cause of post–cardiac surgery delirium is unknown and is probably multifactorial in origin.¹⁵ Most patients with delirium have this complication shortly after awakening from anesthesia,^23,24 and this suggests that intraoperative factors play a major role in the pathogenesis. It is for this reason that we did not include postoperative variables in our analysis of predictors of delirium.

A history of cerebrovascular disease was one of the strongest predictors of delirium in this series, with an OR of 2.15. The increased risk may be explained by the existence of atherosclerosis within the cerebrovascular system, particularly of the carotid arteries.^4,25 Generalized atherosclerosis increases the risk of cerebral embolization, particularly during intraoperative aortic manipulation.²⁶ The finding of diabetes (OR, 1.30) and peripheral vascular disease (OR, 1.34) as independent predictors of delirium may also be a result of their close association with atherosclerotic disease burden.

Previous investigators have observed an association between severity of underlying cardiac disease and postoperative delirium. Heller and associates²⁷ described an increasing prevalence of postoperative delirium with increasing NYHA heart failure classification. Similarly, we found impaired left ventricular ejection fraction (OR, 1.23) and preoperative cardiogenic shock (OR, 1.24) to be independent predictors of delirium. Urgent surgery was also a predictor of delirium (OR, 1.16); this risk factor is a marker of the severity of underlying cardiac pathology.

Preoperative history of atrial fibrillation was an independent predictor of postoperative delirium (OR, 1.35) in this study, possibly because of its widely recognized association with thromboembolization. Several previous investigators have described an association between cerebral embolization during cardiac operations and postoperative neurobehavioral deficits.^20,26,28-30

Prolonged duration of surgery (OR, 1.29) and intraoperative hemofiltration (OR, 1.24) are indicators of increased operative complexity, a factor that has been previously shown to influence postoperative neurologic outcomes.⁵ In addition, prolonged operations involve longer CPB times, another risk factor for neurologic complications.^2,25,31 The effect of prolonged anesthetic time on postoperative delirium is controversial; some investigators report a significant association, and others describe no correlation.³² It is interesting to note that a similar proportion of CABG-CPB and BH patients had a prolonged surgical procedure (Table 3), yet the prevalence of delirium was significantly lower in the BH group. Part of this difference may be related to the avoidance of CPB in the BH group.

A high transfusion requirement was a strong predictor of postoperative delirium (OR, 3.12). However, our database is unable to distinguish between intraoperative and postoperative transfusion administration. Increased transfusion requirement may have therefore partially reflected postoperative complications, making interpretation of this predictor difficult.

Advanced age is one of the most commonly reported independent predictors of postoperative delirium,^25,33,34 probably because of its close association with the atherosclerotic disease process. Approximately one third of our patient population was older than 70 years of age, and our data confirmed that such patients are at increased risk for delirium (Table 2; Appendix 1).

The beneficial effect of BH surgery (OR, 0.14) on the prevalence of postoperative delirium in this series may be due to avoiding the deleterious effects of CPB, as already stated. CPB may lead to a higher prevalence of postoperative delirium because of hypotensive periods during CPB and nonpulsatile blood flow.³⁵ In addition, the risk of gaseous and particulate cerebral embolization, a widely recognized problem during CPB, is avoided in BH surgery.^7,20,28-30 Furthermore, the lower prevalence of delirium in the BH group may be explained by the avoidance of ascending aortic cannulation and the subsequent risk of atherosclerotic embolization. Indeed, aortic manipulation is avoided altogether in those BH patients who undergo minimally invasive direct CABG (MIDCAB).

Preoperative patient characteristics in the BH group revealed a younger mean age and higher left ventricular ejection fraction than in the CABG-CPB group. Furthermore, the number of CABGs was significantly lower than in the CABG-CPB group. This finding was expected, however, given that the BH group was composed of patients who underwent both off-pump CABG for 1 or more bypass grafts and minimally invasive direct CABG for single bypass grafting (that is, left internal thoracic artery to the left anterior descending coronary artery). In addition, the prevalence of severe clinical symptoms (NYHA classification of III or higher and Canadian Cardiovascular Society classification 3) was significantly higher in the CABG-CPB group compared with the BH group.

This study has several limitations. Because of the retrospective design of our study and the lack of randomization, selection bias may have accounted for some of the observed differences in delirium among surgical groups. That is, lower-risk patients may have been selected to undergo BH surgery. The possibility of selection bias, as for all nonrandomized studies, is the main limitation of our study. However, it is important to note that the BH group did not have the lowest prevalence of all independent predictors of delirium (Table 3). In addition, multivariate logistic regression analysis revealed that BH surgery was associated with a lower risk of delirium, even after other risk factors were accounted for. We therefore believe that BH surgery, with subsequent avoidance of CPB and minimization of aortic manipulation, may lead to a lower risk of postoperative delirium. Recently published series comparing postoperative neurocognitive outcome in patients undergoing on- and off-pump coronary bypass operations have confirmed our findings of better results with off-pump CABG.^11-13

Another limitation of this study is the fact that the clinicians who were responsible for making the diagnosis of delirium were not blinded to surgical group status. However, a very large number of clinicians were involved in the diagnosis of delirium, and most had no vested interest in the outcome of our study. Another limitation is that the large number of clinicians involved in our study increases the chance that the diagnosis of delirium was not always consistent from patient to patient. However, the large number of clinicians also increases the generalizability of our findings. Furthermore, independent neurologists were often consulted to confirm the diagnosis of delirium. We therefore believe that our results are relatively unbiased, generalizable, and valid.

	Conclusions

Top Abstract Methods Results Discussion Conclusions Appendix 1 References

 
Postoperative delirium is a common complication after cardiac surgical procedures. Since delirium and other neurologic complications are associated with increased morbidity and resource utilization, it is important to identify their independent predictors. BH surgery without CPB seems to be associated with a decreased risk of postoperative delirium and should be considered as one of the strategies for minimizing cerebral injury during cardiac operations.

	Appendix 1

Top Abstract Methods Results Discussion Conclusions Appendix 1 References

 

Perioperative variables analyzed by univariate analysis: factors that had a statistically significant association with delirium are printed in bold

Variable Prevalence, % (n) P value Patients with delirium (n = 1354) Patients without delirium (n = 14,830) Preoperative variables Age Age < 50 years 2.7% (37) 9.4% (1392) <.0001 Age 50 < 60 years 7.6% (103) 17.5% (2589) <.0001 Age 60 < 70 years 33.9% (459) 38.7% (5746) <.0001 Age 70 < 80 years 48.9% (663) 30.9% (4595) <.0001 Age 80 years 6.8% (92) 3.4% (508) <.0001 Sex (Male) 73.4% (994) 71.0% (10,528) .06 History of syncope 12.3% (167) 9.7% (1444) .002 History of embolism 4.7% (64) 3.1% (455) .002 History of cardiogenic shock 21.0% (285) 10.9% (1622) <.0001 Diabetes mellitus (glucose intolerance treated with diet, oral hypoglycemics, or insulin) 42.5% (576) 32.5% (4817) <.0001 Hyperlipidemia 43.2% (585) 46.5% (6901) .021 Arterial hypertension (patient taking antihypertensive medication before surgery) 70.7% (957) 67.5% (10,017) .017 History of renal disease (history of renal failure or pathologic increased serum creatinine treated medically without hemofiltration and/or dialysis) 8.6% (117) 3.9% (588) <.0001 Dialysis-dependent renal insufficiency 0.7% (10) 0.7% (103) .864 Preoperative infection (infectious disease, including endocarditis) 3.6% (49) 1.9% (290) <.0001 History of cerebrovascular disease (including stroke, TIA, and PRIND) 8.5% (115) 3.2% (474) <.0001 NYHA III 81.7% (1106) 77.3% (11,465) <.0001 LVEF 30% (assessed by angiography or 2-dimensional echocardiography) 14.5% (196) 8.7% (1295) <.0001 History of peripheral vascular disease 29.4% (398) 19.1% (2831) <.0001 Atrial fibrillation (history of preoperative atrial fibrillation) 15.8% (214) 8.5% (1259) <.0001 Urgent operation 35.0% (474) 22.6% (3358) <.0001 History of pulmonary disease (chronic pathologic pulmonary function test) 9.2% (124) 6.7% (995) .001 Prior myocardial infarction 43.3% (586) 42.4% (6290) .565 Emergency surgery (emergency surgery due to complications during coronary angiography and/or PTCA) 0.9% (12) 0.6% (89) .204 CCS 3 34.4% (466) 32.8% (4861) .227 Prior cardiac surgery 6.3% (85) 5.3% (784) .13 Prior CABG 3.8% (52) 3.3% (482) .234 Prior surgery for aortic aneurysm 0.1% (2) 0.3% (50) .319 Prior aortic valve surgery 0.7% (9) 1.0% (153) .252 Prior mitral valve surgery 1.5% (20) 0.9% (144) .087 Intraoperative variables Duration of surgery 3 h 29.3% (397) 20.9% (3094) <.0001 Total CPB time 2 h 21.9% (297) 12.6% (1875) <.0001 Ischemic time 1 h 30.4% (411) 21.3% (3163) <.0001 Intraoperative hemofiltration 16.9% (229) 9.5% (1409) <.0001 Intraoperative hypothermia <32°C 46.9% (635) 36.4% (5405) <.0001 Intraoperative RBC transfusion 1000 mL 6.1% (83) 2.5% (377) <.0001 Intraoperative low cardiac output 3.6% (49) 2.1% (3011) .001 Intraoperative IABP 3.0% (41) 1.9% (280) .006 Intraoperative need for pacemaker stimulation 28.9% (392) 20.0% (2972) <.0001 Use of cardioplegia 81.5% (1103) 77.1% (11,435) <.0001 BH 3.2% (43) 12.1% (1799) <.0001 OPCAB 2.4% (32) 4.9% (733) <.0001 MIDCAB 0.8% (11) 7.2% (1066) <.0001 CABG-CPB 52.4% (706) 57.1% (8211) .024 VALVE-CPB 44.7% (605) 32.5% (4820) <.0001 Valve surgery 44.6% (604) 32.5% (4821) <.0001 Combined surgery (CABG and valvular surgery, ascending aortic surgery, and/or other procedures) 25% (338) 14.6% (2168) <.0001 Double valve surgery 3.9% (53) 2.2% (328) <.0001 OPCAB—conversion to CABG with cardiopulmonary bypass 0.07% (1) 0.2% (30) .513 Aortic valve and/or ascending aortic surgery 12.0% (163) 11.2% (1667) .37 Mitral valve surgery 3.8% (51) 4.4% (657) .714 Intraoperative blood loss 500 mL 1.0% (14) 0.6% (88) .069 Perioperative variables Perioperative RBC transfusion 2000 mL 30.4% (411) 8.5% (1254) <.0001

CABG-CPB, Coronary artery bypass grafting with cardiopulmonary bypass; BH, beating heart surgery; VALVE-CPB, valvular with cardiopulmonary bypass with or without coronary artery bypass grafting; CABG, coronary artery bypass grafting; OPCAB, off-pump coronary artery bypass grafting; MIDCAB, minimally invasive direct coronary artery bypass grafting; RBC, red blood cells; LVEF, left ventricular ejection fraction; PTCA, percutaneous transcoronary angioplasty; CPB, cardiopulmonary bypass; IABP, intra-aortic balloon pump; TIA, transient ischemic attack; PRIND, prolonged reversible ischemic neurologic deficit; NYHA, New York Heart Association heart failure classification; CCS, Canadian Cardiovascular Society angina classification.

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