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Eur J Cardiothorac Surg 2006;30:140-147
© 2006 Elsevier Science NL
a GGZ Delfland, Institute of Mental Health, P.O. Box 5016, 2600 GA Delft, The Netherlands
b Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
c Department of Anesthesia and Intensive Care, Amphia Hospital, Breda, The Netherlands
Received 6 February 2006; received in revised form 28 March 2006; accepted 30 March 2006.
* Corresponding author. Tel.: +31 15 2607607; fax: +31 15 2607785. (Email: giltay{at}dds.nl).
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Abstract |
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 Top Abstract 1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Key Words: Psychosis • Delirium • Epidemiology • Cardiac surgery • Mortality
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1. Introduction |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Delirium is a frequent complication after cardiac surgery. The reported rate of delirium increases with aging [6,10–12], whereas the indications for cardiac surgery are determined by coronary atherosclerosis that is also age-related. Moreover, the age of patients undergoing cardiac operation is increasing [13,14]. In earlier studies with varied methodology and mixed populations, the incidence of delirium after cardiac surgery was approximately 32% [15], and, in more recent studies, the incidence varied between 8 and 23% [6,16,17].
The subgroup (24–58%) of delirious patients who have pronounced psychotic symptoms (i.e., hallucinations and delusions) [2,15,17–19] may be recognized more promptly than delirium by non-psychiatric clinicians. Several prospective cohort studies have identified the incidence and precipitating factors of delirium, but precipitants of psychotic symptoms remain largely unknown. Therefore, our aim was to study predictors of psychotic symptoms and their relationship with adverse outcomes in cardiac surgery patients, and to compare those with the predictors and adverse outcomes associated with delirium (with and without psychotic symptoms).
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2. Materials and methods |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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All 8139 patients who underwent a coronary artery bypass grafting (CABG) and/or heart valve operation between January 1999 and July 2004 were included in the present study. Our anesthetic protocol consisted of induction of anesthesia with the combination of sufentanil (an opioid agent), pancuronium (a muscle relaxant), and either midazolam, or etomidate, or both combined (both being hypnotic agents). This was followed by maintenance of anesthesia using a continuous infusion of sufentanil, combined with either midazolam, sevoflurane (an inhalation anesthetic), or propofol (an intravenous anesthestic). Except for patients undergoing beating heart surgery, cardiopulmonary bypass was established with arterial inflow through the ascending aorta and venous drainage through the right atrium or caval veins. The pump flow rates were maintained between 2.0 and 2.5 L min–1 m–2 as a function of temperature. Mean arterial pressure was aimed at values of at least 60 mmHg. To induce light to moderate systemic hypothermia, the systemic body temperature was lowered between 28 and 34 °C with active rewarming to 36.5 °C at the end of cardiopulmonary bypass surgery.
2.2 Outcome variable and determinants
The primary outcome variable was either the presence or absence of psychotic symptoms (i.e., hallucinations and/or delusions), which was established after cardiac surgery. This was scored as one item in the database till discharge, and assessed by several different physicians working on the general cardiology ward and intensive cardiology care unit. Like in previous studies, a distinction was made between predisposing factors (that may have made the patient more susceptible) and precipitating factors (that may represent a direct somatic cause). Thus, we collected data on three clusters of variables pertaining to (1) preoperative predisposing factors, (2) per- and postoperative precipitating factors, and (3) adverse outcomes.
First, preoperative predisposing factors included demographic variables, general comorbidity, and cardiovascular comorbidity. Demographic variables were age (categorized into <60 years old, 60–70 years old, 
70 years old), sex, and body mass index (<24.9 kg/m2, 25–30 kg/m2, 30 kg/m2). General morbidity variables consisted of active smoking (i.e., smoking during the week preoperatively), chronic obstructive pulmonary disease (COPD, defined as a history of COPD with active treatment), preoperative renal dysfunction (creatinine level < 100 µmol/L, 100–150 µmol/L, 150 µmol/L), dialysis, diabetes mellitus (defined as diabetes mellitus with active treatment with insulin or oral antidiabetica, either type I or II), hemoglobin level (8.0 mmol/L, 7.0–8.0 mmol/L, <7.0 mmol/L). Cardiovascular comorbidity variables consisted of hypertension (blood pressure above 160 systolic, above 90 mmHg diastolic, and/or active treatment for hypertension), history of peripheral vascular disease, history of transient ischemic attack or cerebrovascular accident, history of recent myocardial infarction (no infarction/interval between infarction and cardiothoracic intervention more than 4 week/interval less than 4 weeks ago), cardiac surgery or prior percutaneous coronary intervention (PCI), cardiac arrhythmia, dyspnoea according to the New York Heart Association (NYHA) classification, ejection fraction (good 50%/moderate 25–50%/poor <25%), and left ventricle hypertrophy (diastolic left ventricular wall thickness >1.0 cm on pre- or postoperative echocardiography).
Second, data on per- and postoperative precipitating factors were collected. Since January 2001 information on vital signs and laboratory values during the first 24 h on the intensive care unit was also collected. For 4942 (60.7%) of 8139 patients we had complete data on all these factors, which consisted of the following data: performance of beating heart surgery, performance of a combined CABG and valve operation, minimal nasopharyngeal temperature during surgery (33.0 °C/31.0–33.0 °C/<31 °C), highest heart rate, lowest mean arterial pressure, duration of assisted respiration (0–1 days/2–3 days/4 days), lowest partial pressure of oxygen (11 kPa/9–11 kPa/<9 kPa), fractional O2 during this lowest partial pressure of oxygen (21–40%/40–50%/50–100%), partial pressure of carbon dioxide during this lowest partial pressure of oxygen (4.7–5.9 kPa/<4.7 kPa/5.9 kPa), lowest platelet count (150 mm–2/100–150 mm–2/<100 mm–2), lowest hematocrit (30%/25–30%/<25%), lowest (<3.5 mmol/L) and highest (5.0 mmol/L) potassium levels, lowest (<135 mmol/L) and highest (145 mmol/L) sodium levels, highest creatinine level (<100 µmol/L/100–150 µmol/L/150 µmol/L), highest urea nitrogen level (<7 mmol/L/7.0–9.0 mmol/L/9 mmol/L) and lowest 8-hour urine excretion to assess oliguria (500 mL/300–500 mL/<300 mL), major infection (absent/bacterial infection or sepsis), and neurological morbidity (absent/transient ischemic attack, cerebrovascular accident, or coma).
Third, adverse outcome variables consisted of the length of stay on the intensive care unit (0–3 days/4–6 days/7 days), multi-organ failure or shock, cardiopulmonary resuscitation, and in-hospital death after surgery (defined as death during hospitalization in the Amphia hospital or in one of the affiliated hospitals).
2.3 Statistical analysis
In 8011 of 8139 patients (98%) we had complete data on all preoperative predisposing factors, and in 4907 of 4942 patients (99%) we had complete data on all per- and postoperative precipitating factors. In those patients with some missing values we replaced missing values in categorical variables with the most prevalent value. Patients with and without psychotic symptoms were compared using t tests for independent samples, Mann–Whitney tests for independent samples, or chi-square tests, as appropriate. We assessed univariate relations between the potential predictor variables and psychotic symptoms (i.e., dichotomous variable) by calculating odds ratios and 95% confidence intervals (CI) for all individual variables. We used forward conditional logistic regression analysis for developing predicting models to investigate which of the (1) preoperative predisposing factors and (2) per- and postoperative precipitating factors independently predicted psychotic symptoms with a P-value of 0.05 for entry and 0.10 for removal. The Hosmer–Lemeshow goodness-of-fit test was used to assess the overall fit of these logistic regression models. Finally, we calculated adjusted odds ratios for adverse outcomes in relation to psychotic symptoms by multivariate logistic regression analysis, while age or age creatinine level, dialysis, dyspnoea, ejection fraction, and left ventricular hypertrophy were entered into the model. A two-tailed P
< 0.05 was considered statistically significant. The software used was SPSS 10.0 (Statistical Package for Social Sciences).
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3. Results |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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As univariate predictors, we found that the following variables were statistically significant predictors of psychotic symptoms: high age, presence of COPD, high preoperative creatinine level, history of dialysis, low preoperative hemoglobin level, presence of peripheral vascular disease, cerebrovascular disease, cardiac arrhythmia, presence of dyspnoea, low ejection fraction, and left ventricle hypertrophy. In a multivariate logistic model we found that high age, high preoperative creatinine level, dyspnoea, heart failure, and left ventricle hypertrophy were independent preoperative predisposing factors (Table 1 ).
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3.3 Adverse outcomes
Patients with psychotic symptoms stayed for 6.1 (SD 8.0; interquartile range 1–7) days on the intensive care unit versus 1.8 (SD 3.5; interquartile range 1–2) days for controls (P
< 0.001; Table 3
). Compared with patients without psychotic symptoms, those who developed psychotic symptoms spent a median 3 days longer on the intensive care unit. Multi-organ failure and/or shock were found in 21% (n
= 36) of patients with psychotic symptoms as compared to 5% (n
= 400) of patients without psychotic symptoms. Cardiopulmonary resuscitation was required in 11% (n
= 18) of patients with psychotic symptoms as compared to 2% (n
= 184) of patients without psychotic symptoms. A total of 160 of the 8139 patients (2.0%) died during hospitalization, and 12 (5.6%) of whom had psychotic symptoms (Table 3). The causes of death were 5 from a cardiac cause (42%), 1 from a neurological cause (8%), 1 from an infection (8%), 3 from a respiratory cause (25%), 1 from multi-organ failure (8%), and 1 from an unknown cause (8%).
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4. Discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Our findings indicate that the causes of psychotic symptoms are multifactorial in origin similar to delirium as such, and that the development of psychotic symptoms involves a complex interaction of precipitating factors that act especially on vulnerable patients (with predisposing factors). A high age was a strong independent predisposing factor for psychotic symptoms, which is also an independent risk factor for delirium [6,11,12,21], and may reflect both a lower brain reserve capacity [2,22] and an association with other medical problems (e.g., atherosclerosis, hearing problems, visual impairment). Approximately one third of our patient population was older than 70 years, whereas almost two third of cases with psychotic symptoms were found in this group of elderly patients. Left ventricle hypertrophy, a poor ejection fraction and concomitant dypnoea, may be indices of left ventricular dysfunction, heart failure, and more advanced atherosclerosis. This may increase the risk of sudden drops in cardiac output that can result in hypoxemia and, possibly, psychotic symptoms. Heart failure has previously also been associated with an increased risk of delirium [6,22]. Predisposing factors may help to identify patients who are prone to develop psychotic symptoms.
The strong association with per- and postoperative precipitating factors indicates that these factors may play a role in the pathogenesis. As expected, we found that metabolic disturbances indicated by renal failure and electrolyte imbalance were amongst the most important predictors of delirium [2]. Patients with a lower peroperative temperature were at a higher risk of psychotic symptoms. It has been presumed that mild brain hypothermia contributes to the preservation of cerebral perfusion and oxygenation and lowers the risk of cognitive deficits [23]. Yet, some studies found no or even adverse effects of hypothermia on neurophysiological function [24,25], which might be ascribed to an antithetical lowering of cerebral oxygenation due to increased catecholamines, increased shivering, and a left shift in the oxyhemoglobin dissociation curve. Since we found that hypothermia predisposed to psychotic symptoms, it might be prudent to aim at normothermia or moderate hypothermia with 2–4 °C lowering of temperature in patients at higher risk (e.g., older patients with renal failure and other illnesses). Some risk factors, such as stroke or major infection, had a relatively low incidence in our cohort but were associated with a relatively high risk for psychotic symptoms, which is consistent with previous studies of delirium and encephalopathy [5,18,22]. Cerebrovascular complications are important complications of cardiac surgery [4,5], and ischemic brain injury may also have contributed to the presence of psychotic symptoms in our cases. Cerebral micro- and macroemboli during cardiopulmonary bypass [4,6] may be an important contributor to delirium and psychotic symptoms, and these embolizations may have consisted of air, fat, platelet and blood cell aggregates, fragments of atherosclerotic plaque, or release of thrombus. Finally, a low hematocrit proved to be a risk factor of psychotic symptoms, which is also known to increase the risk of delirium in elderly patients who are hospitalized or operated [12,21]. Like other independent predictive factors (e.g., a poor ejection fraction, dyspnoea, a low partial pressure of oxygen, and stroke), this may also have induced an inadequate cerebral oxygenation. However, we did not find an independent beneficial effect of beating heart surgery, which was found in case of delirium in a previous large cohort study [6]. The extracorporal circulation is thought to lead to brain damage, partly due hemodynamic fluctuations and (air) microemboli [4,6]. We found patients in the beating heart group to be somewhat younger with a better left ventricular function, similar to the study by Bucerius et al. [6]. This suggests that a more healthy population is selected, which may explain better outcomes.
The study also has several limitations. First, there was a relatively small 2.1% incidence of severe psychotic symptoms in this study, while the expected incidence rate of psychotic symptoms would be 8–19%. This may be due to the method of assessment of psychotic symptoms; only severe psychotic symptoms were recorded and many clinicians were involved in the assessment of psychotic symptoms, which may have resulted in underreporting. However, psychosis due to delirium may also have been missed due to its subtle, fluctuating, and multidimensional features. Second, we could not compare psychotic versus non-psychotic delirium, since delirium per se was not ascertained. Since psychotic cases were likely part of the delirious population, it is not surprising that predisposing factors, precipitating factors, and adverse outcomes of psychotic symptoms found in this study closely resemble those for delirium after cardiac surgery in other studies. Third, the relatively low incidence of some potential risk factors (e.g., stroke and major infection) may have resulted in relatively unstable predictive estimates (and wider confidence intervals). Moreover, we had no information on pre-existing cognitive decline. Fourth, the adverse outcome variable of in-hospital death was used instead of mortality in general. Furthermore, adverse outcomes and psychotic symptoms are not independent measures; the longer the stay on intensive care unit, the longer one is at risk to develop psychotic symptoms. The strengths of the present study are the extensive assessment of potential risk factors that were prospectively collected, and the large number of patients.
We conclude that psychotic symptoms were associated with several chronic and peroperative problems. Our results are consistent with the hypothesis that the etiology of psychotic symptoms following cardiac surgery is multifactorial as a ‘final common pathway disorder’, similar to delirium. The association of psychotic symptoms and hypothermic conditions during surgery (i.e., temperature lower than 33 °C) may indicate that deep hypothermia increases the risk of brain dysfunction. The association with adverse outcomes is presumed to be due to a greater severity of illness. Therefore, risk assessment for delirium on internal medicine and surgical wards of the general hospital is very important, and the subgroup with severe psychotic symptoms do not seem to identify patients at a different risk for adverse outcomes. We recommend prompt intensive diagnostic evaluation and therapeutic intervention when delirium with or without hallucinations or delusions occur after surgery, in order to improve clinical outcomes.
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References |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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This article has been cited by other articles:
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  Y.-L. Chang, Y.-F. Tsai, P.-J. Lin, M.-C. Chen, and C.-Y. Liu Prevalence and Risk Factors for Postoperative Delirium in a Cardiovascular Intensive Care Unit Am. J. Crit. Care., November 1, 2008; 17(6): 567 - 575. [Abstract] [Full Text] [PDF]
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