Author + information
- Received November 17, 2000
- Revision received June 26, 2001
- Accepted July 16, 2001
- Published online November 1, 2001.
- ↵*Reprint requests and correspondence:
Dr. Yuji Kadoi, Department of Anesthesiology and Reanimatology, Gunma University, School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan
We sought to examine whether the decrease in jugular venous oxygen saturation (Sjvo2) during cardiopulmonary bypass (CPB) can be used to predict short-term and long-term postoperative cognitive disorders in elderly patients.
It has been reported that elderly patients might be more susceptible to hypoperfusion during CPB.
One hundred eighty-five patients scheduled for elective coronary artery bypass graft surgery were studied. Group 1 (n = 56) was young (<50 years old), group 2 (n = 67) was middle-aged (50 to 69 years old) and group 3 (n = 62) was elderly (>70 years old). After induction of anesthesia, a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to monitor Sjvo2continuously. Hemodynamic variables and arterial and jugular venous blood gases were measured at seven time points.
The cerebral desaturation time (duration when Sjvo2was <50%) and the ratio of the cerebral desaturation time to the total CPB time in group 3 were significantly different from those in groups 1 and 2 (group 1: 20 ± 6 min and 16 ± 5%; group 2: 19 ± 7min and 14 ± 6%; group 3: 34 ± 9min and 24 ± 7%, respectively; p < 0.05). Also, age (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.0 to 1.8, p = 0.02) and desaturation time (OR 1.3, 95% CI 1.0 to 1.4, p = 0.03) were perioperative factors in relation to short-term cognitive impairment. However, age and desaturation time were not perioperative factors in relation to long-term cognitive impairment.
Reduced Sjvo2was associated with short-term cognitive dysfunction in elderly patients.
Central nervous system (CNS) complications continue to be a major cause of morbidity and mortality after cardiac surgery (1). Neuropsychological dysfunction after cardiopulmonary bypass (CPB) has been reported in as much as 79% of patients during the early postoperative period (2).
Several studies have attempted to identify preoperative or intraoperative predictors of cognitive change after CPB (3–6). It has been widely recognized that age is one of the major demographic predictors of postoperative cognitive dysfunction (6). However, the mechanism of cognitive decline in elderly patients after CPB is unknown (5,6).
Newman et al. (5)reported that increased age was a predisposition to impaired cognitive function after cardiac surgery and that this decline in cognitive function in the elderly was not associated with age-related changes in cerebral blood flow (CBF) autoregulation in hypothermic CPB. They also suggested that aging patients might be more susceptible to hypoperfusion that is not detectable by global measures of CBF.
In their study of relatively young patients, Croughwell et al. (3)reported that the state of cerebral desaturation, estimated by the jugular venous oxygen saturation (Sjvo2), during the rewarming period was closely related to postoperative neurologic disorders.
We hypothesized that elderly patients might more frequently suffer from a state of cerebral desaturation during normothermic CPB. However, no studies to date have evaluated the state of cerebral oxygenation in elderly patients during normothermic CPB.
The purpose of this study was to examine whether the decrease in Sjvo2during CPB could be used to predict short-term and long-term postoperative cognitive disorders in elderly patients.
This study had the approval of the Ethics Committee of our institution, and written, informed consent was obtained from all patients. Between May 1994 and April 1999, 241 patients scheduled for elective coronary artery bypass graft surgery (CABG) were approached, and 185 patients agreed to participate in the study. Patients with a history of cerebrovascular disease, diabetes, psychiatric illness, renal disease or active liver disease, as well as those with an education less than seventh grade, were excluded. Patients with moderate or severe atherosclerotic lesions in the ascending aorta or with carotid artery stenosis confirmed by preoperative ultrasonography and magnetic resonance imaging were also excluded.
Patients were assigned to one of three age groups: group 1 (n = 56) was young (<50 years old); group 2 (n = 67) was middle-aged (50 to 69 years old); and group 3 (n = 62) was elderly (>70 years old).
All patients received 10 mg of diazepam orally 1 h before anesthesia. Anesthesia was induced by a dose of 20 μg/kg of fentanyl, 0.2 mg/kg of midazolam and 0.2 mg/kg of vecuronium, and the trachea was intubated. After induction of anesthesia, a pulmonary artery catheter (Vigilance, Swan-Ganz CCO Thermodilution Catheter, Baxter, Irvine, California) was inserted through the right internal jugular vein. For continuous monitoring of Sjvo2, a 4.0F fiberoptic oximetry oxygen saturation catheter (Dual-lumen Oximetry Catheter, Baxter) was inserted into the right jugular bulb using a modified Seldinger technique. This catheter was connected to an analysis system (Explorer System, Baxter) and calibrated in vivo by drawing a blood sample from the catheter (7). The position of the jugular bulb catheter was verified by X-ray film. The Sjvo2was measured and processed in a monitor-computer interface and displayed and stored every 5 s in an Apple Macintosh computer (Apple Macintosh Computer Co., Ltd., Cupertino, California).
The partial pressures of the arterial and jugular venous blood gases were analyzed using a Stat Profile Ultmita (NOVA Biomedical Co., Boston, Massachusetts). All patients were ventilated with 50% oxygen and 50% nitrogen. End-tidal CO2was monitored (Ultima, Datex, Helsinki, Finland) and maintained between 35 and 40 mm Hg. After anesthesia induction, 3 to 5 mg/kg per h of propofol was infused by using a syringe pump and continued until the patients arrived in the intensive care unit. Muscular relaxation was maintained by the intermittent administration of vecuronium. No volatile anesthetic agent was administrated. The tympanic membrane temperature (TT) was continuously monitored by Mon-a-Therm (Mallinckrodt Co., St. Louis, Missouri).
The CPB machine was primed with a crystalloid, nonglucose-containing solution, and a nonpulsatile pump flow rate of 2.2 to 2.5 l/min per m2was maintained. A membrane oxygenator and a 40-μm arterial line filter were used, and the partial arterial pressure of carbon dioxide (Paco2), uncorrected for temperature, was adjusted to normocapnic levels (35 to 40 mm Hg) by varying fresh gas flow to the membrane oxygenator (alpha-stat regulation).
The target nasopharyngeal temperatures were >35°C.
Hematocrit was maintained at >0.20 on CPB, with the addition of blood as necessary. Phenylephrine infusions were used during CPB to maintain a mean arterial pressure (MAP) of 50 to 90 mm Hg.
Intermittently, anterograde blood cardioplegia was administrated at 37°C. Distal coronary anastomoses and proximal anastomoses were performed during a single aortic cross-clamp.
Hemodynamic variables and arterial and jugular venous blood gases were measured as follows: 1) after induction of anesthesia and before the start of the operation; 2) at the onset of CPB; 3) 20 min after CPB; 4) 40 min after CPB; 5) 60 min after CPB; 6) at the end of CPB; and 7) at the end of the operation.
Intraoperative epi-aortic ultrasonography confirmed that none of the patients had moderate or severe atherosclerotic lesions in the ascending aorta.
Cerebral desaturation was defined as Sjvo2<50%, as described by Cook et al. (8).
Neurologic and neuropsychological assessments
All patients underwent a battery of neurologic and neuropsychological tests on the day before the operation and at seven days and six months after the operation, administered by trained specialists, with intraobserver and interobserver validities ensured. The neuropsychological portion of the study design followed the consensus statements on the assessment of CNS disorders after cardiac surgery (6). Cognitive function was assessed using the following tests: 1) Mini-Mental test; 2) Rey auditory verbal learning test; 3) trail-making test, part A; 4) trail-making test, part B; 5) digit span forward; and 6) grooved pegboard.
All data are expressed as the mean value ± SD. After confirmation of equal variance among the groups by use of the Bartlett test, changes in mean values such as hemodynamic variables Sjvo2and TT were compared with the baseline values by using analysis of co-variance. Variables during the first period were used as a co-variate. A comparison of the differences among the three groups at each time point was made. The cerebral desaturation states in the three groups were analyzed by using one-factorial repeated measures analysis of variance. For multiple comparisons, the Scheffé Ftest was used. Differences between the preoperative values and those at seven days and six months after the operation on neuropsychological tests were assessed with the paired ttest. To obtain an indicator of the overall outcome, significant impairment was defined as a decline from preoperative testing of >1 SD on >20% of test measures (at least 2 of 6). Multivariable logistic regression analysis, with the odds ratio (OR), was used to examine the predictive variables of the decrease in Sjvo2<50% during CPB or short-term and long-term adverse outcomes. Statistical significance was set at p < 0.05. All calculations were performed on a Macintosh computer with SPSS (SPSS, Inc., Chicago, Illinois) and Stat View, version 5.0 software packages (Abacus Concepts, Inc., Berkeley, California).
Table 1shows demographic data from the three groups. Height, weight, left ventricular ejection fraction, phenylephrine dosage, aortic clamping time, total CPB time and catecholamine dosage did not differ between the groups. The number of patients with hypertension in group 3 was higher than those in groups 1 and 2.
Table 2shows the variables of the three groups. Mean arterial pressure were decreased during the CPB period in three groups. There were no differences in MAP, cardiac index, and Paco2between the three groups during the study. The Sjvo2value in group 3 was decreased at the onset of CPB, as compared with that at the induction of anesthesia (p < 0.05). However, in groups 1 and 2, there were no changes in Sjvo2throughout the study.
Table 3Aand Table 3Bshows cerebral desaturation data from patients whose Sjvo2values decreased to <50% during CPB. Cerebral desaturation (defined as Sjvo2<50%) during CPB was more frequent in group 3 than in groups 1 and 2. The cerebral desaturation time (duration when Sjvo2was <50%) and the ratio of the cerebral desaturation time to the total CPB time in group 3 were significantly different from those in groups 1 and 2 (group 1: 20 ± 6 min and 16 ± 5%; group 2: 19 ± 7 min and 14 ± 6%; group 3: 34 ± 9 min and 24 ± 7%, respectively; p < 0.05) (Table 3A). In all three groups, cerebral desaturation occurred more frequently during the first 20 min of CPB than in the other periods of CPB. The number of patients with cerebral desaturation during the first 20 min of CPB was higher in group 3 than in groups 1 and 2 (group 1: n = 16; group 2: n = 18; group 3: n = 36; p < 0.05) (Table 3B).
Minor neurologic defects (defined as clinical evidence of focal cerebral infarction, including hemiparesis, visual or gait disturbance, mental changes or a combination of these) were observed in three patients on the seventh day after the operation (group 1: 1/56 [1.8%]; group 2: 1/67 [1.5%]; group 3: 1/62 [1.6%]). Cognitive impairment was observed in 80 (43%) of 185 patients on the seventh day. Cognitive declines were more frequently observed in group 3 than in groups 1 and 2 (group 1: 21/56 [38%]; group 2: 28/67 [42%]; group 3: 31/62 [50%], p < 0.05) (Table 4). We could not examine neuropsychological assessments in 16 patients at six months after the operation. Cognitive impairment at six months was observed in 12 (7.1%) of 169 patients. Cognitive declines were more frequently observed in group 3 than in groups 1 and 2 (group 1: 3/53 [5.7%]; group 2: 3/60 [5%]; group 3: 6/56 [10.7%], p < 0.05).
Age and delta TT (TT at the start of CPB minus TT at 20 min after the start of CPB) was a preoperative factor in relation to the decrease in Sjvo2(age: OR 1.1, 95% confidence interval [CI] 1.0 to 1.3, p = 0.046; delta TT: OR 14, 95% CI 1.9 to 72, p = 0.009) (Table 5A). Also, age (OR 1.3, 95% CI 1.0 to 1.8, p = 0.02) and desaturation time (OR 1.2, 95% CI 1.0 to 1.4, p = 0.03) were perioperative factors in relation to short-term cognitive impairment (Table 5B). However, age and desaturation time were not perioperative factors in relation to long-term cognitive impairment (Table 5C).
The principal findings of this study are: 1) elderly patients had a reduced Sjvo2value as compared with that of the other patients during normothermic CPB; and 2) this reduced Sjvo2was associated with short-term cognitive dysfunction. However, this reduced Sjvo2was not associated with long-term cognitive dysfunction.
Measurement of Sjvo2during the perioperative period
In this study, we evaluated cerebral oxygenation by measuring Sjvo2during CPB. Croughwell et al. (3)reported that the state of cerebral desaturation, estimated by Sjvo2, during the rewarming period was closely related to postoperative neurologic disorders. In addition, Gopinath et al. (9)reported that cerebral desaturation for >10 min in severely head-injured patients was strongly associated with a poor outcome, and the patients with multiple episodes of cerebral desaturation had a 14-fold higher poor outcome than the patients with a single episode of cerebral desaturation. Therefore, measuring Sjvo2during the perioperative period is useful to estimate the adequacy of flow/metabolism coupling in the brain.
Changes in Sjvo2values in the three groups during the study
We observed that a cerebral desaturation state was more frequently observed in elderly patients (>70 years old) than in the other two groups (<70 years old). This reduced Sjvo2was attributable to an imbalance of CBF and cerebral metabolic rate for oxygen (CMRo2). This finding of an imbalance of CBF and CMRo2observed in elderly patients was inconsistent with the data from the Duke University group (5). Newman et al. (5)evaluated the association between age-related decrements in cognition and CBF autoregulation during hypothermic CPB. They reported that age predicted a cognitive decline. However, they found that there was no effect of age on the slope of the CBF response to the changes in MAP, and that coupling of CBF and CMRO2with changing temperature was unaffected by age. Brusino et al. (10)also reported that age did not alter CBF during a hypothermic condition. This discrepancy is attributable to the differences in the method of measurement of cerebral oxygenation, temperature management in CPB, patient demographic data and anesthetic agents used. Newman et al. (5)examined coupling of CBF and CMRo2under hypothermic CPB conditions. In contrast, we examined cerebral oxygenation under normothermic CPB conditions. Temperature management in CPB has a great influence on cerebral circulation, as suggested by Cook et al. (8). In this study, we used propofol as an anesthetic agent. Propofol also has significant effects on CBF and CMRo2(11). In addition, we defined elderly patients as those >70 years old. Roach et al. (1)reported that 32% of their patients were ≥70 years old in a prospective study of 2,108 patients undergoing CABG.
Short-term postoperative cognitive dysfunction
The reduced Sjvo2in this study was associated with short-term postoperative cognitive dysfunction. This implied that an imbalance of CBF and CMRo2during CPB in elderly patients was a possible cause of postoperative cognitive dysfunction. Newman et al. (5,12)suggested that elderly patients were especially vulnerable to inadequate perfusion during CPB, and that hypoperfusion could occur if CBF autoregulation was impaired. In this study, cognitive decline after CABG was more frequently observed in the elderly than in the other groups. This is essentially compatible with other reports. Newman et al. (5)reported that seven of nine neuropsychological measures showed a significant association between increased age and greater cognitive decline after CPB. Our data showed that desaturation time during CPB was also associated with short-term cognitive declines. This finding implies that decreases in Sjvo2during CPB in elderly people should be taken care of promptly.
The TT was slightly decreased at the start of CPB because of the natural cooling. This decrease in TT had a significant effect on the decrease in Sjvo2at 20 min after the start of CPB. Technical assistants had to perform rapid warming to keep the normothermic (>35°C) condition. Nakajima et al. (13)found a significant relationship between the rewarming speed and the proportional decrease in Sjvo2. Therefore, we should take great care with regard to the warming speed at the start of normothermic CPB to prevent the decrease in Sjvo2, especially in elderly patients.
Long-term postoperative cognitive dysfunction
In contrast to short-term cognitive declines, we failed to find the risk factors related to long-term cognitive declines. This finding is consistent with other reports. Robson et al. (14)reported that long-term cognition was not related to the postoperative decrease in Sjvo2. Newman et al. (5)suggested that the etiology of neuropsychological dysfunction after CPB was multifactorial. Embolic events and anesthetic agents may have some effects on postoperative long-term neurologic decline, as suggested by Selnes et al. (6).
In our study, hypertension was more frequently observed in elderly patients than in the other two groups. It is generally believed that the cerebral autoregulation curve in hypertensive patients is shifted to the right and that the lower limit of cerebral perfusion pressure is not 50 mm Hg (15). However, there was no association between reduced Sjvo2during CPB and a history of hypertension in this study. A history of hypertension was not considered to have any effect on our results.
No correlation was found between the integrated area under MAP <50 mm Hg and postoperative cognitive decline in the elderly group. This is inconsistent with the report by Newman et al. (12). They reported that older patients with a lower MAP area <50 mm Hg showed a greater decline in one area of cognitive function. This discrepancy might be attributable to the different management strategies of MAP. In this study, phenylephrine infusions were used during CPB to maintain MAP between 50 and 90 mm Hg. Therefore, the occasions when MAP decreased <50 mm Hg were infrequent throughout the study.
Because of the limited time available for neuropsychological testing perioperatively, we could not cover all major cognitive domains. Also, there were no specific domains concerning the cognitive tests in this study. It is not clear whether reduced Sjvo2was associated with impaired cerebral autoregulation. Further studies are needed to determine whether any correlation exists between Sjvo2reduction and impaired cerebral autoregulation in the elderly.
In this study, we did not examine the amounts of microemboli during CPB. Pugsley et al. (16)reported that neuropsychological deficits after CPB were related to the number of microemboli delivered during the operation. Therefore, we could not rule out the effects of microemboli on postoperative cognitive declines.
Reduced Sjvo2was associated with early cognitive dysfunction in elderly patients. This suggested that we should pay great attention to reduced Sjvo2in the elderly during normothermic CPB.
☆ This study was supported in part by a grant from the Saitama Cardiovascular and Pulmonary Center.
- coronary artery bypass graft surgery
- cerebral blood flow
- cerebral metabolic rate for oxygen
- central nervous system
- cardiopulmonary bypass
- internal jugular (venous) pressure
- mean arterial pressure
- partial arterial pressure of carbon dioxide
- jugular venous oxygen saturation
- tympanic (membrane) temperature
- Received November 17, 2000.
- Revision received June 26, 2001.
- Accepted July 16, 2001.
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