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Ann Thorac Surg 2002;73:1174-1178
© 2002 The Society of Thoracic Surgeons
a Department of Anesthesia, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
b Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Accepted for publication December 16, 2001.
* Address reprint requests to Dr Abildstrom, Department of Anesthesia, Section 4132, Center of Head and Orthopedics, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark
e-mail: habil{at}rh.dk
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Abstract |
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Methods. Before surgery and at discharge, 15 coronary surgery patients were studied. Global and regional CBF were measured using a brain-dedicated single photon emission computed tomography scanner, and neuropsychological testing with seven subtests was performed. Postoperative cognitive dysfunction was defined as a Z score above 2. Normative single photon emission computed tomography data were available from 26 healthy age-matched controls.
Results. Preoperative global CBF was significantly lower in patients compared with controls (53.7 versus 46.1 mL/100 g/min, p = 0.006). After surgery, global CBF significantly decreased in the patient group (46.1 versus 38.6 mL/100 g/min, p = 0.0001). No significant differences were detected in regional CBF. Cognitive dysfunction was identified in 4 of the 15 patients (26.7%, 95% CI 7.8% to 55.1%). No correlation was found between the neuropsychological Z score and global or regional CBF.
Conclusions. The significant decrease in CBF after coronary surgery was uniformly distributed and was not correlated to postoperative cognitive dysfunction.
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Introduction |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
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No correlation until now has been found between changes in cerebral blood flow (CBF) and neuropsychological test performance [2–4]. Studies measuring global CBF [2, 3] might have overlooked regional changes in CBF potentially associated with decline in neuropsychological test performance. A well-established method for the measurement of both regional and global CBF, single photon emission computed tomography (SPECT) [5], is available and is currently used as a diagnostic adjunct in patients with stroke and dementia.
We hypothesized that there may be a correlation between postoperative cognitive dysfunction after cardiac surgery and changes in regional cerebral blood flow measured with SPECT 1 week after surgery. To increase the sensitivity and specificity, we included control data for both SPECT and neuropsychological testing [6].
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Material and methods |
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Data from two control groups were used. A group of 26 healthy age-matched controls underwent SPECT and served to define normal values for global and regional CBF. The controls were recruited through advertisement and had no known cardiovascular or cerebrovascular disease. Neuropsychological normative data from 176 healthy controls of similar age were obtained as the patients were available [8]. These controls had undergone neuropsychological testing three times with the same intervals as the patients, none were admitted to hospital in the study period.
Single photon emission computed tomography (SPECT)
The patients were scanned under identical conditions preoperatively and before discharge at the fifth to seventh postoperative day in a dark quiet room. The patients were awake and in stable physical condition at the postoperative examination (ie, all drainage and intravenous therapy had been terminated and patients were fully recovered and ready for discharge). Global cerebral blood flow (gCBF) was measured by inhalation of 133Xenon using a brain-dedicated SPECT scanner (Tomotomatic 564; Medimatic Inc, Copenhagen, Denmark). 133Xenon was inhaled for 1.5 minutes from a 4-L bag filled with atmospheric air and oxygen with a 133Xenon concentration of 740 MBq/L. The 133Xenon distribution was recorded during uptake and the after 3 minutes of washout. After a filtered back-projection technique with a 32 x 32 matrix, absolute values of flow expressed as mL blood/100 g brain tissue/min were calculated from the slice corresponding to a level 5 cm above the orbitomeatal plane. As changes in hematocrit changes the partition-coefficient (lambda) for 133Xenon, postoperative gCBF values were corrected for individual changes in hematocrit for each patient according to Chen and associates [9]: lambda = 0.171/(0.094 + 0.176 x hematocrit).
The regional cerebral blood flow (rCBF) was determined after the intravenous injection of a dose of 800 to 1,000 MBq Technetium-99 m-HMPAO (Amersham International, London, England). During the injection and the after 10 to 15 minutes, the patients had their eyes closed. The radioactivity distribution in the brain was measured, and a total of 27 consecutive slices parallel to the orbitomeatal plane were obtained. The 27 slices were recompressed to nine slices for regional analysis of the images. After normalization of CBF to mean blood flow in the cerebellum [5], semiquantitative values for rCBF were calculated in four cortical regions of interest: frontal, temporal, parietal, and occipital cortex. For each anatomical region, the value of rCBF in each individual patient both pre- and postoperatively was analyzed with reference to mean values in the control group to determine whether rCBF in a given region was abnormal (ie, more than 2 SD from the control group means in the same region).
Neuropsychological testing
Neuropsychological testing was performed the same day as the SPECT examination (ie, before the operation and postoperatively on the fifth to seventh day), and in addition, 3 months after surgery. The ISPOCD test battery (Table 1)
was applied, which exists in three parallel versions that are given to the patients in random order. Normative data from 176 healthy age-matched controls from Manchester were available [8]. These controls were tested with the same test battery and with the same time intervals as patients, and their test results served as normal material. We used changes in test results between the first test session (baseline) and the postoperative test sessions among the 176 Manchester controls to calculate a mean and SD of differences in test performance. The mean changes were taken as estimated learning effects. These values were used to normalize the test results of the patients.
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Anesthesia and cardiopulmonary bypass
The patients received their ordinary antianginal medication plus diazepam 10 mg orally. In addition, morphine 10 mg and scopolamine 0.4 mg was given intramuscularly 1 hour before induction of anesthesia. After a radial artery catheter had been inserted, anesthesia was induced with midazolam 0.1 mg/kg and fentanyl 20 µg/kg. Orotracheal intubation was facilitated by pancuronium or cis-atracurium 0.1 mg/kg. Anesthesia was maintained with isoflurane 0.4% to 1% and fentanyle bolus doses of 5 µg/kg. Hemodynamic stability with heart rate 45 to 90 beats/min and mean arterial pressure between 60 and 80 mm Hg was maintained by adjusting anesthetic depth, adjusting nitroglycerin infusion, giving intravenous ephedrine bolus doses, and changing volume load.
Before connecting the extracorporal bypass machine, the patient was heparinized with heparin 300 U/kg and supplemented if needed to secure an activated clotting time above 480 seconds. The cardiopulmonary bypass circuit was primed with 1,800 mL Ringer-lactate and 10,000 U of heparin. Cannulation was performed in aorta ascendens and a two-stage cannula in vena cava inferior. Hypothermic (32°C), nonpulsatile cardiopulmonary bypass with a membrane oxygenator was performed using 
-stat technique. During extracorporal circulation, the activated clotting time was kept above 480 seconds with heparin bolus doses of 5,000 U as needed. Pump flow above 2.4 L/min/m2 was maintained at all temperatures. Mean perfusion pressure below 50 mm Hg was treated with bolus doses of phenylepinephrine or increasing pump flow. Perfusion pressure above 80 mm Hg was treated with sodium-nitroprusside infusion and by increasing the anesthetic depth. All peripheral anastomoses were performed with aortic cross-clamping and antegrade crystalloid cardioplegia (St. Thomas II) 10 mL/kg. Cardioplegia 4 mL/kg was supplemented every 20 minutes. The proximal anastomoses were performed with a partially occluding side clamp on beating heart during rewarming.
CPB was weaned at a rectal temperature of 36°C. After termination of CPB, cardiac index was kept above 2.4 L/m2/min, mean arterial pressure between 60 and 90 mm Hg, and left atrial pressure below 12 mm Hg. This was achieved by volume therapy, atrial or ventricular pacing, inotropics, and vasodilatation. After surgery, the patients were transferred to the intensive care unit and trachea was extubated after 4 to 12 hours.
Statistical analysis
Data are reported as means with range and proportions with 95% confidence intervals. The sample size calculation was based on the assumption that half of the patients would have POCD enabling us to compare two equally sized groups. If the difference in rCBF in a given region between the groups would correspond to a standardized difference of 2, then 15 patients would suffice accepting a type 1 error of 5% and a type 2 error of 20%.
Preoperative values of gCBF and rCBF for the patients were compared with those of the controls using Student’s t test. Pre- and postoperative values of gCBF and rCBF for the patients were compared with Student’s t test for paired data. The difference in gCBF and rCBF in the given regions between pre- and postoperative values for the individual patient was calculated. Using Spearman’s rank correlation test, these parameters were correlated with the Z score at the first postoperative test session.
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Results |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
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Neuropsychological test results
The 15 patients were assessed with the neuropsychological test battery and scanned 13.5 (range 4 to 77) days before surgery and postoperatively after 5 (range 4 to 8) days. After 106 (range 58 to 153) days, neuropsychological follow-up was performed. At the first postoperative test, 4 of 15 patients had POCD (ie, an incidence of 26.7% [7.8% to 55.1%]), and 3 months after surgery, 3 out of 15 patients had POCD (ie, 20.0% [4.3 to 48.1%]).
SPECT results
Normal values for gCBF (Table 2)
were defined from SPECT results in 26 elderly healthy volunteers as mean ± 2 SD. Preoperative gCBF in the patients were significantly lower than in the control group. In the patients, the level of CO2 and hemoglobin in blood was significantly lower at the postoperative SPECT. After correcting for the lower concentration of hemoglobin [9], there was a significant decline in postoperative gCBF.
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Comment |
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The incidence of POCD is in accordance with other studies of coronary surgery patients [10, 11]. Smith and associates [2] found a decrease in gCBF in some patients 8 days after cardiac surgery. This change did not correlate with neuropsychological test results. The decrease in gCBF could be related to neuron loss perioperatively as a consequence of either microemboli distributed diffusely in the cerebral circulation, or irreversible damage caused by cerebral ischemia. However, an additional explanation could be low cerebral metabolism caused by residual effects of sedatives given during hospitalization, or a lower level of psychological stress postoperatively.
Hall and associates [4] studied the possible correlation between changes in rCBF during cardiopulmonary bypass using SPECT and neuropsychological decline in cardiac surgery patients. In that study, abnormality in perfusion for a given region was arbitrarily defined as less than 80% of the flow in cerebellum, and cerebral perfusion of the individual patient was defined as having deteriorated if the number of abnormal anatomical regions had increased. According to this definition, 43% of the patients had decreased cerebral perfusion during CPB, but this decrease did not correlate with decline in neuropsychological test performance. In our study, many of the controls had rCBF values less than 80% of the mean flow in cerebellum. If we were to use the same definition of perfusion abnormality as in Hall and associates [4], the majority of the rCBF values for the patients would be abnormal both pre- and postoperatively.
Patients scheduled for coronary surgery had significantly lower gCBF than controls. Arteriosclerosis was an exclusion criterion for controls; none of the patients had previous stroke and there was no description of clinically important carotid stenoses, but the patients may have had general arteriosclerosis. Significantly reduced gCBF in nondemented patients with generalized arteriosclerosis has not previously been described.
Neuropsychological testing is associated with considerable variability and the definition of POCD varies [6, 12]. Our definition of POCD is more restrictive than in most other studies, and few patients had POCD. But as we used a continuous variable for neuropsychological test performance, the Z score, in the correlation analysis, this did not decrease the ability to find a statistically significant correlation.
The SPECT images were parametrically analyzed using standardized region templates defined according to a neuroanatomical atlas. Preferably, structural imaging should have been performed, which enables adjustments for variable neuroanatomy and potential structural lesions. The procedure for normalization of the cortical rCBF values may also be questioned, as we had no imaging data to exclude cerebellar pathology. However, none of the patients had a clinical history or clinical presentation indicating previous lesions or disorders of the central nervous system.
The level of CO2 was significantly lower at the postoperative SPECT examination (Table 2). End-expiratory values were measured. If a mismatch between perfusion and ventilation had occurred after surgery, it is possible that these values are not truly reflecting pCO2 in blood. No correction was made for the change in level of pCO2, as the determining factor is pH. As no sudden changes in pCO2 occurred, it is most likely that the individual patient acid-base status was fully adapted. Hemoglobin concentration had declined significantly in patients at discharge (Table 2) and we corrected gCBF according to Chen and associates [9].
The average decrease in rCBF in patients with POCD was approximately 7%, in contrast to patients without POCD, who had an increase in rCBF of approximately 2% (Table 3); this difference was not statistically significant. The SD was approximately 10%, and our sample size did not allow us to detect such a small difference similar to the level of interexamination variability in healthy subjects, which may be as high as 10% [13].
Global CBF values in patients before coronary artery surgery were significantly lower than for controls. After surgery, we registered a significant decrease in global CBF, but this did not correlate with neuropsychological test results. In general, patients with cognitive deficits had a decrease in regional CBF, in contrast to patients without cognitive deficits. However, this nonsignificant difference between groups corresponded only to the expected interexamination variability.[15]
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Acknowledgments |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsReferences |
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