Department of Anesthesiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
*Corresponding author: Surgical Center Research Hospital, Institute of Medical Science, University of Tokyo, 4-6-1 Shiroganedai, Minato-ku, Tokyo 108-8639, Japan. E-mail: hayashida-todai{at}umin.ac.jp
Accepted for publication: December 17, 2003
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Abstract |
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Methods. We studied 65 children aged between 5 months and 17 yr having surgery to correct non-cyanotic heart disease using hypothermic cardiopulmonary bypass (CPB). During surgery, we measured the Bispectral Index (BIS) and regional cerebral haemoglobin oxygen saturation (SrO2) with near-infrared spectroscopy (NIRS). Cerebral ischaemia was diagnosed if both SrO2 and BIS decreased abruptly when acute hypotension occurred. In each patient, the relationship between SrO2 and arterial blood pressure (AP) was indicated by a plot of mean SrO2 against simultaneous mean AP.
Results. We noted 72 episodes of cerebral ischaemia in 38 patients. Sixty-three ischaemic events were during CPB. Cerebral ischaemia was less frequent in older patients. Cerebral ischaemia was more common and more frequent in children under 4 yr old. Haematocrit during CPB was lower and SrO2 was more dependent on AP in children under 4 yr.
Conclusions. Children less than 4 yr of age are more likely to have cerebral ischaemia caused by hypotension during cardiac surgery. Ineffective cerebral autoregulation and haemodilution during CPB may be responsible.
Br J Anaesth 2004: 92: 6629
Keywords: anaesthesia, paediatric; complications, cerebral ischaemia; measurement techniques, near-infrared spectroscopy; monitoring, bispectral index; monitoring, electroencephalography
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Introduction |
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By using both BIS and NIRS measurements in children having cardiac surgery, we found that transient cerebral ischaemia caused by acute hypotension was frequent, especially in younger children.11 We measured the incidence of cerebral ischaemia using a combination of BIS and NIRS monitoring and hoped to identify factors that could affect the incidence of cerebral ischaemia in children having cardiac surgery.
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Methods |
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Anaesthesia was maintained with sevoflurane in oxygen-enriched air and intermittent doses of fentanyl and vecuronium. We routinely monitored five-lead electrocardiogram, invasive arterial blood pressure (AP), central venous pressure (CVP), oximetry (SpO2), end-tidal carbon dioxide tension (EE'CO2) and oesophageal and rectal temperatures. In addition, we monitored BIS throughout surgery using a processed EEG monitor (A-1050 version 3.4; Aspect Medical Systems, Natick, MA, USA) and four electrodes (Aspect Zipprep) placed on bilateral temporal areas (At1 and At2), with Fpz as the reference and Fp1 as the ground. At the same time we measured regional cerebral haemoglobin oxygen saturation (SrO2) to assess cerebral oxygen delivery,12 13 using a dual-detector three- wavelength NIRS oximeter (PSA-3N; Biomedical Science, Kanazawa, Japan)14 with its emitterdetector placed laterally to the EEG electrode in the mid-forehead Fpz position. Analogue signals of AP, CVP, SpO2, EE'CO2 and SrO2 were sampled at 100 Hz using PowerLab and Chart for Windows (version 4; AD Instruments, Colorado Springs, CO, USA) and the data were recorded with an off-line computer. Digital values of BIS and other processed EEG variables were taken every 5 s and recorded off-line with Microsoft Hyperterminal for Windows.
The CPB circuit was primed with blood-containing (n = 18) or bloodless (n = 47) priming solution (Table 1). After the circulation had been stabilized on CPB, midazolam, fentanyl and vecuronium were given via the CPB circuit and a low concentration of sevoflurane was also given. When CPB was prolonged, the same drugs were added every 1.5 2 h. We induced mild or moderate hypothermia, aiming for a rectal temperature of 2830°C for correction of VSD or an incompetent left heart valve or 3032°C for correction of ASD or a right-sided stenotic lesion. Blood gases and haematocrit were measured every 20 min during CPB. After surgical repair, we gave dobutamine, dopamine and nitroglycerine if necessary during and after weaning from CPB. Sevoflurane was used for maintenance of anaesthesia after CPB.
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Results |
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Group comparisons are summarized in Table 1. There were no differences between the groups in types of heart disease, duration of surgery, duration of CPB, and minimum oesophageal and rectal temperatures. More patients experienced cerebral ischaemia, and more often, in Groups 1, 2 and 3 than in Group 5. Haematocrit values during CPB were less in Groups 1, 2, 3 and 4 than in Group 5. The minimum AP during CPB was lower in Groups 1, 2, 3 and 4 than in Group 5 and the mean AP during CPB was lower in Group 2 than in Groups 4 and 5.
More patients showed a significant relationship between MAP and MSrO2 in Groups 1, 2 and 3 than in Group 5, and slope (SrO2/
AP) was greater in Groups 1, 2 and 3 than in Groups 4 and 5, both during surgery and during the prebypass period. Cerebral ischaemic events and slope (
SrO2/
AP) during the prebypass period became less with increasing age, particularly when age was over 4 yr (Table 1).
By simple regression analysis, the frequency of cerebral ischaemia in each patient correlated inversely with age In particular, age younger than 4 yr was associated with a higher frequency of ischaemia (Fig. 4). Multiple regression analysis was performed on the dependent variable of frequency of cerebral ischaemia using independent variables that could affect this: the minimum and mean AP, the initial, mean and minimum haematocrit, and slope (SrO2/
AP) during surgery and during the prebypass period. The mean haematocrit, the minimum AP and slope (
SrO2/
AP) during the prebypass period gave the highest regression coefficient (r = 0.623, P < 0.0001). The frequency of cerebral ischaemia correlated significantly with slope (
SrO2/
AP) during the prebypass period (standard regression coefficient r = 0.353, P < 0.01) and with the mean haematocrit (r = 0.295, P < 0.01), but not with the minimum AP (r = 0.196, not significant).
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We did not detect any gross neurological deficits after surgery, such as newly developed mental retardation, convulsions or motor palsy.
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Discussion |
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Cerebral ischaemia developed most commonly during CPB. Both haematocrit and AP during CPB were less in children younger than 4 yr, in whom ischaemic events were frequent. On multiple regression analysis, haematocrit but not AP significantly affected the frequency of cerebral ischaemia. More haemodilution, but not lower blood pressure, during CPB contributed to more cerebral ischaemia in the younger children, presumably through greater decreases in CaO2 and thus in cerebral oxygen delivery, irrespective of a reduction in CBF.
Our previous report suggested that cerebral autoregulation may be less effective in younger children, because SrO2, a correlate of cerebral oxygen delivery,1214 tends to change in parallel with changing blood pressure throughout surgery.11 Cerebral oxygenation in children <4 yr of age was more dependent on AP, not only during surgery but also during the prebypass period. Because SrO2 should be related to CBF especially before bypass (i.e. in the absence of acute haemodilution), these results suggest that CBF is more dependent on AP and thus cerebral autoregulation is poor in children <4 yr old. Simple and multiple regression analyses showed that the more frequent cerebral ischaemia in younger children is due primarily to immature autoregulation, indicated by greater slope (SrO2/
AP), and secondarily to more marked haemodilution during CPB.
Information about the development of cerebral autoregulation in children is limited.16 Some studies show no autoregulation in critically ill preterm infants1719 or limited autoregulation in stable preterm infants.20 Younger children, compared with older children, undergoing coarctation repair have lower CBF velocity after aortic clamp release, with less compensation for acute hypotension.21 Compared with adults, even healthy adolescents have a slightly delayed return of CBF velocity in response to transient hypotension.22 Our present study supports these suggestions that cerebral autoregulation is immature during infancy and childhood. Our study also suggests that cerebral autoregulation may develop rapidly during early childhood to become nearly complete by the age of 4 yr. In contrast, one recent study found no differences in cerebral autoregulation in infants, children and adults.23 In that study, blood pressure was gradually changed with a slow infusion of phenylephrine,23 whereas in other studies blood pressure was altered more quickly, causing greater transient changes in CBF velocity.2022
With an abrupt reduction in blood pressure, CBF will decrease for a brief period (12 min) before autoregulation restores CBF.24 Immature autoregulation may take more time to restore CBF, so that a decrease in CBF long and severe enough to depress EEG activities may occur more easily in young children. Even in such children, however, decreases in BIS lasted for no longer than 3 min in most ischaemic events, suggesting that cerebral autoregulation restored CBF and EEG during hypotension, albeit slowly.11 In addition, BIS never reached 0, indicating a total loss of EEG activity and suggesting that the ischaemia we observed was incomplete and that cerebral oxygen delivery was present but reduced, being sufficient to sustain some EEG activities.5 Presumably, by these mechanisms neurological damage did not occur, despite frequent cerebral ischaemia. In this sense, transient ischaemia during paediatric cardiac surgery may not be of grave clinical significance. However, our observation was made only in a small number of subjects, and no other systematic studies have been carried out on transient cerebral ischaemia during paediatric surgery. The clinical significance of transient ischaemia should be assessed in further studies using detailed perioperative neurological examinations. Non-invasive monitoring with BIS and NIRS appears to be useful, especially in children <4 yr old (but >4 months old), as cerebral ischaemic events are frequent and are sometimes prolonged (e.g. >3 min in three of our patients), and prolonged ischaemia can cause irreversible EEG changes during cardiac surgery.1 2 4
The NIRS oximeter cannot indicate the saturation level at which cerebral ischaemia will occur.12 13 By combining NIRS and BIS, we can determine if a reduction in CBF, indicated by a decrease in SrO2, is sufficient to cause cerebral dysfunction. Conversely, we can determine that a decrease in BIS is caused by decreased CBF and not by hypothermia or deepened anaesthesia (Fig. 2) if there is a concurrent reduction in SrO2. Thus the BISNIRS combination can be a convenient ischaemic/anaesthetic monitor.
In conclusion, children less than 4 yr of age are more likely to have transient cerebral ischaemia caused by acute hypotension during cardiac surgery mainly due to ineffective cerebral autoregulation.
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