The acid–base management during moderate hypothermic cardiopulmonary bypass (CPB) using the alpha-stat vs. the pH-stat strategy is a controversial issue [1,2]. During the alpha-stat strategy, the temperature-uncorrected partial pressure of arterial carbon dioxide (PaCO2) is maintained near 40 mmHg while the temperature-corrected PaCO2 is decreased. However, during the pH-stat strategy, the temperature-corrected PaCO2 is maintained near 40 mmHg while the temperature-uncorrected PaCO2 is increased [1-4].
During moderate hypothermic CPB, Murkin and colleagues have shown that the alpha-stat strategy of acid–base management can provide better cerebral autoregulation and flow–metabolic coupling as compared with the pH-stat strategy . However, Yao and colleagues have shown during CPB while using the alpha-stat strategy that the regional cerebral oxygen saturation (RsO2) as monitored by near-infrared spectroscopy (NIRS) decreased as soon as patients were started on CPB and remained decreased throughout bypass . Since CO2 is a major determinant of cerebral blood flow , the decrease in RsO2 may be attributed to the low temperature-corrected PaCO2 associated with the alpha-stat strategy.
The aim of the current study was to investigate in adult patients undergoing coronary artery bypass grafting (CABG) during moderate hypothermic haemodilutional CPB, the effect of alpha-stat vs. pH-stat strategy of acid–base management on the RsO2 as monitored by the INVOS 5100 cerebral oximeter. The INVOS 5100 oximeter is a device based on NIRS and provides a non-invasive and continuous real-time monitoring of RsO2 that indirectly assesses the cerebral oxygen supply-demand balance [8-13].
Fourteen adult patients (ASA II–III, mean age = 63 ± 2.2 yr, mean weight = 78 ± 5.1 kg) of both genders undergoing elective CABG with haemodilutional hypothermic CPB using a membrane oxygenator were included in the study. The study was approved by the Institutional Review Board (IRB) at the American University of Beirut who waived the need for an informed consent since the used cerebral oximetry technique is non-invasive and the PaCO2 values during bypass are within the clinical range.
Patients were pre-medicated with 10 mg oral diazepam. In all patients, while still awake and throughout the whole study, RsO2 was monitored by a cerebral oximeter (INVOS 5100, Somanetics; TYCO Healthcare, CA, USA) using disposable sensors placed to the patient's forehead. Anaesthesia was induced with midazolam (2 mg), thiopentone (3 mg kg−1), lidocaine (2 mg kg−1), sufentanil (25 μg) and rocuronium bromide (1.2 mg kg−1), to be followed by orotracheal intubation and positive pressure ventilation. Anaesthesia was maintained with subsequent doses of sufentanil (1 μg kg−1 h−1), midazolam (0.1 μg kg−1 min−1) and cisatracurium (0.1 mg kg−1 h−1). Intermittent positive pressure ventilation was initiated using 100% oxygen supplemented with 1–2% isoflurane to achieve an end-tidal CO2 in the 35–40 mmHg range. Patients were monitored with 5 leads electrocardiograph (ECG), and a radial artery cannula. Also, a pulmonary artery catheter was inserted for haemodynamic monitoring. Before CPB, patients were given Ringer's solution at a rate of 10 mL kg−1 and an additional 1500 mL was used to prime the membrane oxygenator (Medtronic, Minneapolis, MN, USA). No blood or colloid was added to the prime. After full heparinization (heparin of 4 mg kg−1 to achieve an ACT > 450 s), CPB was started using a non-pulsatile roller pump (Sarns 8000; 3M Health Group, Ann Arbor, MI, USA) at a flow of 2.4 L m−2 min−1. Oxygen flow delivered to the membrane oxygenator was adjusted according to the blood gas results to achieve the alpha-stat strategy for acid–base management. Mean arterial pressure during CPB was maintained between 60 and 70 mmHg using incremental doses of phenylephrine whenever needed. The site for monitoring of body temperature was the venous blood at the entrance of the pump oxygenator. During CPB, body temperature was gradually decreased to 28–30°C and the heart was arrested after aortic cross clamp using cold crystalloid potassium cardioplegia. After 10 min of alpha-stat strategy and while maintaining steady-state body temperature of 28–30°C, a flow of 3–5% CO2 was added to the oxygen flow in order to achieve the pH-stat strategy of acid–base management. After 10 min of pH-stat strategy, while maintaining steady-state body temperature of 28–30°C, the CO2 was discontinued and alpha-stat strategy was resumed throughout the surgery. RsO2, mean arterial pressure, haematocrit (Hct) level and arterial blood gases were recorded before CPB and during the initial alpha-stat phase, the pH-stat phase and the subsequent alpha-stat phase of the CPB. Ten minutes were allowed at each measurement interval which ensured a stable RsO2 level as monitored by the INVOS 5100. Each patient served as his/her own control. Arterial blood gas was immediately subjected to duplicated measurements by a bench blood gas analyser (ABL700; Radiometer, Copenhagen, Denmark), and both temperature-corrected and temperature-uncorrected PaCO2 values were determined. At the end of the coronary grafting and after weaning from CPB, all patients were slowly rewarmed to 37°C and heparin was neutralized with protamine.
A power analysis using a Type I and Type II errors of 5% and 10%, respectively, while considering a clinically significant change in RsO2 of 7.5% and a SD of 8.5% reported in the literature, revealed that 14 patients are needed for this study. The mean and SD of cerebral blood oxygen saturation, the temperature-corrected and temperature-uncorrected PaCO2, and the Hct level were determined during pre-CPB, during moderate (28–30°C) hypothermic phases of the CPB with both alpha-stat and pH-stat strategies for acid–base management. These mean values were compared with the analysis of variance and Scheffé test for post hoc analysis. Statistical significance was considered at P < 0.05.
Mean ± SD of cerebral blood oxygen saturation (RsO2), PaCO2 and Hct at pre-CPB, as well as during the moderate (28–30°C) phase of CPB using the initial alpha-stat strategy, the pH-stat strategy and the subsequent alpha-stat strategy are presented in Table 1.
During bypass, with the initial alpha-stat strategy, the temperature-corrected PaCO2 was 26.7 ± 3.6 mmHg. Shifting to pH-stat strategy, the temperature-corrected PaCO2 increased to 38.9 ± 3.9 mmHg and decreased to 27.9 ± 2.3 mmHg upon resuming the alpha-stat strategy of acid–base balance.
During the pre-bypass period, the Hct level was 38.2 ± 3.5% which decreased significantly during moderate hypothermic bypass. There was no significant different between the Hct levels of the initial alpha-stat strategy (27.1 ± 3.4%), the pH-stat strategy (28.1 ± 3.5%) and the subsequent alpha-stat strategy (28.3 ± 3.6%).
When patients are awake and breathing spontaneously room air, the mean ‘baseline’ RsO2 was 59.6 ± 5.3%. Following anaesthesia and ventilation with 100% oxygen, the mean ‘pre-bypass’ RsO2 increased significantly to 75.9 ± 6.7%. During the moderate hypothermic phase of CPB, while using the alpha-stat strategy (temperature-corrected PaCO2 = 26.7 ± 3.6 mmHg), the RsO2 significantly decreased from a pre-bypass value of 75.9 ± 6.7% down to 62.9 ± 6.3%. Shifting to the pH-stat strategy (temperature-corrected PaCO2 = 38.9 ± 3.9 mmHg), the RsO2 increased significantly up to 72.1 ± 6.6%. Resuming the alpha-stat strategy (temperature-corrected PaCO2 = 27.9 ± 2.3 mmHg) decreased the RsO2 to 62.9 ± 7.8% which was not significantly different from the mean RsO2 of the initial alpha-stat strategy.
Correlating the individual RsO2 values of all patients during the alpha-stat and the pH-stat strategies with the corresponding temperature-corrected PaCO2 values showed a positive and significant correlation (r = 0.53; P < 0.05) between RsO2 and the temperature-corrected PaCO2 (Fig. 1).
In this report, we used the INVOS 5100 cerebral oximeter for monitoring of RsO2. It is a device based on NIRS which can provide non-invasive information and continuous real-time monitoring regarding cerebral perfusion and oxygen supply-demand balance [8-10]. Using a light emitting diode and two sensors placed on the forehead, NIRS reflects the changes in regional cerebral concentration of oxygenated and deoxygenated haemoglobin [6-10], and records a mixed venous indexed value of oxygen saturation which predicts the critical balance between oxygen delivery and consumption . RsO2 does have limitations since it detects regional cerebral oxygenation . However, the oxygen saturation measured by the NIRS is closely related to the oxygen saturation in the jugular bulb, which represents the venous oxygenation of the whole brain  and to partial brain tissue oxygen pressure . Also, the saturation displayed on the monitor is the difference between the skin and skull and cerebral tissue, and hence can eliminate superficial signal contamination and isolates changes in brain oxygen saturation [12,13].
Our present report shows during moderate hypothermic (28–30°C) haemodilutional CPB using the alpha-stat strategy that there is a significant decrease of RsO2 as compared with the pre-bypass value. During hypothermia, the whole body oxygen consumption is decreased according to the Q10 principal that reflects the variation in metabolic activity produced by a 10°C change in temperature [14,15]. However, despite the decrease in metabolism due to moderate hypothermia, the RsO2, which reflects regional cerebral oxygen supply-demand balance, was significantly decreased during the alpha-stat strategy phases. This decrease of RsO2 may be attributed to the decrease in cerebral oxygen supply during hypothermic haemodilutional CPB secondary to low mean arterial pressure and/or pump flow . Also, haemodilution by the non-blood priming solution may be another factor contributing to the decrease of RsO2 . However, it has been previously shown that haemodilution is associated with decreased viscosity and cerebral vasodilation which can partially offset the effect of haemodilution .
During moderate hypothermic haemodilutional CPB in our patients, the decrease in RsO2 may be attributed to the low temperature-corrected PaCO2 associated with the alpha-stat strategy. Shifting from the alpha-stat strategy of acid–base management (temperature-corrected PaCO2 = 26.7 ± 3.6 mmHg) to the pH-stat strategy (temperature-corrected PaCO2 = 38.9 ± 3.9 mmHg), while maintaining the Hct, the pump flow and the mean arterial pressure at the same level, resulted in a significant increase of the RsO2. This increase of the RsO2 during pH-stat strategy, while maintaining all other parameters constant, suggests that the increase of the temperature-corrected PaCO2 may be the main factor affecting the change of RsO2. Correlating the individual RsO2 values in all patients during alpha-stat and pH-stat with the corresponding temperature-corrected PaCO2 values showed a significant positive correlation. PaCO2 is a major determinant of the cerebral blood flow. CO2 diffuses rapidly across the blood–brain barrier, reducing extracellular fluid pH and causing cerebral vasodilation (approximately 4% increase in cerebral blood flow per 1 mmHg). Resuming the alpha-stat strategy after the pH-stat strategy resulted in the return of the mean PaCO2 and RsO2 to their values during the initial alpha-stat strategy.
Comparing the mean RsO2 during moderate hypothermic CPB with the baseline RsO2 in the awake patient breathing room air shows that the mean RsO2 during the pH-stat strategy was much higher (72.1% vs. 59.6%), denoting luxury cerebral perfusion. As shown by Murkin and colleagues , the pH-stat strategy which provides luxury perfusion, results in pressure-dependent cerebral blood flow with impaired cerebral autoregulation and flow–metabolic coupling. In contrast, alpha-stat strategy maintains cerebral autoregulation as well as flow–metabolic coupling . In our patient, the mean RsO2 during the alpha-stat strategy results in a mean RsO2 value of 62.9% which is only moderately higher than the mean baseline RsO2 of 59.6% in the awake patients, suggesting that the alpha-stat strategy can maintain adequate cerebral perfusion while avoiding luxury perfusion during moderate hypothermic CPB.
In conclusion, our report shows that the initiation of moderate hypothermic haemodilutional CPB using the alpha-stat strategy of acid–base management causes a significant decrease in RsO2 when compared with the pre-bypass values. Shifting from the alpha-stat to the pH-stat strategy while maintaining the Hct, the pump flow and the mean arterial pressure at the same level, resulted in a significant increase in the temperature-corrected PaCO2 from 26.7 ± 3.6 to 38.9 ± 3.9 mmHg which was associated with a significant increase of RsO2 from 62.9 ± 6.3% to 72.1 ± 6.6%. However, the mean RsO2 (72.1 ± 6.6%), during pH-stat strategy was much higher than the baseline RsO2 value (59.6 ± 5.3%) in the awake patient breathing room air, denoting luxury cerebral perfusion. In contrast, the mean RsO2 of 62.9 ± 6.3% during alpha-stat strategy was moderately higher than the baseline RsO2, suggesting that the alpha-stat strategy can maintain adequate cerebral oxygen supply-demand balance while avoiding luxury cerebral perfusion during moderate hypothermic haemodilutional CPB.
The authors are grateful to TYCO Healthcare for providing the INVOS 5100 cerebral oximeter and the disposable sensors.
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