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© 2002 European Association of Cardio-Thoracic Surgery
pH-stat blood gas management provides better cerebral perfusion during deep hypothermic retrograde cerebral perfusionDepartment of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan
* Corresponding author. Tel.: +81-52-744-2376; fax: +81-52-744-2383 Received January 15, 2002; received in revised form August 9, 2002; accepted August 26, 2002
We performed a retrospective comparative clinical study to evaluate whether pH-stat (  ) or alpha-stat strategy ( ) provides better perfusion or oxygen metabolism during hypothermic retrograde cerebral perfusion (RCP). The pH-stat group showed significantly lower superior vena cava (SVC) pressure (21±4 versus 27±6 mmHg,  ), apparently lower retrograde cerebral vascular resistance index (7.4±2.1 versus 10.1±3.8 dynes/s cm–5 m–2,  ) but there were no significant differences in RCP flow index, oxygen supply or oxygen extraction between groups. Further studies are necessary to determine which blood gas management is better for RCP, however, pH-stat strategy should be useful in deep hypothermic RCP.
Key Words: Brain protection; Aortic surgery; Brain circulation; Brain metabolism; Acid base management
Retrograde cerebral perfusion (RCP) is an alternative to extend the duration of safe cerebral ischemia during deep hypothermic circulation arrest. RCP was reported as a technique for protection of the brain during aortic arch surgery by Lemole et al. [1], and by Ueda et al. [2], and has become generally accepted as an adjunct in cerebral protection. But the mechanism of brain protection of RCP has not totally understood. We reported that patients who had insufficient RCP flow showed higher incidence of neurological disorder [3]. RCP can not provide adequate cerebral blood flow and its brain protection is limited. Therefore the condition to provide the optimum cerebral circulation should be clarified. In the deep hypothermic cardiopulmonary bypass pH-stat blood gas management had been reported to provide higher cerebral blood flow than alpha-stat management [4]. We hypothesized that pH-stat strategy increased cerebral blood flow and improved oxygen metabolism during RCP under results of our animal experiences. We changed blood gas management during RCP from alpha-stat to pH-stat strategy at April 1996, however, blood gas management of carbon dioxide (CO2) during RCP has not been clarified. The present study was not randomized but a comparative clinical study between alpha-stat and pH-stat strategy; therefore, there were certain limitations in interpreting and evaluating the results. However, this study may be the first clinical trial, which attempts to bring into clearer focus on the advantages or disadvantages of pH-stat blood gas management during RCP. This study should be the first step to establish our hypothesis.
The study group consisted of consecutive 29 patients who underwent elective aortic arch surgery via a midsternotomy under hypothermic cardiac arrest with RCP at Nagoya University between since April 1993 and March 1999. Blood gas management was changed from alpha-stat to pH-stat strategy since April 1996. There were 14 patients with alpha-stat and 15 patients with pH-stat strategy. Clinical profiles were based on age, gender, body surface area (BSA), disease, and procedure. Among patients’ background, there were no significant differences between groups in above clinical profiles (Table 1).
RCP was performed as follows: a patient was placed on cardio-pulmonary bypass (CPB) with bicaval venous drainage and arterial return under general anesthesia with high dose Fentanyl but without Prophocol. Core cooling was applied until approximately 20 °C of nasopharyngeal temperature. CPB was then stopped and RCP started via superior vena cava (SVC) cannula with clamping inferior vena cava (IVC) cannula, by maintaining SVC pressure around 25 mmHg in order to obtain more than 200 ml/min per m2 of RCP flow index, that was our minimum required RCP flow. After reconstruction of aortic arch, RCP was terminated, CPB was resumed and the patient was rewarmed. The pH-stat blood gas management was initiated at 25 °C of the nasopharyngeal temperature during cooling and continued until 25 °C during rewarming. It was managed principally with inhalation of 1 l/min of 100% oxygen mixed with 50–100 ml/min of 100% carbon dioxide into an oxygenator. Flow rate of carbon dioxide gas was adjusted under blood gas analysis in every 15 min. CDI 400 Blood parameter monitoring system (Terumo, Tokyo, Japan) was useful to control precise carbon dioxide gas tension without delay. Blood arterial CO2 was managed ideally to be 40 Torr measured at the patient's body temperature, which was 80–90 Torr measured at 37 °C. During RCP, blood samplings were performed from inflow circuit and effluent blood from cervical branches (sampled mainly from the orifice of the brachiocepharic artery) at 5, 30, 45 and 60 min since RCP initiation. Blood gas analysis was done at both 37 °C and the patient's temperature (ABL 4, Radiometer Co. Ltd.). Perfusion conditions and oxygen metabolism were compared between groups using the following parameters:
2.1. Statistical methods The data were evaluated by using the StatView J-5.0 statistical analysis software. The results were expressed as the mean and a standard deviation. Statistical significance in clinical factors between groups was determined by using the chi-square test and non-paired t-test. The statistical significance of each measurable value was determined by one-way analysis of variance (ANOVA) and multiple comparisons with Scheffe's procedure. Significant difference over time was determined with repeated ANOVA. A P value of less than 0.05 was considered statistically significant.
3.1. Perfusion condition There were no significant differences between groups in the lowest nasopharyngeal temperature but RCP duration was significantly longer in alpha-stat strategy than pH-stat strategy. SVC pressure was significantly lower in pH-stat group (Table 2). While RCP flow index showed no significant differences between groups, vascular resistance during RCP was significantly lower in pH-stat strategy than alpha-stat strategy (Fig. 1). The mean prediction line between arterial carbon dioxide tension and vascular resistance in all samples showed downward-slopping curve. Vascular resistance tended to decrease according to increasing of arterial carbon dioxide tension during RCP. There were no significant changes in flow rate index and vascular resistance at 5, 30, 45 and 60 min since RCP initiation in both groups (Fig. 2a).
3.2. Blood gas Arterial carbon dioxide tension was successfully maintained higher in pH-stat strategy. Average arterial carbon dioxide tension was 88 Torr, ranging 52–196 Torr, which was significant higher than that in alpha-stat strategy. However, average arterial carbon dioxide tension which was measured at the patients’ body temperature in pH-stat strategy showed no significant differences compared with that measured at 37 °C in alpha-stat strategy. Arterial oxygen tension showed no significant differences between groups. Arterial blood pH in pH-stat management showed significant lower values by measured at 37 °C but similar values collected at the patients’ body temperature compared with that in alpha-stat strategy (Table 2).
Hb was significantly lower in pH-stat strategy but there were no significant differences in oxygen supply. Oxygen saturation of effluent blood from cervical vessels was higher in pH-stat strategy than in alpha-stat strategy with significance ( 3.3. Clinical outcome All patients in pH-stat management awaked within 24 h after surgery but four patients in alpha-stat strategy revealed delayed awakens after the second postoperative day (27%). Two patients of alpha-stat group revealed convulsion after surgery. One recovered without any sequel but the other slipped into a coma for 10 days and was diagnosed severe stroke with head computerized tomography. There was no convulsion or coma in pH-stat group but one patient suffered with stroke along the basilar artery. Cognitive brain function has not been evaluated but patients without stroke returned to previous life in both groups. Long term respiratory support more than 48 h was required in half of alpha-stat group but in three patients (20%) in pH-stat group. There was no other morbidity or operative mortality within 30 days in both groups.pH-stat strategy improved neurological recovery and shortened respiratory support period, but there were no significant differences between groups.
Experimental studies showed that RCP supplied blood to the brain during interruption of physiological cerebral circulation and that it minimized ischemic damage of the brain [5–7]. Therefore RCP may be a useful adjunct procedure in cases of hypothermic circulatory arrest because it can extend the period of time during which cerebral circulation can be safely interrupted [8]. But RCP can provide limited brain protection comparing with antegrade perfusion and its efficacy is not uniform in each case [9,10]. Therefore, the RCP condition to provide better cerebral circulation should be clarified. The principal debate over acid base pH management, alpha-stat or pH-stat strategy has concerned the advantages or disadvantages during RCP. Cooling is associated with an alkaline shift in the pH of neutrality of water and blood in a closed system. In pH-stat strategy carbon dioxide gas is added to the oxygen gas mixed in the oxygenator to compensate for the alkaline shift. The resulting respiratory acidosis causes pH to remain constant at 7.40 as determined at the patient's body temperature. pH-stat strategy increases cerebral blood flow resulting from the vasodilation as secondary effect of the added carbon dioxide [11]. The additional cerebral blood flow was thought to provide a useful reserve when low-flow perfusion was required. Aoki et al. performed comparative experimental study, alpha-stat or pH-stat strategy in deep hypothermic circulatory arrest in piglet model. They described that pH-stat strategy provided greater cerebral blood flow than did alpha-stat strategy during hypothermic cardiopulmonary bypass [4]. In our experimental study with mongrel dogs greater cerebral blood flow was obtained associated with higher arterial carbon dioxide tension in both antegrade and retrograde cerebral perfusion in deep hypothermic condition (not published). In the present study pH-stat strategy revealed significantly lower SVC pressure and vascular resistance than did alpha-stat strategy. Carbon dioxide provided better RCP perfusion condition by acting as a vasodilator even during RCP. Lower SVC pressure should be advantage of pH-stat strategy because higher venous pressure may cause brain edema and result in delayed neurological recovery. Hypothermia is associated with a leftward shift in the oxyhemoglobin dissociation curve. The respiratory acidosis due to higher carbon dioxide tension in the pH-stat strategy results in a rightward shift of the oxyhemoglobin curve, which counteracts the leftward shift, induced by hypothermia. This will increase oxygen availability in the hypothermic condition [12]. Ueno et al. performed comparative animal experience of RCP under pH-stat strategy or alpha-stat strategy in mongrel dogs. They reported that pH-stat strategy provide higher cerebral blood flow and cerebral oxygen metabolism rate than did alpha-stat strategy, while there were no differences of oxygen supply nor oxygen extraction [13]. In the present study oxygen saturation of effluent blood from cervical arteries was higher in pH-stat strategy than in alpha-stat one, but there were no significant differences in oxygen supply or oxygen extraction between groups. Basic oxygen metabolism was thought similar in both pH-stat strategy and alpha-stat at the same body temperature. This discrepancy may result in the difference of microcirculation during RCP. We have reported that majority of the blood flow shunted away from the brain capillaries and blood flow through large veno-arterial shunts increases in hypothermic RCP [14]. We speculate that much larger amount of blood flow shunts away through larger veno-arterial shunts in pH-stat strategy than in alpha-stat one during hypothermic RCP. This phenomenon should be one of mechanism, which reduce vascular resistance and increase RCP flow. There exist numerous collateral pathways between the SVC system and IVC system. They also affect RCP perfusion and vascular resistance. Therefore, further study is necessary to clarify cerebral circulation or metabolism during hypothermic RCP managed with pH-stat strategy. Acid base pH management in the hypothermic CPB generally changed from pH-stat strategy to alpha-stat one at the end of 1980, however, the principal debate over alpha-stat strategy or pH-stat one has still concerned. Aoki et al also reported that pH-stat strategy was associated with faster recovery of cerebral high-energy phosphates and intracellular pH than was the alpha-stat strategy after deep hypothermic circulatory arrest [4]. Management of pH-stat strategy needs vexatious regulation for perfusionists. It should be simplified to be generally accepted. We changed blood gas management during RCP from alpha-stat strategy to pH-stat one since 1996 in order to obtain better RCP perfusion condition. This decision was based on our previous report that insufficient perfusion flow during RCP increased neurological morbidity [3]. The present study is not prospective or randomized. There were certain limitations in interpreting and evaluating these results. Neurological recovery improved and temporary neurological disorder decreased after using of pH-stat strategy. Shorter RCP duration in pH-stat group surely contributes these results but better RCP perfusion condition by pH-stat strategy may affect it. pH-stat strategy can provide over the minimum required RCP flow, which was 200 ml/min per m2 under 25 mmHg of SVC pressure in any case. We consider that improvement of RCP perfusion condition by pH-stat strategy may be the best advantage of its clinical use. The pH-stat strategy provided better RCP condition with lower cerebral vascular resistance under lower SVC pressure. Neurological protective effect with pH-stat strategy has not been clarified but neurological recovery improved after change to pH-stat strategy. Further studies are necessary to determine which blood gas management is better for RCP, however, pH-stat strategy should be useful in deep hypothermic RCP. PII: S1569929302000579
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Abstract
1. Introduction
) but oxygen extraction showed no significant difference between groups and no significant changes over time (
