Comparison of Clinical Outcomes Between Alpha-Stat and pH-Stat Strategies During Hypothermic Circulatory Arrest: A Systematic Review

Abstract

Due to the conflicting effects on cerebral perfusion and metabolic control, the optimal acid-base management strategy for hypothermic circulatory arrest remains a matter of ongoing debate, particularly concerning the α-stat and pH-stat approaches. This article presents a systematic review and analysis of the clinical and physiological effectiveness of these two methods in patients undergoing surgery of the aortic arch or ascending aorta. A comprehensive literature search was conducted across PubMed, the Cochrane Library, CINAHL, and ScienceDirect, covering studies published between 2010 and 2025, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Seven studies meeting the inclusion criteria were analyzed, encompassing both pediatric and adult populations. The primary outcomes assessed were cerebral blood flow, oxygenation indices (SjvO₂, CEO₂), cerebral metabolic rate of oxygen, and postoperative neurological recovery. The evidence indicated that pH-stat management led to a more rapid attainment of target hypothermia and enhanced cerebral oxygen delivery in pediatric patients, largely due to CO₂-mediated vasodilation and more uniform cooling. However, these benefits were accompanied by a higher risk of impaired cerebral autoregulation. In contrast, the α-stat strategy preserved physiologic autoregulatory responses, maintained metabolic stability, and was associated with lower postoperative neurological deficits in adult cohorts. Several of the included studies performed quantitative synthesis or meta-analytical comparison, with a trend favoring α-stat in adult patients regarding long-term neurological outcomes. Although pH-stat may offer specific advantages in neonates and young children, α-stat appears to provide a more physiologically appropriate regulation of pH and cerebral hemodynamics in adults. The heterogeneity of study populations, surgical contexts, and outcome measures reinforces the need for an individualized approach. These findings support the consideration of hybrid strategies employing pH-stat during the cooling phase and α-stat during rewarming to balance perfusion benefits and metabolic control. Ultimately, no single strategy demonstrated consistent superiority, and acid-base therapy should be tailored to factors such as patient age, cerebral vulnerability, and procedural complexity.

Keywords: alpha-stat; aortic; arch surgery; cerebral perfusion; circulatory arrest; deep hypothermia; moderate hypothermia; ph-stat.

Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study selection.

A flow diagram representing the study selection process according to PRISMA guidelines. The figure shows the number of records identified, screened, excluded, and included in the final review (n = 7). Adapted from Page et al. [5].

Figure 2. Relationship between cerebral metabolic rate of oxygen (CMRO₂) and temperature.

Illustration created by the authors based on data from Svyatets et al. [10] and Durandy [6].

Figure 3. Cerebral oxygenation metrics: α-stat versus pH-stat.

Comparison of SjvO₂, CEO₂, and AJDO₂ under α-stat and pH-stat blood gas management strategies during hypothermia. pH-stat demonstrated higher cerebral oxygen saturation and reduced oxygen extraction. Illustration created by the authors based on data from Voicu et al. [3].

Figure 4. Forest plot of neurological outcome risk.

Forest plot of neurological outcome risk comparing pH-stat and α-stat blood gas management. Odds ratios and 95% confidence intervals comparing neurological outcomes under pH-stat versus α-stat strategies are shown. The vertical dashed line indicates the null effect (odds ratio = 1.0). Data synthesized from included studies [11-20], based on Yu et al. [7].

Figure 5. Funnel plot of publication bias.

Funnel plot assessing publication bias based on the meta-analysis by Yu et al. [7]. Standard error is plotted against effect size (odds ratio) for each included study. The symmetry of the plot suggests a relatively low risk of publication bias.

Figure 6. Vienna perfusion protocol.

A schematic overview of the Vienna perfusion protocol utilizing moderate hypothermia (28–32°C), α-stat blood gas management, and combined antegrade and retrograde cerebral perfusion. The protocol avoids deep hypothermia to support cerebral autoregulation. Illustration created by the authors based on data from Werner et al. [9]. ACP: antegrade cerebral perfusion; RCP: retrograde cerebral perfusion