Stratification of perioperative risk in patients undergoing major hepato-pancreatico-biliary surgery using cardiopulmonary exercise testing

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Abstract

Contemporary hepatobiliary surgery practice must accurately assess operative risk in increasingly elderly populations with greater co-morbidity. Current methods fail to identify patients at high risk of postoperative complications. Cardiopulmonary exercise testing (CPET) derived anaerobic threshold (AT) and ventilatory equivalence of carbon dioxide (VE/VCO2) are validated predictors of postoperative outcome in major intra-abdominal surgery and outperform contemporary tools of risk evaluation. Despite evidence of improved in-hospital postoperative survival in large centres offering complex curative hepatobiliary surgery, morbidity remains high and long-term survival in the high-risk subset remains poor. This thesis investigated the role of validated CPET-derived markers in predicting perioperative outcomes for a high-risk hepatobiliary surgery population. It was also utilised to study the impact of malignant obstructive jaundice on peripheral oxygen extraction.In a prospective cohort of high-risk patients undergoing liver resection, an AT of 9.9 ml O2/kg/min predicted in-hospital mortality and long-term survival. Below this threshold, AT was 100% sensitive and 75.9% specific for in-hospital mortality (PPV 19%, NPV 100%). Long-term survival below the threshold of 9.9 was significantly worse when compared to those above (mortality HR 1.81). The VE/VCO2 was the most significant predictor of postoperative complications and a threshold of 34.5 provided 84% specificity and 47% sensitivity (PPV 76%, NPV 60%). Amongst the high-risk pancreaticoduodenectomy patients, VE/VCO2 was the single most predictive marker of in-hospital postoperative mortality with an AUC of 0.850 (p=0.020); a threshold value 41 was 75% sensitive and 94.6% specific (PPV 50%, NPV 98.1%). The VE/VCO2 41 was also the only predictor of poor long-term survival (HR 1.90). Notably, AT, Revised Cardiac Risk Index and Glasgow Prognostic Score did not predict outcome after pancreaticoduodenectomy.Patients with malignant obstructive jaundice, evaluated for peripheral oxygen extraction using CPET, showed lower mean peak oxygen consumption (peak VO2) at 63±17.4% of the predicted value. This was noted in absence of any significant pre-existing cardiopulmonary disease and normal respiratory reserve. Normal patterns of oxygen extraction were seen at rest, during incremental work rate and peak exercise levels. Levels of oxygen partial pressure and saturation exceeded baseline values after exercise signifying normal microcirculatory responses. Thus, aerobic capacity was limited by dysfunction in delivery (cardiac output) rather than oxygen extraction.CPET provides useful prognostic adjuncts for early and long-term outcomes in the high-risk patients undergoing major hepatobiliary surgery. These findings provide useful tools for perioperative optimisation of the high-risk patient and plan appropriate level of postoperative care to address mortality and morbidity after surgery.

Layman's Abstract

Contemporary hepatobiliary surgery practice must accurately assess operative risk in increasingly elderly populations with greater co-morbidity. Current methods fail to identify patients at high risk of postoperative complications. Cardiopulmonary exercise testing (CPET) derived parameters are validated predictors of postoperative outcome in major intra-abdominal surgery and outperform contemporary tools of risk evaluation. Despite evidence of improved in-hospital postoperative survival in large centres offering complex curative hepatobiliary surgery, morbidity remains high and long-term survival in the high-risk subset remains poor. This thesis investigated the role of validated CPET-derived markers in predicting perioperative outcomes for a high-risk hepatobiliary surgery population. It was also utilised to study the impact of malignant obstructive jaundice on peripheral oxygen extraction.In a prospective cohort of high-risk patients undergoing liver resection and pancreatico-duodenectomy, CPET provided the strongest prediction of adverse postoperative and long-term outcome. Normal patterns of oxygen extraction were also noted in patients with malignant obstructive jaundice pointing to a primary cardiovascular dysfunction in reduced overall oxygen consumption.CPET provides useful prognostic adjuncts for early and long-term outcomes in the high-risk patients undergoing major hepatobiliary surgery. These findings provide useful tools for perioperative optimisation of the high-risk patient and plan appropriate level of postoperative care to address mortality and morbidity after surgery.

Keyword(s)

Anaerobic threshold; Exercise testing; Hepatic resection; Obstructive jaundice; Pancreaticoduodenectomy; Postoperative complications; Survival

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