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Autonomic dysfunction and perioperative outcome

Whittle, J; (2017) Autonomic dysfunction and perioperative outcome. Doctoral thesis , UCL (University College London). Green open access

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Abstract

OBJECTIVE: To examine the relationship between established autonomic dysfunction, measures of cardiopulmonary physiology and perioperative outcome in high-risk patients presenting for major surgery. SUMMARY BACKGROUND DATA: Experimental data demonstrate that autonomic activity is a key modulator of both cardiovascular and immune function following tissue injury and inflammation. Autonomic dysfunction is associated with adverse outcomes across several medical populations. Whether pre-existing autonomic dysfunction is detrimental following controlled tissue injury (surgery) in humans is unknown. SUMMARY OF STUDIES: Parasympathetic autonomic dysfunction (PAD), defined by impaired heart rate recovery after exercise, was associated with a distinct physiological profile in patients presenting for preoperative Cardiopulmonary Exercise Testing (CPET). This comprised impaired cardiac performance at peak exercise, reduced peak oxygen uptake and anaerobic threshold as well as chronotropic incompetence. Levels of GRK2, a regulator of beta adrenoreceptor and immune/inflammatory activity, in circulating lymphocytes were raised in cells derived from individuals with PAD. Retrospective analysis of outcomes from two prospectively collected colorectal surgical cohorts (n=1047) revealed PAD to be common (>30%) and associated with an increased length of hospital stay (12 days (95% CI: 9-16) vs. 8 days (95% CI: 6-8.5), p=0.01), as well as increased risk of significant Clavien-Dindo defined morbidity, postoperative gastrointestinal function, sepsis and increased 90-day mortality (RR 1.1 (1.007-1.41), p=0.008). Intraoperative haemodynamic data indicated impaired cardiac contractility and increased risk of intraoperative hypotension, possibly contributing to detriments in postoperative outcome. Sympathetic autonomic hyperactivity, defined by excessive anticipatory heart rate rise prior to starting loaded exercise was associated with a different CPET profile to that seen in PAD, defined by evidence of cardiac ischaemia during exercise, resulting in impaired cardiac contractile function at peak effort, but also associated with increased hospital length of stay. Patients with PAD did not necessarily demonstrate sympathetic hyperactivity, but when both were present, physiological performance and postoperative outcomes were further impaired. Conclusions: Both preoperative parasympathetic and sympathetic autonomic dysfunction are associated with impaired perioperative outcomes. These data demonstrate in high risk surgical patients that established autonomic dysregulation is associated with the development of sepsis, myocardial ischaemia, critical illness and mortality following major elective surgery. The autonomic nervous system represents an underexplored target for therapies aimed at reducing the morbidity burden of major surgery.

Type: Thesis (Doctoral)
Title: Autonomic dysfunction and perioperative outcome
Event: UCL (University College London
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Third party copyright material has been removed from ethesis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/1557406
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