Trauma of major surgery: A global problem that is not going away

Abstract

Globally, a staggering 310 million major surgeries are performed each year; around 40 to 50 million in USA and 20 million in Europe. It is estimated that 1-4% of these patients will die, up to 15% will have serious postoperative morbidity, and 5-15% will be readmitted within 30 days. An annual global mortality of around 8 million patients places major surgery comparable with the leading causes of death from cardiovascular disease and stroke, cancer and injury. If surgical complications were classified as a pandemic, like HIV/AIDS or coronavirus (COVID-19), developed countries would work together and devise an immediate action plan and allocate resources to address it. Seeking to reduce preventable deaths and post-surgical complications would save billions of dollars in healthcare costs. Part of the global problem resides in differences in institutional practice patterns in high- and low-income countries, and part from a lack of effective perioperative drug therapies to protect the patient from surgical stress. We briefly review the history of surgical stress and provide a path forward from a systems-based approach. Key to progress is recognizing that the anesthetized brain is still physiologically 'awake' and responsive to the sterile stressors of surgery. New intravenous drug therapies are urgently required after anesthesia and before the first incision to prevent the brain from switching to sympathetic overdrive and activating secondary injury progression such as hyperinflammation, coagulopathy, immune activation and metabolic dysfunction. A systems-based approach targeting central nervous system-mitochondrial coupling may help drive research to improve outcomes following major surgery in civilian and military medicine.

Keywords: Global; Morbidity; Mortality; Perioperative; Surgery; Trauma.

Conflict of interest statement

Geoffrey Dobson is the sole inventor of the ALM concept for cardioplegia, organ preservation, surgery, infection and trauma, and has no financial interests from any entity or organization.

Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Figures

Fig. 1

Perioperative Complications after Non-Cardiac Major Surgery Major surgery and anesthesia are associated with stress-induced activation of the sympathetic nervous system, hemodynamic compromise, hyperinflammation, coagulopathy, immune dysfunction, metabolic imbalances and hypothermia. Large population studies indicate that ∼8% of adult patients will suffer heart ischemia/injury, and 10% of these will die within 30 days [118,119]. Surgical stress also leads to perioperative complications involving brain [120,121], kidney [122], lung [123], liver [124], and possibly the gut microbiome [97]. Atrial fibrillation [125] and infections [126] are also significant complications following major surgery. It is estimated that around 50% of these complications are potentially preventable [[13], [14], [15]].

Fig. 2

A Systems-Based Approach to the Trauma of Surgery Surgical stress triggers a myriad of neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that predispose the patient to further injury. The early drivers of surgical stress are sterile local injury, firing of injured peripheral and visceral afferent nerves which activate the brain's emergency response (see text). During and after major surgery, this system can switch to overdrive and exceed the body's normal tolerances of protection. This can lead to secondary injury, slower healing, poor outcomes, and in some cases, death. From a systems-based perspective surgical stress is levelled at: 1) the CNS, 2) left ventricular-arterial coupling, 3) microvascular blood flow distribution 4) the vascular endothelium/glycocalyx, and 5) the gut microbiome. A hypoperfused vascular endothelium can lead to glycocalyx shedding, systemic hyperinflammation, coagulopathy, platelet dysfunction, immune dysfunction, loss of vascular tone, reduced O2 supply and mitochondrial dysfunction. The hypothesis is that if central and local control of cardiac output and ventricular-arterial coupling can be maintained, the endothelium will not activate and tissue O2 delivery will not be compromised. A potential target therefore is to prevent the “awake’ anesthetised brain from switching into overdrive. This may be achieved by shifting the CNS's autonomic balance from a sympathetically-driven system to a more parasympathetic anti-inflammatory one and improve perioperative outcomes. Modified after Dobson [34].