Abstract
Despite a technically perfect procedure, surgical stress can determine the success or failure of an operation. Surgical trauma is often referred to as the “neglected step-child” of global health in terms of patient numbers, mortality, morbidity, and costs. A staggering 234 million major surgeries are performed every year, and depending upon country and institution, up to 4% of patients will die before leaving hospital, up to 15% will have serious post-operative morbidity, and 5–15% will be readmitted within 30 days. These percentages equate to around 1000 deaths and 4000 major complications every hour, and it has been estimated that 50% may be preventable. New frontline drugs are urgently required to make major surgery safer for the patient and more predictable for the surgeon. We review the basic physiology of the stress response from neuroendocrine to genomic systems, and discuss the paucity of clinical data supporting the use of statins, beta-adrenergic blockers and calcium-channel blockers. Since cardiac-related complications are the most common, particularly in the elderly, a key strategy would be to improve ventricular-arterial coupling to safeguard the endothelium and maintain tissue oxygenation. Reduced O2 supply is associated with glycocalyx shedding, decreased endothelial barrier function, fluid leakage, inflammation, and coagulopathy. A healthy endothelium may prevent these “secondary hit” complications, including possibly immunosuppression. Thus, the four pillars of whole body resynchronization during surgical trauma, and targets for new therapies, are: (1) the CNS, (2) the heart, (3) arterial supply and venous return functions, and (4) the endothelium. This is termed the Central-Cardio-Vascular-Endothelium (CCVE) coupling hypothesis. Since similar sterile injury cascades exist in critical illness, accidental trauma, hemorrhage, cardiac arrest, infection and burns, new drugs that improve CCVE coupling may find wide utility in civilian and military medicine.
Highlights
Major Surgery, Trauma and the Stress Response Major surgery is defined “as any intervention in a hospital operating theater that requires incision, excision, manipulation or suturing of tissue occurring and requiring regional or general anesthesia or profound sedation to control pain” [2]
We review the basic physiology of the stress response from neuroendocrine to genomic systems, and discuss the paucity of clinical data supporting the use of statins, beta-adrenergic blockers and calcium-channel blockers
As the “storm” develops more circulating neutrophils are attracted to the interstitial compartments and damaging O2 free radicals, proteolytic enzymes and more cytokines are produced, tight junctions are breached, mucosal cells proceed to necrosis and apoptosis and endotoxemia and sepsis can develop
Summary
Major Surgery, Trauma and the Stress Response Major surgery is defined “as any intervention in a hospital operating theater that requires incision, excision, manipulation or suturing of tissue occurring and requiring regional or general anesthesia or profound sedation to control pain” [2]. Catecholamine surges and changes in blood volume and shifts during surgery may be a potential target to improve patient outcomes following surgery (see Injury, Inflammation and Multiple Organ Failure, The First Incision, Effects of Anesthesia on the Surgical Stress Response, and Effects of Major Surgery on Other Organs) [7,8,9].
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