Cardiovascular Consequences of Severe Acute Pain
Acute nociceptive pain is a signal of tissue injury and perception is initially adaptive, causing an organism to take steps to decrease the tissue damage. In other words, the ability to sense pain is basically a protective mechanism. Surgery, however, creates an acute pain that is different from the pain of stepping on a nail, because the noxious stimulus is sustained by the sheer volume and severity of the tissue disruption. In general, the response is proportionate to the magnitude of the tissue trauma, although there is a huge degree of variability between individuals.1 In the periphery, the injury causes erythemia, vasodilation and activation of nociceptive receptors. The nociceptive signals are transmitted within peripheral nerves to the spinal cord and rostal. Sustained nociceptive stimuli alter the process to increase nociceptive transmission and hence, the perception of pain. In the periphery this is caused by tissue mediators released by cellular damage causing edema, vasodilation and capillary permeability all of which increase peripheral nociceptive signals within the wound to a maximum (peripheral hypersensitivity). An analogous phenomenon occurs in the dorsal column of the spinal cord. Sustained peripheral nociceptive signals cause accumulation of neurotransmitters in the dorsal column, which lowers the threshold for nociception of the receptors and increases the size of the receptor fields. This has the effect of creating maximum nociceptive transmission (central hypersensitivity).
Direct Cardiovascular Effects
The first cardiovascular consequence of ascending nociception is recruitment of segmental spinal reflexes from interneuronal connections. These spinal reflexes create increased sympathetic activity which increases heart rate, stroke volume and peripheral resistance.2 Increased sympathetic tone also causes visceral vasoconstriction, increased sphincter tone and uncontrolled skeletal muscle activity.2 All of these increase myocardial work and oxygen demand. The response is proportional to the magnitude and duration of the stimulus. The increase in heart rate decreases diastolic filling of the coronary arteries, having the further deleterious effect of decreasing myocardial oxygen delivery during a time when demand is increased. In patients with coronary artery disease, cardiomyopathy or ventricular hypertrophy secondary to aortic stenosis, this supply/demand imbalance can trigger myocardial ischemia.
Increased sympathetic tone can have direct deleterious effect within the heart. Alpha receptors within coronary arteries respond to sympathetic stimulation at a variable threshold level with vasoconstriction.2 The resultant coronary artery spasm can induce angina, myocardial ischemia and even infarction. Coronary vasoconstriction may be even more likely in abnormal coronary arteries.3-4 Analgesia may also be more important in the same patients.5 Hypercoagulability has been implicated in the genesis of angina and myocardial ischemia after major surgery.6 Analgesia has been associated with reduction of this hypercoagulability, presumably by prevention of activation of platelets or improved fibrinolysis.6,7
Peripheral Cardiovascular Effects
There are also deleterious peripheral cardiovascular effects in response to acute pain. Sustained acute pain reduces peripheral blood flow. Decreased venous flow causes stasis and ideal conditions for clotting. Venous thrombosis increases significantly.2 Increased venous thrombosis increases thromboembolic complications. Reduced blood flow increases acute thrombosis in peripheral vascular grafts.6 Reduced renal and hepatic blood flow is observed but not associated with organ injury unless pre-existing chronic organ failure exists. Acute pain may impair fibrinolysis7 which further increases the increased risk for proximal lower extremity thromboembolism, known to be highly associated with pulmonary embolism and morbidity.
Neuroendocrine System Effects
Even more indirect evidence of the effect of severe pain on the cardiovascular system comes from the response of the neuroendocrine system to severe acute pain. The response is multi-factorial but includes cellular, immunological and neuroendocrine consequences. The primary systems that respond to stress are the hypothalamic-pituitary-adrenal axis and activation of the sympathetic nervous system by the adrenal glands. Both result in catecholamine secretion, catabolic hormone secretion, and increased oxygen demand.8 Free fatty acids are increased during stress and also increase myocardial oxygen consumption.9 Thoracic epidural analgesia attenuates pain and reduces the catecholamine surge associated with acute pain.10 Increased sympathetic tone decreases epicardial blood flow by increasing resistance from alpha-receptor stimulation.11 Normal subjects compensate by metabolic messengers, but this can be impaired in patients with coronary artery disease. Paradoxic vasoconstriction can occur in diseased coronaries due to sympathetic stimulation that would produce vasodilation in normal coronaries.12-13 Severe pain activates the stress response2 which increases perioperative cardiac morbidity. Excellent analgesia, however, severely reduces this risk.14
The connection between acute pain and cardiovascular changes is supported observationally. The evidence is indirect but convincing. In humans, epidural analgesia prevents perception of noxious stimulus, reduces nociceptive transmission and prevents/reverses the cardiovascular changes.2,15 Animal evidence connects noxious stimulus with coronary vasoconstriction using methodology not ethically possible in humans. Prevention of noxious stimulus with epidural block increases myocardial oxygen concentration in animals16 and may reduce myocardial ischemia.17
Some of this indirect evidence is confirmed by human studies. Weak evidence suggests less episodes of perioperative myocardial ischemia when nociceptive transmission is reduced by preoperative epidural blockade14,18 or subarachnoid block.19 An overall decrease in cardiovascular complications in patients who received regional anesthesia compared to general anesthesia were observed by Yeager20 although the power of these observations were reduced by randomization issues.