Persistent alterations of the autonomic nervous system after noncardiac surgery

Background: Changes in the sympathetic nervous system may be a cause of postoperative cardiovascular complications. The authors hypothesized that changes in both β-adrenergic receptor (βAR) function (as assessed in lymphocytes) and in sympathetic activity (assessed by plasma catecholamines and by heart rate variability [HRV] measurements obtained from Holter recordings) occur after operation. Methods: The HRV parameters were measured in 28 patients having thoracotomy (n = 14) or laparotomy (n = 14) before and for as long as 6 days after operation. Transthoracic echocardiography was performed before and on postoperative day 2. Lymphocytes were also isolated from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). They were used to examine βAR number (B(max)) and cyclic adenosine monophosphate (cAMP) production after stimulation with isoproterenol and prostaglandin El. In addition, plasma epinephrine, norepinephrine, and cortisol concentrations were determined at similar intervals. Results: After abdominal and thoracic surgery, most time and all frequency indices of HRV decreased significantly, as did B(max) and basal and isoproterenol-stimulated cAMP production. The decrements in HRV correlated with those of B(max) and isoproterenol-stimulated cAMP throughout the first postoperative week and inversely correlated with the increase in heart rate. Plasma catecholamine concentrations did not change significantly from baseline values, but plasma cortisol levels did increase after operation in both groups. Left ventricular ejection fraction was normal in both groups and unaffected by surgery. Conclusions: Persistent downregulation and desensitization of the lymphocyte βAR/adenylyl cyclase system correlated with decrements in time and frequency domain indices of HRV throughout the first week after major abdominal or thoracic surgery. These physiologic alterations suggest the continued presence of adaptive autonomic regulatory mechanisms and may explain why the at-risk period after major surgery appears to be about I week or more.