Sympathetic nervous activation following subarachnoid hemorrhage: Influence of intravenous clonidine
Subarachnoid hemorrhage is often accompanied by systemic complications and cerebral vasospasm. Elevated levels of circulating catecholamines may be involved in the pathophysiology behind these events. The alpha-2-agonist clonidine inhibits sympathetic outflow by a central mechanism. Unrestricted sympathoexcitation may be detrimental and administration of clonidine may be beneficial in these patients. Methods:
Using isotope dilution methodology, norepinephrine kinetic determinations, comprising determination of arterial norepinephrine concentration and rates of norepinephrine spillover to and removal, or clearance, from plasma, were performed on three occasions during the first week after subarachnoid hemorrhage in 25 patients. Eleven of these patients received clonidine (continuous i.v. infusion 5.8 ± 0.7 µg·kg−1·24 h−1) and the remainder, standard therapy. Initial results were compared with 17 healthy age-matched subjects and eight patients suffering from severe traumatic brain injury without traumatic subarachnoid hemorrhage. Results:
Subarachnoid hemorrhage patients exhibited markedly elevated arterial plasma norepinephrine concentrations [3.74 ± 0.48, P < 0.001 vs. healthy subjects (1.59 ± 0.11 nmol/L) and P < 0.05 vs. head trauma patients (1.94 ± 0.29 nmol/L)]. The rate of clearance of norepinephrine from plasma in the subarachnoid patients was also significantly greater than that observed in the healthy subjects (2.66 ± 0.15 vs. 2.14 ± 0.15 L/min, P < 0.05) and the head trauma patients (2.00 ± 0.12 L/min, P < 0.05). Compared with both control groups, on admission the rate of spillover of norepinephrine to plasma following subarachnoid hemorrhage was markedly elevated (9.11 ± 1.12, P < 0.001). Clonidine treatment (continuous i.v. infusion 5.8 ± 0.7 µg·kg−1·24 h−1) did not reduce the increased rate of spillover of norepinephrine to plasma following subarachnoid hemorrhage. Conclusion:
Sympathetic nervous activity is markedly elevated following subarachnoid bleeding. Clonidine had no effect on the rate of norepinephrine spillover to, or clearance from, plasma in these patients. Clearly, further studies are required to elucidate the mechanisms responsible for generating sympathetic nervous activation following subarachnoid hemorrhage.
Document Type: Research Article
Affiliations: 1: Department of Clinical Physiology, Sahlgrenska University Hospital, 2: Department of Anesthesia and Intensive Care, Institute of Surgical Sciences and 3: Department of Neurosurgery, Institute of Neurosciences, Sahlgrenska University Hospital, Göteborg;
Publication date: 01 February 2002