Abstract
BackgroundPostoperative cognitive dysfunction (POCD), common in elderly patients, is thought to be closely associated with intraoperative instability of hemodynamics and excessive excretion of tumor necrosis factor-α (TNF-α). Methoxamine is a blood-pressure increasing drug commonly used for maintaining intraoperative hemodynamics. Methoxamine potentially promotes TNF-α expression, leading to an increased risk of POCD. This study aimed to investigate the dose-dependent effect of methoxamine on the incidence of early POCD and blood TNF-α level.MethodsThis single-center prospective double-blind controlled clinical trial included a total of 300 adult patients (75–90 years old, American Society of Anesthesiologists class II–III) who underwent unilateral hip-joint replacement surgery under epidural anesthesia. Patients were randomly divided into three methoxamine groups (M1, M2, and M3), and one control group (n = 75 per group). During surgery, M1, M2, and M3 patients received intravenous infusion of methoxamine at 2, 3, or 4 μg·kg−1·min−1, respectively; the control group received saline of same volume at the same infusion rate. All patients received standard transfusion to maintain stable circulation. Hemodynamics, cardiovascular events, and serum TNF-α levels were monitored. Mini Mental State Examination was performed both before and after surgery to diagnose POCD.ResultsThe primary outcome of this study was the incidence of POCD, which was higher in the M3 group (18.7%) than in the control group (5.3%), the M1 group (6.7%), or the M2 group (6.7%) (all P < 0.05). The secondary outcomes were the postoperative blood TNF-α level and intraoperative hemodynamic parameters. The postoperative TNF-α level was found to be higher than baseline in all groups and was highest in M3 patients (P < 0.05). The intraoperative hemodynamic parameters showed improved stability in the M1 and M2 groups compared with the control group. However, in the M3 group, abnormally increased intraoperative blood pressure, cardiac output, and systolic stroke volume were observed.ConclusionsIntravenous infusion of methoxamine at 2–3 μg·kg−1·min−1 can maintain stable hemodynamics in elderly patients during epidural anesthesia for hip-joint replacement surgery, without increasing the incidence of POCD. Increasing the dose to 4 μg·kg−1·min−1 provided no further advantages but induced adverse effects on the intraoperative hemodynamics.Trial registrationChinese Clinical Trial Register (Unique identifier: ChiCTR-INR-15007607, retrospectively registered 18 Dec 2015).
Highlights
Postoperative cognitive dysfunction (POCD), common in elderly patients, is thought to be closely associated with intraoperative instability of hemodynamics and excessive excretion of tumor necrosis factor-α (TNF-α)
The peripheral immune system can be activated by surgical injury, leading to the release of various inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), which can diffuse through the blood–brain barrier and cause cognitive deficits [9, 10]
We demonstrated that continuous intravenous infusion of methoxamine (2 μg·kg−1·min−1) can provide safe and effective maintenance of hemodynamics under epidural anesthesia during hip-joint replacement surgery in elderly patients [19]
Summary
Postoperative cognitive dysfunction (POCD), common in elderly patients, is thought to be closely associated with intraoperative instability of hemodynamics and excessive excretion of tumor necrosis factor-α (TNF-α). POCD can significantly interfere with postoperative recovery, increasing patients’ morbidity and mortality rates as well as hospital expenses [5, 6]. It often lasts from a few days to a few weeks after surgery, but has the potential to persist for or occur after several weeks to 7.5 years [7]. It has been demonstrated that beta-adrenoceptor activation suppresses TNF-α release, whereas alpha-adrenoceptor activation stimulates TNF-α release [11, 12]
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