Intravenous Infusion Of Methoxamine Research Articles

Dose-dependent effects of intravenous methoxamine infusion during hip-joint replacement surgery on postoperative cognitive dysfunction and blood TNF-\u03b1 level in elderly patients: a randomized controlled trial

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).

Immediate post renal transplant period and hypertension: concordance between clinic and ambulatory blood pressure

Background: Markedly increased pulse wave velocity (PWV) with aging has been reported in numerous studies. Arterial wave reflection (WR) timing based on of the Augmentation Index (AI) framework does not change appreciably, despite increased PWV. The cause for this apparent discordance has not been established. Although a distal shift of reflecting sites has been proposed, this proposition has been exclusively based on the timing of the inflection point, which is a very limited approach. We hypothesize that AI is not capable of detecting early-systolic effects of reflection, particularly when PWV is high, leading to an apparent reflection-free period in early ejection. Methods: Simultaneous aortic pressure and flow were measured in anesthetized, open-chest dogs (n1⁄45). Intravenous infusion of methoxamine (MTX) and nitroprusside (NTP) were used to increase and decrease WRs, respectively. A coupled left ventricle-arterial system model was used to alter reflection magnitude and timing. Effects of reflection in early-systole were assessed with a systolic pressure-flow ratio (SPFR). Results: SPFR in the case of NTP remained close to aortic characteristic impedance (Zc) [horizontal dashed line] up until peak flow (Fig.1A). In control and MTX, SPFR grew increasingly divergent from Zc before peak flow (Fig.1B-C). Even when an inflection point is observed on the pressure waveform (Fig.1D, inset), SPFR diverges from Zc before the inflection, indicative of early-systole WRs. Modeling studies confirmed the dog experiments in a noise-free environment; only when wave reflections are substantially delayed and/or minimal does SPFR equal Zc in earlysystole. Divergence from this relation is due to WRs. Conclusion:WRs can alter pressure-flow relations in early-systole, prior to time of peak flow and the inflection point on the pressure waveform. Since AI is blind to early-systolic WRs, it should not be used to assess WR timing, especially when PWV is high. This is a particularly important limitation of AI to recognize when studying older subjects as well as those with hypertension in which PWV is elevated. When an appropriate method is used to gauge WR magnitude and timing in earlysystole, elevated PWV is indeed associated with earlier effects of reflections.

Activation of α1-adrenoceptors Inhibits Growth Hormone Secretion in Humans

In order to determine whether an alpha1-adrenergic mechanism is involved in the secretion of Growth Hormone (GH) in humans, we studied the effect of the alpha1-adrenergic-stimulating agent methoxamine on serum GH levels in twelve normal males (age range 22-32 years). Intravenous infusion of methoxamine (dose: 6 microg/kg/min; duration: 150 min) significantly reduced serum GH levels at time 120 and 150, and on integrated concentrations. These data suggest that alpha1-adrenergic receptors inhibit tonic GH secretion in humans.

Adrenergic control mechanism for ACTH secretion in man.

ABSTRACT In order to determine if an adrenergic mechanism is involved in the secretion of corticotrophin (ACTH), the effect of adrenergic-blocking or -stimulating agent on plasma ACTH, cortisol and glucose levels was studied in normal human subjects. The intravenous infusion of methoxamine, an alpha adrenergic-stimulating agent, caused a rise in plasma ACTH and cortisol. This increase in plasma ACTH and cortisol was significantly inhibited by the simultaneous administration of phentolamine, an alpha adrenergic-blocking agent, in combination with methoxamine. The intravenous infusion of propranolol, a beta adrenergic-blocking agent, caused no significant change in plasma ACTH and cortisol, although it enhanced the plasma ACTH response to insulin-induced hypoglycaemia. On the other hand, alpha adrenergicblockade by intravenous infusion of phentolamine significantly suppressed the plasma ACTH response to insulin-induced hypoglycaemia. These studies suggest a stimulatory effect of alpha receptors and a possible inhibitory effect of beta receptors on ACTH secretion in man.

Left ventricular function in patients with chronic obstructive pulmonary disease.

Left ventricular function was assessed in six patients with essentially normal cardiopulmonary function, in five patients with primary myocardial disease, and in 16 patients with chronic obstructive pulmonary disease by determining the response of the ventricle to an increased resistance to ejection. Studies were performed at the time of cardiac catheterization and increased resistance to left ventricular ejection was produced by the intravenous infusion of methoxamine. In the control patients, methoxamine produced an increase in stroke volume index (SVI), in stroke work index (SWI), and stroke power index (SPI), whereas left ventricular end-diastolic pressure (LVEDP) increased only moderately. In contrast SVI, SWI, and SPI fell, whereas LVEDP increased inordinately in the patients with myocardiopathy. The patients with chronic obstructive pulmonary disease responded to the infusion with an increase in SVI, SWI, SPI, and LVEDP comparable to the control patients. Furthermore, in this latter group of patients, a quantitatively similar response was observed in those with essentially normal resting hemodynamics, in those with resting pulmonary hypertension, and in those whose disease had progressed to the stage of right ventricular failure. This study provides no evidence that chronic obstructive pulmonary disease results in chronic impairment of left ventricular function, but on the contrary, has demonstrated that the left ventricle responds normally to an increased pressure load in these patients.