A randomised dose-response study of prophylactic Methoxamine infusion for preventing spinal-induced hypotension during Cesarean delivery

Abstract

Background: α-receptor agonists have been reported to be safe and effective for treating or preventing spinalinduced hypotension during cesarean delivery. As a pure α 1 adrenergic agonist, methoxamine has potential advantages of reducing myocardial oxygen consumption and protecting the heart in obstetric patients compared to phenylephrine. The aim of this study was to determine the optimal prophylactic methoxamine infusion dose that would be effective for preventing spinal-induced hypotension in 50% (ED 50) and 95% (ED 95) of parturients. Methods: Eighty parturients with a singleton pregnancy scheduled for elective cesarean delivery were randomly allocated to receive prophylactic methoxamine infusion at one of four different fixed-rates: 1 μg/kg/min (group M1), 2 μg/kg/min (group M2), 3 μg/kg/min (group M3), or 4 μg/kg/min (group M4). An adequate response was defined as absence of hypotension (maternal SBP < 80% of baseline or SBP < 90 mmHg). The values for ED 50 and ED 95 of prophylactic methoxamine infusion were determined by probit regression model. The outcomes of maternal hemodynamics and fetal status were compared among the groups. Results: The calculated ED 50 and ED 95 (95% confidence interval) of prophylactic methoxamine infusion dose were 2.178 (95% CI 1.564 to 2.680) μg/kg/min and 4.821 (95% CI 3.951 to 7.017) μg/kg/min, respectively. The incidence of hypotension decreased with increasing methoxamine infusion dose (15/20, 11/20, 7/20 and 2/20 in group M1, M2, M3 and M4 respectively, P < 0.001). 1-min Apgar scores and umbilical arterial PaO2 were lower but umbilical arterial PaCO2 was higher in Group M1. No difference was found in the other incidence of adverse effects and neonatal outcomes among groups. Conclusions: Under the conditions of this study, when prophylactic methoxamine infusion was given at a fixedrate based on body weight for preventing spinal-induced hypotension in obstetric patients, the values for ED 50 and ED 95 were 2.178 μg/kg/min and 4.821 μg/kg/min respectively.

The Management of Spinal and Epidural Anesthesia-Related Hypotension in the United States During Cesarean Childbirth

“…Physicians still had to administer boluses of methoxamine during the cesarean section and the randomized control trial (RTC) showed that at lower doses of prophylactic methoxamine infusions, more rescue doses and fluids were necessary (p = 0.0001). The dose-response curve demonstrates an ED50 and ED95 of 2.178 (95% CI 1.564 to 2.680) μg/kg/min and 4.821 (95% CI 3.951 to 7.017) μg/kg/min, respectively [ 12 ].…”

“…Methoxamine is a pure alpha-1 receptor agonist and strictly causes peripheral vasoconstriction [ 17 ]. Studies show that doses of 1-4 μg/kg/min can be used to avoid the complication of maternal hypotension [ 12 ]. While rebound hypertension is a potential side effect of prophylactic methoxamine, the benefits of using it outweigh the risks.…”

α1-Adrenoceptor agonist methoxamine inhibits base excision repair via inhibition of apurinic/apyrimidinic endonuclease 1 (APE1)

“…As a less potent but longer-acting analogue of phenylephrine (generic name Vasoxyl), it has been used as a peripheral vasoconstrictor (blood-pressure-increasing drug) during various surgeries, for example, to improve cognitive dysfunction and blood TNF α-levels during hip replacement surgery in elderly patients (2,3) or as nasal decongestant (4). Importantly, Mox was used in combination with atropine to maintain blood pressure in pregnant women undergoing cesarean delivery (5) in addition to ephedrine (6). Apart from these short-term treatments, Mox has recently been tested in a clinical trial for its capability to increase the anal canal resting pressure in patients with bowel incontinence (7).…”