Haemodynamic Changes After Prophylactic Doses of Ephedrine, Phenylephrine, Norepinephrine Versus Placebo During Induction of General Anaesthesia: A Randomised Trial.

Abstract

Ephedrine, phenylephrine, and norepinephrine are commonly used to manage hypotension during the induction of anaesthesia. The objective of this study was to evaluate whether prophylactic administration of assumed equipotent doses of these vasopressors could maintain systolic arterial blood pressure (SAP) and heart rate (HR) within 80% of baseline for the first 5 min following induction of anaesthesia. This randomised, double-blind, dose-controlled study was conducted at the Day Surgery Unit of Haugesund Hospital, Norway. One hundred and twenty-eight healthy women scheduled for gynaecological surgery were randomly allocated in a 1:1:1:1 ratio to receive prophylactic administration of ephedrine (0.1 mg/kg), phenylephrine (1 μg/kg), norepinephrine (0.1 mg/kg), or placebo (sodium chloride 9 mg/mL) at a volume of 0.1 mL/kg. Anaesthesia was induced using target-controlled infusion (TCI) of propofol and remifentanil. The initial 2.5 min constituted a sedation phase, after which the targets of propofol and remifentanil were increased, and the assigned vasopressor was administered. Beat-to-beat haemodynamic monitoring was performed using the LiDCOplus system. The primary outcome variables were the maximal decrease in SAP and HR within 5 min following bolus administration. Secondary outcome measures included changes in stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR). The absolute changes in SAP (mean ± standard deviation) following vasopressor administration were -27 ± 8.9 (ephedrine), -40 ± 11 (phenylephrine), -41 ± 13 (norepinephrine), and -42 ± 10 (placebo) mmHg. The differences (95% confidence interval [CI]) in the maximal SAP change between placebo and the vasopressors were as follows: ephedrine, -15 (-22, -9.9) mmHg; phenylephrine, -2.3 (-8.8, 4.2) mmHg; and norepinephrine, -1.7 (-8.3, 4.9) mmHg. Relative reductions in SAP from baseline to minimum values were -20% for ephedrine, -30% for phenylephrine, -30% for norepinephrine, and -32% for placebo. The absolute changes (median, interquartile range) in HR with ephedrine, phenylephrine, norepinephrine, and placebo were -10 (-6.2 to -18), -19 (-17 to -26), -23 (-20 to -33), and -15 (-9.5 to -21) bpm, respectively. Relative changes from baseline to minimum values in HR were -17% for ephedrine, -30% for phenylephrine, -37% for norepinephrine, and -22% for placebo. The differences in SV change between groups were small. CO was best preserved with ephedrine (-22% ± 11%), while phenylephrine and norepinephrine were associated with greater reductions (-38% ± 7.8% and -42% ± 9.8%, respectively). SVR increased most markedly in the norepinephrine group, followed by phenylephrine, with the smallest increase observed in the ephedrine group. Prophylactic administration of ephedrine effectively maintained SAP, HR, and CO within the first 5 min following bolus injection at induction with propofol and remifentanil. In contrast, bolus administration of norepinephrine and phenylephrine demonstrated a short duration of action, with SAP comparable to placebo at 5 min. Based on these findings, prophylactic administration of a bolus ephedrine is recommended, whereas prophylactic phenylephrine or norepinephrine injections may not be clinically preferable for bolus use in this context. ClinicalTrials.gov identifier NCT03864094, March 6, 2019 This trial assessed circulatory responses to three different commonly used vasoactive support (vasopressor) drugs given as a single bolus together anesthetic induction propofol and remifentanil, and this in a cardiovascularly healthy adult surgical cohort. Results demonstrated that pharmacodynamic patterns with the three different test drugs, along with a no-prophylactic vasopressor comparitor. Findings showed a favorable profile for ephedrine compared to phenylephrine or noradrenaline if choosing to give a vasopressor in this way.