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IntroductionVasopressor support is often preferred as an efficient and convenient way to raise the blood pressure during surgery and intensive care therapy. However, the optimal vasopressor for ensuring organ blood flow and tissue oxygen delivery during surgery remains undetermined. This study aims to assess the impact of norepinephrine versus phenylephrine on cerebral and non-cerebral organ perfusion and oxygenation during anaesthesia in neurosurgical patients with brain tumours. The study also explores the impact of the vasopressor agents on the distribution of cardiac output between various organs.Methods and analysisThis is an investigator-initiated, double-blinded, randomised clinical trial including 32 patients scheduled for supratentorial brain tumour surgery. The patients are randomised to receive a phenylephrine or norepinephrine infusion during preoperative positron emission tomography (PET) examinations and the following neurosurgical procedure. PET measurements of blood flow and oxygen metabolism in the brain and other organs are performed on the awake subject during anaesthesia, following a 10% and 20% gradual increase in blood pressure from the baseline value. The primary endpoint is the between-group difference in cerebral blood flow. Secondary endpoints include detection of ischaemic brain lesions possibly associated with vasopressor treatment, changes in cerebral oxygen metabolism, non-cerebral organ blood flow and oxygen metabolism, cardiac output, regional cerebral oxygen saturation, autoregulation and distribution of cardiac output between organs.Ethics and disseminationThis study was approved by the Danish National Medical Ethics Committee (20 May 2022; 2203674). Results will be disseminated via peer-reviewed publication and presentation at international conferences.Trial registration numberEudraCT no: 2021-006168-26. ClinicalTrials.gov: NCT06083948.

In recent years, norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia. Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China. Thus, in this randomized, double-blinded study, we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension. In a tertiary women's hospital in Nanjing, China, 102 women were allocated with computer derived randomized number to receive prophylactic 8 μg norepinephrine (group N; n = 52) or 100 μg phenylephrine (group P; n = 50) immediately post-spinal anesthesia, followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80% of the baseline. Our primary outcome was standardized maternal cardiac output (CO) reading from spinal anesthesia until delivery analyzed by a two-step method. Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes. Maternal side effects and neonatal outcomes were collected as well. Compared to group P, women in group N had a higher CO (standardized CO 5.8 ± 0.9 vs. 5.3 ± 1.0 L/min, t = 2.37, P = 0.02) and stroke volume (SV, standardized SV 73.6 ± 17.2 vs. 60.0 ± 13.3 mL, t = 4.52, P < 0.001), and a lower total peripheral resistance (875 ± 174 vs. 996 ± 182 dyne·s/cm, t = 3.44, P < 0.001). Furthermore, the incidence of bradycardia was lower in group N than in group P (2% vs. 14%, P = 0.023), along with an overall higher standardized heart rate (78.8 ± 11.6 vs. 75.0 ± 7.3 beats/min, P = 0.049). Other hemodynamics, as well as maternal side effects and neonatal outcomes, were similar in two groups (P > 0.05). Compared to equivalent phenylephrine, intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia; however, no obvious maternal or neonatal clinical advantages were observed for norepinephrine.

In addition to stabilizing blood pressure (BP), ephedrine and phenylephrine have distinct effects on regional cerebral oxygen saturation (rSO 2 ). However, whether its effect on rSO 2 affects the occurrence of postoperative delirium (POD) remains unclear. Therefore, the aim of this study is to compare the effects of ephedrine and phenylephrine for BP maintenance on the incidence of POD in olderly adults who underwent knee arthroplasty under general anesthesia. One hundred twenty patients who were between 60 and 90 years old and underwent knee arthroplasty were included in this study. The patients were randomly divided into two groups: the ephedrine group and the phenylephrine group. After anesthesia induction, ephedrine and phenylephrine were continuously infused to maintain the intraoperative mean arterial pressure within the normal range (baseline mean arterial pressure ± 20%). The primary outcome measures included the incidence of POD within 1–3 days after surgery. The incidence of POD on the first day after surgery was lower in the ephedrine group than in the phenylephrine group (33% vs. 7%, P  < 0.001). However, there was no significant difference in the incidence of POD between the two groups on the second and third postoperative days. Compared with the phenylephrine group, the ephedrine group experienced significantly greater cardiac output (CO) and rSO 2 ( P  < 0.05). Clinical Trials Registry: ChiCTR2200064849, principal investigator: Changjian Zheng.

Cardiopulmonary bypass (CPB) in cardiac surgery is associated with a high risk of postoperative neurological complications. Perioperative use of vasopressors is common to counteract arterial hypotension in this setting. However, use of α‐agonist vasopressors has been associated with cerebral desaturations. Given that reductions in cerebral oxygen saturation (ScO2 ${S_{{\\mathrm{c}}{{\\mathrm{O}}_2}}}$ ) can increase postoperative neurological dysfunction, we aimed to investigate the impact of noradrenaline (NA) and phenylephrine (PE) on ScO2 ${S_{{\\mathrm{c}}{{\\mathrm{O}}_2}}}$during the CPB period of a cardiac surgery in 36 patients scheduled for an elective cardiac surgery. Patients were randomized to the intra‐operative use of either NA or PE. During CPB, mean arterial pressure (MAP) was elevated pharmacologically to predefined thresholds of 60 and 80 mmHg, while CPB flow was kept constant. The ScO2 ${S_{{\\mathrm{c}}{{\\mathrm{O}}_2}}}$values were recorded for 5 min per MAP threshold. The MAP increased adequately between thresholds of 60 and 80 mmHg (NA, 59 ± 3 vs. 81 ± 3 mmHg and PE, 61 ± 4 vs. 81 ± 3 mmHg; P ˂ 0.01). The ScO2 ${S_{{\\mathrm{c}}{{\\mathrm{O}}_2}}}$decreased between pressure thresholds of 60 and 80 mmHg (NA, 70 ± 11 vs. 69 ± 11 mmHg and PE, 64 ± 11 vs. 63 ± 11 mmHg; P ˂ 0.01). Reduction in ScO2 ${S_{{\\mathrm{c}}{{\\mathrm{O}}_2}}}$did not differ between vasopressors. The mean relative decrease in ScO2 ${S_{{\\mathrm{c}}{{\\mathrm{O}}_2}}}$across groups was 2.0% (95% confidence interval: 0.6 to 2.1). Elevation in MAP mediated solely by vasopressors induces significant decreases in ScO2 ${S_{{\\mathrm{c}}{{\\mathrm{O}}_2}}}$during cardiac surgery under CPB. However, their impact on ScO2 ${S_{{\\mathrm{c}}{{\\mathrm{O}}_2}}}$remains clinically non‐significant according to current guidelines. What is the central question of this study? What is the impact of an elevation in mean arterial pressure, mediated by noradrenaline or phenylephrine, on cerebral oxygenation in patients undergoing cardiac surgery with cardiopulmonary bypass. What is the main finding and its importance? The findings indicate that relative cerebral oxygenation decreased by 2% between 60 and 80 mmHg with noradrenaline and phenylephrine. These statistically significant decreases in cerebral oxygenation have no clinical impact. These results support the safety of increasing mean arterial pressure to the upper limit of recommended mean arterial pressure under cardiopulmonary bypass.

Previous evidence showed that use of phenylephrine was associated with higher umbilical artery pH (UA pH) than ephedrine after elective cesarean delivery (CD). However, the best choice of vasopressor and its effect on funic gases in cases of acute fetal compromise require additional studies. Ninety parturients showing acute fetal compromise during intrapartum period and taken up for CD (category II) under spinal anesthesia were randomized to receive prophylactic infusion of ephedrine 2.5mg/min or phenylephrine 30μg/min. Systolic blood pressure was targeted between 90% and 110% of baseline. Incidence of fetal acidosis (UA pH <7.2 and/or base deficit >12mmol/L) was recorded. Other parameters of cord gases, Apgar score, need for immediate resuscitation, maternal hemodynamics, and adverse events were also compared. Number of neonates showing acidosis with ephedrine or phenylephrine was comparable (P=.22). Of these, newborns with base deficit >12mmol had low 1-minute Apgar scores (n=15/23). The ephedrine group had higher oxygen content in UA (P=.03). There was no adverse neonatal outcome during the period of observation. Incidence of maternal nausea and vomiting was higher with ephedrine than with phenylephrine (22.2% vs 4.4%; P=.02). Maternal bradycardia was observed with phenylephrine (P=.02). Our data report similar fetal acidosis with either phenylephrine or ephedrine administered during spinal anesthesia for treating maternal hypotension in cases of emergency CD. •Fetal acidosis has been reported after spinal anesthesia.•Maintaining baseline blood pressure results in best neonatal outcome in elective CD.•Only retrospective data are available for CD indicated for acute fetal compromise.•We report fetal acidosis using vasopressor during CD for acute fetal compromise.

Spinal anesthesia often causes hypotension, with consequent risk to the fetus. The use of vasopressor agents has been highly recommended for the prevention of spinal anesthesia-induced hypotension during caesarean delivery. Many studies have shown that norepinephrine can provide more stable maternal hemodynamics than phenylephrine. We therefore tested the hypothesis that norepinephrine preserves fetal circulation better than phenylephrine when used to treat maternal hypotension consequent to spinal anesthesia. Prospective, randomized, double-blinded study. Operating room. We recruited 223 parturients with uncomplicated singleton pregnancies who were scheduled for elective caesarean section under combined spinal-epidural anesthesia. The patients received prophylactic intravenous infusion of either 0.08 μg/kg/min norepinephrine or 0.5 μg/kg/min phenylephrine for prevention of spinal anesthesia-induced hypotension. Changes in fetal heart rate and fetal cardiac output before and after spinal anesthesia were measured using noninvasive Doppler ultrasound. 90 subjects who received norepinephrine infusion and 93 subjects who received phenylephrine infusion were ultimately analyzed in the present study. The effects of norepinephrine and phenylephrine on the change of fetal heart rate and fetal cardiac output at 3 and 6 min after spinal block were similar. Although there was a statistically significant decrease in fetal cardiac output at 6 min after subarachnoid block initiation in both the norepinephrine group (mean difference 0.02 L/min; 95% CI, 0–0.04 L/min; P = 0.03) and the phenylephrine group (mean difference 0.02 L/min; 95% CI, 0–0.04 L/min; P = 0.02), it remained within the normal range. Prophylactic infusion of comparable doses of phenylephrine or norepinephrine has similar effects on fetal heart rate and cardiac output changes after spinal anesthesia. Neither phenylephrine nor norepinephrine has meaningful detrimental effects on fetal circulation or neonatal outcomes. •Prophylactic infusion of comparable doses of phenylephrine or norepinephrine has similar effects on fetal heart rate and cardiac output changes after spinal anesthesia.•Neither phenylephrine nor norepinephrine has meaningful detrimental effects on fetal circulation.

Background and Objectives Phenylephrine HCl 10 mg has been used as a nasal decongestant for over 50 years, yet only limited pharmacokinetic and metabolic data are available. The purpose of this study was to evaluate single-dose pharmacokinetics and safety of phenylephrine HCl 10, 20, and 30 mg and to assess cardiovascular tolerability compared with baseline and placebo in healthy volunteers. Methods Twenty-eight adults were enrolled in this randomized, double-blind, placebo-controlled, single-dose, four-treatment crossover study. Subjects remained housed for 6 days to permit time-matched, serial measurements of pulse, blood pressure, and electrocardiograms (ECGs) for baseline and complete treatments on consecutive days. After fasting overnight, subjects were dosed with oral phenylephrine HCl 10, 20, or 30 mg or placebo. Pharmacokinetic blood samples were collected over 7 h, whereas pulse, blood pressure, and ECGs were measured over 12 h. Urine was collected over each 24-h period to quantify phenylephrine and metabolites. Results After oral administration, phenylephrine was rapidly absorbed with median times to maximum plasma concentrations ( t max ) from 0.33 to 0.5 h. For phenylephrine HCl 10, 20, and 30 mg, the mean (standard deviation) maximum concentration ( C max ) was 1354 (954), 2959 (2122), and 4492 (1978) pg/mL, and total systemic exposure [area under the plasma concentration–time curve from time zero to infinity (AUC ∞ )] was 955.8 (278.5), 2346 (983.8), and 3900 (1764) pg·h/mL, respectively. Both parameters increased disproportionally with increasing dose, as β >1 in the power model. Negligible amounts of phenylephrine and phenylephrine glucuronide were excreted in urine. With increasing dose, percentages by dose of phenylephrine sulfate decreased, whereas percentages of 3-hydroxymandelic acid increased. Eight subjects reported nine mild adverse events; one (somnolence) was deemed to be treatment related. Means of time-matched differences in pulse and blood pressure from baseline showed similar fluctuations over 12 h among phenylephrine HCl doses and placebo, although small differences in systolic pressure were observed during the initial 2 h. No apparent dose-related effects were observed for Fridericia-corrected QT interval (QTcF) values, and individual changes from time-matched baseline (DQTcF). Conclusions Maximum and total systemic exposures following singe doses of phenylephrine HCl 10, 20, and 30 mg increased disproportionally with increasing dose. Safety and cardiovascular tolerability were comparable among doses and placebo.

Background Vasopressors are administered to critically ill patients with vasodilatory shock not responsive to volume resuscitation, and less often in cardiogenic shock, and hypovolemic shock. Objectives The objectives are to review safety and efficacy of vasopressors, pathophysiology, agents that decrease vasopressor dose, predictive biomarkers, β1-blockers, and directions for research. Methods The quality of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results Vasopressors bind adrenergic: α1, α2, β1, β2; vasopressin: AVPR1a, AVPR1B, AVPR2; angiotensin II: AG1, AG2; and dopamine: DA1, DA2 receptors inducing vasoconstriction. Vasopressor choice and dose vary because of patients and physician practice. Adverse effects include excessive vasoconstriction, organ ischemia, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. No randomized controlled trials of vasopressors showed a significant difference in 28-day mortality rate. Norepinephrine is the first-choice vasopressor in vasodilatory shock after adequate volume resuscitation. Some strategies that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality while corticosteroids have decreased 28-day mortality significantly in some (two large trials) but not all trials. In norepinephrine-refractory patients, vasopressin or epinephrine may be added. A new vasopressor, angiotensin II, may be useful in profoundly hypotensive patients. Dobutamine may be added because vasopressors may decrease ventricular contractility. Dopamine is recommended only in bradycardic patients. There are potent vasopressors with limited evidence (e.g. methylene blue, metaraminol) and novel vasopressors in development (selepressin). Conclusions Norepinephrine is first choice followed by vasopressin or epinephrine. Angiotensin II and dopamine have limited indications. In future, predictive biomarkers may guide vasopressor selection and novel vasopressors may emerge.

Postoperative delirium (POD) is a common complication in elderly patients. Since ephedrine and phenylephrine have different effects on cerebral perfusion and oxygenation, this randomized controlled trial aimed to compare the impact of these two drugs on the incidence of POD in elderly patients undergoing total hip or knee arthroplasty under general anesthesia. A total of 142 elderly patients, aged 65 to 80 years, who underwent elective surgery for total hip or knee arthroplasty were randomly assigned to either the ephedrine group (Group E) or the phenylephrine group (Group P). POD was evaluated using the 3-minute Diagnostic Confusion Assessment Method (3D-CAM). The primary outcome was the incidence of POD within three days after surgery, while secondary outcomes included the subtypes of delirium, intraoperative hemodynamic changes, intraoperative analgesic consumption, and the occurrence of intraoperative and postoperative adverse events. Delirium occurred in 5 out of 65 cases (7.7%) in Group E and in 15 out of 67 cases (22.4%) in Group P (relative risk [RR], 0.344; 95% confidence interval [CI], 0.132 to 0.891; p = 0.019). Compared to Group P, Group E exhibited a significantly lower incidence of intraoperative bradycardia (RR, 0.241; 95% CI, 0.114 to 0.508; p < 0.001). However, Group E also demonstrated a significantly higher consumption of intraoperative opioids (median difference [MD], 23.0; 95% CI, 2.0 to 25.0 mg; p = 0.020). Notably, despite the higher intraoperative opioid consumption in Group E, there was no statistically significant difference in postoperative pain scores between the two groups (p > 0.05). Additionally, there were no statistically significant differences between the two groups in other indicators, including intraoperative hemodynamic changes and the incidence of postoperative nausea and vomiting (p > 0.05). In conclusion, among elderly patients undergoing hip or knee arthroplasty, the use of ephedrine to correct intraoperative hypotension was associated with a reduced incidence of POD within three days compared to phenylephrine. However, the absence of cerebral oxygen saturation monitoring and the limited follow-up period of only three days for POD assessment represent significant limitations. These factors should be carefully considered when interpreting our results.

Spinal anesthesia-induced hypotension can cause detrimental effects on both the mother and the fetus, and it remains a significant concern in obstetric anesthesia. The use of vasopressors is considered the most reliable and effective approach. Previous studies have shown that norepinephrine appears to be superior to phenylephrine in maintaining maternal heart rate and cardiac output. Therefore, we hypothesize that norepinephrine is more effective than phenylephrine in maintaining neonatal cerebral perfusion when used to prevent spinal anesthesia-induced hypotension. This study is a prospective, double-blinded, randomized trial. We enrolled 216 singleton parturients who were scheduled for elective cesarean delivery. The patients received a prophylactic intravenous infusion of either norepinephrine (0.08 μg/kg/min) or phenylephrine (0.5 μg/kg/min). Maternal cardiac output was not routinely monitored during the study period. Fetal ultrasound examinations were performed, with blood velocity measured in the middle cerebral artery and umbilical artery, and the cerebroplacental ratio calculated. Ninety subjects were ultimately analyzed in each group. The changes in blood velocity in the middle cerebral artery and umbilical artery, as well as the calculated cerebroplacental ratio at 3 and 6 minutes after spinal anesthesia, did not differ significantly between the two groups. The estimated difference of ΔCPR in two groups was - 0.01 (95% CI, -0.05-0.02, P = 0.491) at 3 minutes and was 0.02 (95% CI, -0.01-0.07, P = 0.204) at 6 minutes. Prophylactic infusion of norepinephrine or phenylephrine at comparable doses has similar effects on fetal cerebral perfusion.