Intraoperative Use of Phenylephrine versus Ephedrine and Postoperative Delirium: A Multicenter Retrospective Cohort Study.

BACKGROUND: The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium. METHODS: A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied. RESULTS: Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each µg/kg increase in the cumulative phenylephrine dose). CONCLUSIONS: The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.

Prevention of spinal hypotension during cesarean section: A systematic review and Bayesian network meta-analysis based on ephedrine, phenylephrine, and norepinephrine.

AIM: The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine, phenylephrine, and norepinephrine for the prevention of spinal hypotension during cesarean section. METHODS: The Web of Science, PubMed, EMBASE, Cochrane Library were searched until to May 20, 2022. The indicators included incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, umbilical artery pH, and Apgar scores. RESULTS: About 3125 related records were obtained and 17 RCTs met our eligibility criteria. Based on the results, prophylactic bolus injection of 21-30 mg ephedrine (82%) was the best efficacious option for preventing hypotension, followed by 13-16 µg norepinephrine and 81-120 mg phenylephrine; 121-150 µg phenylephrine had the highest probability (62%) caused reactive hypertension, followed by 11-30 mg ephedrine; phenylephrine was most likely to cause bradycardia in a dose-dependent manner; 81-120 µg phenylephrine had the highest probability (37%) which associated with IONV; 6-12 µg norepinephrine (31%) had the lowest influence on IONV and had highest probability (34%) associated with improving umbilical arterial pH; 13-16 µg norepinephrine had highest probability (67% at 1 min, 49% at 5 min) which associated with improving Apgar scores. CONCLUSIONS: Based on this study, 5-10 mg ephedrine and 13-16 µg norepinephrine prophylactic bolus injection may be the optimum dosage of three drugs prevent spinal-induced hypotension, which has the least impact on maternal and neonatal outcomes.

A randomized comparison of hemodynamic changes in response to a heart rate-dependent phenylephrine/ephedrine protocol versus ephedrine-only for spinal hypotension during elective cesarean section.

AIM: To compare incidences of abnormal heart rate (HR) between the phenylephrine/ephedrine protocol (P/E protocol) against the ephedrine-only (C) protocol, conventionally used for treating predelivery hypotension following spinal anesthesia for cesarean section. METHODS: Two hundred and sixty-eight parturients with pre-delivery hypotension after spinal anesthesia were equally randomized to (1) Group P/E (n = 134), phenylephrine 100 mcg in 10 mL intravenously if HR ≥ 60 beats/min (bpm), or ephedrine 6 mg intravenously if HR < 60 bpm, and 2) Group C (n = 134). The primary outcome was the incidence of the parturients with abnormal HR after vasopressor administration. The secondary outcome was the mean differences of HR and hypotensive periods during the pre-delivery period. RESULTS: There was no significant difference of between-group incidences of bradycardia (12.0% in Group P/E vs 6.7% in Group C, p = 0.136) and tachycardia (26.9% vs 35.8%, p = 0.114). Mean HR was 81.9 bpm (95% confidence interval [CI] 79.9, 84.3) in Group P/E, and 88.8 bpm (86.8, 90.6) in Group C (p < 0.001). The duration of hypotension in relation to the time interval from spinal anesthesia to delivery was 20.9% (95% CI 18.4-23.2) in Group P/E, and 26.5% (23.9-29.3) in Group C (p < 0.01). The calculated area under the curve (AUC) of abnormal HR in relation to time was significantly reduced only in Group P/E (p < 0.010). CONCLUSIONS: The incidences of out-of-range HR were comparable, but the P/E protocol resulted in a lower mean HR and better control of systolic blood pressure than the ephedrine-only protocol.

In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine.

Obesity is a major public health problem worldwide. Only relatively few treatment options are, at present, available for the management of obese patients. Furthermore, treatment of obesity is affected by the widespread misuse of drugs and food supplements. Ephedra sinica is an old medicinal herb, commonly used in the treatment of respiratory tract diseases. Ephedra species contain several alkaloids, including pseudoephedrine, notably endowed with indirect sympathomimetic pharmacodynamic properties. The anorexigenic effect of pseudoephedrine is attributable primarily to the inhibition of neurons located in the hypothalamic paraventricular nucleus (PVN), mediating satiety stimuli. Pseudoephedrine influences lipolysis and thermogenesis through interaction with ß3 adrenergic receptors and reduces fat accumulation through down-regulation of transcription factors related to lipogenesis. However, its use is associated with adverse events that involve to a large extent the cardiovascular and the central nervous system. Adverse events of pseudoephedrine also affect the eye, the intestine, and the skin, and, of relevance, sudden cardiovascular death related to dietary supplements containing Ephedra alkaloids has also been reported. In light of the limited availability of clinical data on pseudoephedrine in obesity, along with its significantly unbalanced risk/benefit profile, as well as of the psychophysical susceptibility of obese patients, it appears reasonable to preclude the prescription of pseudoephedrine in obese patients of any order and degree.

Analgesia Nociception Index (ANI) and ephedrine: a dangerous liasion.

The Analgesia Nociception Index is a dimensionless scale derived from the heart rate variability; by analyzing the heart rate variability oscillations, it reflects the activity of the sympathetic and parasympathetic nervous systems and ultimately helps to evaluate the Nociception-Antinociception balance during anesthesia and surgery. Drugs like ephedrine affect the heart rate variability inducing artifacts in the ANI readings which should be taken into account in the clinical practice and in clinical research.

The efficacy of intramuscular ephedrine in preventing hemodynamic perturbations in patients with spinal anesthesia and dexmedetomidine sedation.

Dexmedetomidine is used for sedation during spinal anesthesia. The sympatholytic effect of dexmedetomidine may exacerbate hypotension and bradycardia with spinal anesthesia. This study investigated the effects of prophylactic intramuscular injection of ephedrine in preventing hypotension and bradycardia occurring through combined use of spinal anesthesia and dexmedetomidine. One hundred sixteen patients scheduled for lower extremity orthopedic surgery were randomized into two groups receiving either ephedrine 20 mg intramuscularly or equivalent amount of 0.9% NaCl, both with dexmedetomidine and spinal anesthesia. The primary endpoint was the incidence of hemodynamic perturbations (hypotension or bradycardia event). The secondary endpoint was a rescue doses of ephedrine and atropine. The incidence of hemodynamic perturbations was significantly lower in the ephedrine group compared with to the saline group (26.3% versus 55.9%, p = 0.001). The rescue doses of atropine (0.09 ± 0.21 versus 0.28 ± 0.41, p = 0.001) and ephedrine (1.04 ± 2.89 versus 2.03 ± 3.25, p = 0.007) were also significantly lower in the ephedrine group. There was no differences in number of patients with hypertensive (7.0% versus 11.9%, p = 0.375) or tachycardia (1.8% versus 3.4% p = 0.581) episodes. The use of ephedrine intramuscular injections may be a safe and efficacious option in preventing hemodynamic perturbations in patients who received spinal anesthesia and sedation using dexmedetomidine.

Treatments for priapism in boys and men with sickle cell disease.

BACKGROUND: Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally 'sickle-shaped' red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals. This is an update of a previously published review. OBJECTIVES: To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries. Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 09 September 2019. Date of most recent search of trial registries and of Embase: 01 October 2019. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing non-surgical or surgical treatment with placebo or no treatment, or with another intervention for stuttering or fulminant priapism. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed the risk of bias of the trials. MAIN RESULTS: Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and a four-arm trial which compared ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence. However, all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome; and from the evidence included in this review, we are uncertain whether stilboestrol, etilefrine or ephedrine reduce the frequency of stuttering priapism as the certainty of the evidence has been assessed as very low. Additionally, we conclude that sildenafil may make little or no difference (low-certainty evidence). Two trials reported on immediate side effects and we are uncertain whether etilefrine or ephedrine reduce the occurrence of these (very low-certainty of evidence) and also conclude that sildenafil may make little or no difference in side effects (low-quality evidence). Given that all of the trials were at risk of bias and all had low participant numbers, we considered the certainty of the evidence to be low to very low. AUTHORS' CONCLUSIONS: There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.

Push dose pressors: Experience in critically ill patients outside of the operating room.

PURPOSE: Evaluate push dose vasopressor (PDP) practice patterns, efficacy, and safety in critically ill patients. METHODS: Critically ill patients receiving phenylephrine or ephedrine PDP from November 2015-March 2017 were included. Patient demographics, medication administration details, vital signs pre- and post-administration, adverse effects, and medications errors were collected. Descriptive data are presented and comparisons were made with paired samples t-test, Wilcoxon Rank Sum and Chi-squared analysis or Fisher's Exact Test as appropriate. RESULTS: A total of 146 patients (155 PDP events) were included; mean age 64.5 ±â€¯13.3 years and 66.4% males, respiratory failure (39.8%) or sepsis (24.9%) admission diagnosis. The surgical intensive care unit (ICU) (44.5%) and medical ICU (33.6%) used PDPs most often, and during the peri-intubation period (57.3%) or for other transient hypotension (38.2%). Following PDP, mean systolic blood pressure (BP), diastolic BP, and heart rate (HR) increased 32.5% (80 to 106 mmHg), 27.2% (48 to 61 mmHg), and 6.4% (93 to 99 bpm), respectively. There were 17 (11.6%) adverse events; most often related to excessive increases in BP or HR and one incidence of dysrhythmia. Thirteen patients (11.2%) had a dose related medication error (phenylephrine dose >200 µg or ephedrine dose >25 mg), nine (6.2%) received PDP with normal/elevated hemodynamics (systolic BP > 100 mmHg or HR > 160 bpm) and 15% while on a continuous infusion vasopressor. CONCLUSION: PDPs were used in a variety of patient diagnoses and for select indications. Overall, they were efficacious but associated with adverse drug events and medication errors.

Ephedrine Alkaloids-Free Ephedra Herb Extract, EFE, Has No Adverse Effects Such as Excitation, Insomnia, and Arrhythmias.

Ephedrine alkaloids-free Ephedra Herb extract (EFE) has been developed to eliminate the adverse effects caused by ephedrine alkaloid-induced sympathetic hyperactivation. Previously, we reported that EFE possesses analgesic, anti-influenza, and cancer metastatic inhibitory effects at comparable levels to that of Ephedra Herb extract (EHE). However, it has not yet been demonstrated that EFE is free from the known side effects of EHE, such as excitation, insomnia, and arrhythmias. In this study, the incidence of these adverse effects was compared between mice administered EHE and those administered EFE. Increased locomotor activity in an open-field test, reduced immobility times in a forced swim test, and reduced sleep times in a pentobarbital-induced sleep test were observed in EHE-treated mice, when compared to the corresponding values in vehicle-treated mice. In contrast, EFE had no obvious effects in these tests. In electrocardiograms, atrial fibrillation (i.e., irregular heart rhythm, absence of P waves, and appearance of f waves) was observed in the EHE-treated mice. It was suggested that this atrial fibrillation was induced by stimulation of adrenaline ß1 receptors, but not by hypokalemia. However, EFE did not affect cardiac electrophysiology. These results suggest that the abovementioned side effects are caused by ephedrine alkaloids in EHE, and that EFE is free from these adverse effects, such as excitation, insomnia, and arrhythmias. Thus, EFE is a promising new botanical drug with few adverse effects.

Spontaneous hepatic rupture in a bodybuilder: a case report and review of the literature.

This article is the first description of a spontaneous hepatic rupture in a young bodybuilder with a history of clenbuterol and ephedrine alkaloid use. The patient presented with a sudden mid-epigastric pain and vomiting. Hemoglobin levels decreased a few hours later and a computed tomography scan was performed which revealed a rupture of the right liver capsule and hemoperitoneum. Two attempts at transarterial embolization did not control the bleeding and a right hemihepatectomy was performed. The pathological report identified a hepatic adenoma, a capsular tear and diffuse peliosis hepatis. The patient was discharged in a good condition after eleven days. Spontaneous hepatic ruptures are rare and life-threatening and are usually described in association with tumors, connective tissue diseases and gestosis. This article is a review of the available literature with regard to this condition, with a focus on its relation to peliosis hepatis and banned substance used by body image fanatics. The present case highlights the challenging diagnosis of this potentially fatal liver complication in a healthy appearing male, the risk associated with the online trade of performance enhancing drugs and its relation with peliosis hepatis.

Ventricular arrhythmias induced by long-term use of ephedrine in two competitive athletes.

Ephedrine is a sympathomimetic substance used by sportsmen as a doping substance because of its stimulating and slimming effects. We report two cases of ventricular arrhythmias induced by abuse of ephedrine in two competitive athletes. Endomyocardial biopsies guided by electroanatomic mapping revealed contraction-band necrosis, a myocardial injury frequently observed in cases of catecholamine excess. Our cases suggest that long-term abuse of ephedrine may result in myocardial damage, and that these structural alterations may promote areas of slow conduction favoring re-entrant ventricular tachyarrhythmias and a long-lasting risk of ventricular arrhythmias.

Closed-loop double-vasopressor automated system vs manual bolus vasopressor to treat hypotension during spinal anaesthesia for caesarean section: a randomised controlled trial.

Hypotension necessitating vasopressor administration occurs commonly during caesarean section under spinal anaesthesia. We developed a novel vasopressor delivery system that automatically administers phenylephrine or ephedrine based on continuous non-invasive arterial pressure monitoring. A phenylephrine bolus of 50 µg was given at 30-s intervals when systolic blood pressure fell < 90% of baseline; an ephedrine bolus of 4 mg was given instead if systolic pressure fell < 90% of baseline together with a heart rate < 60 beats.min(-1). The control group used manual boluses of either phenylephrine 100 µg or ephedrine 8 mg, administered at 1-min intervals based on the same thresholds for systolic pressure and heart rate. This randomised, controlled, double-blinded trial involved 213 healthy women who underwent elective caesarean delivery under spinal anaesthesia using 11 mg hyperbaric bupivacaine with 15 µg fentanyl and 100 µg morphine. The automated vasopressor group had better systolic pressure control, with 37/106 (34.9%) having any beat-to-beat systolic pressure reading < 80% of baseline compared with 63/107 (58.9%) in the control group (p < 0.001). There was no difference in the incidence of reactive hypertension, defined as systolic pressure > 120% of baseline, with 8/106 (7.5%) in the automated vasopressor group vs 14/107 (13.1%) in the control group, or total dose of vasopressors. The automated vasopressor group had lower median absolute performance error of 8.5% vs control of 9.8% (p = 0.013), and reduced incidence of nausea (1/106 (0.9%) vs 11/107 (10.3%), p = 0.005). Neonatal umbilical cord pH, umbilical lactate and Apgar scores were similar. Hence, our system afforded better control of maternal blood pressure and reduced nausea with no increase in reactive hypertension when compared with manual boluses.

Risk factors of more severe hypotension after spinal anesthesia for cesarean section.

BACKGROUND: The aim of this study was to examine the risk factors associated with the use of vasopressors to prevent hypotension that occurs after spinal anesthesia during cesarean section. Although the prophylactic use of vasopressors is already suggested as routine care in many parts of the world, the occurrence of spinal anesthesia-induced hypotension (SAIH) is still common in parturients. METHODS: This retrospective study included parturients receiving elective cesarean deliveries under spinal anesthesia from April 2016 to March 2020. Risk factors related to ephedrine dosage were analyzed using a hurdle model, and risk factors related to SAIH were further analyzed with logistic regression. RESULTS: Five risk factors, namely maternal body mass index (BMI, p < 0.001), baseline systolic blood pressure (SBP, p < 0.001), baseline heart rate (HR, p = 0.047), multiparity ( p = 0.003), and large fetal weight ( p = 0.005) were significantly associated with the requirement for ephedrine. Furthermore, a higher ephedrine dosage was significantly associated with maternal BMI ( p < 0.001), baseline SBP ( p < 0.001), baseline HR ( p < 0.001), multiparity ( p = 0.027), large fetal weight ( p = 0.030), maternal age ( p = 0.009), and twin pregnancies ( p < 0.001). Logistic regression analysis also showed that the same five risk factors-maternal BMI ( p = 0.030), baseline SBP ( p < 0.001), baseline HR ( p < 0.001), multiparity ( p < 0.001), and large fetal weight ( p < 0.001)-were significantly associated with SAIH, even in cases where vasopressors were administered. CONCLUSION: These findings can be useful for clinicians when deciding the dose of prophylactic ephedrine or phenylephrine to prevent SAIH.

Severe blood pressure elevation following ephedrine administration during carotid endarterectomy under general anesthesia: A CARE-compliant case report.

RATIONALE: During carotid endarterectomy (CEA) surgery, blood pressure management is particularly important to prevent cerebrovascular and cardiac complications. Ephedrine is a commonly used vasopressor, however, we report the case of a patient with unusually severe blood pressure elevation following intravenous ephedrine administration during CEA. PATIENT CONCERNS: A 72-year-old man diagnosed with right proximal internal carotid artery stenosis underwent CEA under general anesthesia. After declamping the common carotid artery, blood pressure rapidly increased by 125 mm Hg (from 90 to 215 mm Hg) after ephedrine (4 mg) was administered, but the heart rate was stable. DIAGNOSES: There was an ordinal increase in blood pressure after the same small dose of ephedrine was administered at the early stage of the surgery. And the surgical approach was difficult because he had a high location of carotid bifurcation and a prominent mandibular angle. Because of the anatomical proximity of the cervical sympathetic trunk to the carotid bifurcation and the particularly complicated surgical process in the present case, we postulate the reason for this adverse reaction as transient sympathetic denervation supersensitivity. INTERVENTIONS: Perdipine (0.5 mg) was administered repeatedly to reduce blood pressure. OUTCOMES: After surgery, he was diagnosed with right hypoglossal nerve palsy, and no other abnormal signs were found. CONCLUSION: This case highlights the need for caution in the use of ephedrine, which is commonly used in CEA surgery, wherein blood pressure management is particularly important. Although it is a rare and unpredictable case, α-agonists are considered safer in situations where sympathetic supersensitivity is possible.

Ventricular Tachycardia Following Ephedrine During Dexmedetomidine Dental Procedural Sedation.

We present the case of a 46-year-old man who received ephedrine for hypotension after surgery for a mandibular lesion under intravenous (IV) moderate sedation with dexmedetomidine (DEX) and experienced transient ventricular tachycardia (VT). The patient was scheduled to have cystectomy and multiple apicoectomies for the mandibular periapical infection and the simple bone cyst. Other than obesity, snoring, and a nonalcoholic fatty liver, he denied any other significant medical history, medications, or allergies. The surgery was successful; however, his blood pressure dropped after stopping the DEX infusion. Ephedrine was administered IV several times, which resulted in the onset of VT on the electrocardiogram (ECG). His blood pressure could not be measured at the time, but he was able to respond and breathe independently. A defibrillator was immediately made available. The ECG revealed a spontaneous transition from VT to atrial fibrillation with ST depression. Because he was unable to revert to a normal sinus rhythm, the patient was transferred to a general hospital, where he underwent additional testing. No abnormalities were observed in his heart or brain. After DEX administration, its long-lasting alpha-2 adrenoceptor agonist effects can cause vasodilation and inhibition of sympathetic activity, leading to hypotension in some patients. Should that occur, ephedrine can be used to increase blood pressure, but it may also provoke transient coronary artery spasms and lead to VT. Consequently, extreme caution should be exercised in patients who develop hypotension following DEX administration. We also recognize the significance of regular training sessions, such as advanced cardiac life support programs.

A review of the impact of phenylephrine administration on maternal hemodynamics and maternal and neonatal outcomes in women undergoing cesarean delivery under spinal anesthesia.

Phenylephrine is effective for the management of spinal anesthesia-induced hypotension in parturients undergoing cesarean delivery under spinal anesthesia. While ephedrine was previously considered the vasopressor of choice in obstetric patients, phenylephrine is increasingly being used. This is largely due to studies suggesting improved fetal acid-base status with the use of phenylephrine as well as the low incidence of hypotension and its related side effects with prophylactic phenylephrine regimens. This review highlights the effects of phenylephrine compared with ephedrine on maternal hemodynamics (arterial blood pressure, heart rate, and cardiac output), and occurrence of intraoperative nausea and vomiting. The impact of the administration of phenylephrine as a bolus for the treatment of established hypotension compared with its administration as a prophylactic infusion is discussed. This article also reviews the impact of phenylephrine compared with ephedrine on uteroplacental perfusion, and fetal outcomes such as neonatal acid-base status and Apgar scores. The optimum dosing regimen for phenylephrine administration is also discussed.

Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. Systematic review and cumulative meta-analysis.

BACKGROUND: Phenylephrine use has been recommended over ephedrine for the management of hypotension after spinal anesthesia for elective caesarean section. The evidence for this is rather limited because in previous trials, pH was significantly lower after ephedrine, but absolute values were still within normal range. We pooled the available data to define maternal and neonatal effects of the two vasopressors. METHODS: Literature was identified by a systematic search. Hypotension, hypertension, and bradycardia of the mothers, fetal acidosis defined as a pH < 7.20, and the continuous variables base excess (BE) and arterial pCO(2) of the neonates were recorded. Meta-analysis using the random effects model was performed, and the weighted mean difference (WMD) or risk ratio (RR), and 95% confidence interval (95% CI) were calculated. RESULTS: The criteria for eligibility were fulfilled by 20 trials including 1069 patients. The RR of true fetal acidosis was 5.29 (95%CI 1.62-17.25, ) for ephedrine vs. phenylephrine (P = 0.006). BE values after ephedrine use were significantly lower than after phenylephrine (WMD -1.17; 95% CI -2.01 - -0.33). Umbilical artery pCO(2) did not differ. Mothers treated with ephedrine had a lower risk for bradycardia (RR 0.17; 95%CI 0.07-0.43; P = 0.004). No differences between vasopressors were observed for hypotension and hypertension. CONCLUSIONS: Our analysis could clearly demonstrate a decreased risk of fetal acidosis associated with phenylephrine use. In addition with our findings for BE, this suggests a favorable effect of phenylephrine on fetal outcome parameters. The mechanism of pH depression is not related to pCO(2) .