Evaluation of the early use of norepinephrine in major abdominal surgery on medical and surgical postoperative complications: study protocol for a randomised controlled trial (EPON STUDY).

BACKGROUND: Post-induction anaesthesia often promotes intraoperative hypotension (IOH) that can worsen postoperative outcomes. This study aims to assess the benefit of norepinephrine versus ephedrine at the induction of anaesthesia to prevent postoperative complications following major abdominal surgery by preventing IOH. METHODS AND ANALYSIS: The EPON STUDY is a prospective single-centre randomised controlled trial with the planned inclusion of 500 patients scheduled for major abdominal surgery at the Amiens University Hospital. The inclusion criteria are patients aged over 50 years weighing more than 50 kg with an American Society of Anesthesiologists physical status score of ≥2 undergoing major abdominal surgery under general anaesthesia. Patients are allocated either to the intervention group (n=250) or the standard group (n=250). In the intervention group, the prevention of post-induction IOH is performed with norepinephrine (dilution to 0.016 mg/mL) using an electric syringe pump at a rate of 0.48 mg/h (30 mL/h) from the start of anaesthesia and then titrated to achieve the haemodynamic target. In the control group, the prevention of post-induction IOH is performed with manual titration of ephedrine, with a maximal dose of 30 mg, followed by perfusion with norepinephrine. In both groups, the haemodynamic target to maintain is a mean arterial pressure (MAP) of 65 mm Hg or 70 mm Hg for patients with a medical history of hypertension. An intention-to-treat analysis will be performed. The primary outcome is the Clavien-Dindo score assessed up to 30 days postoperatively. The secondary endpoints are the length of hospital stay and length of stay in an intensive care unit/postoperative care unit; postoperative renal function; postoperative cardiovascular, respiratory, neurological, haematological and infectious complications at 1 month; and volume of intraoperative vascular filling and mortality at 1 month. ETHICS AND DISSEMINATION: Ethical approval was obtained from the committee of protection of the persons of Ile de France in May 2021 (number 21 05 41). The authors will be involved in disseminating the research findings (through attending conferences and co-authoring papers). The results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05276596.

Oral midodrine for prophylaxis against post-spinal anesthesia hypotension during hip arthroplasty in elderly population: a randomized controlled trial.

BACKGROUND: We aimed to evaluate the efficacy of midodrine as a prophylaxis against post-spinal hypotension in elderly patients undergoing hip arthroplasty. METHODS: This randomized controlled trial included elderly patients undergoing hip arthroplasty under spinal anesthesia. Ninety minutes before the procedure, patients were randomized to receive either 5-mg midodrine or placebo (metoclopramide). After spinal anesthesia, mean arterial pressure (MAP) and heart rate were monitored every 2 min for 20 min then every 5 min until the end of the procedure. Post-spinal hypotension (MAP < 80% baseline) was treated with 10 mg ephedrine. The primary outcome was intraoperative ephedrine consumption. Secondary outcomes were the incidence of post-spinal hypotension, bradycardia, and hypertension (MAP increased by > 20% of the baseline reading). RESULTS: We analyzed 29 patients in the midodrine group and 27 in the control group. The intraoperative ephedrine consumption was lower in the midodrine group than in the control group (median [quartiles]: 10 [0, 30] mg versus 30 [20, 43] mg, respectively, P-value: 0.002); and the incidence of intraoperative hypotension was lower in the midodrine group than that in the control group. The incidence of hypertension and bradycardia were comparable between the two groups. CONCLUSION: The use of 5 mg oral midodrine decreased the vasopressor requirements and incidence of hypotension after spinal anesthesia for hip surgery in elderly patients. CLINICAL TRIAL REGISTRATION: This study was registered on September 22, 2022 at clinicaltrials.gov registry, NCT05548985, URL: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05548985 .

Correlation Between Cerebral Tissue Oxygen Saturation and Oxygen Extraction Fraction During Anesthesia: Monitoring Cerebral Metabolic Demand-supply Balance During Vasopressor Administration.

BACKGROUND: The speculation that cerebral tissue oxygen saturation (SctO 2 ) measured using tissue near-infrared spectroscopy reflects the balance between cerebral metabolic rate of oxygen and cerebral oxygen delivery has not been validated. Our objective was to correlate SctO 2 with cerebral oxygen extraction fraction (OEF) measured using positron emission tomography; OEF is the ratio between cerebral metabolic rate of oxygen and cerebral oxygen delivery and reflects the balance between these 2 variables. MATERIALS AND METHODS: This cohort study was based on data collected in a previously published trial assessing phenylephrine versus ephedrine treatment in anesthetized patients undergoing brain tumor surgery. The variables of interest were measured twice over the healthy hemisphere before surgery: the first measurement performed after anesthesia induction and the second measurement performed after induction of a ∼20% increase in blood pressure using either phenylephrine or ephedrine. RESULTS: Data from 24 patients were analyzed. The overall vasopressor-induced relative changes in SctO 2 (ΔSctO 2 ) and OEF (ΔOEF) were 3.16% [interquartile range, -0.73% to 6.04%] and -12.5% [interquartile range, -24.0% to -6.19%], respectively. ΔSctO 2 negatively correlated with ΔOEF after phenylephrine treatment (Spearman rank correlation coefficient [ rs ]=-0.76; P =0.007), ephedrine treatment ( rs =-0.76; P =0.006), and any treatment ( rs =-0.79; P <0.001). ΔSctO 2 significantly associated with ΔOEF based on multivariable analysis with ΔOEF, relative changes in mean arterial pressure, arterial blood oxygen tension, and the bispectral index as covariates ( P =0.036). CONCLUSIONS: The negative correlation between changes in SctO 2 and OEF suggests that SctO 2 may reflect the cerebral metabolic demand-supply balance during vasopressor treatment. The generalizability of our findings in other clinical scenarios remains to be determined.

The Regional Cerebral Oxygen Saturation Effect of Inotropes/Vasopressors Administered to Treat Intraoperative Hypotension: A Bayesian Network Meta-analysis.

One of the main concerns of intraoperative hypotension is adequacy of cerebral perfusion, as cerebral blood flow decreases passively when mean arterial pressure falls below the lower limit of cerebral autoregulation. Treatment of intraoperative hypotension includes administration of drugs, such as inotropes and vasopressors, which have different pharmacological effects on cerebral hemodynamics; there is no consensus on the preferred drug to use. We performed a network meta-analysis (NMA) to pool and analyze data comparing the effect on cerebral oxygen saturation (ScO 2 ) measured by cerebral oximetry of various inotropes/vasopressors used to treat intraoperative hypotension. We searched randomized control trials in Embase, Ovid Medline, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. We included studies that enrolled adult patients undergoing surgery under general/spinal anesthesia that compared at least 2 inotropes/vasopressors to treat hypotension. We reviewed 51 full-text manuscripts and included 9 randomized controlled trials in our study. The primary outcome was change in ScO 2 . Our results showed the likelihood that dopamine, ephedrine, and norepinephrine had the lowest probability of decreasing ScO 2 . The suggested rank order to maintain ScO 2 , from higher to lower, was dopamine

Efficacy of Preoperative Oral Midodrine in Preventing Hypotension After Spinal Anesthesia in Young Adults: A Randomized Controlled Trial.

BACKGROUND: Midodrine was effectively used for prophylaxis against hypotensive syndromes such as postural hypotension and intradialytic hypotension, and during the recovery phase of septic shock. In our study, we aimed to assess the efficacy of prophylactic administration of midodrine tablets before spinal anesthesia in reducing the occurrence of hypotension. METHODS: This randomized placebo-controlled study embraced 67 patients aged 18 to 40 years undergoing elective knee surgery under spinal anesthesia. Patients were randomized to midodrine group (given 10-mg tablets of midodrine) or placebo group (given placebo tablets), and tablets were administered 1 hour before spinal anesthesia (intrathecal injection of 12.5-mg 0.5% hyperbaric bupivacaine and 15-µg fentanyl). The primary outcome was the occurrence of hypotension, defined as a systolic blood pressure <90 mm Hg or <80% of baseline. Secondary outcomes were hemodynamic characteristics (mean arterial pressure [MAP] and heart rate [HR]) after spinal anesthesia, ephedrine dose, and occurrence of complications including bradycardia, vasovagal attacks, reactive hypertension nausea, vomiting, and shivering. RESULTS: The number of patients who became hypotensive after spinal anesthesia was 5 (14.7%) in midodrine group versus 14 (42.4%) in the placebo group; relative risk (95% confidence interval) was 0.35 (0.14-0.85) ( P = .021). The median (interquartile range) total dose of ephedrine was significantly lower in midodrine group 0 (0-10) mg than in placebo group (0 (0-15) mg; the Hodges-Lehmann median difference (95% confidence interval) was 0 (0-5) mg ( P = .015). For MAP data, the group × time interaction was significant ( P = .038), and the MAP was significantly lower in the placebo group than in the midodrine group after intrathecal injection at 2 minutes ( P = .047), 10 minutes ( P = .045), 15 minutes ( P < .001), 20 minutes ( P = .007), 30 minutes ( P =.013), 45 minutes ( P = .029), 60 minutes ( P = .029), and at the end of surgery ( P < .001). For HR data, the group × time interaction was nonsignificant ( P = .807), and the difference in means (95% confidence interval) between groups collapsing over time was -1.4 (-3.1 to 0.2) beats/min ( P = .096). There was no significant difference between the 2 groups regarding the occurrence of complications. CONCLUSIONS: Prophylactic administration of 10-mg midodrine tablets before spinal anesthesia is an effective method in the prevention of hypotension in young adult patients undergoing elective orthopedic knee surgery.

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.

Therapeutic appraisal of ephedrine against rheumatoid arthritis: A new indication.

Ephedra, natural flora has been used traditionally to treat rheumatism since decades. The scientific evidence of anti-rheumatic effect of this plant has also been reported. But the anti-rheumatic activity of major constituent of this plant (ephedrine) has not been evaluated. Based on this, the current study was aimed to assess anti-arthritic activity of ephedrine by using in vitro and in vivo approaches. Correspondingly, enzyme linked immunosorbent assay was performed for the estimation of prostaglandins E2 (PGE2) and tumor necrosis factor-α (TNF-α) in serum of formaldehyde-induced arthritic animals. The results elaborated significant reduction in albumin denaturation and remarkable progress on stabilization of red blood cells outer membrane at higher concentration during in vitro experiments. The ephedrine (40mg/kg) revealed noteworthy (p<0.001) inhibition in paw swelling in animals intoxicated with albumin as well as formaldehyde as compared to animals of control group by in vivo results. In this assay, ephedrine (20 & 40 mg/kg orally) significantly suppressed the level of these inflammatory markers (PGE2 & TNF-α). Ephedrine exhibited anti-arthritic effect by decreasing pro-inflammatory cytokines (PGE2 & TNF-α). This experimental work pharmacologically supports the use of ephedrine as anti-rheumatic drug but limited to evaluate in immunological arthritic model.

Ephedrine versus Phenylephrine Effect on Cerebral Blood Flow and Oxygen Consumption in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial.

BACKGROUND: Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine. METHODS: In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and regional cerebral oxygen saturation. RESULTS: Peritumoral mean ± SD cerebral metabolic rate of oxygen values before and after vasopressor (ephedrine, 67.0 ± 11.3 and 67.8 ± 25.7 µmol · 100 g · min; phenylephrine, 68.2 ± 15.2 and 67.6 ± 18.0 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 1.5 [-13.3 to 16.3] µmol · 100 g · min [P = 0.839]). Corresponding contralateral hemisphere cerebral metabolic rate of oxygen values (ephedrine, 90.8 ± 15.9 and 94.6 ± 16.9 µmol · 100 g · min; phenylephrine, 100.8 ± 20.7 and 96.4 ± 17.7 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 8.2 [-2.0 to 18.5] µmol · 100 g · min [P = 0.118]). Ephedrine significantly increased cerebral blood flow (difference [95% CI], 3.9 [0.7 to 7.0] ml · 100 g · min [P = 0.019]) and regional cerebral oxygen saturation (difference [95% CI], 4 [1 to 8]% [P = 0.024]) in the contralateral hemisphere compared to phenylephrine. The change in oxygen extraction fraction in both regions (peritumoral difference [95% CI], -0.6 [-14.7 to 13.6]% [P = 0.934]; contralateral hemisphere difference [95% CI], -0.1 [- 12.1 to 12.0]% [P = 0.989]) were comparable between groups. CONCLUSIONS: The cerebral metabolic rate of oxygen changes in peritumoral and normal contralateral regions were similar between ephedrine- and phenylephrine-treated patients. In the normal contralateral region, ephedrine was associated with an increase in cerebral blood flow and regional cerebral oxygen saturation compared with phenylephrine.

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.

Effect of vasopressor use on digit survival after replantation and revascularization-A large retrospective cohort study.

PURPOSE: Despite the common use of intraoperative vasopressors in hand microsurgery, the association between intraoperative vasopressor use and digital replant failure has not yet been examined. Our study aims to examine the association between intraoperative vasopressor use (phenylephrine and/or ephedrine) and postoperative digital failure of replanted or revascularized digits. METHODS: All patients from a single tertiary hand center who underwent unilateral digital replantation or revascularization procedures between 2005 and 2016 were included in this retrospective cohort study. The relationship between intraoperative vasopressors used to maintain hemodynamic stability and digit failure was then evaluated using logistic regression. Specifically, phenylephrine (total dose 10-3,600 mcg) and ephedrine (5-110 mg) use were evaluated. RESULTS: During the study period, 281 patients underwent digital replantation or revascularization. Of those, 86 (31%) were given an intraoperative vasopressor. Digit failure was more likely in patients with crush or avulsion injuries compared to clean-cut mechanism (odds ratio [OR] 2.02, p = .02), and in patients with replantation (OR 7.85, p < .0001) as compared to revascularization procedures. Using multivariate logistic regression adjusting for age, sex, smoking status, comorbidities, number of digits injured, injury type, and procedure type, the odds of digital failure with vasopressor use were not increased (p = .84). When evaluating vasopressors used after tourniquet deflation, failure increased with ephedrine use (OR = 2.42, p = .0496) and phenylephrine use (OR = 2.21, p = .31). CONCLUSIONS: The use of vasopressors was not associated with failure if administration of vasopressors was before tourniquet deflation. The administration of vasopressors after tourniquet deflation should be cautioned.

Β-Adrenergic agonist administration is not associated with secondary carcinoid crisis in patients with carcinoid tumor.

BACKGROUND: Patients with carcinoid tumors are at risk for profound intraoperative hypotension known as carcinoid crisis, which catecholamines are traditionally believed to trigger. However, data supporting this are lacking. METHODS: Anesthesia records were retrospectively reviewed for carcinoid patients treated with vasopressors. Hemodynamics for those with crisis were compared between those who received ß-adrenergic agonists (B-AA) versus those who did not. RESULTS: Among 293 consecutive operations, 58 were marked by 161 crises. There was no significant difference in the incidence of paradoxical hypotension with B-AA compared to non-B-AA (p = 0.242). The maximum percent decrease in mean arterial pressure following drug administration was significantly greater in those patients treated with non-B-AA than with B-AA (31.6% vs. 12.5%, p < 0.0001). There were no differences in crisis duration (p = 0.257) or postoperative complication rate (p = 0.896). CONCLUSIONS: ß-Adrenergic agonist use was not associated with paradoxical hypotension, prolonged carcinoid crisis, or postoperative complications in patients with intraoperative carcinoid crisis.

Preventive intramuscular phenylephrine in elective cesarean section under spinal anesthesia: A randomized controlled trial.

BACKGROUND: Phenylephrine is the first-line vasoactive drug in the cesarean section under spinal anesthesia. The rate of hypotension remains high after intravenous preventive use of phenylephrine. However, few studies have investigated the effect of preventive intramuscular phenylephrine via a longer period of usage on fetal and maternal outcomes. METHODS: A total of 99 healthy parturients undergoing elective cesarean delivery were randomly allocated into three groups: M group (preventive intramuscular use of 5 mg phenylephrine), V group (preventive intravenous use of 100 µg phenylephrine), and P group (0.9% normal saline placebo). Rescue phenylephrine, ephedrine and atropine were used intraoperatively to adjust blood pressure and heart rate. The primary outcome was umbilical artery pH. RESULTS: Significant differences in umbilical artery pH (M group: 7.32 ±â€¯0.05 versus V group: 7.25 ±â€¯0.04 versus P group: 7.21 ±â€¯0.03, P < 0.05), fetal acidosis (M group: 3% [n = 33] versus V group: 15% [n = 33] versus P group: 30% [n = 33], P = 0.01) and maternal intraoperative hypotension (M group: 12% [33] versus V group: 39% [33] versus P group: 73% [33], P < 0.0001) were identified among the groups. Multiple linear regression analysis demonstrated that treating arms, neonatal birthweight and the interval from the end of anesthesia to baby delivery were associated with umbilical artery pH. CONCLUSION: Compared with the preventive intravenous use of phenylephrine and placebo, preventive intramuscular phenylephrine exhibited a better neonatal acid-base status and more stable maternal hemodynamics in elective cesarean under spinal anesthesia.

Haemodynamic changes and incisional bleeding after scalp infiltration of dexmedetomidine with lidocaine in neurosurgical patients.

BACKGROUND: The purpose of this randomised controlled study is to compare the haemodynamic changes and the degree of incisional bleeding after scalp infiltration of lidocaine and dexmedetomidine versus lidocaine and epinephrine for patients with hemi-facial spasm undergoing microvascular decompression. METHODS: Fifty-two patients were injected with 5 mL of 1% lidocaine with either dexmedetomidine (2 µg/mL) or epinephrine (1:100,000 dilution) to reduce scalp bleeding. Mean blood pressure and heart rate were recorded every minute for 15 minutes after scalp infiltration. The primary outcome was the incidence of predefined hypotension, which was treated with administration of 4 mg ephedrine as often as needed. The number of administrations and total amount of ephedrine administered were also recorded as a measure of the severity of hypotension. The neurosurgeon scored incisional bleeding by numeric rating scale from 0 (worst) to 10 (best). RESULTS: The incidence of hypotension (68% vs. 34.8%, P = 0.02) and the frequency (P = 0.02) and total dose (P = 0.03) of ephedrine administered were lower in the dexmedetomidine group than in the epinephrine group. In addition, there was no difference in mean blood pressure between the two groups but heart rates were lower in the dexmedetomidine group (P = 0.01). Incisional site bleeding was better with epinephrine (median [interquartile range] of the numeric rating Score: 6 [4] in the dexmedetomidine group and 8 [2] in the epinephrine group; P < 0.001). CONCLUSION: The dexmedetomidine-lidocaine combination may be recommended as a substitute for epinephrine-lidocaine for scalp infiltration in neurosurgical patients, especially neurologically compromised patients.

Evaluation of cardiac output variations with the peripheral pulse pressure to mean arterial pressure ratio.

Cardiac output (CO) optimisation during surgery reduces post-operative morbidity. Various methods based on pulse pressure analysis have been developed to overcome difficulties to measure accurate CO variations in standard anaesthetic settings. Several of these methods include, among other parameters, the ratio of pulse pressure to mean arterial pressure (PP/MAP). The aim of this study was to evaluate whether the ratio of radial pulse pressure to mean arterial pressure (ΔPPrad/MAP) could track CO variations (ΔCO) induced by various therapeutic interventions such as fluid infusions and vasopressors boluses [phenylephrine (PE), norepinephrine (NA) or ephedrine (EP)] in the operating room. Trans-oesophageal Doppler signal and pressure waveforms were recorded in patients undergoing neurosurgery. CO and PPrad/MAP were recorded before and after fluid challenges, PE, NA and EP bolus infusions as medically required during their anaesthesia. One hundred and three patients (mean age: 52 ± 12 years old, 38 men) have been included with a total of 636 sets of measurement. During fluids challenges (n = 188), a positive correlation was found between ΔPPrad/MAP and ΔCO (r = 0.22, p = 0.003). After PE (n = 256) and NA (n = 121) boluses, ΔPPrad/MAP positively tracked ΔCO (r = 0.53 and 0.41 respectively, p < 0.001). By contrast, there was no relation between ΔPPrad/MAP and ΔCO after EP boluses (r = 0.10, p = 0.39). ΔPPrad/MAP tracked ΔCO variations during PE and NA vasopressor challenges. However, after positive fluid challenge or EP boluses, ΔPPrad/MAP was not as performant to track ΔCO which could make the use of this ratio difficult in current clinical practice.

Phenylephrine vs ephedrine in cesarean delivery under spinal anesthesia: A systematic literature review and meta-analysis.

BACKGROUND: In the past 20 years, many studies compared phenylephrine with ephedrine to prevent or treat hypotension in elective or emergency cesarean delivery and parturients with pre-eclampsia. A meta-analysis of the abovementioned trials is needed. METHODS: Several databases (PubMed, Embase, Web of Science and Cochrane Library) were searched from inception to April 2018 for trials comparing phenylephrine with ephedrine in cesarean delivery. The primary outcome is the incidence of maternal hypotension. RESULTS: Thirty-six trials (2439 patients) with elective cesarean delivery, three trials (400 patients) with emergency cesarean delivery and three trials (192 patients) with parturients with pre-eclampsia were included and analyzed. The incidence of hypotension did not differ in the elective surgery group (relative risk 0.83, 95% CI 0.66 to 1.05), emergency surgery group (relative risk 1.02, 95% CI 0.87 to 1.19) and pre-eclamptic parturients group (relative risk 0.93, 95% CI 0.63 to 1.37). The phenylephrine group had a higher incidence of bradycardia and lower incidences of tachycardia and nausea or vomiting in all three patient groups. The phenylephrine group also had lower fetal acidosis rate, higher umbilical artery and vein pH values and less base excess in the elective surgery. The abovementioned outcomes were similar in the emergency surgery group and the pre-eclampsia group. Publication bias for hypotension was detected. However, the trim and fill method demonstrated that the publication bias had little impact on hypotension. Trial sequential analysis of hypotension in elective surgery showed that this meta-analysis lacked a sufficient cumulative sample size and that further studies should be included. CONCLUSION: Phenylephrine and ephedrine were both effective in maintaining hemodynamic balance. Newborns benefited more from phenylephrine in elective cesarean delivery, but not in emergency cesarean delivery or in parturients with pre-eclampsia. More trials should be included to achieve more conclusive results.

Sinus arrest with prolonged asystole due to the trigeminocardiac reflex during application of local anaesthetic in the nasal mucosa.

The trigeminocardiac reflex (TCR) is defined as a sudden onset of parasympathetic dysrhythmias during stimulation of the trigeminal nerve. We describe a peripheral variation of TCR during manipulation of the nasal mucosa. A 42-year-old patient suffering from severe obstructive sleep apnoea was scheduled for surgical treatment. After inducted anaesthesia, the surgeon infiltrated the nasal mucosa with a local anaesthetic. The patient immediately showed an asystole and was treated with ephedrine and five chest compressions, despite spontaneous sinus rhythm return after ceasing of manipulation. Treatment with atropine established this TCR episode and ensured an event-free surgery.The authors present here, for the first time, a prolonged asystole caused by the TCR, triggered by minimal manipulation of the nasal mucosa. This severe manifestation of peripheral TCR demonstrates its importance in daily clinical business. This case was treated according to a modified treatment algorithm for all subtypes of TCR which is presented here.

Effect of the menstrual cycle on circulation during combined spinal-epidural anaesthesia.

BACKGROUND: From adolescence to menopause, hormone levels during the menstrual cycle affect various body systems, from the cardiovascular system to the water and electrolyte balance. This study investigated the effect of different phases of the menstrual cycle on circulatory function relative to changes in body position and combined spinal-epidural anaesthesia (CSEA). METHODS: Forty-six women were selected who underwent scheduled gynaecological surgery, were classified as American Society of Anesthesiology (ASA) I-II, and met the test criteria. The sample was divided into the follicular and corpus luteal groups. Preoperative heart rate and blood pressure measurements were taken from the supine and standing positions. Heart rate measurements as well as systolic, diastolic, and mean blood pressure measurements were taken upon entering the operating room, at the beginning of the spinal-epidural anaesthesia, and 10, 20, and 30 min after anaesthesia was administered. RESULTS: The heart rates of patients in the corpus luteal group were higher than those of patients in the follicular group both before and after anaesthesia (P <  0.05). Significantly more ephedrine was used during the first 30 min of CSEA in the corpus luteal group than in the follicular group (P <  0.05). CONCLUSIONS: Although the effect was slight, women in the follicular phase were better able to compensate and tolerate circulatory fluctuations than those in the luteal phase.

Selective Intraoperative Vasopressor Use Is Not Associated with Increased Risk of DIEP Flap Complications.

BACKGROUND: During deep inferior epigastric perforator (DIEP) flap cases, anesthesiologists commonly avoid intravenous vasopressor administration because of the theoretical concern of inducing vasospasm, thrombosis, or congestion in the vessels of the anastomosis, potentially resulting in poor flap perfusion and ischemia and necessitating revision. In the setting of hypotension, however, vasopressor administration may actually improve outcomes by augmenting flap perfusion by means of increased mean arterial pressure. METHODS: The authors reviewed 475 consecutive DIEP flap cases in 333 patients at a single large academic medical center over a 3-year period, addressing potential confounders using univariate analyses. RESULTS: Ephedrine administration was significantly associated with decreased risk of intraoperative flap complications (OR, 0.88), including vasospasm, thrombosis, and congestion requiring revision, compared with controls, after controlling for the severity and duration of hypotension. Phenylephrine had no significant association with complication rates. Vasopressor administration was not associated with an increased risk of reoperation in the setting of necrosis within 60 days. CONCLUSIONS: Ephedrine treatment for hypotension during DIEP flap cases is associated with decreased intraoperative flap complication rates compared with controls who did not receive vasopressors, whereas phenylephrine has no significant association. The common clinical practice of complete abstinence from vasopressors out of concern for worsening DIEP flap outcomes is not supported by this study. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

[Trigemino-cardiac reflex in skull base surgery].

OBJECTIVE: To explore the mechanism, clinical features, and prognosis of Trigemino-cardiac reflex (TCR) during skull base operations. METHODS: A retrospective analysis was performed on 291 patients with skull base disease from Jan. 2009 to Oct. 2015 in Peking University First Hospital. By reviewing the patients' operative data and anaesthetic electrical record, and we picked out all the patients who suffered from TCR during the operation and analyzed their surgical procedures, clinical features, influence factors, and prognosis. TCR was defined as a drop in mean arterial blood pressure (MABP) and the heart rate (HR) of more than 20% to the baseline values before the stimulus and coinciding with the manipulation of the trigeminal nerve. RESULTS: In all the 291 patients receiving skull base surgery, 9 patients suffering TCR for 19 times during the operation were found. These 9 cases included three acoustice schwannomas, one trigeminal schwannoma, one petroclival meningioma, one epidermoid cyst in cerebellopontine angle, one cavernous sinus cavernous hemangioma, one pituitary adenoma, and one trigeminal neuralgia. The trigger of TCR was related to manipulation, retraction, and stimulation of the trunk or branches of trigeminal nerve. The baseline heart rate was 62-119/min [mean (79.4±14.6) /min] and dropped about 29.0%-66.4% (mean 44.3%) to 22-60 /min [mean (44.2±9.6) /min] after TCR. The baseline mean arterial blood pressure was 75-103 mmHg [mean (87.5±7.8) mmHg] and dropped about 23.4%-47.2% (mean 37.3%) to 45-67 mmHg [mean (54.9±6.3) mmHg] after TCR. During the 19 times of TCR, heart rate and blood pressure could return to baseline in a short time while stopping manipulation (8 times), using atropine (8 times, dose 0.5-1.0 mg, mean 0.69 mg), using ephedrine hydrochloride (one time, 15 mg), using epinephrine (one time, 1 mg), and using dopamine (one time, 2 mg). TCR also could be triggered again by a second stimulation. There was no relative cardiologic complication or neurological deficit in the postoperative 24 hours. CONCLUSION: TCR is a short neural reflex with a drop in blood pressure and heart rate coinciding with the manipulation of the trigeminal nerve in skull base surgery. Correct recognition, intensive observation, and essential management of TCR will lead to a good prognosis.

Effects of pneumoperitoneum on severe hypernatremia in an adult patient who underwent laparoscopic surgery of hydatid cysts.

We describe the first case of severe hypernatremia associated to laparoscopic surgery for hydatid cyst in an adult patient after the use of hypertonic saline solution with complete resolution. Severe hypernatremia is an unusual fact at the immediate postoperative period but may have fatal consequences for the patient and need immediate action. The patient reached a serum sodium concentration of 179 mmol/L without adverse effects after 6 days of treatment. Laparoscopy could play a crucial role in Na+ absorption due to high intraabdominal pressure caused by the pneumoperitoneum and its limitations to avoid peritoneal absorption of hypertonic saline solution. The relation between this surgical technique and the severe complication is discussed. More experience is needed in terms of safety for the patient.