Tony Gin

A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery.

This quantitative systematic review compared the efficacy and safety of ephedrine with phenylephrine for the prevention and treatment of hypotension during spinal anesthesia for cesarean delivery. Seven randomized controlled trials (n = 292) were identified after a systematic search of electronic databases (MEDLINE, EMBASE, The Cochrane Controlled Trials Registry), published articles, and contact with authors. Outcomes assessed were maternal hypotension, hypertension and bradycardia, and neonatal umbilical cord blood pH values and Apgar scores. For the management (prevention and treatment) of maternal hypotension, there was no difference between phenylephrine and ephedrine (relative risk [RR] of 1.00; 95% confidence interval [CI], 0.96–1.06). Maternal bradycardia was more likely to occur with phenylephrine than with ephedrine (RR of 4.79; 95% CI, 1.47–15.60). Women given phenylephrine had neonates with higher umbilical arterial pH values than those given ephedrine (weighted mean difference of 0.03; 95% CI, 0.02–0.04). There was no difference between the two vasopressors in the incidence of true fetal acidosis (umbilical arterial pH value of <7.2; RR of 0.78; 95% CI, 0.16–3.92) or Apgar score of <7 at 1 and 5 min. This systematic review does not support the traditional idea that ephedrine is the preferred choice for the management of maternal hypotension during spinal anesthesia for elective cesarean delivery in healthy, nonlaboring women.

BIS-guided anesthesia decreases postoperative delirium and cognitive decline.

Background: Previous clinical trials and animal experiments have suggested that long-lasting neurotoxicity of general anesthetics may lead to postoperative cognitive dysfunction (POCD). Brain function monitoring such as the bispectral index (BIS) facilitates anesthetic titration and has been shown to reduce anesthetic exposure. In a randomized controlled trial, we tested the effect of BIS monitoring on POCD in 921 elderly patients undergoing major noncardiac surgery. Methods: Patients were randomly assigned to receive either BIS-guided anesthesia or routine care. The BIS group had anesthesia adjusted to maintain a BIS value between 40 and 60 during maintenance of anesthesia. Routine care group had BIS measured but not revealed to attending anesthesiologists. Anesthesia was adjusted according to traditional clinical signs and hemodynamic parameters. A neuropsychology battery of tests was administered before and at 1 week and 3 months after surgery. Results were compared with matched control patients who did not have surgery during the same period. Delirium was measured using the confusion assessment method criteria. Results: The median (interquartile range) BIS values during the maintenance period of anesthesia were significantly lower in the control group, 36 (31 to 49), compared with the BIS-guided group, 53 (48 to 57), P<0.001. BIS-guided anesthesia reduced propofol delivery by 21% and that for volatile anesthetics by 30%. There were fewer patients with delirium in the BIS group compared with routine care (15.6% vs. 24.1%, P=0.01). Although cognitive performance was similar between groups at 1 week after surgery, patients in the BIS group had a lower rate of POCD at 3 months compared with routine care (10.2% vs. 14.7%; adjusted odds ratio 0.67; 95% confidence interval, 0.32-0.98; P=0.025). Conclusions: BIS-guided anesthesia reduced anesthetic exposure and decreased the risk of POCD at 3 months after surgery. For every 1000 elderly patients undergoing major surgery, anesthetic delivery titrated to a range of BIS between 40 and 60 would prevent 23 patients from POCD and 83 patients from delirium.

A systematic review (meta-analysis) of the accuracy of the mallampati tests to predict the difficult airway

The original and modified Mallampati tests are commonly used to predict the difficult airway, but there is controversy regarding their accuracy. We searched MEDLINE and other databases for prospective studies of patients undergoing general anesthesia in which the results of a preoperative Mallampati test were compared with the subsequent rate of difficult airway (difficult laryngoscopy, difficult intubation, or difficult ventilation as reference tests). Forty-two studies enrolling 34,513 patients were included. The definitions of the reference tests varied widely. For predicting difficult laryngoscopy, both versions of the Mallampati test had good accuracy (area under the summary receiver operating characteristic (sROC) curve = 0.89 ± 0.05 and 0.78 ± 0.05, respectively). For predicting difficult intubation, the modified Mallampati test had good accuracy (area under the sROC curve = 0.83 ± 0.03) whereas the original Mallampati test was poor (area under the sROC curve = 0.58 ± 0.12). The Mallampati tests were poor at identifying difficult mask ventilation. Publication bias was not detected. Used alone, the Mallampati tests have limited accuracy for predicting the difficult airway and thus are not useful screening tests.

A dose-response study of prophylactic intravenous ephedrine for the prevention of hypotension during spinal anesthesia for cesarean delivery.

We performed a randomized, double-blinded dose-finding study of IV ephedrine for prophylaxis for hypotension in 80 women who received an IV crystalloid preload and spinal anesthesia for elective cesarean delivery. One minute after the intrathecal injection, patients were given saline control or ephedrine 10, 20, or 30 mg IV for 30 s. Systolic arterial pressure (SAP) in the first 12 min after the spinal injection was greater in the 30-mg group compared with other groups (P < 0.05). Hypotension occurred in 7 patients (35%) in the 30-mg group compared with 19 (95%), 17 (85%), and 16 (80%) patients in the control and 10- and 20-mg groups, respectively (P < 0.0001). Maximum decrease in SAP was smaller in the 30-mg group (mean lowest SAP 87% of baseline, range 58%–105%) compared with other groups (P < 0.01). Reactive hypertension occurred in 9 patients (45%) in the 30-mg group (mean highest SAP 120% of baseline, range 104%–143%) compared with 2 (10%), 1 (5%), and 5 (25%) patients in the other groups (P = 0.009). Heart rate changes, total ephedrine requirement, incidence of nausea and vomiting, and neonatal outcome were similar among groups. The proportion of patients with umbilical arterial pH < 7.2 was 10.5%, 25%, 42%, and 22% in the control, 10-, 20-, and 30-mg groups, respectively (P = 0.12). We conclude that the smallest effective dose of ephedrine to reduce the incidence of hypotension was 30 mg. However, this dose did not completely eliminate hypotension, nausea and vomiting, and fetal acidosis, and it caused reactive hypertension in some patients. Implications We investigated different doses of IV ephedrine as prophylaxis for hypotension during spinal anesthesia for cesarean delivery and found that the smallest effective dose was 30 mg. However, this dose did not completely eliminate hypotension, caused reactive hypertension in some patients, and did not improve neonatal outcome.

Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage (IMASH) A Randomized, Double-Blinded, Placebo-Controlled, Multicenter Phase III Trial

Background and Purpose— Pilot clinical trials using magnesium sulfate in patients with acute aneurysmal subarachnoid hemorrhage have reported trends toward improvement in clinical outcomes. This Phase III study aimed to compare intravenous magnesium sulfate infusion with saline placebo among such patients. Methods— We recruited patients with aneurysmal subarachnoid hemorrhage within 48 hours of onset from 10 participating centers. The patients were randomly assigned to magnesium sulfate infusion titrated to a serum magnesium concentration twice the baseline concentration or saline placebo for 10 to 14 days. Patients and assessors were blinded to treatment allocation. The study is registered at www.strokecenter.org/trials (as Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage [IMASH]) and www.ClinicalTrials.gov (NCT00124150). Results— Of the 327 patients recruited, 169 were randomized to receive treatment with intravenous magnesium sulfate and 158 to receive saline (placebo). The proportions of patients with a favorable outcome at 6 months (Extended Glasgow Outcome Scale 5 to 8) were similar, 64% in the magnesium sulfate group and 63% in the saline group (OR, 1.0; 95% CI, 0.7 to 1.6). Secondary outcome analyses (modified Rankin Scale, Barthel Index, Short Form 36, and clinical vasospasm) also showed no significant differences between the 2 groups. Predefined subgroups included age, admission World Federation of Neurological Surgeons grade, pre-existing hypertension, intracerebral hematoma, intraventricular hemorrhage, location of aneurysm, size of aneurysm, and mode of aneurysm treatment. In none of the subgroups did the magnesium sulfate group show a better outcome at 6 months. Conclusions— The results do not support a clinical benefit of intravenous magnesium sulfate infusion over placebo infusion in patients with acute aneurysmal subarachnoid hemorrhage.

A Randomized Double-Blinded Comparison of Phenylephrine and Ephedrine Infusion Combinations to Maintain Blood Pressure During Spinal Anesthesia for Cesarean Delivery: The Effects on Fetal Acid-Base Status and Hemodynamic Control

BACKGROUND: Phenylephrine and ephedrine are both used to maintain arterial blood pressure during spinal anesthesia for cesarean delivery. Usually, either drug is given alone but several previous studies have described combining the drugs. However, the effect of varying the proportion of vasopressors in such combinations has not been reported. METHODS: One-hundred-twenty-five parturients having spinal anesthesia for elective cesarean delivery were randomized to receive an IV infusion of phenylephrine and ephedrine combined in one of five different concentration ratios. Assuming phenylephrine 100 μg to be approximately equipotent to ephedrine 8 mg, the groups contained the proportional potency equivalent of 100%, 75%, 50%, 25% or 0% of phenylephrine and 0%, 25%, 50%, 75% or 100%, respectively, of ephedrine. The infusions were adjusted to maintain systolic blood pressure (SBP) near baseline until uterine incision. Hemodynamic changes and umbilical cord blood gases were compared. RESULTS: As the proportion of phenylephrine decreased and proportion of ephedrine increased among the groups, the following significant trends were detected: the incidences of hypotension and nausea/vomiting increased, the median magnitude of deviations of SBP above or below baseline and the bias for SBP to be above baseline increased, maternal heart rate was faster, fetal pH and base excess decreased, umbilical arterial oxygen content decreased and umbilical venous Po2 increased. CONCLUSIONS: When varying combinations of phenylephrine and ephedrine were given by infusion to maintain arterial blood pressure during spinal anesthesia for cesarean delivery, as the proportion of phenylephrine decreased and the proportion of ephedrine increased, hemodynamic control was reduced and fetal acid-base status was less favorable. Combinations of phenylephrine and ephedrine appear to have no advantage compared with phenylephrine alone when administered by infusion for the prevention of hypotension associated with spinal anesthesia for cesarean delivery.

Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: a prospective randomized pilot study.

We performed a randomized, double-blind, pilot study on magnesium sulfate (MgSO4) infusion for aneurysmal subarachnoid hemorrhage (SAH). Sixty patients with SAH were randomly allocated to receive either MgSO4 80 mmol/day or saline infusion for 14 days. Patients also received intravenous nimodipine. Episodes of vasospasm were treated with hypertensive and hypervolemic therapy. Neurologic status was assessed 6 months after hemorrhage using the Barthel index and Glasgow Outcome Scale. Incidences of cardiac and pulmonary complications were also recorded. Patient characteristics, severity of SAH, and surgical treatment did not differ between groups. The incidence of symptomatic vasospasm decreased from 43% in the saline group to 23% in patients receiving MgSO4 infusion, but it did not reach statistical significance, P=0.06. For patients who had transcranial Doppler-detected vasospasm, defined as mean flow velocity >120 cm/s and a Lindegaard index >3, the duration was shorter in the magnesium group compared with controls (P<0.01). There was, however, no difference between groups in functional recovery or Glasgow Outcome Scale score. The incidence of adverse events such as brain swelling, hydrocephalus, and nosocomial infection was also similar in patients receiving MgSO4 or saline. In this small pilot study, MgSO4 infusion for aneurysmal SAH is feasible. On the basis of the preliminary data, a larger study recruiting approximately 800 patients is required to test for a possible neuroprotective effect of magnesium after SAH.

Prophylactic ephedrine prevents hypotension during spinal anesthesia for Cesarean delivery but does not improve neonatal outcome: a quantitative systematic review.

PurposeThe objective of this systematic review was to assess the effectiveness and safety of ephedrine compared with control when given prophylactically to prevent hypotension during spinal anesthesia for Cesarean delivery.SourceRandomized, controlled trials obtained through MEDLINE, EMBASE, the Cochrane Controlled Trials Registry, contact with leading experts, and a reference list of published articles were analyzed. The following keywords were utilized: spinal anesthesia, hypotension, Cesarean section, pregnancy complications, pregnancy outcome, fetal outcome, neonatal outcome, umbilical blood cord gases, vasopressor and ephedrine. Clinical trials were considered if they compared prophylactic ephedrine, given by any dose or route,vs control.Principal findingsThe 14 clinical trials identified included data from a total of 641 patients. Ephedrine was more effective than control for preventing hypotension (relative risk [RR], 0.73; 95% confidence interval [Cl], 0.63 to 0.86). Most importantly, there was no difference in the risk of fetal acidosis, defined as umbilical arterial pH < 7.2 (RR, 1.36; 95% Cl, 0.55 to 3.35) or the incidence of low Apgar scores (< 7 or < 8) at one minute (RR, 0.77; 95% Cl, 0.29 to 2.06) and five minutes (RR, 0.72; 95% Cl, 0.24 to 2.19).ConclusionsProphylactic ephedrine is more effective than control for preventing hypotension during spinal anesthesia for elective Cesarean delivery but a clinically relevant positive effect on neonatal outcome was not observed. Therefore, the routine use of prophylactic ephedrine to prevent any adverse effects of maternal hypotension following spinal anesthesia for Cesarean delivery is not supported by the current systematic review.RésuméObjectifÉvaluer l’efficacité et l’innocuité de l’éphédrine, comparée à un témoin, administrée de manière prophylactique pour prévenir l’hypotension pendant la rachianesthésie lors de l’accouchement par Césarienne.SourceNous avons analysé des essais randomisés et contrôlés obtenus de MEDLINE, EMBASE, l’Index Cochrane des essais randomisés et contrôlés, personnes-ressources autorisées et une liste de références d’articles publiés. Les mots clés ont été : spinal anesthesia, hypotension, Cesarean section, pregnancy complications, pregnancy outcome, fetal outcome, neonatal outcome, umbilical blood cord gases, vasopressor et ephedrine. Nous n’avons considéré que les essais cliniques qui comparaient l’éphédrine prophylactique à un témoin, sans égard à la dose et à la voie d’administration.Constatations principalesLes 14 essais cliniques retenus comportaient des données sur 641 patientes. Léphédrine a été plus efficace que le médicament témoin dans la prévention de l’hypotension (risque relatif [RR], 0,73 ; intervalle de confiance [IC] de 95 %, 0,63 à 0,86). Le plus important est l’absence de différence de risque d’acidose fœtale, définie par un pH de l’artère ombilicale < 7,2 (RR, 1,36 ;IC de 95 %, 0,55 à 3,35) ou l’incidence d’indice d’Apgar < 7 ou < 8 à une minute (RR, 0,77 ; IC 95 %, 0,29 à 2,06) et à cinq minutes (RR, 0,72 ; IC 95 %, 0,24 à 2,19).ConclusionLadministration préventive d’éphédrine agit plus efficacement qu’un médicament témoin contre l’hypotension pendant la rachianesthésie pour Césarienne, mais aucun effet positif de pertinence clinique sur l’évolution néonatale n’est observé. Notre revue systématique ne corrobore donc pas l’usage courant d’éphédrine prophylactique comme prévention de tout effet indésirable sur l’hypotension maternelle suivant la rachianesthésie pendant la césarienne.

Chronic postsurgical pain after nitrous oxide anesthesia

Summary Chronic postsurgical pain was common after major surgery in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA) trial. Nitrous oxide administration was associated with a decrease in the risk of chronic wound pain after surgery. ABSTRACT Nitrous oxide is an antagonist at the N‐methyl‐D‐aspartate receptor and may prevent the development of chronic postsurgical pain. We conducted a follow‐up study in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA) trial patients to evaluate the preventive analgesic efficacy of nitrous oxide after major surgery. The ENIGMA trial was a randomized controlled trial of nitrous oxide‐based or nitrous oxide‐free general anesthesia in patients presenting for noncardiac surgery lasting more than 2 hours. Using a structured telephone interview, we contacted all ENIGMA trial patients recruited in Hong Kong (n = 640). We recorded the severity of postsurgical pain of at least 3 months’ duration that was not due to disease recurrence or a pre‐existing pain syndrome, using the modified Brief Pain Inventory. The impact of postsurgical pain on quality of life was also measured. Pain intensity, opioid and other analgesic requirements during the first week of surgery, were retrieved from the trial case report form and medical records. A total of 46 (10.9%) patients reported pain that persisted from the index surgery, and 39 (9.2%) patients had severe pain. In addition, patients with chronic pain rated poorly in all attributes of the quality‐of‐life measures compared with those who were pain free. In a multivariate analysis, nitrous oxide decreased the risk of chronic postsurgical pain. In addition, severe pain in the first postoperative week, wound complication, and abdominal incision increased the risk of chronic pain. In conclusion, chronic postsurgical pain was common after major surgery in the ENIGMA trial. Intraoperative nitrous oxide administration was associated with a reduced risk of chronic postsurgical pain.

Gastric emptying following brain injury: Effects of choice of sedation and intracranial pressure

ObjectiveTo compare the effects of opioid and nonopioid sedation on gastric emptying.DesignProspective, randomized trial.SettingUniversity teaching hospital ICU.Patients21 brain injured patients requiring sedation, mechanical ventilation and intracranial pressure (ICP) monitoring for >24h.InterventionsPatients were randomized to receive infusions of either morphine plus midazolam (M), or propofol (P). Gastric emptying was assessed by the paracetamol absorption technique and by residual volumes following a 200 ml test feed.measuerments and resultsPre-sedation Glasgow Coma Score, mean ICP and the presence of bowel sounds were noted. Plasma concentrations of paracetamol were measured over 3 h following a 1 g gastric dose. There were no differencese in median peak paracetamol concentration (M, 18.5 versus P, 20.8 mg/l), median time to peak concentration (M, 20 versus P, 25 min), median area under the concentration-time curve (AUC), or in the median residual volumes at 1 h (M, 14 versus P, 10.5 ml) and 2 h (M, 5 versus P, 3 ml). In patients with ICP>20 mmHg, paracetamol concentrations were lower (p<0.05), and AUC after 30 min was lower (165 mg·min/l versus 411 mg·min/l,p=0.023). Mean ICP was correlated with AUC (Kendall rankp=0.027). Gastric emptying did not correlate with initial Glasgow Coma Score or presence of bowel sounds.ConclusionsGastric emptying is not improved in patients with brain injury by avoiding morphine (1–8 mg/h) in the sedative regimen. Intracranial hypertension is associated with reduced gastric emptying.