Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery.

BACKGROUND: During spinal anesthesia for cesarean delivery, phenylephrine can cause reflexive decreases in maternal heart rate and cardiac output. Norepinephrine has weak ß-adrenergic receptor agonist activity in addition to potent α-adrenergic receptor activity and therefore may be suitable for maintaining blood pressure with less negative effects on heart rate and cardiac output compared with phenylephrine. METHODS: In a randomized, double-blinded study, 104 healthy patients having cesarean delivery under spinal anesthesia were randomized to have systolic blood pressure maintained with a computer-controlled infusion of norepinephrine 5 µg/ml or phenylephrine 100 µg/ml. The primary outcome compared was cardiac output. Blood pressure heart rate and neonatal outcome were also compared. RESULTS: Normalized cardiac output 5 min after induction was greater in the norepinephrine group versus the phenylephrine group (median 102.7% [interquartile range, 94.3 to 116.7%] versus 93.8% [85.0 to 103.1%], P = 0.004, median difference 9.8%, 95% CI of difference between medians 2.8 to 16.1%). From induction until uterine incision, for norepinephrine versus phenylephrine, systolic blood pressure and stroke volume were similar, heart rate and cardiac output were greater, systemic vascular resistance was lower, and the incidence of bradycardia was smaller. Neonatal outcome was similar between groups. CONCLUSIONS: When given by computer-controlled infusion during spinal anesthesia for cesarean delivery, norepinephrine was effective for maintaining blood pressure and was associated with greater heart rate and cardiac output compared with phenylephrine. Further work would be of interest to confirm the safety and efficacy of norepinephrine as a vasopressor in obstetric patients.

Risk of perioperative respiratory complications and postoperative morbidity in a cohort of adults exposed to passive smoking.

OBJECTIVE: To evaluate the risks of perioperative respiratory complications and postoperative morbidity associated with active and passive cigarette smoking. BACKGROUND: Environmental tobacco smoke is associated with perioperative respiratory events in children, but its effect in adults is unknown. METHODS: We conducted a cohort study of 736 adult patients receiving general anesthesia for major elective surgery. Patients were classified according to their self-reported smoking history and urinary cotinine concentration within 48 hours before surgery. The main outcomes were composite measures of perioperative respiratory complications and postoperative morbidity on the third day after surgery. RESULTS: There were 313 (42.5%) never-smokers (reference group), 92 (12.5%) passive nonsmokers, 157 (21.3%) ex-smokers without environmental tobacco smoke exposure, 53 (7.2%) passive ex-smokers, and 121 (16.4%) smokers. The incidence of perioperative respiratory complications and postoperative morbidity was 9.5% [95% confidence interval (CI), 7.5-11.8] and 29.2% (95% CI, 26.0-32.6), respectively. Smoking was significantly associated with an increased risk of perioperative respiratory complications [relative risk (RR), 4.40; 95% CI, 2.20-8.80] and postoperative morbidity (RR, 1.86; 95% CI, 1.22-2.83). Although passive smoking was not associated with the risk of perioperative respiratory complications, the risk of postoperative morbidity was increased in passive nonsmokers (RR, 1.51; 95% CI, 1.04-2.21) and passive ex-smokers (RR, 2.21; 95% CI, 1.39-3.50). CONCLUSIONS: One in 5 adults was exposed to environmental tobacco smoke before surgery. Passive cigarette smoking showed very little, if any, increased risk of perioperative respiratory complications. Both active exposure and passive exposure to cigarette smoke increased the risk of postoperative morbidity.

The accuracy of urinary cotinine immunoassay test strip as an add-on test to self-reported smoking before major elective surgery.

INTRODUCTION: Smoking is a preventable cause of perioperative complications. An accurate and rapid classification of smoking status is essential as up to 35% of smokers deny smoking before surgery. We compared the diagnostic performance of a preoperative urinary cotinine immunoassay test strip (NicAlert®) as an add-on test to patient's self-reported smoking status. METHODS: Four hundred and sixty-five patients undergoing major elective surgery self-reported their smoking history and provided a sample for measuring urinary cotinine concentration by liquid chromatography tandem mass spectrometry (reference standard) and NicAlert®. Using the "either test positive" rule, the gain in diagnostic performance for NicAlert® add-on test was assessed using relative positive and negative likelihood ratios (LRs) and area under the receiver operating characteristic curve (AUROC) with 95% CIs. RESULTS: Of the 60 patients with a positive reference standard (adjusted cotinine ≥ 50 ng/ml), 10 (16.7%) denied current cigarette smoking. The NicAlert® add-on test had better test performance measures (sensitivity = 95.0%, specificity = 94.8%) than self-reported smoking history alone (sensitivity = 83.3%, specificity = 95.0%). The relative positive and negative LRs were 1.09 (95% CI = 0.95-1.24) and 0.30 (95% CI = 0.12-0.78), respectively. The AUROC for the NicAlert® add-on test (0.90; 95% CI = 0.84-0.96) was significantly higher than for the self-reported smoking history alone (0.78; 95% CI = 0.69-0.88) (p = .006). CONCLUSION: The NicAlert® add-on test strategy had excellent diagnostic test performance for identifying current smokers who are expected to have a high risk of perioperative complications.

Placental transfer and fetal metabolic effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery.

BACKGROUND: Use of ephedrine in obstetric patients is associated with depression of fetal acid-base status. The authors hypothesized that the mechanism underlying this is transfer of ephedrine across the placenta and stimulation of metabolism in the fetus. METHODS: A total of 104 women having elective Cesarean delivery under spinal anesthesia randomly received infusion of phenylephrine (100 microg/ml) or ephedrine (8 mg/ml) titrated to maintain systolic blood pressure near baseline. At delivery, maternal arterial, umbilical arterial, and umbilical venous blood samples were taken for measurement of blood gases and plasma concentrations of phenylephrine, ephedrine, lactate, glucose, epinephrine, and norepinephrine. RESULTS: In the ephedrine group, umbilical arterial and umbilical venous pH and base excess were lower, whereas umbilical arterial and umbilical venous plasma concentrations of lactate, glucose, epinephrine, and norepinephrine were greater. Umbilical arterial Pco2 and umbilical venous Po2 were greater in the ephedrine group. Placental transfer was greater for ephedrine (median umbilical venous/maternal arterial plasma concentration ratio 1.13 vs. 0.17). The umbilical arterial/umbilical venous plasma concentration ratio was greater for ephedrine (median 0.83 vs. 0.71). CONCLUSIONS: Ephedrine crosses the placenta to a greater extent and undergoes less early metabolism and/or redistribution in the fetus compared with phenylephrine. The associated increased fetal concentrations of lactate, glucose, and catecholamines support the hypothesis that depression of fetal pH and base excess with ephedrine is related to metabolic effects secondary to stimulation of fetal beta-adrenergic receptors. Despite historical evidence suggesting uteroplacental blood flow may be better maintained with ephedrine, the overall effect of the vasopressors on fetal oxygen supply and demand balance may favor phenylephrine.

The adsorption of vancomycin by polyacrylonitrile, polyamide, and polysulfone hemofilters.

The aim of this study was to characterize vancomycin adsorption by polyacrylonitrile (PAN), polyamide, and polysulfone hemofilters using an in vitro model of hemofiltration. Vancomycin (36 mg) was added to a blood-crystalloid mixture of known volume (target concentration of 50 mg/L) and pumped around a closed circuit. Adsorption, which was calculated from the fall in concentration over 120 min, was significantly greater by 0.6-m(2) PAN filters (10.08 +/- 2.26 mg) than by 0.6-m(2) polyamide (5.20 +/- 1.82 mg) or 0.7-m(2) polysulfone (4.80 +/- 2.40 mg) filters (P < 0.05). Cumulative adsorption was not changed by the addition of 500-mL lactated Ringer's solution (to reduce the circulating vancomycin concentration). These data show that although adsorption of vancomycin by PAN, polyamide, and polysulfone hemofilters occurs, the absolute adsorption is small. Adsorption is dependent on filter material and is not reversed by a decrease in circulating concentration.

Adsorption of amikacin, a significant mechanism of elimination by hemofiltration.

We used an in vitro model of continuous venovenous hemofiltration (CVVH) to characterize amikacin adsorption by polyacrylonitrile (PAN) and polyamide filters. A blood-crystalloid mixture dosed with amikacin was pumped from a reservoir through a hemofiltration circuit and back to the reservoir. All ultrafiltrate was also returned to the reservoir. The level of adsorption was calculated from the fall in the amikacin concentration. The dose and the initial concentration of amikacin were varied, as were the pH, the type of hemofilter, and the hemofilter surface area. The reversibility of adsorption and the effect of repeated dosing were also studied. The level of adsorption by 0.6-m2 PAN filters was significantly greater than that by 0.6-m2 polyamide filters. Adsorption was increased by increasing the dose of amikacin even when the initial concentration was unchanged. It was unaffected by the pH (pH 6.8 or 7.4) or the hemofilter surface area (0.6 m2 or 0.9 m2). Repeated doses of amikacin resulted in further adsorption. In a saturation experiment, the maximum adsorptive capacity of 0.6-m2 PAN hemofilters was at least 546.9 mg (range, 427.6 to 577.5 mg). The adsorption of amikacin by hemofilters is irreversible and was associated with the dose and the hemofilter material but not the hemofilter surface area. Close monitoring of peak amikacin levels should be considered for patients receiving CVVH with PAN hemofilters.

Isoflurane dosage for equivalent intraoperative electroencephalographic suppression in patients with and without epidural blockade.

UNLABELLED: We conducted a prospective, randomized, controlled trial to establish the effect of epidural blockade on isoflurane requirements for equivalent intraoperative electroencephalographic (EEG) suppression. Fifty patients undergoing abdominal hysterectomy received combined epidural and general anesthesia or general anesthesia alone with isoflurane and alfentanil. Isoflurane was administered by computer-controlled closed-loop feedback to maintain an EEG 95% spectral edge frequency of 17.5 Hz, a target chosen on the basis of a pilot study. In epidural patients, end-tidal isoflurane concentration (FE'(ISO)) was 0.19% smaller (95% confidence interval [CI], -0.32% to -0.06%; P < 0.01), mean arterial blood pressure was 17 mm Hg lower (95% CI, -24 to -9 mm Hg; P < 0.0001), and body temperature was 0.4 degrees C lower (95% CI, -0.7 to 0 degrees C; P < 0.05) than in controls. EEG bispectral index (BIS) was 4 points higher (95% CI, 1 to 7; P < 0.05). EEG median frequency and heart rate were similar in both groups. Epidural patients were 76% more likely (95% CI, 58% to 94%; P < 0.001) to require metaraminol for hypotension and were 28% more likely (95% CI, 3% to 53%; P < 0.05) to require glycopyrrolate for bradycardia. After surgery, the time to eye opening in epidural patients was 2.3 min shorter (95% CI, -4.2 to -0.5 min; P < 0.05). Time to eye opening correlated better with FE'(ISO) in the last 30 s of anesthesia (FE'(ISO) = 0.07 x time to eye opening + 0.31; r(2) = 0.59; P < 0.0001) than with BIS from the same period (BIS = 64 - 1.25 x time to eye opening; r(2) = 0.22; P < 0.001) (P < 0.0001). To maintain similar intraoperative spectral edge frequency, patients receiving combined epidural and general anesthesia require 21% less isoflurane than those receiving general anesthesia alone. This smaller isoflurane dose is associated with faster emergence from anesthesia. IMPLICATIONS: The dose of general anesthetic required to maintain similar intraoperative suppression of brain electrical activity is 21% less in patients with nerve blockade than in those without. This dose reduction results in faster waking times in patients with nerve blockade, which may reflect lighter intraoperative anesthesia. The dose of general anesthetic required to maintain similar intraoperative suppression of brain electrical activity is 21% less in patients with nerve blockade than in those without. This dose reduction results in faster waking times in patients with nerve blockade, which may reflect lighter intraoperative anesthesia.