Kim S. Khaw

Prevention of hypotension during spinal anesthesia for cesarean delivery: an effective technique using combination phenylephrine infusion and crystalloid cohydration.

Background: Many methods for preventing hypotension during spinal anesthesia for cesarean delivery have been investigated, but no single technique has proven to be effective and reliable. This randomized study studied the efficacy of combining simultaneous rapid crystalloid infusion (cohydration) with a high-dose phenylephrine infusion. Methods: Nonlaboring patients scheduled to undergo elective cesarean delivery received an intravenous infusion of 100 &mgr;g/min phenylephrine that was started immediately after spinal injection and titrated to maintain systolic blood pressure near baseline values until uterine incision. In addition, patients received infusion of lactated Ringers solution that was given either rapidly (group 1, n = 57) or at a minimal maintenance rate (group 0, n = 55). Maternal hemodynamic changes and neonatal condition were compared. Results: Six patients were excluded from analysis. Only 1 of 53 patients (1.9% [95% confidence interval, 0.3–9.9%]) in group 1 experienced hypotension versus 15 of 53 patients (28.3% [95% confidence interval, 18.0–41.6%]) in group 0 (P = 0.0001). Compared with group 0, patients in group 1 had greater values for the following: serial measurements of systolic blood pressure (P = 0.02), minimum recorded systolic blood pressure (P = 0.0002), and minimum recorded heart rate (P = 0.013). Total phenylephrine consumption was smaller in group 1 compared with group 0 (P = 0.008). Neonatal outcome and maternal side effects were similar between groups. Conclusions: Combination of a high-dose phenylephrine infusion and rapid crystalloid cohydration is the first technique to be described that is effective for preventing hypotension during spinal anesthesia for cesarean delivery.

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.

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 &mgr;g/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 &bgr;-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.

Comparison of metaraminol and ephedrine infusions for maintaining arterial pressure during spinal anesthesia for elective cesarean section.

Background Although ephedrine is usually recommended as the first-line vasopressor in obstetrics, its superiority over other vasopressors has not been proven in humans. Methods In a double-blind study, the authors randomized women having elective cesarean section with spinal anesthesia to receive an intravenous infusion of ephedrine, starting at 5 mg/min (n = 25), or metaraminol, starting at 0.25 mg/min (n = 25), titrated to maintain systolic arterial pressure in the target range 90–100% of baseline. Umbilical cord gases, maternal hemodynamics, uterine artery pulsatility index, and Apgar scores were compared. Results Systolic arterial pressure was maintained more closely in the target range in the metaraminol group compared with the ephedrine group. In the metaraminol group, umbilical arterial p H was greater (median and interquartile range, 7.31 and 7.31–7.33 vs. 7.24 and 7.14–7.29;P < 0.0001), and umbilical venous p H was greater (7.36 and 7.35–7.38 vs. 7.33 and 7.26–7.34;P < 0.0001) compared with the ephedrine group. No patient in the metaraminol group had umbilical arterial p H less than 7.2, compared with nine patients (39%) in the ephedrine group (P = 0.0005). Apgar scores were similar between groups. Changes in uterine artery pulsatility index were similar between groups. Conclusions When used by infusion to maintain arterial pressure during spinal anesthesia for cesarean section, metaraminol was associated with less neonatal acidosis and more closely controlled titration of arterial pressure compared with ephedrine.

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.

Maternal and neonatal effects of remifentanil at induction of general anesthesia for cesarean delivery: a randomized, double-blind, controlled trial.

Background:Use of remifentanil during general anesthesia for cesarean delivery has been described, but its maternal and neonatal effects have not been investigated by a controlled study. Methods:In a randomized, double-blind, controlled study, patients undergoing elective cesarean delivery received an intravenous bolus of 1 &mgr;g/kg remifentanil (n = 20) or saline (n = 20) immediately before induction of general anesthesia. The authors compared maternal hemodynamic changes and neonatal condition and measured plasma concentrations of remifentanil. Results:The maximum increase in systolic arterial pressure from baseline after induction was smaller in the remifentanil group (median, 9 [range, −17 to 31] mmHg) compared with the control group (42 [6–73] mmHg, median difference, 33 mmHg; 95% confidence interval of difference, 23–45 mmHg; P < 0.0001). Maximum recorded values were smaller in the remifentanil group compared with the control group for systolic and mean arterial pressure and maternal heart rate. Apgar scores and time to sustained respiration were similar between groups. Two neonates in the remifentanil group were considered clinically depressed at birth and were given a single dose of naloxone. Remifentanil crossed the placenta with an umbilical venous/maternal arterial concentration ratio of 0.73 (SD, 0.17) and an umbilical arterial/umbilical venous concentration ratio of 0.60 (0.23). Conclusions:A single bolus of 1 &mgr;g/kg remifentanil effectively attenuated hemodynamic changes after induction and tracheal intubation. However, remifentanil crosses the placenta and may cause mild neonatal depression and thus should be used for clear maternal indications when adequate facilities for neonatal resuscitation are available.

Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery.

BACKGROUND: The use of norepinephrine for maintaining blood pressure (BP) during spinal anesthesia for cesarean delivery has been described recently. However, its administration by titrated manually controlled infusion in this context has not been evaluated. METHODS: In a double-blinded, randomized controlled trial, 110 healthy women having spinal anesthesia for elective cesarean delivery were randomly allocated to 1 of 2 groups. In group 1, patients received an infusion of 5 µg/mL norepinephrine that was started at 30 mL/h (2.5 µg/min) immediately after intrathecal injection and then manually adjusted within the range 0–60 mL/h (0–5 µg/min), according to values of systolic BP measured noninvasively at 1-minute intervals until delivery, with the objective of maintaining values near baseline. In group 2, no prophylactic vasopressor was given, and a bolus of 1 mL norepinephrine 5 µg/mL (5 µg) was given whenever systolic BP decreased to <80% of the baseline value. The study protocol was continued until delivery. The primary outcomes of the study were the incidence of hypotension and the overall stability of systolic BP control versus baseline compared using performance error calculations. In addition, the incidence and timing of hypotension were further compared using survival analysis. RESULTS: Three patients were excluded from the analysis. Nine patients (17%) in group 1 had 1 or more episodes of hypotension versus 35 (66%) in group 2 (P < .001). Performance error calculations showed that on average, systolic BP was maintained closer to baseline (P < .001) in group 1. Survival curve analysis showed a significant difference between groups (log-rank test P < .001). Four patients in each group had a recorded heart rate <60 beats/min (P = .98). Despite a much greater rate of administration of norepinephrine in group 1 (median, 61.0 [interquartile range, 47.0–72.5] µg) versus group 2 (5.0 [0–18.1] µg) (P < .001), there was no difference in neonatal outcome as assessed by Apgar scores and umbilical cord blood gas analysis. CONCLUSIONS: In patients having spinal anesthesia for elective cesarean delivery, a manually titrated infusion of 5 µg/mL of norepinephrine was effective for maintaining BP and decreasing the incidence of hypotension, with no detectable detrimental effect on neonatal outcome. Further investigation of the use of dilute norepinephrine infusions for routine use in obstetric patients is suggested.

Spinal ropivacaine for cesarean delivery: A comparison of hyperbaric and plain solutions

We compared, in this prospective, randomized, double-blinded study, the characteristics of spinal anesthesia with plain and hyperbaric ropivacaine for elective cesarean delivery. We hypothesized that the addition of glucose would change the onset, offset, and extent of motor and sensory block from intrathecal ropivacaine. Forty ASA physical status I–II women were given 25 mg of either ropivacaine (n = 20) or ropivacaine in 8.3% glucose (n = 20) intrathecally, via a combined spinal/epidural technique in the right lateral position. Sensory changes to ice and pinprick and motor block (Bromage score) were recorded at 2.5-min intervals. Adequate anesthesia for surgery was achieved in all patients in the Hyperbaric group, whereas in the Plain group, five (25%) patients required epidural top-up because of insufficient rostral spread (P < 0.05). With hyperbaric ropivacaine, we found the following: higher cephalic spread (median [range] maximum block height to pinprick, T1 [T4 to C2] versus T3 [T11 to C3], P < 0.001); lower coefficient of variation of maximum block height (17.7% vs 21.9%); faster onset to T4 dermatome (mean [sd] 7.7 [4.9] vs 16.4 [14.1] min, P = 0.015); and faster recovery to L1 (189.0 [29.6] vs 215.5 [27.0] min, P = 0.01). The onset of complete motor block (9.9 [5.3] vs 13.8 [5.4] min, P = 0.027) and complete recovery (144.8 [28.4] vs 218.5 [56.8] min, P < 0.001) was also faster. No neurologic symptoms were found at 24 h.

Spinal ropivacaine for cesarean section: a dose-finding study.

Background The dose–response relation for spinal ropivacaine is undetermined, and there are few data available for obstetric patients. Methods In a prospective, randomized, double-blind investigation, the authors studied 72 patients undergoing elective cesarean delivery. An epidural catheter was placed at the L2–L3 vertebral interspace. Lumbar puncture was then performed at the L3–L4 vertebral interspace, and patients were randomized to receive a dose of spinal ropivacaine diluted to 3 ml with normal saline: 10 mg (n = 12), 15 mg (n = 20), 20 mg (n = 20), or 25 mg (n = 20). Sensory changes assessed by ice and pin prick and motor changes assessed by modified Bromage score were recorded at timed intervals. A dose was considered effective if an upper sensory level to pin prick of T7 or above was achieved and epidural supplementation was not required intraoperatively. Results Anesthesia was successful in 8.3, 45, 70, and 90% of the 10-, 15-, 20-, and 25-mg groups, respectively. A sigmoid dose–response curve and a probit log dose–response plot were obtained, and the authors determined the ED50 (95% confidence interval) to be 16.7 (14.1–18.8) mg and the ED95 (95% confidence interval) to be 26.8 (23.6–34.1) mg. Duration of sensory and motor block and degree of motor block, but not onset of anesthesia, were positively related to dose. Conclusions The ED50 and estimated ED95 for spinal ropivacaine were 16.7 and 26.8 mg, respectively. Ropivacaine is a suitable agent for spinal anesthesia for cesarean delivery.

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 &bgr;-adrenergic receptor agonist activity in addition to potent &agr;-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 &mgr;g/ml or phenylephrine 100 &mgr;g/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.