Bee B. Lee

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.

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.

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.

Metaraminol infusion for maintenance of arterial blood pressure during spinal anesthesia for cesarean delivery: the effect of a crystalloid bolus.

We randomly allocated women having elective cesarean delivery to receive either no bolus (Control Group, n = 31) or 20 mL/kg lactated Ringer’s solution (Bolus Group, n = 35) IV before spinal anesthesia. An infusion of metaraminol started at 0.25 mg/min was titrated to maintain systolic arterial blood pressure in the target range 90%–100% of baseline. The total dose of metaraminol required up to the time of uterine incision was similar between the Control Group and the Bolus Group (3.62 ± 1.20 vs 3.27 ± 1.39 mg, P = 0.3). However, the Control Group required more metaraminol in the first 5 min (1.29 ± 0.60 vs 0.96 ± 0.58 mg, P = 0.025) and a faster maximum infusion rate (0.45 ± 0.20 vs 0.32 ± 0.13 mg/min, P = 0.002) compared with the Bolus Group. There was no difference between groups in regards to changes in systolic arterial blood pressure or heart rate over time, or maternal or neonatal outcome. We conclude that when metaraminol is used to maintain arterial pressure during spinal anesthesia for cesarean delivery, crystalloid bolus is not essential provided that sufficient vasopressor is given in the immediate postspinal period.

The effect of the addition of epinephrine on early systemic absorption of epidural ropivacaine in humans.

The addition of epinephrine to ropivacaine has not been recommended because ropivacaine has intrinsic vasoconstrictor properties. However, few pharmacokinetic data are available on the addition of epinephrine to epidural ropivacaine in humans. In this prospective, double-blinded study, we randomized patients having elective abdominal hysterectomy to receive epidural ropivacaine 1.5 mg/kg, diluted in 15 mL, either with (epinephrine group, n = 12) or without (plain group, n = 12) epinephrine 5 &mgr;g/mL and then measured arterial and venous plasma concentrations of ropivacaine at intervals up to 180 min. We found that arterial and venous plasma ropivacaine concentrations were smaller in the epinephrine group compared with the plain group in the first 60 min after the drug administration (P < 0.01). Mean (± sd) maximum total plasma ropivacaine concentration was smaller in the epinephrine group (arterial, 0.92 ± 0.32 &mgr;g/mL; venous, 0.82 ± 0.33 &mgr;g/mL) compared with the plain group (1.31 ± 0.39 &mgr;g/mL and 1.31 ± 0.50 &mgr;g/mL, respectively;P = 0.01). Time to maximum total plasma ropivacaine concentration was not significantly different between groups (mean ± sd; arterial, 16 ± 2 min; venous, 23 ± 2 min in the epinephrine group versus 9 ± 2 min and 12 ± 3 min, respectively, in the plain group;P = 0.08). Arterial plasma ropivacaine concentrations were larger than venous concentrations during the first hour (P < 0.01); the arterio-venous difference decreased exponentially, and the rate and magnitude of this decrease was unaffected by epinephrine. We conclude that the addition of epinephrine 5 &mgr;g/mL to ropivacaine reduced the early systemic plasma concentrations of ropivacaine after epidural injection and may be useful for decreasing the risk of toxicity from systemic absorption of epidural ropivacaine.

Dose-response study of epidural ropivacaine for labor analgesia

Background Ropivacaine has been introduced for use in epidural analgesia in labor. However, there have been few formal dose–response studies of ropivacaine in this setting. Methods The authors performed a prospective, randomized, double-blind study examining the effectiveness of five different doses of ropivacaine (10, 20, 30, 40, and 50 mg) administered epidurally in a volume of 10 ml to establish analgesia in 66 parturients who were in active labor with cervical dilatation less than 4 cm. A dose was considered effective when the visual analog scale pain score decreased by 50% or more from baseline. Results A sigmoid dose–response curve and a probit log dose–response plot (linear regression coefficient, r = 0.84; coefficient of determination, r2 = 0.71) were obtained. The ED50 (median effective dose) obtained based on the maximum likelihood estimation was 18.4 mg (95% confidence interval, 13.4–25.4 mg). Time to onset of analgesia, duration of analgesia, time to two-segment regression of sensory block level, and incidence of motor block were not affected by the dosage of ropivacaine administered (P = 0.93, 0.12, 0.55, and 0.39, respectively). However, the upper level of sensory block was dose-related (P < 0.01). Conclusion In a traditional dose–response study, the ED50 of ropivacaine required to initiate epidural analgesia in early labor was found to be 18.4 mg (95% confidence interval, 13.4–25.4 mg).

Epidural infusions for labor analgesia: a comparison of 0.2% ropivacaine, 0.1% ropivacaine, and 0.1% ropivacaine with fentanyl.

Background and Objectives Epidural infusion of 0.2% ropivacaine is recommended by the manufacturer for labor analgesia, but lower concentrations may be effective. The objective of this study was to compare 0.1% ropivacaine with 0.2% ropivacaine and to examine the effect of addition of fentanyl. Methods In a randomized double-blind study, 58 nulliparous laboring parturients had epidural analgesia established with 0.2% ropivacaine and were then randomized to receive one of the following epidural infusions at 10 mL/h: 0.2% ropivacaine (group R2, n = 19), 0.1% ropivacaine (group R1, n = 19), or 0.1% ropivacaine with 2 μg/mL fentanyl (group RF, n = 20). Supplementary analgesia was provided on request with 5-mL boluses of 0.2% ropivacaine. Results All solutions provided effective analgesia during early labor, with all groups requiring similar numbers of supplementary top-ups. Visual analog pain scores in groups R2 and RF were equivalent and lower than in group R1 (P = .006). Hypotension was more frequent in group RF compared with groups R2 and R1 (P = .014). Patient and midwife satisfaction and obstetric and neonatal outcomes were similar among groups. Maternal venous plasma concentrations of ropivacaine were greater in group R2 compared with groups R1 and RF (P = .008), but umbilical venous concentrations were similar. Conclusions We conclude that epidural infusion of 0.1% ropivacaine alone at 10 mL/h provided adequate analgesia in the first stage of labor, and that the addition of 2 μg/mL fentanyl to that concentration improved analgesia to a quality similar to 0.2% ropivacaine alone.

Vertebral osteomyelitis and psoas abscess occurring after obstetric epidural anesthesia

Background and Objectives Back pain and infectious complications occasionally occur after epidural anesthesia in obstetrics, and accurate diagnosis can be difficult. We report a patient who developed low back pain soon after obstetric epidural anesthesia and was diagnosed 6 months later with lumbar vertebral osteomyelitis, discitis, and a psoas abscess. Case Report A 34-year-old woman developed persistent low back pain after receiving epidural anesthesia for labor analgesia and cesarean delivery. After 6 months, a diagnosis of lumbar vertebral osteomyelitis, discitis, and psoas abscess was made, and surgery was performed. Because of the temporal and anatomical relationships between epidural catheterization and the development of symptoms, the preceding epidural anesthesia was initially suspected as a potential cause. However, because the posterior spinal elements were unaffected and the infectious agent was subsequently identified as tuberculous, the cause was eventually determined as unlikely to be related to the epidural procedure. Conclusion Investigation of severe back pain after epidural anesthesia should include consideration of infectious causes, such as vertebral osteomyelitis and discitis, which may not be causally related to the epidural catheterization itself.

The limitations of ropivacaine with epinephrine as an epidural test dose in parturients.

he ideal composition of epidural test doses isundetermined. Although lidocaine/epinephrineis well described, some clinicians use a smallinitial dose of the local anesthetic they have chosen forthe block (1). Ropivacaine 0.75% has been used forepidural anesthesia in obstetrics (2), but initial dosesof 2–3 mL failed to detect IV catheters (2,3), resultingin a seizure in one case (3). Addition of epinephrine toropivacaine was suggested as a marker for IV injection(3), but this has not been investigated. Moreover, al-though ropivacaine has been used for spinal anesthe-sia (4–6), the clinical effects of intrathecal ropivacaine,and thus criteria for identifying its inadvertent intra-thecal injection, have not been fully delineated. There-fore, we designed a randomized, double-blindedstudy to determine whether ropivacaine-epinephrinecould be used as an effective test dose in parturientshaving elective cesarean delivery.