Transfer of methohexital across the perfused human placenta.

STUDY OBJECTIVES: To evaluate the transfer properties of methohexital and the influence of protein binding using the in vitro human placental perfusion model. DESIGN: Fresh term human placentae from healthy parturients were perfused bidirectionally via a cannulated fetal chorionic artery and vein and needles placed into the maternal intervillous space. Maternal-to-fetal (M-->F) and fetal-to-maternal (F-->M) transfer and ultimate distribution of methohexital was investigated using a closed (recirculating) placental perfusion model. SETTING: Obstetric anesthesia laboratories of two university medical centers. PATIENTS: No patient participation occurred as placentae were obtained after delivery. INTERVENTION: M-->F and F-->M transfer of methohexital was compared in vitro in perfusates with equal protein concentrations (2 g/100 mL in both perfusates) or albumin-simulated physiologic protein binding concentrations (maternal 8 g/100 mL; fetal 4 g/100 mL). MEASUREMENTS AND MAIN RESULTS: Data obtained consisted of measurements of methohexital and antipyrine concentrations by high-performance liquid chromatography. Glucose and lactate concentrations and perfusate loss were measured to assess placental viability. Methohexital protein binding was assessed at 2, 4, and 8 g/100 mL of albumin by equilibrium dialysis. The transfer index of 0.83 +/- 0.11 for the M-->F perfusions was significantly greater (p < or = 0.05) than in the F-->M direction (0.61 +/- 0.04) when albumin concentration was equal in both perfusates. This transfer asymmetry disappeared when albumin concentrations simulating maternal (8 g/100 mL) versus fetal (4 g/100 mL) protein concentrations in the perfusate were used (M-->F 0.87 +/- 0.12 and F-->M 0.95 +/- 0.11). CONCLUSION: Methohexital readily crosses the placenta in both directions. Protein binding has significant effects on the degree of transfer of methohexital at any time when compared with antipyrine and its ultimate fetal/maternal distribution.

Analgesia, pruritus, and ventilation exhibit a dose-response relationship in parturients receiving intrathecal fentanyl during labor.

UNLABELLED: Several studies have characterized the 50% and 95% effective doses (ED50 and ED95, respectively) of intrathecal sufentanil for labor analgesia. Few have investigated these same criteria for the less expensive alternative, fentanyl. In addition, the ventilatory effects of intrathecal fentanyl at clinically relevant doses are unclear. We performed this study to establish the dose-response relationship of intrathecal fentanyl for both analgesia and ventilatory depression. Ninety parturients in active early labor (< or = 5 cm dilation) received intrathecal fentanyl 5, 7.5, 10, 15, 20, or 25 micrograms in a double-blinded, randomized fashion (n = 15 patients in each group). Parturients were monitored for degree of pain (measured using a 100-mm visual analog pain scale), blood pressure, arterial oxygen saturation (SaO2), respiratory rate, ETCO2, and fetal heart rate 0, 1, 5, 10, 15, 20, 25, and 30 min after the administration of intrathecal fentanyl. An absolute visual analog pain scale score < or = 25 mm was defined a priori as analgesic success. The percentage of parturients who achieved analgesic success was used to construct quantal dose-response curves, from which the ED50 and ED95 values were derived for the total population (mixed parity) and the nulliparous and multiparous subpopulations separately. Overall ED50 and ED95 values (95% CI) were 5.5 (3.4-7.2) and 17.4 (13.8-27.1) micrograms, respectively. Nulliparous values were lower (5.3 and 15.9 micrograms, respectively) than multiparous values (6.9 and 26.0 micrograms, respectively) but were within the 95% CIs of the total population. Pruritus incidence in parturients with analgesic success displayed a dose-response relationship identical to that seen for analgesia. ETCO2 displayed a dose-related increase, particularly at doses > or = 15 micrograms, without concomitant changes in respiratory rate or SaO2, which suggests a decrease in tidal volume. Even in the absence of overt signs or symptoms of somnolence, intrathecal fentanyl at doses within the effective analgesic range induced a change in ventilation that may last longer than the 30-min period we studied. IMPLICATIONS: Intrathecal fentanyl induces rapid and satisfying dose-dependent analgesia in early labor; however, it also produces dose-related decreases in ventilation in the absence of overt somnolence.

Determination of the analgesic dose-response relationship for epidural fentanyl and sufentanil with bupivacaine 0.125% in laboring patients.

STUDY OBJECTIVE: To establish the analgesic effective doses as defined as a visual analog pain scale (VAS) of at least 10 for 95% of parturients (ED95) receiving either epidural fentanyl or sufentanil with bupivacaine 0.125% for labor analgesia. DESIGN: Double-blind, randomized controlled study. SETTING: Two tertiary-care teaching hospitals. PATIENTS: 100 female patients, at full-term pregnancy, in active early labor (< 5 cm cervical dilation) and requesting obstetric anesthesia services for labor analgesia. INTERVENTIONS: Patients were randomized and equally distributed to receive one of ten epidural dosing regimens of bupivacaine 0.125% alone or with either fentanyl 25, 50, 75, or 100 micrograms or sufentanil 5, 10, 15, 20, or 25 micrograms in a 10-ml bolus after a 3-ml test dose of bupivacaine 0.25%. MEASUREMENTS AND MAIN RESULTS: VAS scores were obtained from each parturient using a 10-cm plastic VAS slide rule at times 0, 1, 5, 10, 15, 20, 25, and 30 minutes, and then again when the patient requested additional analgesia. Analgesic duration and demographic and obstetric data also were obtained. Using a log-probit dose-response analysis, analgesic success as defined as a VAS of at least 10 with each opioid dose was plotted and an ED95 value of 8 micrograms and 50 micrograms was established for sufentanil and fentanyl, respectively, in bupivacaine 0.125%. No statistical difference was detected for analgesic duration or incidence of side effects between analgesic groups. CONCLUSIONS: Epidural analgesia with fentanyl and sufentanil in bupivacaine 0.125% behaves in a dose-response fashion allowing for the determination of equipotent dose of each.

Determination of the dose-response relationship for intrathecal sufentanil in laboring patients.

Multiple studies have investigated the efficacy of intrathecal opioids, particularly sufentanil, in laboring parturients. However, until the important pharmacological indices of the 50% and 95% effective doses (ED50 and ED95, respectively) are defined, reliable comparative studies among drugs at equipotent doses cannot be performed. This study was performed to establish the dose-response relationship of intrathecal sufentanil analgesia in labor. Sixty parturients presenting in active labor received intrathecal sufentanil 2.5 (n = 10), 5.0 (n = 10), 7.5 (n = 10), 10.0 (n = 10), 12.5 (n = 10), or 15.0 (n = 10) microg in a blind, randomized fashion. Patient 100-mm visual analog pain scale (VAS) scores, fetal heart rate (FHR), blood pressure, and heart rate were recorded at 0, 1, 5, 10, 15, 20, 25, and 30 min after administration of sufentanil and then again when the patient requested additional analgesia. Absolute VAS < or =25 mm was considered an analgesic success. Percent responders was used to construct a dose-response curve and calculate ED50 and ED95. The ED50 and ED95 for intrathecal sufentanil in laboring parturients were 2.6 (1.8-3.2, 95% confidence interval) and 8.9 (7.5-11.5) microg, respectively. There was a trend toward increasing analgesic duration with increasing sufentanil dose. The maternal side effect profile was not different among groups. FHR did not appreciably change for any group or individual studied. Assisted delivery and cesarean section rates were similar for all groups. Intrathecal sufentanil provides rapid onset of analgesia for labor. The ED50 and ED95 values established in this study should help to provide benchmarks both for the safe clinical use of intrathecal sufentanil for labor and for future comparison studies with other intrathecal analgesic techniques.

Cricoid pressure: teaching the recommended level.

The Sellick maneuver or cricoid pressure is an effective means of preventing passive aspiration of gastric contents. Recent studies recommend a pressure of 20 newtons (N) when the patient is awake, increasing to 30-40 N with unconsciousness. This study was proposed to determine whether with education and practice, anesthesia providers and assistants could be taught a recommended cricoid pressure and retain this skill. Cricoid force was measured using a life-size laryngotracheal model on a calibrated infant scale. Fifty-three participants were divided into six groups: MD faculty; CA-1, 2, and 3 Residents; certified registered nurse anesthetists (CRNA); and Others. Each was asked to apply pressure to the blinded model to simulate application of the Sellick's maneuver to an "awake" and "unconscious" patient on four occasions: before instruction of the recommended pressures (Preinstruction), after being informed of the recommended magnitudes of 20 N/awake and 30-40 N/anesthetized (Postinstruction), after a period of unblinded practice (Postpractice), and 3 mo or longer after practice (Follow-up). Initial attempts revealed inadequate force by all participants, "awake" and "anesthetized". All participants were able to learn the recommended amount of applied pressure and were able to retain this knowledge after 3 mo. This model represents an easy and practical means of teaching the application of the optimal level of force to practitioners and assistants.