Gordon Lyons

Determination of the Minimum Local Analgesic Concentrations of Epidural Bupivacaine and Lidocaine in Labor

The aim of this study was to devise a clinical model to determine the effective concentrations in 50% of patients (EC50) for bupivacaine and lidocaine in the first stage of labor and define EC50 as the minimum local analgesic concentration (MLAC).This should allow the determination of relative analgesic potency and, subsequently, the local anesthetic sparing efficacy of other epidural analgesics. Parturients not exceeding 5 cm cervical dilation who requested epidural analgesia were enrolled. The two studies involved 81 women (bupivacaine n = 41, lidocaine n = 40). After a lumbar epidural catheter was placed, 20 mL of the concentration of local anesthetic being tested was given. The concentration was determined by the response of the previous patient to a higher or lower concentration using doubleblinded, up-down sequential allocation. Efficacy was assessed using 100-mm visual analog pain scores with less than 10 mm within 1 h defined as effective. MLAC was determined using the formula of Dixon and Massey. Results show MLAC bupivacaine 0.065% (95% confidence interval [CI] 0.045-0.085), MLAC lidocaine 0.37% (95% CI 0.32-0.42), equivalent to 2 and 14 mmol solutions, respectively. Thus bupivacaine was 5.7 times more potent than lidocaine in weighted and 7 times more potent in molar ratios at analgesic EC50, in the volume of local anesthetic studied. (Anesth Analg 1995;81:833-7)

Thromboelastography Identifies Sex-Related Differences in Coagulation

Thromboelastography is an in vitro, point-of-care monitor of whole blood coagulation. Thromboelastography studies have demonstrated a hypercoagulable state during pregnancy. Perhaps the hypercoagulability is attributable to female sex hormones. The aim of the study was to determine if sex, in addition to pregnancy, affected thromboelastography variables by studying male and female (pregnant and nonpregnant) volunteers. Thromboelastography showed significant (P <0.01) differences in sex, with a significant (P < 0.0001) trend of increasing whole blood coagulability from men through nonpregnant to pregnant women. The thromboelastograph, used as a diagnostic tool, shows that women have more whole blood coagulability than men. Implications The thromboelastograph, used as a diagnostic tool, shows that women have more whole blood coagulability than men.

Minimum local analgesic dose of intrathecal bupivacaine in labor and the effect of intrathecal fentanyl

BackgroundCombining bupivacaine with fentanyl for intrathecal analgesia in labor is well recognized, but dosages commonly used are arbitrarily chosen and may be excessive. This study aimed to determine the median effective dose (ED50) of intrathecal bupivacaine, defined as the minimum local analgesic dose (MLAD), and then use this to assess the effect of different doses of fentanyl. MethodsIn this double-blind, randomized, prospective study, 124 parturients receiving combined spinal epidural analgesia at 2–6-cm cervical dilatation were allocated to one of four groups to receive bupivacaine alone or with 5, 15, or 25 &mgr;g fentanyl, using the technique of up–down sequential allocation. Analgesic effectiveness was assessed using 100-mm visual analog pain scores, with less than or equal to 10 mm within 15 min defined as effective. MLAD was calculated using the formula of Dixon and Massey. Pruritus and duration of spinal analgesia were also recorded. ResultsMinimum local analgesic dose of intrathecal bupivacaine was 1.99 mg (95% confidence interval, 1.71, 2.27). There were similar significant reductions in MLAD (P < 0.001) for all bupivacaine–fentanyl groups compared with bupivacaine control. There was a dose-dependent increase in both pruritus and duration of spinal analgesia with increasing fentanyl (P < 0.0001). ConclusionUnder the conditions of this study, the addition of intrathecal fentanyl 5 &mgr;g offers a similar significant bupivacaine dose-sparing effect as 15 and 25 &mgr;g. Analgesia in the first stage of labor can be achieved using lower doses of fentanyl, resulting in less pruritus but with a shortening of duration of action.

Levobupivacaine for epidural analgesia in labor : The sparing effect of epidural fentanyl

Evidence suggests that levobupivacaine has similar pharmacodynamic properties to racemic bupivacaine. We sought to investigate whether this similarity extends to opioid sparing when levobupivacaine is used for epidural analgesia in laboring women by quantifying the effect of fentanyl on the minimum local analgesic concentration (MLAC) of levobupivacaine. One-hundred-six women requesting epidural analgesia for labor pain were recruited in this randomized, double-blinded, up-down sequential allocation study. Each received 20 mL of one of three test solutions: levobupivacaine control, levobupivacaine and fentanyl 2 &mgr;g/mL, or levobupivacaine and fentanyl 3 &mgr;g/mL. The initial levobupivacaine concentration was 0.07% wt/vol in each group, with subsequent concentrations of levobupivacaine being determined by the response of the previous patient (testing interval 0.01% wt/vol). Efficacy was accepted if the visual analog score decreased to 10 mm or less on a 100-mm scale within 30 min. The MLAC of levobupivacaine in the control group was 0.091% wt/vol (95% CI, 0.052–0.130). Fentanyl at concentrations of 2 &mgr;g/mL and 3 &mgr;g/mL significantly reduced the MLAC of levobupivacaine to 0.047% wt/vol (95% CI, 0.023–0.072) and 0.050% wt/vol (95% CI, 0.035–0.065), respectively (P < 0.001). A dose-dependent effect was not demonstrated. We conclude that fentanyl significantly reduces levobupivacaine requirements for epidural analgesia in labor. Implications Determination of minimum local analgesic concentrations by the technique of sequential allocation allows the interaction between epidural opioids and local anesthetics to be quantified. This study demonstrates that the addition of fentanyl significantly reduces levobupivacaine requirements for epidural analgesia.

Intraoperative awareness during general anesthesia for cesarean delivery.

Intraoperative awareness is defined as the spontaneous recall of an event occurring during general anesthesia. A move away from rigid anesthetic protocols, which were designed to limit drug transmission across the placenta, has reduced the incidence of awareness during cesarean delivery to approximately 0.26%. Nevertheless, it remains an undesirable complication with potential for the development of posttraumatic stress disorder. Assessing depth of anesthesia remains a challenge for the anesthesia provider as clinical signs are unreliable and there is no sensitive and specific monitor. Bispectral Index monitoring with the goal of scores <60 has been recommended to prevent awareness. Induction drugs vary in their ability to produce amnesia and the period of hypnotic effect is affected by the rate at which they are redistributed. After initiation of anesthesia, volatile anesthetics should be administered to a target of 0.7 minimum alveolar anesthetic concentration, which has been shown to consistently achieve mean Bispectral Index scores <60. Because of its rapid uptake, nitrous oxide remains an important adjunct to reduce the risk of awareness during emergency cesarean delivery. In the absence of fetal compromise, there is no rationale for an inspired oxygen concentration above 0.33. Deeper levels of anesthesia reduce the incidence of awareness; current evidence does not suggest an increased risk of tocolysis or fetal morbidity.

Minimum Analgesic Dose of Epidural Sufentanil for First-stage Labor Analgesia: A Comparison between Spontaneous and Prostaglandin-induced Labors in Nulliparous Women

Background The aim of this prospective, double-blind, sequential allocation study was to compare the effects of spontaneous and prostaglandin-induced labor on the minimum analgesic dose of epidural sufentanil in the first stage of labor. Methods Seventy healthy, nulliparous women, at more than 37 weeks’ gestation with cervical dilatation from 2 to 4 cm, requesting epidural pain relief in labor were enrolled. The subjects were assigned to two different groups according to whether labor was spontaneous or induced with dinoprostone 0.5 mg. Parturients received 10 ml of the study solution through a lumbar epidural catheter. The initial dose was sufentanil 25 &mgr;g, and subsequent doses were determined by the response of the previous patient in the same group using up–down sequential allocation. The analgesic effectiveness was assessed using 100-mm visual analog pain scores. The up–down sequences were analyzed using the method of independent paired reversals and probit regression. Results The minimum analgesic dose of sufentanil in spontaneous labor was 22.2 &mgr;g (95% CI: 19.6, 22.8) and 27.3 &mgr;g (95% CI: 23.8, 30.9) in induced labor. The minimum analgesic dose of sufentanil in induced labor was significantly greater (P = 0.0014) than that in spontaneous labor (95% CI difference: 2.9, 9.3) by a factor of 1.3 (95% CI: 1.1, 1.5). Conclusion Prostaglandin induction of labor produces a significantly greater analgesic requirement than does spontaneous labor.

A Comparison of Minimum Local Anesthetic Volumes and Doses of Epidural Bupivacaine (0.125% w/v and 0.25% w/v) for Analgesia in Labor

BACKGROUND: In this study we sought to determine and compare the minimum local anesthetic volumes (MLAV) and doses (MLAD) of two concentrations of bupivacaine for epidural pain relief in labor, and to quantify the effect on dose. METHODS: Eighty women were randomized in a double-blind manner to receive a first bolus of either plain bupivacaine 0.125% (w/v) or 0.25% (w/v). The arbitrary starting volume was 15 mL. Subsequent volumes were decided by sequential allocation according to analgesic efficacy. A visual analog pain score ≤10 (0–100) within 30 min, indicated effective analgesia. The next woman received a decrement of 2 mL. A failure of the visual analog pain score to reach ≤10 was followed by a 2 mL increment for the next woman. RESULTS: Using the formula of Dixon and Massey, MLAV and MLAD, with 95% confidence intervals (CI) were calculated for each concentration. MLAV was 13.6 mL (95% CI 12.4–14.8), with bupivacaine 0.125% (w/v), and 9.2 mL (95% CI 6.9–11.5) with bupivacaine 0.25% (w/v). The difference was highly significant (P = 0.002). MLAD for these volumes were 17.0 mg (95% CI 15.5–18.5), and 23.1 mg (17.2–28.9), respectively (P = 0.045). CONCLUSIONS: Bupivacaine 0.125% (w/v) when compared with 0.25% (w/v) produced equivalent analgesia with a 50% increase in volume, but with a 25% reduction in dose. Any reduction in dose, without loss of efficacy, reduces risk of toxicity and improves safety.

The effect of epidural fentanyl on the minimum local analgesic concentration of epidural chloroprocaine in labor

The minimum local analgesic concentration (MLAC) has been defined as the median effective local analgesic concentration (EC50) in a 20-mL volume in the first stage of labor. The aim of this study was to determine the local anesthetic sparing efficacy of epidural fentanyl by its effect on the MLAC of chloroprocaine. Fifty-six parturients, not exceeding 7 cm cervical dilation, who requested epidural analgesia were allocated to one of two groups in this double-blind, randomized, prospective study. After placing a lumbar epidural catheter, 20 mL of the solution being tested was given: chloroprocaine (n = 28) or chloroprocaine with fentanyl 3 micro g/mL (60 micro g) (n = 28). The concentration of chloroprocaine was determined by the response of the previous patient to a higher or lower concentration using up-down sequential allocation. Analgesic efficacy was assessed using 100-mm visual analog pain scores with 10 mm or less within 30 min defined as effective. The MLAC of chloroprocaine was reduced from 0.43% wt/vol to 0.26% wt/vol by fentanyl (P = 0.023). Thus, the addition of epidural fentanyl 3 micro g/mL (60 micro g) resulted in a significant 40% reduction in the MLAC of chloroprocaine in the first stage of labor. (Anesth Analg 1996;83:987-90)

Effect of maternal facial oxygen on neonatal behavioural scores during elective Caesarean section with spinal anaesthesia.

Background and objective: For many, the administration of additional oxygen to the women receiving regional anaesthesia for Caesarean section is traditional, but for others it is controversial because of doubts about its efficacy. The aim of our study was to determine if beneficial effects of maternal oxygen therapy on the fetus could be revealed using a neonatal behavioural scoring system. Methods: Sixty women with a normal singleton pregnancy beyond 36 weeks gestation, undergoing elective Caesarean section under spinal anaesthesia were randomized into two groups: Group 1 received air and oxygen mixture through a Hudson style face mask (FiO2 of 0.21–0.25). Group 2 received FiO2 of 0.40–0.60 through an identical Hudson style face mask. Neurologic Adaptive Capacity Score on all the infants within 5 min of birth and between 10 and 24 h after the Caesarean delivery was performed. Apgar score, umbilical venous blood oxygen tension and umbilical artery standardized base excess were recorded. Results: Initial Neurologic Adaptive Capacity Scores at birth in Groups 1 and 2 were 32.6 (SD 4.6) and 31.3 (SD 4.3), respectively. Latter scores were 36.0 (SD 3.0) and 36.5 (SD 1.9), respectively. Neither were statistically significant. There were no significant differences between the groups for any of the recorded variables. Conclusions: Administering maternal oxygen using a standard commercial Hudson style face mask does not appear to significantly improve oxygen delivery to, nor does it influence acidosis or behavioural effects in, the normal neonate at elective Caesarean delivery with spinal anaesthesia.

Language: another cause of publication bias.

Some years ago I was researching the effects of gender on coagulation using the thromboelastograph. As a spin off, I explored the feasibility of studying the coagulation effects of female sex hormones by following changes during the menstrual cycle. The literature search was not encouraging, but there was a study in Russian that appeared to do just this. At some cost to our meagre funds I paid for a translation only to find that the cycle in question was not menstrual but lunar. I tell this story to illustrate that, outside the confines of our own language, we have no or little idea of what is out there. The scope of the undiscovered body of work written in languages other than English is unknown, as is its quality.