Mrinalini Balki

Oxytocin requirements at elective cesarean delivery: a dose-finding study.

OBJECTIVE: Oxytocin is frequently used by intravenous bolus and infusion to minimize blood loss and prevent postpartum hemorrhage at cesarean delivery. Current dosing regimens are arbitrary whereas large doses may pose a serious risk to the mother. The purpose of this study was to estimate the minimum effective intravenous bolus dose of oxytocin (ED90) required for adequate uterine contraction at elective cesarean in nonlaboring women. METHODS: A randomized, single-blinded study was undertaken in 40 healthy term pregnant women presenting for elective cesarean under spinal anesthesia. Oxytocin was administered by bolus according to a biased coin up-and-down sequential allocation scheme with increments or decrements of 0.5 IU. Uterine contraction was assessed by the obstetrician, who was blinded to the dose of oxytocin, as either satisfactory or unsatisfactory. After achieving sustained uterine contraction, an infusion of 40 mU/min of oxytocin was started. Oxytocin-induced adverse effects and intraoperative complications were recorded and blood loss was estimated. Data were interpreted by parametric analysis based on logistic regression model and nonparametric analyses at 95% confidence intervals (CIs). RESULTS: The ED90 of oxytocin as determined by logistic regression model fitted to the data was estimated to be 0.35 IU (95% CI 0.18–0.52 IU), with nonparametric estimates of 97.1% (95% CI 84.9–99.8%) response rate at 0.5 IU, and 100% (95% CI 92.2–100%) at 1.0 IU. The estimated blood loss was 693 ± 487 mL (mean ± standard deviation). CONCLUSION: The bolus dose of oxytocin used at elective cesarean deliveries in nonlaboring women can be significantly reduced while maintaining effective uterine contraction. Alteration in practice will likely reduce the potential adverse effects of this drug when given in large bolus doses, but may require modification of the techniques to remove the placenta.

Ultrasound Imaging of the Lumbar Spine in the Transverse Plane: The Correlation Between Estimated and Actual Depth to the Epidural Space in Obese Parturients

BACKGROUND: Prepuncture lumbar ultrasound scanning is a reliable tool to facilitate labor epidural needle placement in nonobese parturients. In this study, we assessed prepuncture lumbar ultrasound scanning as a tool for estimating the depth to the epidural space and determining the optimal insertion point in obese parturients. METHODS: We studied 46 obese parturients, with prepregnancy body mass index (BMI) >30 kg/m2, requesting labor epidural analgesia. Ultrasound imaging was done by one of the investigators to identify the midline, the intervertebral space, and the distance from the skin to the epidural space (ultrasound depth, UD) at the level of L3–4. Subsequently, an anesthesiologist blinded to the UD located the epidural space through the predetermined insertion point and marked the actual distance from the skin to the epidural space (needle depth, ND) on the needle with a sterile marker. The agreement between the UD and the ND was calculated using the Pearson correlation coefficient and a paired t-test. Bland-Altman analysis was used to determine the 95% limits of agreement between the UD and the ND. RESULTS: The prepregnancy BMI ranged from 30 to 79 kg/m2, and the BMI at delivery was 33–86 kg/m2. The Pearson correlation coefficient between the UD and the ND was 0.85 (95% confidence interval: 0.75–0.91), and the concordance correlation coefficient was 0.79 (95% confidence interval: 0.71–0.88). The mean (±sd) ND and UD were 6.6 ± 1.0 cm and 6.3 ± 0.8 cm, respectively (difference = 0.3 cm, P = 0.002). The 95% limits of agreement were 1.3 cm to −0.7 cm. Epidural needle placement using the predetermined insertion point was done without reinsertion at a different puncture site in 76.1% of parturients and without redirection in 67.4%. CONCLUSIONS: We found a strong correlation between the ultrasound-estimated distance to the epidural space and the actual measured needle distance in obese parturients. We suggest that prepuncture lumbar ultrasound may be a useful guide to facilitate the placement of epidural needles in obese parturients.

Patient satisfaction with awake craniotomy for tumor surgery: a comparison of remifentanil and fentanyl in conjunction with propofol.

In this study we compared the effectiveness of the use of remifentanil to fentanyl in conjunction with propofol in providing conscious sedation for awake craniotomy for tumor surgery and to assess patient satisfaction with both techniques. The ability to maintain appropriate levels of sedation, adequate analgesia, and hemodynamic stability was assessed in 50 patients randomized to receive either fentanyl or remifentanil. All complications were documented. Patients were interviewed at 1 h, 4 h, and 24 h after surgery to note their recall of procedure and pain and their overall satisfaction. There were no differences in sedation and pain scores or in hemodynamic and respiratory variables between the two groups. The incidence of intraoperative complications was not different (fentanyl, 14; remifentanil, 16). Respiratory complications occurred in 9 (18%) patients (fentanyl 6, remifentanil 3). The recall and satisfaction scores were not different; 93% of all patients were completely satisfied at all interview times. The use of remifentanil infusion in conjunction with propofol is a good alternative to fentanyl and propofol for conscious sedation for the awake craniotomy and these techniques are both well accepted by the patient.

Minimum Oxytocin Dose Requirement After Cesarean Delivery for Labor Arrest

OBJECTIVE: To estimate the minimum effective intravenous dose of oxytocin required for adequate uterine contraction after cesarean delivery for labor arrest. METHODS: A randomized single-blinded study was undertaken in 30 parturients undergoing cesarean deliveries under epidural anesthesia for labor arrest despite intravenous oxytocin augmentation. Oxytocin was administered as a slow intravenous bolus immediately after delivery of the infant, according to a biased coin up-down sequential allocation scheme. After assisted spontaneous delivery of the placenta, the obstetrician, blinded to the oxytocin dose, assessed uterine contraction as either satisfactory or unsatisfactory. Additional boluses of oxytocin were administered as required, followed by a maintenance infusion. Data were interpreted and analyzed by a logistic regression model at 95% confidence intervals. RESULTS: All patients received oxytocin infusions at a mean ± standard deviation of 9.8 ± 6.3 hours before cesarean delivery (maximum infusion dose 10.3 ± 8.2 mU/min). The minimum effective dose of oxytocin required to produce adequate uterine response in 90% of women (ED90) was estimated to be 2.99 IU (95% confidence interval 2.32–3.67). The estimated blood loss was 1,178 ± 716 mL. CONCLUSION: Women requiring cesarean delivery for labor arrest after oxytocin augmentation require approximately 3 IU rapid intravenous infusion of oxytocin to achieve effective uterine contraction after delivery. This dose is 9 times more than previously reported after elective cesarean delivery in nonlaboring women at term, suggesting oxytocin receptor desensitization from exogenous oxytocin administration during labor. Therefore, alternative uterotonic agents, rather than additional oxytocin, may achieve superior uterine contraction and control of blood loss during cesarean delivery for labor arrest. LEVEL OF EVIDENCE: I

Remifentanil patient-controlled analgesia for labour: optimizing drug delivery regimens.

PurposeA pilot study was undertaken to compare the efficacy of two regimens of intravenous patient-controlled analgesia (PCA) with remifentanil for labour analgesia.MethodsTwenty term parturients requesting labour analgesia were randomized to receive one of two regimens of intravenous remifentanil. The initial settings in both groups consisted of an infusion of 0.025 μg·kg-1·min-1, a PCA bolus of 0.25 μg·kg-1 and a lockout interval of two minutes. In Group A, the infusion was increased in a stepwise manner from 0.025 to 0.05, 0.075 and 0.1 μg·kg-1·min-1 as required; the bolus was kept constant at 0.25 μg·kg-1. In Group B, the bolus was increased from 0.25 to 0.5, 0.75 and 1 μg·kg-1 as necessary; the infusion was kept constant at 0.025 μg·kg-1·min-1. Maternal pain, satisfaction and sedation scores, remifentanil requirement, and side effects were recorded.ResultsMean pain and patient satisfaction scores, and cumulative doses of remifentanil were similar in the two groups. The overall incidence of side effects was greater in Group B (P = 0.0007), with drowsiness observed in 100% of patients, as compared to 30% in Group A (P = 0.003). The minimum oxygen saturation levels were 94.3% ± 2.6% and 92.2% ± 3.8% in Groups A and B respectively (P = 0.19).ConclusionsAlthough pain and satisfaction scores were similar in both groups, the regimen used in Group A was associated with fewer side effects compared to the Group B dosing regimen. This pilot study suggests that remifentanil intravenous PCA is efficacious for labour analgesia as a bolus of 0.25 μg·kg-1, with a lockout interval of two minutes and continuous infusion of 0.025-0.1 μg·kg-1·min-1. The potential for respiratory depression mandates close respiratory monitoring. Large-scale trials to evaluate safety issues are warranted.RésuméObjectifUne étude pilote a été entreprise afin de comparer l’efficacité de deux régimes intraveineux d’analgésie contrôlée par le patient (ACP) avec du rémifentanil pour le travail obstétrical.MéthodeVingt parturientes à terme demandant une analgésie pour le travail ont été randomisées à recevoir l’un de deux régimes de rémifentanil intraveineux. Les réglages de base dans les deux groupes consistaient en une perfusion de 0,025 μg·kg-1 ·min-1, un bolus ACP de 0,25 μg·kg-1 et un intervalle d’interdiction de deux minutes. Dans le groupe A, la perfusion a été augmentée par paliers de 0,025 à 0,05, 0,075 et 0,1 μg·kg-1 ·min-1 au besoin; le bolus a été maintenu constant à 0,25 μg·k-1. Dans le groupe B, le bolus a été augmenté de 0,25 à 0,5, 0,75 et 1 μg·kg-1 au besoin; la perfusion a été maintenue constante à 0,025 μg·kg-1·min-1. Les douleurs maternelles, les scores de satisfaction et de sédation, les besoins en rémifentanil et les effets secondaires ont été enregistrés.RésultatLes scores moyens de douleur et de satisfaction des patientes ainsi que les doses cumulatives de rémifentanil ont atteint des résultats similaires dans les deux groupes. L’incidence totale d’effets secondaires était plus élevée dans le groupe B(P = 0,007), avec des cas de somnolence chez 100 % des patientes comparativement à 30 % dans le groupe A (P = 0,003). Le minimum de saturation en oxygène était de 94,3 % ± 2,6% et 92,2 % ± 3,8 % dans les groupes A et B respectivement (P = 0,19).ConclusionBien que les scores de douleur et de satisfaction étaient similaires dans les deux groupes, le régime utilisé par le groupe A a été associé à moins d’effets secondaires que le régime de dosage du groupe B. Cette étude pilote suggère que l’ACP intraveineuse au rémifentanil est efficace pour l’analgésie pour le travail en bolus de 0,25 μg·kg-1, avec un intervalle d’interdiction de deux minutes et une perfusion continue de 0,025 - 0,1 μg·kg-1 ·min-1. Toutefois, un monitorage respiratoire attentif est nécessaire en raison du potentiel de développement de dépressions respiratoires. Des essais à grande échelle pour évaluer les questions d’innocuité sont requis.

ED95 of phenylephrine to prevent spinal-induced hypotension and/or nausea at elective cesarean delivery

BACKGROUND The purpose of this trial was to determine the 95% effective dose (ED95) of phenylephrine by intermittent i.v. bolus, to prevent spinal-induced hypotension and/or nausea at elective cesarean delivery. METHODS The study was conducted in a double-blinded fashion in 50 patients undergoing elective cesarean delivery under spinal anesthesia. The dose of phenylephrine was determined using up-down sequential allocation, modified by a variation of the Narayana rule. Systolic pressure and heart rate were assessed every minute until uterine incision. The first patient was assigned a 40-microg dose, and the dose to subsequent patients varied by 10-microg increments or decrements. An adequate response was defined as absence of hypotension (systolic pressure <80% of baseline) and nausea. The study solution was given immediately after spinal administration, without prior pressure measurement, and thereafter when the systolic pressure was <or=control values. fell below baseline. The ED95 was determined by a logistic model with non-log-transformed doses, using Firths penalized maximum likelihood method with 95% confidence intervals based on penalized profile likelihood. RESULTS The ED95 of phenylephrine was estimated as 159 microg (95% confidence interval: 122-371 microg), although the largest dose given in the study was only 120 microg. Hypertension (systolic blood pressure >120% of baseline) was observed in 14 cases, immediately after intrathecal injection and prophylactic phenylephrine administration in all cases. CONCLUSION The ED95 of phenylephrine, administered as intermittent boluses to prevent pre-delivery spinal-induced hypotension and/or nausea at elective cesarean delivery, is at least 122 microg (lower limit of the confidence interval). The safety of this dose warrants further studies.

Oxytocin Pretreatment Decreases Oxytocin-induced Myometrial Contractions in Pregnant Rats in a Concentration-dependent But Not Time-dependent Manner

Recent biomolecular studies have shown that continuous exposure of human myometrial cells to oxytocin results in a significant loss of responsiveness to subsequent oxytocin stimulation, perhaps because of desensitization of the oxytocin receptors. However, it is unclear whether this phenomenon results in a reduction of the contractile activity of the uterine muscle in humans or animals. The objective of our study was to investigate the in vitro response of the uterine muscle of pregnant rats to oxytocin, following preexposure to varying concentrations of oxytocin, for varying durations. Longitudinal myometrial strips were isolated from 16 pregnant Wistar rats at 19 to 21 days of gestation and preexposed to oxytocin 10-10 or 10-8 mol/L (experimental groups) or physiological salt solution (control groups) for 1- or 4-hour period. All muscle strips were then subjected to a dose-response study with oxytocin 10-10 to 10-5 mol/L. The area under the curve, frequency, and amplitude of contractions were recorded and compared between the groups. The area under the curve, frequency, and amplitude of the oxytocin-induced contractions were all significantly suppressed in the groups preexposed to oxytocin 10 -8 mol/L compared to either the control groups (P < .0001) or the groups preexposed to oxytocin 10-10 mol/L (P < .0001). There was no difference in the oxytocin-induced myometrial contractions between the groups preexposed to oxytocin for either the 1- or 4-hour periods. The inhibition of the oxytocin-induced contractile response of pregnant rat myometrium is observed as early as 1 hour of preexposure to oxytocin and is dependent on the preexposed oxytocin concentration and not on the duration of its exposure.

Oxytocin pretreatment attenuates oxytocin-induced contractions in human myometrium in vitro.

Background:Oxytocin receptor desensitization has been shown to occur in humans at biomolecular level and in isolated rat myometrium; however, its effect on human myometrial contractility has not been demonstrated. The objective of this in vitro study was to investigate the contractile response of human pregnant myometrium to oxytocin after pretreatment with different concentrations of oxytocin for variable durations. Methods:Myometrial samples were obtained from 62 women undergoing elective cesarean deliveries under regional anesthesia. The strips were pretreated with oxytocin 10−10, 10−8, 10−5 M, or physiological salt solution (control) for 2, 4, 6, or 12 h, followed by a dose–response testing with oxytocin 10−10 to 10−5 M. Amplitude and frequency of contractions, motility index, and area under the curve during the dose–response period were recorded, analyzed with linear regression models, and compared among groups. Results:Pretreatment with oxytocin 10−5 and 10−8 M significantly reduced motility index (estimate [standard error]: −0.771 [0.270] square root units, P = 0.005 and −0.697 [0.293], P = 0.02, respectively) and area under the curve (−3.947 [1.909], P = 0.04 and −4.241 [2.189], P = 0.05, respectively) compared with control group, whereas pretreatment with oxytocin 10−10 M did not significantly attenuate contractions. Increase in duration of oxytocin pretreatment from 2 to 12 h significantly decreased amplitude (type 3 generalized estimating equation analysis: chi-square = 14.0; df = 3; P = 0.003), motility index (chi-square = 9.3; df = 3; P = 0.03), and area under the curve (chi-square = 10.5; df = 3; P = 0.02), but not the frequency of oxytocin-induced contractions. Conclusion:Pretreatment with oxytocin decreases oxytocin-induced myometrial contractions in a concentration and time-dependent manner, likely as a function of the oxytocin receptor desensitization phenomenon.

Blood Transfusion for Primary Postpartum Hemorrhage: A Tertiary Care Hospital Review

OBJECTIVE To describe the common characteristics, clinical management, and outcome of patients requiring blood transfusion within 24 hours of delivery. METHODS We conducted a retrospective cohort study of patients who received blood transfusion for postpartum hemorrhage (PPH) in the first 24 hours post-delivery, over a five-year period (2000-2005). The medical records of patients were reviewed to obtain information about demographics, pregnancy and delivery characteristics, transfusion data, and complications. RESULTS The overall blood transfusion rate for PPH was 0.31% (104/33,631 deliveries). The rate of blood transfusion in women who had a Caesarean section during labour was 0.49%, whereas in women who had a vaginal delivery or elective Caesarean section it was 0.28% and 0.23%, respectively. Antenatal risk factors for PPH were identified in 61% of patients, and 39% of patients developed intrapartum risk factors. The most important etiological factors were uterine atony (38.5%) and retained products of conception (33.7%). Twenty-one percent of the patients developed coagulopathy, and 24% required admission to the intensive care unit. CONCLUSION Severe primary PPH requiring blood transfusion can be predicted in the majority of patients on the basis of antenatal risk factors, while the remaining patients require vigilant monitoring for risk factors during labour and delivery. In the multidisciplinary effort to prevent and control major PPH, we should re-evaluate the pharmacotherapy for PPH and ensure careful removal of retained placental tissue after delivery.

Sonoanatomy of the lumbar spine of pregnant women at term.

Background and Objectives: Spinal ultrasound offers valuable information to facilitate the placement of lumbar neuraxial anesthesia. Lumbar spine sonograms are unique, and aspects may appear atypical at times, particularly the ligamentum flavum (LF). The objective of this study was to describe the sonoanatomy of the lumbar spine and to determine the frequency of atypical images of the LF in pregnant women at term. Methods: Using a 2-5 MHz curvilinear transducer, we imaged all the lumbar interspaces in the left and right paramedian longitudinal and transverse planes. The images were categorized as typical, atypical or inconclusive. The primary outcome was the presence of an atypical image of the LF in the transverse plane. The distance from the skin to the epidural space, and the dural sac width, were also measured. Results: One hundred subjects were studied. All the images in the longitudinal planes were conclusive and typical, whereas the number of inconclusive images in the transverse plane increased from L1-L2 to L5-S1 (1, 0, 4, 9, and 34, respectively). The incidence of atypical LF images in the transverse plane was 2.0% at L1-L2, 1.0% at L2-L3, 3.1% at L3-L4, 19.8% at L4-L5, and 28.8% at L5-S1. Conclusions: The paramedian longitudinal sonograms of the lumbar spine are of superior quality to those obtained in the transverse plane. When using the transverse approach, a high incidence of inconclusive sonograms should be expected in the lower segments. The incidence of atypical LF images, especially in the upper lumbar segments, warrants further investigation because it can have implications for the epidural technique.