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Background Current recommendations for women undergoing cesarean delivery include 15° left tilt for uterine displacement to prevent aortocaval compression, although this degree of tilt is practically never achieved. We hypothesized that under contemporary clinical practice, including a crystalloid coload and phenylephrine infusion targeted at maintaining baseline systolic blood pressure, there would be no effect of maternal position on neonatal acid base status in women undergoing elective cesarean delivery with spinal anesthesia. Methods Healthy women undergoing elective cesarean delivery were randomized (nonblinded) to supine horizontal (supine, n = 50) or 15° left tilt of the surgical table (tilt, n = 50) after spinal anesthesia (hyperbaric bupivacaine 12 mg, fentanyl 15 μg, preservative-free morphine 150 μg). Lactated Ringer’s 10 ml/kg and a phenylephrine infusion titrated to 100% baseline systolic blood pressure were initiated with intrathecal injection. The primary outcome was umbilical artery base excess. Results There were no differences in umbilical artery base excess or pH between groups. The mean umbilical artery base excess (± SD) was −0.5 mM (± 1.6) in the supine group (n = 50) versus −0.6 mM (± 1.5) in the tilt group (n = 47) (P = 0.64). During 15 min after spinal anesthesia, mean phenylephrine requirement was greater (P = 0.002), and mean cardiac output was lower (P = 0.014) in the supine group. Conclusions Maternal supine position during elective cesarean delivery with spinal anesthesia in healthy term women does not impair neonatal acid–base status compared to 15° left tilt, when maternal systolic blood pressure is maintained with a coload and phenylephrine infusion. These findings may not be generalized to emergency situations or nonreassuring fetal status.

Current recommendations for women undergoing cesarean delivery include 15° left tilt for uterine displacement to prevent aortocaval compression, although this degree of tilt is practically never achieved. We hypothesized that under contemporary clinical practice, including a crystalloid coload and phenylephrine infusion targeted at maintaining baseline systolic blood pressure, there would be no effect of maternal position on neonatal acid base status in women undergoing elective cesarean delivery with spinal anesthesia.Healthy women undergoing elective cesarean delivery were randomized (nonblinded) to supine horizontal (supine, n = 50) or 15° left tilt of the surgical table (tilt, n = 50) after spinal anesthesia (hyperbaric bupivacaine 12 mg, fentanyl 15 μg, preservative-free morphine 150 μg). Lactated Ringer's 10 ml/kg and a phenylephrine infusion titrated to 100% baseline systolic blood pressure were initiated with intrathecal injection. The primary outcome was umbilical artery base excess.There were no differences in umbilical artery base excess or pH between groups. The mean umbilical artery base excess (± SD) was -0.5 mM (± 1.6) in the supine group (n = 50) versus -0.6 mM (± 1.5) in the tilt group (n = 47) (P = 0.64). During 15 min after spinal anesthesia, mean phenylephrine requirement was greater (P = 0.002), and mean cardiac output was lower (P = 0.014) in the supine group.Maternal supine position during elective cesarean delivery with spinal anesthesia in healthy term women does not impair neonatal acid-base status compared to 15° left tilt, when maternal systolic blood pressure is maintained with a coload and phenylephrine infusion. These findings may not be generalized to emergency situations or nonreassuring fetal status.

Background: Because of the lack of large obstetric anesthesia databases, the incidences of serious complications related to obstetric anesthesia remain unknown. The Society for Obstetric Anesthesia and Perinatology developed the Serious Complication Repository Project to establish the incidence of serious complications related to obstetric anesthesia and to identify risk factors associated with each. Methods: Serious complications were defined by the Society for Obstetric Anesthesia and Perinatology Research Committee which also coordinated the study. Thirty institutions participated in the approximately 5-yr study period. Data were collected as part of institutional quality assurance and sent to the central project coordinator quarterly. Results: Data were captured on more than 257,000 anesthetics, including 5,000 general anesthetics for cesarean delivery. There were 157 total serious complications reported, 85 of which were anesthesia related. High neuraxial block, respiratory arrest in labor and delivery, and unrecognized spinal catheter were the most frequent complications encountered. A serious complication occurs in approximately 1:3,000 (1:2,443 to 1:3,782) obstetric anesthetics. Conclusions: The Serious Complication Repository Project establishes the incidence of serious complications in obstetric anesthesia. Because serious complications related to obstetric anesthesia are rare, there were too few complications in each category to identify risk factors associated with each. However, because many of these complications can lead to catastrophic outcomes, it is recommended that the anesthesia provider remains vigilant and be prepared to rapidly diagnose and treat any complication.

Background Morphine sulfate has long been used for analgesia, but clinical applications can be limited by side effects, tolerance, and potential for addiction at therapeutic doses. An agent that produces therapeutic analgesia when coadministered with low-dose morphine could have important clinical uses. The anticonvulsant agent gabapentin has been identified as having antihyperalgesic properties acting on the alpha2delta1 subunit of N-type voltage-activated calcium channels on dorsal root ganglia neurons. In this study, intrathecal gabapentin, which by itself is ineffective when administered spinally, was combined with low-dose morphine and tested in an acute bradykinin-induced pancreatitis model in rats. Methods An intrathecal catheter was surgically inserted into the subarachnoid space of male Sprague-Dawley rats. A laparotomy was performed for ligation and cannulation of the bile-pancreatic duct. Rats were pretreated intrathecally with artificial cerebrospinal fluid, gabapentin, morphine, or combined gabapentin and morphine 30 min before bradykinin injection into the bile-pancreatic duct. Spontaneous behavioral activity (cage crossing, rearing, and hind limb extension) was monitored before drug injection (baseline) and after bradykinin injection into the bile-pancreatic duct to assess visceral pain. Results Spinal pretreatment with up to 300 microg gabapentin alone was not effective in reducing hind limb extension in this model, but did restore some cage crossing and rearing behaviors. Spinal treatment with low-dose morphine reduced hind limb extension only. Spinal pretreatment with combined gabapentin and subtherapeutic doses of morphine sulfate resulted in restoration of all spontaneous behaviors to surgical baseline levels including elimination of hind limb extension. Conclusion Combined spinal administration of gabapentin and low doses of morphine significantly reduces pain-related behaviors in this acute rat pancreatitis model, whereas these agents were ineffective when used alone in this dose range. These data suggest that the alpha2delta1 subunit of the N-type voltage-activated Ca2+ channels is involved in transmission of this visceral pain, likely through effects on primary afferent endings in the spinal cord. Thus, gabapentin may be an effective adjuvant to initial low dose spinal opioid therapy for clinical management of visceral pain.

BACKGROUND: Chronic pain after surgery occurs in 10-40% of individuals, including 5-20% of women after cesarean delivery in previous reports. Pain and depression 2 months after childbirth are independently associated with more severe acute post-delivery pain. Here we examine other predictors of pain at 2 months and determine the incidence of pain at 6 and 12 months after childbirth. METHODS: Following Institutional Review Board approval, 1228 women were interviewed within 36 h of delivery. Of these, 937 (76%) were successfully contacted by telephone at 2 months, and, if they had pain, at 6 and 12 months after delivery. The primary outcome measure was presence of pain which began at the time of delivery. We also generated a model of severity of acute post-delivery pain and 2 month pain and depression. RESULTS: Pain which began at the time of delivery was remarkably rare 6 and 12 months later (1.8% and 0.3% [upper 95% confidence limit, 1.2%], respectively). Past history of pain and degree of tissue damage at delivery accounted for 7.0% and 16.7%, respectively, of one aspect in the variability in acute post-delivery pain. Neither of these factors was associated with incidence of pain 2 months later. CONCLUSIONS: Using a definition of new onset pain from delivery, we show a remarkably low incidence of pain 1 yr after childbirth, including those with surgical delivery. Additionally, degree of tissue trauma and history of chronic pain, risk factors for pain 2 months after other surgery, were unimportant to pain 2 months after cesarean or vaginal delivery.

Background β2-Adrenergic receptor (β2AR) activity influences labor. Its genotype affects the incidence of preterm delivery. We determined the effect of β2AR genotype on term labor progress and maternal pain. Methods We prospectively enrolled 150 nulliparous parturients in the third trimester and obtained sensory thresholds, demographic information, and DNA. Cervical dilation, pain scores, and labor management data were extracted with associated times. The association of genetic and demographic factors with labor was tested using mixed effects models. Results Parturients who express Gln at the 27 position of the β2AR had slower labor (P < 0.03). They progressed from 1-10 cm dilation in approximately 21 h compared with 14 h among other patients. Asian ethnicity, previously associated with slower labor, is highly associated with this polymorphism (P < 0.0001). Heavier and black patients had slower latent labor (P < 0.01, 0.01). Neuraxial analgesia was associated with slower labor progress (P < 0.0001). It could take up to 36 h for parturients who were black and/or more than median weight (165 lb) to transition from 1 cm cervical dilation to active labor. However, after this active phase began, labor rates among these patients were similar to that of other parturients. Conclusions We detected a strong association between β2AR genotype and slower labor. Asian ethnicity may be a proxy for β2AR genotype. Black women and those of higher than average weight have slower latent labor. These results confirm many of the associations found when this mathematical model was applied to a large retrospective cohort, further validating this approach to description and analysis of labor progress.

In order to examine the clinical potential of desflurane in humans, a randomized, controlled study was designed to compare emergence times in patients undergoing elective surgery with desflurane or isoflurane anesthesia

Background Maternal hypotension is common after spinal anesthesia for cesarean delivery. There is wide variability in the incidence and severity of hypotension and in the response to treatment. The beta2 adrenoceptor (beta2AR) possesses several polymorphic sites. Codons 16 (Arg16Gly) and 27 (Glu27Gln) have been shown to affect desensitization of the receptor. The goal of this study was to determine whether genetic variants of the beta2AR alter incidence of hypotension or the amount of vasopressor treatment required during spinal anesthesia for cesarean delivery. Methods One hundred seventy healthy women undergoing elective cesarean delivery were studied. Spinal anesthesia was performed with 12 mg hyperbaric bupivacaine, 25 microg fentanyl, and 200 microg morphine. Hypotension was treated with ephedrine and/or phenylephrine intravenously, and beta2AR genotype at codons 16 and 27 was determined. Analysis of variance was used to compare variables between genotypes, with data expressed as mean +/- SD. Results Ephedrine or phenylephrine was used in more than 90% of patients, with no difference in the incidence of hypotension between beta2AR genotypes. However, there was a significant effect of genotype on the amount of vasopressor required. Gly16 homozygotes received significantly less ephedrine (18 +/- 14 mg) than Arg16 homozygotes (28 +/- 13 mg) and Arg16Gly heterozygotes (30 +/- 20 mg; P = 0.0005). Glu27 homozygotes required significantly less ephedrine than Gln 27 homozygotes (14 +/- 13 vs. 30 +/- 19 mg; P = 0.002). Gln27Glu heterozygotes received less ephedrine than Gln27 homozygotes (23 +/- 16 vs. 30 +/- 19 mg; P = 0.03). Conclusions Glycine at position 16 and/or glutamate at position 27 of the beta2AR leads to lower vasopressor use for treatment of hypotension during spinal anesthesia.

Unlabelled BACKGROUND. Changes in the sympathetic nervous system may be a cause of postoperative cardiovascular complications. The authors hypothesized that changes in both beta-adrenergic receptor (betaAR) function (as assessed in lymphocytes) and in sympathetic activity (assessed by plasma catecholamines and by heart rate variability [HRV] measurements obtained from Holter recordings) occur after operation. Methods The HRV parameters were measured in 28 patients having thoracotomy (n = 14) or laparotomy (n = 14) before and for as long as 6 days after operation. Transthoracic echocardiography was performed before and on postoperative day 2. Lymphocytes were also isolated from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). They were used to examine betaAR number (Bmax) and cyclic adenosine monophosphate (cAMP) production after stimulation with isoproterenol and prostaglandin E1. In addition, plasma epinephrine, norepinephrine, and cortisol concentrations were determined at similar intervals. Results After abdominal and thoracic surgery, most time and all frequency indices of HRV decreased significantly, as did Bmax and basal and isoproterenol-stimulated cAMP production. The decrements in HRV correlated with those of Bmax and isoproterenol-stimulated cAMP throughout the first postoperative week and inversely correlated with the increase in heart rate. Plasma catecholamine concentrations did not change significantly from baseline values, but plasma cortisol levels did increase after operation in both groups. Left ventricular ejection fraction was normal in both groups and unaffected by surgery. Conclusions Persistent downregulation and desensitization of the lymphocyte betaAR/adenylyl cyclase system correlated with decrements in time and frequency domain indices of HRV throughout the first week after major abdominal or thoracic surgery. These physiologic alterations suggest the continued presence of adaptive autonomic regulatory mechanisms and may explain why the at-risk period after major surgery appears to be about 1 week or more.

In order to examine the clinical potential of desflurane (difluoromethyl-1-fluoro-2,2,2-trifluoroethyl ether) in humans, a randomized, controlled study was designed to compare time of emergence from anesthesia in patients undergoing elective surgery under desflurane anesthesia to that of patients under isoflurane anesthesia. Twenty-eight patients were randomly divided into four groups. Group 1 received isoflurane 0.65 MAC; group 2, desflurane 0.65 MAC; group 3, isoflurane 1.25 MAC; and group 4, desflurane 1.25 MAC. Anesthesia was induced with sodium thiopental, and N2O 60% was added to the volatile agent. Mean anesthetic exposure times (min [mean +/- SD]) were 108 +/- 49 in group 1, 132 +/- 46 in group 2, 147 +/- 74 in group 3, and 166 +/- 71 in group 4, with no significant differences between groups. The times from discontinuation of anesthetic gases until patients opened their eyes and squeezed the investigator's hand in response to a command were averaged and recorded as "emergence time." Emergence time was significantly less with desflurane than with isoflurane given at the same MAC. Patients receiving isoflurane 0.65 MAC responded to commands 15.6 +/- 4.3 min after discontinuation of the anesthetic; patients in the desflurane 0.65 MAC group responded in 8.8 +/- 2.7 min (P less than 0.01). Emergence time for isoflurane 1.25 MAC was 30.0 +/- 11.0 min; for desflurane 1.25 MAC it was 16.1 +/- 6.0 min (P less than 0.05). Our results confirm that emergence from desflurane anesthesia is more rapid than from isoflurane.