Is crystalloid co-loading necessary to prevent spinal hypotension during elective cesarean delivery? A randomized double-blind trial.

BACKGROUND: Hypotension is common during spinal anesthesia for cesarean delivery. Preventive strategies include fluid loading and phenylephrine. We hypothesized that if prophylactic phenylephrine infusion is used, omission of fluid loading would be non-inferior to fluid co-loading in maintaining cardiac output. We assumed that if there was a difference, the increase in cardiac output would be greater in the no-loading than in the co-loading group. METHODS: Term pregnant women scheduled for elective cesarean delivery were randomized to receive 1 L crystalloid co-loading or maintenance fluids only. Phenylephrine was titrated to maintain blood pressure. Changes in cardiac output following spinal anesthesia were the primary outcome. The study was powered as a non-inferiority trial, allowing the no-loading arm to have a 50% greater change in cardiac output. Heart rate, dose of phenylephrine, occurrence of nausea and vomiting, Apgar scores and neonatal acid base status were secondary outcomes. RESULTS: Data from 63 women were analyzed. In contrast to our hypothesis, there was 33% less increase in cardiac output with no loading (ratio 0.67, 95% CI 0.15 to 1.36), and 60% greater reduction of cardiac output with no loading (ratio 1.6, 95% CI 1.0 to 2.7). Total dose of phenylephrine was higher in the no-loading group. There may be a less favorable neonatal acid base status without volume loading. CONCLUSION: Omission of crystalloid co-loading leads to a decrease in cardiac output which has a potentially unfavorable impact on neonatal acid base status. We conclude that crystalloid co-loading may be useful in the presence of phenylephrine infusion.

Role of cosyntropin in the prevention of post-dural puncture headache: a propensity-matched retrospective analysis.

BACKGROUND: Post-dural puncture headache (PDPH) is a well-documented complication of accidental dural puncture in obstetric patients. Reports have shown successful treatment with adrenocorticotropic hormone (ACTH) but evidence remains low and limited. In this retrospective analysis, we assessed whether prophylactic administration of cosyntropin, a synthetic derivative of ACTH, reduced the incidence of PDPH after accidental dural puncture in parturients. METHOD: The study population included 132 women with an accidental dural puncture over a three-year period (June 1, 2018 to Oct 31, 2021) at a large tertiary-care center. Patient electronic medical records were reviewed for patient characteristics, prophylactic administration of cosyntropin, PDPH diagnosis, and need for epidural blood patch. Typically, 1 mg of cosyntropin was administered as an intravenous bolus or infusion post-delivery. The propensity score was calculated based on the following factors: age, body mass index, and placement of an intrathecal catheter. Patients were matched allowing 10% variation in scores to reduce potential treatment assignment bias. RESULTS: A total of 115 patients were included in the final analysis. Intravenous cosyntropin was administered to 65 patients (55.6%). Among those who received cosyntropin, 37 (56.9%) developed PDPH compared with 29 patients (58%) in the no-cosyntropin group (P = 0.08). Epidural blood patch was performed in 21 patients (56.8%) who received cosyntropin and 13 patients (61.7%) who did not (P = 0.70). CONCLUSION: Prophylactic administration of cosyntropin is not associated with a reduced incidence of PDPH.

A study of the pharmacokinetics and pharmacodynamics of oxytocin at elective caesarean delivery.

Oxytocin is widely used to prevent atonic postpartum haemorrhage after caesarean delivery. Initial treatment failure rates are high and inadequate dosing may contribute. Excessive doses, however, are associated with serious adverse effects. The pharmacokinetic data from this context are sparse and there is a lack of data in the immediate postpartum minutes after an initiating bolus. The pharmacodynamic data from this context are exclusively from dose-effect studies, with some suggesting that higher doses of oxytocin are required to provide adequate uterine tone in obese compared with non-obese women. We aimed to perform a pharmacokinetic and pharmacodynamic study that would facilitate more precise weight-based oxytocin dosing. We measured arterial oxytocin concentration, uterine tone and haemodynamic parameters in 25 women in the first 40 min after exogenous oxytocin administration at elective caesarean delivery. Serum oxytocin concentrations varied considerably between individuals. We constructed a one-compartment pharmacokinetic model of exogenous oxytocin deposition, after its administration with an initiating bolus and a maintenance infusion, at elective caesarean delivery. Body weight was evaluated as a potential covariate but was not included in the model due to lack of statistically significant reduction in the objective function. We calculated the volume of distribution and clearance (mean [coefficient of variation]) as 156.1 l [18%] and 83 ml.s-1 [32%] but found no within-individual correlation between serum oxytocin concentration and uterine tone or haemodynamic parameters. In conclusion, we observed a large variation in serum oxytocin concentrations between individuals receiving similar doses of oxytocin and were unable to establish weight-based dosing of exogenous oxytocin at caesarean delivery. Our findings suggest that future studies on oxytocin pharmacokinetics would need large sample sizes. In the absence of such data, oxytocin dosing should continue to be guided by uterine tone assessments and adjusted according to a strategy based on the best evidence from dose-effect studies.

Efficacy of regional blocks or local anaesthetic infiltration for analgesia after caesarean delivery: a network meta-analysis of randomised controlled trials.

Caesarean delivery is common and can cause severe postoperative pain but injection of local anaesthetic at various sites for regional blocks or local anaesthetic infiltration may reduce this. We aimed to compare and rank these sites. We searched PubMed, Google Scholar, EMBASE and CENTRAL to June 2021 for randomised controlled trials and performed a random-effects Bayesian model network meta-analysis. The primary outcome was dose of parenteral morphine equivalents in the first 24 postoperative hours. We used surface under cumulative ranking probabilities to order techniques. We analysed 114 trials (8730 participants). The ordered mean (95% credible interval) reduction in morphine equivalents, from 34 mg with placebo, were as follows: ilio-inguinal 15 (1-32) mg; ilio-inguinal-iliohypogastric 13 (6-19) mg; transversalis fascia 11 (4-26) mg; erector spinae 11 (10-32); transverse abdominis 9 (4-13) mg; wound catheter infusion 8 (2-15) mg; quadratus lumborum 8 (1-15) mg; wound infiltration 8 (2-13) mg; and no intervention -4 (-10 to 2) mg. Ordered efficacies for injection sites were different for other relevant outcomes, including pain (to 4-6 h and to 24 h) and time to rescue analgesia: there was no single preferred route of injection. The ordered mean (95% credible interval) reduction in dynamic pain scores (0-10 scale) at 24 h compared with placebo were as follows: wound infusion 1.2 (0.2-2.1); erector spinae 1.3 (-0.5 to 3.1); quadratus lumborum 1.0 (0.1-1.8); ilio-inguinal-iliohypogastric 0.6 (-0.5 to 1.8); transverse abdominis 0.6 (-0.1 to 1.2); wound infiltration 0.5 (-0.3 to 1.3); transversalis fascia -0.8 (-3.4 to 1.9); ilio-inguinal -0.9 (-3.6 to 1.7); and no intervention -0.8 (-1.8 to 0.2). We categorised our confidence in effect sizes as low or very low.

Oxytocin: at birth and beyond. A systematic review of the long-term effects of peripartum oxytocin.

Oxytocin is one of the most commonly used medications during labour and delivery. Recent insights from basic neuroscience research suggest that the uterotonic effects of oxytocin may arguably be trivial when compared with its profound effects on higher-order human behaviour. The purpose of this review is to highlight the potential consequences of manipulating oxytocinergic signalling during the peripartum period and its long-term impact on the maternal-infant dyad. We identified four domains where modulation of oxytocinergic signalling might be consequential: postpartum depression; breastfeeding; neurodevelopment; and chronic pain, and performed a literature search to address the impact of peripartum oxytocin administration. We have shown modest, but inconsistent, evidence linking peripartum oxytocin administration with postpartum depression. Breastfeeding success appeared to be negatively correlated with peripartum oxytocin exposure, perhaps secondary to impaired primitive neonatal reflexes and maternal-infant bonding. The association between perinatal oxytocin exposure and subsequent development of neurodevelopmental disorders such as autism in the offspring was weak, but these studies were limited by the lack of information on the cumulative dose. Finally, we identified substantial evidence for analgesic and anti-hypersensitivity effects of oxytocin which might partly explain the low incidence of chronic pain after caesarean birth. Although most data presented here are observational, our review points to a compelling need for robust clinical studies to better dissect the impact of peripartum oxytocin administration, and as stewards of its use, increase the precision with which we administer oxytocin to prevent overuse of the drug.