Prediction of breakthrough pain during labour neuraxial analgesia: comparison of machine learning and multivariable regression approaches.

INTRODUCTION: Risk-prediction models for breakthrough pain facilitate interventions to forestall inadequate labour analgesia, but limited work has used machine learning to identify predictive factors. We compared the performance of machine learning and regression techniques in identifying parturients at increased risk of breakthrough pain during labour epidural analgesia. METHODS: A single-centre retrospective study involved parturients receiving patient-controlled epidural analgesia. The primary outcome was breakthrough pain. We randomly selected 80% of the cohort (training cohort) to develop three prediction models using random forest, XGBoost, and logistic regression, followed by validation against the remaining 20% of the cohort (validation cohort). Area-under-the-receiver operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were used to assess model performance. RESULTS: Data from 20 716 parturients were analysed. The incidence of breakthrough pain was 14.2%. Of 31 candidate variables, random forest, XGBoost and logistic regression models included 30, 23, and 15 variables, respectively. Unintended venous puncture, post-neuraxial analgesia highest pain score, number of dinoprostone suppositories, neuraxial technique, number of neuraxial attempts, depth to epidural space, body mass index, pre-neuraxial analgesia oxytocin infusion rate, maternal age, pre-neuraxial analgesia cervical dilation, anaesthesiologist rank, and multiparity, were identified in all three models. All three models performed similarly, with AUC 0.763-0.772, sensitivity 67.0-69.4%, specificity 70.9-76.2%, PPV 28.3-31.8%, and NPV 93.3-93.5%. CONCLUSIONS: Machine learning did not improve the prediction of breakthrough pain compared with multivariable regression. Larger population-wide studies are needed to improve predictive ability.

Association of renin-angiotensin-aldosterone system genetic polymorphisms with maternal hypotension during spinal anaesthesia for caesarean delivery: a retrospective cohort study.

BACKGROUND: Unless prevented, hypotension occurs in up to 80% of normotensive women undergoing spinal anaesthesia for caesarean delivery. Renin-angiotensin-aldosterone system genetic polymorphisms have been associated with hypertensive disease, but few studies investigated effects on blood pressure regulation under spinal anaesthesia. We postulated that these polymorphisms increased vasodilation and maternal hypotension during spinal anaesthesia. METHODS: A retrospective secondary analysis of data from four prospective trials with similar inclusion/exclusion criteria evaluating phenylephrine/ephedrine delivery systems during spinal anaesthesia for elective caesarean delivery. Angiotensin type-1 receptor (AT1R) (A1166C), angiotensin-converting enzyme (ACE) (I/D), and aldosterone synthase CYP11B2 (C344T) polymorphisms were identified from stored specimens. The associations between the polymorphisms and hypotension (systolic blood pressure <80% of baseline), and vasopressor use, were determined by univariable and multivariable regression. RESULTS: Of 556 patients, 378 (68.0%) had hypotension. The AC/CC genotypes of AT1R (A1166C) were associated with hypotension by univariable analysis (OR 2.70, 95% CI 1.38 to 5.28, P=0.004]) and multivariable analysis (OR 3.65, [95% CI 1.68 to 7.94, P=0.004]) after adjustment for age, race, intravenous fluid volume, and block height. No difference in vasopressor use or adverse maternal or fetal outcomes were noted. Baseline characteristics were similar, with the exception of higher baseline blood pressure, block height, and intravenous fluid volume in the hypotensive group. There was no significant association between ACE and CYP11B2 polymorphisms and hypotension. CONCLUSION: AC/CC genotypes of AT1R (A1166C) polymorphism were associated with maternal hypotension under spinal anaesthesia for caesarean delivery. An association with cardiovascular indices and high-risk parturients should be examined.

Incidence and risk factors for epidural re-siting in parturients with breakthrough pain during labour epidural analgesia: a cohort study.

INTRODUCTION: Epidural re-siting is one of the significant events during labour epidural analgesia that may result in decreased patient satisfaction. The aim of our study was to investigate the incidence of and factors associated with epidural re-siting in parturients using epidural analgesia, with an emphasis on those with breakthrough pain. METHODS: A retrospective cohort study of 10170 parturients who received labour epidural analgesia. The primary outcome was the incidence of epidural re-siting (binary data). Univariate and multivariate logistic regression analysis were performed to find associated risk factors for re-siting. RESULTS: Less than 1% (0.85%, 86/10170) of the women in the study had their epidural re-sited. Amongst the subset of women with breakthrough pain, the incidence of epidural re-siting was higher (4.7%, 68/1454). Most of the women who had their epidural re-sited had experienced breakthrough pain (79%, 68/86). Amongst all parturients, the presence of breakthrough pain (OR=21.31), hypotension (OR=4.18) and venous puncture (OR=2.74) were significantly associated with re-siting. Amongst the parturients with breakthrough pain who required epidural re-siting, lower cervical dilatation (OR=0.81), higher number of episodes of breakthrough pain (OR=1.83) and patchy block (OR=4.37) were significantly associated with re-siting. The areas-under-curves of two multivariate models were 0.894 and 0.806 respectively. CONCLUSION: In our institution, the incidence of epidural catheter re-siting was low in all patients. However, the majority of patients whose catheters were re-sited had exhibited breakthrough pain. The risk factors associated with the need for re-siting of catheters in all patients differed from those who had breakthrough pain.

Hyperbaric vs. isobaric bupivacaine for spinal anaesthesia for elective caesarean section: a Cochrane systematic review.

Both isobaric and hyperbaric bupivacaine have been used for spinal anaesthesia for elective caesarean section, but it is not clear if one is better than the other. The primary objective of this systematic review was to determine the effectiveness and safety of hyperbaric bupivacaine compared with isobaric bupivacaine administered during spinal anaesthesia for elective caesarean section. We included 10 studies with 614 subjects in the analysis. There was no evidence of differences either in the risk of conversion to general anaesthesia, with a relative risk (95%CI) of 0.33 (0.09-1.17) (very low quality of evidence), or in the need for supplemental analgesia, the relative risk (95%CI) being 0.61 (0.26-1.41) (very low quality of evidence). There was also no evidence of a difference in the use of ephedrine, the amount of ephedrine used, nausea and vomiting, or headache. Hyperbaric bupivacaine took less time to reach a sensory block height of T4, with a mean difference (95%CI) of -1.06 min (-1.80 to -0.31). Due to the rarity of some outcomes, dose variability, use of adjuvant drugs and spinal technique used, future clinical trials should look into using adequate sample size to investigate the primary outcome of the need for supplemental analgesia.

A case series of vital signs-controlled, patient-assisted intravenous analgesia (VPIA) using remifentanil for labour and delivery.

Intravenous remifentanil patient-controlled analgesia can be used during labour as an alternative to epidural analgesia. Adverse effects of opioids, including hypoxia and bradycardia, may lead to maternal morbidity and mortality. We devised an interactive feedback system based on a clinical proportional algorithm, to continuously monitor for adverse effects to enhance safety and better titrate analgesia. This vital signs-controlled, patient-assisted intravenous analgesia with remifentanil used a prototype delivery system linked to a pulse oximeter that evaluated maternal oxygen saturation and heart rate continuously. With this system, we detected oxygen saturation < 95% for more than 60 s in 15 of 29 subjects (52%); and heart rate < 60 min-1 for more than 60 s in 7 of 29 subjects (24%) during use. The system automatically responded appropriately by reducing the dosages and temporarily halting remifentanil administration, thus averting further hypoxia and bradycardia.