Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Epidural analgesia is often used for pain relief during labour and childbirth, and involves administration of local anaesthetics (LA) into the epidural space resulting in sensory blockade of the abdomen, pelvis, and perineum. Epidural opioids are often co-administered to improve analgesia. Administration of epidural medications can be accomplished by basal infusion (BI) or automated mandatory bolus (AMB). With BI, medications are administered continuously, while AMB involves injecting medications at set time intervals. Patient-controlled epidural analgesia (PCEA) on top of AMB or BI enables patients to initiate additional boluses of epidural medications.  The superior method of delivering epidural medications would result in lower incidence of pain requiring anaesthesiologist intervention (breakthrough pain). Also, it should be associated with lower incidence of epidural-related adverse effects including caesarean delivery, instrumental delivery (use of forceps or vacuum devices), prolonged duration of labour analgesia, and LA consumption. However, clear evidence of the superiority of one technique over the other is lacking. Also, differences in the initiation of epidural analgesia such as combined spinal-epidural (CSE) (medications given into the intrathecal space in addition to the epidural space) compared to epidural only, and medications used (types and doses of LA or opioids) may not have been accounted for in previous reviews.  Our prior systematic review suggested that AMB reduces the incidence of breakthrough pain compared to BI with no significant difference in the incidence of caesarean delivery or instrumental delivery, duration of labour analgesia, and LA consumption. However, several studies comparing AMB and BI have been performed since then, and inclusion of their data may improve the precision of our effect estimates. OBJECTIVES: To assess the benefits and harms of AMB versus BI for maintaining labour epidural analgesia in women at term. SEARCH METHODS: We searched CENTRAL, Wiley Cochrane Library), MEDLINE, (National Library of Medicine), Embase(Elseiver), Web of Science (Clarivate), the WHO-ICTRP (World Health Organization) and ClinicalTrials.gov (National Library of Medicine) on 31 December 2022. Additionally, we screened the reference lists of relevant trials and reviews for eligible citations, and we contacted authors of included studies to identify unpublished research and ongoing trials. SELECTION CRITERIA: We included all randomised controlled studies that compared bolus dosing AMB with continuous BI during epidural analgesia. We excluded studies of women in preterm labour, with multiple pregnancies, with fetal malposition, intrathecal catheters, those that did not use automated delivery of medications, and those where AMB and BI were combined. DATA COLLECTION AND ANALYSIS: We used standard methodology for systematic review and meta-analysis described by Cochrane. Primary outcomes included: incidence of breakthrough pain requiring anaesthesiologist intervention; incidence of caesarean delivery; and incidence of instrumental delivery. Secondly, we assessed the duration of labour; hourly LA consumption in bupivacaine equivalents, maternal satisfaction after fetal delivery, and neonatal Apgar scores.  The following subgroup analyses were chosen a priori: epidural alone versus CSE technique; regimens that used PCEA versus those that did not; and nulliparous versus combination of nulli- and multi-parous women. We used the GRADE system to assess the certainty of evidence associated with our outcome measures. MAIN RESULTS: We included 18 studies of 4590 women, of which 13 enrolled healthy nulliparous women and five included healthy nulli- and multiparous women. All studies excluded women with preterm or complicated pregnancies. Techniques used to initiate epidural analgesia differed between the studies: seven used combined spinal epidural, 10 used epidural, and one used dural puncture epidural (DPE). There was also variation in analgesics used. Eight studies utilised ropivacaine with fentanyl, three used ropivacaine with sufentanil, two utilised levobupivacaine with sufentanil, one used levobupivacaine with fentanyl, and four utilised bupivacaine with fentanyl. Most of the studies were assessed to have low risk of randomisation, blinding, attrition, and reporting biases, except for allocation concealment where eight studies were assessed to have uncertain risk and three with high risk. Our results showed that AMB was associated with lower incidence of breakthrough pain compared to BI (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.55 to 0.91; I2 = 57%) (16 studies, 1528 participants), and lower hourly LA consumption in bupivacaine equivalents (mean difference (MD) -0.84 mg/h; 95% CI -1.29 to -0.38, I2 = 87%) (16 studies, 1642 participants), both with moderate certainty. AMB was associated with an estimated reduction in breakthrough pain incidence of 29.1% (incidence 202 per 1000, 95% CI 157 to 259), and was therefore considered clinically significant. The incidence of caesarean delivery (RR 0.85; 95% CI 0.69 to 1.06; I2 = 0%) (16 studies, 1735 participants) and instrumental delivery (RR 0.85; 95% CI 0.71 to 1.01; I2 = 0%) (17 studies, 4550 participants) were not significantly, both with moderate certainty. There was no significant difference in duration of labour analgesia (MD -8.81 min; 95% CI -19.38 to 1.77; I2 = 50%) (17 studies, 4544 participants) with moderate certainty. Due to differences in the methods and timing of outcome measurements, we did not pool data for maternal satisfaction and Apgar scores. Results reported narratively suggest AMB may be associated with increased maternal satisfaction (eight studies reported increased satisfaction and six reported no difference), and all studies showed no difference in Apgar scores. WIth the exception of epidural alone versus CSE which found significant subgroup differences in LA consumption between AMB and BI, no significant differences were detected in the remaining subgroup analyses. AUTHORS' CONCLUSIONS: Overall, AMB is associated with lower incidence of breakthrough pain, reduced LA consumption, and may improve maternal satisfaction. There were no significant differences between AMB and BI in the incidence of caesarean delivery, instrumental delivery, duration of labour analgesia, and Apgar scores. Larger studies assessing the incidence of caesarean and instrumental delivery are required.

Innate Immune and Neuronal Genetic Markers Are Highly Predictive of Postoperative Pain and Morphine Patient-Controlled Analgesia Requirements in Indian but Not Chinese or Malay Hysterectomy Patients.

OBJECTIVE: Pain severity and opioid requirements in the postoperative period show substantial and clinically significant inter-patient variation due mainly to factors such as age, surgery type, and duration. Genetic factors have not been adequately assessed except for the neuronal OPRM1 rs1799971 and COMT rs4680, whereas the contribution of innate immune signaling pathway genetics has seldom been investigated. SETTING: Hospital surgical ward. SUBJECTS: Women (107 Indian, 184 Malay, and 750 Han Chinese) undergoing total hysterectomy surgery. METHODS: Morphine consumption, preoperative pain, and postoperative pain were evaluated in relation to genetic variability comprising 19 single-nucleotide polymorphisms (SNPs) in 14 genes involved in glial activation, inflammatory signaling, and neuronal regulation, plus OPRM1 (1 SNP) and COMT (3 SNPs). RESULTS: Pre- and postoperative pain and age were associated with increased and decreased morphine consumption, respectively. In Chinese patients, only 8% of the variability in consumption could be explained by these nongenetic and genetic (BDNF, IL1B, IL6R, CRP, OPRM1, COMT, MYD88) factors. However, in Indian patients, 41% of morphine consumption variability could be explained by age (explaining <3%) and variants in OPRM1 rs1799971, CRP rs2794521, TLR4 rs4986790, IL2 rs2069762, COMT rs4818, TGFB1 rs1800469, and IL6R rs8192284 without controlling for postoperative pain. CONCLUSIONS: This is the highest known value reported for genetic contributions (38%) to morphine use in the acute postoperative pain setting. Our findings highlight the need to incorporate both genetic and nongenetic factors and consider ethnicity-dependent and nonadditive genotypic models in the assessment of factors that contribute to variability in opioid use.

Analysis of SCN9A Gene Variants for Acute and Chronic Postoperative Pain and Morphine Consumption After Total Hysterectomy.

BACKGROUND: Single nucleotide polymorphisms (SNPs) of the voltage-gated sodium channel alpha subunit gene (SCN9A) have been associated with pain in various settings. The aim of this study was to investigate the association of the SNPs to evaluate the influence of common gene variants on chronic postoperative pain (CPSP) and other related pain variables in a cohort of patients who underwent a scheduled hysterectomy. METHODS: DNA samples from a cohort of 1,075 patients who underwent a scheduled total hysterectomy in our hospital were genotyped for three common SCN9A SNPs using TaqMan assays. Multivariate logistic regression models were used to quantify the association between independent covariates such as pain threshold, pain endurance, pain scores, morphine use, and the presence of chronic pain. RESULTS: Frequencies of the minor alleles were different between the different ethnic groups. There was a statistically significant association of rs16851799 with morphine consumption and self-reported postoperative pain for the 1,038 subjects genotyped, with the TT genotype reporting higher pain and using more morphine. For the subpopulation of 446 subjects with chronic pain data, there was a similar association with self-reported postoperative pain and tolerance of pressure pain. Univariate analysis also showed a statistically significant association of rs16851799 with CPSP, whereas multivariable analysis revealed a similar association of rs4387806 with this outcome. There were three haplotypes with different relative frequencies for the CPSP and non-CPSP groups. CONCLUSIONS: Our results showed that SCN9A polymorphisms could play a role in acute pain perception and the susceptibility to chronic pain.

Deep sequencing analysis to identify novel and rare variants in pain-related genes in patients with acute postoperative pain and high morphine use.

PURPOSE: Most of the genetic variants that are reported to be associated with common pain phenotypes and analgesic use are common polymorphisms. The objective of our study was to identify new variants and investigate less common genetic variants that are usually not included in either small single-gene studies or high-throughput genotyping arrays. PATIENTS AND METHODS: From a cohort of 1075 patients who underwent a scheduled total abdominal hysterectomy, 92 who had higher self-rated pain scores and used more morphine were selected for the re-sequencing of 105 genes. RESULTS: We identified over 2400 variants in 104 genes. Most were intronic with frequencies >5%. There were 181 novel variants, of which 30 were located in exons: 17 nonsynonymous, 10 synonymous, 2 non-coding RNA, and 1 stop-gain. For known variants that are rare (population frequency <1%), the frequencies of 54 exonic variants and eight intronic variants for the sequenced samples were higher than the weighted frequencies in the Genome Aggregation Database for East and South Asians (P-values ranging from 0.000 to 0.046). Overall, patients who had novel and/or rare variants used more morphine than those who only had common variants. CONCLUSION: Our study uncovered novel variants in patients who reported higher pain and used more morphine. Compared with the general population, rare variants were more common in this group.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Childbirth may cause the most severe pain some women experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour and is considered to be the reference standard. Traditionally epidural analgesia has been delivered as a continuous infusion via a catheter in the epidural space, with or without the ability for the patient to supplement the analgesia received by activating a programmable pump to deliver additional top-up doses, known as patient-controlled epidural analgesia (PCEA). There has been interest in delivering maintenance analgesic medication via bolus dosing (automated mandatory bolus - AMB) instead of the traditional continuous basal infusion (BI); recent randomized controlled trials (RCTs) have shown that the AMB technique leads to improved analgesia and maternal satisfaction. OBJECTIVES: To assess the effects of automated mandatory bolus versus basal infusion for maintaining epidural analgesia in labour. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the World Health Organization International Clinial Trials Registry Platform (WHO-ICTRP) and ClinicalTrials.gov on 16 January 2018. We screened the reference lists of all eligible trials and reviews. We also contacted authors of included studies in this field in order to identify unpublished research and trials still underway, and we screened the reference lists of the included articles for potentially relevant articles. SELECTION CRITERIA: We included all RCTs that compared the use of bolus dosing AMB with continuous BI for providing pain relief during epidural analgesia for labour in women. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: risk of breakthrough pain with the need for anaesthetic intervention; risk of caesarean delivery; risk of instrumental delivery. Secondary outcomes included: duration of labour; local anaesthetic consumption. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 12 studies with a total of 1121 women. Ten studies enrolled healthy nulliparous women only and two studies enrolled healthy parous women at term as well. All studies excluded women with complicated pregnancies. There were variations in the technique of initiation of epidural analgesia. Seven studies utilized the combined spinal epidural (CSE) technique, and the other five studies only placed an epidural catheter without any intrathecal injection. Seven studies utilized ropivacaine: six with fentanyl and one with sufentanil. Two studies used levobupivacaine: one with sufentanil and one with fentanyl. Three used bupivacaine with or without fentanyl. The overall risk of bias of the studies was low.AMB probably reduces the risk of breakthrough pain compared with BI for maintaining epidural analgesia for labour (from 33% to 20%; risk ratio (RR) 0.60; 95% confidence interval (CI) 0.39 to 0.92, 10 studies, 797 women, moderate-certainty evidence). AMB may make little or no difference to the risk of caesarean delivery compared to BI (15% and 16% respectively; RR 0.92; 95% CI 0.70 to 1.21, 11 studies, 1079 women, low-certainty evidence).AMB may make little or no difference in the risk of instrumental delivery compared to BI (12% and 9% respectively; RR 0.75; 95% CI 0.54 to 1.06, 11 studies, 1079 women, low-certainty evidence). There is probably little or no difference in the mean duration of labour with AMB compared to BI (mean difference (MD) -10.38 min; 95% CI -26.73 to 5.96, 11 studies, 1079 women, moderate-certainty evidence). There is probably a reduction in the hourly consumption of local anaesthetic with AMB compared to BI for maintaining epidural analgesia during labour (MD -1.08 mg/h; 95% CI -1.78 to -0.38, 12 studies, 1121 women, moderate-certainty evidence). Five out of seven studies reported an increase in maternal satisfaction with AMB compared to BI for maintaining epidural analgesia for labour; however, we did not pool these data due to their ordinal nature. Seven studies reported Apgar scores, though there was significant heterogeneity in reporting. None of the studies showed any significant difference between Apgar scores between groups. AUTHORS' CONCLUSIONS: There is predominantly moderate-certainty evidence that AMB is similar to BI for maintaining epidural analgesia for labour for all measured outcomes and may have the benefit of decreasing the risk of breakthrough pain and improving maternal satisfaction while decreasing the amount of local anaesthetic needed.

Hyperbaric versus isobaric bupivacaine for spinal anaesthesia for caesarean section.

BACKGROUND: Bupivacaine is an amide local anaesthetic used in hyperbaric and isobaric forms. These are administered intrathecally into the spine to provide regional anaesthesia for caesarean section. Several trials have compared hyperbaric and isobaric bupivacaine but none have conclusively shown the benefit of either. This review was first published in 2013 and updated in 2016. OBJECTIVES: Our objectives were to:1. Determine the effectiveness of hyperbaric bupivacaine compared to isobaric bupivacaine for spinal anaesthesia in women undergoing caesarean section;2. Determine the safety of hyperbaric bupivacaine compared to isobaric bupivacaine for spinal anaesthesia in women undergoing caesarean section. SEARCH METHODS: We originally searched the following databases to January 2011: CENTRAL, MEDLINE and Embase.For this update, we reran our search in the above databases from January 2011 to March 2016; two studies are awaiting a response from authors for assessment and will be dealt with when we next update the review.We imposed no language restriction. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) involving parturients undergoing spinal anaesthesia for elective caesarean section that compared the use of hyperbaric with isobaric bupivacaine. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. The data that were extracted included the number of events and the sample sizes in both the intervention and control groups. For continuous outcomes, we extracted mean and standard deviation.We reported odds ratios (ORs) and risk ratios (RRs) for binary outcomes, and mean differences (MDs) for continuous outcomes. MAIN RESULTS: We included three new RCTs in this update, which now comprises 10 studies with a total of 614 participants. We judged most trials as having uncertain risk of bias regarding randomization. Other than this, the overall risk of bias was low. Most included trials had small sample sizes. All of the trials assessed the primary outcome of conversion to general anaesthesia. Ten trials comparing anaesthesia performed with hyperbaric and isobaric bupivacaine failed to show any difference in need for conversion to general anaesthesia (RR 0.33, 95% CI 0.09 to 1.17, 614 participants, very low quality of evidence). Nine trials also failed to show a difference in the need for supplemental analgesics (RR 0.61, 95% CI 0.26 to 1.41, 554 participants, very low quality of evidence). Four trials comparing requirement for ephedrine did not show any difference (RR 0.89, 95% CI 0.57 to 1.38, 256 participants, very low quality of evidence). Seven trials did not provide convincing evidence of difference in nausea and vomiting (RR 0.99, 95% CI 0.57 to 1.72, 433 participants, low quality of evidence). Three trials failed to show a difference in headache (OR 1.82, 95% CI 0.47 to 6.99, 234 participants, low quality of evidence). Two trials showed that the time until sensory block to the thoracic 4th (T4) spinal level was shorter with hyperbaric bupivacaine (MD -1.06 minutes, 95% CI -1.80 to -0.31, 128 participants, moderate quality of evidence). Six trials showed no difference in the amount of ephedrine used (RR 0.23, 95% CI -1.65 to 2.12, 386 participants, moderate quality of evidence). Three trials failed to show any difference in high block (RR 0.88, 95% CI 0.16 to 4.90, 205 participants). AUTHORS' CONCLUSIONS: Data are limited for some of the outcomes. Reporting of the included trials is less than optimal. For these reasons the overall quality of evidence is low or very low for most of the outcomes, based on the GRADE method of assessment. This review found that intrathecal hyperbaric bupivacaine had a more rapid onset of sensory blockade at the 4th thoracic vertebra (T4) level than isobaric bupivacaine. Hower, despite incorporating more data in the analysis, we found little evidence that the need for conversion to general anaesthesia and supplemental analgesia differed between the hyperbaric or isobaric bupivacaine groups. This is mainly due to the rarity of these outcomes, variability in the dose, use of adjuvant drugs and differences in the technique used for regional anaesthesia. There were no differences in the adverse effects studied. Any possible advantage of hyperbaric bupivacaine needs to be confirmed in larger randomized trials. In future research, criteria for conversion to general anaesthesia need to be defined objectively and applied uniformly.

Ethnicity-dependent influence of innate immune genetic markers on morphine PCA requirements and adverse effects in postoperative pain.

Although several genetic factors have been associated with postsurgical morphine requirements, those involving the innate immune system and cytokines have not been well investigated. The aim of this study was to investigate the contribution of genetic variability in innate immune signalling pathways to variability in morphine dosage after elective caesarean section under spinal anaesthesia in 133 Indian, 230 Malay, and 598 Han Chinese women previously studied. Twenty single nucleotide polymorphisms in 14 genes involved in glial activation (TLR2, TLR4, MYD88, MD2), inflammatory signalling (IL2, IL6, IL10, IL1B, IL6R, TNFA, TGFB1, CRP, CASP1), and neuronal regulation (BDNF) were newly investigated, in addition to OPRM1, COMT, and ABCB1 genetic variability identified previously. Postsurgical patient-controlled analgesia morphine use (mg/24 hours) was binned into 6 normally distributed groups and scored 0 to 5 to facilitate step-down multiple linear regression analysis of genetic predictors, controlling for ethnicity and nongenetic variables. Ethnicity, OPRM1 rs1799971 (increased), TLR2 rs3804100 (decreased), and an interaction between ethnicity and IL1B rs1143634 (increased), predicted 9.8% of variability in morphine use scores in the entire cohort. In the Indian cohort, 14.5% of the variance in morphine use score was explained by IL1B rs1143634 (increased) and TGFB1 rs1800469 (decreased). In Chinese patients, the incidence of postsurgical pain was significantly higher in variant COMT rs4680 genotypes (P = 0.0007) but not in the Malay or Indian cohorts. Innate immune genetics may contribute to variability in postsurgical opioid requirements in an ethnicity-dependent manner.

Modern neuraxial labour analgesia.

PURPOSE OF REVIEW: Neuraxial analgesia is considered the gold standard of labour analgesia as it provides the most effective method of pain relief during childbirth. In this article, we explore the recent advances in the initiation and maintenance of epidural analgesia. RECENT FINDINGS: Patient-controlled epidural analgesia, computer-integrated patient-controlled epidural analgesia, intermittent epidural bolus (programmed intermittent bolus, automated mandatory bolus) and variable frequency automated mandatory bolus administration are techniques that allow the individualized titration and optimization of labour analgesia. The debate has moved on to finding the optimal settings for epidural bolus dosing, time intervals and frequency for epidural analgesia with the hope of improving safety and efficacy as well as patient satisfaction. SUMMARY: We examine these recent developments in pump technology and epidural delivery systems and evaluate how these have enhanced the mothers' birthing experiences.

Early versus late initiation of epidural analgesia for labour.

BACKGROUND: Pain during childbirth is arguably the most severe pain some women may experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour. Many women have concerns regarding its safety. Furthermore, epidural services and anaesthetic support may not be available consistently across all centres. Observational data suggest that early initiation of epidural may be associated with an increased risk of caesarean section, but the same findings were not seen in recent randomised controlled trials. More recent guidelines suggest that in the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labour. The choice of analgesic technique, agent, and dosage is based on many factors, including patient preference, medical status, and contraindications. There is no systematically reviewed evidence on the maternal and foetal outcomes and safety of this practice. OBJECTIVES: This systematic review aimed to summarise the effectiveness and safety of early initiation versus late initiation of epidural analgesia in women. We considered the obstetric and fetal outcomes relevant to women and side effects of the treatments, including risk of caesarean section, instrumental birth and time to birth. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 February 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (January 1966 to February 2014), Embase (January 1980 to February 2014) and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised controlled trials involving women undergoing epidural labour analgesia that compared early initiation versus late initiation of epidural labour analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted the data and assessed the trial quality. Data were checked for accuracy. MAIN RESULTS: We included nine studies with a total of 15,752 women.The overall risk of bias of the studies was low, with the exception of performance bias (blinding of participants and personnel).The nine studies showed no clinically meaningful difference in risk of caesarean section with early initiation versus late initiation of epidural analgesia for labour (risk ratio (RR) 1.02; 95% confidence interval (CI) 0.96 to 1.08, nine studies, 15,499 women, high quality evidence). There was no clinically meaningful difference in risk of instrumental birth with early initiation versus late initiation of epidural analgesia for labour (RR 0.93; 95% CI 0.86 to 1.01, eight studies, 15,379 women, high quality evidence). The duration of second stage of labour showed no clinically meaningful difference between early initiation and late initiation of epidural analgesia (mean difference (MD) -3.22 minutes; 95% CI -6.71 to 0.27, eight studies, 14,982 women, high quality evidence). There was significant heterogeneity in the duration of first stage of labour and the data were not pooled.There was no clinically meaningful difference in Apgar scores less than seven at one minute (RR 0.96; 95% CI 0.84 to 1.10, seven studies, 14,924 women, high quality evidence). There was no clinically meaningful difference in Apgar scores less than seven at five minutes (RR 0.96; 95% CI 0.69 to 1.33, seven studies, 14,924 women, high quality evidence). There was no clinically meaningful difference in umbilical arterial pH between early initiation and late initiation (MD 0.01; 95% CI -0.01 to 0.03, four studies, 14,004 women, high quality evidence). There was no clinically meaningful difference in umbilical venous pH favouring early initiation (MD 0.01; 95% CI -0.00 to 0.02, four studies, 14,004 women, moderate quality evidence). AUTHORS' CONCLUSIONS: There is predominantly high-quality evidence that early or late initiation of epidural analgesia for labour have similar effects on all measured outcomes. However, various forms of alternative pain relief were given to women who were allocated to delayed epidurals to cover that period of delay, so that is it hard to assess the outcomes clearly. We conclude that for first time mothers in labour who request epidurals for pain relief, it would appear that the time to initiate epidural analgesia is dependent upon women's requests.

Use of hyperbaric versus isobaric bupivacaine for spinal anaesthesia for caesarean section.

BACKGROUND: Bupivacaine is an amide local anaesthetic used in hyperbaric and isobaric forms. These are administered intrathecally into the spine to provide regional anaesthesia for caesarean section. Several trials have compared hyperbaric and isobaric bupivacaine but none have conclusively shown benefit of either. OBJECTIVES: This systematic review aimed to summarize the effectiveness and safety of hyperbaric versus isobaric bupivacaine in providing anaesthesia for caesarean section. We considered the adequacy of anaesthesia for completion of caesarean section and the need for interventions to treat complications. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), MEDLINE (January 1966 to May 2011) and EMBASE (January 1980 to May 2011). We handsearched journals. We imposed no language restriction. We reran our search in the above databases from January 2011 to January 2013; the studies are awaiting assessment and will be dealt with when we update the review. SELECTION CRITERIA: We included all randomized controlled trials involving parturients undergoing spinal anaesthesia for elective caesarean section that compared the use of hyperbaric with isobaric bupivacaine. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. The data that were extracted included the number of events and the sample sizes in both the intervention and control groups. For continuous outcomes, we extracted mean and standard deviation.We reported odds ratios and risk ratios (RR) for binary outcomes and mean differences (MD) for continuous outcomes. MAIN RESULTS: We included six studies with a total of 394 patients in this review. Anaesthesia performed with hyperbaric bupivacaine appeared to be less likely to need conversion to general anaesthesia (two studies, 158 patients included in meta-analysis; RR 0.17, 95% confidence interval (CI) 0.03 to 0.94). There was no difference in the need for supplemental analgesics. The time till sensory block to the T4 level was also shorter with hyperbaric bupivacaine (two studies, 126 patients; MD -1.06 minutes, 95% CI -1.80 to -0.31). There were no other significant differences between the two anaesthetics. AUTHORS' CONCLUSIONS: The criteria for conversion to general anaesthesia should be clearly defined in future research. This review found that intrathecal hyperbaric bupivacaine had a more rapid onset of sensory blockade at the T4 level than isobaric bupivacaine. It may also result in less need for conversion to general anaesthesia and supplemental analgesia. However, due to the rarity of this outcome, variability in the dose, use of adjuvant drugs and differences in the technique used for regional anaesthesia the evidence is weak. Any apparent advantage of hyperbaric bupivacaine needs to be confirmed in larger randomized trials. There were no differences in the adverse effects studied.

Influence of mu-opioid receptor variant on morphine use and self-rated pain following abdominal hysterectomy.

UNLABELLED: A common variant in the mu-opioid receptor gene (OPRM1) has been associated with response to opioid analgesia. Our previous data revealed significantly higher amounts of morphine self-administered by patients carrying the 118G allele compared to those with the 118A allele after elective cesarean section. In this study, the association of this genetic variation with pressure pain, postoperative pain scores, and amount of morphine used was investigated in 973 patients undergoing scheduled total hysterectomy under general anesthesia. Preoperative pressure pain threshold and tolerance were also measured for most patients. For pressure pain, OPRM1 genotype was not significantly associated with either pain threshold or pain tolerance. Statistically significant associations were found for postoperative pain and the total amount of morphine used, with the GG group reporting higher pain scores and using the most morphine. When analysis was stratified by ethnic group, differences in weight-adjusted morphine for the 3 genotypic groups were also significant for the Chinese and Asian Indians. These results extend our previous finding on the association of higher self-reported pain and morphine use for acute postoperative pain with OPRM1 118G to patients who had total hysterectomy under general anesthesia. PERSPECTIVE: In a large cohort of patients undergoing hysterectomy, we found large variability in the self-rated pain scores and the amount of morphine required for pain relief. Both are associated with OPRM1 genotypes and preoperative experimental pressure pain threshold. Experimental pressure pain tolerance is also associated with postoperative pain.

A randomised trial of the analgesic efficacy of ultrasound-guided transversus abdominis plane block after caesarean delivery under general anaesthesia.

CONTEXT: Previous studies examining the efficacy of transversus abdominis plane block after caesarean section have mostly been in parturients under spinal anaesthesia. OBJECTIVES: We postulated that the advantage of performing transversus abdominis plane block after caesarean section might be even more obvious after general anaesthesia, resulting in reduced 24-h consumption of morphine. DESIGN, SETTING, PATIENTS AND INTERVENTIONS: In this single centre, randomised double-blind controlled trial, 40 women who underwent caesarean delivery under general anaesthesia were allocated randomly to receive a transversus abdominis plane block or no block. In those who received the block, 20 ml of levobupivacaine 2.5 mg ml was deposited bilaterally into the transversus abdominis plane under ultrasound guidance using a Sonosite Titan (SonoSite, Bothell, Washington, USA) 7-13 MHz linear transducer at the end of surgery when the patient was still anaesthetised. MAIN OUTCOME MEASURES: We recorded patient-controlled intravenous morphine use for 24 h, pain scores at rest and activity, sedation, nausea and vomiting, use of antiemetic medication and overall maternal satisfaction. The primary outcome was 24-h morphine consumption. RESULTS: Patients who received the transversus abdominis plane block used significantly less morphine in 24 h than those in the control group [12.3 (2.6) vs. 31.4 mg (3.1), P<0.001) and had higher satisfaction scores [16 (80%) vs. 5 (25%), P = 0.012). There were no differences between groups in the visual analogue pain scores, sedation level, nausea and vomiting or the use of antiemetic medication. CONCLUSION: Ultrasound-guided transversus abdominis plane block reduced morphine consumption following caesarean section under general anaesthesia, with increased maternal satisfaction.

Anesthesia considerations in the obese gravida.

Obesity is associated with serious morbidity during pregnancy, and obese women also are at a high risk of developing complications during labor, leading to an increased risk for instrumental and Cesarean deliveries. The engagement of the obstetrical anesthetist in the management of this group of high-risk patients should be performed antenatally so that an appropriate management strategy can be planned in advance to prevent an adverse outcome. Good communication between all care providers is essential. The obese patient in labor should be encouraged to have a functioning epidural catheter placed early in labor. Apart from providing analgesia and alleviating physiological derangements during labor, the presence of a functioning epidural catheter can also be used to induce anesthesia quickly in the event of an emergency cesarean section, thus avoiding a general anesthesia, which has exceedingly high risks in the obese parturient. Successful management of the obese patient necessitates a comprehensive strategy that encompasses a multidisciplinary and holistic approach from all care-providers.

The ongoing challenges of regional and general anaesthesia in obstetrics.

The increasing trend of caesarean section in the setting of increasing maternal age, obesity and other concomitant diseases will continue to challenge the obstetric anaesthetist in his/her task of providing regional and general anaesthesia. The challenges of providing anaesthesia for an emergency caesarean section, particularly the risks of general anaesthesia, will be debated. The need for involvement of a multidisciplinary team, good communication and challenges surrounding the provision of anaesthesia to such patients are discussed.

A randomized comparison of low doses of hyperbaric bupivacaine in combined spinal-epidural anesthesia for cesarean delivery.

BACKGROUND: The aim of our study was to investigate the block characteristics of intrathecal hyperbaric bupivacaine 7, 8, or 9 mg administered during combined spinal-epidural anesthesia for cesarean delivery and to elucidate the dose that produces adequate sensory blockade for surgery while minimizing the incidence of hypotension, high neuroblockade, and the need for intraoperative epidural supplementation. METHODS: Sixty women presenting for elective cesarean delivery were randomly assigned to one of the 3 groups. Group 7 received intrathecal hyperbaric bupivacaine 7 mg, Group 8 received 8 mg, and Group 9 received 9 mg. Women in all 3 groups received intrathecal morphine 100 microg and IV hydroxyethyl starch 15 mL/kg at the time of initiation of combined spinal-epidural anesthesia. Surgery began when a sensory level of T4 was achieved. Patients were monitored for block characteristics and side effects by a blinded observer. Our primary outcome was the maximum cephalad sensory block height. RESULTS: There was a difference in the maximum extent of cephalad sensory block among groups (Group 7: median T2 [interquartile range T2-T3]; Group 8: median T2 [T1-T2]; Group 9: median T1 [C8-T2]; P = 0.02). However, the time taken to reach T4 was similar in all 3 groups. The incidence of hypotension requiring vasopressors was different among groups (30% in Group 7, 55% in Group 8, and 70% in Group 9; P = 0.04). No patient had inadequate anesthesia. Neonatal outcomes were similar in all 3 groups. CONCLUSION: The lowest dose of hyperbaric bupivacaine (7 mg) provided equally rapid onset and effective anesthesia for cesarean delivery while reducing the incidence of hypotension compared with 8 and 9 mg. However, because of its shorter duration of anesthesia, it may be feasible only when the block can be reinforced using a functional epidural catheter.

Ethnicity and OPRM variant independently predict pain perception and patient-controlled analgesia usage for post-operative pain.

BACKGROUND: Morphine consumption can vary widely between individuals even for identical surgical procedures. As mu-opioid receptor (OPRM1) is known to modulate pain perception and mediate the analgesic effects of opioid compounds in the central nervous system, we examined the influence of two OPRM polymorphisms on acute post-operative pain and morphine usage in women undergoing elective caesarean delivery. RESULTS: Data on self-reported pain scores and amount of total morphine use according to patient-controlled analgesia were collected from 994 women from the three main ethnic groups in Singapore. We found statistically significant association of the OPRM 118A>G with self-administered morphine during the first 24-hour postoperative period both in terms of total morphine (p = 1.7 x 10(-5)) and weight-adjusted morphine (p = 6.6 x 10(-5)). There was also significant association of this OPRM variant and time-averaged self-rated pain scores (p = 0.024). OPRM 118G homozygotes used more morphine and reported higher pain scores than 118A carriers. Other factors which influenced pain score and morphine usage include ethnicity, age and paying class. CONCLUSION: Our results suggest that ethnicity and OPRM 118A>G genotype are independent and significant contributors to variation in pain perception and postoperative morphine use in patients undergoing cesarean delivery.

Colloid preload versus coload for spinal anesthesia for cesarean delivery: the effects on maternal cardiac output.

BACKGROUND: Spinal anesthesia for cesarean delivery may cause severe maternal hypotension, and a decrease in cardiac output (CO) and blood flow to the placenta. Fluid preloading with crystalloid is ineffective due to rapid redistribution. A "coload" given at the time of cerebrospinal fluid identification may be more effective. Our null hypothesis was that there would be no difference between the effect of a colloid preload (15 mL/kg hydroxyethyl starch (HES) 130/0.4 [Voluven 6%]) and an identical coload on maternal CO and the incidence of hypotension after spinal anesthesia for cesarean delivery. Secondary outcomes studied were neonatal acid- base status and predelivery vasopressor requirements. METHODS: Forty ASA PS I and II women scheduled for elective cesarean delivery were recruited. Patients were randomized to Group P (preload of 15 mL/kg HES) or Group C (coload, given when cerebrospinal fluid identified). Heart rate, arterial blood pressure, stroke volume and CO measurements were recorded at baseline, every minute for 10 min, and every 2.5 min interval for 10 min with the USCOM ultrasonic CO monitor. Spinal anesthesia was performed at the L3/4 interspace in the right lateral position. Arterial blood pressure was maintained at 90%-100% of baseline values using IV phenylephrine boluses. RESULTS: Demographic, anesthetic, and surgical characteristics were similar. There were no between-group differences in baseline systolic blood pressure, heart rate, and colloid volume. CO and stroke volume were significantly increased in Group P (P = 0.01) in the 5 min after spinal anesthesia. This increase in CO was not sustained at 10 min. There were no significant between-group differences in the incidence of hypotension, absolute arterial blood pressure values (P = 0.73), predelivery median (range) phenylephrine requirements (300[0-1000] in Group P versus 150 [0-850]microg in Group C, P = 0.24), or neonatal outcome as measured by Apgar scores and umbilical arterial and venous blood gas values. CONCLUSION: Intravascular volume expansion with 15 mL/kg HES 130/0.4 given as a preload, but not coload, significantly increased maternal CO for the first 5 min after spinal anesthesia for cesarean delivery, however, maternal and neonatal outcomes were not different.

Failure of augmentation of labor epidural analgesia for intrapartum cesarean delivery: a retrospective review.

In this study, we aimed to identify the incidence and predictive factors associated with failed labor epidural augmentation for cesarean delivery. Data of parturients, who had received neuraxial labor analgesia and who subsequently required intrapartum cesarean delivery during an 18-mo period, were retrospectively studied. Predictors associated with failure of extension of epidural analgesia in the presence of adequate time for onset of epidural anesthesia were identified by univariate logistic regression. Of the 1025 parturients, 1.7% had failed epidural extension. Predictors of failed epidural anesthesia included initiation of labor analgesia with plain epidural technique (compared to combined spinal-epidural) (P = 0.001), >or=2 episodes of breakthrough pain during labor (P < 0.001) and prolonged duration of neuraxial labor analgesia (P = 0.02).

A randomized controlled trial of three patient-controlled epidural analgesia regimens for labor.

BACKGROUND: Patient-controlled epidural analgesia (PCEA) is a safe and effective mode of maintaining labor analgesia; however, the ideal PCEA regimen is controversial. METHODS: In this prospective, randomized, double-blind study, we examined the analgesic efficacy of demand-only PCEA and PCEA with background infusion. We recruited 300 nulliparous parturients. Analgesia was initiated with intrathecal ropivacaine 2 mg and fentanyl 15 microg and maintained with epidural ropivacaine 0.1% with fentanyl 2 microg/mL. Parturients were randomized to one of three groups. Group 0: demand-only PCEA, bolus of 5 mL, lockout interval of 15 min. Group 5: background infusion of 5 mL/h, bolus of 5 mL, lockout interval of 12 min. Group 10: background infusion of 10 mL/h, bolus of 5 mL, lockout interval of 10 min. The maximum dose of all groups was 20 mL/h. The primary outcome was incidence of breakthrough pain. Secondary outcomes included intrapartum pain scores, neuraxial blockade characteristics, side effects, the total and hourly volume of ropivacaine, neonatal outcomes, and obstetric outcomes. RESULTS: The incidence of breakthrough pain and the maximum visual analog scale (0-100 mm scale) pain scores were higher in Group 0 versus Groups 5 and 10 (43% vs 17% and 11%, P < 0.001 and 37 +/- 28 vs 22 +/- 26 and 16 +/- 25 [mean +/- SD], P < 0.001), respectively. Group 10 had a longer duration of effective analgesia compared with Group 0 (mean 895 min, 95% CI 823-966 vs 565 min, 95% CI 454-677, P < 0.001) and increased ropivacaine consumption, and was associated with a longer duration of the second stage of labor. CONCLUSION: Demand-only PCEA (5-mL bolus, 15-min lockout interval) resulted in less local anesthetic consumption but an increased incidence of breakthrough pain, higher pain scores, shorter duration of effective analgesia, and lower maternal satisfaction, when compared with PCEA with background infusion (5-mL bolus, 10-12-min lockout interval, and 5-10 mL/h infusion).