Flouroscopic versus conventional epidural blood patch in obstetrics: A retrospective cohort study.

BACKGROUND: Epidural blood patch is a common effective treatment for postdural puncture headache after accidental dural puncture during labor and may be done in conventional or fluoroscopy-guided methods. The aim of this study was to compare intensity of headache at the time of discharge from the hospital and to compare blood volumes injected in conventional epidural blood patches versus fluoroscopic-guided blood patches and evaluate the side effects of both method of treatment. METHODS: Between the years 2010 and 2020, 84 patients who were diagnosed with postdural puncture headache received either a conventional epidural blood patch or a fluoroscopic-guided blood patch. Blood volumes were compared and evaluation of side effects was made based on data collected during and after the procedure. RESULTS: Eighty-four patients were included in this study. Fifty-two women in the conventional epidural blood patch group and 32 in the fluoroscopic-guided blood patch group. Women in the conventional epidural blood patch group received statistically significantly higher doses of blood than women in the fluoroscopic-guided blood patch group: conventional method 29 ml IQR [23-36] versus fluoroscopic method 16 ml, IQR [12-18], p < .001 with no difference in headache pain intensity at hospital release. There was no difference between groups in hospital length of stay, or persistent PDPH. There was also no difference chronic headache or backache between the two groups. CONCLUSIONS: Women who received fluoroscopic epidural blood patch required a much lower volume of blood injected while there was no difference between groups in headache pain intensity at discharge.

Renal ischemic adverse drug events related to tranexamic acid in women of child-bearing age: an analysis of pharmacovigilance data.

PURPOSE: In response to a large trial, the World Health Organization broadened their recommendation on tranexamic acid to be used for post-partum hemorrhage. A 2013 French periodic safety update report warned of an abnormally high rate of renal cortical necrosis associated with tranexamic acid and other drugs for severe post-partum hemorrhage. We aimed to identify the reporting incidence of adverse thrombo-embolic events among women in child-bearing age who received tranexamic acid, with a focus on renal vascular and ischemic conditions. METHODS: We analyzed individual case safety reports (ICSRs) on renal vascular and ischemic conditions, pulmonary thrombotic and embolic conditions, and peripheral embolism and thrombosis from the database of the World Health Organization - Uppsala Monitoring Centre (WHO-UMC). ICSRs were restricted to reports including tranexamic acid as a suspected drug, sex reported as female, and reported age between 18 and 44 years. Reporting odds ratios (RORs) and 95% confidence intervals (95% CIs) were calculated by comparing ICSRs on tranexamic acid to all other drugs in VigiBase. RESULTS: Within 2245 included ICSRs on tranexamic acid, we identified 29 reports of adverse renal vascular and ischemic conditions, 42 reports of pulmonary thrombotic and embolic conditions, and 41 reports of peripheral embolism and thrombosis. RORs were statistically significant by 32.6-fold (32.62, 95% CI: 22.50-47.29), 2.5-fold (2.52, 95% CI: 1.85-3.42), and 2.7-fold (2.67, 95% CI: 1.96-3.64), respectively, when compared to any other drug within VigiBase. CONCLUSION: Tranexamic acid might bear an increased risk for renal ischemic adverse drug events in women of child-bearing age.

Association Between Hyperbaric Bupivacaine Dose and Maternal Hypotension: Retrospective Database Study of 8226 Women Undergoing Cesarean Delivery Under Spinal Anesthesia.

BACKGROUND: Low-dose (≤8 mg) hyperbaric bupivacaine for spinal anesthesia during cesarean delivery results in reduced efficacy, yet as a secondary outcome was associated with reduced frequency of spinal-induced hypotension. Our primary aim was to investigate the relationship between hyperbaric bupivacaine dose and the occurrence of spinal-induced hypotension for cesarean delivery. METHODS: Retrospective study of cesarean delivery under spinal or combined spinal anesthesia with hyperbaric bupivacaine in 1 academic institution (2 centers-tertiary and district) from 2012 to 2018. Data were retrieved from the anesthesia information management systems (Metavision, iMDsoft, Tel Aviv, Israel) and the hospital information system, including potential confounding factors, maternal age and weight, hypertensive disease of pregnancy, single/multiple gestation, gestational age, vasopressor administration, planned/urgent surgery, position during anesthesia placement (sitting/lateral), and anesthesiologist seniority. Spinal-induced hypotension was defined as systolic blood pressure that either dropped >20% from baseline or <100 mm Hg. The primary outcome of interest was the incidence of spinal-induced hypotension according to hyperbaric bupivacaine dose. Logistic regression was used to characterize the association between the dose of hyberbaric bupivacaine and spinal-induced hypotension after adjusting for confounding factors. RESULTS: A total of 8226 women were identified. The hyperbaric bupivacaine dose administered was <9 mg for 2395 (29.1%), 9-9.5 mg for 1031 (12.5%), 10 mg for 4155 (50.5%), and >10 mg for 645 (7.8%). We used a cutoff (<10 vs ≥10 mg) to assess for the primary outcome, using multivariable logistic regression. The incidence of at least 1 spinal-induced hypotension episode was higher in patients who received ≥10 mg hyperbaric bupivacaine, 75.8% vs 62.9% for doses below 10 mg, P < .0001; however, even women with lower doses had hypotension. Hyperbaric bupivacaine dose <10 mg was associated with a lower incidence of spinal hypotension, adjusted odds ratio (OR) of 0.774, 95% confidence interval (CI), 0.669-0.897, and P = .0006, adjusted for confounding factors.Umbilical cord pH was available for 2684 (32.6%) cases. There were significantly more neonates with pH < 7.2, among women who received hyperbaric bupivacaine ≥10 mg (10.1%) versus women who received <10 mg (6.8%), P = .0032; however, in the adjusted model, hyperbaric bupivacaine dose ≥10 mg was not associated with pH < 7.2 and an OR of 0.955 (95% CI, 0.631-1.446, P = .829). CONCLUSIONS: Our major finding was that hypotension occurred at all doses of hyperbaric bupivacaine, yet occurrence of spinal hypotension was significantly associated with doses ≥10 mg after adjustment for potential confounders.

The relationship between resited epidural catheters after secondary epidural catheter failure and vaginal delivery: A retrospective case-control study.

BACKGROUND: There are cases where epidural analgesia is initially effective but subsequently fails and needs to be resited. We evaluated the rate of normal vaginal delivery and operative delivery among parturients who had resited epidurals compared to parturients with epidurals that were not resited. METHODS: A retrospective electronic medical review of parturients with a singleton gestation attempting normal vaginal delivery under epidural analgesia between the years 2012-2016 was conducted. Resited epidurals were defined as epidurals that were considered effective but subsequently removed and reinserted. For each resited epidural, two previous and two consecutive deliveries of parturients with normally functioning epidural catheter inserted by the same anesthesiologist were matched controls (non-resited epidurals). RESULTS: There were 35,984 attempted vaginal deliveries with 118 resited epidurals and 472 non-resited epidurals. When adjusted for nulliparity, oxytocin administration, sex and weight of the baby, and maternal BMI, labor epidural catheter replacement was not associated with need for instrumental or caesarean delivery, (OR 1.5, 95% CI 0.91-2.49, P = .11). CONCLUSIONS: Need for labor epidural catheter replacement does not appear to be associated with need for operative delivery based on this single-centre cohort analysis.

Intrathecal hydrophilic opioids for abdominal surgery: a meta-analysis, meta-regression, and trial sequential analysis.

BACKGROUND: Intrathecal hydrophilic opioids decrease systemic opioid consumption after abdominal surgery and potentially facilitate enhanced recovery. A meta-analysis is needed to quantify associated risks and benefits. METHODS: A systematic search was performed to find RCTs investigating intrathecal hydrophilic opioids in abdominal surgery. Caesarean section and continuous regional or neuraxial techniques were excluded. Several subgroup analyses were prespecified. A conventional meta-analysis, meta-regression, trial sequential analysis, and provision of GRADE scores were planned. RESULTS: The search yielded 40 trials consisting of 2500 patients. A difference was detected in 'i.v. morphine consumption' at Day 1 {mean difference [MD] -18.4 mg, (95% confidence interval [CI]: -22.3 to -14.4)} and Day 2 (MD -25.5 mg [95% CI: -30.2 to -20.8]), pain scores at Day 1 in rest (MD -0.9 [95% CI: -1.1 to -0.7]) and during movement (MD -1.2 [95% CI: -1.6 to -0.8]), length of stay (MD -0.2 days [95% CI: -0.4 to -0.1]) and pruritus (relative risk 4.3 [95% CI: 2.5-7.5]) but not in nausea or sedation. A difference was detected for respiratory depression (odds ratio 5.5 [95% CI: 2.1-14.2]) but not when two small outlying studies were excluded (odds ratio 1.4 [95% CI: 0.4-5.2]). The level of evidence was graded as high for morphine consumption, in part because the required information size was reached. CONCLUSIONS: This study showed important opioid-sparing effects of intrathecal hydrophilic opioids. Our data suggest a dose-dependent relationship between the risk of respiratory depression and the dose of intrathecal opioids. Excluding two high-dose studies, intrathecal opioids have a comparable incidence of respiratory depression as the control group. CLINICAL TRIAL REGISTRATION: PROSPERO-registry: CRD42018090682.

Fluid loading therapy to prevent spinal hypotension in women undergoing elective caesarean section: Network meta-analysis, trial sequential analysis and meta-regression.

BACKGROUND: Fluid loading is one of the recognised measures to prevent hypotension due to spinal anaesthesia in women scheduled for a caesarean section. OBJECTIVE: We aimed to evaluate the current evidence on fluid loading in the prevention of spinal anaesthesia-induced hypotension. DESIGN: Systematic review and network meta-analysis with trial sequential analysis and meta-regression. DATA SOURCES: Medline, Epub, Embase.com (Embase and Medline), Cochrane Central, Web of Science and Google Scholar were used. ELIGIBILITY CRITERIA: Only randomised controlled trials were used. Patients included women undergoing elective caesarean section who received either crystalloid or colloid fluid therapy as a preload or coload. The comparator was a combination of either a different fluid or time of infusion. RESULTS: A total of 49 studies (4317 patients) were included. Network meta-analysis concluded that colloid coload and preload offered the highest chance of success (97 and 67%, respectively). Conventional meta-analysis showed that crystalloid preload is associated with a significantly higher incidence of maternal hypotension than colloid preload: risk ratio 1.48 (95% CI 1.29 to 1.69, P < 0.0001, I = 60%). However, this result was not supported by Trial Sequential Analysis. There was a significant dose-response effect for crystalloid volume preload (regression coefficient = -0.073), which was not present in the analysis of only double-blind studies. There was no dose-response effect for the other fluid regimes. CONCLUSION: Unlike previous meta-analysies, we found a lack of data obviating an evidence-based recommendation. In most studies, vasopressors were not given prophylactically as is recommended. Studies on the best fluid regimen in combination with prophylactic vasopressors are needed. Due to official european usage restrictions on the most studied colloid (HES), we recommend crystalloid coload as the most appropriate fluid regimen. TRIAL REGISTRATION: CRD42018099347.

Perioperative intravenous ketamine for acute postoperative pain in adults.

BACKGROUND: Inadequate pain management after surgery increases the risk of postoperative complications and may predispose for chronic postsurgical pain. Perioperative ketamine may enhance conventional analgesics in the acute postoperative setting. OBJECTIVES: To evaluate the efficacy and safety of perioperative intravenous ketamine in adult patients when used for the treatment or prevention of acute pain following general anaesthesia. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to July 2018 and three trials registers (metaRegister of controlled trials, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)) together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: We sought randomised, double-blind, controlled trials of adults undergoing surgery under general anaesthesia and being treated with perioperative intravenous ketamine. Studies compared ketamine with placebo, or compared ketamine plus a basic analgesic, such as morphine or non-steroidal anti-inflammatory drug (NSAID), with a basic analgesic alone. DATA COLLECTION AND ANALYSIS: Two review authors searched for studies, extracted efficacy and adverse event data, examined issues of study quality and potential bias, and performed analyses. Primary outcomes were opioid consumption and pain intensity at rest and during movement at 24 and 48 hours postoperatively. Secondary outcomes were time to first analgesic request, assessment of postoperative hyperalgesia, central nervous system (CNS) adverse effects, and postoperative nausea and vomiting. We assessed the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included 130 studies with 8341 participants. Ketamine was given to 4588 participants and 3753 participants served as controls. Types of surgery included ear, nose or throat surgery, wisdom tooth extraction, thoracotomy, lumbar fusion surgery, microdiscectomy, hip joint replacement surgery, knee joint replacement surgery, anterior cruciate ligament repair, knee arthroscopy, mastectomy, haemorrhoidectomy, abdominal surgery, radical prostatectomy, thyroid surgery, elective caesarean section, and laparoscopic surgery. Racemic ketamine bolus doses were predominantly 0.25 mg to 1 mg, and infusions 2 to 5 µg/kg/minute; 10 studies used only S-ketamine and one only R-ketamine. Risk of bias was generally low or uncertain, except for study size; most had fewer than 50 participants per treatment arm, resulting in high heterogeneity, as expected, for most analyses. We did not stratify the main analysis by type of surgery or any other factor, such as dose or timing of ketamine administration, and used a non-stratified analysis.Perioperative intravenous ketamine reduced postoperative opioid consumption over 24 hours by 8 mg morphine equivalents (95% CI 6 to 9; 19% from 42 mg consumed by participants given placebo, moderate-quality evidence; 65 studies, 4004 participants). Over 48 hours, opioid consumption was 13 mg lower (95% CI 10 to 15; 19% from 67 mg with placebo, moderate-quality evidence; 37 studies, 2449 participants).Perioperative intravenous ketamine reduced pain at rest at 24 hours by 5/100 mm on a visual analogue scale (95% CI 4 to 7; 19% lower from 26/100 mm with placebo, high-quality evidence; 82 studies, 5004 participants), and at 48 hours by 5/100 mm (95% CI 3 to 7; 22% lower from 23/100 mm, high-quality evidence; 49 studies, 2962 participants). Pain during movement was reduced at 24 hours (6/100 mm, 14% lower from 42/100 mm, moderate-quality evidence; 29 studies, 1806 participants), and 48 hours (6/100 mm, 16% lower from 37 mm, low-quality evidence; 23 studies, 1353 participants).Results for primary outcomes were consistent when analysed by pain at rest or on movement, operation type, and timing of administration, or sensitivity to study size and pain intensity. No analysis by dose was possible. There was no difference when nitrous oxide was used. We downgraded the quality of the evidence once if numbers of participants were large but small-study effects were present, or twice if numbers were small and small-study effects likely but testing not possible.Ketamine increased the time for the first postoperative analgesic request by 54 minutes (95% CI 37 to 71 minutes), from a mean of 39 minutes with placebo (moderate-quality evidence; 31 studies, 1678 participants). Ketamine reduced the area of postoperative hyperalgesia by 7 cm² (95% CI -11.9 to -2.2), compared with placebo (very low-quality evidence; 7 studies 333 participants). We downgraded the quality of evidence because of small-study effects or because the number of participants was below 400.CNS adverse events occurred in 52 studies, while 53 studies reported of absence of CNS adverse events. Overall, 187/3614 (5%) participants receiving ketamine and 122/2924 (4%) receiving control treatment experienced an adverse event (RR 1.2, 95% CI 0.95 to 1.4; high-quality evidence; 105 studies, 6538 participants). Ketamine reduced postoperative nausea and vomiting from 27% with placebo to 23% with ketamine (RR 0.88, 95% CI 0.81 to 0.96; the number needed to treat to prevent one episode of postoperative nausea and vomiting with perioperative intravenous ketamine administration was 24 (95% CI 16 to 54; high-quality evidence; 95 studies, 5965 participants). AUTHORS' CONCLUSIONS: Perioperative intravenous ketamine probably reduces postoperative analgesic consumption and pain intensity. Results were consistent in different operation types or timing of ketamine administration, with larger and smaller studies, and by higher and lower pain intensity. CNS adverse events were little different with ketamine or control. Perioperative intravenous ketamine probably reduces postoperative nausea and vomiting by a small extent, of arguable clinical relevance.

Obstetric analgesia - update 2016.

Neuraxial labor analgesia can be initiated via combined spinal-epidural (CSE) or stand-alone epidural. Pros and cons of these techniques are outlined in this review. In recent years computer-integrated patient-controlled epidural analgesia (CI-PCEA) and programed intermittent epidural boluses (PIEB) have been developed, adding to continuous infusion and PCEA for the maintenance of neuraxial analgesia. Postdural puncture headache (PDPH) and fever can occur secondary to labor epidural that both have clinical relevance for the care givers. Insights into the mechanism of epidural fever and treatment strategies for PDPH are outlined. Due to the increase in obesity the specific considerations for this patient group are discussed. New data have been presented for remifentanil, an ultra-shortly acting opioid, that is used in obstetric analgesia. Without breaking new data, the use of nitrous oxide especially by midwives has a kind of renaissance, and this will be discussed, too.

Prevention of Spinal Anesthesia-Induced Hypotension During Cesarean Delivery by 5-Hydroxytryptamine-3 Receptor Antagonists: A Systematic Review and Meta-analysis and Meta-regression.

BACKGROUND: Hypotension remains a frequent complication of spinal anesthesia, increasing the risk of nausea and vomiting, altered mental status, and aspiration. The aim of this systematic review and meta-analysis was to determine whether 5-hydroxytryptamine3 (5-HT3) receptor antagonists, administered before the initiation of spinal anesthesia, mitigate hypotension. METHODS: After a systematic literature search in various databases, randomized placebo-controlled double-blind trials studying the preventive effect of 5-HT3 receptor antagonists were included. A random-effects model was applied, risk ratio (RR, binary variables) or weighted mean difference (continuous variables) with 95% confidence intervals (CIs) were calculated. The primary outcome was the incidence of hypotension. RESULTS: Seventeen trials (8 obstetric, 9 non-obstetric) reporting on 1604 patients were identified. Ondansetron in doses from 2 to 12 mg was studied in 12 trials. Prophylactic 5-HT3 administration significantly reduced the risk of hypotension in the combined analysis of 17 trials, RR 0.54 (95% CI 0.36-0.81, I = 79%). In obstetric trials, the RR was 0.52, 95% CI 0.30-0.88, I = 87% (number needed to treat 4). In non-obstetric studies, the 95% CIs were wide and included a clinically relevant reduction in the risk of hypotension (RR 0.50, 95% CI 0.22-1.16; I = 66%). Contour-enhanced funnel plots confirmed publication bias. Meta-regression showed a significant ondansetron dose response in non-obstetric patients (ß = -0.355, P = .04). In the combined and in the obstetric-only analysis, the risk of bradycardia was significantly reduced as was the use of phenylephrine equivalents. CONCLUSIONS: 5-HT3 antagonists are effective in reducing the incidence of hypotension and bradycardia; the effects are moderate and are only significant in the subgroup of patients undergoing cesarean delivery. The effects in the non-obstetric population are not significant.

The Effect of Combined Spinal-Epidural Versus Epidural Analgesia in Laboring Women on Nonreassuring Fetal Heart Rate Tracings: Systematic Review and Meta-analysis.

BACKGROUND: Combined spinal-epidural labor analgesia has gained popularity, but it is unclear whether this technique is associated with a higher incidence of nonreassuring fetal heart rate (FHR) tracings compared with epidural analgesia. Our meta-analysis aimed at comparing the incidence of nonreassuring FHR tracings between the 2 neuraxial techniques. METHODS: Databases were searched to identify randomized controlled trials that compared the incidence of nonreassuring FHR tracings, as defined in the individual studies, after combined spinal-epidural versus epidural analgesia in laboring women. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. We performed a subgroup analysis for studies using low-dose epidural bupivacaine concentrations (≤0.125%) for epidural analgesia. RESULTS: Seventeen trials including 3947 parturients were retrieved that compared the 2 neuraxial techniques. All trials used intrathecal opioids in 1 study arm. The pooled effect estimate of low- and high-dose epidural bupivacaine studies together showed a significantly increased risk of nonreassuring FHR tracings with the combined technique (RR 1.31, 95% CI 1.02-1.67, P = .03, I = 18%). A subgroup analysis of 10 trials using low-dose epidural bupivacaine found a RR for nonreassuring FHR tracings between combined spinal-epidural and epidural analgesia of 1.12, 95% CI 0.93-1.34, P = .18. In a sensitivity analysis of those low-dose epidural bupivacaine studies that ensured blinding of the outcome assessor, the RR was 1.41, 95% CI 0.99-2.02, P = .06. CONCLUSIONS: Combined spinal-epidural labor analgesia was associated with a higher risk of nonreassuring FHR tracings than epidural analgesia alone. In the subgroup analysis comparing combined spinal-epidural with low-dose epidural labor analgesia, the 95% CI contains a clinically significant difference between groups; moreover, the 95% CI overlaps with the 95% CI of the comparison of the combined low- and high-dose epidural techniques. Therefore, it cannot be concluded that there was no difference between combined spinal-epidural and low-dose epidural techniques.

Nonobstetric anesthesia during pregnancy.

PURPOSE OF REVIEW: Nonobstetric anesthesia during pregnancy is challenging - not only for the anesthetist. Owing to the difficulties of ethical consent for randomized studies in this special patient group, the available evidence is quite low. Nevertheless, recently several guidelines for the management of pregnant patients undergoing nonobstetric anesthesia have been published. We review the current guidelines developed under the auspices of the Society of American Gastrointestinal Endoscopic Surgeons, guidelines for the management of difficult and failed tracheal intubation in obstetrics, as well as guidelines for the management of a pregnant trauma patient. RECENT FINDINGS: The algorithms for management of the difficult airway during pregnancy should be made available in every institution that cares for pregnant women. During laparoscopic surgery strict limitation of the pneumoperitoneal pressure to avoid maternal hypercapnia and fetal acidosis is strongly recommended. An injured pregnant woman should be transferred to a maternity facility when the injury is not life or limb threatening. In case of major trauma, stabilization and care of the woman is priority. SUMMARY: Several guidelines with high relevance for the care of pregnant women undergoing nonobstetric surgery have been published. Although the level of evidence may be low they can probably contribute to an improvement in the care and outcome of this patient group.

The effect of adding a background infusion to patient-controlled epidural labor analgesia on labor, maternal, and neonatal outcomes: a systematic review and meta-analysis.

BACKGROUND: Patient-controlled epidural analgesia (PCEA) has gained popularity, but it is still unclear whether adding a background infusion confers any benefit. METHODS: A systematic literature search in PubMed, Embase, CINAHL, LILACS, CENTRAL, Clinicaltrials.gov, and ISI WOS was performed to identify randomized controlled double-blind trials that compare PCEA-only with PCEA combined with a continuous infusion (PCEA + CI) in parturients. The data were subjected to meta-analyses using the random-effects model. Our primary outcome was the incidence of instrumental vaginal delivery. Secondary outcomes were incidences of spontaneous vaginal and cesarean deliveries, duration of labor, analgesic outcomes, maternal outcomes (visual analog scale scores for pain, maternal satisfaction, nausea, pruritus, hypotension), and neonatal outcomes (Apgar score, umbilical artery pH). RESULTS: We identified 7 trials with a low risk of bias, reporting on 891 parturients, for inclusion in our systematic review. The risk of instrumental vaginal delivery was increased in the PCEA + CI group, risk ratio (RR) 1.66 (95% confidence interval 1.08-2.56, P = 0.02; I = 0%); the RR for cesarean delivery was 0.83 (95% confidence interval 0.61-1.13, I = 0%). The second stage of labor was prolonged (weighted mean difference 12.3 minutes, 95% confidence interval 5.1-19.5 minutes, P = 0.0008; I = 0%) in the PCEA + CI group. Fewer patients in the PCEA + CI group required physician-administered boluses (RR 0.35 [95% confidence interval 0.25-0.47, P < 0.00001; I = 0%]). No differences regarding maternal adverse events (nausea, pruritus, hypotension) or neonatal outcomes (Apgar scores <7, umbilical artery pH) were observed. CONCLUSIONS: On the basis of current evidence, no conclusion can be drawn regarding the risks or benefits of adding a continuous background infusion to PCEA compared with PCEA-only epidural labor analgesia. Further high-quality studies involving a sufficient number of patients are required.

Is general anaesthesia for caesarean section associated with postpartum haemorrhage? Systematic review and meta-analysis.

BACKGROUND: Postpartum haemorrhage (PPH) remains a leading cause of maternal morbidity and mortality. The odds for PPH were about eight times higher following general anaesthesia compared with neuraxial anaesthesia in a recent retrospective study. We aimed to conduct a systematic review and meta-analysis of the effect of type of anaesthesia (general vs. neuraxial) on estimated blood loss and transfusion requirements after caesarean section. METHODS: A systematic literature search was performed. The quality of eligible reports was assessed using the Oxford Quality Scale. Data were subjected to meta-analysis using the random effects model. RESULTS: The search identified 18 articles including 12,330 parturients. Meta-analysis of randomised controlled trials (RCTs) found a significant difference in blood loss, favouring neuraxial anaesthesia (spinal and epidural) when comparing with general anaesthesia {weighted mean difference -106.11 ml [95% confidence interval (CI) -209.80, -2.42 ml], P = 0.04}. In further analyses, we found a significant difference after epidural compared with general anaesthesia but not after spinal compared with general anaesthesia. Based on RCTs, there was no significantly increased risk of blood transfusions with general anaesthesia. Analysis of non-randomised studies found a significantly higher transfusion requirement after general anaesthesia (risk ratio 5.06, 95% CI 2.47-10.36, P < 0.00001). The incidence of hypotension and the amount of fluid given were higher in the neuraxial anaesthesia groups. CONCLUSION: General anaesthesia is associated with a higher blood loss than neuraxial anaesthesia. However, based on high-quality studies, the need for blood transfusion was not greater. The higher blood loss with general anaesthesia is therefore of uncertain clinical relevance.

An explorative analysis of pharmacovigilance data of oxytocin and its analogue carbetocin, with a focus on haemodynamic adverse effects.

BACKGROUND: Oxytocin and its analogue carbetocin are uterotonics whose prophylactic use is recommended to prevent postpartum haemorrhage, which is one of the leading causes of maternal deaths worldwide. However, both drugs can cause specific adverse effects and haemodynamic challenges. AIM: The aim of this work was to exploratively examine reports of adverse drug events of both drugs and to establish a comparative haemodynamic profile. METHOD: Using data extracted from the World Health Organization's pharmacovigilance database VigiBase, a descriptive analysis was performed of all reports for oxytocin and carbetocin as a suspected or interacting drug followed by a disproportionality analysis for haemodynamic events. Reporting odds ratios (ROR) of carbetocin for hypertension, hypotension, tachycardia, and bradycardia were calculated, with oxytocin-related reports serving as comparators. RESULTS: Oxytocin and carbetocin were mentioned as suspected or interacting drugs in 11,258 and 374 reports, respectively. Resulting RORs for carbetocin were 3.45 (95%CI: 1.72-6.92) for hypertension, 2.65 (1.64-4.28) for hypotension, 2.84 (1.79-4.49) for tachycardia, and 2.00 (0.87-4.60) for bradycardia, when compared to oxytocin. Of 231 patients for whom oxytocin-related tachycardia was reported, 2.6% died, and of 91 patients for whom bradycardia was reported, 2.2% died. No deaths were reported with carbetocin for any of the haemodynamic adverse events. CONCLUSION: Compared to oxytocin, carbetocin showed an elevated reporting for adverse hypertension, hypotension, and tachycardia in pharmacovigilance data. Clinicians should be aware of their patients' individual susceptibility and the possibility of haemodynamic deterioration until causal inferences are possible.

Labour epidural analgesia and anti-infectious management of the neonate: a meta-analysis.

BACKGROUND: A known side effect of labour epidural analgesia (EDA) is maternal fever. It is unclear whether this has effects on the anti-infectious management of the neonate. METHODS: A systematic literature search and a hand search of abstract publications were conducted. Studies reporting sepsis evaluation or antibiotic treatment were further assessed. For meta-analysis, risk ratio (RR) and 95% confidence interval (CI) were calculated using the random effects model. RESULTS: Five relevant articles reporting on 4667 parturients were identified; three were observational studies and two were randomised controlled trials (RCT). The RR for sepsis workup of all studies analysed together was 2.58 (95% CI, 1.06-6.27, P=0.04). The RR for antibiotic treatment of the neonate was 2.76 (95% CI, 1.20-6.31, P=0.02). When considering the RCTs alone, the RRs for sepsis evaluation and antimicrobial treatment were still significantly elevated. DISCUSSION: Our data suggest that EDA-related maternal hyperthermia results in an increased likelihood of sepsis workup and antibiotic treatment of the infant. A crucial question is whether EDA-related maternal hyperthermia is truly infectious. If not, administration of antibiotics would not be justified and may be dangerous.

Optimal uterotonic management.

Uterotonics play an important role in the management of postpartum haemorrhage (PPH), often caused by uterine atony. The World Health Organization (WHO) recommends the application of uterotonics for all births. Oxytocin, considered the first-line uterotonic, binds to a G protein-coupled receptor which is subject to down sensitization upon repeated or prolonged administration of oxytocin. Consequently, a uterotonic with a different mechanism of action should be chosen early when oxytocin does not restore uterine tone. Choice of the second-line uterotonic is determined by institutional preferences as well as by maternal co-morbidities since most uterotonics have cardiovascular side effects. Slow injection of all uterotonics is strongly recommended to blunt these reactions. Methylergometrine and carboprost should, therefore, be avoided in many cardiovascular pathologies. Carbetocin is a chemical modification of oxytocin with a longer half-time, and therefore one bolus of carbetocin is usually sufficient. Its heat stability makes it an ideal candidate in resource-restricted settings.

Accuracy of Spinal Anesthesia Drug Concentrations in Mixtures Prepared by Anesthetists.

OBJECTIVE: Medication errors include the indirect dosing of drugs. For spinal anesthesia mixtures of local anesthetics, opioids are drawn from ampoules and combined in a syringe, according to clinical practice. We set out to determine the accuracy of the drug mixtures. METHODS: Physicians of our department were invited to prepare the mixture used for spinal anesthesia for cesarean section, consisting of 10-mg hyperbaric bupivacaine (2-mL volume), 20-µg fentanyl (0.4-mL volume), and 100-µg morphine (0.1-mL volume). Concentrations of these drugs were determined by means of high performance liquid chromatography. Interindividual and intraindividual variations were assessed. RESULTS: We analyzed 96 samples from 31 physicians. Fifty-one percent of the measured bupivacaine concentrations were in ±10% deviation range of the intended concentration; 17% of the fentanyl and 24% of the morphine concentrations were in this range. A total of 2.1% of the samples had a bupivacaine concentration corresponding to a dose of 8 mg or less, and 11.5% of the samples had a morphine concentration corresponding to a dose of 150 µg or greater. Intraindividual variations were 10.9% for bupivacaine, 24.7% for fentanyl, and 38.9% for morphine. CONCLUSIONS: Our results show a high deviation of the obtained from the intended concentrations. Two percent of the samples had bupivacaine concentrations that probably resulted into an insufficient analgesia, and 11% of the samples had morphine concentrations that, according to guidelines, would require a longer monitoring period than with the intended dose.

The Impact of a 22-Month Multistep Implementation Program on Speaking-Up Behavior in an Academic Anesthesia Department.

BACKGROUND: Speaking-up is a method of assertive communication that increases patient safety but often encounters barriers. Numerous studies describe programs introducing speaking-up with varying success; the common denominator seems to be the need for a multimodal and sustained approach to achieve the required change in behavior and culture for safer health care. METHODS: Before implementing a 22-month multistep program for establishing and strengthening speaking-up at our institution, we assessed perceived safety culture using the "Safety Attitudes Questionnaire." After program completion, participants completed parts of the same Safety Attitudes Questionnaire relevant to speaking-up, and preresult and postresult were compared. In addition, levels of speaking-up and assertive communication were compared with a Swiss benchmark using results from the "Speaking-up About Patient Safety Questionnaire." RESULTS: Safety Attitudes Questionnaire scores were significantly higher after program completion in 2 of 3 answered questions (median [first quartile, third quartile), 5.0 [4.0, 5.0] versus 4.0 [4.0, 5.0], P = 0.0002, and 5.0 [4.0, 5.0] versus 4.0 [4.0, 4.0] P = 0.002; n = 34). Our composite score on the Speaking-up About Patient Safety Questionnaire was significantly higher (mean ± SD, 5.9 ± 0.7 versus 5.2 ± 1.0; P < 0.001) than the benchmark (n = 65). CONCLUSIONS: A long-term multimodal program for speaking-up was successfully implemented. Attitude and climate toward safety generally improved, and postprogram perceived levels of assertive communication and speaking-up were higher than the benchmark. These results support current opinion that multimodal programs and continued effort are required, but that speaking-up can indeed be strengthened.