Intrathecal catheterisation after observed accidental dural puncture in labouring women: update of a meta-analysis and a trial-sequential analysis.

BACKGROUND: Our meta-analysis from 2013 showed that inserting a catheter intrathecally after an observed accidental dural puncture can reduce the need for epidural blood patch in labouring women requesting epidural analgesia. We updated our conventional meta-analysis and added a trial-sequential analysis (TSA). METHODS: A systematic literature search was conducted to identify studies that compared inserting the catheter intrathecally with an epidural catheter re-site or with no intervention. The extracted data were pooled and the risk ratio (RR) and 95% confidence interval (95%CI) for the incidence of post-dural puncture headache (PDPH) was calculated, using the random effects model. A contour-enhanced funnel plot was constructed. A TSA was performed and the cumulative Z score, monitoring and futility boundaries were constructed. RESULTS: Our search identified 13 studies, reporting on 1653 patients, with a low risk of bias. The RR for the incidence of PDPH was 0.82 (95%CI 0.71 to 0.95) and the RR for the need for epidural blood patch was 0.62 (95%CI 0.49 to 0.79); heterogeneity of both analyses was high. The TSA showed that the monitoring or futility boundaries were not crossed, indicating insufficient data to exclude a type I error of statistical analysis. Contour-enhanced funnel plots were symmetric, suggesting no publication bias. CONCLUSIONS: Conventional meta-analyses showed for the first time that intrathecal catheterisation can reduce the incidence of PDPH. However, TSA did not corroborate this finding. Despite increasing use in clinical practice there is no firm evidence on which to base a definite conclusion.

Difficult epidural placement in obese and non-obese pregnant women: a systematic review and meta-analysis.

INTRODUCTION: The increasing rates of obese pregnant women who receive epidural analgesia during delivery make it necessary to evaluate the rate of epidural failure and difficulties during epidural placement in these women. METHODS: PubMed, Embase, Medline and Google scholar were searched systematically until December 2017 for articles reporting epidural failure and/or difficulties in epidural placement in obese pregnant women and non-obese pregnant women. We excluded studies that used ultrasound during epidural placement. Outcomes were defined as first-pass success or multiple attempts. Quality assessment of the literature was performed in accordance with an adjusted Newland-Ottawa Scale. Two groups of women were defined (body mass index (BMI) ≥30 kg/m2 and BMI <30 kg/m2). Statistical analysis was performed using OpenMetaAnalyst software. RESULTS: Initially 221 articles were identified, of which we included eight in the systematic review and four in the meta-analyses. Five out of six studies reported an association between BMI and epidural failure and four out of five studies reported an association between BMI and difficult epidural placement or multiple attempts. The odds ratios (OR) for epidural failure were 1.82 [95% CI 1.23 to 2.68] and for multiple attempts 2.21 [95% CI 1.39 to 3.52], both of these ORs applying to obese pregnant women compared to non-obese pregnant women. CONCLUSION: The findings suggest that obesity in pregnant women increases the risk of epidural failure and difficult epidural placement during delivery at least two-fold, and that this risk increases with increasing BMI.

Methods and considerations concerning cardiac output measurement in pregnant women: recommendations of the International Working Group on Maternal Hemodynamics.

Cardiac output (CO), along with blood pressure and vascular resistance, is one of the most important parameters of maternal hemodynamic function. Substantial changes in CO occur in normal pregnancy and in most obstetric complications. With the development of several non-invasive techniques for the measurement of CO, there is a growing interest in the determination of this parameter in pregnancy. These techniques were initially developed for use in critical-care settings and were subsequently adopted in obstetrics, often without appropriate validation for use in pregnancy. In this article, methods and devices for the measurement of CO are described and compared, and recommendations are formulated for their use in pregnancy, with the aim of standardizing the assessment of CO and peripheral vascular resistance in clinical practice and research studies on maternal hemodynamics. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Ephedrine versus phenylephrine as a vasopressor for spinal anaesthesia-induced hypotension in parturients undergoing high-risk caesarean section: meta-analysis, meta-regression and trial sequential analysis.

BACKGROUND: Phenylephrine is the preferred vasopressor for the prevention and treatment of spinal anaesthesia-induced hypotension during caesarean section, because studies on low-risk elective patients found it to have a less detrimental effect on umbilical artery pH compared with ephedrine. However, limited data exist from high-risk parturients and parturients with uteroplacental insufficiency. METHODS: We systematically searched for randomised, controlled, double-blinded trials of these two vasopressors in high-risk caesarean sections. We applied conventional meta-analysis, trial sequential analysis, computing the required information size that would exclude type I and II errors, contour-enhanced funnel plot testing for publication bias, meta-regression to assess the dose-response relationship, and the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE). The incidence of fetal acidosis (umbilical arterial pH <7.2) was the primary outcome. RESULTS: Eight trials (712 patients) with low risk of bias were identified. Pooling six studies of patients with preeclampsia and other reasons for fetal compromise, as well as subgroup analysis of the preeclampsia studies, revealed no significant differences in the incidence of fetal acidosis. Trial sequential analysis showed that the required information size was not reached. The funnel plot was not suggestive of publication bias. Meta-regression showed no dose-response relationship. The GRADE score was moderate quality. CONCLUSIONS: Despite several studies and a large number of patients there was insufficient evidence to make a recommendation for choice of vasopressor in high-risk caesarean section. Trials with adequate power to detect differences in the incidence of fetal acidosis between ephedrine and phenylephrine are required to provide evidence-based guidance.

Combined spinal-epidural anesthesia with non-invasive ventilation during cesarean delivery of a woman with a recent diagnosis of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is the most common neurodegenerative upper and lower motor neuron disease in adults but is not common in women of child-bearing age. We present a case of a pregnant woman who was diagnosed with amyotrophic lateral sclerosis and developed respiratory distress at 32 weeks-of-gestation. She underwent a cesarean delivery under combined spinal-epidural anesthesia with non-invasive ventilation. This resulted in a successful outcome for both the mother and the baby.

[High-risk obstetrics in tertiary centres: anaesthetist, hybrid operating suite and obstetric critical care unit]. / Hoogcomplexe verloskunde in derdelijnscentra.

The frequency of pregnancy-related morbidity has increased over recent decades, as has the number of patients with complex congenital cardiac anomalies reaching fertile age, resulting in an increasing number of high-risk pregnancies. In order to optimalise maternal and foetal outcome in these patients, not only is the availability of optimal in-hospital facilities (e.g. obstetric critical care unit, hybrid operating suite) important, but also a multidisciplinary approach which is mandatory for successful maternal and foetal outcome. The role of a dedicated obstetric anaesthetist in this multidisciplinary team is essential. In contrast with other Western countries, in the Netherlands this has so far been underestimated. Obstetric anaesthetists should also be part of multidisciplinary obstetric care in high-risk patients during pregnancy, thus optimalising conditions for successful delivery and maternal and foetal outcome.

ENDOCRINOLOGY IN PREGNANCY: Pheochromocytoma in pregnancy: case series and review of literature.

Pheochromocytoma in pregnancy is extremely rare. Early recognition is crucial as antepartum diagnosis can largely decrease maternal and fetal mortality rates. As symptoms of pheochromocytoma are rather similar to those of other far more common causes of hypertension during pregnancy, timely diagnosis is a challenge. In pregnant patients, similar to non-pregnant patients, increased plasma and/or 24-h urine (nor)metanephrine concentrations most reliably confirm the diagnosis of pheochromocytoma. MRI and ultrasound are the only imaging modalities that can be used safely during pregnancy to localize the tumor. During pregnancy, pretreatment consists of alpha blockade as usual. However, dosing of α-adrenergic receptor blockers during pregnancy is a challenge as hypertension must be treated while preserving adequate uteroplacental circulation. When the diagnosis is made within the first 24 weeks of pregnancy, it is generally recommended to remove the tumor in the second trimester, while resection is generally postponed till after delivery when the diagnosis is made in the third trimester and medical pretreatment is sufficient. Both during and after pregnancy, laparoscopic surgery is the preferred approach for resection of the tumor. There is no consensus in literature about the preferred route and timing of delivery. Therefore, in our opinion, decisions should be made on an individual basis by an experienced and dedicated multidisciplinary team. Over the last decades, maternal and fetal prognosis has improved considerably. Further increasing awareness of this rare diagnosis and treatment of these patients by a dedicated team in a tertiary referral hospital are critical factors for optimal maternal and fetal outcome.

Epidural Analgesia with Ropivacaine during Labour in a Patient with a SCN5A Gene Mutation.

SCN5A gene mutations can lead to ion channel defects which can cause cardiac conduction disturbances. In the presence of specific ECG characteristics, this mutation is called Brugada syndrome. Many drugs are associated with adverse events, making anesthesia in patients with SCN5A gene mutations or Brugada syndrome challenging. In this case report, we describe a pregnant patient with this mutation who received epidural analgesia using low dose ropivacaine and sufentanil during labour.

Rectal acetaminophen does not reduce morphine consumption after major surgery in young infants.

BACKGROUND: The safety and value of acetaminophen (paracetamol) in addition to continuous morphine infusion has never been studied in newborns and young infants. We investigated the addition of acetaminophen to evaluate whether it decreased morphine consumption in this age group after major thoracic (non-cardiac) or abdominal surgery. METHODS: A randomized controlled trial was performed in 71 patients given either acetaminophen 90-100 mg kg(-1) day(-1)or placebo rectally, in addition to a morphine loading dose of 100 microg kg(-1) and 5-10 microg kg(-1) h(-1) continuous infusion. Analgesic efficacy was assessed using Visual Analogue Scale (VAS) and COMFORT scores. Extra morphine was administered if VAS was > or = 4. RESULTS: We analysed data of 54 patients, of whom 29 received acetaminophen and 25 received placebo. Median (25-75th percentile) age was 0 (0-2) months. Additional morphine bolus requirements and increases in continuous morphine infusion were similar in both groups (P = 0.366 and P = 0.06, respectively). There was no significant difference in total morphine consumption, respectively, 7.91 (6.59-14.02) and 7.19 (5.45-12.06) mug kg(-1) h(-1) for the acetaminophen and placebo group (P = 0.60). COMFORT [median (25-75th percentile) acetaminophen 10 (9-12) and placebo 11 (9-13)] and VAS [median (25-75th percentile) acetaminophen 0.0 (0.0-0.2) and placebo 0.0 (0.0-0.3)] scores did not differ between acetaminophen and placebo group (P = 0.06 and P = 0.73, respectively). CONCLUSIONS: Acetaminophen, as an adjuvant to continuous morphine infusion, does not have an additional analgesic effect and should not be considered as standard of care in young infants, 0-2 months of age, after major thoracic (non-cardiac) or abdominal surgery.

Pharmacokinetics of single dose intravenous propacetamol in neonates: effect of gestational age.

AIM: To investigate the pharmacokinetics and pharmacodynamics of single dose propacetamol in preterm and term infants on the first day of life. METHODS: Neonates were stratified by gestational age. Preterm (< 37 weeks) and term (37-41 weeks) infants received a single dose of propacetamol in the first 24 hours of life when they had minor, painful procedures or as additional treatment in infants receiving opioids. Blood samples were taken from an arterial line, and pain was evaluated by a multidimensional pain scale. Results were reported as mean (SD). Student's t and Wilcoxon tests were used to compare the groups. RESULTS: Thirty neonates were included, 10 of which were term infants. Serum half life was 277 (143) minutes in the preterm infants and 172 (59) minutes in the term infants (p < 0.05). Clearance was 0.116 (0.08) litre/kg/h in the preterm infants and 0.170 (0.06) litre/kg/h in the term infants (p < 0.05). Gestational age correlated with serum half life (r = -0.46). No effect of sex or administration of prenatal steroids was found on the pharmacokinetics of paracetamol. In neonates who only received propacetamol (n = 15), the level of analgesia seemed to be associated with the therapeutic (> 5 mg/l) level. CONCLUSIONS: A correlation was found between gestational age and the serum half life of propacetamol. The maturational trend of clearance and half life in preterm and term neonates is in line with data on the pharmacokinetics of propacetamol beyond the newborn period.

Acetaminophen in cerebrospinal fluid in children.

BACKGROUND: There are few studies describing acetaminophen (APAP) cerebrospinal fluid (CSF) concentrations in children. This current study was undertaken in children--from neonates to adolescents--in order to investigate age-related changes in the plasma to CSF equilibration half-time (Teq) of APAP. METHODS: Children (n=41) 1 week to 18 years of age undergoing (semi) elective surgery for placement or revision of a ventriculo-peritoneal shunt or insertion of a temporary external ventricular drain received a loading dose of 30-40 mg/kg APAP 1 h before scheduled surgery. Blood and CSF samples for APAP concentration analysis were collected during surgery. In those children with a temporary external drain, blood and CSF sampling were extended into the postoperative period. APAP and CSF pharmacokinetics were estimated using non-linear mixed-effects models. Size was standardized to a 70-kg person using allometric "1/4 power models". RESULTS: Median (25-75th percentile) age and weight of the patients included in this study were 12 months (3-62 months) and 10.0 kg (5.8-20.0 kg). Median (25-75th percentile) time between APAP loading dose administration and collection of blood samples and median time (25-75th percentile) between APAP loading dose and collection of CSF were, respectively, 125 min (95-210 min) and 133 min (33-202 min). The population mean Teq, standardized to a 70-kg person, was 1.93 h (CV 43%), an estimate similar to that described in adults (2.1 h). There was no relationship between age and Teq other than that predicted by size. APAP plasma concentrations ranged from 0.0 mg/l to 33.0 mg/l, APAP CSF concentrations ranged from 0.0 mg/l to 21.0 mg/l. CONCLUSION: Size rather than blood-brain-barrier maturation determines Teq changes with age in children. We predict a neonate (3.5 kg), 1-year-old child (10 kg), 5-year-old child (20 kg), 10-year-old child (30 kg) and adult (70 kg) to have Teq values of 0.9, 1, 1.4, 1.6, and 1.93 h, respectively.

Analgesic efficacy of rectal versus oral acetaminophen in children after major craniofacial surgery.

BACKGROUND: Analgesic acetaminophen (INN, paracetamol) plasma concentrations after major surgery in neonates and infants have not yet been established in the literature. We therefore conducted a study in our intensive care unit. METHODS: Forty children, mean (standard deviation) age, 10.3 (2.3) months, received 20 mg/kg acetaminophen either orally (n = 20) or rectally (n = 20) every 6 hours after a rectal loading dose (40 mg/kg) during elective craniofacial correction. Blood samples were taken 1 hour before and 2 hours after administration of acetaminophen maintenance doses; pain scores were obtained every 3 hours. RESULTS: Acetaminophen plasma concentrations were higher in patients receiving rectal acetaminophen (mean area under the concentration-time curve [AUC], 171.2 mg x h/L) than in patients receiving oral acetaminophen (mean AUC, 111.9 mg x h/L). Pain scores were higher in patients receiving oral acetaminophen. However, after exclusion of the patients who vomited from the group receiving oral acetaminophen, acetaminophen plasma concentrations and pain scores did not differ between the groups. There was no relation between acetaminophen plasma concentrations and pain scores. Although 9 of all 40 patients (22.5%) did not reach the expected analgesic acetaminophen plasma concentrations of 10- to 20 mg/L, <7.5% of the visual analog scale pain scores exceeded 4 cm, which was considered as a cutoff point. CONCLUSION: These are the first data showing that the analgesic acetaminophen plasma concentration after major surgery in this age group does not always reach the 10 to 20 mg/L level. These data also show that, after a rectal loading dose of 40 mg/kg has been given during surgery, the best way of administering acetaminophen after craniofacial surgery is the rectal route.