Anesthetic management of patients with peripartum cardiomyopathy.

PURPOSE OF REVIEW: Cardiovascular disease is increasingly emerging as a cause of peripartum morbidity and mortality. Peripartum cardiomyopathy (PPCM) is defined as pregnancy-related heart failure with a reduced left ventricular ejection fraction <45%. PPCM develops in the peripartum phase and is not an aggravation of an existing prepregnancy cardiomyopathy. Anesthesiologists typically encounter these patients in the peripartum phase in a variety of settings and should be aware of this pathology and its implications for the perioperative management of parturients. RECENT FINDINGS: PPCM has been investigated increasingly over the last few years. Significant progress has been made in the assessment of global epidemiology, pathophysiological mechanisms, genetics and treatment. SUMMARY: Although PPCM is an overall rare pathology, patients can potentially be encountered by any anesthesiologist in many different settings. Therefore, it is important to be aware of this disease and understand the basic implications for anesthetic management. Severe cases often require early referral to specialized centers for advanced hemodynamic monitoring and pharmacological or mechanical circulatory support.

Neurodevelopmetal effects of maternal blood pressure management with noradrenaline during general anaesthesia for nonobstetric surgery in the pregnant rabbit model.

In pregnant women, anaesthesia-induced hypotension is commonly treated using phenylephrine or noradrenaline, the rationale being to maintain uterine perfusion pressure and thereby uterine blood flow. Evidence for this strategy during general anaesthesia for nonobstetric surgery is absent. To analyse the effects of treating anaesthesia-induced hypotension with noradrenaline on brain development of rabbit foetuses of mothers subjected to general anaesthesia for nonobstetric surgery. We hypothesised that treatment of maternal hypotension would improve foetal outcomes. Randomised controlled laboratory study using 21 pregnant rabbits (does) at 28 days of gestation. Two hours of sevoflurane anaesthesia for a laparotomy without treatment of anaesthesia-induced hypotension (hypotension group) or with maintaining maternal mean arterial pressure above 80% of the awake value using noradrenaline (noradrenaline group). In the control group, does remained untouched. At term, all pups were delivered by caesarean section. One day later, the neurobehaviour of the pups was assessed and brains were harvested. Neuron density in the frontal cortex for the comparison of noradrenaline groups versus hypotension groups was the primary outcome; the neurobehavioural scores and other histological outcomes were secondary outcomes. In the noradrenaline groups and hypotension groups, neuron density in the frontal cortex was similar (1181 ±â€Š162 versus 1189 ±â€Š200 neurons mm-2, P  = 0.870). However, significantly less foetal survival, lower sensory scores in neurobehavioural assessment and less proliferation were observed in the noradrenaline group when compared with the hypotension group. Neuron densities in other regions, total cell densities, biometrics and synaptogenesis were not affected. There were no differences between the control group and hypotension group. During general anaesthesia for nonobstetric surgery in rabbits, treatment of anaesthesia-induced hypotension using noradrenaline did not affect neuron densities but was associated with impaired foetal outcomes according to several secondary outcome parameters. Further studies are needed to investigate any clinical relevance and to determine the target blood pressure in pregnant women during general anaesthesia.KEY POINTSIn pregnant women, anaesthesia-induced hypotension is commonly treated using phenylephrine or noradrenaline, with the rationale to maintain uterine perfusion pressure and thereby uterine blood flow.Evidence for this strategy during general anaesthesia for nonobstetric surgery is absent.We investigated the effects of treating anaesthesia-induced hypotension with noradrenaline on the brain development of rabbit foetuses, of mothers subjected to general anaesthesia for nonobstetric surgery.We hypothesised that treatment of maternal hypotension would improve foetal outcomes.Neuron densities were similar but significantly less foetal survival, impaired neurobehaviour and less proliferation were observed after treatment of anaesthesia-induced hypotension with noradrenaline, compared with untreated hypotension.

Effects of general anaesthesia during pregnancy on neurocognitive development of the fetus: a systematic review and meta-analysis.

BACKGROUND: The US Food and Drug Administration warned that exposure of pregnant women to general anaesthetics may impair fetal brain development. This review systematically evaluates the evidence underlying this warning. METHODS: PubMed, EMBASE, and Web of Science were searched from inception until April 3, 2020. Preclinical and clinical studies were eligible. Exclusion criteria included case reports, in vitro models, chronic exposures, and exposure only during delivery. Meta-analyses were performed on standardised mean differences. The primary outcome was overall effect on learning/memory. Secondary outcomes included markers of neuronal injury (apoptosis, synapse formation, neurone density, and proliferation) and subgroup analyses. RESULTS: There were 65 preclinical studies included, whereas no clinical studies could be identified. Anaesthesia during pregnancy impaired learning and memory (standardised mean difference -1.16, 95% confidence interval -1.46 to -0.85) and resulted in neuronal injury in all experimental models, irrespective of the anaesthetic drugs and timing in pregnancy. Risk of bias was high in most studies. Rodents were the most frequently used animal species, although their brain development differs significantly from that in humans. In a minority of studies, anaesthesia was combined with surgery. Monitoring and strict control of physiological homeostasis were below preclinical and clinical standards in many studies. The duration and frequency of exposure and anaesthetic doses were often much higher than in clinical routine. CONCLUSION: Anaesthesia-induced neurotoxicity during pregnancy is a consistent finding in preclinical studies, but translation of these results to the clinical situation is limited by several factors. Clinical observational studies are needed. PROSPERO REGISTRATION NUMBER: CRD42018115194.

Successful resuscitation after hyperkalemic cardiac arrest during liver transplantation by converting veno-venous bypass to veno-arterial ECMO.

INTRODUCTION: Intraoperative cardiac arrest (ICA) is a feared complication during liver transplantation (LTx), typically occurring during reperfusion. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used for post-reperfusion cardiac arrest. CASE REPORT: We present a case of successful resuscitation after hyperkalemic ICA during the pre-anhepatic phase of a second liver transplantation by converting veno-venous bypass (VVB) to VA-ECMO. DISCUSSION: While this technique has been recommended for ICA during reperfusion, it has never been reported during the pre-anhepatic phase. VA-ECMO can be a lifesaving extension to cardiopulmonary resuscitation for ICA during LTx with beneficial neurological outcome by providing perfusion while the cause of ICA is reversed. CONCLUSION: Conversion of VVB to VA-ECMO should be considered in all patients who suffer from ICA during LTx with use of VVB. With VVB installed, conversion to VA-ECMO is fast and effective. If VVB is not used, early VA-ECMO should be considered for ICA.

Effects of Maternal Abdominal Surgery on Fetal Brain Development in the Rabbit Model.

INTRODUCTION: Anesthesia during pregnancy can impair fetal neurodevelopment, but effects of surgery remain unknown. The aim is to investigate effects of abdominal surgery on fetal brain development. Hypothesis is that surgery impairs outcome. METHODS: Pregnant rabbits were randomized at 28 days of gestation to 2 h of general anesthesia (sevoflurane group, n = 6) or to anesthesia plus laparoscopic appendectomy (surgery group, n = 13). On postnatal day 1, neurobehavior of pups was assessed and brains harvested. Primary outcome was neuron density in the frontal cortex, and secondary outcomes included neurobehavioral assessment and other histological parameters. RESULTS: Fetal survival was lower in the surgery group: 54 versus 100% litters alive at birth (p = 0.0442). In alive litters, pup survival until harvesting was 50 versus 69% (p = 0.0352). No differences were observed for primary outcome (p = 0.5114) for surviving pups. Neuron densities were significantly lower in the surgery group in the caudate nucleus (p = 0.0180), but not different in other regions. No differences were observed for secondary outcomes. Conclusions did not change after adjustment for mortality. CONCLUSION: Abdominal surgery in pregnant rabbits at a gestational age corresponding to the end of human second trimester results in limited neurohistological changes but not in neurobehavioral impairments. High intrauterine mortality limits translation to clinical scenario, where fetal mortality is close to zero.

Cardiac interventions in pregnancy and peripartum - a narrative review of the literature.

In the UK, mortality rate during pregnancy/in the peripartal period is 14.1 per 100,000 maternities with heart disease being the leading cause of non-obstetric maternal mortality (10% to 15% of all maternal deaths). Owing to the advances in the treatment of congenital heart disease (CHD), an increasing percentage of women has reached childbearing age, making CHD nowadays the most frequent cardiovascular disease during pregnancy in the Western world. In the pregnant woman, several adaptive changes occur in the cardiovascular and pulmonary system that in the worst case can lead to cardiovascular collapse in women with pre-existing heart disease. If medical management is not sufficient, cardiac interventions have to be considered, including percutaneous endovascular interventions, cardiac surgery, the use of extracorporeal membrane oxygenation or the placement of assist devices. While all these interventions seem to be relatively safe for the mother, fetal mortality remains considerably high. A thorough understanding of maternal physiology during pregnancy and of the perfusion of the feto-maternal unit is mandatory for the successful management of pregnant patients in need of cardiac (surgical) interventions.

Maternal surgery during pregnancy has a transient adverse effect on the developing fetal rabbit brain.

BACKGROUND: Recently, the US Food and Drug Administration called for cautious use of anesthetic drugs during pregnancy. In 0.2-2% of pregnancies, nonobstetric surgery is being performed. The consequences of anesthesia during pregnancy on fetal development remain unclear, and preclinical studies in relevant animal models may help to elucidate them. OBJECTIVE: To assess the effect of maternal anesthesia and surgery during pregnancy on the developing fetal brain, using a rabbit model. MATERIALS AND METHODS: This is a randomized, sham-controlled study in time-mated pregnant does at 28 days of gestation (term = 31 days), which corresponds to the end of the second trimester in humans. Anesthesia was induced in 14 does (155 pups) with propofol and maintained with 4 vol% (equivalent to 1 minimum alveolar concentration) sevoflurane for 2 hours, and a laparotomy with minimal organ manipulation was performed (surgery group). Maternal vital signs (blood pressure, heart rate, peripheral and cerebral oxygen saturation, temperature, end-tidal CO2, pH, lactate) were continuously monitored. Sham controls consisted of 7 does (74 pups) undergoing invasive hemodynamic monitoring for 2 hours without sedation. At term, does underwent cesarean delivery under ketamine-medetomidine sedation and local anesthesia. Pups either underwent motor and sensory neurologic testing followed by euthanasia at day 1 or daily neurodevelopment testing for 2 weeks and extensive neurologic assessment at 5 and 7 weeks (open field and object recognition test, T-maze, and radial-arm maze). Brains were harvested for histologic assessment of neuron density and synaptophysin expression. RESULTS: Blood gases and vital parameters were stable in both groups. On postnatal day 1, surgery pups had significant lower motor (25 ± 1 vs 23 ± 3; P = .004) and sensory (16 ± 2 vs 15 ± 2; P = .005) neurobehavioral scores and lower brain-to-body weight ratios (3.7% ± 0.6% vs 3.4% ± 0.6%; P = .001). This was accompanied by lower neuron density in multiple brain regions (eg, hippocampus 2617 ± 410 vs 2053 ± 492 neurons/mm2; P = .004) with lower proliferation rates and less synaptophysin expression. Furthermore, surgery pups had delayed motor development during the first week of life, for example with hopping appearing later (6 ± 5 vs 12 ± 3 days; P = .011). Yet, by 7 weeks of age, neurobehavioral impairment was limited to a reduced digging behavior, and no differences in neuron density or synaptophysin expression were seen. CONCLUSION: In rabbits, 2 hours of maternal general anesthesia and laparotomy, with minimal organ and no fetal manipulation, had a measurable impact on neonatal neurologic function and brain morphology. Pups had a slower motoric neurodevelopment, but by 7 weeks the effect became almost undetectable.

The effect of xenon-augmented sevoflurane anesthesia on intraoperative hemodynamics and early postoperative neurocognitive function in children undergoing cardiac catheterization: A randomized controlled pilot trial.

BACKGROUND: In adults, xenon has only minimal hemodynamic side effects when compared with other anesthetics. Moreover, in preclinical experiments, xenon has been demonstrated to possess cardio- and neuroprotective properties. Altogether, the favorable hemodynamic profile combined with its potential for organ-protection could render xenon an attractive option for anesthesia in children with cardiovascular compromise. AIMS: The aim of this study was to explore safety and feasibility of sevoflurane-augmented xenon anesthesia in school-aged children and to assess early postoperative neurocognitive effects of xenon-sevoflurane and sevoflurane anesthesia when compared to a control group that did not have anesthesia. METHODS: Forty children aged 4-12 years, suffering from congenital heart disease, undergoing diagnostic or interventional cardiac catheterization were randomized to either xenon-augmented sevoflurane anesthesia or sevoflurane alone. Safety was assessed by the incidence of intraprocedural hemodynamic instability and feasibility by anesthetic depth and respiratory profile. In addition, neurocognitive performance was assessed preoperatively, 2 hours after discharge from PACU and at 24 hours after anesthesia using the Amsterdam Neuropsychological Tasks system. A healthy control group of 22 age- and gender-matched children not exposed to anesthesia underwent an identical neurocognitive test battery, at comparable time intervals. RESULTS: Overall hemodynamics did not differ between groups. Xenon-sevoflurane anesthesia resulted in decreased intraoperative ephedrine requirements (median [IQR]) (0.00 mg/kg [0.00-0.00] vs 0.00 mg/kg [0.00-0.01], P = 0.047). Only neurocognitive tests in the domain of alertness were significantly impaired 2 hours postoperatively in both anesthesia groups in comparison with the control group (alertness variability: P = 0.02, odds ratio 5.8), but recovered at 24 hours. For working memory, inhibition, cognitive flexibility, and motor coordination tasks, no significant interaction effects of anesthesia were found in the early postoperative period. CONCLUSION: In this pilot trial, xenon-augmented sevoflurane anesthesia in school-aged children was feasible, and associated with decreased ephedrine requirements. All children exposed to anesthesia showed impaired neurocognitive performance in the immediate postoperative period when compared to control children; however, without significant differences between both treatment groups.

Xenon as an Adjuvant to Propofol Anesthesia in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery: A Pragmatic Randomized Controlled Clinical Trial.

BACKGROUND: Xenon was shown to cause less hemodynamic instability and reduce vasopressor needs during off-pump coronary artery bypass (OPCAB) surgery when compared with conventionally used anesthetics. As xenon exerts its organ protective properties even in subanesthetic concentrations, we hypothesized that in patients undergoing OPCAB surgery, 30% xenon added to general anesthesia with propofol results in superior hemodynamic stability when compared to anesthesia with propofol alone. METHODS: Fifty patients undergoing elective OPCAB surgery were randomized to receive general anesthesia with 30% xenon adjuvant to a target-controlled infusion of propofol or with propofol alone. The primary end point was the total intraoperative dose of norepinephrine required to maintain an intraoperative mean arterial pressure >70 mm Hg. Secondary outcomes included the perioperative cardiorespiratory profile and the incidence of adverse and serious adverse events. RESULTS: Adding xenon to propofol anesthesia resulted in a significant reduction of norepinephrine required to attain the predefined hemodynamic goals (cumulative intraoperative dose: median [interquartile range]: 370 [116-570] vs 840 [335-1710] µg, P = .001). In the xenon-propofol group, significantly less propofol was required to obtain a similar depth of anesthesia as judged by clinical signs and the bispectral index (propofol effect site concentration [mean ± SD]: 1.8 ± 0.5 vs 2.8 ± 0.3 mg, P≤ .0001). Moreover, the xenon-propofol group required significantly less norepinephrine during the first 24 hours on the intensive care unit (median [interquartile range]: 1.5 [0.1-7] vs 5 [2-8] mg, P = .048). Other outcomes and safety parameters were similar in both groups. CONCLUSIONS: Thirty percent xenon added to propofol anesthesia improves hemodynamic stability by decreasing norepinephrine requirements in patients undergoing OPCAB surgery.

Xenon as an adjuvant to sevoflurane anesthesia in children younger than 4 years of age, undergoing interventional or diagnostic cardiac catheterization: A randomized controlled clinical trial.

BACKGROUND: Xenon has repeatedly been demonstrated to have only minimal hemodynamic side effects when compared to other anesthetics. Moreover, in experimental models, xenon was found to be neuroprotective and devoid of developmental neurotoxicity. These properties could render xenon attractive for the anesthesia in neonates and infants with congenital heart disease. However, experience with xenon anesthesia in children is scarce. AIMS: We hypothesized that in children undergoing cardiac catheterization, general anesthesia with a combination of sevoflurane with xenon results in superior hemodynamic stability, compared to sevoflurane alone. METHODS: In this prospective, randomized, single-blinded, controlled clinical trial, children with a median age of 12 [IQR 3-36] months undergoing diagnostic/interventional cardiac catheterization were randomized to either general anesthesia with 50-65vol% xenon plus sevoflurane or sevoflurane alone. The primary outcome was the incidence of intraprocedural hemodynamic instability, defined as the occurrence of: (i) a heart rate change >20% from baseline; or (ii) a change in mean arterial blood pressure >20% from baseline; or (iii) the requirement of vasopressors, inotropes, chronotropes, or fluid boluses. Secondary endpoints included recovery characteristics, feasibility criteria, and safety (incidence of emergence agitation and postoperative vomiting. RESULTS: After inclusion of 40 children, the trial was stopped as an a priori planned blinded interim analysis revealed that the overall rate of hemodynamic instability did not differ between groups [100% in both the xenon-sevoflurane and the sevoflurane group. However, the adjuvant administration of xenon decreased vasopressor requirements, preserved better cerebral oxygen saturation, and resulted in a faster recovery. Xenon anesthesia was feasible (with no differences in the need for rescue anesthetics in both groups). CONCLUSION: Our observations suggest that combining xenon with sevoflurane in preschool children is safe, feasible, and facilitates hemodynamic management. Larger and adequately powered clinical trials are warranted to investigate the impact of xenon on short- and long-term outcomes in pediatric anesthesia.

Alizapride and ondansetron for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic gynaecological surgery: A double-blind, randomised, placebo-controlled noninferiority study.

BACKGROUND: Postoperative nausea and vomiting (PONV) can be prevented. Alizapride is an established antiemetic that may be effective in this role. OBJECTIVE: Our primary objective was to test the hypothesis that alizapride is noninferior to ondansetron for the prophylaxis of PONV. DESIGN: A randomised, placebo-controlled, double-blinded noninferiority study. SETTING: University hospitals of Leuven, Belgium, from November 2008 to July 2011. PATIENTS: A total of 523 patients undergoing laparoscopic gynaecological surgery were included in the study. Reasons for exclusion were American Society of Anesthesiologists (ASA) greater than 2, hypersensitivity to the study medication, pregnancy, mental disorders, psychiatric illness or consumption of antiemetic drugs within 24 h before initiation of the study. INTERVENTION: Patients received either alizapride 100 mg, ondansetron 4 mg or placebo intravenously 30 min before the end of surgery. MAIN OUTCOME MEASURES: The main outcome measures included the incidences of postoperative nausea (PON) and postoperative vomiting (POV) during the stay in the postanaesthetic care unit (PACU), with noninferiority testing for alizapride versus ondansetron. The region of noninferiority was defined as a relative difference in incidence of 25%. Secondary outcome was the incidence of PONV in the PACU and after 24 h. RESULTS: In the alizapride group, 32% of the patients experienced PON during the PACU stay, compared with 28% in the ondansetron group [relative risk 1.13, 90% confidence interval (CI) 0.87 to 1.46], exceeding the predefined margin of noninferiority. With respect to the incidences of POV during the PACU stay, 12.8% of the patients randomised to receive alizapride experienced POV, compared with 7.7% of who received ondansetron (relative risk 1.67, 90% CI 1.00 to 2.87). The incidences of PON and POV in the placebo group during the PACU stay were 34.2 and 9.8%, respectively. The 24-h incidences of PONV were lower than expected in this high-risk group of patients and were similar at 39.3, 36.8 and 31.5% in the placebo, alizapride and ondansetron groups, respectively (χ², P = 0.36). Patients treated with ondansetron required significantly less rescue medication than placebo-treated patients (P = 0.035). Due to the lower than expected incidences of PONV in this study, the power to conclude any noninferiority of alizapride was reduced to only 41%. CONCLUSION: We found no evidence to support the noninferiority of alizapride 100 mg when compared with ondansetron 4 mg for the intraoperative prophylaxis of PONV. However, the lower than expected incidences of PONV reduced the power of this study to conclude noninferiority or confirm significant beneficial effects for either antiemetic for PON and POV during the PACU stay. TRIAL REGISTRATION: Eudra CT 2008-004789-20.

Anesthesia for pregnant women with pulmonary hypertension.

PURPOSE OF REVIEW: Purpose of review is to summarize and highlight recent advances in the management of pregnant patients with pulmonary hypertension. RECENT FINDINGS: Despite recent advances in the therapy of pulmonary hypertension, prognosis for pregnant patients with pulmonary hypertension remains poor with high maternal mortality. Pregnancy is still considered contraindicated in these patients. If pregnancy occurs, referral to a tertiary hospital and a multidisciplinary approach ensure the best possible outcome. All pregnant patients with pulmonary hypertension should be counseled for a termination of pregnancy. If the patient wants to continue the pregnancy despite strong recommendations for therapeutic interruption, specific pulmonary hypertension therapy has to be initiated, adjusted, and/or augmented. A close clinical follow-up of the mother throughout the entire pregnancy is of utmost importance. Elective caesarean section in week 34-36 is recommended as preferred mode of delivery, preferentially under epidural or low-dose combined spinal-epidural anesthesia. Because of an acute increase in pulmonary vascular resistance and delivery-associated acute volume overload, the immediate postpartum period carries the highest risk for acute right ventricular failure necessitating close monitoring and treatment on an ICU. SUMMARY: Anesthesiologists involved in the management of pregnant patients with pulmonary hypertension must have detailed knowledge of pathophysiological alterations in pregnancy and during birth, cardiac (patho)physiology, cardiovascular and obstetric pharmacology, hemodynamic monitoring, and echocardiography. Both regional and general anesthesia have typical adverse effects that can severely jeopardize the cardiovascular system in patients with pulmonary hypertension, and should therefore be anticipated/prevented/rapidly treated by the attending anesthesiologist.

General anesthesia for caesarean section.

PURPOSE OF REVIEW: For most anaesthesiologists, the clinical experience with general anaesthesia for caesarean section is very low. General anaesthesia is mostly performed for emergency grade 1 caesarean section and due to a lack of time to apply a neuraxial anaesthesia technique. Unfortunately, the majority of anaesthesiologists rely on historical and partly outdated approaches in this stressful situation. We propose an evidence-based approach to general anaesthesia for caesarean section. RECENT FINDINGS: Rapid sequence induction using propofol and rocuronium should become the standard for general anaesthesia in the obstetric patient. Short-acting opioids are still not given routinely but should never be withheld in case of severe preeclampsia. Cricoid pressure can only be accurately performed by trained caregivers and should be released if intubation appears to be difficult. Supra-glottic airway devices may safely be used in fasted, nonobese elective caesarean section, but endotracheal intubation remains the gold standard, especially in emergency caesarean section in labouring women. Both sevoflurane and propofol are appropriate for the maintenance of general anaesthesia during caesarean section. Awareness remains a major concern in obstetric anaesthesia. SUMMARY: We present a review of recent evidence on general anaesthesia for caesarean section.

Epidural neostigmine and clonidine improves the quality of combined spinal epidural analgesia in labour: a randomised, double-blind controlled trial.

BACKGROUND: In labour analgesia, the combination of epidural clonidine and neostigmine as adjuvants to local anaesthetics and opioids is under investigation to provide a longer duration of initial spinal analgesia with local anaesthetics and/or opioids. OBJECTIVES: To evaluate the quality of analgesia with epidural neostigmine and clonidine, added to initial spinal analgesia, and to test the hypothesis that the incidence of breakthrough pain could be reduced and patient satisfaction improved. DESIGN: Randomised double-blind controlled trial. SETTING: University Hospital of Leuven in Belgium. PARTICIPANTS: One hundred healthy, term (≥37 weeks) parturients. INTERVENTION: All patients received initial spinal analgesia with ropivacaine and sufentanil. Fifteen minutes after spinal injection, 10 ml of a solution containing neostigmine 500 µg and clonidine 75 µg, or 10 ml physiological saline alone was injected epidurally. Patient-controlled analgesia with ropivacaine and sufentanil was then made available. MAIN OUTCOME MEASURES: The incidence of breakthrough pain, patient satisfaction and hourly ropivacaine use. RESULTS: Ropivacaine use decreased significantly by 32.6% in the neostigmine/clonidine (NC) group [11.6 ±â€Š4.2 vs. 17.2 ±â€Š5.3 mg h in the NC group and placebo (P) group, respectively] and a significant difference in breakthrough pain was noted; only 3% in group NC had breakthrough pain compared with 36% in group P. Patient satisfaction was better after 1 h in group NC compared with group P (P <0.05) but not different after 24 h (visual analogue scale score 97 ±â€Š5 vs. 88 ±â€Š11 mm after 1 h; 92 ±â€Š10 vs. 90 ±â€Š14 mm after 24 h). CONCLUSION: The administration of epidural clonidine and neostigmine as adjuvants, following spinal injection of local anaesthetic, improves the quality of analgesia with less ropivacaine consumption, higher patient satisfaction 1 h after administration and a decrease in breakthrough pain compared to standard combined spinal and epidural analgesia and patient-controlled epidural analgesia with ropivacaine and sufentanil.

Introduction and history of anaesthesia-induced neurotoxicity and overview of animal models.

Brain development is initiated at around 3 weeks of gestation. The peak velocity of brain weight gain occurs around birth, with the neural circuitry subsequently being refined until at least 20 years of age. Antenatal and postnatal general anaesthesia suppresses neuronal firing during this critical period and may therefore impair brain development, referred to as "anaesthesia-induced neurotoxicity". Whilst up to 1% of children are exposed to general anaesthesia antenatally (e.g., as an innocent bystander to maternal laparoscopic appendectomy), 15% of children under 3 years of age undergo general anaesthesia postnatally (e.g., otorhinolaryngologic surgery). In this article, the history of preclinical and clinical research in anaesthesia-induced neurotoxicity will be reviewed, starting from the pioneering preclinical study in 1999 until the most recent systematic reviews. The mechanisms of anaesthesia-induced neurotoxicity are introduced. Finally, an overview of the methods used in preclinical studies will be provided, with a comparison of the different animal models that have been employed to investigate this phenomenon.