Pre-operative femoral nerve block for hip fracture-A systematic review with meta-analysis.

BACKGROUND: Pre-operative pain management of hip fracture patients is complex. Femoral nerve block (FNB) is used for hip fractures to reduce pain and demand for systematic analgesia. The objective of the study was to systematically investigate the efficacy of single-shot FNB for hip fracture patients. METHODS: Five databases were searched from inception until 8 May 2019. We included randomized controlled trials (RCT's) assessing pain relief in patients with hip fractures. Intervention was pre-operative FNB compared to any systemic analgesic (eg opioids, non-steroidal anti-inflammatory drugs or paracetamol). Primary outcomes assessed were pre-operative pain and use of rescue analgesics. Secondary outcome was cognitive impairment. We present a bias assessment, a meta-analysis and a grading of certainty of evidence. RESULTS: We included five trials (n = 254), where participants received FNB 30 minutes or more prior to surgery; all were judged as having high risk of bias. All studies found significantly decreased pain scores at least once in the intervention group compared to the control group. Meta-analysis on the primary outcome of pain showed significance. Mean difference was -2.13 point (in cm) (CI:-3.53,-0.72) on visual analogue scale in the intervention group, but is judged low on certainty. CONCLUSIONS: The quantity of evidence supporting pre-operative single-shot FNB for hip fractures is very low, and the certainty of evidence supporting pre-operative single-shot FNB for hip fractures is low. No studies using ultrasound guided technique were identified. Data on non-ultrasound guided FNB's suggest a decreased pain score compared to the use of systemic analgesia.

Butyrylcholinesterase deficiency and its clinical importance in anaesthesia: a systematic review.

Butyrylcholinesterase deficiency prolongs the effects of the drugs it degrades; succinylcholine and mivacurium. Existing literature on butyrylcholinesterase deficiency is dominated by genetic and biochemical studies. We searched MEDLINE, Embase, Web of Science and Biosis to systematically review the causes and clinical consequences of butyrylcholinesterase deficiency. We considered outcomes clinically relevant if neuromuscular blockade, induced by succinylcholine or mivacurium, was assessed using clinical criteria or neuromuscular monitoring. We included 66 studies: 25 randomised controlled trials; 13 clinically controlled trials; 26 prospective observational studies; 1 retrospective study; and 1 qualitative study. Data heterogeneity precluded quantitative synthesis. Studies described genetic, physiological, acquired or pharmacologically induced causes of butyrylcholinesterase deficiency. The prolongation of neuromuscular blockade by butyrylcholinesterase deficiency was most pronounced with homozygosity of a genetic variant, but other more common factors included increasing age, pregnancy, severe liver disease, burn injuries and drug interactions.

Systematic review of the effects of fascia iliaca compartment block on hip fracture patients before operation.

BACKGROUND: Fascia iliaca compartment block is used for hip fractures in order to reduce pain, the need for systemic analgesia, and prevent delirium, on this basis. This systematic review was conducted to investigate the analgesic and adverse effects of fascia iliaca block on hip fracture in adults when applied before operation. METHODS: Nine databases were searched from inception until July 2016 yielding 11 randomised and quasi-randomised controlled trials, all using loss of resistance fascia iliaca compartment block, with a total population of 1062 patients. Meta-analyses were conducted comparing the analgesic effect of fascia iliaca compartment block on nonsteroidal anti-inflammatory drugs (NSAIDs), opioids and other nerve blocks, preoperative analgesia consumption, and time to perform spinal anaesthesia compared with opioids and time for block placement. RESULTS: The analgesic effect of fascia iliaca compartment block was superior to that of opioids during movement, resulted in lower preoperative analgesia consumption and a longer time for first request, and reduced time to perform spinal anaesthesia. Block success rate was high and there were very few adverse effects. There is insufficient evidence to conclude anything on preoperative analgesic consumption or first request thereof compared with NSAIDs and other nerve blocks, postoperative analgesic consumption for preoperatively applied fascia iliaca compartment block compared with NSAIDs, opioids and other nerve blocks, incidence and severity of delirium, and length of stay or mortality. CONCLUSIONS: Fascia iliaca compartment block is an effective and relatively safe supplement in the preoperative pain management of hip fracture patients.

Effects of avoidance or use of neuromuscular blocking agents on outcomes in tracheal intubation: a Cochrane systematic review.

Cohort studies have indicated that avoidance of neuromuscular blocking agents (NMBA) is a risk factor for difficult tracheal intubation. However, the impact of avoiding NMBA on tracheal intubation, possible adverse effects, and postoperative discomfort has not been evaluated in a systematic review of randomised trials. We searched several databases for trials published until January 2017. We included randomised controlled trials comparing the effect of avoiding vs using NMBA. Two independent authors assessed risk of bias and extracted data. The risk of random errors was assessed by trial sequential analysis (TSA). We included 34 trials (3565 participants). In the four trials judged to have low risk of bias, there was an increased risk of difficult tracheal intubation with no use of NMBA [random-effects model, risk ratio (RR) 13.27, 95% confidence interval (CI) 8.19-21.49, P<0.00001, TSA-adjusted CI 1.85-95.04]. The result was confirmed when including all trials, (RR 5.00, 95% CI 3.49-7.15, P<0.00001, TSA-adjusted CI 1.20-20.77). There was a significant risk of upper airway discomfort or injury by avoiding NMBA (RR=1.37, 95% CI 1.09-1.74, P=0.008, TSA-adjusted CI 1.00-1.86). None of the trials reported mortality. Avoiding NMBA was significantly associated with difficult laryngoscopy, (RR 2.54, 95% CI 1.53-4.21, P=0.0003, TSA-adjusted CI 0.27-21.75). In a clinical context, one must balance arguments for using NMBA when performing tracheal intubation.

A systematic review and consensus definitions for standardised end-points in perioperative medicine: pulmonary complications.

BACKGROUND: There is a need for robust, clearly defined, patient-relevant outcome measures for use in randomised trials in perioperative medicine. Our objective was to establish standard outcome measures for postoperative pulmonary complications research. METHODS: A systematic literature search was conducted using MEDLINE, Web of Science, SciELO, and the Korean Journal Database. Definitions were extracted from included manuscripts. We then conducted a three-stage Delphi consensus process to select the optimal outcome measures in terms of methodological quality and overall suitability for perioperative trials. RESULTS: From 2358 records, the full texts of 81 manuscripts were retrieved, of which 45 met the inclusion criteria. We identified three main categories of outcome measure specific to perioperative pulmonary outcomes: (i) composite outcome measures of multiple pulmonary outcomes (27 definitions); (ii) pneumonia (12 definitions); and (iii) respiratory failure (six definitions). These were rated by the group according to suitability for routine use. The majority of definitions were given a low score, and many were imprecise, difficult to apply consistently, or both, in large patient populations. A small number of highly rated definitions were identified as appropriate for widespread use. The group then recommended four outcome measures for future use, including one new definition. CONCLUSIONS: A large number of postoperative pulmonary outcome measures have been used, but most are poorly defined. Our four recommended outcome measures include a new definition of postoperative pulmonary complications, incorporating an assessment of severity. These definitions will meet the needs of most clinical effectiveness trials of treatments to improve postoperative pulmonary outcomes.

Peripheral nerve block in ankle fracture surgery: a qualitative study of patients' experiences.

Peripheral nerve blocks are popular as a mode of anaesthesia for limb surgery and their beneficial effects are well documented in elective surgery. However, concerns have been raised about potential rebound pain outweighing the benefits in acute ankle fracture surgery. Furthermore, pain scores and morphine consumption do not provide a full picture, as pain is subjective. To evaluate the clinical usefulness of peripheral nerve blocks, we explored patients' expectations and experiences by means of semi-structured interviews analysed with systematic text condensation. We obtained ethical approval and informed consent and sampled purposively among adult patients scheduled for ankle surgery with nerve blocks as the primary mode of anaesthesia. Patients were interviewed within 48 h postoperatively. Data saturation was reached after 13 interviews. We found that, despite pre-emptive ibuprofen and paracetamol, some patients did experience excruciating rebound pain for up to 2 h, although most had little or no pain. The patients had doubts about what to do when the block wore off, which led to a risk of unnecessary pain levels or morphine overuse. Patients had difficulty understanding the effect and course of the nerve blocks. They had misunderstandings regarding the blocks' effect on sensation, resulting in fear of feeling pain during surgery and of permanent nerve damage after surgery. However, patients valued the mental alertness, ability to ambulate and efficient pain relief provided by the blocks. We recommend that patients be given thorough and repeated information as we feel this is crucial in preventing undesirable responses from patients, and is likely to increase the overall clinical usefulness of nerve blocks in acute limb surgery.

The impact of lifestyle risk factors on the rate of infection after surgery for a fracture of the ankle.

AIMS: Lifestyle risk factors are thought to increase the risk of infection after acute orthopaedic surgery but the evidence is scarce. We aimed to investigate whether smoking, obesity and alcohol overuse are risk factors for the development of infections after surgery for a fracture of the ankle. PATIENTS AND METHODS: We retrospectively reviewed all patients who underwent internal fixation of a fracture of the ankle between 2008 and 2013. The primary outcome was the rate of deep infection and the secondary outcome was any surgical site infection (SSI). Associations with the risk factors and possible confounding variables were analysed univariably and multivariably with backwards elimination. RESULTS: A total of 1043 patients were included; 64 (6.1%) had a deep infection and 146 (14.0%) had SSI. Obesity was strongly associated with both outcomes (odds ratio (OR) 2.21, p = 0.017 and OR 1.68, p = 0.032) in all analyses. Alcohol overuse was similarly associated, though significant only in unadjusted analyses. Surprisingly, smoking did not yield statistically significant associations with infections. CONCLUSION: These findings suggest that obesity and possibly alcohol overuse are independent risk factors for the development of infection following surgery for a fracture of the ankle. This large study brings new evidence concerning these common risk factors; although prospective studies are needed to confirm causality. Cite this article: Bone Joint J 2017;99-B:225-30.

Thromboelastography (TEG) or rotational thromboelastometry (ROTEM) to monitor haemostatic treatment in bleeding patients: a systematic review with meta-analysis and trial sequential analysis.

Coagulopathy and severe bleeding are associated with high mortality. We evaluated haemostatic treatment guided by the functional viscoelastic haemostatic assays, thromboelastography or rotational thromboelastometry in bleeding patients. We searched for randomised, controlled trials irrespective of publication status, publication date, blinding status, outcomes published or language from date of inception to 5 January 2016 in six bibliographic databases. We included 17 trials (1493 participants), most involving cardiac surgery. Thromboelastography or rotational thromboelastometry seemed to reduce overall mortality compared to any of our comparisons (3.9% vs. 7.4%, RR (95% CI) 0.52 (0.28-0.95); I2 = 0%, 8 trials, 717 participants). However, the quality of evidence is graded as low due to the high risk of bias, heterogeneity, imprecision and low event rate. Thromboelastography or rotational thromboelastometry significantly reduced the proportion of patients transfused with red blood cells (RR (95% CI) 0.86 (0.79-0.94); I2 = 0%, 10 trials, 832 participants), fresh frozen plasma (RR (95% CI) 0.57 (0.33-0.96); I2 = 86%, 10 trials, 832 participants) and platelets (RR (95% CI) 0.73 (0.60-0.88); I2 = 0%, 10 studies, 832 participants). There was no difference in proportion needing surgical re-interventions (RR (95% CI) 0.75 (0.50-1.10); I2 = 0%, 9 trials, 887 participants). Trial sequential analysis of mortality suggests that only 54% of the required information size has been reached so far. Transfusion strategies guided by thromboelastography or rotational thromboelastometry may reduce the need for blood products in patients with bleeding, but the results are mainly based on trials of elective cardiac surgery involving cardiopulmonary bypass, with low-quality evidence.

High-content analysis of factors affecting gold nanoparticle uptake by neuronal and microglial cells in culture.

Owing to their ubiquitous distribution, expected beneficial effects and suspected adverse effects, nanoparticles are viewed as a double-edged sword, necessitating a better understanding of their interactions with tissues and organisms. Thus, the goals of the present study were to develop and present a method to generate quantitative data on nanoparticle entry into cells in culture and to exemplarily demonstrate the usefulness of this approach by analyzing the impact of size, charge and various proteinaceous coatings on particle internalization. N9 microglial cells and both undifferentiated and differentiated SH-SY5Y neuroblastoma cells were exposed to customized gold nanoparticles. After silver enhancement, the particles were visualized by epipolarization microscopy and analysed by high-content analysis. The value of this approach was substantiated by assessing the impact of various parameters on nanoparticle uptake. Uptake was higher in microglial cells than in neuronal cells. Only microglial cells showed a distinct size preference, preferring particles with a diameter of 80 nm. Positive surface charge had the greatest impact on particle uptake. Coating with bovine serum albumin, fetuin or protein G significantly increased particle internalization in microglial cells but not in neuronal cells. Coating with wheat germ agglutinin increased particle uptake in both N9 and differentiated SH-SY5Y cells but not in undifferentiated SH-SY5Y cells. Furthermore, internalization was shown to be an active process and indicators of caspase-dependent apoptosis revealed that gold nanoparticles did not have any cytotoxic effects. The present study thus demonstrates the suitability of gold nanoparticles and high-content analysis for assessing numerous variables in a stringently quantitative and statistically significant manner. Furthermore, the results presented herein showcase the feasibility of specifically targeting nanoparticles to distinct cell types.

Post-anaesthetic emergence delirium in adults: incidence, predictors and consequences.

BACKGROUND: Emergence delirium (ED) after general anaesthesia (GA) is a well-known phenomenon, yet the risk factors are still unclear. The aims of this study were to determine the incidence and independent predictors of ED and secondly to determine to which degree ED has any relevant, clinical consequences to medical staff as well as to patients. METHOD: This prospective, observational cohort study assessed adult patients emerging from GA in the operating room, using the Richmond Agitation-Sedation Scale (RASS). Signs of ED, defined as RASS≥1 along with possible clinical consequences were noted. Patients with ED were re-evaluated in the post-anaesthesia care unit (PACU) and concomitant patient and anaesthesia related factors were noted. RESULTS: Among the 1970 patients enrolled, 73 (3.7%) showed signs of ED when emerging from anaesthesia. When reassessed in PACU, the number had declined to 25 patients (1.3%). Male sex, endotracheal tube (ETT) and volatile anaesthetics were found to be significantly related to developing ED after anaesthesia. In 20 cases, additional staff had to be called for and in one case, an i.v. access was accidentally removed. Neither patients nor staff were hurt. CONCLUSION: Male sex, volatile anaesthetics and ETT were factors significantly related to ED. Whether gender, choice of respiratory devices and anaesthetics are true predictors or derived factors of surgery procedures, duration of surgery and the patients' physical condition need further investigation. The most notable clinical consequence of ED was the need of additional staff in order to restrain the agitated patient.

Multidisciplinary team training reduces the decision-to-delivery interval for emergency Caesarean section.

BACKGROUND: Emergency Caesarean section is performed when the life of the pregnant woman and/or the foetus is considered at risk. A 30-min standard for the decision-to-delivery interval (DDI) is a common practice and is supported by national organisations including The Danish Society of Obstetrics and Gynaecology. Danish obstetric departments report the DDI to a national database. A national arbitrarily set standard recommends that 95% of ECSs should be achieved within the 30-min DDI standard. In 2011, 34.4% of ECSs, performed at our hospital, were achieved within the 30-min time frame. This study aims to evaluate the effect of a simulation-based team training programme on the proportion of ECSs achieved within a 30-min time frame. METHOD: We performed an interventional before-and-after study. We evaluated a total of one hundred 30-min ECSs before and after the intervention. The primary outcome of interest was the proportion of 30-min ECSs achieved within a 30-min time frame. RESULTS: A total of 20 team training courses were held during May/June 2013. These courses trained 239 of 252 team members (comprised of: 36 obstetricians, 45 scrub nurses, 83 midwives, 38 anaesthesiologists, 37 nurse anaesthetists) in handling of 30-min ECS. This corresponds to 95% of staff. The proportion of 30-min ECSs achieved within a 30-min time frame was higher after team training (87.5%, 95% CI 79.2-93.4%) compared with before training (74.0%, 95% CI 64.0-82.4%) (P = 0.017). CONCLUSION: Team training may contribute positively to an increase in the proportion of ECSs achieved within a 30-min time frame.

Transversus abdominis plane (TAP) block after robot-assisted laparoscopic hysterectomy: a randomised clinical trial.

BACKGROUND: Transversus abdominis plane (TAP) block is widely used as a part of pain management after various abdominal surgeries. We evaluated the effect of TAP block as an add-on to the routine analgesic regimen in patients undergoing robot-assisted laparoscopic hysterectomy. METHODS: In a prospective blinded study, 70 patients scheduled for elective robot-assisted laparoscopic hysterectomy were randomised to receive either TAP block (ropivacaine 0.5%, 20 ml on each side) or sham block (isotonic saline 0.9%, 20 ml on each side). All patients had patient-controlled analgesia (PCA) with morphine on top of paracetamol and ibuprofen or diclofenac. For the first 24 post-operative hours, we monitored PCA morphine consumption and pain scores with visual analogue scale (VAS) at rest and while coughing. Post-operative nausea and number of vomits (PONV) were recorded. RESULTS: Sixty-five patients completed the study, 34 receiving TAP block with ropivacaine and 31 receiving sham block with isotonic saline. We found no differences in median (interquartile range) morphine consumption the first 24 h between the TAP block group [17.5 mg (6.9-36.0 mg)] and the placebo group [17.5 mg (2.9-38.0 mg)] (95% confidence interval 10.0-22.6 mg, P = 0.648). No differences were found for VAS scores between the two groups, calculated as area under the curve/1-24 h, neither at rest (P = 0.112) nor while coughing (P = 0.345), or for PONV between groups. CONCLUSIONS: In our study, the TAP block combined with paracetamol and Nonsteroidal anti-inflammatory drugs (NSAID) treatment, had no effect on morphine consumption, VAS pain scores, or frequency of nausea and vomiting after robot-assisted laparoscopic hysterectomy compared with paracetamol and NSAID alone.

Randomized multicentre feasibility trial of intermediate care versus standard ward care after emergency abdominal surgery (InCare trial).

BACKGROUND: Emergency abdominal surgery carries a considerable risk of death and postoperative complications. Early detection and timely management of complications may reduce mortality. The aim was to evaluate the effect and feasibility of intermediate care compared with standard ward care in patients who had emergency abdominal surgery. METHODS: This was a randomized clinical trial carried out in seven Danish hospitals. Eligible for inclusion were patients with an Acute Physiology And Chronic Health Evaluation (APACHE) II score of at least 10 who were ready to be transferred to the surgical ward within 24 h of emergency abdominal surgery. Participants were randomized to either intermediate care or standard surgical ward care after surgery. The primary outcome was 30-day mortality. RESULTS: In total, 286 patients were included in the modified intention-to-treat analysis. The trial was terminated after the interim analysis owing to slow recruitment and a lower than expected mortality rate. Eleven (7·6 per cent) of 144 patients assigned to intermediate care and 12 (8·5 per cent) of 142 patients assigned to ward care died within 30 days of surgery (odds ratio 0·91, 95 per cent c.i. 0·38 to 2·16; P = 0·828). Thirty (20·8 per cent) of 144 patients assigned to intermediate care and 37 (26·1 per cent) of 142 assigned to ward care died within the total observation period (hazard ratio 0·78, 95 per cent c.i. 0·48 to 1·26; P = 0·310). CONCLUSION: Postoperative intermediate care had no statistically significant effect on 30-day mortality after emergency abdominal surgery, nor any effect on secondary outcomes. The trial was stopped prematurely owing to slow recruitment and a much lower than expected mortality rate among the enrolled patients. REGISTRATION NUMBER: NCT01209663 (http://www.clinicaltrials.gov).

Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.

BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Mortality and postoperative care pathways after emergency gastrointestinal surgery in 2904 patients: a population-based cohort study.

BACKGROUND: Emergency major gastrointestinal (GI) surgery carries a considerable risk of mortality and postoperative complications. Effective management of complications and appropriate organization of postoperative care may improve outcome. The importance of the latter is poorly described in emergency GI surgical patients. We aimed to present mortality data and evaluate the postoperative care pathways used after emergency GI surgery. METHODS: A population-based cohort study with prospectively collected data from six Capital Region hospitals in Denmark. We included 2904 patients undergoing major GI laparotomy or laparoscopy surgery between January 1, 2009, and December 31, 2010. The primary outcome measure was 30 day mortality. RESULTS: A total of 538 patients [18.5%, 95% confidence interval (CI): 17.1-19.9] died within 30 days of surgery. In all, 84.2% of the patients were treated after operation in the standard ward, with a 30 day mortality of 14.3%, and 4.8% were admitted to the intensive care unit (ICU) after a median stay of 2 days (inter-quartile range: 1-6). When compared with 'admission to standard ward', 'admission to standard ward before ICU admission' and 'ICU admission after surgery' were independently associated with 30 day mortality; odds ratio 5.45 (95% CI: 3.48-8.56) and 3.27 (95% CI: 2.45-4.36), respectively. CONCLUSIONS: Mortality in emergency major GI surgical patients remains high. Failure to allocate patients to the appropriate level of care immediately after surgery may contribute to the high postoperative mortality. Future research should focus on improving risk stratification and evaluating the effect of different postoperative care pathways in emergency GI surgery.

Does anaesthesia with nitrous oxide affect mortality or cardiovascular morbidity? A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: The role of nitrous oxide in modern anaesthetic practice is contentious. One concern is that exposure to nitrous oxide may increase the risk of cardiovascular complications. ENIGMA II is a large randomized clinical trial currently underway which is investigating nitrous oxide and cardiovascular complications. Before the completion of this trial, we performed a systematic review and meta-analysis, using Cochrane methodology, on the outcomes that make up the composite primary outcome. METHODS: We used conventional meta-analysis and trial sequential analysis (TSA). We reviewed 8282 abstracts and selected 138 that fulfilled our criteria for study type, population, and intervention. We attempted to contact the authors of all the selected publications to check for unpublished outcome data. RESULTS: Thirteen trials had outcome data eligible for our outcomes. We assessed three of these trials as having a low risk of bias. Using conventional meta-analysis, the relative risk of short-term mortality in the nitrous oxide group was 1.38 [95% confidence interval (CI) 0.22-8.71] and the relative risk of long-term mortality in the nitrous oxide group was 0.94 (95% CI 0.80-1.10). In both cases, TSA demonstrated that the data were far too sparse to make any conclusions. There were insufficient data to perform meta-analysis for stroke, myocardial infarct, pulmonary embolus, or cardiac arrest. CONCLUSION: This systematic review demonstrated that we currently do not have robust evidence for how nitrous oxide used as part of general anaesthesia affects mortality and cardiovascular complications.

Induction of cytochrome P450 enzymes in primary equine hepatocyte culture.

In this study, we established cell culture conditions for primary equine hepatocytes allowing cytochrome P450 enzyme (CYP) induction experiments. Hepatocytes were isolated after a modified method of Bakala et al. (2003) and cultivated on collagen I coated plates. Three different media were compared for their influence on morphology, viability and CYP activity of the hepatocytes. CYP activity was evaluated with the fluorescent substrate 7-benzyloxy-4-trifluoromethylcoumarin. Induction experiments were carried out with rifampicin, dexamethasone or phenobarbital. Concentration-response curves for induction with rifampicin were created. Williams' medium E showed the best results on morphology and viability of the hepatocytes and was therefore used for the following induction experiments. Cells cultured in Dulbecco's Modified Eagle Medium were not inducible. Incubation with rifampicin increased the CYP activity in two different hepatocyte preparations in a dose dependent manner (EC50=1.20 µM and 6.06 µM; Emax=4.1- and 3.4-fold induction). No increase in CYP activity was detected after incubation with dexamethasone or phenobarbital. The hepatocyte culture conditions established in this study proved to be valuable for investigation of the induction of equine CYPs. In further studies, other equine drugs can be evaluated for CYP induction with this in vitro system.

Elective caesarean section at 38 weeks versus 39 weeks: neonatal and maternal outcomes in a randomised controlled trial.

OBJECTIVES: To investigate whether elective caesarean section before 39 completed weeks of gestation increases the risk of adverse neonatal or maternal outcomes. DESIGN: Randomised controlled multicentre open-label trial. SETTING: Seven Danish tertiary hospitals from March 2009 to June 2011. POPULATION: Women with uncomplicated pregnancies, a single fetus, and a date of delivery estimated by ultrasound scheduled for delivery by elective caesarean section. METHODS: Perinatal outcomes after elective caesarean section scheduled at a gestational age of 38 weeks and 3 days versus 39 weeks and 3 days (in both groups ±2 days). MAIN OUTCOME MEASURES: The primary outcome was neonatal intensive care unit (NICU) admission within 48 hours of birth. Secondary outcomes were neonatal depression, NICU admission within 7 days, NICU length of stay, neonatal treatment, and maternal surgical or postpartum adverse events. RESULTS: Among women scheduled for elective caesarean section at 38⁺³ weeks 88/635 neonates (13.9%) were admitted to the NICU, whereas in the 39⁺³ weeks group 76/637 neonates (11.9%) were admitted (relative risk [RR] 0.86, 95% confidence interval [95% CI] 0.65-1.15). Neonatal treatment with continuous oxygen for more than 1 day (RR 0.31; 95% CI 0.10-0.94) and maternal bleeding of more than 500 ml (RR 0.79; 95% CI 0.63-0.99) were less frequent in the 39 weeks group, but these findings were insignificant after adjustment for multiple comparisons. The risk of adverse neonatal or maternal outcomes, or a maternal composite outcome (RR 1.1; 95% CI 0.79-1.53) was similar in the two intervention groups. CONCLUSIONS: This study found no significant reduction in neonatal admission rate after ECS scheduled at 39 weeks compared with 38 weeks of gestation.