Efficacy of locoregional analgesic techniques after laparotomy for gynecologic cancer: a systematic review.

OBJECTIVE: To determine which locoregional techniques are effective in managing post-operative pain in major open oncologic gynecologic surgery in terms of pain scores and opioid consumption when epidural analgesia is not a feasible option. METHODS: A systematic review of the literature, based on the Preferred Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, was conducted. The ROB-2 assessment was used to assess bias. The primary outcomes were opioid consumption and post-operative pain scores. Secondary outcomes included post-operative markers such as time to mobilization and bowel movement. RESULTS: A total of nine studies (n=714) were included in the analysis. Eight studies had a low risk of bias. Five different forms of locoregional analgesia were described. Eight studies compared with placebo and one study compared rectus sheath block with epidural analgesia. Three of the five studies investigating transversus abdominis plane (TAP) blocks showed an improvement in pain scores and opioid consumption when compared with the placebo group. One study investigating rectus sheath blocks and another investigating paravertebral blocks demonstrated significantly less opioid consumption and improved pain scores at certain time points. The studies investigating continuous wound infiltration and superior hypogastric plexus block found no significant effect. No adverse effects of locoregional anesthesia were found. CONCLUSION: Our study showed that TAP blocks, rectus sheath blocks, and paravertebral blocks may decrease opioid consumption and improve pain scores in patients undergoing open abdominal surgery for gynecologic cancer. Additionally, these techniques might serve as a viable alternative for patients with contraindications to epidural analgesia.

Perioperative transfusion study (PETS): Does a liberal transfusion protocol improve outcome in high-risk cardiovascular patients undergoing non-cardiac surgery? A randomised controlled pilot study.

BACKGROUND: Small studies have shown that patients with advanced coronary artery disease might benefit from a more liberal blood transfusion strategy. The goal of this pilot study was to test the feasibility of a blood transfusion intervention in a group of vascular surgery patients who have elevated cardiac troponins in rest. METHODS: We conducted a single-centre, randomised controlled pilot study. Patients with a preoperative elevated high-sensitive troponin T undergoing non-cardiac vascular surgery were randomised between a liberal transfusion regime (haemoglobin >10.4 g/dL) and a restrictive transfusion regime (haemoglobin 8.0-9.6 g/dL) during the first 3 days after surgery. The primary outcome was defined as a composite endpoint of all-cause mortality, myocardial infarction or unscheduled coronary revascularization. RESULTS: In total 499 patients were screened; 92 were included and 50 patients were randomised. Postoperative haemoglobin was different between the intervention and control group; 10.6 versus 9.8, 10.4 versus 9.4, 10.9 versus 9.4 g/dL on day one, two and three respectively (p < 0.05). The primary outcome occurred in four patients (16%) in the liberal transfusion group and in two patients (8%) in control group. CONCLUSION: This pilot study shows that the studied transfusion protocol was able to create a clinically significant difference in perioperative haemoglobin levels. Randomisation was possible in 10% of the screened patients. A large definitive trial should be possible to provide evidence whether a liberal transfusion strategy could decrease the incidence of postoperative myocardial infarction in high risk surgical patients.

Spontaneous recovery from neuromuscular block after a single dose of a muscle relaxant in pediatric patients: A systematic review using a network meta-analytic and meta-regression approach.

BACKGROUND: Age-related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put pediatric patients at risk of postoperative residual curarization (PORC). To date, the duration of neuromuscular blocking agent effect in children has not been analyzed in a quantitative review. The current meta-analysis aimed to compare spontaneous recovery following administration of various types and doses of neuromuscular blocking agents and to quantify the effect of prognostic variables associated with the recovery time in pediatric patients. METHOD: We searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25-75), and to ≥90% train-of-four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25-75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random-effects network and pairwise meta-analyses along with meta-regression were used to evaluate the results. RESULTS: We used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta-analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25-75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log-linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2-11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d-12 M), respectively. We found a negative log-linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance. CONCLUSIONS: The times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent.

Prognostic models for outcome prediction following in-hospital cardiac arrest using pre-arrest factors: a systematic review, meta-analysis and critical appraisal.

BACKGROUND: Several prediction models of survival after in-hospital cardiac arrest (IHCA) have been published, but no overview of model performance and external validation exists. We performed a systematic review of the available prognostic models for outcome prediction of attempted resuscitation for IHCA using pre-arrest factors to enhance clinical decision-making through improved outcome prediction. METHODS: This systematic review followed the CHARMS and PRISMA guidelines. Medline, Embase, Web of Science were searched up to October 2021. Studies developing, updating or validating a prediction model with pre-arrest factors for any potential clinical outcome of attempted resuscitation for IHCA were included. Studies were appraised critically according to the PROBAST checklist. A random-effects meta-analysis was performed to pool AUROC values of externally validated models. RESULTS: Out of 2678 initial articles screened, 33 studies were included in this systematic review: 16 model development studies, 5 model updating studies and 12 model validation studies. The most frequently included pre-arrest factors included age, functional status, (metastatic) malignancy, heart disease, cerebrovascular events, respiratory, renal or hepatic insufficiency, hypotension and sepsis. Only six of the developed models have been independently validated in external populations. The GO-FAR score showed the best performance with a pooled AUROC of 0.78 (95% CI 0.69-0.85), versus 0.59 (95%CI 0.50-0.68) for the PAM and 0.62 (95% CI 0.49-0.74) for the PAR. CONCLUSIONS: Several prognostic models for clinical outcome after attempted resuscitation for IHCA have been published. Most have a moderate risk of bias and have not been validated externally. The GO-FAR score showed the most acceptable performance. Future research should focus on updating existing models for use in clinical settings, specifically pre-arrest counselling. Systematic review registration PROSPERO CRD42021269235. Registered 21 July 2021.

A Systematic Review on Long-Term Postsurgical Pain Outcomes; What Is the Effect of Upper Extremity Regional Anesthesia?

BACKGROUND: Chronic pain is a recognized complication of surgery, and it has been hypothesized that regional anesthesia might reduce the risk of development of chronic pain after upper extremity surgery. METHODS: A systematic literature review was performed to assess whether in patients undergoing elective upper extremity surgery (P), regional anesthesia (I), compared to general anesthesia (C), would result in lower long-term (>3 months) postoperative pain intensity (O). We included randomized and nonrandomized controlled trials (RCTs). Our primary outcome was numerical rating score or visual analogue scale for pain, at >3 months postoperatively. The Embase, Medline ALL, Web of Science Core Collections, Cochrane Central Register of Controlled Trials, and Google Scholar databases were searched for all reports assessing pain at >3 months after upper extremity surgery under general versus regional anesthesia. Secondary outcomes were: opioid prescription filling, complex regional pain syndrome (CRPS) incidence, the Mayo Wrist Score (MWS), and scores on the Disability of the Arm, Shoulder and Hand (DASH) questionnaire. Quality (or certainty) of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Risk-of-bias was assessed using the Cochrane tool for randomized trials (RoB 2.0) and nonrandomized trials (ROBINS-I). RESULTS: This review included 14 studies, comprising 7 RCTs and 7 nonrandomized studies. Six of the 7 studies (4 RCTs, N = 273; 2 nonrandomized studies, N = 305) using a pain score, our primary outcome, report comparable long-term postoperative pain scores after regional and general anesthesia. Six of the 7 studies using our secondary outcomes report comparable long-term outcomes in terms of opioid prescription filling (2 retrospective cohort studies [RCSs], N = 89,256), CRPS incidence (1 RCT, N = 301), MWS (1 RCT and 1 RCS, N = 215), and DASH score (1 RCT, N = 36). Comparable outcomes were reported in all 7 RCTs (N = 778) and in 5 of the 7 nonrandomized studies, comprising 5 RCSs (N = 89,608). Two prospective observational studies (POSTs), comprising 279 patients, report a statistically significant difference in outcomes, with less pain and better DASH scores after brachial plexus anesthesia. All 14 studies provided moderate to very low certainty evidence, and there was a serious risk of bias due to confounding bias in 5 of the 7 nonrandomized studies (N = 631). CONCLUSIONS: The results of this review indicate that upper extremity regional anesthesia, compared to general anesthesia, is unlikely to change pain intensity at >3 months postoperatively.

Alternatives to the in-person anaesthetist-led preoperative assessment in adults undergoing low-risk or intermediate-risk surgery: A scoping review.

BACKGROUND: The design of the optimal preoperative evaluation is a much debated topic, with the anaesthetist-led in-person evaluation being most widely used. This approach is possibly leading to overuse of a valuable resource, especially in low-risk patients. Without compromising patient safety, we hypothesised that not all patients would require this type of elaborate evaluation. OBJECTIVE: The current scoping review aims to critically appraise the range and nature of the existing literature investigating alternatives to the anaesthetist-led preoperative evaluation and their impact on outcomes, to inform future knowledge translation and ultimately improve perioperative clinical practice. DESIGN: A scoping review of the available literature. DATA SOURCES: Embase, Medline, Web-of-Science, Cochrane Library and Google Scholar. No date restriction was used. ELIGIBILITY CRITERIA: Studies in patients scheduled for elective low-risk or intermediate-risk surgery, which compared anaesthetist-led in-person preoperative evaluation with non-anaesthetist-led preoperative evaluation or no outpatient evaluation. The focus was on outcomes, including surgical cancellation, perioperative complications, patient satisfaction and costs. RESULTS: Twenty-six studies with a total of 361 719 patients were included, reporting on various interventions: telephone evaluation, telemedicine evaluation, evaluation by questionnaire, surgeon-led evaluation, nurse-led evaluation, other types of evaluation and no evaluation up to the day of surgery. Most studies were conducted in the United States and were either pre/post or one group post-test-only studies, with only two randomised controlled trials. Studies differed largely in outcome measures and were of moderate quality overall. CONCLUSIONS: A number of alternatives to the anaesthetists-led in-person preoperative evaluation have already been researched: that is telephone evaluation, telemedicine evaluation, evaluation by questionnaire and nurse-led evaluation. However, more high-quality research is needed to assess viability in terms of intraoperative or early postoperative complications, surgical cancellation, costs, and patient satisfaction in the form of Patient-Reported Outcome Measures and Patient-Reported Experience Measures.

Perioperative Mortality in Pediatric Patients: A Systematic Review of Risk Assessment Tools for Use in the Preoperative Setting.

BACKGROUND: There are multiple preoperative risk scores for pediatric mortality. The aim of this study was to systematically describe and compare the existing studies of patient-specific multispecialty risk prediction scores for perioperative mortality in pediatric populations, with the goal of guiding clinicians on which may be most appropriate for use in the preoperative setting. METHODS: This study is a systematic literature review of published journal articles that presented the development, extension/updating, and/or validation of a risk core that predicted all-cause mortality (up to 30 days postoperatively) in pediatric patients undergoing a procedure in which anesthesia was used. Scores needed to be applicable to surgeries in more than one noncardiac surgical specialty and had to be able to be calculated by the anesthesiologist at the time of the preanesthetic assessment. Two investigators independently screened studies for inclusion and assessed study quality in the domains of clinical applicability, feasibility/ease of use in the clinical setting, and risk of bias. RESULTS: A total of 1,681 titles were retrieved. Of these, 10 studies met inclusion criteria: 9 reported the development and validation of scores, and 1 was an external validation of an existing score. Seven studies used varying years of multicenter data from the National Surgical Quality Improvement Program-Pediatric Participant Use File for development and/or validation. The unadjusted rate of mortality in the studies ranged from 0.3 to 3.6%. The preoperative predictors of mortality used in score development included patient demographics, preoperative therapies, and chronic conditions, among others. All models showed good discrimination upon validation (area under the receiver operating characteristics curve greater than 0.8). Most risk scores had high or unclear risks of bias. CONCLUSIONS: There are numerous scores available for the prediction of mortality in pediatric populations, all of which exhibited good performance. However, many have high or unclear risks of bias, and most have not undergone external validation.

Optic Nerve Sheath Viscoelastic Properties: Re-Examination of Biomechanical Behavior and Clinical Implications.

BACKGROUND: Meta-analyses show a variable relationship between optic nerve sheath diameter (ONSD) and the presence of raised intracranial pressure (ICP). Because optic nerve sheath (ONS) tissue can be deformed, it is possible that ONSD reflects not only the current ICP but also prior deforming biomechanical exposures. In this post hoc analysis of two published data sets, we characterize ONS Young's modulus (E, mechanical stress per unit of strain) and calculate threshold pressure for plastic deformation. METHODS: The authors of two previously published articles contributed primary data for these unique post hoc analyses. Human cadaveric ex vivo measurements of ONSD (n = 10) and luminal distending pressure (range 5 to 65 mm Hg) were used to calculate E and the threshold pressure for plastic deformation. Clinical in vivo measurements of ONSD and ICP during endotracheal tube suction from patients with traumatic brain injury (n = 15) were used to validate the ex vivo cadaveric findings. RESULTS: Ex vivo ONS estimate of E was 140 ± 1.3 mm Hg (mean ± standard error), with evidence of plastic deformation occurring with distending pressure at 45 mm Hg. Similar E (71 ± 10 mm Hg) was estimated in vivo with an average ICP of 34 ± 2 mm Hg. CONCLUSIONS: Ex vivo, ONS plastic deformation occurs at levels of pressure commonly seen in patients with raised ICP, leading to distortion of the ICP-ONSD relationship. This evidence of plastic deformation may illustrate why meta-analyses fail to identify a single threshold in ONSD associated with the presence of raised ICP. Future studies characterizing time-dependent viscous characteristics of the ONS will help determine the time course of ONS tissue biomechanical behavior.

Observer Variability as a Determinant of Measurement Error of Ultrasonographic Measurements of the Optic Nerve Sheath Diameter: A Systematic Review.

BACKGROUND: Ultrasonographic measurements of the diameter of the sheath of the optic nerve can be used to assess intracranial pressure indirectly. These measurements come with measurement error. OBJECTIVE: Our aim was to estimate observer's measurement error as a determinant of ultrasonographic measurement variability of the optic nerve sheath diameter. METHODS: A systematic search of the literature was conducted in Embase, Medline, Web of Science, the Cochrane Central Register of Trials, and the first 200 articles of Google Scholar up to April 19, 2021. Inclusion criteria were the following: healthy adults, B-mode ultrasonography, and measurements 3 mm behind the retina. Studies were excluded if standard error of measurement could not be calculated. Nine studies featuring 389 participants (median 40; range 15-100) and 22 observers (median 2; range 1-4) were included. Standard error of measurement and minimal detectable differences were calculated to quantify observer variability. Quality and risk of bias were assessed with the Guidelines for Reporting Reliability and Agreement Studies. RESULTS: The standard error of measurement of the intra- and interobserver variability had a range of 0.10-0.41 mm and 0.14-0.42 mm, respectively. Minimal detectable difference of a single observer was 0.28-1.1 mm. Minimal detectable difference of multiple observers (range 2-4) was 0.40-1.1 mm. Quality assessment showed room for methodological improvement of included studies. CONCLUSIONS: The standard errors of measurement and minimal detectable differences of ultrasonographic measurements of the optic nerve sheath diameter found in this review with healthy participants indicate caution should be urged when interpreting results acquired with this measurement method in clinical context.

Long-term neurodevelopment in children born with esophageal atresia: a systematic review.

BACKGROUND: Although the survival rate of esophageal atresia (EA) has increased to over 90%, the risk of functional long-term neurodevelopmental deficits is uncertain. Studies on long-term outcomes of children with EA show conflicting results. Therefore, we provide an overview of the current knowledge on the long-term neurodevelopmental outcome of children with EA. METHODS: We performed a structured literature search in Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google scholar on November 8, 2020 with the keywords 'esophageal atresia', 'long-term outcome', 'motor development', 'cognitive development', and 'neurodevelopment'. RESULTS: The initial search identified 945 studies, of which 15 were included. Five of these published outcomes of multiple tests or tested at multiple ages. Regarding infants, one of six studies found impaired neurodevelopment at 1 year of age. Regarding preschoolers, two of five studies found impaired neurodevelopment; the one study assessing cognitive development found normal cognitive outcome. Both studies on motor function reported impairment. Regarding school-agers, the one study on neurodevelopmental outcome reported impairment. Cognitive impairment was found in two out of four studies, and motor function was impaired in both studies studying motor function. CONCLUSIONS: Long-term neurodevelopment of children born with EA has been assessed with various instruments, with contrasting results. Impairments were mostly found in motor function, but also in cognitive performance. Generally, the long-term outcome of these children is reason for concern. Structured, multidisciplinary long-term follow-up programs for children born with EA would allow to timely detect neurodevelopmental impairments and to intervene, if necessary.

Midlatency auditory evoked potentials during anesthesia in children: A narrative review.

The brain is considered as the major target organ of anesthetic agents. Despite that, a reliable means to monitor its function during anesthesia is lacking. Mid latency auditory evoked potentials are known to be sensitive to anesthetic agents and might therefore be a measure of hypnotic state in pediatric patients. This review investigates the available literature describing various aspects of mid latency auditory evoked potential monitoring in pediatric anesthesia.

Associations of perioperative characteristics with motor function in preschool children born with esophageal atresia.

BACKGROUND: Children born with esophageal atresia experience long-term neurodevelopmental deficits, with unknown origin. AIMS: To find associations between perioperative variables during primary esophageal atresia repair and motor function at age 5 years. METHODS: This ambidirectional cohort study included children born with esophageal atresia who consecutively had been operated on in the Erasmus MC-Sophia Children's Hospital, University Medical Center, Rotterdam, from January 2007 through June 2013. The perioperative data of this cohort were collected retrospectively; the motor function data prospectively. RESULTS: After exclusion of patients with syndromal congenital diseases (n = 8) and lost to follow-up (n = 10), the data of 53 children were included. The mean (SD) total motor function impairment z-score at 5 years of age was -0.66 (0.99), significantly below normal (p < .001). In multivariable linear regression analysis, number of postoperative days endotracheal intubation (B = -0.211, 95% CI: -0.389 to -0.033, p = .021) was negatively associated with motor outcome, whereas high blood pressure (B = 0.022, 95% CI 0.001 to 0.042, p = .038) was positively associated. Preoperative nasal oxygen supplementation versus room air (B = 0.706, 95% CI: 0.132 to 1.280, p = .016) was positively associated with motor outcome, which we cannot explain. CONCLUSIONS: Motor function in 5-year-old esophageal atresia patients was impaired and negatively associated with the number of postoperative days of endotracheal intubation and positively associated with high blood pressure. Prospective studies with critical perioperative monitoring and monitoring during stay at the intensive care unit are recommended.

A Nationwide Retrospective Analysis of Out-of-Hospital Pediatric Cardiopulmonary Resuscitation Treated by Helicopter Emergency Medical Service in the Netherlands.

OBJECTIVE: There is generally limited but conflicting literature on the incidence, causes, and outcomes of pediatric out-of-hospital cardiac arrest. This study was performed to determine the incidence and outcome of pediatric out-of-hospital cardiac arrest reported by all helicopter emergency medical services in the Netherlands and to provide a description of causes and treatments and, in particular, a description of the specific interventions that can be performed by a physician-staffed helicopter emergency medical service. METHODS: A retrospective analysis was performed of all documented pediatric (0 < 18 years of age) out-of-hospital cardiac arrests from July 2015 to July 2017, attended by all 4 Dutch helicopter emergency medical service teams. RESULTS: Two hundred two out-of-hospital cardiac arrests were identified. The overall incidence in the Netherlands is 3.5 out-of-hospital cardiac arrests in children per 100,000 pediatric inhabitants. The overall survival rate for out-of-hospital cardiac arrest was 11.4%. Eleven (52%) of the survivors were in the drowning group and between 12 and 96 months of age. CONCLUSION: Helicopter emergency medical services are frequently called to pediatric out-of-hospital cardiac arrests in the Netherlands. The survival rate is normal to high compared with other countries. The 12- to 96-month age group and drowning seem to have a relatively favorable outcome.

Postoperative Hypotension after Noncardiac Surgery and the Association with Myocardial Injury.

BACKGROUND: Intraoperative hypotension has been associated with postoperative morbidity and early mortality. Postoperative hypotension, however, has been less studied. This study examines postoperative hypotension, hypothesizing that both the degree of hypotension severity and longer durations would be associated with myocardial injury. METHODS: This single-center observational cohort was comprised of 1,710 patients aged 60 yr or more undergoing intermediate- to high-risk noncardiac surgery. Frequent sampling of hemodynamic monitoring on a postoperative high-dependency ward during the first 24 h after surgery was recorded. Multiple mean arterial pressure (MAP) absolute thresholds (50 to 75 mmHg) were used to define hypotension characterized by cumulative minutes, duration, area, and time-weighted-average under MAP. Zero time spent under a threshold was used as the reference group. The primary outcome was myocardial injury (a peak high-sensitive troponin T measurement 50 ng/l or greater) during the first 3 postoperative days. RESULTS: Postoperative hypotension was common, e.g., 2 cumulative hours below a threshold of 60 mmHg occurred in 144 (8%) patients while 4 h less than 75 mmHg occurred in 824 (48%) patients. Patients with myocardial injury had higher prolonged exposures for all characterizations. After adjusting for confounders, postoperative duration below a threshold of 75 mmHg for more than 635 min was associated with myocardial injury (adjusted odds ratio, 2.68; 95% CI, 1.46 to 5.07, P = 0.002). Comparing multiple thresholds, cumulative durations of 2 to 4 h below a MAP threshold of 60 mmHg (adjusted odds ratio, 3.26; 95% CI, 1.57 to 6.48, P = 0.001) and durations of more than 4 h less than 65 mmHg (adjusted odds ratio, 2.98; 95% CI, 1.78 to 4.98, P < 0.001) and 70 mmHg (adjusted odds ratio, 2.18; 95% CI, 1.37 to 3.51, P < 0.001) were also associated with myocardial injury. Associations remained significant after adjusting for intraoperative hypotension, which independently was not associated with myocardial injury. CONCLUSIONS: In this study, postoperative hypotension was common and was independently associated with myocardial injury.

Neurological outcome after extracorporeal cardiopulmonary resuscitation for in-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: In-hospital cardiac arrest (IHCA) is a major adverse event with a high mortality rate if not treated appropriately. Extracorporeal cardiopulmonary resuscitation (ECPR), as adjunct to conventional cardiopulmonary resuscitation (CCPR), is a promising technique for IHCA treatment. Evidence pertaining to neurological outcomes after ECPR is still scarce. METHODS: We performed a comprehensive systematic search of all studies up to December 20, 2019. Our primary outcome was neurological outcome after ECPR at any moment after hospital discharge, defined by the Cerebral Performance Category (CPC) score. A score of 1 or 2 was defined as favourable outcome. Our secondary outcome was post-discharge mortality. A fixed-effects meta-analysis was performed. RESULTS: Our search yielded 1215 results, of which 19 studies were included in this systematic review. The average survival rate was 30% (95% CI 28-33%, I2 = 0%, p = 0.24). In the surviving patients, the pooled percentage of favourable neurological outcome was 84% (95% CI 80-88%, I2 = 24%, p = 0.90). CONCLUSION: ECPR as treatment for in-hospital cardiac arrest is associated with a large proportion of patients with good neurological outcome. The large proportion of favourable outcome could potentially be explained by the selection of patients for treatment using ECPR. Moreover, survival is higher than described in the conventional CPR literature. As indications for ECPR might extend to older or more fragile patient populations in the future, research should focus on increasing survival, while maintaining optimal neurological outcome.

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.

Monitoring Depth of Hypnosis: Mid-Latency Auditory Evoked Potentials Derived aepEX in Children Receiving Desflurane-Remifentanil Anesthesia.

BACKGROUND: The aepEXplus monitoring system, which uses mid-latency auditory evoked potentials to measure depth of hypnosis, was evaluated in pediatric patients receiving desflurane-remifentanil anesthesia. METHODS: Seventy-five patients, 1-18 years of age (stratified for age; 1-3, 3-6, 6-18 years, for subgroup analyses), were included in this prospective observational study. The aepEX and the bispectral index (BIS) were recorded simultaneously, the latter serving as a reference. The ability of the aepEX to detect different levels of consciousness, defined according to the University of Michigan Sedation Scale, investigated using prediction probability (Pk), and receiver operating characteristic (ROC) analysis, served as the primary outcome parameter. As a secondary outcome parameter, the relationship between end-tidal desflurane and the aepEX and BIS values were calculated by fitting in a nonlinear regression model. RESULTS: The Pk values for the aepEX and the BIS were, respectively, .68 (95% CI, 0.53-0.82) and .85 (95% CI, 0.73-0.96; P = .02). The aepEX and the BIS had an area under the ROC curve of, respectively, 0.89 (95% CI, 0.80-0.95) and 0.76 (95% CI, 0.68-0.84; P = .04). The maximized sensitivity and specificity were, respectively, 81% (95% CI, 61%-93%) and 86% (95% CI, 74%-94%) for the aepEX at a cutoff value of >52, and 69% (95% CI, 56%-81%) and 70% (95% CI, 57%-81%) for the BIS at a cutoff value of >65. The age-corrected end-tidal desflurane concentration associated with an index value of 50 (EC50) was 0.59 minimum alveolar concentration (interquartile range: 0.38-0.85) and 0.58 minimum alveolar concentration (interquartile range: 0.41-0.70) for, respectively, the aepEX and BIS (P = .69). Age-group analysis showed no evidence of a difference regarding the area under the ROC curve or EC50. CONCLUSIONS: The aepEX can reliably differentiate between a conscious and an unconscious state in pediatric patients receiving desflurane-remifentanil anesthesia.

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems.

Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not known. We have measured plasma levels of cefazolin and clindamycin in in vitro pediatric CPB systems. We have tested three types of CPB systems. All systems were primed and spiked with clindamycin and cefazolin. Samples were taken at different time points to measure the recovery of cefazolin and clindamycin. Linear mixed model analyses were performed to assess if drug recovery was different between the type of CPB system and sampling time point. The experiments were conducted at a tertiary university hospital. 81 samples were analyzed. There was a significant difference in the recovery over time between CPB systems for cefazolin and clindamycin (P < .001). Cefazolin recovery after 180 minutes was 106% (95% CI: 91-123) for neonatal, 99% (95% CI: 85-115) for infant, and 77% (95% CI: 67-89) for pediatric systems. Clindamycin recovery after 180 minutes was 143% (95% CI: 116-177) for neonatal, 111% (95% CI: 89-137) for infant, and 120% (95% CI: 97-149) for pediatric systems. Clindamycin recovery after 180 minutes compared to the theoretical concentration was 0.4% for neonatal, 1.2% for infants, and 0.6% for pediatric systems. The recovery of cefazolin was high in the neonatal and infant CPB systems and moderate in the pediatric system. We found a large discrepancy between the theoretical and measured concentrations of clindamycin in all tested CPB systems.

The effect of midazolam as premedication on the quality of postoperative recovery after laparotomy: a randomized clinical trial.

PURPOSE: Despite the uncertain effects of anxiolytic premedication with benzodiazepines on the quality of postoperative recovery, perioperative benzodiazepine administration is still a common practice in many hospitals. We evaluated the effect of premedication with midazolam on the quality of recovery in hospitalized patients undergoing a laparotomy. METHODS: We conducted a single-centre randomized placebo-controlled, double-blinded clinical trial from July 2014 to September 2015. We included 192 patients aged > 18 yr scheduled for elective laparotomy with a planned postoperative stay of ≥ three days. Participants were randomized into two groups to receive either midazolam 3 mg or sodium chloride 0.9% intravenously as premedication prior to surgery. Patients were followed up for up to one week after surgery. The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day (POD) 3. The secondary outcomes included the QoR-40 score on POD 7, and the State-Trait Anxiety Inventory, State-Trait Anger Scale, Multidimensional Fatigue Inventory, and the Hospital Anxiety and Depression Scale scores. RESULTS: The mean (standard deviation) postoperative QoR-40 scores on POD 3 were not significantly different in the midazolam group compared with controls [166.4 (17.0) vs 163.9 (19.8), respectively; mean difference, 2.3; 95% confidence interval, - 2.9 to 8.4; P = 0.35]. There were no between-group differences in any of the secondary outcomes. CONCLUSIONS: Administration of midazolam as premedication for laparotomy patients did not improve the quality of recovery up to one week after surgery. General prescription of midazolam as premedication can be questioned and might only suit some patients. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01993459); registered 29 October, 2013.

In Vitro Recovery of Sufentanil, Midazolam, Propofol, and Methylprednisolone in Pediatric Cardiopulmonary Bypass Systems.

OBJECTIVES: To evaluate in vitro drug recovery in cardiopulmonary bypass (CPB) systems used for pediatric cardiac surgery. DESIGN: Observational in vitro study. SETTING: Single-center university hospital. PARTICIPANTS: In vitro CPB systems used for pediatric cardiac surgery. INTERVENTIONS: Three full neonatal, infant, and pediatric CPB systems were primed according to hospital protocol and kept running for 6 hours. Midazolam, propofol, sufentanil, and methylprednisolone were added to the venous side of the systems in doses commonly used for induction of general anesthesia. Blood samples were taken from the postoxygenator side of the circuit immediately after injection of the drugs and after 2, 5, 7, 10, 30, 60, 180, and 300 minutes. MEASUREMENTS AND MAIN RESULTS: Linear mixed model analyses were performed to assess the relationship between log-transformed drug concentration (dependent variable) and type of CPB system and sample time point (independent variables). The mean percentage of drug recovery after 60 and 180 minutes compared with T1 was 41.7% (95% confidence interval [CI] 35.9-47.4) and 23.0% (95% CI 9.2-36.8) for sufentanil, 87.3% (95% CI 64.9-109.7) and 82.0% (95% CI 64.6-99.4) for midazolam, 41.3% (95% CI 15.5-67.2) and 25.0% (95% CI 4.7-45.3) for propofol, and 119.3% (95% CI 101.89-136.78) and 162.0% (95% CI 114.09-209.91) for methylprednisolone, respectively. CONCLUSIONS: The present in vitro experiment with neonatal, infant, and pediatric CPB systems shows a variable recovery of routinely used drugs with significant differences between drugs, but not between system categories (with the exception of propofol). The decreased recovery of mainly sufentanil and propofol could lead to suboptimal dosing of patients during cardiac surgery with CPB.