The effects of dexmedetomidine on intraoperative neurophysiologic monitoring modalities during corrective scoliosis surgery in pediatric patients: A systematic review.

BACKGROUND: During scoliosis surgery, motor evoked potentials (MEP), and somatosensory evoked potentials (SSEP) have been reported to be affected by the use of higher doses of anesthetic agents. Dexmedetomidine, a sympatholytic agent, an alpha-2 receptor agonist, has been used as an adjunctive agent to lower anesthetic dose. However, there is conflicting evidence regarding the effects of dexmedetomidine on the intraoperative neurophysiological monitoring of MEP and SSEP during surgery, particularly among pediatric patients. OBJECTIVES: This systematic review aimed to determine whether, during spinal fusion surgery in pediatric patients with scoliosis, dexmedetomidine alters MEP amplitude or SSEP latency and amplitude and, if so, whether different doses of dexmedetomidine display different effects (PROSPERO registration number CRD42022300562). METHODS: We searched PubMed, Scopus, and Cochrane Library on January 1, 2022 and included randomized controlled trials, observational cohort and case-control studies and case series investigating dexmedetomidine in the population of interest and comparing against a standardized anesthesia regimen without dexmedetomidine or comparing multiple doses of dexmedetomidine. Animal and in vitro studies and conference abstracts were excluded. RESULTS: We found substantial heterogeneity in the risk of bias (per Cochrane-preferred tools) of the included articles (n = 5); results are summarized without meta-analysis. Articles with the lowest risk of bias indicated that dexmedetomidine was associated with MEP loss and that higher doses of dexmedetomidine increased risk. In contrast, articles reporting no association between dexmedetomidine and MEP loss suffered from higher risk of bias, including suspected or confirmed problems with confounding, outcome measurement, participant selection, results reporting, and lack of statistical transparency and power. CONCLUSION: Given the limitations of the studies available in the literature, it would be advisable to conduct rigorous randomized controlled trials with larger sample sizes to assess the effects of dexmedetomidine use of in scoliosis surgery in pediatric patients.

Multiorgan talks in the presence of brain injury.

PURPOSE OF REVIEW: The brain is the command center of the rest of the body organs. The normal multiorgan talks between the brain and the rest of the body organs are essential for the normal body homeostasis. In the presence of brain injury, the disturbed talks between the brain and the rest of body organs will result in several pathological conditions. The aim of this review is to present the most recent findings for the pathological conditions that would result from the impaired multiorgan talks in the presence of brain injury. RECENT FINDINGS: The brain injury such as in acute ischemic stroke, subarachnoid hemorrhage and traumatic brain injury will result in cascade of pathological talks between the brain and the rest of body organs. These pathological talks could result in pathological conditions such as cardiomyopathy, acute lung and kidney injuries, impaired liver functions, and impaired gut barrier permeability as well. SUMMARY: Better understanding of the pathological conditions that could result from the impaired multiorgan talks in the presence of brain injury will open the doors for precise targeted therapies in the future for myriad of pathological conditions.

Stroke thrombectomy perioperative anesthetic and hemodynamic management.

There is an ongoing debate about the optimal anesthetic and hemodynamic management of acute stoke patients with large vessel occlusion undergoing endovascular mechanical thrombectomy. Several prospective and retrospective analyses, and randomized controlled trials, attempted to address the challenges of using different anesthetic modalities in acute stroke patients requiring mechanical thrombectomy. We review the advantages and disadvantages of monitored anesthesia care, local anesthesia, conscious sedation, and general anesthesia, along with the relevance of hemodynamic management and perioperative oxygenation status in these complex patients.

Subfascial versus extrafascial ultrasound-guided stellate ganglion block in patients with post-mastectomy sympathetically mediated pain: A randomized clinical trial.

Background: Despite being a well-described intervention, the optimal anatomical approach to perform a stellate ganglion block (SGB) has been disputed. We compared the subfascial and extrafascial ultrasound-guided (USG) SGB. Methods: A randomised clinical trial was conducted, consisting of 50 patients in two groups. Group I received SGB via the subfascial approach while Group II received an SGB via the extrafascial approach. The primary endpoint was successful sympathetic blockade (as indicated by a measured temperature rise of ≥2°C). Secondary endpoints included analgesic efficiency (extent of early onset of pain relief as indicated by >50% improvement in Visual Analogue Scale (VAS) score at 300's post-procedure); occurrence of Horner's syndrome; extent of local anaesthetic distribution; and adverse events. Results: The mean increase in sympathetic blockade was significantly higher in the subfascial group (2.6 ± 0.6°C; p = .003). Analgesic efficacy was also significantly higher in the subfascial group (p < .001). The difference in the average dermatomal spread of local anaesthetic down to T2 and up to C4 between the groups was also statistically significant (p = .021 and p = .019, respectively). Conclusions: The degree of temperature rise, pain relief and occurrence of Horner's syndrome were higher in the subfascial than the extrafascial group. The subfascial approach to SGB, with a limited volume of local anaesthetic agent, is a more reliable technique when compared to the extrafascial approach.

Tidal Volume and Positive End-expiratory Pressure and Postoperative Hypoxemia during General Anesthesia: A Single-center Multiple Crossover Factorial Cluster Trial.

BACKGROUND: Intraoperative mechanical ventilation is a major component of general anesthesia. The extent to which various intraoperative tidal volumes and positive end-expiratory pressures (PEEP) effect on postoperative hypoxia and lung injury remains unclear. We hypothesized that adults having orthopedic surgery, ventilation using different tidal volumes and PEEP levels affect the oxygenation within first hour in the postoperative care unit. METHODS: We conducted a two-by-two factorial crossover cluster trial at the Cleveland Clinic Main Campus. We enrolled patients having orthopedic surgery with general anesthesia who were assigned to factorial clusters with tidal volumes of 6 or 10 ml/kg of predicted body weight and to PEEP of 5 or 8 cm H2O in 1-week clusters. The primary outcome was the effect of tidal volume or PEEP on time-weighted average peripheral oxygen saturation measured by pulse oximetry divided by the fraction of inspired oxygen (Spo2/Fio2 ratio) during the initial postoperative hour. RESULTS: We enrolled 2,860 patients who had general anesthesia for orthopedic surgery from September 2018 through October 2020. The interaction between tidal volume and PEEP was not significant (P = 0.565). The mean ± SD time-weighted average of Spo2/Fio2 ratio was 353 ± 47 and not different in patients assigned to high and low tidal volume (estimated effect, 3.5%; 97.5% CI, -0.4% to 7.3%; P = 0.042), for those assigned to high and low PEEP (estimated effect, -0.2%; 97.5% CI, -4.0% to 3.6%; P = 0.906). We did not find significant difference in ward Spo2/Fio2 ratio, pulmonary complications, and duration of hospitalization among patients assigned to various tidal volumes and PEEP levels. CONCLUSIONS: Among adults having major orthopedic surgery, postoperative oxygenation is similar, with tidal volumes between 6 and 10 ml/kg and PEEP between 5 and 8 cm H2O. Our results suggest that any combination of tidal volumes between 6 and 10 ml/kg and PEEP between 5 versus 8 ml cm H2O can be used safely for orthopedic surgery.

Oxygen Saturation and Postoperative Mortality in Patients With Acute Ischemic Stroke Treated by Endovascular Thrombectomy.

BACKGROUND: Monitored anesthesia care (MAC) and general anesthesia (GA) with endotracheal intubation are the 2 most used techniques for patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy. We aimed to test the hypothesis that increased arterial oxygen concentration during reperfusion period is a mechanism underlying the association between use of GA (versus MAC) and increased risk of in-hospital mortality. METHODS: In this retrospective cohort study, data were collected at the Cleveland Clinic between 2013 and 2018. To assess the potential mediation effect of time-weighted average oxygen saturation (Spo2) in first postoperative 48 hours between the association between GA versus MAC and in-hospital mortality, we assessed the association between anesthesia type and post-operative Spo2 tertiles (exposure-mediator relationship) through a cumulative logistic regression model and assessed the association between Spo2 and in-hospital mortality (mediator-outcome relationship) using logistic regression models. Confounding factors were adjusted for using propensity score methods. Both significant exposure-mediator and significant mediator-outcome relationships are needed to suggest potential mediation effect. RESULTS: Among 358 patients included in the study, 104 (29%) patients received GA and 254 (71%) received MAC, with respective hospital mortality rate of 19% and 5% (unadjusted P value <.001). GA patients were 1.6 (1.2, 2.1) (P < .001) times more likely to have a higher Spo2 tertile as compared to MAC patients. Patients with higher Spo2 tertile had 3.8 (2.1, 6.9) times higher odds of mortality than patients with middle Spo2 tertile, while patients in the lower Spo2 tertile did not have significant higher odds compared to the middle tertile odds ratio (OR) (1.8 [0.9, 3.4]; overall P < .001). The significant exposure-mediator and mediator-outcome relationships suggest that Spo2 may be a mediator of the relationship between anesthetic method and mortality. However, the estimated direct effect of GA versus MAC on mortality (ie, after adjusting for Spo2; OR [95% confidence interval {CI}] of 2.1 [0.9-4.9]) was close to the estimated association ignoring Spo2 (OR [95% CI] of 2.2 [1.0-5.1]), neither statistically significant, suggesting that Spo2 had at most a modest mediator role. CONCLUSIONS: GA was associated with a higher Spo2 compared to MAC among those treated by endovascular thrombectomy for AIS. Spo2 values that were higher than the middle tertile were associated with higher odds of mortality. However, GA was not significantly associated with higher odds of death. Spo2 at most constituted a modest mediator role in explaining the relationship between GA versus MAC and mortality.

Chronic Use of Angiotensin Converting Enzyme Inhibitors and/or Angiotensin Receptor Blockers is Not Associated With Stroke After Noncardiac Surgery: A Retrospective Cohort Analysis.

BACKGROUND: Inhibition of the renin-angiotensin-aldosterone pathways reduces blood pressure and proliferation of vascular smooth muscles and may therefore reduce the risk of stroke. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for at least 6 months have fewer postoperative strokes after non-neurological, noncarotid, and noncardiac surgeries than those who do not. METHODS: We considered adults who had noncardiac surgery at the Cleveland Clinic between January 2005 and December 2017. After excluding neurological and carotid surgeries, we assessed the confounder-adjusted association between chronic use of ACEIs/ARBs (during 6 preoperative months) and the incidence of postoperative stroke using logistic regression models. RESULTS: Postoperative strokes occurred in 0.26% (27/10,449) of patients who were chronic ACEI/ARBs users and in 0.18% (112/62,771) of those who were not. There was no significant association between ACEI/ARB use and postoperative stroke, with an adjusted odds ratio of 1.15 (95% confidence interval [CI]: 0.91-1.44; P =0.24). Secondarily, there was no association between exposures to ACEIs and postoperative stroke, versus no such exposure (adjusted odds ratio 0.88, 95% CI: 0.65-1.19; P =0.33). Similarly, there was no association between exposure to ARBs and postoperative stroke, versus no such exposure (adjusted odds ratio 1.05, 95% CI: 0.75-1.48; P =0.75). CONCLUSION: We did not detect an effect of chronic ACEI/ARB use on postoperative strokes in patients who had non-neurological, noncarotid and noncardiac surgery; however, power was extremely limited.

Co-Presentation of Posterior Reversible Encephalopathy Syndrome in a Patient with Post-Dural Puncture Headache.

INTRODUCTION: Post-dural puncture headache (PDPH) is a well-known complication of neuraxial anesthesia, but the occurrence of seizures and vision loss within a few days after dural puncture could be alarming. Posterior reversible encephalopathy syndrome (PRES) is associated with reversible edema and leukoencephalopathy in the posterior parieto-occipital cortex. We report the co-presentation of PRES and PDPH after labor epidural analgesia. CASE PRESENTATION: A 25-year-old multiparous African-American woman was admitted for evaluation of new-onset seizures and headache in the postpartum period. She had a recent history of multiple needle insertion attempts and inadvertent dural puncture during epidural analgesia for delivery. Soon after delivery, she was diagnosed with PDPH and was treated with an epidural blood patch, with no relief of symptoms. Six days later, she developed sudden-onset transient blindness, seizures, and altered sensorium, and magnetic resonance imaging of the brain revealed white matter changes suggestive of PRES. CONCLUSION: PRES is an uncommon complication of cerebrospinal fluid leak and intracranial hypotension. We report the occurrence of PRES in a patient with no known risk factors except a traumatic dural tap. Is it important to expand the differentials for headache after dural puncture to encompass PRES as a possibility, especially in patients with a delayed presentation of seizures and cortical blindness.

Sugammadex Versus Neostigmine for Reversal of Rocuronium Neuromuscular Block in Patients Having Catheter-Based Neurointerventional Procedures: A Randomized Trial.

BACKGROUND: Catheter-based endovascular neurointerventions require deep neuromuscular blocks during the procedure and rapid subsequent recovery of strength to facilitate neurological evaluation. We tested the primary hypothesis that sugammadex reverses deep neuromuscular blocks faster than neostigmine reverses moderate neuromuscular blocks. METHODS: Patients having catheter-based cerebral neurointerventional procedures were randomized to: (1) deep rocuronium neuromuscular block with posttetanic count 1 to 2 and 4-mg/kg sugammadex as the reversal agent or (2) moderate rocuronium neuromuscular block with train-of-four (TOF) count 1 during the procedure and neuromuscular reversal with 0.07-mg/kg neostigmine to a maximum of 5 mg. Recovery of diaphragmatic function was assessed by ultrasound at baseline before the procedure and 90 minutes thereafter. The primary outcome-time to reach a TOF ratio ≥0.9 after administration of the designated reversal agent-was analyzed with a log-rank test. Secondary outcomes included time to successful tracheal extubation and the difference between postoperative and preoperative diaphragmatic contraction speed and distance. RESULTS: Thirty-five patients were randomized to sugammadex and 33 to neostigmine. Baseline characteristics and surgical factors were well balanced. The median time to reach TOF ratio ≥0.9 was 3 minutes (95% confidence interval [CI], 2-3 minutes) in patients given sugammadex versus 8 minutes (95% CI, 6-10 minutes) in patients given neostigmine. Sugammadex was significantly faster by a median of 5 minutes (95% CI, 3-6 minutes; P < .001). However, times to tracheal extubation and diaphragmatic function at 90 minutes did not differ significantly. CONCLUSIONS: Sugammadex reversed deep rocuronium neuromuscular blocks considerably faster than neostigmine reversed moderate neuromuscular blocks. However, times to extubation did not differ significantly, apparently because extubation was largely determined by the time required for awaking from general anesthesia and because clinicians were willing to extubate before full neuromuscular recovery. Sugammadex may nonetheless be preferable to procedures that require a deep neuromuscular block and rapid recovery.

Metal-Bound Methisazone; Novel Drugs Targeting Prophylaxis and Treatment of SARS-CoV-2, a Molecular Docking Study.

SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn-Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.

The diagnostic and prognostic role of neutrophil-to-lymphocyte ratio in COVID-19: a systematic review and meta-analysis.

Background: The world urgently requires surrogate markers to diagnose COVID-19 and predict its progression. The severity is not easily predicted via currently used biomarkers. Critical COVID-19 patients need to be screened for hyperinflammation to improve mortality but expensive cytokine measurement is not routinely conducted in most laboratories. The neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker in patients with various diseases. We evaluated the diagnostic and prognostic accuracy of the NLR in COVID-19 patients.Methods: We searched for relevant articles in seven databases. The quantitative analysis was conducted if at least two studies were evaluating the NLR role in COVID-19.Results: We included 8,120 individuals, including 7,482 COVID-19 patients, from 32 articles. Patients with COVID-19 had significantly higher levels of NLR compared to negative individuals. Advanced COVID-19 stages had significantly higher levels of NLR than earlier stages.Expert Opinion: We found significantly higher levels of NLR in advanced stages compared to earlier stages of COVID-19 with good accuracy to diagnose and predict the disease outcome, especially mortality prediction. A close evaluation of critical SARS-CoV-2 patients and efficient early management are essential measures to decrease mortality. NLR could help in assessing the resource allocation in severe COVID-19 patients even in restricted settings.

Roadmap for Conducting Neuroscience Research in the COVID-19 Era and Beyond: Recommendations From the SNACC Research Committee.

The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of neuroscience research. At the 2020 Society of Neuroscience in Anesthesiology and Critical Care (SNACC) Annual Meeting, the SNACC Research Committee met virtually to discuss research challenges encountered during the COVID-19 pandemic along with possible strategies for facilitating research activities. These challenges and recommendations are included in this Consensus Statement. The objectives are to: (1) provide an overview of the disruptions and challenges to neuroscience research caused by the COVID-19 pandemic, and; (2) put forth a set of consensus recommendations for strengthening research sustainability during and beyond the current pandemic. Specific recommendations are highlighted for adapting laboratory and human subject study activities to optimize safety. Complementary research activities are also outlined for both laboratory and clinical researchers if specific investigations are impossible because of regulatory or societal changes. The role of virtual platforms is discussed with respect to fostering new collaborations, scheduling research meetings, and holding conferences such that scientific collaboration and exchange of ideas can continue. Our hope is for these recommendations to serve as a valuable resource for investigators in the neurosciences and other research disciplines for current and future research disruptions.

Deep Hypothermic Circulatory Arrest in the Pediatric Population Undergoing Cardiac Surgery With Electroencephalography Monitoring: A Systematic Review and Meta-Analysis.

OBJECTIVE: Cardiac surgery for repair of congenital heart defects poses unique hazards to the developing brain. Deep hypothermic circulatory arrest (DHCA) is a simple and effective method for facilitating a bloodless surgical field during congenital heart defect repair. There are, however, some concerns that prolonged DHCA increases the risk of nervous system injury. The electroencephalogram (EEG) is used in adult and, to a lesser extent, pediatric cardiac procedures as a neuromonitoring method. The present study was performed to assess outcomes following DHCA with EEG monitoring in the pediatric population. DESIGN: In this systematic review and meta-analysis, the PubMed, Cochrane Central Register of Controlled Trials, Scopus, Institute of Science Index, and Embase databases were searched from inception for relevant articles. A fixed- or random-effects model, as appropriate, was used. SETTING: Surgical setting. PARTICIPANTS: Pediatric population (≤18 y old). INTERVENTIONS: DHCA (18°C) with EEG monitoring. MEASUREMENTS AND MAIN RESULTS: Nineteen articles with 1,267 pediatric patients ≤18 years were included. The event rate of clinical and EEG seizures among patients who underwent DHCA was 12.9% and 14.9%, respectively. Mortality was found to have a 6.3% prevalence. A longer duration of DHCA was associated with a higher risk of EEG seizure and neurologic abnormalities. In addition, seizures were associated with increased neurologic abnormalities and neurodevelopmental delay. CONCLUSIONS: EEG and neurologic abnormalities were common after DHCA. A longer duration of DHCA was found to lead to more EEG seizure and neurologic abnormalities. Moreover, EEG seizures were more common than clinical seizures. Seizures were found to be associated with increased neurologic abnormalities and neurodevelopmental delay.

Association between postoperative haemoglobin and myocardial injury after noncardiac surgery: a retrospective cohort analysis.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is common, mostly silent, and a strong predictor of postoperative mortality. MINS appears to result from myocardial supply-demand mismatch. Recent data support restrictive perioperative transfusion strategies that can result in low postoperative haemoglobin concentrations. Whether low postoperative haemoglobin is associated with myocardial injury remains unknown. We therefore tested the hypothesis that anaemia is associated with an increased risk of myocardial injury in adults having noncardiac surgery. METHODS: We conducted a retrospective analysis of adults ≥45 yr old who had routine postoperative troponin T (TnT) monitoring after noncardiac surgery at the Cleverland Clinic (including those enrolled in the PeriOperative ISchemic Evaluation-2 Trial [POISE-2], the Safety of Addition of Nitrous Oxide to General Anaesthesia in At-risk Patients Having Major Non-cardiac Surgery [ENIGMA-II], Vascular Events In Noncardiac Surgery Patients Cohort Evaluation Study [VISION], and Anaesthetic Depth and Complications After Major Surgery [BALANCED] trial). Patients with baseline increase in TnT and non-ischaemic aetiologies for TnT increase were excluded. The association between postoperative haemoglobin concentration during the 3 initial postoperative days and the incidence of MINS (fourth-generation TnT ≥0.03 ng ml-1 judged as attributable to ischaemia) was assessed using a time-varying covariate Cox proportional hazards survival analysis. RESULTS: Among 6141 patients, 4480 were analysed. The incidence of MINS was 155/4480 (3.5%), ranging from 0/345 (0%) among patients whose lowest postoperative haemoglobin exceeded 13 g dl-1 to 52/611 (8.5%) in patients whose minimum postoperative haemoglobin was <8 g dl-1. The confounder-adjusted hazard ratio [95% confidence interval] for having MINS was 1.29 [1.16-1.42] for every 1 g dl-1 decrease in postoperative haemoglobin in a time-varying covariate analysis. Similar associations were identified in sensitivity analyses. CONCLUSION: Lower postoperative haemoglobin values are associated with MINS. Whether this association is modifiable by prevention or treatment of anaemia remains to be determined.

Antistasis Retrograde Flow Vascular Catheter: A Novel Solution to Thrombogenicity: A Computational Fluid Dynamics Study.

BACKGROUND: Catheter-related thrombosis (CRT) is a serious complication of vascular catheters. Retrograde catheter insertion has been shown to decrease pericatheter hemostasis and thrombosis, but it is technically challenging. The current in silico trial is an analytical approach to evaluating different approaches to designing retrograde flow into a vascular catheter. METHODS: The novel catheter design aims to provide antistasis retrograde flow (ASRF) of fluid through multiple backward-directed side openings, with a self-closing terminal opening to facilitate standard insertion. Four different models of the catheter were evaluated by computational fluid dynamic studies, with retrograde-angled openings of 15°, 30°, 45°, and 60° to the long axis of the catheter. RESULTS: ASRF successfully reduced the areas of fluid stagnation in models with 15° and 30° openings. Models with 45° and 60° did not significantly reduce stagnation. ASRF is reversed by the main bloodstream after a few millimeters. The novel catheter design achieved a slightly higher saline flow rate compared with the standard catheter (89.75, 91.72, 94.13, and 94.26 mL/min for 15°, 30°, 45°, and 60° designs, respectively, versus 86.93 mL/min for the standard catheter). CONCLUSIONS: The novel ASRF vascular catheter reduces pericatheter fluid stasis and has the potential to reduce CRT. Further in vitro and in vivo trials are warranted to validate these findings and evaluate clinical efficacy.

Association between Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers and Postoperative Delirium.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve cognitive function. The authors therefore tested the primary hypothesis that preoperative use of angiotensin inhibitors is associated with less delirium in critical care patients. Post hoc, the association between postoperative use of angiotensin system inhibitors and delirium was assessed. METHODS: The authors conducted a single-site cohort study of adults admitted to Cleveland Clinic critical care units after noncardiac procedures between 2013 and 2018 who had at least one Confusion Assessment Method delirium assessment. Patients with preexisting dementia, Alzheimer's disease or other cognitive decline, and patients who had neurosurgical procedures were excluded. For the primary analysis, the confounder-adjusted association between preoperative angiotensin inhibitor use and the incidence of postoperative delirium was assessed. Post hoc, the confounder-adjusted association between postoperative angiotensin system inhibitor use and the incidence of delirium was assessed. RESULTS: The incidence of delirium was 39% (551 of 1,396) among patients who were treated preoperatively with angiotensin system inhibitors and 39% (1,344 of 3,468) in patients who were not. The adjusted odds ratio of experiencing delirium during critical care was 0.98 (95% CI, 0.86 to 1.10; P = 0.700) for preoperative use of angiotensin system inhibitors versus control. Delirium was observed in 23% (100 of 440) of patients who used angiotensin system inhibitors postoperatively before intensive care discharge, and in 41% (1,795 of 4,424) of patients who did not (unadjusted P < 0.001). The confounder-adjusted odds ratio for experiencing delirium in patients who used angiotensin system inhibitors postoperatively was 0.55 (95% CI, 0.43 to 0.72; P < 0.001). CONCLUSIONS: Preoperative use of angiotensin system inhibitors is not associated with reduced postoperative delirium. In contrast, treatment during intensive care was associated with lower odds of delirium. Randomized trials of postoperative angiotensin-converting enzymes inhibitors and angiotensin receptor blockers seem justified.

Timing of Tracheostomy in Pediatric Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Tracheostomy is a very common clinical intervention in critically ill adult patients. The indications for tracheostomy procedures in pediatric patients with complex conditions have increased dramatically in recent years, but there are currently no guidelines on the optimal timing of tracheostomy in pediatric patients undergoing prolonged ventilation. DATA SOURCES: We performed a systematic search of the existing literature in MEDLINE via PubMed and Embase databases and the Cochrane Library to identify clinical trials, observational studies, and cohort studies that compare early and late tracheostomy in children. The date of the last search was August 27, 2018. Included articles were subjected to manual searching. STUDY SELECTION: Studies in mechanically ventilated children that compared early with late tracheostomy were included. DATA EXTRACTION: Data were extracted into a spreadsheet and copied into Review Manager 5.3 (The Cochrane Collaboration, Copenhagen, Denmark). DATA SYNTHESIS: Data were meta-analyzed using an inverse variance, random effects model. Continuous outcomes were calculated as mean differences with 95% CIs, and dichotomous outcomes were calculated as Mantel-Haenszel risk ratios with 95% CIs. We included eight studies (10 study arms). These studies were all retrospective cohort studies. Early tracheostomy was associated with significant reductions in mortality, days on mechanical ventilation, and length of intensive care and total hospital stay, although the lack of randomized, controlled trials limits the validity of these findings. Although variance was imputed for some studies, these conclusions did not change after removing these studies from the analysis. CONCLUSIONS: In children on mechanical ventilation, early tracheostomy may improve important medical outcomes. However, our data demonstrate the urgent need for high-quality, randomized controlled trials in the pediatric population.