Κυριακή 27 Δεκεμβρίου 2020

Dexmedetomidine Provides Cardioprotection During Early or Late Reperfusion Mediated by Different Mitochondrial K+-Channels

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imageBackground: Cardioprotective interventions—such as pharmacological postconditioning—are a promising strategy to reduce deleterious consequences of ischemia and reperfusion injury (I/RI) in the heart, especially as timing and onset of myocardial infarction are unpredictable. Pharmacological postconditioning by treatment with dexmedetomidine (Dex), an α2-adrenoreceptor agonist, during reperfusion protects hearts from I/RI, independently of time point and duration of application during the reperfusion phase. The mitochondrial ATP-sensitive K+ (mKATP) and mitochondrial large-conductance calcium-sensitive potassium channel (mBKCa) play a pivotal role in mediating this cardioprotective effect. Therefore, we investigated whether Dex-induced cardioprotection during early or late reperfusion is mediated variously by these mitochondrial K+-channels. METHODS: Hearts of male Wistar rats were randomized into 8 groups and underwent a protocol of 15 minutes adaption, 33 minutes ischemia, and 60 minutes reperfusion in an in vitro Langendorff-system. A 10-minute treatment phase was started directly (first subgroup, early reperfusion) or 30 minutes (second subgroup, late reperfusion) after the onset of reperfusion. Control (Con) hearts received vehicle only. In the first subgroup, hearts were treated with 3 nM Dex, 100 µM mKATP-channel blocker 5-hydroxydecanoate (5HD) or 1 µM mBKCa-channel blocker Paxilline (Pax) alone or with respective combinations (5HD + Dex, Pax + Dex). Hearts of the second subgroup received Dex alone (Dex30') or in combination with the respective blockers (5HD + Dex30', Pax + Dex30'). Infarct size was determined with triphenyltetrazoliumchloride staining. Hemodynamic variables were recorded during the whole experiment. RESULTS: During early reperfusion (first subgroup), the infarct size reducing effect of Dex (Con: 57% ± 9%, Dex: 31% ± 7%; P
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Retrograde Autologous Priming in Cardiac Surgery: Results From a Systematic Review and Meta-analysis

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imageBackground: Retrograde autologous priming (RAP) before cardiopulmonary bypass (CPB) may minimize allogeneic red cell transfusion. We conducted a systematic review of the literature to examine the impact of RAP on perioperative allogeneic red cell transfusions in cardiac surgical patients. METHODS: This study involved a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating the use of RAP in cardiac surgery involving CPB. The primary outcome was intraoperative allogeneic red cell transfusion. Secondary outcomes included whole hospital allogeneic transfusions and adverse events such as acute kidney injury (AKI) and stroke. RESULTS: A total of 11 RCTs (n = 1337 patients) were included, comparing RAP patients (n = 674) to control (n = 663). In addition, 10 observational studies (n = 2327) were included, comparing RAP patients (n = 1257) to control (n = 1070). Overall, RAP was associated with a significantly reduced incidence of intraoperative red cell transfusion (n = 18 studies; odds ratio [OR] = 0.34; 95% confidence interval [CI], 0.22–0.55, P
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The Effects of Nitroglycerin on the Oxytocin Dose–Response Profile in Oxytocin-Desensitized and Naïve Human Myometrium: An In Vitro Study

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imageBackground: Nitroglycerin is used for acute reduction in uterine tone. Prolonged oxytocin exposure causes desensitization of oxytocin receptors. It is unknown if nitroglycerin exposure impacts the subsequent action of oxytocin in the setting of oxytocin receptor desensitization. This study investigated the effects of nitroglycerin on oxytocin-desensitized and oxytocin-naïve human myometrium and the subsequent response to oxytocin dose–response testing in vitro. METHODS: Myometrial samples from 17 elective cesarean deliveries were divided into strips and allocated to 1 of 4 groups: (1) oxytocin desensitized and no nitroglycerin; (2) oxytocin desensitized and nitroglycerin; (3) oxytocin naïve and nitroglycerin; and (4) oxytocin naïve and no nitroglycerin. Final analysis included 28 strips per group. Nitroglycerin groups were exposed to incremental concentrations of nitroglycerin, while no nitroglycerin groups were kept in control (physiological salt) solution. All groups then underwent oxytocin dose–response testing. Primary outcome was motility index (amplitude × frequency; grams × contractions per 10 minutes [g·c/10 min]). Secondary outcomes were amplitude (g), frequency (contractions/10 minutes), and area under the curve (g·s). All outcomes (nitroglycerin and oxytocin dose–response periods) were expressed as a percentage change from baseline. Values were log transformed, compared using regression modeling and reported as the ratio of 2 ge ometric means (relative difference). RESULTS: No significant difference was observed in motility index following nitroglycerin administration in oxytocin-desensitized versus oxytocin-naïve groups (relative difference = 19.0%; 95% confidence interval [CI], −32.6 to 109.9; P = .55). On oxytocin dose–response testing, motility index was highest in oxytocin-naïve and no nitroglycerin samples (group 4) (1.356 g·c/10 minutes) followed by oxytocin-naïve and nitroglycerin (group 3) (0.882 g·c/10 minutes), oxytocin-desensitized and no nitroglycerin (group 1) (0.769 g·c/10 minutes), and oxytocin-desensitized and nitroglycerin (group 2) (0.651 g·c/10 minutes) samples. Motility index was significantly reduced in group 1 vs 4 (relative difference = −43.3%; 95% CI, −66.5 to −4.1; P = .034) and group 2 vs 4 (relative difference = −52.0%; 95% CI, −70.9 to −20.8; P = .004). While in groups 3 vs 4, both amplitude (relative difference = −17.8%; 95% CI, −30.9 to −2.2; P = .27) and area under the curve (AUC; relative dif ference = −17.5%; 95% CI, −30.7 to −1.8; P = .030) were reduced. CONCLUSIONS: Nitroglycerin-induced relaxation was not different between oxytocin-desensitized and oxytocin-naïve human myometrial strips in vitro. However, oxytocin-induced contractility was attenuated after nitroglycerin exposure in both oxytocin-desensitized and oxytocin-naïve samples, with maximum attenuation observed in desensitized tissues. This finding warrants further clinical studies to explore uterine responsiveness to oxytocin in women with oxytocin-augmented labors after nitroglycerin administration.
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Pediatric Anesthesia Severe Adverse Events Leading to Anesthetic Morbidity and Mortality in a Tertiary Care Center in a Low- and Middle-Income Country: A 25-Year Audit

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imageBackground: The analysis of adverse events, including morbidity and mortality (M&M), helps to identify subgroups of children at risk and to modify clinical practice. There are scant data available from low- and middle-income countries. Our aim was to estimate the proportion of pediatric patients with various severe adverse events in the perioperative period extending to 48 hours and to describe the clinical situations and causes of those events. METHODS: We reviewed the M&M database of the Department of Anesthesiology between 1992 and 2016. A data collection tool was developed, and the outcomes were standardized. Each case was reviewed independently and subsequently discussed between 2 reviewers to identify a major primary causative factor. RESULTS: The total number of pediatric cases during this period was 48,828. Seventy-six significant adverse events were identified in 39 patients (8 patients [95% confidence interval {CI}, 5.7–10.9] per 10,000). Thirteen patients had multisystem involvement, and hence the total number of events exceeded the number of patients. Respiratory events were the most common (33.5%). Thirteen patients had perioperative cardiac arrest within 48 hours of surgery (2.6 [95% CI, 1.3–4.3] per 10,000), 7 of these were infants (54%), 5 of whom had congenital heart disease (CHD). Eleven of these 39 patients died within 48 hours (2.0 [95% CI, 1.1–4.0] per 10,000). In 13 cases, anesthesia was assessed to be the predominant cause of morbidity (2.6 per 10,000), whereas in 26 cases, it contributed partially (5.32 per 10,000). There was only 1 death solely related to anesthesia (0.2 per 10,000), and this death occurred before the start of surgery. CONCLUSIONS: Adverse events were uncommon. Respiratory complications were the most frequent (33%). Infants, especially those with CHD, were identified as at a higher risk for perioperative cardiac arrest, but this association was not tested statistically. Twenty-eight percent of the patients who suffered events died within 48 hours. Increased access to anesthesia drugs and practice improvements resulted in a decline in perioperative cardiac arrests.
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Incidence of Anaphylaxis to Sugammadex

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imageBackground: Sugammadex is a modified cyclodextrin that is being increasingly used in anesthetic practice worldwide for the reversal of the aminosteroid neuromuscular blockers rocuronium and vecuronium. Its safety profile, however, is incompletely understood. One such aspect is the incidence of anaphylactic reactions that occur after its administration. While several case reports exist in the literature, there is a paucity of information on the actual incidence of anaphylactic reactions. METHODS: A single-center retrospective chart review identified patients who experienced anaphylaxis to sugammadex in the institutional electronic medical record system. These charts were then reviewed to determine whether the etiology of anaphylaxis was sugammadex administration. RESULTS: Two patients experienced anaphylaxis to sugammadex, which occurred in a single institution cohort of 19,821 patients who received 23,446 total doses. This rate is markedly lower than the 1/300 that the manufacturer's package insert states and also lower than the 1/2500 that the only other large cohort study performed has reported. CONCLUSIONS: The incidence of anaphylaxis to sugammadex in this cohort of patients was 2 of 19,821 patients, who received a total of 23,446 doses.
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Stickler Syndrome: Airway Complications in a Case Series of 502 Patients

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imageBackground: Patients with Stickler syndrome often require emergency surgery and are often anesthetized in nonspecialist units, typically for retinal detachment repair. Despite the occurrence of cleft palate and Pierre-Robin sequence, there is little published literature on airway complications. Our aim was to describe anesthetic practice and complications in a nonselected series of Stickler syndrome cases. To our knowledge, this is the largest such series in the published literature. METHODS: We retrospectively identified patients with genetically confirmed Stickler syndrome who had undergone general anesthesia in a major teaching hospital, seeking to identify factors that predicted patients who would require more than 1 attempt to correctly site an endotracheal tube (ETT) or supraglottic airway device (SAD). Patient demographics, associated factors, and anesthetic complications were collected. Descriptive statistical analysis and logistic regression modeling were performed. RESULTS: Five hundred and two anesthetic events were analyzed. Three hundred ninety-five (92.7%) type 1 Stickler and 63 (96.9%) type 2 Stickler patients could be managed with a single attempt of passing an ETT or SAD. Advanced airway techniques were required on 4 occasions, and we report no major complications. On logistic regression, modeling receding mandible (P = .0004) and history of cleft palate (P = .0004) were significantly associated with the need for more than 1 attempt at airway manipulation. CONCLUSIONS: The majority of Stickler patients can be anesthetized safely with standard management. If patients have a receding mandible or history of cleft, an experienced anesthetist familiar with Stickler syndrome should manage the patient. We recommend that patients identified to have a difficult airway wear an alert bracelet.
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Financial and Clinical Ramifications of Introducing a Novel Pediatric Enhanced Recovery After Surgery Pathway for Pediatric Complex Hip Reconstructive Surgery

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imageBackground: Enhanced recovery after surgery pathways confer significant perioperative benefits to patients and are currently well described for adult patients undergoing a variety of surgical procedures. Robust data to support enhanced recovery pathway use in children are relatively lacking in the medical literature, though clinical benefits are reported in targeted pediatric surgical populations. Surgery for complex hip pathology in the adolescent patient is painful, often requiring prolonged courses of opioid analgesia. Postoperative opioid-related side effects may lead to prolonged recovery periods and suboptimal postoperative physical function. Excessive opioid use in the perioperative period is also a major risk factor for the development of opioid misuse in adolescents. Perioperative opioid reduction strategies in this vulnerable population will help to mitigate this risk. METHODS: A total of 85 adolescents undergoing complex hip reconstructive surgery were enrolled into an enhanced recovery after surgery pathway (October 2015 to December 2018) and were compared with 110 patients undergoing similar procedures in previous years (March 2010 to September 2015). The primary outcome was total perioperative opioid consumption. Secondary outcomes included hospital length of stay, postoperative nausea, intraoperative blood loss, and other perioperative outcomes. Total cost of care and specific charge sectors were also assessed. Segmented regression was used to assess the effects of pathway implementation on outcomes, adjusting for potential confounders, including the preimplementation trend over time. RESULTS: Before pathway implementation, there was a significant downward trend over time in average perioperative opioid consumption (−0.10 mg total morphine equivalents/90 days; 95% confidence interval [CI], −0.20 to 0.00) and several secondary perioperative outcomes. However, there was no evidence that pathway implementation by itself significantly altered the prepathway trend in perioperative opioid consumption (ie, the preceding trend continued). For postanesthesia care unit time, the downward trend leveled off significantly (pre: −5.25 min/90 d; 95% CI, −6.13 to −4.36; post: 1.04 min/90 d; 95% CI, −0.47 to 2.56; Change: 6.29; 95% CI, 4.53–8.06). Clinical, laboratory, pharmacy, operating room, and total charges were significantly associated with pathway implementation. There was no evidence that pathway implementation significantly altered the prepathway trend in other secondary outcomes. CONCLUSIONS: The impacts of our pediatric enhanced recovery pathway for adolescents undergoing complex hip reconstruction are consistent with the ongoing improvement in perioperative metrics at our institution but are difficult to distinguish from the impacts of other initiatives and evolving practice patterns in a pragmatic setting. The ERAS pathway helped codify and organize this new pattern of care, promoting multidisciplinary evidence-based care patterns and sustaining positive preexisting trends in financial and clinical metrics.
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The Attributable Mortality of Postoperative Bleeding Exceeds the Attributable Mortality of Postoperative Venous Thromboembolism

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imageBackground: Bleeding and venous thromboembolic disease are considered important sources of postoperative morbidity and mortality. Clinically, treatment of these 2 disorders is often competing. We sought to better understand the relative contributions of bleeding and venous thromboembolic disease to postoperative attributable mortality in a national cohort. METHODS: A retrospective analysis of the 2006–2017 American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database was performed to assess the adjusted odds ratio and attributable mortality for postoperative bleeding and venous thromboembolism, adjusted by year. RESULTS: After adjustment for confounding variables, bleeding exhibited a high postoperative attributable mortality in every year studied. Venous thromboembolism appeared to contribute minimal attributable mortality. CONCLUSIONS: Bleeding complications are a consistent source of attributable mortality in surgical patients, while the contribution of venous thromboembolic disease appears to be minimal in this analysis. Further studies are warranted to better understand the etiology of this disparity.
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Machine Learning Applied to Registry Data: Development of a Patient-Specific Prediction Model for Blood Transfusion Requirements During Craniofacial Surgery Using the Pediatric Craniofacial Perioperative Registry Dataset

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imageBackground: Craniosynostosis is the premature fusion of ≥1 cranial sutures and often requires surgical intervention. Surgery may involve extensive osteotomies, which can lead to substantial blood loss. Currently, there are no consensus recommendations for guiding blood conservation or transfusion in this patient population. The aim of this study is to develop a machine-learning model to predict blood product transfusion requirements for individual pediatric patients undergoing craniofacial surgery. METHODS: Using data from 2143 patients in the Pediatric Craniofacial Surgery Perioperative Registry, we assessed 6 machine-learning classification and regression models based on random forest, adaptive boosting (AdaBoost), neural network, gradient boosting machine (GBM), support vector machine, and elastic net methods with inputs from 22 demographic and preoperative features. We developed classification models to predict an individual's overall need for transfusion and regression models to predict the number of blood product units to be ordered preoperatively. The study is reported according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) checklist for prediction model development. RESULTS: The GBM performed best in both domains, with an area under receiver operating characteristic curve of 0.87 ± 0.03 (95% confidence interval) and F-score of 0.91 ± 0.04 for classification, and a mean squared error of 1.15 ± 0.12, R-squared (R2) of 0.73 ± 0.02, and root mean squared error of 1.05 ± 0.06 for regression. GBM feature ranking determined that the following variables held the most information for prediction: platelet count, weight, preoperative hematocrit, surgical volume per institution, age, and preoperative hemoglobin. We then produced a calculator to show the number of units of blood that should be ordered preoperatively for an individual patient. CONCLUSIONS: Anesthesiologists and surgeons can use this continually evolving predictive model to improve clinical care of patients presenting for craniosynostosis surgery.
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Analgesic Effect of Intraoperative Intravenous S-Ketamine in Opioid-Naïve Patients After Major Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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imageBackground: Severe pain often accompanies major spine surgery. Opioids are the cornerstone of postoperative pain management but their use can be limited by numerous side effects. Several studies claim that adjuvant treatment with intravenous (IV) ketamine reduces opioid consumption and pain after back surgery. However, the exact role of ketamine for this indication is yet to be elucidated. We compared 2 different doses of S-ketamine with placebo on postoperative analgesic consumption, pain, and adverse events in adult, opioid-naïve patients after lumbar fusion surgery. METHODS: One hundred ninety-eight opioid-naïve patients undergoing lumbar spinal fusion surgery were recruited to this double-blind trial and randomly assigned into 3 study groups: Group C (placebo) received a preincisional IV bolus of saline (sodium chloride [NaCl] 0.9%) followed by an intraoperative IV infusion of NaCl 0.9%. Both groups K2 and K10 received a preincisional IV bolus of S-ketamine (0.5 mg/kg); in group K2, this was followed by an intraoperative IV infusion of S-ketamine (0.12 mg/kg/h), while in group K10, it was followed by an intraoperative IV infusion of S-ketamine (0.6 mg/kg/h). Postoperative analgesia was achieved by an IV patient-controlled analgesia (IV PCA) device delivering oxycodone. The primary end point was cumulative oxycodone consumption at 48 hours after surgery. The secondary end points included postoperative pain up to 2 years after surgery, adverse events, and level of sedation and confusion in the immediate postoperative period. RESULTS: The median [interquartile range (IQR)] cumulative oxycodone consumption at 48 hours was 154.5 [120] mg for group K2, 160 [109] mg for group K10, and 178.5 [176] mg for group C. The estimated difference was −24 mg between group K2 and group C (97.5% confidence interval [CI], −73.8 to 31.5; P = .170) and −18.5 mg between group K10 and C (97.5% CI, 78.5–29.5; P = .458). There were no significant differences between groups. Postoperative pain scores were significantly lower in both ketamine treatment groups at the fourth postoperative hour but not later during the 2-year study period. The higher ketamine dose was associated with more sedation. Otherwise, differences in the occurrence of adverse events between study groups were nonsignificant. CONCLUSIONS: Neither a 0.12 nor a 0.6 mg/kg/h infusion of intraoperative IV S-ketamine was superior to the placebo in reducing oxycodone consumption at 48 hours after lumbar fusion surgery in an opioid-naïve adult study population. Future studies should assess ketamine's feasibility in specific study populations who most benefit from reduced opioid consumption.
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Daily Caffeine Consumption Does Not Influence Acupuncture Analgesia in Healthy Individuals: A Preliminary Study

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imageAnimal studies suggest that caffeine may interfere with acupuncture analgesia. This study investigated the modulation effect of daily caffeine intake on acupuncture analgesia in 27 healthy subjects using a crossover design. We found that real acupuncture increased pain thresholds compared to sham acupuncture. Further, there was no association between caffeine intake measurements of daily caffeine use, duration of caffeine consumption, or their interaction and preacupuncture and postacupuncture pain threshold changes. Our findings suggest that daily caffeine intake may not influence acupuncture anal gesia in the cohort of healthy subjects who participated in study.
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