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BACKGROUND: An intraoperative transfer of care from one anesthesia provider to another, or handover, may result in information loss and contribute to adverse patient outcomes. In 2019 the authors undertook a quality improvement effort to increase the use of a structured intraoperative handover tool incorporated in the electronic medical record. The authors hypothesized that intraoperative handovers of anesthesia care would be associated with adverse patient outcomes, and that increased use of a structured tool would attenuate this effect. METHODS: This study included adult patients undergoing noncardiac surgery of at least 1 h duration performed during the period 2016 to 2021. Cases with a handover were identified if either there was a change of attending anesthesiologist or change of nurse anesthetist or resident for more than 35 min. The primary outcome was the occurrence of a composite of postoperative mortality and major postoperative morbidity. The effect of the intervention was analyzed by examining the quarterly change in odds ratio for the primary outcome for cases with and without a handover. RESULTS: A total of 121,077 cases, 40.4% of which had a handover, were included. After weighting, the composite outcome was statistically associated with handovers (3,517 of 48,986 [7.2%] in handover cases vs. 4,470 of 72,091 [6.2%] in nonhandover cases; odds ratio, 1.08; 95% CI, 1.04 to 1.12). Time series analysis showed a marked increase in usage of the structured tool after the initial intervention. The odds ratio for the composite outcome showed a significant decrease over time after the initial intervention (t = -3.97; P < 0.001), with the slope of the odds ratio versus time curve decreasing from 0.002 (95% CI, 0.001 to 0.004; P = 0.018) to -0.011 (95% CI, -0.01 to -0.018; P < 0.001). CONCLUSIONS: Intraoperative handovers are significantly associated with adverse outcomes even after controlling for multiple confounding variables. Use of a structured handover tool during anesthesia care may attenuate the adverse effect.
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Anestesia , Anestesiologia , Transferência da Responsabilidade pelo Paciente , Adulto , Humanos , Melhoria de Qualidade , Estudos Retrospectivos , Anestesia/efeitos adversosRESUMO
Because up to 12% of obstetric patients meet criteria for the diagnosis of thrombocytopenia in pregnancy, it is not infrequent that the anesthesiologist must decide whether to proceed with a neuraxial procedure in an affected patient. Given the potential morbidity associated with general anesthesia for cesarean delivery, thoughtful consideration of which patients with thrombocytopenia are likely to have an increased risk of spinal epidural hematoma with neuraxial procedures, and when these risks outweigh the relative benefits is important to consider and to inform shared decision making with patients. Because there are substantial risks associated with withholding a neuraxial analgesic/anesthetic procedure in obstetric patients, every effort should be made to perform a bleeding history assessment and determine the thrombocytopenia etiology before admission for delivery. Whereas multiple other professional societies (obstetric, interventional pain, and hematologic) have published guidelines addressing platelet thresholds for safe neuraxial procedures, the US anesthesia professional societies have been silent on this topic. Despite a paucity of high-quality data, there are now meta-analyses that provide better estimations of risks. An interdisciplinary taskforce was convened to unite the relevant professional societies, synthesize the data, and provide a practical decision algorithm to help inform risk-benefit discussions and shared decision making with patients. Through a systematic review and modified Delphi process, the taskforce concluded that the best available evidence indicates the risk of spinal epidural hematoma associated with a platelet count ≥70,000 × 106/L is likely to be very low in obstetric patients with thrombocytopenia secondary to gestational thrombocytopenia, immune thrombocytopenia (ITP), and hypertensive disorders of pregnancy in the absence of other risk factors. Ultimately, the decision of whether to proceed with a neuraxial procedure in an obstetric patient with thrombocytopenia occurs within a clinical context. Potentially relevant factors include, but are not limited to, patient comorbidities, obstetric risk factors, airway examination, available airway equipment, risk of general anesthesia, and patient preference.
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Anestesia Obstétrica/normas , Consenso , Perinatologia/normas , Sociedades Médicas/normas , Trombocitopenia/terapia , Comitês Consultivos/normas , Anestesia Obstétrica/métodos , Feminino , Humanos , Perinatologia/métodos , Gravidez , Trombocitopenia/diagnósticoRESUMO
BACKGROUND: Frequent hand hygiene by anesthesia personnel may be an important factor in reducing contamination of IV lines and medication access ports and may reduce hospital-acquired infections. Measurement of hand hygiene frequency at the individual clinician level by direct observation or electronic devices is cumbersome and expensive. We developed and validated a simple method for estimating hand hygiene frequency by individual anesthesia providers and utilized it in a quality improvement initiative to increase hand hygiene use. METHODS: Pump-style, alcohol-based hand hygiene container weight at the anesthesia work station was measured before and after each surgical operation and converted to estimated number of accesses (pumps) per hour. Video observation was used to validate the estimated hand hygiene use. A quality improvement initiative utilized periodic measurement of hand hygiene frequency via the validated method, and incorporated individual provider feedback, email reminders, monthly departmental performance reports, and reminders in the electronic anesthesia record. Segmented linear regression was used to evaluate the effect of the intervention on hand hygiene use. RESULTS: Delivered product per pump was consistent for containers at least half-full and averaged (mean ± SD) 0.92 ± 0.13 g per pump. Video observation in 26 cases showed a strong correlation between observed hand hygiene episodes and estimated hand hygiene use frequency based on weight change of the container (linear regression, R = 0.97, P < .0001). Median hand hygiene frequency was near 0 at baseline but increased progressively throughout the intervention period (segmented linear regression, overall R = 0.76, P < .0001; change of intercept or mean hand hygiene after initiation of intervention [parameter estimate ± SE] [0.970 ± 0.29], P = .0008). CONCLUSIONS: A low-cost, simple method for measuring individual anesthesia clinician use of hand hygiene intraoperatively based on container weight change is feasible and sufficiently accurate to support a quality improvement initiative to increase its use.
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Anestesiologistas , Atitude do Pessoal de Saúde , Desinfecção das Mãos , Higienizadores de Mão , Conhecimentos, Atitudes e Prática em Saúde , Controle de Infecções/métodos , Padrões de Prática Médica , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Humanos , Reprodutibilidade dos Testes , Fatores de Tempo , Gravação em Vídeo , Pesos e MedidasRESUMO
BACKGROUND: Fever and increased maternal interleukin-6 (IL-6) plasma levels in labor are associated with an increased risk of adverse events in offspring, including neonatal seizures, cerebral palsy, and low intelligence scores at school age. However, the neural changes in the neonate that might mediate the adverse effects of maternal noninfectious fever are not fully characterized. This study was designed to test the hypothesis that induced maternal noninfectious fever alters neonatal neural progenitor cell proliferation and enhances microglial activation in the rat dentate gyrus of the hippocampus. METHODS: Systemic vehicle or IL-6 was given 3 times to near-term pregnant rats (n = 7/group) every 90 minutes, and maternal core temperature was recorded. Neonatal brains were processed and analyzed for dentate gyrus cell proliferation (using Ki-67, n = 10/group, and glial fibrillary acidic protein, n = 6/group) and resident microglia activation (using ionized calcium-binding adaptor protein-1 [Iba-1], n = 6/group). In separate studies, the authors assessed microglia proliferation using Ki-67/Iba-1 costaining (n = 5/group). RESULTS: Compared to controls, exposure to IL-6 resulted in significant maternal temperature increase [mean temperature difference 0.558°C (95% CI, 0.417-0.698; P < .0001)]. Following maternal IL-6, Ki-67 cell proliferation in the dentate gyrus was 55 % higher in neonates whose mother received IL-6 (38.8 ± 9.2) compared with those that received vehicle (25.1 ± 7.8); mean difference 13.7 (95% CI, 5.68-21.71); (P = .0021). Glial fibrillary acidic protein cell proliferation was 40% higher in the neonatal dentate gyrus whose mother received IL-6 when compared to controls (713 ± 85.52 vs 500 ± 115); mean difference 212 (95% CI, 82.2-343.4); (P = .004). Resident microglial activation was 90% higher in the dentate gyrus of neonates whose mother received IL-6 when compared to controls (71.8 ± 9.3 vs 37.8 ± 5.95); mean Iba-1 in stained cells was significantly different between IL-6 and vehicle groups 34 (95% CI, 23.94-44.05); (P < .0001). Proliferating microglia, determined by the colocalization of Ki-67 and Iba-1, were not different in the vehicle (8.8 % ± 3.19 %) and the IL-6 (5.6% ± 2.3%) groups (mean difference 3.2% (95% CI, -0.8-7.25) (P = .1063). CONCLUSIONS: IL-6 is sufficient to induce maternal systemic temperature increases in near-term pregnant rats as well as neuronal, glial, and neuroinflammatory changes in the dentate gyrus of the neonatal hippocampus. These alterations might disrupt fetal neurodevelopment during a vulnerable period.
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Giro Denteado/metabolismo , Febre/fisiopatologia , Interleucina-6/sangue , Exposição Materna/efeitos adversos , Microglia/metabolismo , Prenhez , Animais , Lesões Encefálicas/sangue , Cálcio/metabolismo , Proliferação de Células , Feminino , Feto/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Inflamação , Mães , Gravidez , Complicações na Gravidez , Ratos , TemperaturaRESUMO
BACKGROUND: Intrapartum maternal fever is associated with several adverse neonatal outcomes. Intrapartum fever can be infectious or inflammatory in etiology. Increases in interleukin 6 and other inflammatory markers are associated with maternal fever. Magnesium has been shown to attenuate interleukin 6-mediated fever in animal models. We hypothesized that parturients exposed to intrapartum magnesium would have a lower incidence of fever than nonexposed parturients. METHODS: In this study, electronic medical record data from all deliveries at Northwestern Memorial Hospital (Chicago, Illinois) between 2007 and 2014 were evaluated. The primary outcome was intrapartum fever (temperature at or higher than 38.0°C). Factors associated with the development of maternal fever were evaluated using a multivariable logistic regression model. Propensity score matching was used to reduce potential bias from nonrandom selection of magnesium administration. RESULTS: Of the 58,541 women who met inclusion criteria, 5,924 (10.1%) developed intrapartum fever. Febrile parturients were more likely to be nulliparous, have used neuraxial analgesia, and have been delivered via cesarean section. The incidence of fever was lower in women exposed to magnesium (6.0%) than those who were not (10.2%). In multivariable logistic regression, women exposed to magnesium were less likely to develop a fever (adjusted odds ratio = 0.42 [95% CI, 0.31 to 0.58]). After propensity matching (N = 959 per group), the odds ratio of developing fever was lower in women who received magnesium therapy (odds ratio = 0.68 [95% CI, 0.48 to 0.98]). CONCLUSIONS: Magnesium may play a protective role against the development of intrapartum fever. Future work should further explore the association between magnesium dosing and the incidence of maternal fever.
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Parto Obstétrico/efeitos adversos , Febre/epidemiologia , Febre/prevenção & controle , Magnésio/administração & dosagem , Saúde Materna , Adulto , Estudos Transversais , Parto Obstétrico/métodos , Registros Eletrônicos de Saúde , Feminino , Humanos , Incidência , Gravidez , Estudos RetrospectivosRESUMO
BACKGROUND: Women laboring with epidural analgesia experience fever much more frequently than do women who chose other forms of analgesia, and maternal intrapartum fever is associated with numerous adverse consequences, including brain injury in the fetus. We developed a model of noninfectious inflammatory fever in the near-term pregnant rat to simulate the pathophysiology of epidural-associated fever and hypothesized that it would produce fetal brain inflammation. METHODS: Twenty-four pregnant Sprague-Dawley rats were studied at 20 days gestation (term: 22 days). Dams were treated by injection of rat recombinant interleukin (IL)-6 or vehicle at 90-minute intervals, and temperature was monitored every 30 minutes. Eight hours after the first treatment, dams were delivered of fetuses and then killed. Maternal IL-6 was measured at delivery. Fetal brains (n = 24) were processed and stained for ED-1/CD68, a marker for activated microglia, and cell counts in the lateral septal and hippocampal brain regions were measured. Fetal brains were also stained for cyclooxygenase-2 (COX-2), a downstream marker of neuroinflammation. Eight fetal brains were further analyzed for quantitative forebrain COX-2 by Western blotting compared to a ß-actin standard. Maternal temperature and IL-6 levels were compared between treatments, as were cell counts, COX-2 staining, and COX-2 levels by Mann-Whitney U test, repeated-measures analysis of variance, or Fisher exact test, as appropriate. RESULTS: Injection of rat IL-6 at 90-minute intervals produced an elevation of maternal temperature compared to vehicle (P < .0001). IL-6 levels were elevated to clinically relevant levels at delivery in IL-6 compared to vehicle-treated animals (mean ± standard deviation: 923 ± 97 vs 143 ± 94 pg/mL, P = .0006). ED-1-stained cells were present in significantly higher numbers in fetal brains from IL-6 compared to saline-treated dams (median [interquartile range]: caudal hippocampus, 99 [94-104] and 64 [57-68], respectively, P = .002; lateral septum, 102 [96-111] and 68 [65-69], respectively, P = .002), as well as COX-2 immunostaining (lateral septum, 22 [20-26] and 17 [15-18], respectively, P = .005; dorsal hippocampus, 27 [22-32] and 16 [14-19], respectively, P = .013) and quantitative COX-2 Western blotting activity (mean ± standard error of the mean: vehicle, 0% of ß-actin intensity versus IL-6, 41.5% ± 24%, P < .001). CONCLUSIONS: Noninfectious inflammatory fever is inducible in the near-term pregnant rat by injection of IL-6 at levels comparable to those observed during human epidural labor analgesia. Maternal IL-6 injection causes neuroinflammation in the fetus.
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Analgesia Epidural/efeitos adversos , Encéfalo/metabolismo , Feto/metabolismo , Febre/metabolismo , Mediadores da Inflamação/metabolismo , Animais , Encéfalo/patologia , Feminino , Feto/patologia , Febre/etiologia , Febre/patologia , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are recommended as first-line treatment of renal angiomyolipoma associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sporadic LAM), but follow-up is limited. Longer term efficacy and tolerability data from a Phase 3, double-blind, placebo-controlled trial are presented. METHODS: Following favorable results from the primary analysis (data cutoff 30 June 2011) of the EXIST-2 trial, patients still receiving study treatment were allowed to enter an open-label extension. Everolimus was initiated at 10 mg once daily and titrated based on tolerability. The primary outcome was angiomyolipoma response rate (≥ 50% reduction from baseline in target lesion volumes). Safety was a secondary endpoint. RESULTS: As of the cutoff date (1 May 2013), 112 patients had received everolimus, and the response rate in 107 patients with angiomyolipoma (median duration of medication exposure of 28.9 months) was 54%. The proportion of patients achieving angiomyolipoma reductions of ≥ 30% and ≥ 50% increased over time, reaching 81.6% (62/76) and 64.5% (49/76), respectively, by Week 96. No everolimus-treated patients experienced renal bleeding. The long-term safety profile was consistent with previous reports; adverse events (AEs) were mostly Grade 1/2, and there were no new safety issues. The frequency of emerging AEs and severe AEs lessened over time. CONCLUSIONS: Longer term everolimus treatment appeared safe and effective in patients with TSC- or sporadic LAM-associated renal angiomyolipoma not requiring surgical intervention. Continued reduction in angiomyolipoma volume was demonstrated, and there was no angiomyolipoma-related bleeding; AEs were predictable and generally manageable. TRIAL REGISTRATION: clinicaltrialsgov identifier: NCT00790400 (http://clinicaltrials.gov/ct2/show/NCT00790400).
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Angiomiolipoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Everolimo/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Linfangioleiomiomatose/tratamento farmacológico , Esclerose Tuberosa/tratamento farmacológico , Adolescente , Adulto , Angiomiolipoma/patologia , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Rim/patologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND/AIMS: The phase III placebo-controlled RADIANT-2 trial investigated the efficacy of everolimus plus octreotide long-acting repeatable (LAR) in patients with advanced neuroendocrine tumors (NET) associated with carcinoid syndrome. Here we report a secondary analysis based on the previous somatostatin analogue (SSA) exposure status of patients enrolled in RADIANT-2. METHODS: Patients were randomly assigned to receive oral everolimus 10 mg/day plus octreotide LAR 30 mg intramuscularly (i.m.) or to receive matching placebo plus octreotide LAR 30 mg i.m. every 28 days. SSA treatment before study enrollment was permitted. Patient characteristics and progression-free survival (PFS) were analyzed by treatment arm and previous SSA exposure status. RESULTS: Of the 429 patients enrolled in RADIANT-2, 339 were previously exposed to SSA (95% received octreotide); 173 of 339 patients were in the everolimus plus octreotide LAR arm. All patients had a protocol-specified history of secretory symptoms, but analysis by type showed that more patients who previously received SSA therapy had a history of flushing symptoms (77%), diarrhea (86%), or both (63%) compared with SSA-naive patients (62, 62, and 24%, respectively). Patients who received everolimus plus octreotide LAR had longer median PFS regardless of previous SSA exposure (with: PFS 14.3 months, 95% confidence interval, CI, 12.0-20.1; without: 25.2 months, 95% CI, 12.0-not reached) compared with patients who received placebo plus octreotide LAR (with: 11.1 months, 95% CI, 8.4-14.6; without: 13.6 months, 95% CI, 8.2-22.7). CONCLUSION: Everolimus in combination with octreotide improves PFS in patients with advanced NET associated with carcinoid syndrome, regardless of previous SSA exposure.
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Everolimo/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Octreotida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Quimioterapia Combinada , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Octreotida/efeitos adversos , Resultado do Tratamento , Adulto JovemAssuntos
Analgesia Epidural , Analgesia Obstétrica , Complicações na Gravidez , Feminino , Humanos , Gravidez , RopivacainaRESUMO
BACKGROUND: Because of the lack of large obstetric anesthesia databases, the incidences of serious complications related to obstetric anesthesia remain unknown. The Society for Obstetric Anesthesia and Perinatology developed the Serious Complication Repository Project to establish the incidence of serious complications related to obstetric anesthesia and to identify risk factors associated with each. METHODS: Serious complications were defined by the Society for Obstetric Anesthesia and Perinatology Research Committee which also coordinated the study. Thirty institutions participated in the approximately 5-yr study period. Data were collected as part of institutional quality assurance and sent to the central project coordinator quarterly. RESULTS: Data were captured on more than 257,000 anesthetics, including 5,000 general anesthetics for cesarean delivery. There were 157 total serious complications reported, 85 of which were anesthesia related. High neuraxial block, respiratory arrest in labor and delivery, and unrecognized spinal catheter were the most frequent complications encountered. A serious complication occurs in approximately 1:3,000 (1:2,443 to 1:3,782) obstetric anesthetics. CONCLUSIONS: The Serious Complication Repository Project establishes the incidence of serious complications in obstetric anesthesia. Because serious complications related to obstetric anesthesia are rare, there were too few complications in each category to identify risk factors associated with each. However, because many of these complications can lead to catastrophic outcomes, it is recommended that the anesthesia provider remains vigilant and be prepared to rapidly diagnose and treat any complication.
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Anestesia Obstétrica/efeitos adversos , Morte Materna , Perinatologia/normas , Complicações Pós-Operatórias/diagnóstico , Sociedades Médicas/normas , Anestesia Obstétrica/tendências , Feminino , Humanos , Recém-Nascido , Morte Materna/tendências , Perinatologia/tendências , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Gravidez , Sociedades Médicas/tendênciasRESUMO
BACKGROUND: Previously we demonstrated that a computer algorithm based on bedside airway examinations and facial photographs accurately classified easy and difficult airways. The extent of the ability of anesthesiologists to perform the same task is unknown. We hypothesized that providing photographs would add to the predictive ability of anesthesiologists over that achieved when provided only with the Mallampati (MP) score and the thyromental distance (TMD). We further hypothesized that human observers would implicitly bias their predictions toward more sensitive determination of difficult airways, rather than more specific determination of easy airways. METHODS: Residents, fellows, and attending anesthesiologists with varying levels of experience (N = 160) were presented with MP and TMD information from 80 Caucasian men subjects. The same subjects' data, accompanied by 3 facial photographs in head-on and right and left profiles, were also presented. Anesthesiologists classified the airways as easy or difficult according to specified criteria ("easy" defined as a single attempt with a Macintosh 3 blade resulting in a grade 1 laryngoscopic view; "difficult" defined as >1 attempt by an operator with at least 12 months anesthesia experience, grade 3 or 4 laryngoscopic view, need for a second operator, or nonelective use of an alternative airway device). Accuracy, sensitivity, and specificity were calculated for each anesthesiologist. We further developed a cost function to quantify a relative bias toward avoiding an unexpectedly difficult intubation versus overpreparing for an easy intubation. RESULTS: One hundred sixty respondents completed the study. Presenting photographs improved respondents' sensitivity and accuracy in classifying airways, though specificity decreased slightly. Overall accuracy when given photographs was 61.6% (95% confidence interval, 60.8%-62.4%), which was significantly lower than the computer's performance of 87.5% (t test, P < 0.0001). Presentation of photographs, compared with MP and TMD alone, caused anesthesiologists to change their prediction from easy to difficult more frequently if the patients were obese (weight or body mass index), despite not having data on weight or height available. The cost function demonstrated that anesthesiologists strongly preferred to enhance sensitivity (detecting difficult airways) as compared with specificity (detecting easy airways), with a ratio of 6.5:1 (95% confidence interval, 4.9:1-8.4:1). CONCLUSIONS: Anesthesiologists can derive useful information from facial appearance that enhances the prediction of a difficult airway over that achieved when presented with MP and TMD data alone. Anesthesiologists implicitly bias their predictions toward detection of difficult airways, compared with the true incidence of difficult airways, at the expense of accuracy and specificity. This behavior may be rational for cognitive tasks in which the costs of failure are strongly asymmetric.
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Face/anatomia & histologia , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Reconhecimento Visual de Modelos , Algoritmos , Anestesiologia/métodos , Peso Corporal , Humanos , Internato e Residência , Laringoscopia/métodos , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos TestesRESUMO
Respiratory failure is a common perioperative complication. The risk of respiratory failure can be reduced with effective preoperative evaluation, preventative measures, and knowledge of evidence-based management techniques. Effective preoperative screening methods include ARISCAT scoring, OSA screening, and the LAS VEGAS score (including the ASA physical status score). Evaluation by the six-minute walk test and a routine pulmonary physical exam has been shown to be effective at predicting postoperative pulmonary complications, whereas evidence on the predictive power of pulmonary function tests and chest radiography has been inconclusive. Preoperative smoking cessation and lung expansion maneuvers have been shown to decrease the risk of pulmonary complications postoperatively. Intraoperative management techniques that decrease the pulmonary complication risk include neuromuscular blockade reversal with sugammadex, limiting surgical times to less than 3 h when possible, lung-protective ventilation techniques, and multimodal analgesia to decrease opioid usage. In the immediate postoperative period, providers should be prepared to quickly treat bronchospasm, hypoventilation, and upper airway obstruction. For post-surgical patients who remain in the hospital, the risk of pulmonary complications can be decreased with lung expansion techniques, adequate analgesia, automated continuous postoperative ward monitoring, non-invasive ventilatory support, and early mobilization. This article was written to analyze the available literature on this topic in order to learn and practice the prevention of perioperative respiratory failure when caring for patients on a daily basis.
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BACKGROUND AND OBJECTIVE: Sotrovimab 500 mg administered by a single intravenous (IV) infusion has been granted special approval for emergency use in Japan for treatment of SARS-CoV-2 infection in adults and children aged ≥ 12 years weighing ≥ 40 kg. This Phase 1, single-dose study investigated the pharmacokinetics, safety, and tolerability of IV or intramuscular (IM) sotrovimab 500 mg doses versus placebo in healthy Japanese and Caucasian volunteers. METHODS: This was a two-part, Phase 1, randomized, placebo-controlled, single-blind study. In Part 1, participants received a single sotrovimab 500 mg IV infusion or matching placebo on Day 1. In Part 2, participants received a single sotrovimab 500 mg IM dose or matching placebo on Day 1, administered as two 4 mL injections. RESULTS: There was no effect of ethnicity on the peak or total serum exposure of IV sotrovimab through Week 18; after adjusting for body weight, the point estimate and 90 % confidence interval for the ratio of total exposure between Japanese and Caucasian participants fell within conventional bioavailability bounds (80-125%). Geometric mean Cmax and AUClast following a single IM administration of sotrovimab were higher in Japanese participants compared with Caucasian participants, even after adjustment for body weight. Overall, a single IV or IM dose of sotrovimab was well tolerated by both Japanese and Caucasian participants. CONCLUSIONS: After adjusting for body weight, exposures following a single IV dose of sotrovimab 500 mg were similar between Japanese and Caucasian participants, and higher in Japanese participants following IM administration. Higher exposures were not associated with any safety signals. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT04988152.
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Anticorpos Neutralizantes , COVID-19 , Adulto , Criança , Humanos , Japão/epidemiologia , Voluntários Saudáveis , Método Simples-Cego , SARS-CoV-2 , Anticorpos Monoclonais Humanizados/efeitos adversos , Peso Corporal , Método Duplo-CegoRESUMO
This case report was written with the assistance of the large language model known as ChatGPT, a form of generative artificial intelligence that can write grammatically correct and semantically meaningful prose on a multitude of topics. Here, it has assisted us in presenting a case of anesthetic management for a case of Juvenile Hyaline Fibromatosis (JHF), an extremely rare genetic disorder that is part of a spectrum of diseases presently characterized as Hyaline Fibromatosis Syndrome (HFS), which also includes a more severe variant presenting in infancy. HFS is caused by autosomal recessive mutations in the ANTXR2 (anthrax toxin receptor cell adhesion molecule 2) gene, which binds collagen IV and laminin, suggesting that it may be involved in extracellular matrix adhesion. Defects in this molecule lead to abnormal deposition of hyaline material in perivascular areas, presenting as cutaneous lesions, joint contractures, and in some cases internal organ dysfunction. Anesthetic management of patients with JHF may present difficulties with patient positioning and airway management. Most reports of anesthetic management concern children with severe disease and adult reports are uncommon. We present a case of JHF in a 39-year-old woman managed for resection of a lower extremity cutaneous lesion. The anesthetic management of this relatively minor case was uneventful, but the process of drafting this report with the assistance of the new software tool ChatGPT was informative of both its strengths and limitations.
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STUDY OBJECTIVE: The hypothesis that the exclusive use of the commonly used vasopressor phenylephrine during the intraoperative period in noncardiac surgery is associated with postoperative acute kidney injury (AKI) was tested. DESIGN: A retrospective cohort analysis of 16,306 adults undergoing major noncardiac surgery who either did or did not receive phenylephrine was conducted. The primary outcome was the association of the use of phenylephrine with the risk of postoperative AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression models with all independently associated potential confounders, and an exploratory model considering only patients with no untreated minutes of hypotension (post-phenylephrine in the exposed cohort, or entire case in the unexposed cohort) were used in the analysis. SETTING: The study was conducted in a tertiary care university hospital where a total of 8,221 patients were exposed to phenylephrine, and 8,085 were not. RESULTS: In unadjusted analysis, phenylephrine exposure was associated with an increased risk of AKI (OR 1.615, 95% CI [1.522-1.725], p < 0.001). In an adjusted model including several variables associated with AKI, phenylephrine remained associated with AKI (OR 1.325 [1.153-1.524]), as did post-phenylephrine exposure lengths of hypotension. Exclusion of patients with >1 min of post-phenylephrine exposure hypotension, also demonstrated that phenylephrine use was associated with AKI (OR 1.478, [1.245-1.753]). CONCLUSIONS: The exclusive use of intraoperative phenylephrine is associated with an increased risk of postoperative renal injury. Anesthesiologists must consider a balanced approach to correct hypotension under anesthesia, including judicious choices for fluids, inotropic support when indicated, and an appropriate adjustment of the plane of anesthesia.
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Injúria Renal Aguda , Hipotensão , Adulto , Humanos , Estudos Retrospectivos , Fenilefrina/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hipotensão/tratamento farmacológico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Fatores de RiscoRESUMO
BACKGROUND: Many students elect to take gap years in between graduating college and matriculating into medical school. At an academic institution, investigators can be limited in conducting research due to clinical endeavors. Utilizing a structured, clinical research, gap-year program with students called clinical research technicians (CRTs) can aid both investigators conducting research and students applying to graduate health programs. In this original article, we sought to understand CRT and investigator perceptions of and experiences in the program. METHODS: We distributed a survey to past and present CRTs and the investigators with whom they worked at Atrium Health Wake Forest Baptist Medical Center. We conducted thematic and sentiment analyses of the survey results. We also collected data on grant approvals, research funding awards, and CRT, clinical research nurse, and clinical research coordinator salaries. RESULTS: We received responses from 20/29 investigators and 21/22 CRTs. We identified five themes for the investigator survey, including research accuracy and precision; research output; alleviating responsibilities; cost; and likelihood of referral. We identified five themes for the CRT survey, including future career assistance; physician career insights; mentorship; likelihood of referral; and other. The majority of respondents strongly agreed or agreed with the survey statements. The majority of comments were coded as positive. All of CRTs were accepted into a graduate health profession program. CONCLUSIONS: Our program's success demonstrates how a structured, clinical research, gap-year program for premedical students can serve as a new educational tool and important research infrastructure resource for hospitals.