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INTRODUCTION: Tracheal intubation in the Intensive Care Unit (ICU) can be challenging as patients often have anatomic and physiologic characteristics that make intubation particularly difficult. Video laryngoscopy (VL) has been shown to improve first attempt success compared to direct laryngoscopy (DL) in many clinical settings and may be an option for ICU intubations. METHODS: All intubations performed in this academic medical ICU during a 13-month period were entered into a prospectively collected quality control database. After each intubation, the operator completed a standardized form evaluating multiple aspects of the intubation including: patient demographics, difficult airway characteristics (DACs), method and device(s) used, medications used, outcomes and complications of each attempt. Primary outcome was first attempt success. Secondary outcomes were grade of laryngoscopic view, ultimate success, esophageal intubations, and desaturation. Multivariate logistic regression was performed for first attempt and ultimate success. RESULTS: Over the 13-month study period (January 2012-February 2013), a total of 234 patients were intubated using VL and 56 patients were intubated with DL. First attempt success for VL was 184/234 (78.6%; 95% CI 72.8 to 83.7) while DL was 34/56 patients (60.7%; 95% CI 46.8 to 73.5). Ultimate success for VL was 230/234 (98.3%; 95% CI 95.1 to 99.3) while DL was 52/56 patients (91.2%; 95% CI 81.3 to 97.2). In the multivariate regression model, VL was predictive of first attempt success with an odds ratio of 7.67 (95% CI 3.18 to 18.45). VL was predictive of ultimate success with an odds ratio of 15.77 (95% CI 1.92 to 129). Cormack-Lehane I or II view occurred 199/234 times (85.8%; 95% CI 79.5 to 89.1) and a median POGO (Percentage of Glottic Opening) of 82% (IQR 60 to 100) with VL, while Cormack-Lehane I or II view occurred 34/56 times (61.8%; 95% CI 45.7 to 71.9) and a median POGO of 45% (IQR 0 to 78%) with DL. VL reduced the esophageal intubation rate from 12.5% with DL to 1.3% (P = 0.001) but there was no difference in desaturation rates. CONCLUSIONS: In the medical ICU, video laryngoscopy resulted in higher first attempt and ultimate intubation success rates and improved grade of laryngoscopic view while reducing the esophageal intubation rate compared to direct laryngoscopy.
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Unidades de Terapia Intensiva , Intubação Intratraqueal/métodos , Laringoscopia/métodos , Gravação em Vídeo , Esôfago , Humanos , Resultado do TratamentoRESUMO
RATIONALE: Video laryngoscopy has overcome the need to align the anatomic axes to obtain a view of the glottic opening to place a tracheal tube. However, despite this advantage, a large number of attempts are unsuccessful. There are no existing data on anatomic characteristics in critically ill patients associated with a failed first attempt at laryngoscopy when using video laryngoscopy. OBJECTIVES: To identify characteristics associated with first-attempt failure at intubation when using video laryngoscopy in the intensive care unit (ICU). METHODS: This is an observational study of 906 consecutive patients intubated in the ICU with a video laryngoscope between January 2012 and January 2016 in a single-center academic medical ICU. After each intubation, the operator completed a data collection form, which included information on difficult airway characteristics, device used, and outcome of each attempt. Multivariable regression models were constructed to determine the difficult airway characteristics associated with a failed first attempt at intubation. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in sex, age, reason for intubation, or device used between first-attempt failures and first-attempt successes. First-attempt successes more commonly reported no difficult airway characteristics were present (23.9%; 95% confidence interval [CI], 20.7-27.0% vs. 13.3%; 95% CI, 8.0-18.8%). In logistic regression analysis of the entire 906-patient database, blood in the airway (odds ratio [OR], 2.63; 95% CI, 1.64-4.20), airway edema (OR, 2.85; 95% CI, 1.48-5.45), and obesity (OR, 1.59; 95% CI, 1.08-2.32) were significantly associated with first-attempt failure. Data collection on limited mouth opening and secretions began after the first 133 intubations, and we fit a second logistic model to examine cases in which these additional difficult airway characteristics were collected. In this subset (n = 773), the presence of blood (OR, 2.73; 95% CI, 1.60-4.64), cervical immobility (OR, 3.34; 95% CI, 1.28-8.72), and airway edema (OR, 3.10; 95% CI, 1.42-6.70) were associated with first-attempt failure. CONCLUSIONS: In this single-center study, presence of blood in the airway, airway edema, cervical immobility, and obesity are associated with higher odds of first-attempt failure, when intubation was performed with video laryngoscopy in an ICU.
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Intubação Intratraqueal/métodos , Laringoscopia/métodos , Sistema Respiratório/fisiopatologia , Gravação em Vídeo , Idoso , Arizona , Cuidados Críticos/métodos , Bases de Dados Factuais , Feminino , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/instrumentação , Modelos Logísticos , Lesão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Avaliação de Processos e Resultados em Cuidados de SaúdeRESUMO
RATIONALE: Urgent tracheal intubation is performed frequently in intensive care units and incurs higher risk than when intubation is performed under more controlled circumstances. Video laryngoscopy may improve the chances of successful tracheal intubation on the first attempt; however, existing comparative data on outcomes are limited. OBJECTIVES: To compare first-attempt success and complication rates during intubation when using video laryngoscopy compared with traditional direct laryngoscopy in a tertiary academic medical intensive care unit. METHODS: We prospectively collected and analyzed data from a continuous quality improvement database of all intubations in one medical intensive care unit between January 1, 2012, and December 31, 2014. Propensity matching and multivariable logistic regression were used to reduce the risk of bias and control for confounding. MEASUREMENTS AND MAIN RESULTS: A total of 809 intubations took place over the study period. Of these, 673 (83.2%) were performed using video laryngoscopy and 136 (16.8%) using direct laryngoscopy. First-attempt success with video laryngoscopy was 80.4% (95% confidence interval [CI], 77.2-83.3%) compared with 65.4% (95% CI, 56.8-73.4%) for intubations performed with direct laryngoscopy (P < 0.001). In a propensity-matched analysis, the odds ratio for first-attempt success with video laryngoscopy versus direct laryngoscopy was 2.81 (95% CI, 2.27-3.59). The rate of arterial oxygen desaturation events during the first intubation attempt was significantly lower for video laryngoscopy than for direct laryngoscopy (18.3% vs. 25.9%; P = 0.04). The rate of esophageal intubation during any attempt was also significantly lower for video laryngoscopy (2.1% vs. 6.6%; P = 0.008). CONCLUSIONS: Video laryngoscopy was associated with significantly improved odds of first-attempt success at tracheal intubation by nonanesthesiologists in a medical intensive care unit. Esophageal intubation and oxygen desaturation occurred less frequently with the use of video laryngoscopy. Randomized clinical trials are needed to confirm these findings.
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Unidades de Terapia Intensiva/organização & administração , Intubação Intratraqueal/métodos , Laringoscopia/métodos , Cirurgia Vídeoassistida/métodos , Idoso , Arizona , Feminino , Humanos , Intubação Intratraqueal/normas , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Melhoria de Qualidade , Centros de Atenção TerciáriaRESUMO
We developed a molecular genetic model to investigate glucocorticoid receptor (GR) signaling in human bronchial epithelial cells in response to the therapeutic steroid budesonide. Based on a genetic selection scheme using the human Chago K1 cell line and integrated copies of a glucocorticoid-responsive herpes simplex virus thymidine kinase gene and a green fluorescent protein gene, we isolated five Chago K1 variants that grew in media containing budesonide and ganciclovir. Three spontaneous budesonide-resistant subclones were found to express low levels of GR, whereas two mutants isolated from ethylmethane sulfonate-treated cultures contained normal levels of GR protein. Analysis of the GR coding sequence in the budesonide-resistant subclone Ch-BdE5 identified a novel Val to Met mutation at amino acid position 575 (GRV575M) which caused an 80% decrease in transcriptional regulatory functions with only a minimal effect on ligand binding activity. Homology modeling of the GR structure in this region of the hormone binding domain and molecular dynamic simulations suggested that the GRV575M mutation would have a decreased affinity for the LXXLL motif of p160 coactivators. To test this prediction, we performed transactivation and glutathione-S-transferase pull-down assays using the p160 coactivator glucocorticoid interacting protein 1 (GRIP1)/transcriptional intermediary factor 2 and found that GRV575M transcriptional activity was not enhanced by GRIP1 in transfected cells nor was it able to bind GRIP1 in vitro. Identification of the novel GRV575M variant in human bronchial epithelial cells using a molecular genetic selection scheme suggests that functional assays performed in relevant cell types could identify subtle defects in GR signaling that contribute to reduced steroid sensitivities in vivo.
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Brônquios/fisiologia , Budesonida/farmacologia , Receptores de Glucocorticoides/genética , Mucosa Respiratória/fisiologia , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Sítios de Ligação , Carcinoma Broncogênico , Linhagem Celular , Linhagem Celular Tumoral , Resistência a Medicamentos , Ganciclovir/farmacologia , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Humanos , Neoplasias Pulmonares , Metionina , Dados de Sequência Molecular , Mucosa , Mutação de Sentido Incorreto , Proteínas Recombinantes de Fusão/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Transfecção , ValinaRESUMO
RATIONALE: The use of neuromuscular blocking agents (NMBAs) has been shown to be valuable in improving successful tracheal intubation in the operating room and emergency department. However, data on NMBA use in critically ill intensive care unit (ICU) patients are lacking. Furthermore, there are no data on NMBA use with video laryngoscopy. OBJECTIVES: To evaluate the effect of NMBA use on first-attempt success (FAS) with tracheal intubation in the ICU. METHODS: Single-center observational study of 709 consecutive patients intubated in the medical ICU of a university medical center from January 1, 2012 to June 30, 2014. Data were collected prospectively through a continuous quality improvement program on all patients intubated in the ICU over the study period. Data relating to patient demographics, intubation, and complications were analyzed. We used propensity score (propensity to use an NMBA) matching to generate 5,000 data sets of cases (failed first intubation attempts) matched to controls (successful first attempts) and conditional logistic regression to analyze the results. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in patient demographics, except median total difficult airway characteristics were higher in the non-NMBA group (2 vs. 1, P < 0.001). There were significant differences in the sedative used between groups and the operator level of training. More patients who were given NMBAs received etomidate (83 vs. 35%) and more patients in the non-NMBA group received ketamine (39 vs. 9%) (P < 0.001). The FAS for NMBA use was 80.9% (401/496) compared with 69.6% (117/168) for non-NMBA use (P = 0.003). The summary odds ratio for FAS when an NMBA was used from the propensity matched analyses was 2.37 (95% confidence interval, 1.36-4.88). In the subgroup of patients intubated with a video laryngoscope, propensity-adjusted odds of FAS with the use of an NMBA was 2.50 (1.43-4.37; P < 0.001). There were no differences in procedurally related complications between groups. CONCLUSIONS: After controlling for potential confounders, this propensity-adjusted analysis demonstrates improved odds of FAS at intubation in the ICU with the use of an NMBA. This improvement in FAS is seen even with the use of a video laryngoscope.
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Manuseio das Vias Aéreas/métodos , Unidades de Terapia Intensiva , Intubação Intratraqueal/métodos , Laringoscopia/métodos , Bloqueio Neuromuscular/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Gravação em VídeoRESUMO
RATIONALE: Airway management in the intensive care unit (ICU) is challenging, as many patients have limited physiologic reserve and are at risk for clinical deterioration if the airway is not quickly secured. In academic medical centers, ICU intubations are often performed by trainees, making airway management education paramount for pulmonary and critical care trainees. OBJECTIVES: To improve airway management education for our trainees, we developed a comprehensive training program including an 11-month simulation-based curriculum. The curriculum emphasizes recognition of and preparation for potentially difficult intubations and procedural skills to maximize patient safety and increase the likelihood of first-attempt success. METHODS: Training is provided in small group sessions twice monthly using a high-fidelity simulation program under the guidance of a core group of two to three advanced providers. The curriculum is designed with progressively more difficult scenarios requiring critical planning and execution of airway management by the trainees. Trainees consider patient position, preoxygenation, optimization of hemodynamics, choice of induction agents, selection of appropriate devices for the scenario, anticipation of difficulties, back-up plans, and immediate postintubation management. Clinical performance is monitored through a continuous quality improvement program. MEASUREMENTS AND MAIN RESULTS: Sixteen fellows have completed the program since July 1, 2013. In the 18 months since the start of the curriculum (July 1, 2013-December 31, 2014), first-attempt success has improved from 74% (358/487) to 82% (305/374) compared with the 18 months before implementation (P = 0.006). During that time there were no serious complications related to airway management. Desaturation rates decreased from 26 to 17% (P = 0.002). Other complication rates are low, including aspiration (2.1%), esophageal intubation (2.7%), dental trauma (0.8%), and hypotension (8.3%). First-attempt success in a 6-month period after implementation (July 1, 2014-December 31, 2014) was significantly higher (82.1 compared with 70.9%, P = 0.03) than during a similar 6-month period before implementation (July 1, 2012-December 31, 2012). CONCLUSIONS: This comprehensive airway curriculum is associated with improved first-attempt success rate for intensive care unit intubations. Such a curriculum holds the potential to improve patient care.
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Competência Clínica , Cuidados Críticos , Bolsas de Estudo/métodos , Intubação Intratraqueal , Laringoscopia/educação , Pneumologia/educação , Treinamento por Simulação/métodos , Idoso , Manuseio das Vias Aéreas , Currículo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Noninvasive positive-pressure ventilation (NIPPV) use has increased in the treatment of patients with respiratory failure. However, despite decreasing the need for intubation in some patients, there are no data regarding the risk of intubation-related complications associated with delayed intubation in adult patients who fail NIPPV. The objective of this study is to evaluate the odds of a composite complication of intubation following failed NIPPV compared to patients intubated primarily in the medical intensive care unit (ICU). METHODS: This is a single-center retrospective cohort study of 235 patients intubated between 1 January 2012 and 30 June 2013 in a medical ICU of a university medical center. A total of 125 patients were intubated after failing NIPPV, 110 patients were intubated without a trial of NIPPV. Intubation-related data were collected prospectively through a continuous quality improvement (CQI) program and retrospectively extracted from the medical record on all patients intubated on the medical ICU. A propensity adjustment for the factors expected to affect the decision to initially use NIPPV was used, and the adjusted multivariate regression analysis was performed to evaluate the odds of a composite complication (desaturation, hypotension, or aspiration) with intubation following failed NIPPV versus primary intubation. RESULTS: A propensity-adjusted multivariate regression analysis revealed that the odds of a composite complication of intubation in patients who fail NIPPV was 2.20 (CI 1.14 to 4.25), when corrected for the presence of pneumonia or acute respiratory distress syndrome (ARDS), and adjusted for factors known to increase complications of intubation (total attempts and operator experience). When a composite complication occurred, the unadjusted odds of death in the ICU were 1.79 (95% CI 1.03 to 3.12). CONCLUSIONS: After controlling for potential confounders, this propensity-adjusted analysis demonstrates an increased odds of a composite complication with intubation following failed NIPPV. Further, the presence of a composite complication during intubation is associated with an increased odds of death in the ICU.
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Molecular analysis of steroid-regulated gene expression in freshly isolated human eosinophils is difficult due to the inherent high rate of spontaneous apoptosis and elevated levels of endogenous ribonucleases. To circumvent these limitations, we determined if the human eosinophilic cell line EoL-1 could serve as an in vitro model of glucocorticoid signaling. We found by optimizing growth conditions in low serum-containing media that dexamethasone (Dex) treatment of EoL-1 cells induced an apoptotic pathway that was inhibited by interleukin-5 (IL-5). Moreover, gene expression profiling using RNA from untreated EoL-1 cells and from freshly isolated human eosinophils identified 380 commonly expressed genes, including the eosinophil markers granule major basic protein, prostaglandin-endoperoxide synthase 1 and arachidonate 15-lipoxygenase. Expression profiling was performed using EoL-1 cells that had been treated with dexamethasone for 0, 4, 12, 24 and 48h identifying 162 genes as differentially expressed. Two of the most highly upregulated genes based on expression profiling were the transcription factor Ets-2 and the MHC Class II genes (Q, R, and P). Expression of these genes in EoL-1 cells was shown to be dexamethasone-induced at the RNA and protein levels which is consistent with the known function of Ets-2 in controlling cell cycle progression and the role of MHC Class II antigens in mediating eosinophil functions.
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Proteínas de Ligação a DNA , Eosinófilos/metabolismo , Regulação Neoplásica da Expressão Gênica , Regulação da Expressão Gênica , Glucocorticoides/farmacologia , Proteínas Repressoras , Ribonucleases , Fatores de Transcrição , Regulação para Cima , Adulto , Apoptose , Araquidonato 15-Lipoxigenase/biossíntese , Proteínas Sanguíneas/biossíntese , Northern Blotting , Western Blotting , Diferenciação Celular , Separação Celular , DNA Complementar/metabolismo , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Proteínas Granulares de Eosinófilos , Citometria de Fluxo , Genes MHC da Classe II , Humanos , Marcação In Situ das Extremidades Cortadas , Interleucina-5/antagonistas & inibidores , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Prostaglandina-Endoperóxido Sintases/biossíntese , Proteína Proto-Oncogênica c-ets-2 , Proteínas Proto-Oncogênicas/biossíntese , RNA/metabolismo , Transdução de Sinais , Fatores de Tempo , Transativadores/biossíntese , Células Tumorais CultivadasRESUMO
PURPOSE: The purpose of this study is to describe the current state of bedside ultrasound use and training among critical care (CC) training programs in the United States. MATERIALS AND METHODS: This was a cross-sectional survey of all program directors for Accreditation Council for Graduate Medical Education accredited programs during the 2012 to 2013 academic year in CC medicine, surgical CC, pulmonary and critical care, and anesthesia CC. Availability, current use, and barriers to training in CC ultrasound were assessed. RESULTS: Sixty of 195 (31%; 95% confidence interval [CI], 24%-38%) program directors responded. Most of the responding programs had an ultrasound system available for use (54/60, 90%; 95% CI, 79%-96%) and identified ultrasound training as useful (59/60, 98%; 95% CI, 91%-100%) but lacked a formal curriculum (25/60, 42%; 95% CI, 29%-55%) or trained faculty (mean percentage of faculty trained in ultrasound: pulmonary and critical care, 25%; surgical CC, 33%; anesthesia CC, 20%; CC medicine, 7%), and relied on informal teaching (45/60, 77%; 95% CI, 62%-85%). Faculty with expertise (53/60, 88%; 95% CI, 77%-95%), simulation training (60/60, 100%; 95% CI, 94%-100%), establishing and meeting required number of examinations (47/60, 78%; 95% CI, 66%-88%), and regular review sessions (49/60, 82%; 95% CI, 70%-90%) were identified as necessary to improve ultrasound training. Most responding programs (32/35 91%; 95% CI, 77%-98%) without a formal curriculum plan to create one in the next 5 years. CONCLUSIONS: This study identified deficiencies in current training, suggesting a need for a formal curriculum for bedside ultrasound training in CC fellowship programs.
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Cuidados Críticos , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassom/educação , Acreditação , Estudos Transversais , Coleta de Dados , Docentes de Medicina/provisão & distribuição , Bolsas de Estudo , Feminino , Humanos , Ultrassom/organização & administração , Ultrassom/estatística & dados numéricos , Estados UnidosRESUMO
BACKGROUND: Albumin is broadly prescribed for critically ill patients although it does not have a mortality benefit over crystalloids. One common use of albumin is to promote diuresis. Objectives To compare urine output in patients treated with furosemide with and without albumin and to assess other variables possibly associated with enhanced diuresis. METHODS: A retrospective study was conducted on patients in a medical intensive care unit who received furosemide therapy as a continuous infusion with and without 25% albumin for more than 6 hours. Primary end points were urine output and net fluid loss. RESULTS: A total of 31 patients were included in the final analysis. Mean urine output in patients treated with furosemide alone did not differ significantly from output in patients treated with furo-semide plus albumin at 6, 24, and 48 hours: mean output, 1119 (SD, 597) mL vs 1201 (SD, 612) mL, P = .56; 4323 (SD, 1717) mL vs 4615 (SD, 1741) mL, P = .42; and 7563 mL (SD, 2766) vs 7432 (SD, 2324) mL, P = .94, respectively. Additionally, net fluid loss did not differ significantly between the 2 groups at 6, 24, and 48 hours. Higher concentrations of serum albumin did not improve urine output. The only independent variable significantly associated with enhanced urine output at 24 and 48 hours was increased fluid intake. CONCLUSION: Addition of albumin to a furosemide infusion did not enhance diuresis obtained with furosemide alone in critically ill patients.
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Diurese/efeitos dos fármacos , Furosemida/administração & dosagem , Hipoalbuminemia/tratamento farmacológico , Albumina Sérica/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Arizona , Cuidados Críticos/métodos , Diuréticos/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Albumina Sérica/farmacologia , Adulto JovemRESUMO
Glucocorticoids (GCs) are the most common group of medications used in the treatment of allergic and autoimmune disorders. They produce potent anti-inflammatory effects by inducing or repressing the expression of target genes. Although most patients with allergic diseases and autoimmune disorders respond to GC therapy, a small subset of patients demonstrate persistent tissue inflammation despite treatment with high doses of GCs. This condition results from an interaction between susceptibility genes, the host's environment, and immunologic factors. The treatment of these patients requires a systematic approach to rule out underlying conditions that lead to steroid resistance or treatment failure, as well as the use of alternative strategies to inhibit tissue inflammation.