Difficult Airway Characteristics Associated with First-Attempt Failure at Intubation Using Video Laryngoscopy in the Intensive Care Unit.

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.

Failure to achieve first attempt success at intubation using video laryngoscopy is associated with increased complications.

The purpose of this investigation was to investigate the association between first attempt success and intubation-related complications in the Intensive Care Unit after the widespread adoption of video laryngoscopy. We further sought to characterize and identify the predictors of complications that occur despite first attempt success. This was a prospective observational study of consecutive intubations performed with video laryngoscopy at an academic medical Intensive Care Unit. Operator, procedural, and complication data were collected. Multivariable logistic regression was used to examine the relationship between the intubation attempts and the occurrence of one or more complications. A total of 905 patients were intubated using a video laryngoscope. First attempt success occurred in 739 (81.7 %), whereas >1 attempt was needed in 166 (18.3 %). One or more complications occurred in 146 (19.8 %) of those intubated on the first attempt versus 107 (64.5 %, p < 0.001) of those requiring more than one attempt. Logistic regression analysis shows that >1 attempt is associated with 6.4 (95 % CI 4.4-9.3) times the adjusted odds of at least one complication. Pre-intubation predictors of at least one complication despite first attempt success include vomit or edema in the airway as well as the presence of hypoxemia or hypotension. There are increased odds of complications with even a second attempt at intubation in the Intensive Care Unit. Complications occur frequently despite a successful first attempt, and as such, the goal of airway management should not be simply first attempt success, but instead first attempt success without complications.

Schwann Cells Increase Prostate and Pancreatic Tumor Cell Invasion Using Laminin Binding A6 Integrin.

Human pancreatic and prostate cancers metastasize along nerve axons during perineural invasion. The extracellular matrix laminin class of proteins is an abundant component of both myelinated and non-myelinated nerves. Analysis of human pancreatic and prostate tissue revealed both perineural and endoneural invasion with Schwann cells surrounded or disrupted by tumor, respectively. Tumor and nerve cell co-culture conditions were used to determine if myelinating or non-myelinating Schwann cell (S16 and S16Y, respectively) phenotype was equally likely to promote integrin-dependent cancer cell invasion and migration on laminin. Conditioned medium from S16 cells increased tumor cell (DU145, PC3, and CFPAC1) invasion into laminin approximately 1.3-2.0 fold compared to fetal bovine serum (FBS) treated cells. Integrin function (e.g., ITGA6p formation) increased up to 1.5 fold in prostate (DU145, PC3, RWPE-1) and pancreatic (CFPAC1) cells, and invasion was dependent on ITGA6p formation and ITGB1 as determined by function-blocking antibodies. In contrast, conditioned medium isolated from S16Y cells (non-myelinating phenotype) decreased constitutive levels of ITGA6p in the tumor cells by 50% compared to untreated cells and decreased ITGA6p formation 3.0 fold compared to S16 treated cells. Flow cytometry and western blot analysis revealed loss of ITGA6p formation as reversible and independent of overall loss of ITGA6 expression. These results suggest that the myelinating phenotype of Schwann cells within the tumor microenvironment increased integrin-dependent tumor invasion on laminin.

Neuromuscular blockade improves first-attempt success for intubation in the intensive care unit. A propensity matched analysis.

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.

Macrophage-dependent cleavage of the laminin receptor α6ß1 in prostate cancer.

The laminin-binding integrin α6ß1 plays a major role in determining the aggressive phenotype of tumor cells during metastasis. Our previous work has shown that cleavage of the α6ß1 integrin to produce the structural variant α6pß1 on tumor cell surfaces is mediated by the serine protease urokinase plasminogen activator (uPA). Cleavage of α6ß1 increases tumor cell motility, invasion, and prostate cancer metastasis, and blockage of uPA inhibits α6pß1 production. In human tumors, uPA and uPAR are expressed in tumor cells and tumor-associated macrophages (TAM). TAMs localize to solid tumors and contribute to increased tumor growth and the metastatic phenotype. In this study, we utilized a coculture system of PC-3 prostate tumor cells and macrophages [12-O-tetradecanoylphorbol-13-acetate (TPA)-differentiated human leukemia HL-60 cells] to investigate the hypothesis that macrophages stimulate the production of the prometastatic variant α6pß1 on human prostate cancer cells via the uPA/uPAR axis. Our results indicate that adherent macrophages cocultured with PC-3 cells increased PC-3 uPAR mRNA, uPAR cell surface protein expression and α6 integrin cleavage. The stimulation does not require macrophage/tumor cell contact because macrophage conditioned medium is sufficient for increased uPAR transcription and α6 cleavage-dependent PC-3 cell invasion. The increased cleavage was dependent on uPAR because production was blocked by silencing RNA-targeting uPAR. These results indicate that macrophages can stimulate uPA/uPAR production in tumor cells which results in α6 integrin cleavage. These data suggest that TAMs promote prometastatic integrin-dependent pericellular proteolysis.