Cameron Hypes

Mechanism of Abasic Lesion Bypass Catalyzed by a Y-family DNA Polymerase

The 3 million-base pair genome of Sulfolobus solfataricus likely undergoes depurination/depyrimidination frequently in vivo. These unrepaired abasic lesions are expected to be bypassed by Dpo4, the only Y-family DNA polymerase from S. solfataricus. Interestingly, these error-prone Y-family enzymes have been shown to be physiologically vital in reducing the potentially negative consequences of DNA damage while paradoxically promoting carcinogenesis. Here we used Dpo4 as a model Y-family polymerase to establish the mechanistic basis for DNA lesion bypass. While showing efficient bypass, Dpo4 paused when incorporating nucleotides directly opposite and one position downstream from an abasic lesion because of a drop of several orders of magnitude in catalytic efficiency. Moreover, in disagreement with a previous structural report, Dpo4-catalyzed abasic bypass involves robust competition between the A-rule and the lesion loop-out mechanism and is governed by the local DNA sequence. Analysis of the strong pause sites revealed biphasic kinetics for incorporation indicating that Dpo4 primarily formed a nonproductive complex with DNA that converted slowly to a productive complex. These strong pause sites are mutational hot spots with the embedded lesion even affecting the efficiency of five to six downstream incorporations. Our results suggest that abasic lesion bypass requires tight regulation to maintain genomic stability.

The Physiologically Difficult Airway.

Airway management in critically ill patients involves the identification and management of the potentially difficult airway in order to avoid untoward complications. This focus on difficult airway management has traditionally referred to identifying anatomic characteristics of the patient that make either visualizing the glottic opening or placement of the tracheal tube through the vocal cords difficult. This paper will describe the physiologically difficult airway, in which physiologic derangements of the patient increase the risk of cardiovascular collapse from airway management. The four physiologically difficult airways described include hypoxemia, hypotension, severe metabolic acidosis, and right ventricular failure. The emergency physician should account for these physiologic derangements with airway management in critically ill patients regardless of the predicted anatomic difficulty of the intubation.

Extracorporeal membrane oxygenation (ECMO) for critically ill adults in the emergency department: History, current applications, and future directions

Extracorporeal membrane oxygenation (ECMO) is a mode of extracorporeal life support that augments oxygenation, ventilation and/or cardiac output via cannulae connected to a circuit that pumps blood through an oxygenator and back into the patient. ECMO has been used for decades to support cardiopulmonary disease refractory to conventional therapy. While not robust, there are promising data for the use of ECMO in acute hypoxemic respiratory failure, cardiac arrest, and cardiogenic shock and the potential indications for ECMO continue to increase. This review discusses the existing literature on the potential use of ECMO in critically ill patients within the emergency department.

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.

Video Laryngoscopy Improves Odds of First-Attempt Success at Intubation in the Intensive Care Unit. A Propensity-matched Analysis

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.

The Impact of a Comprehensive Airway Management Training Program for Pulmonary and Critical Care Medicine Fellows. A Three-Year Experience

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.

Failed noninvasive positive-pressure ventilation is associated with an increased risk of intubation-related complications

BackgroundNoninvasive 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).MethodsThis 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.ResultsA 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).ConclusionsAfter 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.

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.

Management of Patients with Predicted Difficult Airways in an Academic Emergency Department

BACKGROUND Patients with difficult airways are sometimes encountered in the emergency department (ED), however, there is a little data available regarding their management. OBJECTIVES To determine the incidence, management, and outcomes of patients with predicted difficult airways in the ED. METHODS Over the 1-year period from July 1, 2015 to June 30, 2016, data were prospectively collected on all patients intubated in an academic ED. After each intubation, the operator completed an airway management data form. Operators performed a pre-intubation difficult airway assessment and classified patients into routine, challenging, or difficult airways. All non-arrest patients were included in the study. RESULTS There were 456 patients that met inclusion criteria. Fifty (11%) had predicted difficult airways. In these 50 patients, neuromuscular blocking agents (NMBAs) were used in 40 (80%), an awake intubation technique with light sedation was used in 7 (14%), and no medications were used in 3 (6%). In the 40 difficult airway patients who underwent NMBA facilitated intubation, a video laryngoscope (GlideScope 21, Verathon, Bothell, WA and C-MAC 19, Karl Storz, Tuttlingen, Germany) was used in each of these, with a first-pass success of 90%. In the 7 patients who underwent awake intubation, a video laryngoscope was used in 5, and a flexible fiberoptic scope was used in 2. Ketamine was used in 6 of the awake intubations. None of these difficult airway patients required rescue with a surgical airway. CONCLUSIONS Difficult airways were predicted in 11% of non-arrest patients requiring intubation in the ED, the majority of which were managed using an NMBA and a video laryngoscope with a high first-pass success.

154: REASON FOR FAILED ATTEMPTS AT LARYNGOSCOPY DIFFERS BETWEEN VIDEO AND DIRECT LARYNGOSCOPES

Crit Care Med 2015 • Volume 43 • Number 12 (Suppl.) at initiation of ECMO and PELOD score at initiation of ECMO, revealed that a state of fluid overload during the entire ECMO run increased the odds of death during ECMO therapy (OR=8.5, p = 0.04). Conclusions: A state of fluid overload during ECMO therapy increased mortality while on ECMO. Efforts should be taken to minimize a patient’s net fluid balance while receiving ECMO therapy.