Association Between Difficult Airway Predictors and Failed Prehosptial Endotracheal Intubation.

OBJECTIVE: Difficult airway predictors (DAPs) are associated with failure of endotracheal intubation (ETI) in the emergency department (ED). The purpose of this study was to determine if DAPs are associated with failure of prehospital ETI. METHODS: This retrospective study compared the prevalence of DAPs in cases of failed prehospital ETI successfully intubated in the ED (FPH/SED) with cases with no prehospital attempt that were successfully intubated in the ED on the first attempt by a physician using direct laryngoscopy (NPH/SED). All cases were transported by ground or air to an academic, level-1 trauma center. RESULTS: A total of 1377 ED ETIs were performed; 161 FPH/SED and 530 NPH/SED were identified. The odds ratios with 95% confidence intervals (CIs) of finding DAPs in the FPH/SED group compared with the NPH/SED group was blood = 5.80 (95% CI, 3.89-8.63), vomit = 2.01 (95% CI, 1.25-3.21), short neck = 2.67 (95% CI, 1.39-5.03), neck immobility = 2.52 (95% CI, 1.72-3.67), airway edema = 10.52 (95% CI, 4.15-29.92), facial trauma = 4.64 (95% CI, 2.91-7.39), and large tongue = 3.08 (95% CI, 1.75-5.40). When grouped by the number of DAPs per case (0, 1, 2, 3, or ≥ 4), the odds of multiple DAPs in cases of FPH/SED compared with NPH/SED ranged from 2.89 (95% CI, 1.71-4.90) with 1 DAP to 24.55 (95% CI, 10.60-56.90) with ≥ 4 DAPs. CONCLUSION: Cases of FPH/SED have more DAPs than NPH/SEDs.

Prevalence of difficult airway predictors in cases of failed prehospital endotracheal intubation.

BACKGROUND: Difficult airway predictors (DAPs) are associated with failed endotracheal intubation (ETI) in the emergency department (ED). However, little is known about the relationship between DAPs and failed prehospital ETI. OBJECTIVE: Our aim was to determine the prevalence of common DAPs among failed prehospital intubations. METHODS: We reviewed a quality-improvement database, including all cases of ETI in a single ED, over 3 years. Failed prehospital (FP) ETI was defined as a case brought to the ED after attempted prehospital ETI, but bag-valve-mask ventilation, need for a rescue airway (supraglottic device, cricothyrotomy, etc.), or esophageal intubation was discovered at the ED. Physicians performing ETI evaluated each case for the presence of DAPs, including blood/emesis, facial/neck trauma, airway edema, spinal immobilization, short neck, and tongue enlargement. RESULTS: There were a total of 1377 ED ETIs and 161 had an FP-ETI (11.8%). Prevalence of DAPs in cases with FP-ETI was obesity 13.0%, large tongue 18.0%, short neck 13%, small mandible 4.3%, cervical immobility 49.7%, blood in airway 57.8%, vomitus in airway 23.0%, airway edema 12.4%, and facial or neck trauma 32.9%. The number of cases with FP-ETI and 0, 1, 2, 3, or 4 or more DAPs per case was 22 (13.6%), 43 (26.7%), 23 (24.3%), 42 (26.1%), and 31 (19.3%), respectively. CONCLUSIONS: DAPs are common in cases of FP-ETI. Some of these factors may be associated with FP-ETI. Additional study is needed to determine if DAPs can be used to identify patients that are difficult to intubate in the field.

Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L.

The DNMT3-like protein, DNMT3L, is required for germ line DNA methylation, although it is inactive as a DNA methyltransferase per se. Previous studies have shown that DNMT3L physically associates with the active de novo DNA methyltransferases, DNMT3A and DNMT3B, and stimulates their catalytic activities in a cell culture system. However, the mechanism by which DNMT3L stimulates de novo methylation remains unclear. Here, we have purified the full-length human DNMT3A2 and DNMT3L proteins and determined unique conditions that allow for the proper reconstitution of the stimulation of DNMT3A2 de novo methyltransferase activity by DNMT3L. These conditions include the use of buffers resembling physiological conditions and the preincubation of the two proteins. Under these conditions, maximal stimulation is reached at equimolar amounts of DNMT3L and DNMT3A2 proteins, and the catalytic efficiency of DNMT3A2 is increased up to 20-fold. Biochemical analysis revealed that whereas DNMT3L on its own does not significantly bind to the methyl group donor, S-adenosyl-L-methionine (SAM), it strongly increases the binding of SAM to DNMT3A2. DNA binding, on the contrary, was not appreciably improved. Analysis of DNA methyltransferase complexes in solution using size exclusion chromatography revealed that DNMT3A2 forms large structures of heterogeneous sizes, whereas DNMT3L appears as a monomer. Binding of DNMT3L to DNMT3A2 promotes a dramatic reorganization of DNMT3A2 subunits and leads to the formation of specific complexes with enhanced DNA methyltransferase activity and increased SAM binding.