Evaluation of Glial and Neuronal Blood Biomarkers Compared With Clinical Decision Rules in Assessing the Need for Computed Tomography in Patients With Mild Traumatic Brain Injury.

Importance: In 2018, the combination of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) levels became the first US Food and Drug Administration-approved blood test to detect intracranial lesions after mild to moderate traumatic brain injury (MTBI). How this blood test compares with validated clinical decision rules remains unknown. Objectives: To compare the performance of GFAP and UCH-L1 levels vs 3 validated clinical decision rules for detecting traumatic intracranial lesions on computed tomography (CT) in patients with MTBI and to evaluate combining biomarkers with clinical decision rules. Design, Setting, and Participants: This prospective cohort study from a level I trauma center enrolled adults with suspected MTBI presenting within 4 hours of injury. The clinical decision rules included the Canadian CT Head Rule (CCHR), New Orleans Criteria (NOC), and National Emergency X-Radiography Utilization Study II (NEXUS II) criteria. Emergency physicians prospectively completed data forms for each clinical decision rule before the patients' CT scans. Blood samples for measuring GFAP and UCH-L1 levels were drawn, but laboratory personnel were blinded to clinical results. Of 2274 potential patients screened, 697 met eligibility criteria, 320 declined to participate, and 377 were enrolled. Data were collected from March 16, 2010, to March 5, 2014, and analyzed on August 11, 2021. Main Outcomes and Measures: The presence of acute traumatic intracranial lesions on head CT scan (positive CT finding). Results: Among enrolled patients, 349 (93%) had a CT scan performed and were included in the analysis. The mean (SD) age was 40 (16) years; 230 patients (66%) were men, 314 (90%) had a Glasgow Coma Scale score of 15, and 23 (7%) had positive CT findings. For the CCHR, sensitivity was 100% (95% CI, 82%-100%), specificity was 33% (95% CI, 28%-39%), and negative predictive value (NPV) was 100% (95% CI, 96%-100%). For the NOC, sensitivity was 100% (95% CI, 82%-100%), specificity was 16% (95% CI, 12%-20%), and NPV was 100% (95% CI, 91%-100%). For NEXUS II, sensitivity was 83% (95% CI, 60%-94%), specificity was 52% (95% CI, 47%-58%), and NPV was 98% (95% CI, 94%-99%). For GFAP and UCH-L1 levels combined with cutoffs at 67 and 189 pg/mL, respectively, sensitivity was 100% (95% CI, 82%-100%), specificity was 25% (95% CI, 20%-30%), and NPV was 100%; with cutoffs at 30 and 327 pg/mL, respectively, sensitivity was 91% (95% CI, 70%-98%), specificity was 20% (95% CI, 16%-24%), and NPV was 97%. The area under the receiver operating characteristic curve (AUROC) for GFAP alone was 0.83; for GFAP plus NEXUS II, 0.83; for GFAP plus NOC, 0.85; and for GFAP plus CCHR, 0.88. The AUROC for UCH-L1 alone was 0.72; for UCH-L1 plus NEXUS II, 0.77; for UCH-L1 plus NOC, 0.77; and for UCH-L1 plus CCHR, 0.79. The GFAP biomarker alone (without UCH-L1) contributed the most improvement to the clinical decision rules. Conclusions and Relevance: In this cohort study, the CCHR, the NOC, and GFAP plus UCH-L1 biomarkers had equally high sensitivities, and the CCHR had the highest specificity. However, using different cutoff values reduced both sensitivity and specificity of GFAP plus UCH-L1. Use of GFAP significantly improved the performance of the clinical decision rules, independently of UCH-L1. Together, the CCHR and GFAP had the highest diagnostic performance.

Endotracheal tube placement confirmation: 100% sensitivity and specificity with sustained four-phase capnographic waveforms in a cadaveric experimental model.

BACKGROUND: Waveform capnography is considered the gold standard for verification of proper endotracheal tube placement, but current guidelines caution that it is unreliable in low-perfusion states such as cardiac arrest. Recent case reports found that long-deceased cadavers can produce capnographic waveforms. The purpose of this study was to determine the predictive value of waveform capnography for endotracheal tube placement verification and detection of misplacement using a cadaveric experimental model. METHODS: We conducted a controlled experiment with two intubated cadavers. Tubes were placed within the trachea, esophagus, and hypopharynx utilizing video laryngoscopy. We recorded observations of capnographic waveforms and quantitative end-tidal carbon dioxide (ETCO2) values during tracheal versus extratracheal (i.e., esophageal and hypopharyngeal) ventilations. RESULTS: 106 and 89 tracheal ventilations delivered to cadavers one and two, respectively (n=195) all produced characteristic alveolar waveforms (positive) with ETCO2 values ranging 2-113mmHg. 42 esophageal ventilations (36 to cadaver one and 6 to cadaver two), and 6 hypopharyngeal ventilations (4 to cadaver one and 2 to cadaver two) all resulted in non-alveolar waveforms (negative) with ETCO2 values of 0mmHg. Esophageal and hypopharyngeal measurements were categorized as extratracheal (n=48). A binary classification test showed no false negatives or false positives, indicating 100% sensitivity (NPV 1.0, 95%CI 0.98-1.00) and 100% specificity (PPV 1.0, 95%CI 0.93-1.00). CONCLUSION: Though current guidelines question the reliability of waveform capnography for verifying endotracheal tube location during low-perfusion states such as cardiac arrest, our findings suggest that it is highly sensitive and specific.

The effectiveness of out-of-hospital use of continuous end-tidal carbon dioxide monitoring on the rate of unrecognized misplaced intubation within a regional emergency medical services system.

STUDY OBJECTIVE: We evaluate the association between out-of-hospital use of continuous end-tidal carbon dioxide (ETCO2) monitoring and unrecognized misplaced intubations within a regional emergency medical services (EMS) system. METHODS: This was a prospective, observational study, conducted during a 10-month period, on all patients arriving at a regional Level I trauma center emergency department who underwent out-of-hospital endotracheal intubation. The regional EMS system that serves the trauma service area is composed of multiple countywide systems containing numerous EMS agencies. Some of the EMS agencies had independently implemented continuous ETCO2 monitoring before the start of the study. The main outcome measure was the unrecognized misplaced intubation rate with and without use of continuous ETCO2 monitoring. RESULTS: Two hundred forty-eight patients received out-of-hospital airway management, of whom 153 received intubation. Of the 153 patients, 93 (61%) had continuous ETCO2 monitoring, and 60 (39%) did not. Forty-nine (32%) were medical patients, 104 (68%) were trauma patients, and 51 (33%) were in cardiac arrest. The overall incidence of unrecognized misplaced intubations was 9%. The rate of unrecognized misplaced intubations in the group for whom continuous ETCO2 monitoring was used was zero, and the rate in the group for whom continuous ETCO2 monitoring was not used was 23.3% (95% confidence interval 13.4% to 36.0%). CONCLUSION: No unrecognized misplaced intubations were found in patients for whom paramedics used continuous ETCO2 monitoring. Failure to use continuous ETCO2 monitoring was associated with a 23% unrecognized misplaced intubation rate.