ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury.

STUDY OBJECTIVE: Laboratory evidence indicates that progesterone has potent neuroprotective effects. We conducted a pilot clinical trial to assess the safety and potential benefit of administering progesterone to patients with acute traumatic brain injury. METHODS: This phase II, randomized, double-blind, placebo-controlled trial was conducted at an urban Level I trauma center. One hundred adult trauma patients who arrived within 11 hours of injury with a postresuscitation Glasgow Coma Scale score of 4 to 12 were enrolled with proxy consent. Subjects were randomized on a 4:1 basis to receive either intravenous progesterone or placebo. Blinded observers assessed patients daily for the occurrence of adverse events and signs of recovery. Neurologic outcome was assessed 30 days postinjury. The primary safety measures were differences in adverse event rates and 30-day mortality. The primary measure of benefit was the dichotomized Glasgow Outcome Scale-Extended 30 days postinjury. RESULTS: Seventy-seven patients received progesterone; 23 received placebo. The groups had similar demographic and clinical characteristics. Laboratory and physiologic characteristics were similar at enrollment and throughout treatment. No serious adverse events were attributed to progesterone. Adverse and serious adverse event rates were similar in both groups, except that patients randomized to progesterone had a lower 30-day mortality rate than controls (rate ratio 0.43; 95% confidence interval 0.18 to 0.99). Thirty days postinjury, the majority of severe traumatic brain injury survivors in both groups had relatively poor Glasgow Outcome Scale-Extended and Disability Rating Scale scores. However, moderate traumatic brain injury survivors who received progesterone were more likely to have a moderate to good outcome than those randomized to placebo. CONCLUSION: In this small study, progesterone caused no discernible harm and showed possible signs of benefit.

Proxy identification: a time-dependent analysis.

OBJECTIVES: To describe the availability of next-of-kin (NOK) for proxy consent over the 24-hour time period following presentation of major trauma patients to a Level I trauma center. METHODS: The study was conducted by using a prospective, observational study design. Consecutive patients meeting predefined major trauma criteria during a three-month study period were enrolled and followed until NOK were contacted, or up to 24 hours. Survival analysis was used to determine the probability of NOK contact during the 24-hour follow-up period. RESULTS: Three hundred fifty (92%) of 382 subjects had NOK contacted during the follow-up period. The probabilities (95% confidence intervals [CIs]) of NOK contact at the time of arrival (t = 0) and 2, 4, 6, and 24 hours postpresentation were 0.25 (95% CI = 0.21 to 0.30), 0.68 (95% CI = 0.63 to 0.72), 0.77 (95% CI = 0.73 to 0.82), 0.80 (95% CI = 0.76 to 0.84), and 0.87 (95% CI = 0.84 to 0.90), respectively. The median time to contact was 40 minutes (95% CI = 27 to 54 min). CONCLUSIONS: One third of the trauma patients in this study did not have NOK available two hours following arrival in the emergency department. For time-critical research protocols, the time to NOK contact can significantly impact the ability to ensure prompt enrollment and treatment in clinical trials. Further studies are needed to assess the generalizability and consistency of these data.

Interrater reliability of criteria used in assessing blunt head injury patients for intracranial injuries.

OBJECTIVE: To determine the interrater reliability of potential predictor variables that may be used to construct a clinical decision rule for emergency computed tomography of the head in blunt head injury victims. METHODS: As a substudy of the NEXUS II study of blunt head trauma, physicians from 21 different emergency departments performed paired evaluations of patients undergoing computed tomography of the head after blunt head injury. Each physician independently determined, for each subject, the presence or absence of each of 19 separate clinical characteristics. The physicians were either residents or attending physicians in the participating emergency departments. Paired responses on a sample of 3,951 patients were compared for raw level of agreement and for interrater concordance using the kappa statistic. If the lower margin of the 95% confidence interval for raw agreement was at least 85% and was equal to or greater than 0.50 for kappa, this was predetermined to represent substantial interrater agreement. RESULTS: There was substantial interobserver agreement by both measures for 17 of the 19 candidate variables in patients with blunt head trauma. Interobserver agreement was substantial for all candidate variables except presence of seizure (kappa = 0.57 [95% CI = 0.47 to 0.67]; raw agreement = 96.5%) and abnormal cerebellar function (kappa = 0.54 [95% CI = 0.41 to 0.67]; raw agreement = 96.5%). CONCLUSIONS: The clinicians in our study had a substantial level of agreement regarding most clinical criteria assessed in this large sample of patients with blunt head injury.

Validity of a decision rule to reduce cervical spine radiography in elderly patients with blunt trauma.

STUDY OBJECTIVES: A decision instrument based on 5 clinical criteria has been shown to be highly sensitive in selecting patients who require cervical spine imaging after blunt trauma, while simultaneously reducing overall imaging. We examine the performance of this instrument in the elderly and explore some of the common features of geriatric cervical spine injury (CSI). METHODS: The National Emergency X-radiography Utilization Study (NEXUS) was a prospective, observational, multicenter study conducted at 21 geographically diverse centers. We analyzed the performance of the NEXUS decision instrument among patients at least 65 years of age. RESULTS: The study group consisted of 2,943 (8.6%) geriatric patients, representing 8.6% of the entire NEXUS sample. The rate of CSI was twice as great in these patients as it was in nongeriatric patients (4.59% versus 2.19%). Odontoid fractures were particularly common in geriatric patients, accounting for 20% of geriatric fractures compared with 5% of nongeriatric fractures. The frequency of patients meeting NEXUS criteria was similar in the 2 groups, with 14% of geriatric patients and 12.5% of nongeriatric patient classified as low risk. CSI occurred in only 2 low-risk geriatric patients, and these patients' injuries met our preset definition of a clinically insignificant injury. The sensitivity of the NEXUS decision instrument for clinically significant injury in the geriatric group was therefore 100% (95% confidence interval 97.1% to 100%). CONCLUSION: The prevalence of CSI, and especially odontoid fracture, is relatively increased among geriatric patients with blunt trauma. The NEXUS decision instrument can be applied safely to these patients, with an expected reduction in cervical imaging comparable with that achieved in nongeriatric patients.