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Department of Emergency Medicine

Department of Emergency Medicine

2012- December R3 Journal Review

Zafonte R, et al. Effect of Citicoline on Functional and Cognitive Status Among Patients With Traumatic  Brain Injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA 2012;308(19):1993-2000. The COBRIT trial investigates the ability of citicoline to positively affect functional and cognitive status in people with various degrees of traumatic brain injury (TBI). This phase 3, double-blind, placebo-controlled, 2-group, randomized clinical trial was conducted between July 20, 2007, and February 4, 2011, at 8 US level 1 trauma centers. This trial investigated effects of citicoline (an endogenous compound that is a key component of neuronal membranes) vs placebo in 1213 patients with TBI, that were classified as complicated mild, moderate, or severe. Patients included were 18-70 years of age and had non-penetrating TBI that required inpatient acute hospitalization. Specific GCS scores and various neuroimaging criteria were established and implemented for criteria to be included. Patients that were excluded included: bilaterally fixed and dilated pupils, pregnancy, imminent death or current life-threatening disease, prisoner, currently enrolled in another study, acetylcholinesterase inhibitor use within the 2 weeks prior to injury, or evidence of serious psychiatric and neurologic disorders. The primary intervention was a ninety-day regimen of daily enteral or oral citicoline (2000 mg) or placebo. The primary outcome of this study was functional status and cognitive performance at 90 days, measured by the 9 components of the TBI Clinical Trials Network Core Battery. Rates of favorable improvement for the Glasgow Outcome Scale–Extended were 35.4% in the citicoline group and 35.6% in the placebo group. This suggests that the citicoline and placebo groups did not differ significantly at the 90-day evaluation. The secondary outcome (a 180-day evaluation) again did not differ with respect to the primary outcome.

Without major limitations, this randomized clinical trial indicates that there is no statistically significant benefit of citicoline, when compared to a placebo, as an acute and post-acute treatment modality among patients with varying degrees of TBI.  Approved for therapy for TBI in 59 countries throughout the world, the COBRIT study effectively queries the worldwide use of citicoline in TBI therapy. As initial providers in patients who suffer from traumatic brain injuries, this study continues to support that there are yet to be effective medical pharmacotherapies in the management of TBI.

- Crum 

Park DW, Chun BC, Kwon SS et al. Red blood cell transfusions are associated with lower mortality in patients with severe sepsis and septic shock: A propensity-matched analysis. Crit Care Med 2012. 40(12):3140-3145. This was a propensity-matched analysis of a prospective observational multicenter ICU Korean database that evaluated the effects of RBC transfusion in patients with severe sepsis and septic shock on mortality. They evaluated 1054 patients with sepsis, 407 of which received blood transfusions. While they found that transfused patients had a higher overall mortality (transfused vs. not transfused 28-day and in-hospital mortality rates was 32.7% vs. 17.3%; p < .001 and 41.3% vs. 20.3%; p < .001, respectively), when matched using the propensity analysis, those receiving transfusion had lower mortality (transfusion vs. not transfused risk of 7-day 9.2% vs. 27.0%; p < .001 and 28-day 24.3% vs. 38.8%; p = .007, and in-hospital mortality rates 31.6% vs. 42.8%; p = .044). This study carries the limitations of being an observed and matched analysis. It demonstrates that those who receive transfusions are generally sicker, however, in this propensity-matched analysis, suggests that if patients are matched to patients with similar severity of illness, then mortality decreases when transfused RBC. This study echoes other observational studies that have shown increase mortality with transfusion, however, attempts to control for severity of illness with matching and suggests an actual decreased mortality.

- Hunt

Flores G, et al.  Errors of Medical Interpretation and Their Potential Clinical Consequences: A Comparison of Professional Versus Ad Hoc Versus No Interpreters, Ann Emerg Med 2012. 60(5): 545-553. This was a cross-sectional error analysis of audiotaped pediatric ED interviews in two large pediatric EDs in Massachusetts. Patients and/or their parents were self-identified as Spanish speaking with limited proficiency in English. 57 audiotaped conversations were analyzed and assigned one of three categories: professional interpreter, ad hoc (family, hospital staff) interpreter, or no interpreter. Multiple blinded individuals independently transcribed each audiotape into English and Spanish, and the results were compared. 1,884 interpreter errors were noted (mean of 33 errors per conversation), 18% were deemed to have potential clinical consequence. Overall number of errors were similar in the 3 groups, but professional interpreters were much less likely to make an error of false-fluency (using a non-word or incorrectly interpreting a word) and had a significant decrease in the chance of making an error of clinical consequence (12% rate for professional, 22% ad hoc, and 20% for no interpreter). 

This study did an excellent job of attempting a very difficult task, and used multiple checks and inter-rater safeguards to minimize bias. Overall they showed good evidence that there is a nearly 2 fold reduction in potentially clinically significant errors with the use of professional interpreters. This was a relatively well population (pediatric ED = viral illnesses, pharyngitis, AOM) and they did not share and or did not try to tie these conversations to actual outcomes or return visits. This would probably require a significantly greater number of conversations which would be logistically difficult with the resource intensity of analyzing these conversations so closely. Extrapolating this to the adult population, I think this error rate would be higher since there were often 2 parents to give a history, the child sometimes spoke English, and the adult patient is often themselves sick which may limit their ability to communicate with an interpreter. The consequences of causing a potentially clinically important error may be greater in our adult populations too, where certain morbidity and mortality related conditions are more prevalent.

- Cotton