The Roles of Protocols and Protocolization in Improving Outcome From Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Our Phase-I parallel-cohort study suggested that managing severe traumatic brain injury (sTBI) in the absence of intracranial pressure (ICP) monitoring using an ad hoc Imaging and Clinical Examination (ICE) treatment protocol was associated with superior outcome vs nonprotocolized management but could not differentiate the influence of protocolization from that of the specific protocol. Phase II investigates whether adopting the Consensus REVised Imaging and Clinical Examination (CREVICE) protocol improved outcome directly or indirectly via protocolization. METHODS: We performed a Phase-II sequential parallel-cohort study examining adoption of the CREVICE protocol from no protocol vs a previous protocol in patients with sTBI older than 13 years presenting ≤24 hours after injury. Primary outcome was prespecified 6-month recovery. The study was done mostly at public South American centers managing sTBI without ICP monitoring. Fourteen Phase-I nonprotocol centers and 5 Phase-I protocol centers adopted CREVICE. Data were analyzed using generalized estimating equation regression adjusting for demographic imbalances. RESULTS: A total of 501 patients (86% male, mean age 35.4 years) enrolled; 81% had 6 months of follow-up. Adopting CREVICE from no protocol was associated with significantly superior results for overall 6-month extended Glasgow Outcome Score (GOSE) (protocol effect = 0.53 [0.11, 0.95], P = .013), mortality (36% vs 21%, HR = 0.59 [0.46, 0.76], P < .001), and orientation (Galveston Orientation and Amnesia Test discharge protocol effect = 10.9 [6.0, 15.8], P < .001, 6-month protocol effect = 11.4 [4.1, 18.6], P < .005). Adopting CREVICE from ICE was associated with significant benefits to GOSE (protocol effect = 0.51 [0.04, 0.98], P = .033), 6-month mortality (25% vs 18%, HR = 0.55 [0.39, 0.77], P < .001), and orientation (Galveston Orientation and Amnesia Test 6-month protocol effect = 9.2 [3.6, 14.7], P = .004). Comparing both groups using CREVICE, those who had used ICE previously had significantly better GOSE (protocol effect = 1.15 [0.09, 2.20], P = .033). CONCLUSION: Centers managing adult sTBI without ICP monitoring should strongly consider protocolization through adopting/adapting the CREVICE protocol. Protocolization is indirectly supported at sTBI centers regardless of resource availability.

Testing the Impact of Protocolized Care of Patients With Severe Traumatic Brain Injury Without Intracranial Pressure Monitoring: The Imaging and Clinical Examination Protocol.

BACKGROUND: Most patients with severe traumatic brain injury (sTBI) in low- or-middle-income countries and surprisingly many in high-income countries are managed without intracranial pressure (ICP) monitoring. The impact of the first published protocol (Imaging and Clinical Examination [ICE] protocol) is untested against nonprotocol management. OBJECTIVE: To determine whether patients treated in intensive care units (ICUs) using the ICE protocol have lower mortality and better neurobehavioral functioning than those treated in ICUs using no protocol. METHODS: This study involved nineteen mostly public South American hospitals. This is a prospective cohort study, enrolling patients older than 13 years with sTBI presenting within 24 h of injury (January 2014-July 2015) with 6-mo postinjury follow-up. Five hospitals treated all sTBI cases using the ICE protocol; 14 used no protocol. Primary outcome was prespecified composite of mortality, orientation, functional outcome, and neuropsychological measures. RESULTS: A total of 414 patients (89% male, mean age 34.8 years) enrolled; 81% had 6 months of follow-up. All participants included in composite outcome analysis: average percentile (SD) = 46.8 (24.0) nonprotocol, 56.9 (24.5) protocol. Generalized estimating equation (GEE) used to account for center effects (confounder-adjusted difference [95% CI] = 12.2 [4.6, 19.8], P = .002). Kaplan-Meier 6-month mortality (95% CI) = 36% (30%, 43%) nonprotocol, 25% (19%, 31%) protocol (GEE and confounder-adjusted hazard ratio [95% CI] = .69 [.43, 1.10], P = .118). Six-month Extended Glasgow Outcome Scale for 332 participants: average Extended Glasgow Outcome Scale score (SD) = 3.6 (2.6) nonprotocol, 4.7 (2.8) protocol (GEE and confounder-adjusted and lost to follow-up-adjusted difference [95% CI] = 1.36 [.55, 2.17], P = .001). CONCLUSION: ICUs managing patients with sTBI using the ICE protocol had better functional outcome than those not using a protocol. ICUs treating patients with sTBI without ICP monitoring should consider protocolization. The ICE protocol, tested here and previously, is 1 option.

Treatment with IgM-enriched immunoglobulin in sepsis: a matched case-control analysis.

The therapeutic potential of IgM-enriched immunoglobulin preparations (IgGAM) in sepsis remains a field of debate. The use of polyclonal immunoglobulins as adjuvant therapy (Esen & Tugrul, 2009; Kaukonen et al., 2014; Molnár et al., 2013; Taccone et al., 2009) has been shown to improve clinical outcomes in terms of mortality. This study analyze the impact of IgM-enriched IgG (IgGM) as additional immunomodulation. Patients and methods: This is a retrospective registry of 1196 patients with severe sepsis and septic shock from nine Intensive Care Units in Colombia, from routine clinical practice; 220 patients treated with IgGAM were registered. Fully matched comparators for severity and type of infection selected among patients non-treated with IgGAM. Mortality after 28 days was 30.5% among IgGAM-treated patients and 40.5% among matched comparators. Results: Multivariate Cox regression analysis showed IgGAM treatment to be the only variable protective from death after 28 days (hazard ratio 0.62; 0.45-0.86; p: 0.004). Results reinforce the importance of IgGAM treatment for favorable outcome after septic shock and are in line with recent published meta-analyses. This study showed that treatment with IgGM in patients with sepsis was an independent modulator of the 28-day associated with a lower mortality.

A clinical decision rule to predict intracranial hypertension in severe traumatic brain injury.

OBJECTIVE: While existing guidelines support the treatment of intracranial hypertension in severe traumatic brain injury (TBI), it is unclear when to suspect and initiate treatment for high intracranial pressure (ICP). The objective of this study was to derive a clinical decision rule that accurately predicts intracranial hypertension. METHODS: Using Delphi methods, the authors identified a set of potential predictors of intracranial hypertension and a clinical decision rule a priori by consensus among a group of 43 neurosurgeons and intensivists who have extensive experience managing severe TBI without ICP monitoring. To validate these predictors, the authors used data from a Latin American trial (n = 150; BEST TRIP). To report on the performance of the rule, they calculated sensitivity, specificity, and positive and negative predictive values with 95% confidence intervals. In a secondary analysis, the rule was validated using data from a North American trial (n = 131; COBRIT). RESULTS: The final predictors and the clinical decision rule were approved by 97% of participants in the consensus working group. The predictors are divided into major and minor criteria. High ICP would be considered suspected in the presence of 1 major or ≥ 2 minor criteria. Major criteria are: compressed cisterns (CT classification of Marshall diffuse injury [DI] III), midline shift > 5 mm (Marshall DI IV), or nonevacuated mass lesion. Minor criteria are: Glasgow Coma Scale (GCS) motor score ≤ 4, pupillary asymmetry, abnormal pupillary reactivity, or Marshall DI II. The area under the curve for the logistic regression model that contains all the predictors was 0.86. When high ICP was defined as > 22 mm Hg, the decision rule performed with a sensitivity of 93.9% (95% CI 85.0%-98.3%), a specificity of 42.3% (95% CI 31.7%-53.6%), a positive predictive value of 55.5% (95% CI 50.7%-60.2%), and a negative predictive value of 90% (95% CI 77.1%-96.0%). The sensitivity of the clinical decision rule improved with higher ICP cutoffs up to a sensitivity of 100% when intracranial hypertension was defined as ICP > 30 mm Hg. Similar results were found in the North American cohort. CONCLUSIONS: A simple clinical decision rule based on a combination of clinical and imaging findings was found to be highly sensitive in distinguishing patients with severe TBI who would suffer intracranial hypertension. It could be used to identify patients who require ICP monitoring in high-resource settings or start ICP-lowering treatment in environments where resource limitations preclude invasive monitoring.Clinical trial registration no.: NCT02059941 (clinicaltrials.gov).

Development of a Severe Traumatic Brain Injury Consensus-Based Treatment Protocol Conference in Latin America.

BACKGROUND: Severe traumatic brain injury (sTBI) is a significant global health problem disproportionately affecting low- and middle-income countries (LMICs). Management of intracranial hypertension in sTBI is crucial to survival and optimal recovery. Practitioners in high-income countries routinely use intracranial pressure (ICP) monitors although their usefulness has been questioned. ICP monitors are usually unavailable in LMICs. No consensus-based/tested protocols or literature exists for sTBI treatment without ICP monitoring. METHODS: Investigators developed serial SurveyMonkey surveys for Latin American neurointensivists and neurosurgeons to determine current practice. These clinicians had extensive routine ongoing experience in sTBI without ICP monitoring. Surveys were administered and analyzed before/during/after a 2015 Buenos Aires consensus conference. Investigators identified areas of convergence blinded from colleagues' responses. A 47-clinician task force, representing 15 countries, who routinely manage patients with sTBI without monitors developed consensus-based treatment guidelines during a 3-day facilitated conference. RESULTS: Elements were added to the protocol at an 80% agreement threshold. Follow-on surveys resolved remaining elements to 97% agreement. The protocol addresses both tapering (on improvement) and neuroworsening. Staged treatment options were identified, plus unique clinical practice issues. This process introduced a research method to a large multidisciplinary group of LMIC clinicians. This report describes the process used to develop an LMIC-specific protocol that is transferable to other diseases/injuries. The protocol is being tested in 5 LMICs. CONCLUSIONS: We derived consensus-based guidelines for sTBI treatment without ICP monitoring, and introduced a research method to a large multidisciplinary group of LMIC clinicians naive to such methods.

Traqueobronquitis y neumonía asociadas a ventilación mecánica en unidades de cuidado intensivo de Latinoamérica: epidemiología, curso clínico y desenlaces (Estudio LATINAVE) / Epidemiology, clinical evolution and outcomes of tracheobronchitis and pneumonia associated with mechanical ventilation in intensive care units of Latin America (LATINAVE study)

Introducción: Las infecciones asociadas a ventilación mecánica son causa importante de morbimortalidad en el paciente crítico. La diferenciación entre traqueobronquitis y neumonía no es siempre fácil, y es controvertida. Algunos trabajos describen aumento de mortalidad, mayor estancia en Unidades de Cuidado Intensivo (UCI), mayor requerimiento de ventilación mecánica e incremento de costos en pacientes con traqueobronquitis asociada a ventilador (TAV), sin diferencias significativas en pacientes con neumonía asociada a ventilador (NAV). Estos estudios no describen el comportamiento clínico y epidemiológico de la TAV y la NAV como 2 entidades independientes, por lo que es necesario describirlo. Métodos: Estudio multicéntrico de cohorte prospectiva, de pacientes adultos que desarrollaron TAV o NAV durante su estancia en UCI, entre noviembre de 2013 y octubre de 2014. A cada una de las variables demográficas, clínicas, de laboratorio y de desenlace, como tiempo de ventilación mecánica, estancia hospitalaria y muerte, se le realizó análisis descriptivo; para evaluar las diferencias entre los grupos se utilizó test de chi cuadrado, t de Student o U de Mann Whitney. Resultados: Se incluyó a 143 pacientes, con edad promedio de 55 años, 57% eran hombres, de 6 países en Latinoamérica; 63% con NAV y 37% con TAV. Las comorbilidades más frecuentes fueron cardiovascular (44%) y neurológica (30%); esta última fue más frecuente en TAV (41,5 vs. 23%; p = 0,02). No se encontró diferencia en APACHE II de ingreso. El índice SOFA fue mayor en NAV (8 vs. 5; p = 0,02). No hubo diferencias en el aislamiento microbiológico, ni en los patrones de resistencia bacteriana entre las 2 entidades. Se observó mayor número de complicaciones cardiovasculares y SDRA en pacientes con NAV. No se encontró diferencia entre los 2 grupos en estancia en UCI, los días de ventilación mecánica ni en mortalidad. Conclusiones: La prevalencia de TAV fue mayor a lo descrito hasta ahora en la literatura. No se encontraron diferencias significativas en el aislamiento microbiológico, la resistencia bacteriana ni el esquema antibiótico utilizado en los 2 grupos. Aunque la NAV cursó con mayor proporción de complicaciones médicas asociadas, el hallazgo de una estancia hospitalaria, tiempo de ventilación mecánica y mortalidad similares sustenta la importancia clínica de la TAV.

Introduction: The infections associated with mechanical ventilation are a major cause of morbidity and mortality in critically ill patients. Limited studies report increased mortality and intensive care units (ICU) stays, requirements for mechanical ventilation and higher costs in ventilator-associated tracheobronchitis (TAV) in comparison to patients with ventilator-associated pneumonia (NAV). These studies do not describe the clinical and epidemiological behavior in the same population as independent entities, so it is necessary to describe the epidemiology of patients with TAV and NAV. Methods: Multicenter cross-sectional study of adult patients who developed TAV and/or NAV during their stay in the ICU in 2013 to 2014. A descriptive analysis was performed on each of the variables. For qualitative variables we assessed differences between groups using the Chi-squared test; for continuous variables, we used Student's t test or the Mann Whitney U test. Results: A total of 147 patients from 6 countries in Latin America were included; 63% with NAV and 37% with TAV. The average age was 55 years; 57% male. The most frequent comorbidity was cardiovascular (44%) and neurological (30%), the latter was more frequent in those with TAV (41.5 vs. 23%, P = .02). No differences were found in APACHE II on entry, but the difference appears in the SOFA index (8 vs. 5, P = .02). There were no differences in microbiological isolation, or bacterial resistance patterns between the 2 entities. A greater number of cardiovascular complications and ARDS were observed in patients with NAV. The ICU stay, days on mechanical ventilation and mortality were not different between the 2 groups. Conclusions: The TAV prevalence was higher than heretofore described in the literature. No significant differences were found in the microbiological isolation, bacterial resistance and antibiotic therapy used in the 2 groups, which might suggest that therapeutic approach be similar to that recommended for NAV. No differences were observed in clinical outcomes such as hospital stay, duration of mechanical ventilation and mortality, although NAV was associated with a greater proportion of medical complications.