Dutch Prospective Observational Study on Prehospital Treatment of Severe Traumatic Brain Injury: The BRAIN-PROTECT Study Protocol.

Background: Severe traumatic brain injury (TBI) is associated with a high mortality rate and those that survive commonly have permanent disability. While there is a broad consensus that appropriate prehospital treatment is crucial for a favorable neurological outcome, evidence to support currently applied treatment strategies is scarce. In particular, the relationship between prehospital treatments and patient outcomes is unclear. The BRAIN-PROTECT study therefore aims to identify prehospital treatment strategies associated with beneficial or detrimental outcomes. Here, we present the study protocol. Study Protocol: BRAIN-PROTECT is the acronym for BRAin INjury: Prehospital Registry of Outcome, Treatments and Epidemiology of Cerebral Trauma. It is a prospective observational study on the prehospital treatment of patients with suspected severe TBI in the Netherlands. Prehospital epidemiology, interventions, medication strategies, and nonmedical factors that may affect outcome are studied. Multivariable regression based modeling will be used to identify confounder-adjusted relationships between these factors and patient outcomes, including mortality at 30 days (primary outcome) or mortality and functional neurological outcome at 1 year (secondary outcomes). Patients in whom severe TBI is suspected during prehospital treatment (Glasgow Coma Scale score ≤ 8 in combination with a trauma mechanism or clinical findings suggestive of head injury) are identified by all four helicopter emergency medical services (HEMS) in the Netherlands. Patients are prospectively followed up in 9 participating trauma centers for up to one year. The manuscript reports in detail the objectives, setting, study design, patient inclusion, and data collection process. Ethical and juridical aspects, statistical considerations, as well as limitations of the study design are discussed. Discussion: Current prehospital treatment of patients with suspected severe TBI is based on marginal evidence, and optimal treatment is basically unknown. The BRAIN-PROTECT study provides an opportunity to evaluate and compare different treatment strategies with respect to patient outcomes. To our knowledge, this study project is the first large-scale prospective prehospital registry of patients with severe TBI that also collects long-term follow-up data and may provide the best available evidence at this time to give useful insights on how prehospital care can be improved.

Etomidate and seizure duration in electroconvulsive therapy: is there a dose-dependent relation?

OBJECTIVE: The objective of this study was to determine if there is a dose-dependent relation between etomidate and motor and electroencephalogram (EEG) seizure duration in electroconvulsive therapy (ECT). METHODS: Seventy-four patients who received at least 3 ECT treatments with etomidate as an anesthetic were included. The association between seizure duration established by EEG and the cuff method, and etomidate dose (in mg/kg) was assessed retrospectively within individual patients, using mixed-effects model analysis with random intercept and random slope. Generalized estimating equation analysis was used to assess whether chances of reaching an adequate seizure depended on dose. RESULTS: A small negative association between dose of etomidate and motor and EEG seizure duration was found with a maximum correlation of -0.21. This correlation is considered weak and therefore lacks clinical significance. Higher doses of etomidate decreased the chances of an adequate seizure with an odds ratio of 0.68 per 0.1-mg/kg increase in etomidate (95% confidence interval, 0.52-0.90, P-value: 0.007). With a maximum dose of 0.3 mg/kg, 94.1% of the seizures were adequate (95% confidence interval, 91.0-96.2). CONCLUSIONS: Our data confirm that there is no clinically relevant dose-dependent relation between etomidate and seizure duration in ECT when etomidate is administered as advised in current international guidelines.

Haemostatic and cranial computed tomography characteristics in patients with acute and delayed coagulopathy after isolated traumatic brain injury.

PRIMARY OBJECTIVE: To investigate whether the development of coagulopathy at different stages after isolated traumatic brain injury (TBI) is associated with distinct cranial computed tomography characteristics. RESEARCH DESIGN: Retrospective cohort study in 226 patients with moderate-to-severe isolated TBI who were categorized as subjects without coagulopathy or with acute temporary, acute sustained or delayed coagulopathy. METHODS AND PROCEDURES: Coagulopathy was defined as an activated partial thromboplastin time >40 seconds and/or prothrombin time (PT) >1.2 and/or platelet count <120*10(9)l(-1). Cranial CT scans were assigned to the six-point Traumatic Coma Data Bank (TCDB) CT-classification. MAIN OUTCOMES AND RESULTS: Coagulopathy occurred in 44% of patients in the first 24-hours post-trauma. Patients with acute, sustained coagulopathy showed a prolonged PT (1.64 ± 0.89) when compared to patients without (1.03 ± 0.07), acute temporary (1.27 ± 0.22) or delayed coagulopathy (1.08 ± 0.06; p < 0.05). Patients with acute temporary or delayed coagulopathy had the worst TCDB CT classification scores, while mortality rates were the highest in patients with sustained or delayed coagulopathy. CONCLUSIONS: Not only the mere presence of coagulopathy, but also the course of haemostatic alterations following neurotrauma may hold predictive value for patient outcome, irrespective of the severity level of cerebral injury.

Acute and delayed mild coagulopathy are related to outcome in patients with isolated traumatic brain injury.

INTRODUCTION: The relationship between isolated traumatic brain injury (TBI) associated coagulopathy and patient prognosis frequently lacks information regarding the time course of coagulation disorders throughout the post-traumatic period. This study was conducted to assess the prevalence and time course of post-traumatic coagulopathy in patients with isolated TBI and the relationship of these hemostatic disorders with outcome. METHODS: The local Human Subjects Committee approved the study. We retrospectively studied the medical records of computed tomography (CT)-confirmed isolated TBI patients with an extracranial abbreviated injury scale (AIS) <3 who were primarily referred to a Level 1 trauma centre in Amsterdam (n = 107). Hemostatic parameters including activated partial thromboplastin time (aPTT), prothrombin time (PT), platelet count, hemoglobin, hematocrit, glucose, pH and lactate levels were recorded throughout a 72-hour period as part of a routine standardized follow-up of TBI. Coagulopathy was defined as a aPPT >40 seconds and/or a PTT in International Normalized Ratio (INR) >1.2 and/or a platelet count <120*109/l. RESULTS: Patients were mostly male, aged 48 ± 20 years with a median injury severity score of 25 (range 20 to 25). Early coagulopathy as diagnosed in the emergency department (ED) occurred in 24% of all patients. The occurrence of TBI-related coagulopathy increased to 54% in the first 24 hours post-trauma. In addition to an increased age and disturbed pupillary reflex, both coagulopathy upon ED arrival and during the first 24 hours post-trauma provided an independent prognostic factor for unfavorable outcome (odds ratio (OR) 3.75 (95% CI 1.07 to 12.51; P = 0.04) and OR 11.61 (2.79 to 48.34); P = 0.003). CONCLUSIONS: Our study confirms a high prevalence of early and delayed coagulopathy in patients with isolated TBI, which is strongly associated with an unfavorable outcome. These data support close monitoring of hemostasis after TBI and indicate that correction of coagulation disturbances might need to be considered.

Effect of secondary prehospital risk factors on outcome in severe traumatic brain injury in the context of fast access to trauma care.

BACKGROUND: Prevention of secondary prehospital risk factors such as hypoxia and hypotension is likely to improve patient prognosis in severe traumatic brain injury (TBI). Because the Dutch trauma care organization is characterized by fast access to specialized trauma care due to the geographical situation, we investigated whether and to what extend secondary risk factors, such as hypoxia and hypotension, and measures, such as endotracheal intubation, affect outcome in severe TBI in the context of a region with fast access to trauma care. METHODS: The medical records of 339 subsequent computed tomography-confirmed patients with TBI with a Glasgow coma scale (GCS) score≤8 who were primarily referred to a Level I trauma center in Amsterdam or Nijmegen in the Netherlands were retrospectively analyzed. RESULTS: Multinomial logistic regression revealed that the strongest outcome predictors in our population were a disturbed pupillary reflex (odds ratio [OR], 5.8), a GCS score of 3 (OR, 4.9), and arterial hypotension (OR, 3.5). Interestingly, we observed no differences between intubated and nonintubated patients with respect to metabolic and respiratory parameters or mortality whereby the injury severity score was slightly higher in endotracheally intubated patients (32 [25-41]) versus nonintubated patients (25 [22-29]). CONCLUSION: In agreement with others, GCS, a disturbed pupil reflex, and arterial hypotension were predictive for the prognosis of primarily referred patients with severe TBI in the Netherlands. In contrast, in the perspective of slightly higher injury scores in intubated patients, prehospital endotracheal intubation was not predictive for patient outcome.

Profound effects of cardiopulmonary bypass priming solutions on the fibrin part of clot formation: an ex vivo evaluation using rotation thromboelastometry.

OBJECTIVES: Dilutional coagulopathy as a consequence of cardiopulmonary bypass (CPB) system priming may also be affected by the composition of the priming solution. The direct effects of distinct priming solutions on fibrinogen, one of the foremost limiting factors during dilutional coagulopathy, have been minimally evaluated. Therefore, the authors investigated whether hemodilution with different priming solutions distinctly affects the fibrinogen-mediated step in whole blood clot formation. DESIGN: Prospective observational laboratory study. SETTING: University hospital laboratory. PARTICIPANTS: Eight male healthy volunteers. INTERVENTIONS: Blood samples diluted with gelatin-, albumin-, or hydroxyethyl starch (HES)-based priming solutions were ex-vivo evaluated for clot formation by rotational thromboelastometry. MEASUREMENTS AND MAIN RESULTS: The intrinsic pathway (INTEM) coagulation time increased from 186 +/- 19 seconds to 205 +/- 16, 220 +/- 17, and 223 +/- 18 seconds after dilution with gelatin-, albumin-, or HES-containing prime solutions (all p < 0.05 v baseline). The extrinsic pathway (EXTEM) coagulation time was only minimally affected by hemodilution. Moreover, all 3 priming solutions significantly reduced the INTEM and EXTEM maximum clot firmness. The HES-containing priming solution induced the largest decrease in the maximum clot firmness attributed to fibrinogen, from 13 +/- 1 mm (baseline) to 6 +/- 1 mm (p < 0.01 v baseline). CONCLUSIONS: All studied priming solutions prolonged coagulation time and decreased clot formation, but the fibrinogen-limiting effect was the most profound for the HES-containing priming solution. These results suggest that the composition of priming solutions may distinctly affect blood clot formation, in particular with respect to the fibrinogen component in hemostasis.

The next step in learning from sentinel events in healthcare.

OBJECTIVE: The aim of this study was to evaluate the current status of handling and learning from sentinel events (SEs) in Dutch academic hospitals and to develop a basis for the first steps in a joint and transparent approach to improve learning from SEs. DESIGN: Survey by the Netherlands Federation of University Medical Centres (NFU) as part of the project 'Quality-based Governance'. PARTICIPANTS AND SETTING: All eight Dutch University Medical Centres (UMCs). RESULTS: Three methods are used to identify the root cause of SEs: the Systematic Incident Reconstruction and Evaluation, Prevention and Recovery Information System for Monitoring and Analysis or TRIPOD method. Experts with different backgrounds are involved in the analysis of SEs. UMCs have different policies regarding the selection of recommendations for implementation. Some UMCs implement all recommendations formulated by the analysis team and in some UMCs the head of the involved department selects recommendations for implementation. No predetermined criteria have been established for this selection. Most UMCs confirm that similar SEs reoccur, which might be due to the quality of the analysis of the SEs or the quality of the recommendations. CONCLUSION: There is a large variety in handling SEs in Dutch academic hospitals and standards for the selection of recommendations are lacking. A next step to decrease the number of (similar) SEs lies in a joint and transparent approach to objectively assess recommendations and further define strategies for successful implementation. Selecting high-quality recommendations for implementation has the potential to lead to a decrease in the number of (similar) SEs and increase in the quality and safety of Dutch healthcare.

Evaluation of repatriation parameters: does medical history matter?

BACKGROUND: Aeromedical repatriation of patients is an expanding service due to the growing number of travelers worldwide. Of these repatriated patients, a small number require specialized transportation due to severe medical complications. We evaluated the medical in-flight records of Dutch patients with severe disease or polytrauma who were repatriated by air from 1998 to 2002 via one of the largest Dutch alarm centers. We questioned how this Dutch population of repatriated patients is demographically distributed and whether this population is a priori at high risk for acute medical complications that need specialized medical attention. RESULTS: Seventy-seven of 115 repatriated patients were 50 years and older, of which most were male (73%). Fifty patients had no significant medical history, whereas the remaining 65 patients suffered from comorbidities such as cardiovascular disease or cancer. In patients aged 18 to 49 years, one third of all patients were repatriated due to traumatic fractures. In the older age category, the main reasons for repatriation were cardiopulmonary incidents. There was an equal distribution in the primary medical reason for repatriation as defined by need for trauma/neurological support and ventilation or circulatory support. Of note, 82% of the 65 patients who traveled with a chronic disease condition were repatriated due to worsening of this particular condition. CONCLUSIONS: The present study shows that an aeromedical repatriation service is frequently employed by travelers with a history of chronic disease who develop medical complications. The growing number of repatriated elderly patients and/or patients with preexisting comorbidities requires development of secure pretravel risk assessment and adaptation of the medical service level in foreign countries.