Consensus statement from the international consensus meeting on post-traumatic cranioplasty.

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

Variation in the practice of tracheal intubation in Europe after traumatic brain injury: a prospective cohort study.

Traumatic brain injury patients frequently undergo tracheal intubation. We aimed to assess current intubation practice in Europe and identify variation in practice. We analysed data from patients with traumatic brain injury included in the prospective cohort study collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI) in 45 centres in 16 European countries. We included patients who were transported to hospital by emergency medical services. We used mixed-effects multinomial regression to quantify the effects on pre-hospital or in-hospital tracheal intubation of the following: patient characteristics; injury characteristics; centre; and trauma system characteristics. A total of 3843 patients were included. Of these, 1322 (34%) had their tracheas intubated; 839 (22%) pre-hospital and 483 (13%) in-hospital. The fit of the model with only patient characteristics predicting intubation was good (Nagelkerke R2 64%). The probability of tracheal intubation increased with the following: younger age; lower pre-hospital or emergency department GCS; higher abbreviated injury scale scores (head and neck, thorax and chest, face or abdomen abbreviated injury score); and one or more unreactive pupils. The adjusted median odds ratio for intubation between two randomly chosen centres was 3.1 (95%CI 2.1-4.3) for pre-hospital intubation, and 2.7 (95%CI 1.9-3.5) for in-hospital intubation. Furthermore, the presence of an anaesthetist was independently associated with more pre-hospital intubation (OR 2.9, 95%CI 1.3-6.6), in contrast to the presence of ambulance personnel who are allowed to intubate (OR 0.5, 95%CI 0.3-0.8). In conclusion, patient and injury characteristics are key drivers of tracheal intubation. Between-centre differences were also substantial. Further studies are needed to improve the evidence base supporting recommendations for tracheal intubation.

History of cervical spine surgery: from nihilism to advanced reconstructive surgery.

STUDY DESIGN: Review of literature. OBJECTIVES: To review and analyze the evolution of cervical spine surgery from ancient times to current practice. The aim is to present an accessible overview, primarily intended for a broad readership. METHODS: Descriptive literature review and analysis of the development of cervical spine surgery from the prehistoric era until today. RESULTS: The first evidence for surgical treatment of spinal disorders dates back to approximately 1500 BC. Conservative approaches to treatment have been the hallmark for thousands of years, but over the past 50 years progress has been rapid. We illustrate how nations have added elements to this complex subject and how knowledge has surpassed borders and language barriers. Transferral of knowledge occurred from Babylon (Bagdad) to Old Egypt, to the Greek and Roman empires and finally via the Middle East (Bagdad and Damascus) back to Europe. Recent advances in the field of anesthesia, imaging and spinal instrumentation have changed long-standing nihilism in the treatment of cervical spine pathologies to the current practice of advanced reconstructive surgery of the cervical spine. A critical approach to the evaluation of benefits and complications of these advanced surgical techniques for treatment of cervical spine disorders is required. CONCLUSION: Advances in surgery now permit full mechanical reconstruction of the cervical spine. However, despite substantial experimental progress, spinal cord repair and restoration of lost functions remain a challenge. Modern surgeons are still looking for the best way to manage spine disorders.

Neuromonitoring in traumatic brain injury.

Current approaches to monitoring in severe traumatic brain injury (TBI) include a wide array of modalities, providing insight into pressure parameters, oxygenation, perfusion, electrophysiology and metabolism of the brain. The intent of "multimodality monitoring" is to obtain a better understanding of what is going on within the brain of an individual patient in order to target treatment more appropriately. In this review we highlight the current status of neuromonitoring for TBI with a specific focus on how advanced analysis and integration of these parameters may be used to implement more personalized treatment approaches. In particular, combining information from different parameters and performing dynamic testing offers the potential to better understand the pathophysiological mechanisms active in the brain of a particular patient. Rather than persisting in a standardized "one size fits all" approach to therapy or continuing down the separate tracts of goal directed therapy, we suggest to think more in terms of "individualized therapeutic strategies" more focused on the specific requirements of each patient. Given the considerable data overload in multimodality monitoring and the complexity in interpretation of signals from multiple sources, specific attention needs to be directed to data processing and user-friendly displays. Intense collaboration and interaction between clinicians, basic researchers, IT-experts, nurses and industry will be required to further advance the fields towards more personalized approaches.

Massive swelling of Surgicel® Fibrillar™ hemostat after spinal surgery. Case report and a review of the literature.

BACKGROUND: Oxidized regenerated cellulose is commonly used in many surgical fields as a hemostatic agent. Complications related to swelling or compression after application of small portions of Surgicel® Fibrillar™ have not yet been described. PATIENTS: We report on a 65-year-old woman who was operated for a high-grade spinal stenosis at the L2-L3 level. Small portions of Surgicel® Fibrillar™ were used to control bleeding from the epidural venous plexus. The immediate postoperative course was uneventful. However, one day after surgery, the patient complained about progressive worsening pain at the operated level. A non-contrast lumbar CT scan showed no evidence of a postoperative hematoma or other complication. MR imaging showed a horseshoe-shaped mass compressing the dural sac at the operated level from posterior and both sides. Because we suspected a postoperative hematoma, the patient was re-operated. No hemorrhage was seen but instead we found large, swollen firm pieces of Surgicel® Fibrillar™ compressing the dural sac. These pieces were removed. RESULT: Postoperatively no neurological deficit or pain was present. Histological examination of the removed mass of Surgicel® Fibrillar™ revealed only the presence of blood, fibrin and an amorphous eosinophilic content. There was no sign of any inflammation. CONCLUSION: On the basis of this experience, we advise caution with the use of hemostatic agents during spinal surgery and - if used - strongly advise the removal of Surgicel® Fibrillar™ after the hemostasis has been achieved to avoid the development of complications due to a mass effect.

New approaches to increase statistical power in TBI trials: insights from the IMPACT study.

INTRODUCTION: None of the multi-centre phase III randomized controlled trials (RCTs) performed in TBI have convincingly demonstrated efficacy. Problems in clinical trial design and analysis may have contributed to these failures. Clinical trials in the TBI population pose several complicated methodological challenges, related especially to the heterogeneity of the population. In this paper we examine the issue of heterogeneity within the IMPACT (International Mission on Prognosis and Clinical Trial design in TBI) database and investigate the application of conventional and innovative methods for the statistical analysis of trials in TBI. METHODS AND RESULTS: Simulation studies in the IMPACT database (N = 9205) showed substantial gains in efficiency with covariate adjustment. Adjusting for 7 important predictors yielded up to a 28% potential reduction in trial size. Ongoing analyses on the potential benefit of ordinal analysis, such as proportional odds and sliding dichotomy, gave promising results with even larger potential reductions in trial size. CONCLUSION: The statistical power of RCTs in TBI can be considerably increased by applying covariate adjustment and by ordinal analysis methods of the GOS. These methods need to be considered for optimizing future TBI trials.

Coagulation disorders after traumatic brain injury.

BACKGROUND: Over the past decade new insights in our understanding of coagulation have identified the prominent role of tissue factor. The brain is rich in tissue factor, and injury to the brain may initiate disturbances in local and systemic coagulation. We aimed to review the current knowledge on the pathophysiology, incidence, nature, prognosis and treatment of coagulation disorders following traumatic brain injury (TBI). METHODS: We performed a MEDLINE search from 1966 to April 2007 with various MESH headings, focusing on head trauma and coagulopathy. We identified 441 eligible English language studies. These were reviewed for relevance by two independent investigators. A meta-analysis was performed to calculate the frequencies of coagulopathy after TBI and to determine the association of coagulopathy and outcome, expressed as odds ratios. RESULTS: Eighty-two studies were relevant for the purpose of this review. Meta-analysis of 34 studies reporting the frequencies of coagulopathy after TBI, showed an overall prevalence of 32.7%. The presence of coagulopathy after TBI was related both to mortality (OR 9.0; 95%CI: 7.3-11.6) and unfavourable outcome (OR 36.3; 95%CI: 18.7-70.5). CONCLUSIONS: We conclude that coagulopathy following traumatic brain injury is an important independent risk factor related to prognosis. Routine determination of the coagulation status should therefore be performed in all patients with traumatic brain injury. These data may have important implications in patient management. Well-performed prospective clinical trials should be undertaken as a priority to determine the beneficial effects of early treatment of coagulopathy.

Ethical considerations on consent procedures for emergency research in severe and moderate traumatic brain injury.

Therapeutic trials in TBI are subject to principles of Good Clinical Practice (GCP), to national legislation, and to international and European ethical concepts and regulations [e.g. 13]. The guiding principles underlying these investigations of treatment are respect for autonomy of research subjects, protection against discomfort, risk, harm and exploitation and the prospect of some benefit. Patients with significant TBI are mentally incapacitated, thus prohibiting obtaining consent directly from the subject. Various approaches to consent procedures are used as surrogate to subject consent: proxy consent, consent by an independent physician and waiver of consent. These approaches are reviewed. A questionnaire soliciting opinions was mailed to 148 EBIC (European Brain Injury Consortium) associated neuro-trauma centers in 19 European countries. 48% respondents believe that relatives were not able to make a balanced decision, 72% believed that consent procedures are a significant factor causing decrease in enrollment rate and 83% stated that consent procedures delay initiation of study treatment, resulting in possible harm if the agent has shown to be effective. 64% of the respondents considered TBI an emergency situation in which clinical research could be initiated under the emergency exception for consent. In new European legislation, emergency research under waiver of consent is not permitted. Nevertheless, we consider that randomising patients with TBI into carefully evaluated trial protocols without prior consent may be considered ethically justified.

Clinical trials in traumatic brain injury: current problems and future solutions.

Over the past decade many neuroprotective agents have been developed with the hope of being able to improve outcome in patients with traumatic brain injury. Unfortunately, none of the phase III trials performed have convincingly demonstrated efficacy in the overall population. A common misconception is that consequently these agents are ineffective. Such has not been proven and some trials show evidence of efficacy in subgroups of the population studied. The negative results, as reported in the overall population, may in part be caused by specific aspects of the TBI population, as well as by aspects of clinical trial design and analysis. Clinical trials in TBI pose several complicated design issues. Methodological challenges relate particularly to heterogeneity of the population and to outcome assessment. Heterogeneity pertains both to the range of pathologies included in TBI, and to prognostic factors, each causing specific problems. Mechanistic and/or prognostic targeting, as well as possibilities for covariate adjustment, are suggested as possible solutions to deal with the problems of heterogeneity. The aim in most trials was to demonstrate a 10% absolute improvement in favorable outcome in patients with head injury. This may be considered overoptimistic and unrealistic in relation to the heterogeneous patient population. Specific problems are further incurred by the use of the dichotomized Glasgow Outcome Scale as primary outcome measure. Optimal statistical power may expected to be present when the point of dichotomization results in a 50:50 distribution of outcome categories. It is proposed to differentiate the point of dichotomization according to prognostic risk profile, in order to maintain statistical power. Solutions described may be expected to enhance chances of demonstrating benefit of potentially effective neuroprotective agents in future studies. The complexity of problems occurring in clinical trial design and analysis in TBI is such that a strong and sustained multidisciplinary input and effort is required from all experts involved in the field of neurotrauma.

Brain tissue oxygen response in severe traumatic brain injury.

OBJECTIVE: To investigate clinical relevance and prognostic value of brain tissue oxygen response (TOR: response of brain tissue pO(2) to changes in arterial pO(2)) in traumatic brain injury (TBI). PATIENTS AND METHODS: In a prospective cohort study TOR was investigated in 41 patients with severe TBI (Glasgow Coma Score < or =8) in whom continuous monitoring of brain tissue oxygen pressure (PbrO(2)) was performed.TOR was investigated each day over a five day period for 15 minutes by increasing FiO(2) on the ventilator setting. FiO(2) was increased directly from baseline to 1.0 for a period of 15 minutes under stable conditions (145 tests). In 34 patients the effect of decreasing PaCO(2) was evaluated on TOR by performing the same test after increasing inspiratory minute volume on the ventilator setting to 20% above baseline. Arterial blood gas analysis was performed before and after changing ventilator settings. Multimodality monitoring, including PbrO(2) was performed in all patients. Outcome at six months was evaluated according to the Glasgow Outcome Scale. For statistical analysis the Mann-whitney U-test was used for ordinally distributed variables, and the Chi-square test for categorical variables. Predictive value of TOR was analyzed in a multivariable model. RESULTS: 145 tests were available for analysis. Baseline PbrO(2) varied from 4.0 to 50 mmHg at PaO(2) values of 73-237 mmHg. At FiO(2) settings of 1.0, PbrO(2) varied from 9.1-200 mmHg and PaO(2) from 196-499 mmHg. Three distinct patterns of response were noted: response type A is characterized by a sharp increase in PbrO(2), reaching a plateau within several minutes; type B by the absence of a plateau, and type C by a short plateau phase followed by a subsequent further increase in PbrO(2). Patterns characterized by a stable plateau (type A), considered indicative of intact regulatory mechanisms, were seen more frequently from 48 hours after injury on. If present within the first 24 hours after injury such a response was related to more favorable outcome (p = 0.06). Mean TOR of all tests was 0.73 +/- 0.59 with an median TOR of 0.58. Patients with an unfavourable outcome had a higher TOR (1.03 +/- 0.60) during the first 24 hours, compared to patients with a favorable outcome (0.61 +/- 0.51; p = 0.02). Multiple logistic regression analysis supported the independent predictive value of tissue oxygen response for unfavorable outcome (odds ratio 4.8). During increased hyperventilation, mean TOR decreased substantially from 0.75 +/- 0.54 to 0.65 +/- 0.45 (p = 0.06; Wilcoxon test). Within the first 24 hours after injury a decrease in TOR following hyperventilation was significantly related to poorer outcome (p = 0.01). CONCLUSIONS: Evaluation of TOR affords insight in (disturbances in) oxygen regulation after traumatic brain injury, is of prognostic value and may aid in identifying patients at (increased) risk for ischemia.

Traumatic brain injury: classification of initial severity and determination of functional outcome.

PURPOSE: The aim of the present manuscript is to review current methods for classifying initial severity and final outcome in traumatic brain injury (TBI) and to suggest a direction and form of further research. METHOD: The literature on valid and reliable measurements used in TBI-research for classifying initial severity and final outcome was reviewed. RESULTS: Classifying initial severity in patients with head injury according to clinical condition or CT-parameters is valid. Classifying outcome according to measurement tools of disability showed adequate validity and reliability. CONCLUSIONS: Future research in TBI outcome, particularly in rehabilitation medicine, should focus on determinants of outcome, identifying those patients who will have the greatest chance of benefiting from intensive rehabilitation programmes. More research is needed to determine the long-term functional outcome in TBI, the long-term socio-economic costs, and the influence of behavioural problems on family cohesion. Finally, validation of outcome measures is required in the TBI-population; the relative value of various outcome measures needs to be determined, and the usefulness and applicability of measures for health related quality of life in TBI should be established.

Serial transcranial Doppler measurements in traumatic brain injury with special focus on the early posttraumatic period.

BACKGROUND: Cerebral ischemia is considered a key factor in the development of secondary damage after Traumatic Brain Injury (TBI). Studies on Cerebral Blood Flow (CBF) have documented decreased flow in over 50% of patients with TBI, studied in the acute phase. Transcranial Doppler (TCD) sonography is a non-invasive technique, permitting frequent or continuous measurements of blood flow velocity in the basal cerebral arteries. OBJECTIVES: To investigate the potential of TCD to detect decreased blood flow velocity in the early phase after TBI;To investigate whether flow velocity differs between hemispheres in patients with focal lesions versus those with more diffuse injuries;To investigate if decreased blood flow velocity is indicative of cerebral ischemia, as evidenced by measurements of brain tissue pO(2). METHODS: TCD examinations were performed in 57 patients with severe TBI (GCS