Traumatic Brain Injury

Study of therapeutic hypothermia (32 to 35°C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial): outcome of the pilot phase of the trial

Authors: Andrews PJ, Sinclair LH, Harris B, Baldwin MJ, Battison CG, Rhodes JK, Murray G, De Backer D.

BACKGROUND: Clinical trials in traumatic brain injury (TBI) are challenging. Previous trials of complex interventions were conducted in high-income countries, reported long lead times for site setup and low screened-to-recruitment rates.In this report we evaluate the internal pilot phase of an international, multicentre TBI trial of a complex intervention to assess: design and implementation of an online case report form; feasibility of recruitment (sites and patients); feasibility and effectiveness of delivery of the protocol.
METHODS: All aspects of the pilot phase of the trial were conducted as for the main trial. The pilot phase had oversight by independent Steering and Data Monitoring committees.
RESULTS: Forty sites across 12 countries gained ethical approval. Thirty seven of 40 sites were initiated for recruitment. Of these, 29 had screened patients and 21 randomized at least one patient. Lead times to ethics approval (6.8 weeks), hospital approval (18 weeks), interest to set up (61 weeks), set up to screening (11 weeks), and set up to randomization (31.6 weeks) are comparable with other international trials. Sixteen per cent of screened patients were eligible. We found 88% compliance rate with trial protocol.
CONCLUSION: The pilot data demonstrated good feasibility for this large international multicentre randomized controlled trial of hypothermia to control intracranial pressure. The sample size was reduced to 600 patients because of homogeneity of the patient group and we showed an optimized cooling intervention could be delivered.Trial registration Current Controlled Trials: ISRCTN34555414.

Lessons from the Intracranial Pressure Monitoring-Trial in TBI patients

Authors: Sarrafzadeh AS, Smoll NR, Unterberg AW.

BACKGROUND: Monitoring of intracranial pressure (ICP) has been used for decades in patients with severe traumatic brain injury (TBI) and is recommended in the Guidelines of the Brain Trauma Foundation. It is the standard of care in most industrialized countries.
METHODS: Chesnut et al. have now performed the first randomized trial of ICP monitoring in patients with severe TBI. Patients were randomly assigned to one of two specific protocols - ICP monitoring (n=157) or imaging and clinical exam (n=167). The study was conducted in Latin America, where ICP-monitoring is not the standard of care in most hospitals.
RESULTS: Six months after injury, patients groups had similar scores on functional status and cognition and similar cumulative mortality. Patients who underwent ICP monitoring had a significantly lower intensity of brain-specific treatment and received fewer treatments for intracranial hypertension.
CONCLUSION: The benefit of this study is that ICP-monitoring - and more advanced multimodal monitoring allows a tailored treatment avoiding an overtherapy of drugs with unfavorable side effects. For low income countries, the results of this trial are encouraging, though efforts should be done to further improve after ICU-care and outcome. However, we guard against the use of this data to reform European and North American treatment guidelines. The authors have proven that neurosurgery can be studied in an elegant fashion. Thanks to their team of neurosurgeons and neurointensivists, the outcome of TBI-patients will continue to improve, driven by clinical practice guidelines.

National Variability in Intracranial Pressure Monitoring and Craniotomy for Children with Moderate to Severe Traumatic Brain Injury

Authors: Van Cleve W, Kernic MA, Ellenbogen RG, Wang J, Zatzick DF, Bell MJ, Wainwright MS, Groner JI, Mink RB, Giza CC, Boyle LN, Mitchell PH, Rivara FP, Vavilala MS; for the PEGASUS (Pediatric Guideline Adherence and Outcomes) Project.

BACKGROUND: Traumatic brain injury (TBI) is a significant cause of mortality and disability in children. Intracranial pressure monitoring (ICPM) and craniotomy/craniectomy (CRANI) may affect outcomes. Sources of variability in the use of these interventions remain incompletely understood.

OBJECTIVE: To analyze sources of variability in the use of ICPM and CRANI.

METHODS: Retrospective cross-sectional study of patients with moderate/severe pediatric TBI using data submitted to the American College of Surgeons National Trauma Databank.

RESULTS: We analyzed data from 7,140 children at 156 US hospitals during 7 continuous years. 27.4% of children had ICPM, while 11.7% had a CRANI. Infants had lower rates of ICPM and CRANI than older children. A lower rate of ICPM was observed among children hospitalized at combined pediatric/adult trauma centers than children treated at adult-only trauma centers (RR 0.80, 95% CI 0.66 - 0.97). For ICPM and CRANI, 18.5% and 11.6%, respectively, of residual model variance was explained by between-hospital variation in care delivery, but almost no correlation was observed between within-hospital tendency towards performing these procedures.

CONCLUSION: Infants received less ICPM than older children, and children hospitalized at pediatric trauma centers received less ICPM than children at adult-only trauma centers. In addition, significant between-hospital variability existed in the delivery of ICPM and CRANI to children with moderate-severe TBI.

Pressure is only part of the story in traumatic brain injured patients; focal cerebral blood flow goes to zero in some patients with adequate cerebral perfusion pressure

Authors: Chovanes G, Richards RM.

INTRODUCTION: The pathophysiology of traumatic brain injury (TBI) is still not clearly understood. Recently, a decompressive craniectomy trial (1) and a trial of intracranial pressure (ICP) treatment with ICP monitoring vs no monitoring (2) failed to support the concept that increases in ICP are exclusively responsible for TBI mortality and morbidity. To analyze the role ICP, cerebral perfusion pressure (CPP = BP-ICP), and cerebral blood flow (CBF) play in head injury, we monitored brain injured patients' ICP, blood pressure (BP), CPP, and focal cerebral blood flow (fCBF), recording the real-time data for computer analysis.
METHODS: 20 patients with severe brain injury were monitored with recordings of ICP, BP, CPP, and fCBF every minute. 17 patients had severe closed TBI, 1 gunshot wound, and 2 intracerebral hemorrhages. 13 patients lived (GCS 3-9, average 5), 7 died (GCS 3-7, average 5). Of the 7 patients who died, 5 had technically adequate recordings before and as death supervened. Graphs were prepared of time vs CPP, ICP and fCBF and reviewed for the time course of fCBF deterioration vs CPP elevation. If CPP obviously and substantially decreased before fCBF decreased, that was termed a pressure death. However, if CPP stayed adequate and fCBF still decreased to zero, that was termed a non-pressure death.
RESULTS: Three patients had a pressure death (Fig 1), and 2 patients had a non-pressure death (Fig 2).
CONCLUSION: This may be the first real-time documentation of non-CPP dependent brain death as expressed by fCBF. There are pathological processes in the injured brain that do not directly involve increases in ICP and decreases in CPP. Heretofore clinical treatment efforts in brain injury have focused on ICP: other mechanisms are also extant and should be further investigated so as to more successfully treat brain injury.

Mathematical Modelling of Near-Infrared Spectroscopy Signals and Intracranial Pressure in Brain-Injured Patients

Authors: Highton D, Panovska-Griffiths J, Smith M, Elwell CE.

Raised intracranial pressure (ICP) is a key concern following acute brain injury as it may be associated with cerebral hypoperfusion and poor outcome. In this research we describe a mathematical physiological model designed to interpret cerebral physiology from neuromonitoring: ICP, near-infrared spectroscopy and transcranial Doppler flow velocity. This aims to characterise the complex dynamics of cerebral compliance, cerebral blood volume, cerebral blood flow and their regulation in individual patients. Analysis of data from six brain-injured patients produces cohesive predictions of cerebral biomechanics suggesting reduced cerebral compliance, reduced volume compensation and impaired blood flow autoregulation. Patient-specific physiological modelling has the potential to predict the key biomechanical and haemodynamic changes following brain injury in individual patients, and might be used to inform individualised treatment strategies.

Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury

Authors: Bouzat P, Sala N, Payen JF, Oddo M.

Monitoring and management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is a standard of care after traumatic brain injury (TBI). However, the pathophysiology of so-called secondary brain injury, i.e., the cascade of potentially deleterious events that occur in the early phase following initial cerebral insult---after TBI, is complex, involving a subtle interplay between cerebral blood flow (CBF), oxygen delivery and utilization, and supply of main cerebral energy substrates (glucose) to the injured brain. Regulation of this interplay depends on the type of injury and may vary individually and over time. In this setting, patient management can be a challenging task, where standard ICP/CPP monitoring may become insufficient to prevent secondary brain injury. Growing clinical evidence demonstrates that so-called multimodal brain monitoring, including brain tissue oxygen (PbtO2), cerebral microdialysis and transcranial Doppler among others, might help to optimize CBF and the delivery of oxygen/energy substrate at the bedside, thereby improving the management of secondary brain injury. Looking beyond ICP and CPP, and applying a multimodal therapeutic approach for the optimization of CBF, oxygen delivery, and brain energy supply may eventually improve overall care of patients with head injury. This review summarizes some of the important pathophysiological determinants of secondary cerebral damage after TBI and discusses novel approaches to optimize CBF and provide adequate oxygen and energy supply to the injured brain using multimodal brain monitoring.


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