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Intracranial Pressure Trajectories: A Novel Approach to Informing Severe Traumatic Brain Injury Phenotypes.

ABSTRACT: OBJECTIVES:Intracranial pressure in traumatic brain injury is dynamic and influenced by factors like injury patterns, treatments, and genetics. Existing studies use time invariant summary intracranial pressure measures thus potentially losing critical information about temporal trends. We identified longitudinal intracranial pressure trajectories in severe traumatic brain injury and evaluated whether they predicted outcome. We further interrogated the model to explore whether ABCC8 polymorphisms (a known cerebraledema regulator) differed across trajectory groups. DESIGN:Prospective observational cohort. SETTING:Single-center academic medical center. PATIENTS:Four-hundred four severe traumatic brain injury patients. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We used group-based trajectory modeling to identify hourly intracranial pressure trajectories in days 0-5 post traumatic brain injury incorporating risk factor adjustment (age, sex, Glasgow Coma Scale 6score, craniectomy, primary hemorrhage pattern). We compared 6-month outcomes (Glasgow Outcome Scale, Disability Rating Scale, mortality) and ABCC8 tag-single-nucleotide polymorphisms associated with cerebral edema (rs2237982, rs7105832) across groups. Regression models determined whether trajectory groups predicted outcome. A six trajectory group model best fit the data, identifying cohorts differing in initial intracranial pressure, evolution, and number/proportion of spikes greater than 20?mm Hg. There were pattern differences in age, hemorrhage type, and craniectomy rates. ABCC8 polymorphisms differed across groups. GOS (p = 0.006), Disability Rating Scale (p = 0.001), mortality (p < 0.0001), and rs2237982 (p = 0.035) differed across groups. Unfavorable outcomes were surprisingly predicted by both low intracranial pressure trajectories and sustained intracranial hypertension. Intracranial pressure variability differed across groups (p < 0.001) and may reflect preserved/impaired intracranial elastance/compliance. CONCLUSIONS:We employed a novel approach investigating longitudinal/dynamic intracranial pressure patterns in traumatic brain injury. In a risk adjusted model, six groups were identified and predicted outcomes. If validated, trajectory modeling may be a first step toward developing a new, granular approach for intracranial pressure phenotyping in conjunction with other phenotyping tools like biomarkers and neuroimaging. This may be particularly relevant in light of changing traumatic brain injury demographics toward the elderly.

SUBMITTER: Jha RM

PROVIDER: S-EPMC6185785 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Intracranial Pressure Trajectories: A Novel Approach to Informing Severe Traumatic Brain Injury Phenotypes.

Jha Ruchira M RM Elmer Jonathan J Zusman Benjamin E BE Desai Shashvat S Puccio Ava M AM Okonkwo David O DO Park Seo Young SY Shutter Lori A LA Wallisch Jessica S JS Conley Yvette P YP Kochanek Patrick M PM

Critical care medicine 20181101 11

<h4>Objectives</h4>Intracranial pressure in traumatic brain injury is dynamic and influenced by factors like injury patterns, treatments, and genetics. Existing studies use time invariant summary intracranial pressure measures thus potentially losing critical information about temporal trends. We identified longitudinal intracranial pressure trajectories in severe traumatic brain injury and evaluated whether they predicted outcome. We further interrogated the model to explore whether ABCC8 polym ...[more]

PMID: 30119071

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Project description:ImportanceIntracranial pressure (ICP) monitoring is a mainstay of therapy for children with traumatic brain injury (TBI), but its overall association with patient outcome is unclear.ObjectiveTo test the hypothesis that ICP monitoring is associated with improved functional survival of children with severe TBI.Design, setting, and participantsA propensity-weighted effectiveness analysis was conducted using 2 linked national databases with data from 30 US children's hospitals from January 1, 2007, to December 31, 2012, on 3084 children with severe TBI. Clinical events including neurosurgical procedures were identified using validated computable phenotypes. Data analysis was conducted from September 1, 2016, to March 1, 2017.ExposurePlacement of an ICP monitor.Main outcomes and measuresA composite of hospital mortality, discharge to hospice, or survival with placement of new tracheostomy and gastrostomy tubes.ResultsOf the 3084 children in the study (1128 girls and 1956 boys; mean [SD] age, 7.03 [5.44] years), 1002 (32.4%) underwent ICP monitoring, with substantial hospital variation (6% to 50% by hospital). Overall, 484 children (15.7%) experienced the primary composite outcome. A propensity approach using matching weights generated good covariate balance between those who did and those who did not undergo ICP monitoring. Using a propensity-weighted logistic regression model clustered by hospital, no statistically significant difference was found in functional survival between monitored and unmonitored patients (odds ratio of poor outcome among those who underwent ICP monitoring, 1.31; 95% CI, 0.99-1.74). In a prespecified secondary analysis, no difference in mortality was found (odds ratio, 1.16; 95% CI, 0.89-1.50). Prespecified subgroup analyses of children younger and older than 2 years of age and among those with unintentional and inflicted (intentional) injuries also showed no difference in outcome with ICP monitoring.Conclusions and relevanceWith the use of linked national data and validated computable phenotypes, no evidence was found of a benefit from ICP monitoring on functional survival of children with severe TBI. Intracranial pressure monitoring is a widely but inconsistently used technology with incompletely demonstrated effectiveness. A large prospective cohort study or randomized trial is needed.

Project description:Intracranial-pressure monitoring is considered the standard of care for severe traumatic brain injury and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed.We conducted a multicenter, controlled trial in which 324 patients 13 years of age or older who had severe traumatic brain injury and were being treated in intensive care units (ICUs) in Bolivia or Ecuador were randomly assigned to one of two specific protocols: guidelines-based management in which a protocol for monitoring intraparenchymal intracranial pressure was used (pressure-monitoring group) or a protocol in which treatment was based on imaging and clinical examination (imaging-clinical examination group). The primary outcome was a composite of survival time, impaired consciousness, and functional status at 3 months and 6 months and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of protocol assignment. This composite measure was based on performance across 21 measures of functional and cognitive status and calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance).There was no significant between-group difference in the primary outcome, a composite measure based on percentile performance across 21 measures of functional and cognitive status (score, 56 in the pressure-monitoring group vs. 53 in the imaging-clinical examination group; P=0.49). Six-month mortality was 39% in the pressure-monitoring group and 41% in the imaging-clinical examination group (P=0.60). The median length of stay in the ICU was similar in the two groups (12 days in the pressure-monitoring group and 9 days in the imaging-clinical examination group; P=0.25), although the number of days of brain-specific treatments (e.g., administration of hyperosmolar fluids and the use of hyperventilation) in the ICU was higher in the imaging-clinical examination group than in the pressure-monitoring group (4.8 vs. 3.4, P=0.002). The distribution of serious adverse events was similar in the two groups.For patients with severe traumatic brain injury, care focused on maintaining monitored intracranial pressure at 20 mm Hg or less was not shown to be superior to care based on imaging and clinical examination. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01068522.).

Project description:Purpose of reviewStandard clinical protocols for treating cerebral edema and intracranial hypertension after severe TBI have remained remarkably similar over decades. Cerebral edema and intracranial hypertension are treated interchangeably when in fact intracranial pressure (ICP) is a proxy for cerebral edema but also other processes such as extent of mass lesions, hydrocephalus, or cerebral blood volume. A complex interplay of multiple molecular mechanisms results in cerebral edema after severe TBI, and these are not measured or targeted by current clinically available tools. Addressing these underpinnings may be key to preventing or treating cerebral edema and improving outcome after severe TBI.Recent findingsThis review begins by outlining basic principles underlying the relationship between edema and ICP including the Monro-Kellie doctrine and concepts of intracranial compliance/elastance. There is a subsequent brief discussion of current guidelines for ICP monitoring/management. We then focus most of the review on an evolving precision medicine approach towards cerebral edema and intracranial hypertension after TBI. Personalization of invasive neuromonitoring parameters including ICP waveform analysis, pulse amplitude, pressure reactivity, and longitudinal trajectories are presented. This is followed by a discussion of cerebral edema subtypes (continuum of ionic/cytotoxic/vasogenic edema and progressive secondary hemorrhage). Mechanisms of potential molecular contributors to cerebral edema after TBI are reviewed. For each target, we present findings from preclinical models, and evaluate their clinical utility as biomarkers and therapeutic targets for cerebral edema reduction. This selection represents promising candidates with evidence from different research groups, overlap/inter-relatedness with other pathways, and clinical/translational potential. We outline an evolving precision medicine and translational approach towards cerebral edema and intracranial hypertension after severe TBI.

Project description:To examine the use of intracranial pressure monitors and treatment for elevated intracranial pressure in children 24 months old or younger with traumatic brain injury in North Carolina between April 2009 and March 2012 and compare this with a similar cohort recruited 2000-2001.Prospective, observational cohort study.Twelve PICUs in North Carolina.All children 24 months old or younger with traumatic brain injury, admitted to an included PICU.None.The use of intracranial pressure monitors and treatments for elevated intracranial pressure were evaluated in 238 children with traumatic brain injury. Intracranial pressure monitoring (risk ratio, 3.7; 95% CI, 1.5-9.3) and intracranial pressure therapies were more common in children with Glasgow Coma Scale less than or equal to 8 compared with Glasgow Coma Scale greater than 8. However, only 17% of children with Glasgow Coma Scale less than or equal to 8 received a monitoring device. Treatments for elevated intracranial pressure were more common in children with monitors; yet, some children without monitors received therapies traditionally used to lower intracranial pressure. Unadjusted predictors of monitoring were Glasgow Coma Scale less than or equal to 8, receipt of cardiopulmonary resuscitation, nonwhite race. Logistic regression showed no strong predictors of intracranial pressure monitor use. Compared with the 2000 cohort, children in the 2010 cohort with Glasgow Coma Scale less than or equal to 8 were less likely to receive monitoring (risk ratio, 0.5; 95% CI, 0.3-1.0), although the estimate was not precise, or intracranial pressure management therapies.Children in the 2010 cohort with a Glasgow Coma Scale less than or equal to 8 were less likely to receive an intracranial pressure monitor or hyperosmolar therapy than children in the 2000 cohort; however, about 10% of children without monitors received therapies to decrease intracranial pressure. This suggests treatment heterogeneity in children 24 months old or younger with traumatic brain injury and a need for better evidence to support treatment recommendations for this group of children.

Project description:Intracranial pressure (ICP) monitoring is widely used in the management of patients with severe traumatic brain injury (TBI). However, there is limited evidence about the efficacy of ICP monitoring in older subjects (aged ≥65 years). This study evaluated the effect of intraventricular ICP monitoring on the outcome of older adults suffering from a severe TBI.This prospective, observational study included 166 older TBI patients (aged ≥65 years) with Glasgow Coma scale (GCS) scores lower than 9 at admission. The study cohort was divided into two groups, intraventricular ICP monitoring and non-ICP monitoring. The primary outcome was in-hospital mortality. The secondary outcomes included the Glasgow Outcome Scale (GOS) score 6 months after injury, the ICU and total hospital lengths of stay, and mechanical ventilation days.There were 80 patients in the intraventricular ICP monitoring group and 86 patients in non-ICP monitoring group. There was no statistical difference between groups in demographics and severity of head injury. Patients treated with intraventricular ICP monitoring had lower in-hospital mortality (33.8 % vs 51.2 %, P < 0.05), a higher 6-month GOS score (3.0 ± 1.4 vs 2.5 ± 1.2 P < 0.05), and a lower dosage (514 ± 246 g vs 840 ± 323 g, P < 0.0001) and shorter duration (7.2 ± 3.6 days vs 8.4 ± 4.3 days, P < 0.01) of mannitol use. However, the ICU length of stay (14.3 ± 6.4 days vs 11.6 ± 5.8 days, P < 0.01) and mechanical ventilation days (6.7 ± 3.5 days vs 5.6 ± 2.4 days, P < 0.05) were longer in the ICP monitoring group. The total length of hospital stay did not differ between the two groups (28.5 ± 12.1 days vs 26.1 ± 13.5 days, P = 0.23).Intraventricular ICP monitoring may have beneficial effects on the decreased in-hospital mortality and improved 6-month outcome of older patients with severe TBI. However, given that this was an observational study conducted in a single institution, further well-designed randomized control trials are needed to evaluate the effect of intraventricular ICP monitoring on the outcome of older severe TBI patients.

Project description:BackgroundAmong people who have suffered a traumatic brain injury, increased intracranial pressure continues to be a major cause of early death; it is estimated that about 11 people per 100 with traumatic brain injury die. Indomethacin (also known as indometacin) is a powerful cerebral vasoconstrictor that can reduce intracranial pressure and, ultimately, restore cerebral perfusion and oxygenation. Thus, indomethacin may improve the recovery of a person with traumatic brain injury.ObjectivesTo assess the effects of indomethacin for adults with severe traumatic brain injury.Search methodsWe ran the searches from inception to 23 August 2019. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8) in the Cochrane Library, Ovid MEDLINE, Ovid Embase, CINAHL Plus (EBSCO), four other databases, and clinical trials registries. We also screened reference lists and conference abstracts, and contacted experts in the field.Selection criteriaOur search criteria included randomised controlled trials (RCTs) that compared indomethacin with any control in adults presenting with severe traumatic brain injury associated with elevated intracranial pressure, with no previous decompressive surgery.Data collection and analysisTwo review authors independently decided on the selection of the studies. We followed standard Cochrane methods.Main resultsWe identified no eligible studies for this review, either completed or ongoing.Authors' conclusionsWe found no studies, either completed or ongoing, that assessed the effects of indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. Thus, we cannot draw any conclusions about the effects of indomethacin on intracranial pressure, mortality rates, quality of life, disability or adverse effects. This absence of evidence should not be interpreted as evidence of no effect for indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. It means that we have not identified eligible research for this review.

Dataset Information

Intracranial Pressure Trajectories: A Novel Approach to Informing Severe Traumatic Brain Injury Phenotypes.

Publications

Intracranial Pressure Trajectories: A Novel Approach to Informing Severe Traumatic Brain Injury Phenotypes.

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