Effect of intracranial pressure monitoring on survival in severe traumatic brain injury: a meta-analysis of randomized trials

BACKGROUND Intracranial pressure (ICP) monitoring remains a cornerstone recommendation in the management of severe traumatic brain injury (sTBI), as outlined by the Brain Trauma Foundation (BTF). Classified as a Level IIb recommendation, ICP monitoring is advocated to detect and manage intracranial hypertension, a critical determinant of outcomes in TBI. This recommendation reflects moderate-quality evidence supporting its use to guide therapeutic decisions and improve patient care. However, the clinical efficacy of ICP monitoring in improving survival and functional recovery remains a topic of ongoing debate. While guidelines endorse its integration into standard care protocols, evidence from studies such as the BEST TRIP trial Chesnut et al.1 has questioned its superiority over approaches based solely on imaging and clinical assessments. In addition, advancements in multimodal approaches, including the integration of ICP monitoring with brain oxygenation, as evaluated in the BOOST-II study Okonkwo et al.,2 suggest potential improvements in functional outcomes and survival. These findings are promising but underscore the necessity of larger trials to validate such strategies. Furthermore, considerations around complications associated with ICP monitoring, though minimal in experienced centers, and the economic implication of prolonged ICU stays demand careful evaluation. This meta-analysis aimed to consolidate the available evidence on the impact of ICP monitoring on key clinical outcomes, including mortality, functional recovery, and monitoring-related complications. By synthesizing data from pivotal studies, this review seeks to clarify the role of ICP monitoring in contemporary TBI management and identify priorities for future research. METHODS The study was designed following the Cochrane Collaboration Handbook for Systematic Review of Interventions and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines. Eligibility criteria We restricted inclusion in this meta-analysis to randomized controlled trials (RCTs) that compared patients’ ICP monitoring or non-monitoring after severe traumatic brain injury (GCS 3-8). The included studies were required to report at least one of the following outcomes of interest: (1) functional outcomes (neurological recover GCS>8); (2) complications related to ICP monitoring; (3) length of stay in the Intensive Care Unit (ICU); (4) control of intracranial pressure; (5) mortality. We excluded studies that do not perform analysis only of invasive and non-invasive intracranial pressure measurements. Search strategy and data extraction We systematically searched the United States National Library of Medicine (PubMed), Embase, and the Cochrane Central Register of Controlled Trials from inception to November 2024 using the following search strategy: (Severe Traumatic Brain Injury" OR "Severe Head Injury") AND ("Intracranial Pressure Monitoring" OR "ICP Monitoring" OR "Intracranial Pressure Device") AND ("Clinical Outcomes" OR "Mortality" OR "Functional Recovery" OR "Complications). We extracted the data from individual studies according to predefined search criteria. Disagreements were resolved by consensus among the authors. Endpoints and subgroup analysis The primary outcome of interest was mortality for any cause and functional outcome based on the Glasgow Outcome Scale Extended (GOS-E). Secondary outcomes of interest included length of stay in the ICU (Medium) and control of intracranial Pressure (typically ≤20 mmHg). We performed a subgroup analysis comparing the effects of eptifibatide as an adjuvant therapy to thrombolysis versus thrombolysis alone. Quality assessment The quality assessment of the RCTs was performed using Cochrane’s Risk of Bias 2 (RoB 2) tool11. This evaluation classifies studies as high, medium (some concerns), or low regarding bias within five domains. Two independent reviewers (G. S and A. L. M. S.) conducted the quality assessments, which were then reviewed and approved by a third (S.S). Statistical analysis We evaluated treatment effects for binary endpoints using pooled relative risk (RR) and odds ratios (OR), each with 95% confidence intervals (95%CI). Effect size variation and heterogeneity were evaluated through I2 and Tau2 statistics. We used a fixed-effect model for endpoints with I2 <25% and Der Simonian and Laird random-effect models for pooled outcomes with high heterogeneity. All statistical analyses were conducted using R, version 4.2.3 (R Foundation for Statistical Computing). RESULTS Initially, 790 articles were identified, of which 148 from PubMed, 387 from Embase, 219 from Web of Science, 36 from Cochrane Library. After repeated studies detection, 500 articles were excluded, leaving 490 articles for abstract/full-text screening. A meticulous selection was conducted, resulting in 27 final articles being sought for retrieval. Of these final articles, 19 were excluded and did not proceed to the data extraction, leaving five final studies to be included in the analysis. The reasons for exclusion were as follows: non-comparative studies; and unclear data and non-randomized studies. The PRISMA flow diagram illustrates the selection process of studies included in the systematic review. A total of 356 records were initially identified through database searches: 48 from PubMed, 42 from Cochrane, and 266 from Embase. After removing 92 duplicate records, 294 studies remained for screening. Of these, 179 were excluded following human review, leaving 115 studies for full-text retrieval. All 115 reports were successfully retrieved, and 13 were assessed for eligibility. Nine reports were excluded due to lack of relevant outcomes or for not being randomized controlled trials. Ultimately, four studies were included in the systematic review. Information regarding the study selection process is summarized in Figure 1. Study selection The table (Table 1)1-4 presents a comparative overview of four major RCTs investigating the use of ICP monitoring in patients with severe TBI. The studies are characterized based on country of origin, median patient age, ICU length of stay, ICP-related complications, and reported mortality rates. • Cooper et al.3 (DECRA) was conducted in Australia, New Zealand, and Saudi Arabia, enrolling patients with a median age of 25 years. The median ICU stay was 12 days. Although specific complication rates were not reported, the study noted the occurrence of surgical site infections. The reported mortality rate was 19%. • Hutchinson et al.4 (RESCUEicp) included participants from the UK, Europe, and Asia, with a median age of 33 years and an ICU stay of 12 days. ICP-related complications included cerebrospinal fluid (CSF) leaks, seizures, and infections; however, the exact percentages were not specified. The mortality rate was 27%. • Okonkwo et al.2 (BOOST-II) was a United States-based study with a median patient age of 35 years. The duration of ICU stay and complications were not reported (NR). The mortality rate observed was 22%. • Chesnut et al.1 (BEST TRIP) involved populations from Bolivia, Ecuador, and Guatemala, with a median age of 29 years and an ICU stay of 13 days. Pressure ulcers were reported in 19% of patients. The highest mortality rate among the studies was recorded in this trial, at 39%. Patient outcomes ICP monitoring led to a significantly longer ICU stay, reflecting potentially increased resource utilization, but it did not significantly impact mortality. Complications related to monitoring were minimal, and no major adverse effects were observed. Further research is needed to explore the effects of ICP monitoring on long-term functional outcomes and quality of life. Length of stay in Intensive Care Unit The meta-analysis showed a modest but statistically significant reduction in ICU length of stay among patients who received ICP monitoring compared to those who did not (Figure 2). The mean difference (MD) was -0.75 days (95%CI -1.25 to -0.25), favoring the ICP group. Heterogeneity across studies was low (I2=25.7%, τ2=0.0672, p=0.2573), indicating reasonable consistency in findings. While the absolute difference in ICU stay duration is relatively small, this result may reflect subtle improvements in clinical management facilitated by ICP monitoring. Further studies are needed to clarify whether this reduction translates into meaningful clinical or economic benefits. Mortality after intracranial pressure monitoring The meta-analysis revealed no statistically significant difference in mortality between patients who received intracranial pressure (ICP) monitoring and those who did not (Figure 3). The pooled OR was 1.07 (95%CI 0.83 to 1.37), indicating a slight, non-significant increase in mortality in the ICP group. Heterogeneity among the studies was negligible (I2=0.0%, τ2=0, p=0.6752), suggesting high consistency across trials. Overall, these findings do not support a mortality benefit associated with the use of ICP monitoring in severe traumatic brain injury. Complications related to intracranial pressure monitoring Complications associated with ICP monitoring include infection, hemorrhage, and malpositioning of the monitoring device. Across the four randomized controlled trials included in this review — BEST TRIP,1 DECRA,3 RESCUEicp,4 and BOOST-II2 — the overall complication rate was low and generally not significantly different between ICP-monitored and control groups. For instance, in the BEST TRIP trial, the adverse events attributed directly to ICP monitoring did not exceed those seen in the non-monitoring group, though pressure ulcer incidence was higher among the monitored patients (19 vs. 8%).1 In RESCUEicp and BOOST-II, no significant differences in infection or hemorrhage rates were reported between study arms. Risk of bias assessment Risk of bias was assessed using the RoB 2 tool. All included trials were randomized and reported allocation concealment. Blinding of participants and personnel was generally not feasible due to the nature of the interventions, but outcome assessors were blinded in all four studies. Attrition bias was low across all trials due to minimal loss to follow-up. Selective reporting was not identified. Overall, the risk of bias was considered low for all studies. The figures summarize the risk of bias evaluation of the four RCTs included in this meta-analysis using the Cochrane RoB 2 tool. Figure 4 ("Summary plot") presents the distribution of bias judgments across five domains: • D1: Randomization – Two studies showed high risk of bias, and two presented some concerns due to issues related to allocation concealment and sequence generation. • D2: Deviations from intended interventions – One study raised some concerns, while the remaining three were considered low risk. • D3: Missing outcome data – All studies were rated as low risk in this domain. • D4: Measurement of the outcome – All four studies had low risk of bias in outcome measurement. • D5: Selection of the reported result – All included studies were classified as low risk, suggesting adherence to pre-specified outcome reporting. Figure 5 ("Traffic Light") provides a visual synthesis of the RoB 2 assessment for each study (BEST TRIP, DECRA, RESCUEicp, and BOOST-II). The overall risk of bias was: • BEST TRIP – Some concerns (mainly due to randomization). • DECRA – Low risk. • RESCUEicp – Some concerns. • BOOST-II – High risk (notably in the randomization and reporting domains). This risk of bias assessment highlights important methodological limitations in some of the trials, particularly concerning the randomization process and deviations from intended protocols. These factors must be considered when interpreting the pooled results of this meta-analysis. DISCUSSION The role of ICP monitoring in the management of severe TBI remains controversial, despite its widespread adoption and inclusion in clinical guidelines. According to the BTF’s 4th edition guidelines, ICP monitoring is recommended (Level II B) for comatose patients with severe TBI (GCS 3–8) and abnormal CT scans, or in patients with normal CT scans but with risk factors (e.g., age >40 years, motor posturing, or hypotension).5 Evidence from the DECRA trial demonstrated that decompressive craniectomy reduced ICP and ICU length of stay but was associated with worse functional outcomes at six months post-injury.3 Conversely, the RESCUEicp trial found that late decompressive craniectomy in patients with refractory ICP elevation led to increased survival, though with a higher proportion of patients in a vegetative or severely disabled state.4 The BEST TRIP study, unique in being conducted in low- and middle-income countries (LMICs), compared ICP-guided therapy to a protocol based on imaging and clinical examination and found no significant difference in mortality or functional outcome.1 This raised concerns about the universal applicability of ICP monitoring, particularly in resource-limited settings. The BOOST-II trial suggested that ICP-guided therapy augmented with brain tissue oxygen (PbtO2) monitoring might improve outcomes, though definitive conclusions require further studies.2 Although ICP monitoring allows more targeted and dynamic management, its effect on long-term outcomes is still debated. Factors such as timing, thresholds, multimodal monitoring, and individual patient characteristics likely play roles in outcomes. The heterogeneity in study designs and patient populations also contributes to conflicting results. CONCLUSION This systematic review and meta-analysis of four major RCTs — BEST TRIP, DECRA, RESCUEicp, and BOOST-II — highlights the complexity and nuance of using ICP monitoring in the management of severe TBI. While current BTF guidelines support its use in specific patient populations, the evidence suggests that ICP monitoring alone may not be sufficient to improve outcomes unless coupled with protocolized and responsive treatment strategies. The variability in outcomes across trials underscores the need for individualized patient-centered approaches, considering local resources, patient demographics, and injury severity. Further high-quality multicenter trials are warranted to refine the indications and methodologies of ICP monitoring, integrating newer technologies and outcome metrics. The inclusion of long-term neurocognitive and quality-of-life outcomes will be essential to fully understand the benefit of ICP monitoring in severe TBI care.