Publication

• Title: A trial of intracranial-pressure monitoring in traumatic brain injury
• Acronym: BEST:TRIP (Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure)
• Year: 2012
• Journal published in: The New England Journal of Medicine
• Citation: Chesnut RM, Temkin N, Carney N, et al. A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med. 2012;367:2471-2481.

Context & Rationale

• Background

  • Invasive intracranial pressure (ICP) monitoring had become a de facto standard in many ICUs for severe traumatic brain injury (TBI), embedded in practice pathways and guideline recommendations, despite limited randomised evidence.
  • Clinicians faced a persistent evidentiary tension: ICP monitoring is invasive and resource-intensive (with haemorrhage/infection risks), yet the biological plausibility of preventing/treating intracranial hypertension is strong.
  • Globally, access to ICP monitors is variable; the trialists sought evidence relevant to both high-resource and resource-limited environments where clinicians rely on neurological examination and CT imaging.
• Research Question/Hypothesis

  • Does protocolised management guided by invasive ICP monitoring improve patient-centred outcomes compared with protocolised management guided by serial imaging and clinical examination in severe TBI?
  • Hypothesis (superiority): ICP-guided management would reduce mortality and improve functional/neuropsychological recovery versus the imaging–clinical strategy.
• Why This Matters

  • Addresses a longstanding gap: widespread adoption of an invasive monitoring technology without prior definitive RCT evidence of outcome benefit.
  • Clarifies whether outcome gains (if any) are attributable to the monitor itself versus the structured, protocol-driven behaviours that often accompany monitoring.
  • Provides an evidence anchor for guideline writers and health systems deciding where to invest: devices, training, imaging capability, staffing, and protocol implementation.

Design & Methods

• Research Question: In adolescents/adults with severe TBI, does ICP-guided protocolised acute management improve functional, neuropsychological, and survival outcomes versus a protocolised imaging–clinical examination strategy?
• Study Type: Multicentre, randomised, parallel-group superiority trial in six hospitals in Bolivia and Ecuador; stratified randomisation (site, severity group, age group) with variable block sizes; open-label clinical management with blinded outcome assessment; investigator-initiated (methods and trial infrastructure previously detailed).¹
• Population:
  • Setting: ICU management of severe TBI in participating trauma hospitals (Bolivia and Ecuador).
  • Key inclusion criteria: age ≥13 years; severe TBI (GCS 3–8, with motor-score substitutes if intubated); closed head injury; admission (or deterioration) within 24 hours permitting randomisation and protocol initiation.
  • Key exclusion criteria: penetrating injury; pregnancy; inability to obtain consent; no ICU bed available; no ICP monitor available; incarceration; planned withdrawal/limitations of therapy; anticipated inability to complete follow-up (e.g., no stable contact information).
• Intervention:
  • ICP-guided strategy (Pressure-Monitoring Group): placement of an intraparenchymal ICP monitor; tiered management driven by ICP/CPP targets (ICP threshold 20 mm Hg; CPP target 50–70 mm Hg); treatment escalation based on sustained intracranial hypertension and/or cerebral perfusion compromise.
  • Protocolised therapies: sedation/analgesia and physiological optimisation, hyperosmolar therapy, ventilatory adjustments (including hyperventilation when indicated), barbiturate therapy, and neurosurgical options (including decompressive craniectomy) as per the prespecified tiered pathway.
• Comparison:
  • Imaging–clinical examination strategy (Imaging–Clinical Examination Group): tiered management driven by scheduled/triggered CT imaging and neurological examination (including deterioration signals and radiological signs of raised ICP), without continuous ICP data.
  • Co-interventions: the same broad categories of brain-directed therapies were available, but their initiation/escalation was triggered by clinical/CT criteria rather than ICP/CPP thresholds.
• Blinding: Treating teams could not be blinded to monitoring strategy; outcome assessors were masked to group assignment for follow-up assessments.
• Statistics: A total of 324 patients (162/group) provided 80% power (two-sided α=0.05) to detect a 10 percentage point increase in good or moderate recovery on the GOS-E (from 51.4% to 61.4%), corresponding to an odds ratio of 1.5, with concordant improvement across other components (simulation-based composite test); primary analysis by intention-to-treat using a blocked Wilcoxon test adjusted for stratification variables; secondary outcomes analysed with proportional odds regression or Cox models as appropriate; one interim efficacy analysis planned (O’Brien–Fleming boundaries; nominal p≈0.005 at interim).
• Follow-Up Period: Acute hospital course (including 14-day outcomes); structured follow-up at 3 and 6 months (primary composite integrates hospital discharge, 3-month, and 6-month components).

Key Results

This trial was not stopped early. One blinded interim efficacy analysis was conducted when approximately half of subjects completed the 6-month assessment; the trial continued to full enrolment and follow-up.

• No improvement was demonstrated in the primary 21-item composite outcome (median percentile 56 vs 53; proportional odds ratio 1.09; 95% CI 0.74 to 1.58; P=0.49) or in 6-month mortality (39% vs 41%; hazard ratio 1.10; 95% CI 0.77 to 1.57; P=0.60).
• The imaging–clinical strategy drove substantially more treatment intensity (integrated treatment-hours median 125 vs 69; proportional odds ratio 2.36; 95% CI 1.60 to 3.47; P<0.001), with more hypertonic saline (72% vs 58%) and hyperventilation (73% vs 60%).
• Overall serious adverse events were similar (45% vs 46%), but invasive monitoring had catheter-related complications in 6% and decubitus ulcers were more frequent in the ICP-guided strategy (12% vs 5%).

Internal Validity

• Randomisation and allocation: Stratified randomisation by site, severity group, and age group with variable block sizes; allocation implemented via a local database tool with telephone back-up if needed (coin flip), which is a potential (but limited) vulnerability to allocation integrity if processes were not strictly standardised.
• Dropout/exclusions: 324 patients were randomised; follow-up completeness for the composite relied on having sufficient component measures or known death status; 6-month GOS-E categories were reported among those with available 6-month outcome data (not all randomised participants contributed to all components).
• Performance/detection bias: Clinicians could not be blinded; this heightens the risk of differential co-interventions by design (a key feature of the strategies). Follow-up outcome assessment was masked, reducing detection bias for structured long-term outcomes.
• Protocol adherence: Protocol deviations included no ICP monitor inserted in 6/157 (4%) assigned to ICP-guided care (without contraindication) and ICP monitor inserted in 2/167 (1%) assigned to imaging–clinical care.
• Baseline characteristics: Broadly comparable groups at randomisation (e.g., age median 29 years in both groups; male 91% vs 84%; both pupils reactive 78% vs 76%); some imbalance existed in CT strata (normal CT 8% vs 14%), but overall severity markers were similar.
• Timing: Randomisation and protocol initiation were designed for the early injury window (within 24 hours of injury or deterioration), aligning with the period of highest intracranial hypertension risk.
• Dose: In the ICP-guided arm, ICP monitoring duration was substantial (mean 4.5 ± 3.5 days; median 3.5 [IQR 1.9–6.6] days), indicating that the intervention was delivered over a clinically meaningful window.
• Separation of the variable of interest: Clear separation occurred in downstream care processes: integrated brain-specific treatment intensity median 69 vs 125 treatment-hours (proportional odds ratio 2.36; 95% CI 1.60 to 3.47; P<0.001); hypertonic saline 58% vs 72% (proportional odds ratio 1.95; 95% CI 1.19 to 3.22; P=0.008); hyperventilation 60% vs 73% (proportional odds ratio 2.16; 95% CI 1.29 to 3.61; P=0.003); barbiturates 24% vs 13% (proportional odds ratio 0.46; 95% CI 0.25 to 0.83; P=0.02).
• Outcome assessment and statistical rigour: Primary endpoint and analysis plan were prespecified (simulation-powered composite; intention-to-treat; blocked Wilcoxon with adjustment for stratification variables); the composite enhances power for consistent directional effects but reduces intuitive interpretability of effect size in clinical units.

Conclusion on Internal Validity: Overall, internal validity appears moderate-to-strong: randomisation and masked outcome assessment were robust, protocol delivery achieved substantial process separation, and analyses were prespecified; however, open-label management (by necessity) and protocol deviations (including crossovers and non-placement of monitors) introduce some risk of performance-related bias.

External Validity

• Population representativeness: The cohort was predominantly young (median age 29 years) and male; enrolled in Latin American trauma hospitals with local trauma system characteristics that may differ from high-income settings (prehospital care, transfer patterns, ICU staffing, and imaging access).
• Applicability of the comparison strategy: The imaging–clinical arm was highly protocolised and depended on repeated clinical assessment and CT imaging; this may not reflect “usual care” in many systems (either because imaging is less available or because care is less protocol-driven).
• Technology generalisability: The intervention used intraparenchymal monitoring; results may not fully extrapolate to systems where ventricular catheters are common (with CSF drainage as a therapeutic component).
• Clinical translation: Findings are most transportable to settings capable of delivering structured, protocolised severe TBI care (whether guided by ICP or by exam/CT), rather than to settings where either strategy cannot be implemented reliably.

Conclusion on External Validity: External validity is context-dependent: the trial is highly informative for protocolised severe TBI management models, but generalisability to older TBI populations, to systems with different monitoring modalities, and to settings without frequent CT/standardised neurocritical care resources may be limited.

Strengths & Limitations

• Strengths:
  • Addresses a major evidentiary gap with a randomised design in an area dominated by observational inference.
  • Large multicentre trial for this question, with prespecified statistical methods tailored to complex outcomes (composite percentile approach).
  • Clear process separation between strategies (treatment intensity and specific interventions differed materially).
  • Masked outcome assessment for structured follow-up outcomes.
• Limitations:
  • Compares two protocolised strategies; does not directly answer “ICP monitoring versus usual care” where usual care is unstructured or resource-constrained.
  • Primary composite outcome is methodologically defensible but clinically non-intuitive; clinicians may struggle to map a percentile difference to bedside meaning.
  • Open-label management unavoidably permits differential co-interventions; protocol deviations (crossovers and non-placement of monitors) could dilute true effects.
  • Setting and case-mix (younger cohort, Latin American centres) may not mirror older or more comorbid populations in other regions.

Interpretation & Why It Matters

• Clinical meaning

  When severe TBI care is protocolised and resourced to allow intensive serial neurological assessment and CT-based decision-making, adding invasive ICP monitoring did not improve the prespecified composite outcome or 6-month mortality in this trial.
• What changed at the bedside

  The choice of monitoring strategy substantially changed treatment behaviour: the imaging–clinical strategy used more hypertonic saline and hyperventilation and delivered higher overall brain-specific treatment intensity, whereas the ICP strategy used barbiturates more often and had fewer brain-specific treatment days.
• Implication for systems

  The trial supports a central concept: outcomes may depend as much on consistent delivery of structured neurocritical care (protocols, monitoring discipline, timely escalation/de-escalation) as on the presence of a specific monitoring device.

Controversies & Subsequent Evidence

• Interpretation error (device vs strategy): The trial compared two intensive, protocolised management strategies (ICP-triggered vs exam/CT-triggered), not “ICP monitoring versus no monitoring” in typical unstructured practice; editorial and subsequent consensus papers emphasised that misreading the trial as proving ICP monitoring is useless is a category error.²⁴⁵
• Control arm intensity and generalisability: Correspondence highlighted that the imaging–clinical strategy in BEST:TRIP required sustained clinical scrutiny and CT access; where such resources or protocols are absent, the trial may not represent usual care (and therefore does not settle the question for low-monitoring, low-imaging environments).³
• Composite primary endpoint: The 21-component percentile-based composite increases sensitivity to a consistent directional effect across domains, but it can obscure which patient-centred dimensions (mortality, function, cognition, ICU course) are actually changing and by how much in clinically interpretable units; this was a recurrent focus of methodological discussion in editorials and the consensus interpretation.²⁵
• Therapeutic intensity as a mediator: BEST:TRIP demonstrated that monitoring strategy substantially alters therapy (e.g., hypertonic saline and hyperventilation were more common in the imaging–clinical strategy), raising the critical downstream question: does ICP monitoring primarily prevent overtreatment, prevent undertreatment, or simply change the pattern of treatment without net outcome benefit?⁵
• Meta-analyses and observational evidence remain heterogeneous: Systematic reviews/meta-analyses pooling predominantly observational data have reported variable associations between ICP monitoring and mortality/functional outcome, with results sensitive to study design, confounding control, and case-mix.⁶
• Modern comparative effectiveness studies: Large registry-based analyses and causal-inference approaches have produced differing estimates of benefit/harm and highlight persistent confounding risk (e.g., more severe patients are more likely to receive monitors; centres that monitor may differ systematically in broader ICU capability).⁷⁸⁹
• Guidelines after BEST:TRIP: Major guidelines continued to recommend ICP monitoring in selected severe TBI populations where resources and expertise permit, while explicitly acknowledging the low certainty of evidence and the central role of protocolised, high-quality neurocritical care.¹⁰
• Consensus algorithms (SIBICC) reflect a “protocol-first” evolution: Post-BEST:TRIP expert consensus has emphasised stepwise algorithms for ICP/CPP management (and for combined ICP + brain tissue oxygen monitoring) aimed at standardising escalation/de-escalation and avoiding therapeutic excess, echoing the trial’s central lesson about protocolised care.¹¹¹²

Summary

• BEST:TRIP randomised 324 severe TBI patients to ICP-guided protocolised management versus a protocolised imaging–clinical examination strategy in six Latin American centres.
• No difference was shown in the prespecified 21-item composite outcome (median percentile 56 vs 53; proportional odds ratio 1.09; 95% CI 0.74 to 1.58; P=0.49) or 6-month mortality (39% vs 41%; hazard ratio 1.10; 95% CI 0.77 to 1.57; P=0.60).
• The strategies produced substantial process-of-care separation: the imaging–clinical strategy used more hypertonic saline and hyperventilation and had higher overall treatment intensity (median 125 vs 69 treatment-hours; P<0.001).
• Serious adverse events were similar overall (45% vs 46%); catheter-related complications occurred in 6% of monitored patients.
• The trial is best interpreted as evidence about competing protocolised management strategies rather than a definitive verdict on ICP monitoring in all settings and all standards of care.

Further Reading

Other Trials

• RCT2011Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med. 2011;364(16):1493-1502.
• RCT2015Andrews PJD, Sinclair HL, Rodriguez A, et al. Hypothermia for intracranial hypertension after traumatic brain injury. N Engl J Med. 2015;373(25):2403-2412.
• RCT2016Hutchinson PJ, Kolias AG, Timofeev IS, et al. Trial of decompressive craniectomy for traumatic intracranial hypertension. N Engl J Med. 2016;375(12):1119-1130.
• RCT2017Okonkwo DO, Shutter LA, Moore C, et al. Brain tissue oxygen monitoring and management in severe traumatic brain injury: a phase II randomized trial. Crit Care Med. 2017;45(11):1907-1914.

Systematic Review & Meta Analysis

• SR/MA2015Yuan Q, Wu X, Sun Y, et al. Impact of intracranial pressure monitoring on mortality in patients with severe traumatic brain injury: a systematic review and meta-analysis. J Neurosurg. 2015;122(3):574-587.
• SR/MA2016Shen J, Pan J, Fan Z, et al. Effects of intracranial pressure monitoring on mortality in patients with severe traumatic brain injury: a meta-analysis. PLoS One. 2016;11:e0168901.
• SR/MA2021Wang Z, et al. Effects of intracranial pressure monitoring on mortality in patients with severe traumatic brain injury: a systematic review and meta-analysis. Ann Palliat Med. 2021;10:10867-10877.
• SR/MA2022Han J, et al. Intracranial pressure monitoring in severe traumatic brain injury: a systematic review and meta-analysis. BioMed Res Int. 2022;2022:1956908.
• Umbrella2024Florez-Perdomo WA, et al. Intracranial pressure monitoring in traumatic brain injury: an umbrella review. J Neurointensive Care. 2024;7:18-28.

Observational Studies

• Obs2005Cremer OL, van Dijk GW, van Wensen E, et al. Effect of intracranial pressure monitoring and targeted intensive care on functional outcome after severe head injury. Crit Care Med. 2005;33(10):2207-2213.
• Obs2008Mauritz W, Janciak I, Wilbacher I, Rusnak M. Severe traumatic brain injury in Austria: introduction of systematic management and effect on outcome. Intensive Care Med. 2008;34:1208-1215.
• Obs2013Alali AS, Fowler RA, Mainprize TG, et al. Intracranial pressure monitoring in severe traumatic brain injury: results from the American College of Surgeons Trauma Quality Improvement Program. J Neurotrauma. 2013;30(20):1737-1746.
• Obs2021Robba C, Poole D, McNett M, et al. Intracranial pressure monitoring in neurocritical care: the SYNAPSE-ICU study. Lancet Neurol. 2021;20(7):548-558.
• Obs2023Nattino G, et al. Impact of intracranial pressure monitoring on survival and neurological outcomes among adults with severe traumatic brain injury: a comparative effectiveness study. JAMA Netw Open. 2023;6(9):e2334214.

Guidelines

• Guideline2017Carney N, Totten AM, O’Reilly C, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery. 2017;80(1):6-15.
• Consensus2014Le Roux P, Menon DK, Citerio G, et al. Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care. Intensive Care Med. 2014;40(9):1189-1209.
• Consensus2019Hawryluk GWJ, Aguilera S, Buki A, et al. A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med. 2019;45(12):1783-1794.
• Consensus2020Chesnut RM, Aguilera S, Buki A, et al. A management algorithm for adult patients with both brain oxygen and intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med. 2020;46(5):919-929.

Notes

• For most ordinal/continuous outcomes, the trial reported proportional odds ratios from proportional odds regression; values >1 generally indicate a better disposition for the ICP-guided strategy (and for length-of-stay endpoints, a tendency towards fewer days).
• The BEST:TRIP control strategy was not “no monitoring”; it was an intensive, protocolised programme driven by neurological examination and CT imaging, which is central to correct interpretation.

Overall Takeaway

BEST:TRIP is a landmark because it randomised severe TBI patients to two competing, protocolised neurocritical care strategies and found no outcome advantage to an ICP-guided approach over an intensive imaging–clinical strategy. The lasting contribution is not a simple “for or against ICP monitors” message, but a demonstration that structured, consistent delivery of severe TBI care can be operationalised without continuous ICP data—and that the choice of monitoring strategy meaningfully shapes therapeutic intensity.

Bibliography

• 1Carney N, Petroni G, Lujan S, et al. Intracranial pressure monitoring in severe traumatic brain injury in Latin America: process and methods for a multicenter randomized controlled trial. J Neurotrauma. 2012;29(11):2022-2029.
• 2Ropper AH. Brain in a box. N Engl J Med. 2012;367(26):2539-2541.
• 3Rubiano AM, Puyana JC, Mukherjee D, et al. Intracranial-pressure monitoring in traumatic brain injury. N Engl J Med. 2013;368(18):1748-1752.
• 4Chesnut RM. Intracranial pressure monitoring: headstone or a new head start. The BEST TRIP trial in perspective. Intensive Care Med. 2013;39(4):771-774.
• 5Chesnut RM, Temkin N, Dikmen S, et al. A consensus-based interpretation of the BEST TRIP trial: treatment of traumatic brain injury based on imaging and clinical examination or intracranial pressure monitoring. J Neurotrauma. 2015;32(22):1722-1724.
• 6Yuan Q, Wu X, Sun Y, et al. Impact of intracranial pressure monitoring on mortality in patients with severe traumatic brain injury: a systematic review and meta-analysis. J Neurosurg. 2015;122(3):574-587.
• 7Alali AS, Fowler RA, Mainprize TG, et al. Intracranial pressure monitoring in severe traumatic brain injury: results from the American College of Surgeons Trauma Quality Improvement Program. J Neurotrauma. 2013;30(20):1737-1746.
• 8Nattino G, et al. Impact of intracranial pressure monitoring on survival and neurological outcomes among adults with severe traumatic brain injury: a comparative effectiveness study. JAMA Netw Open. 2023;6(9):e2334214.
• 9Robba C, Poole D, McNett M, et al. Intracranial pressure monitoring in neurocritical care: the SYNAPSE-ICU study. Lancet Neurol. 2021;20(7):548-558.
• 10Carney N, Totten AM, O’Reilly C, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery. 2017;80(1):6-15.
• 11Hawryluk GWJ, Aguilera S, Buki A, et al. A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med. 2019;45(12):1783-1794.
• 12Chesnut RM, Aguilera S, Buki A, et al. A management algorithm for adult patients with both brain oxygen and intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med. 2020;46(5):919-929.