Highlights
- •Brain tissue oxygen (PbtO2) monitoring and optimisation may improve TBI outcomes.
- •We conducted a systematic review/meta-analysis of RCTs of PbtO2-guided management.
- •Our findings suggest that PbtO2-guided management:
- •Increased survival and reduced intracranial pressure.
- •Did not increase respiratory or cardiovascular adverse events.
- •No significant association was identified with improved functional outcomes.
- •The certainty of the available evidence is very low.
- •It is not possible to make any definitive treatment recommendations.
Abstract
Keywords
Abbreviations:
RCT (Randomized Controlled Trial), TBI (Traumatic Brain Injury), ICU (Intensive Care Unit)1. Introduction
1.1 Description of the condition
1.2 Description of the intervention
- Xie Q.
- Wu H.-B.
- Yan Y.-F.
- Liu M.
- Wang E.-S.
1.3 Why it is important to do this review
1.4 Objectives
2. Methods
2.1 Registration
2.2 Data sources and searches
2.3 Study selection
2.4 Data extraction
2.5 Risk of bias and GRADE quality of evidence
2.6 Data synthesis
3. Results
3.1 Results of the search
Monash University. The BONANZA trial- a randomised controlled trial that is testing whether a management strategy guided by early brain tissue oxygen monitoring in patients in with severe traumatic brain injury improves long term neurological and functional outcomes. International Clinical Trials Registry Platform [Internet]. World Health Organization. [date unknown] Available from: http://www.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12619001328167 2019. [Identifier: ACTRN12619001328167].
University Hospital, Grenoble. Impact of Early Optimization of Brain Oxygenation on Neurological Outcome After Severe Traumatic Brain Injury (OXY-TC). ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US); 2000-2016 Available from: https://clinicaltrials.gov/ct2/show/NCT02754063 [Identifier: NCT02754063].

3.2 Included studies
Study and Year | Setting | Methods | Participants | Interventions | Outcomes |
---|---|---|---|---|---|
Lee, 2010 | Single ICU in Taiwan recruiting Sept 2006- August 2007 | Single centre randomised controlled trial | 45 participants (16 ICP/CPP, 15 ICP/CPP and mild hypothermia, 14 PbtO2, ICP/CPP and mild hypothermia) with severe non-penetrating TBI after craniotomy (GCS 4–8) aged 12–70 years | Group A: ICP/CPP-guided management Group B (Control): ICP/CPP-guided management and mild hypothermia Group C (Intervention): PbtO2 and ICP/CPP-guided management and mild hypothermia | -Glasgow Outcome Scale at 6 months (mean and favourable defined as ≥ 4) -Mortality -Length of ICU Stay -Length of Hospital Stay -Healthcare Cost -Complications -ICP (mean) -Cpk (medical treatment process capability) |
Lin, 2015 | 6 neurosurgical ICUs in Taiwan recruiting Jan 2009-Dec 2010. | Prospective, multi-centre phase III Randomised Controlled Trial | 50 participants (27 ICP, 23 ICP/PbtO2) with moderate (GCS 9–12) and severe (GCS < 8) TBI aged 17–70 years ∼ 70 % severe TBI (initial GCS 3–8). | Control: ICP-guided management Intervention: ICP and PbtO2-guided management | -Glasgow Outcome Scale (1, 3 and 6 months) -Glasgow Outcome Scale Extended (1, 3 and 6 months) -Mortality (1, 3 and 6 months) -ICP (mean and hypertensive events) -Physiologic data: CPP, PaCO2, GCS, PaO2 -Pulmonary complications |
Okonkwo, 2017 | 10 ICUs in level 1 trauma centres in US. Dates of recruitment not stated. | Two-arm, single-blind, prospective randomized controlled multicenter phase II trial | 119 participants (ICP 62, ICP and PbtO2 57) with non-penetrating severe TBI (GCS 3–8) aged > 14 years | Control: ICP-guided management Intervention: ICP and PbtO2-guided management | -Glasgow Outcome Scale Extended at 6 months (mean and favourable outcome GOSE 5–8) -Disability Rating Scale at 6 months -Mortality at 6 months -Serious adverse events -Brain hypoxia (burden, depth, proportion of time) -ICP (hypertension burden, depth, proportion of time) |
Study | ICP ≥ 20 mmHg and PbtO2 ≥ 20 mmHg | ICP < 20 mmHg and PbtO2 < 20 mmHg | ICP ≥ 20 mmHg and PbtO2 < 20 mmHg |
---|---|---|---|
Lee 2010 | Elevating the head end of the bed Sedation Paralysis Mannitol | Increase CPP until PbtO2 values reach 20 mmHg through fluid and vasopressors *found that increasing FiO2 did not increase PbtO2 | Elevating the head end of the bed Sedation Paralysis Mannitol Increase CPP until PbtO2 values reach 20 mmHg through fluid and vasopressors *found that increasing FiO2 did not increase PbtO2 |
Lin 2015 | Mannitol Glycerol Colloid Sedatives Decompressive craniectomy | 100% FiO2 challenge If 100% FiO2 needed for > 5 h or PbtO2 not increased by FiO2 challenge: CPP increased to 80 mmHg PaCO2 increased to 40 mmHg | Normalization of PbtO2 considered most important strategy |
Okonkwo 2017 | Tier 1: 1. Adjust head of bed 2. Ensure temperature < 38 °C 3. Adjust pharmacologic analgesia and sedation 4. CSF drainage (if EVD available) 5. Standard dose Mannitol (0.25–1.0 g/kg) as bolus infusion 6. Hypertonic saline Tier 2: 1. Adjust ventilatory rate to lower PaCO2 to 32–35 mmHg. 2. High dose Mannitol > 1 g/kg 3. Repeat CT to determine if increased size of intracranial mass lesions 4. Treat surgically remediable lesions with craniotomy according to guidelines 5. Adjust temperature to 35–37 °C, using active cooling measures Tier 3 (optional): 1. Pentobarbitol coma, according to local protocol 2. Decompressive craniectomy 3. Adjust temperature to 32–34.5 °C using active cooling measures 4. Neuromuscular blockade | Tier 1: 1. Adjust head of bed 2. Ensure temperature < 38 °C 3. Increase CPP to 70 mmHg with fluid bolus 4. Optimize hemodynamics 5. Increase PaO2 by increasing FiO2 to 60% 6. Increase PaO2 by adjusting PEEP 7. Add EEG monitoring 8. Consider adding AED's, either Dilantin or Keppra, for 1 week only. Tier 2: 1. Increase PaO2 by increasing FiO2 to 100% 2. Increase PaO2 by adjusting PEEP 3. Increase CPP up to a max of 70 mmHg with vasopressors 4. Adjust ventilatory rate to increase PaCO2 to 45–50 mmHg. 5. Transfuse PRBCs to goal Hgb > 10 g/dL 6. Decrease ICP to < 10 mmHg. 6a. CSF drainage 6b. Increased sedation | Tier 1: 1. Adjust head of bed 2. Ensure temperature < 38 °C 3. Pharmacologic analgesia and sedation 4. CSF drainage (if EVD available) 5. Increase CPP to a max of 70 mmHg with fluid bolus 6. Standard dose Mannitol (0.25–0.5 mg/kg) as bolus infusion 7. Hypertonic saline 8. Increase PaO2 by increasing FiO2 to 60% 9. Increase FiO2 by increasing PEEP 10. Consider EEG monitoring 11. Consider adding AED's, either Dilantin or Keppra, for 1 week only. Tier 2: 1. High dose Mannitol 1 g/kg or frequent boluses standard dose mannitol 2. Increase CPP up to a max of 70 mmHg with vasopressors 3. Increase PaO2 by increasing FiO2 to 100% 4. Increase FiO2 by increasing PEEP 5. Transfuse to goal Hgb > 10 g/dL 6. Repeat CT to determine if increased size of intracranial mass lesions 7. Treat surgically remediable lesions with craniotomy according to guidelines 8. Adjust temperature to 35–37 °C, using active cooling measures Tier 3 (optional): 1. Pentobarbitol coma 2. Decompressive craniectomy 3. Adjust temperature to 32–34.5 °C using active cooling measures 4. Neuromuscular blockade |
3.3 Risk of bias in included studies

3.4 Effects of interventions
3.4.1 Neurological outcome at 6 months

3.5 Mortality

3.6 Respiratory adverse events

3.7 Cardiovascular adverse events

3.8 Mean ICP

3.9 Sensitivity analysis

3.10 GRADE assessment for certainty of evidence
Certainty assessment | № of patients | Effect | Certainty | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
№ of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | PbtO2 and ICP-guided management | ICP-guided management | Relative (95% CI) | Absolute (95% CI) | |
Favourable neurologic outcome at 6 months | |||||||||||
3 | randomised trials | serious a | not serious | not serious | very serious b | none | 37/90 (41.1%) | 27/95 (28.4%) | RR 1.42 (0.97 to 2.08) | 119 more per 1,000 (from 9 fewer to 307 more) | ⊕○○○ VERY LOW |
Mortality | |||||||||||
3 | randomised trials | serious a | serious c | not serious | very serious b | none | 15/90 (16.7%) | 29/95 (30.5%) | RR 0.54 (0.31 to 0.93) | 140 fewer per 1,000 (from 211 fewer to 21 fewer) | ⊕○○○ VERY LOW |
Intracranial Pressure (ICP) | |||||||||||
2 | randomised trials | serious a | serious c | not serious | very serious b | none | 37 | 42 | – | MD 4.62 lower (8.27 lower to 0.98 lower) | ⊕○○○ VERY LOW |
Adverse Respiratory Events | |||||||||||
3 | randomised trials | serious a | not serious | not serious | very serious b | none | 10/94 (10.6%) | 8/104 (7.7%) | RR 1.37 (0.59 to 3.21) | 28 more per 1,000 (from 32 fewer to 170 more) | ⊕○○○ VERY LOW |
Cardiovascular Adverse Events | |||||||||||
2 | randomised trials | serious a | not serious | not serious | very serious b | none | 12/71 (16.9%) | 9/77 (11.7%) | RR 1.44 (0.65 to 3.20) | 51 more per 1,000 (from 41 fewer to 257 more) | ⊕○○○ VERY LOW |
4. Discussion
4.1 Summary of main results
4.2 Agreements and disagreements with other studies or reviews
- Xie Q.
- Wu H.-B.
- Yan Y.-F.
- Liu M.
- Wang E.-S.
- Xie Q.
- Wu H.-B.
- Yan Y.-F.
- Liu M.
- Wang E.-S.
4.3 Limitations of this review
5. Implications for research
Funding
Declaration of Competing Interest
Appendix.
- 1.Brain injuries, traumatic AND Oxygen AND Monitoring.
- 2.TBI AND multimodality monitoring.
- 3.PbtO2.
- 4.Glasgow Outcome Scale AND Brain injuries, traumatic AND Oxygen.
- 5.Neurocritical care AND Oxygen.
Cochrane library
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