Department of Anaesthesia and Intensive Care, Centre Hospitalier Universitaire Grenoble, Universitaire Grenoble Alpes, Grenoble, France; INSERM U1216, Grenoble Institut Neurosciences, Grenoble, France.
Department of Anaesthesia and Intensive Care, Centre Hospitalier Universitaire Rennes, Rennes, France.
Lancet Neurol. 2023 Nov;22(11):1005-1014. doi: 10.1016/S1474-4422(23)00290-9.
Optimisation of brain oxygenation might improve neurological outcome after traumatic brain injury. The OXY-TC trial explored the superiority of a strategy combining intracranial pressure and brain tissue oxygen pressure (PbtO) monitoring over a strategy of intracranial pressure monitoring only to reduce the proportion of patients with poor neurological outcome at 6 months.
We did an open-label, randomised controlled superiority trial at 25 French tertiary referral centres. Within 16 h of brain injury, patients with severe traumatic brain injury (aged 18-75 years) were randomly assigned via a website to be managed during the first 5 days of admission to the intensive care unit either by intracranial pressure monitoring only or by both intracranial pressure and PbtO monitoring. Randomisation was stratified by age and centre. The study was open label due to the visibility of the intervention, but the statisticians and outcome assessors were masked to group allocation. The therapeutic objectives were to maintain intracranial pressure of 20 mm Hg or lower, and to keep PbtO (for those in the dual-monitoring group) above 20 mm Hg, at all times. The primary outcome was the proportion of patients with an extended Glasgow Outcome Scale (GOSE) score of 1-4 (death to upper severe disability) at 6 months after injury. The primary analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew consent or had protocol violations. This trial is registered with ClinicalTrials.gov, NCT02754063, and is completed.
Between June 15, 2016, and April 17, 2021, 318 patients were randomly assigned to receive either intracranial pressure monitoring only (n=160) or both intracranial pressure and PbtO monitoring (n=158). 27 individuals with protocol violations were not included in the modified intention-to-treat analysis. Thus, the primary outcome was analysed for 144 patients in the intracranial pressure only group and 147 patients in the intracranial pressure and PbtO group. Compared with intracranial pressure monitoring only, intracranial pressure and PbtO monitoring did not reduce the proportion of patients with GOSE score 1-4 (51% [95% CI 43-60] in the intracranial pressure monitoring only group vs 52% [43-60] in the intracranial pressure and PbtO monitoring group; odds ratio 1·0 [95% CI 0·6-1·7]; p=0·95). Two (1%) of 144 participants in the intracranial pressure only group and 12 (8%) of 147 participants in the intracranial pressure and PbtO group had catheter dysfunction (p=0.011). Six patients (4%) in the intracranial pressure and PbtO group had an intracrebral haematoma related to the catheter, compared with none in the intracranial pressure only group (p=0.030). No significant difference in deaths was found between the two groups at 12 months after injury. At 12 months, 33 deaths had occurred in the intracranial pressure group: 25 (76%) were attributable to the brain trauma, six (18%) were end-of-life decisions, and two (6%) due to sepsis. 34 deaths had occured in the intracranial pressure and PbtO group at 12 months: 25 (74%) were attributable to the brain trauma, six (18%) were end-of-life decisions, one (3%) due to pulmonary embolism, one (3%) due to haemorrhagic shock, and one (3%) due to cardiac arrest.
After severe non-penetrating traumatic brain injury, intracranial pressure and PbtO monitoring did not reduce the proportion of patients with poor neurological outcome at 6 months. Technical failures related to intracerebral catheter and intracerebral haematoma were more frequent in the intracranial pressure and PbtO group. Further research is needed to assess whether a targeted approach to multimodal brain monitoring could be useful in subgroups of patients with severe traumatic brain injury-eg, those with high intracranial pressure on admission.
The French National Program for Clinical Research, La Fondation des Gueules Cassées, and Integra Lifesciences.
优化脑氧合可能改善创伤性脑损伤后的神经功能预后。OXY-TC 试验探讨了结合颅内压和脑组织氧压（PbtO）监测的策略相对于仅进行颅内压监测的策略，以降低 6 个月时神经功能预后不良的患者比例的优越性。
我们在 25 家法国三级转诊中心进行了一项开放性、随机对照优效性试验。在脑损伤后 16 小时内，将年龄在 18-75 岁之间的严重创伤性脑损伤患者通过网站随机分配，在入住重症监护病房的前 5 天内接受颅内压监测或同时接受颅内压和 PbtO 监测。研究按年龄和中心分层。由于干预措施的可见性，该研究为开放性标签，但统计学家和结局评估者对分组分配进行了盲法。治疗目标是始终将颅内压维持在 20mmHg 或更低，并将 PbtO（对于双监测组的患者）保持在 20mmHg 以上。主要结局是损伤后 6 个月时扩展格拉斯哥结局量表（GOSE）评分 1-4 分（死亡至重度残疾）的患者比例。主要分析报告了改良意向治疗人群，该人群包括除了撤回同意或存在方案违规的所有随机分配患者。该试验在 ClinicalTrials.gov 上注册，编号为 NCT02754063，现已完成。
2016 年 6 月 15 日至 2021 年 4 月 17 日期间，318 名患者被随机分配接受颅内压监测（n=160）或颅内压和 PbtO 监测（n=158）。27 名存在方案违规的个体未纳入改良意向治疗分析。因此，144 名接受颅内压监测的患者和 147 名接受颅内压和 PbtO 监测的患者进行了主要结局分析。与颅内压监测相比，颅内压和 PbtO 监测并未降低 GOSE 评分 1-4 分的患者比例（颅内压监测组 51%[95%CI 43-60] vs 颅内压和 PbtO 监测组 52%[43-60]；比值比 1.0[95%CI 0.6-1.7]；p=0.95）。颅内压监测组的 144 名参与者中有 2 名（1%）和颅内压和 PbtO 监测组的 147 名参与者中有 12 名（8%）发生导管功能障碍（p=0.011）。颅内压和 PbtO 监测组的 6 名患者（4%）发生与导管相关的颅内血肿，而颅内压监测组无此情况（p=0.030）。两组在损伤后 12 个月时的死亡率无显著差异。在损伤后 12 个月时，颅内压组发生 33 例死亡：25 例（76%）归因于脑创伤，6 例（18%）为临终决策，2 例（6%）归因于脓毒症。颅内压和 PbtO 监测组在 12 个月时有 34 例死亡：25 例（74%）归因于脑创伤，6 例（18%）为临终决策，1 例（3%）归因于肺栓塞，1 例（3%）归因于失血性休克，1 例（3%）归因于心脏骤停。
在严重的非穿透性创伤性脑损伤后，颅内压和 PbtO 监测并不能降低 6 个月时神经功能预后不良的患者比例。颅内压和 PbtO 监测组的与颅内导管和颅内血肿相关的技术故障更频繁。需要进一步研究评估严重创伤性脑损伤患者亚组中，如入院时颅内压较高的患者，是否可以使用多模态脑监测的靶向方法。
法国国家临床研究计划、La Fondation des Gueules Cassées 和 Integra Lifesciences。
