Department of Intensive Care Medicine, Research VUmc Intensive Care, Amsterdam Cardiovascular Science, Amsterdam Infection and Immunity Institute, Amsterdam Medical Data Science, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.
Department of Anesthesiology, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.
JAMA. 2021 Sep 14;326(10):940-948. doi: 10.1001/jama.2021.13011.
Hyperoxemia may increase organ dysfunction in critically ill patients, but optimal oxygenation targets are unknown.
To determine whether a low-normal Pao2 target compared with a high-normal target reduces organ dysfunction in critically ill patients with systemic inflammatory response syndrome (SIRS).
DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical trial in 4 intensive care units in the Netherlands. Enrollment was from February 2015 to October 2018, with end of follow-up to January 2019, and included adult patients admitted with 2 or more SIRS criteria and expected stay of longer than 48 hours. A total of 9925 patients were screened for eligibility, of whom 574 fulfilled the enrollment criteria and were randomized.
Target Pao2 ranges were 8 to 12 kPa (low-normal, n = 205) and 14 to 18 kPa (high-normal, n = 195). An inspired oxygen fraction greater than 0.60 was applied only when clinically indicated.
Primary end point was SOFARANK, a ranked outcome of nonrespiratory organ failure quantified by the nonrespiratory components of the Sequential Organ Failure Assessment (SOFA) score, summed over the first 14 study days. Participants were ranked from fastest organ failure improvement (lowest scores) to worsening organ failure or death (highest scores). Secondary end points were duration of mechanical ventilation, in-hospital mortality, and hypoxemic measurements.
Among the 574 patients who were randomized, 400 (70%) were enrolled within 24 hours (median age, 68 years; 140 women [35%]), all of whom completed the trial. The median Pao2 difference between the groups was -1.93 kPa (95% CI, -2.12 to -1.74; P < .001). The median SOFARANK score was -35 points in the low-normal Pao2 group vs -40 in the high-normal Pao2 group (median difference, 10 [95% CI, 0 to 21]; P = .06). There was no significant difference in median duration of mechanical ventilation (3.4 vs 3.1 days; median difference, -0.15 [95% CI, -0.88 to 0.47]; P = .59) and in-hospital mortality (32% vs 31%; odds ratio, 1.04 [95% CI, 0.67 to 1.63]; P = .91). Mild hypoxemic measurements occurred more often in the low-normal group (1.9% vs 1.2%; median difference, 0.73 [95% CI, 0.30 to 1.20]; P < .001). Acute kidney failure developed in 20 patients (10%) in the low-normal Pao2 group and 21 patients (11%) in the high-normal Pao2 group, and acute myocardial infarction in 6 patients (2.9%) in the low-normal Pao2 group and 7 patients (3.6%) in the high-normal Pao2 group.
Among critically ill patients with 2 or more SIRS criteria, treatment with a low-normal Pao2 target compared with a high-normal Pao2 target did not result in a statistically significant reduction in organ dysfunction. However, the study may have had limited power to detect a smaller treatment effect than was hypothesized.
ClinicalTrials.gov Identifier: NCT02321072.
高氧血症可能会增加危重病患者的器官功能障碍，但最佳氧合目标尚不清楚。
确定与高正常目标相比，低正常 Pao2 目标是否会降低患有全身炎症反应综合征 (SIRS) 的危重病患者的器官功能障碍。
设计、地点和参与者：荷兰 4 个重症监护病房的多中心随机临床试验。招募时间为 2015 年 2 月至 2018 年 10 月，随访截止日期为 2019 年 1 月，纳入标准为成人患者符合 2 个或更多 SIRS 标准，预计住院时间超过 48 小时。共有 9925 名患者进行了资格筛选，其中 574 名符合入选标准并被随机分组。
目标 Pao2 范围为 8 至 12 kPa（低正常组，n=205）和 14 至 18 kPa（高正常组，n=195）。仅在临床需要时应用吸入氧分数大于 0.60。
SOFARANK，通过序贯器官衰竭评估 (SOFA) 评分的非呼吸成分量化的非呼吸器官衰竭的排名结果，在研究的前 14 天内总和。参与者的排名从器官衰竭改善最快（得分最低）到器官衰竭恶化或死亡（得分最高）。次要终点为机械通气时间、院内死亡率和低氧血症测量。
在随机分组的 574 名患者中，400 名（70%）在 24 小时内入组（中位年龄 68 岁；140 名女性[35%]），所有患者均完成了试验。两组之间的中位 Pao2 差异为-1.93 kPa（95% CI，-2.12 至-1.74；P<0.001）。低正常 Pao2 组的中位 SOFARANK 评分-35 分，高正常 Pao2 组-40 分（中位数差异，10 [95% CI，0 至 21]；P=0.06）。机械通气时间的中位数无显著差异（3.4 天与 3.1 天；中位数差异，-0.15 [95% CI，-0.88 至 0.47]；P=0.59）和院内死亡率（32%与 31%；比值比，1.04 [95% CI，0.67 至 1.63]；P=0.91）。低正常组更常发生轻度低氧血症测量（1.9%与 1.2%；中位数差异，0.73 [95% CI，0.30 至 1.20]；P<0.001）。低正常 Pao2 组有 20 名（10%）患者发生急性肾损伤，高正常 Pao2 组有 21 名（11%）患者发生急性心肌梗死。
在患有 2 个或更多 SIRS 标准的危重病患者中，与高正常 Pao2 目标相比，使用低正常 Pao2 目标治疗并未导致器官功能障碍的统计学显著降低。然而，该研究可能没有足够的效力来检测比假设更小的治疗效果。
ClinicalTrials.gov 标识符：NCT02321072。
