Permissive hypercapnia in extremely low birthweight infants (PHELBI)

在德国每年出生的4000名极低出生体重儿中，有一半患有支气管肺发育不良(BPD)或在婴儿期死亡，造成重大负担。由于救命的机械通气是导致肺损伤的部分原因，较温和的低潮气量机械通气可显著降低BPD的发生率，但与较高的动脉二氧化碳分压(PaCO2)值有关。因此，在不增加呼吸机设置的情况下接受较高的PaCO2值可能会导致较低的潮气量和更温和的机械通气，但也可能增加脑血流量和颅内出血的风险。然而，之前所有测试这种方法的临床试验都受到样本量不足和研究组之间PaCO2差异非常小的阻碍，未能显示出明显的益处。尽管缺乏可靠的疗效和安全数据，但在许多新生儿重症监护病房中，越来越多地使用更高的PaCO2目标。因此，迫切需要一项精心设计的试验。我们建议进行一项多中心试验，将两个非常不同的PaCO2目标范围的婴儿数量随机分为两个不同的目标范围，这是迄今为止进行的最大研究的两倍。这项试验将回答悬而未决的问题，并深刻影响全球新生儿临床护理，因为研究结果可以立即实施。

Half of the 4000 extremely low birthweight infants born in Germany every year develop bronchopulmonary dysplasia (BPD) or die during infancy, resulting in a significant burden. Because the life-saving mechanical ventilation is partly responsible for the lung injury, more gentle ventilation with lower tidal volumes may significantly reduce the incidence of BPD, but will be associated with higher arterial partial pressure of carbon dioxide (PaCO2) values. Accepting higher PaCO2 values without increasing ventilator settings may therefore lead to lower tidal volumes and more gentle mechanical ventilation but may also increase cerebral blood flow and the risk for intracranial hemorrhages. All previous clinical trials testing this approach, however, were hampered by insufficient sample sizes and very small PaCO2 differences between study groups, and failed to demonstrate clear benefits. Despite the lack of sound efficacy and safety data, higher PaCO2 targets have been increasingly used in many neonatal intensive care units. Therefore, a well-designed trial is urgently needed. We propose to perform a multicenter trial randomizing more than twice as many infants as the largest study performed till now to two strongly different PaCO2 target ranges. This trial will answer the open questions and profoundly influence neonatal clinical care worldwide, as the findings can be immediately implemented.