Meservey Amber, Krishnan Govind, Green Cynthia L, Morrison Samantha, Rackley Craig R, Kraft Bryan D
Department of Medicine, Duke University School of Medicine, Durham, NC.
Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC.
Crit Care Explor. 2023 Aug 21;5(8):e0957. doi: 10.1097/CCE.0000000000000957. eCollection 2023 Aug.
Carbon monoxide (CO) is an endogenous signaling molecule that activates cytoprotective programs implicated in the resolution of acute respiratory distress syndrome (ARDS) and survival of critical illness. Because CO levels can be measured in blood as carboxyhemoglobin, we hypothesized that carboxyhemoglobin percent (COHb%) may associate with mortality.
To examine the relationship between COHb% and outcomes in patients with ARDS requiring venovenous extracorporeal membrane oxygenation (ECMO), a condition where elevated COHb% is commonly observed.
Retrospective cohort study.
Academic medical center ICU.
Patients were included that had ARDS on venovenous ECMO.
We examined the association between COHb% and mortality using a Cox proportional hazards model. Secondary outcomes including ECMO duration, ventilator weaning, and hospital and ICU length of stay were examined using both subdistribution and causal-specific hazard models for competing risks. We identified 109 consecutive patients for analysis. Mortality significantly decreased per 1 U increase in COHb% below 3.25% (hazard ratio [HR], 0.35; 95% CI, 0.15-0.80; = 0.013) and increased per 1 U increase above 3.25% (HR, 4.7; 95% CI, 1.5-14.7; = 0.007) reflecting a nonlinear association ( = 0.006). Each unit increase in COHb% was associated with reduced likelihood of liberation from ECMO and mechanical ventilation, and increased time to hospital and ICU discharge (all < 0.05). COHb% was significantly associated with hemolysis but not with initiation of hemodialysis or blood transfusions.
In patients with ARDS on venovenous ECMO, COHb% is a novel biomarker for mortality exhibiting a U-shaped pattern. Our findings suggest that too little CO (perhaps due to impaired host signaling) or excess CO (perhaps due to hemolysis) is associated with higher mortality. Patients with low COHb% may exhibit the most benefit from future therapies targeting anti-oxidant and anti-inflammatory pathways such as low-dose inhaled CO gas.
一氧化碳（CO）是一种内源性信号分子，可激活与急性呼吸窘迫综合征（ARDS）的缓解及危重病存活相关的细胞保护程序。由于血液中的一氧化碳水平可通过碳氧血红蛋白进行测量，我们推测碳氧血红蛋白百分比（COHb%）可能与死亡率相关。
研究在需要静脉-静脉体外膜肺氧合（ECMO）的ARDS患者中，COHb%与预后之间的关系，在这种情况下通常会观察到COHb%升高。
回顾性队列研究。
学术医疗中心重症监护病房。
纳入接受静脉-静脉ECMO治疗的ARDS患者。
我们使用Cox比例风险模型研究COHb%与死亡率之间的关联。对于竞争风险，使用亚分布和因果特异性风险模型检查包括ECMO持续时间、脱机、住院时间和重症监护病房住院时间在内的次要结局。我们确定了109例连续患者进行分析。在COHb%低于3.25%时，每升高1个单位，死亡率显著降低（风险比[HR]，0.35；95%置信区间，0.15 - 0.80；P = 0.013），而在高于3.25%时，每升高1个单位，死亡率增加（HR，4.7；95%置信区间，1.5 - 14.7；P = 0.007），反映出非线性关联（P = 0.006）。COHb%每升高1个单位，与脱离ECMO和机械通气的可能性降低以及出院和重症监护病房出院时间延长相关（均P < 0.05）。COHb%与溶血显著相关，但与开始血液透析或输血无关。
在接受静脉-静脉ECMO治疗的ARDS患者中，COHb%是一种呈现U型模式的新型死亡率生物标志物。我们的研究结果表明，CO过少（可能由于宿主信号受损）或过多（可能由于溶血）均与较高死亡率相关。COHb%低的患者可能从未来针对抗氧化和抗炎途径的治疗中获益最大，如低剂量吸入一氧化碳气体。
