Highly concentrated supplemental oxygen given after cardiac arrest often led to arterial hyperoxia, which in turn raised the risk of in-hospital mortality, according to an observational study in the June 2 issue of JAMA.
Ironically, mortality rates after exposure to too much oxygen were greater than mortality rates after oxygen deprivation – the very indication for which supplemental oxygen is given, said Dr. J. Hope Kilgannon of the department of emergency medicine at Cooper University Hospital, Camden, N.J., and her associates (JAMA 2010;303:2165-71).
“This is the first large multicenter study documenting the association between [post-resuscitation] hyperoxia and poor clinical outcome,” the researchers noted. “These data support the hypothesis that high oxygen delivery in the post–cardiac arrest setting may have adverse effects.”
Current American Hospital Association guidelines for cardiopulmonary resuscitation advocate the use of 100% oxygen to maximize the chance of restoring spontaneous circulation. “However, after circulation is successfully restored, clinicians frequently maintain [supplemental oxygen] for variable periods,” the investigators said.
Controversy has arisen recently regarding that routine practice, because it is feared that too much oxygen may trigger neuronal injury and apoptosis. However, there has been a lack of clinical data on the issue, they added.
Dr. Kilgannon and her colleagues used data from a network of adult intensive-care units across the United States to study the question. The database included medical, surgical, and multidisciplinary ICUs from a variety of community, academic, private, public, urban, suburban, and rural hospitals.
They assessed 6,326 adults who received CPR after nontraumatic cardiac arrest and were admitted to a participating ICU in 2001-2005. Hyperoxia was defined as an arterial partial pressure of oxygen (PaO2) of 300 mm Hg or greater on the first arterial blood gas obtained on admission.
Hyperoxia was common, affecting 18% of patients. Approximately half of those patients had a PaO2 of 400 mm Hg or greater.
Most patients (63%) developed hypoxia, defined as a PaO2 of less than 60 mm Hg, and the remaining 19% maintained normal blood oxygen levels.
In-hospital mortality was greatest in the group with hyperoxia, at 63%, compared with 57% in the hypoxia group and 45% in the normoxia group, Dr. Kilgannon and her associates said. A further analysis of the data revealed that hyperoxia was an independent and strong predictor of in-hospital death (732 of 1,156 patients).
Moreover, patients with hyperoxia who survived to hospital discharge were significantly more likely to have poor functional outcomes (38%) than those with normoxia (29%).
“Analogous to the concept that hyperoxia exposure may be associated with harm in the resuscitation of neonates, the ongoing oxidant stress with hyperoxic reperfusion may be capable of worsening anoxic brain injury in adult patients with post-cardiac arrest syndrome,” the researchers said.
The observational study could not determine causality, but its findings “provide scientific rationale for clinical trials of controlled reoxygenation during the postresuscitation period,” they added.
The true incidence of hyperoxia is probably much higher than 18%, given that the investigators used “a rather conservative definition” of the disorder, noted Dr. Patrick M. Kochanek and Dr. Hülya Bayir of the University of Pittsburgh in an editorial comment accompanying the report.
They concurred that a large clinical trial of the issue is warranted to resolve whether clinicians should be more meticulous about titrating oxygenation after cardiac arrest, “and whether an alarm threshold should be set for arterial saturation ... after return of spontaneous circulation” (JAMA 2010;303:2190-1).
In addition, “unconventional resuscitation strategies that [have been] considered but heretofore unproven (such as intermittent, controlled, or even delayed reperfusion)” are now being investigated, they said.
The study was supported by the Emergency Medicine Foundation, the U.S. National Institutes of Health, the U.S. National Institute of General Medical Sciences, and the U.S. National Heart, Lung, and Blood Institute.
Dr. Kilgannon had no financial disclosures. One of Dr. Kilgannon’s associates reported receiving support from Ikaria Inc. and Spectral Diagnostics Inc. Dr. Kochanek and Dr. Bayir were supported by the U.S. Army and the National Institutes of Health. Dr. Kochanek reported being a co–patent holder on Emergency, Preservation, and Resuscitation.
Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
根据6月2日发表于《美国医学会杂志》(JAMA)上的一项观察性研究，心脏骤停后高浓度吸氧通常可导致动脉高氧，这反过来增加了院内病死风险。
新泽西州卡姆登市库柏大学医院急诊科的J. Hope Kilgannon博士及其同事表示，缺氧是吸氧的适应证，但具有讽刺意味的是，吸氧过多后的病死率高于缺氧后的病死率(JAMA 2010;303:2165-71)。
研究者指出，“这项大规模多中心研究首次发现，复苏后高氧与临床转归不佳之间存在关联。这些数据支持心脏骤停后高浓度吸氧可产生不良影响的假说。”
目前美国医院协会的心肺复苏(CPR)指南主张使用100%氧气来最大程度地恢复自主循环。研究者说：“但在循环成功恢复后，临床医生经常将吸氧方案维持一定时间。”
最近，这一常规做法引起了争议，因为有人担心吸氧过多可触发神经元损伤和凋亡。 但他们补充说，这方面的临床数据一直较为缺乏。
Kilgannon博士及其同事使用来自美国成人重症监护病房(ICU)网络的数据来对该问题进行了研究。该数据库涵盖来自不同社区医院、学术医院、私立医院、公立医院、城市医院、郊区医院和农村医院的内科ICU、外科ICU和综合性ICU。
他们对2001~2005年间6,326例在非创伤性心脏骤停后接受CPR的ICU住院成人患者进行了评价。高氧定义为入院时首次动脉血气分析所测得的动脉血氧分压(PaO2)≥300 mmHg。
高氧较为常见，见于18%的患者。约半数患者的PaO2≥400 mm Hg。
大部分患者(63%)出现缺氧(定义为PaO2低于60 mm Hg)，其余19%患者的血氧水平维持正常。
Kilgannon博士及其同事表示，院内病死率在高氧组中最高(63%)，其次为缺氧组(57%)和正常血氧组(45%)。进一步分析数据发现，高氧是院内死亡(732例 /1,156例)的独立强烈预测因子。
此外，存活至出院的高氧患者(38%)明显比正常血氧患者(29%)更易出现功能转归不佳。
研究者说：“上述结果与以下观点类似，即高氧暴露可能与新生儿复苏中所见的损伤相关，并且高氧再灌注产生的持续氧化应激可加重心脏骤停后综合征成人患者的缺血性脑损伤。”
他们补充说，该观察性研究未能明确因果关系，但其结果“为进行有关复苏后控制性再吸氧的临床试验提供了科学依据。”
匹兹堡大学的Patrick M. Kochanek博士和Hülya Bayir博士在随刊编者按中对该研究评论道，鉴于研究者对高氧采用的是“更为保守的定义”，高氧的真正发生率可能比18%要高得多。
他们一致认为，需开展大规模临床试验，以探讨临床医生是否应实施更为严谨的心脏骤停后吸氧措施，“以及是否应为自主循环恢复后的动脉血氧饱和度设定警戒阈值” (JAMA 2010;303:2190-1)。
此外，他们表示，目前正在对“已经过考虑但尚未经过证实的非传统复苏策略(如间断性、控制性或甚至延迟性再灌注)”进行研究。
该研究获急诊医学基金会、美国国立卫生研究院、美国国立综合医学研究所和美国国立心肺血液研究所的支持。
Kilgannon博士声明无任何经济利益关系。Kilgannon博士的一位同事声明获得Ikaria公司和Spectral Diagnostics公司的支持。Kochanek博士和Bayir博士声明获得美国陆军和国立卫生研究所的支持。Kochanek博士声明是紧急保护与复苏方法的共同专利持有者。
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