Department of Pharmacy Practice, Irma Lerma Rangel College of Pharmacy, TX A&M University, Houston, TX, USA.
Department of Pharmacy, The University of Texas Medical Branch, Galveston, TX, USA.
Clin Toxicol (Phila). 2024 May;62(5):334-342. doi: 10.1080/15563650.2024.2348108. Epub 2024 Jun 12.
Pulmonary edema is a rare complication occurring after naloxone administration, but the causal relationship remains insufficiently investigated. We aimed to determine the likelihood of naloxone as the causative agent in published cases of pulmonary edema.
A literature search was conducted across multiple databases, utilizing database-specific search terms such as "pulmonary edema/chemically induced" and "naloxone/adverse effects." Each case report was evaluated using the Naranjo scale, a standardized causality assessment algorithm.
We identified 49 published case reports of pulmonary edema following naloxone administration. The median total dose of naloxone was 0.2 mg for patients presenting following a surgical procedure and 4 mg for out-of-hospital opioid overdoses. Based on the Naranjo scale, the majority of cases were classified as "possible" ( = 38) or "probable" ( = 11) adverse reactions, while no "definite" cases of naloxone-induced pulmonary edema were identified. Many patients were classified as "possible" due to limited patient information or other potential risks, such as fluid administration or airway obstruction. Forty-six of 49 patients survived (94 percent).
Pulmonary edema may occur after both low and high doses of naloxone; however, low doses were primarily reported in the surgical population. Despite this complication, the majority of patients survived. Furthermore, no case report in our analysis was classified as a "definite" case of naloxone-induced pulmonary edema which limits the establishment of causality. Future studies should explore patient risk factors, including surgical versus outpatient setting and opioid-naïve versus opioid-tolerant for developing pulmonary edema and employ a causality assessment algorithm.
These case reports suggest pulmonary edema can occur following naloxone administration, irrespective of dose. According to the Naranjo scale, there were no definite cases of naloxone-induced pulmonary edema. Overall, we suggest the benefits of naloxone administration outweigh the risks. Naloxone should be administered to treat opioid overdoses while monitoring for the development of pulmonary edema.
肺水肿是纳洛酮给药后罕见的并发症，但因果关系仍未得到充分研究。我们旨在确定纳洛酮在已发表的肺水肿病例中作为致病因素的可能性。
通过多个数据库进行文献检索，使用数据库特定的搜索词，如“肺水肿/化学诱导”和“纳洛酮/不良反应”。使用标准化因果关系评估算法——Naranjo 量表评估每个病例报告。
我们确定了 49 例纳洛酮给药后肺水肿的已发表病例报告。接受手术的患者纳洛酮的总剂量中位数为 0.2mg，院外阿片类药物过量的患者为 4mg。根据 Naranjo 量表，大多数病例被归类为“可能”（ = 38）或“很可能”（ = 11）不良反应，而没有确定的纳洛酮引起的肺水肿病例。许多患者因患者信息有限或其他潜在风险（如液体给药或气道阻塞）而被归类为“可能”。49 例患者中有 46 例存活（94%）。
肺水肿可能发生在低剂量和高剂量的纳洛酮之后；然而，低剂量主要在手术人群中报道。尽管存在这种并发症，但大多数患者存活下来。此外，我们分析中的没有病例报告被归类为纳洛酮引起的肺水肿的“确定”病例，这限制了因果关系的确立。未来的研究应探讨患者的风险因素，包括手术与门诊环境、阿片类药物耐受与非耐受，以确定发生肺水肿的风险，并采用因果关系评估算法。
这些病例报告表明，肺水肿可在纳洛酮给药后发生，而与剂量无关。根据 Naranjo 量表，没有纳洛酮引起的肺水肿的确定病例。总的来说，我们认为纳洛酮给药的益处大于风险。纳洛酮应在治疗阿片类药物过量时给药，同时监测肺水肿的发生。
