240 An Investigation into the Link Between Naloxone and Pulmonary Edema

Abstract

Though naloxone has proven to be an effective opioid reversal agent, the largely unsubstantiated theory that high doses of naloxone can cause pulmonary edema prevents many healthcare providers from initially administering it in high doses. This is especially problematic given high prevalence fentanyl and its analogues, which typically require higher doses of Narcan for reversal. The purpose of this study is to investigate the correlation between naloxone dosages and route and the corresponding rates of development of pulmonary complications. This is a retrospective, observational, cross-sectional study of patients who were treated with naloxone during out-of-hospital transport by Emergency Medical Services (EMS) or in the emergency department (ED) at an urban level 1 trauma center and three associated free-standing EDs over a two year period. For the purpose of this investigation, we defined low doses of naloxone as ≤2 mg, moderate doses of naloxone as >2 mg to ≤4 mg, and high doses of naloxone as >4 mg. Hospital records were scrutinized for naloxone dosing, route of administration (intranasal, intra-osseous, intravenous, mixed, or unknown), and development of pulmonary complications. In total, 639 patients received naloxone and were included in the study. A total of 422 (69.2%) of the patients received low doses of naloxone, 138 (21.6%) received moderate doses of naloxone, and 79 (12.4%) received high doses of naloxone. A total of 13 (2.0%) were ultimately diagnosed with pulmonary complications. Of the patients who were diagnosed with pulmonary complications, six of them were diagnosed with pneumonia, four of them were diagnosed with aspiration pneumonia, and three of them were diagnosed with pulmonary edema. Of the patients who developed pulmonary complications, eight had received a low dose of naloxone, four had received a moderate dose of naloxone, and one had received a high dose of naloxone. There was no significant difference of the development of pulmonary edema, pneumonia, or aspiration pneumonia in the patients who received low, moderate, or high doses of naloxone (p values 0.711, 0.271, and 0.551 respectively). A total of 13 out of the 639 patients who received naloxone for resuscitation developed pulmonary complications. Of the patients who received high-dose naloxone, only one of developed pulmonary complications compared to eight from the low-dose group. There was no significant difference in the development of pulmonary complications between the groups who had received naloxone exclusively through an IV or intranasally (p=0.342). There were no differences in pulmonary edema, aspiration pneumonia or pneumonia between those who received high, medium or low doses of naloxone. Receiving a high dose of naloxone was not associated with a longer hospital stay than the groups who received moderate and low doses.