Case Studies in Toxicology: Start Low and Go Slow
What is the optimal dosing of naloxone and proper patient management?
It is essential for clinicians to remember that the ultimate goal of naloxone administration in the ED is to reverse ventilatory depression—not to restore a patient to a normal mental status.4 In fact, full awakening, in addition to precipitating OWS, may lead to difficult interpersonal situations in the ED, since such patients often insist on leaving the ED before the effects of naloxone wear off. This situation places the EP in the undesirable position of discharging a patient who may predictably relapse—though unlikely to die—after release.5
Management in the Hospital Setting. Given the advanced medical care environment in a hospital, the approach to opioid overdose patients can be metered. This means providing temporary noninvasive mechanical ventilatory support through BVM or laryngeal mask airways, which allow both oxygenation and ventilation (reducing the patient’s partial pressure of carbon dioxide), prior to giving naloxone.6 Studies on animal models have shown that lowering the partial pressure of carbon dioxide reduces the catecholamine response to naloxone.7
Although recent literature and textbook recommendations regarding naloxone dosages vary,1 the safest initial dose of naloxone in the hospital setting is 0.04 mg (40 mcg) IV, or 0.08 mg (80 mcg) intramuscularly (IM).8 Whether given by IV or IM route, frequent reassessment of the adequacy of spontaneous ventilatory effort and oxygenation are required.
While the rate of opioid reversal is slower when giving lower doses of naloxone, this approach reduces the severity of precipitated OWS. In fact, in most patients who receive low-dose naloxone administration will not awaken but will develop life-sustaining spontaneous ventilation.8
By monitoring of the patient’s ventilatory rate and depth, along with capnometry and pulse oximetry (without providing exogenous oxygen), the EP can identify the need for additional naloxone. Since the half-life of naloxone is shorter than that of many opioids, proper ventilatory monitoring is essential to assess for the waning of naloxone’s effects and return of respiratory depression.
Treatment in the Nonhospital Setting. Emergency medical service (EMS) workers typically, and often by situational necessity, approach opioid overdose patients more aggressively than do EPs in the ED. Although some EMS systems utilize the IV route, most EMS workers, like laypersons, administer an initial naloxone dose of 0.4 mg IM or 2 or 4 mg intranasally (IN). Due to the slower rate of absorption and lower bioavailability (with IN administration), both IM and IN naloxone equate to roughly 0.08 mg IV.
For patients in whom there is no risk for opioid dependence, the initial dose of naloxone is relatively inconsequential, and higher doses can be safely administered. However, for most patients, including those in the ED setting, in whom one cannot be certain of their depth of dependence, the safest approach is to “start low and go slow” with naloxone administration, while providing supportive care.
Case Conclusion
The patient was not opioid-naïve, explaining the catecholamine surge and related cardiovascular dysfunction and pulmonary edema. The pneumomediastinum and pulmonary aspiration were due to the violent retching and vomiting. After being admitted to the ICU, the patient was started on vancomycin and piperacillin/tazobactam for empiric coverage for mediastinal emphysema. She was kept NPO, assessed by cardiothoracic surgery, and treated with gentle fluid hydration.
A repeat CT showed a stable pneumomediastinum. Her hypoxia, tachycardia, and hypotension gradually improved over about 6 hours. The following day, the patient’s mental status normalized, and she discharged herself from the hospital against medical advice.
