The empiric use of naloxone in patients with altered mental status: a reappraisal. STUDY OBJECTIVE: To determine whether clinical criteria (respirations of 12 or less, mitotic pupils, and circumstantial evidence of opiate abuse) could predict response to naloxone in patients with acute alteration of mental status (AMS) and to evaluate whether such criteria predict a final diagnosis of presence or absence of opiate overdose as accurately as response to naloxone. CASES AND SETTING: Seven hundred thirty patients with AMS who received naloxone for diagnostic or therapeutic purposes at the discretion of two large, urban, paramedic base teaching hospitals. METHODS: We reviewed paramedic run sheets and audiotapes on all 730 patients as well as available hospital records of all patients who demonstrated any response to naloxone to determine whether overdose was responsible for their clinical presentations. We also reviewed hospital records for a selected sample of naloxone nonresponders. MAIN RESULTS AND CONCLUSION: Only 25 patients (3.4%) demonstrated a complete response to naloxone, whereas 32 (4.4%) manifested a partial or equivocal response. Nineteen of 25 complete responders (76%), two of 26 partial responders (8%) (with known final diagnosis), and four of 195 non-responders (2%) (with known final diagnosis) were ultimately diagnosed as having overdosed. Respirations of 12 or less or the presence of any one of the three clinical findings as a group were each highly sensitive in predicting response to naloxone, and at least as sensitive as response to naloxone in predicting a diagnosis of opiate overdose. Selective administration of naloxone for AMS would have decreased the use of this drug by 75% to 90% while still administering it to virtually all naloxone responders who had a final diagnosis of opiate overdose. 