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Ketamine has been used as part of a multimodal analgesia regime in opioid abusers undergoing general anesthesia. We studied the opioid-sparing effect of a very low-dose bolus of ketamine as part of moderate sedation for opioid abuse patients undergoing extracorporeal shock wave lithotripsy.In this randomized, placebo-controlled clinical trial, 190 opioid abusers were enrolled. They were stratified into 2 blocks based on their daily opioid consumption. Both blocks were then randomized to receive 0.1 mg/kg IV ketamine (group K) or placebo (group P). Lithotripsy was performed under moderate sedation with intermittent bolus doses of remifentanil (0.2 µg/kg) to alleviate pain. The total remifentanil dose (primary outcome) and respiratory adverse events (secondary outcome) were compared in the 2 groups.Remifentanil administration in the group with low-opioid consumers was 1.6 ± 0.4 µg/kg (group P) compared with 1.0 ± 0.2 µg/kg in group K (confidence interval [CI]of difference 95%, 0.4–0.7; P < 0.001). Patients who had high-opioid consumption received 2.0 ± 0.5 µg/kg (group P) vs 1.5 ± 0.3 µg/kg (group K) remifentanil (CIof difference 95%, 0.40–0.75; P < 0.001). Ready to discharge time was statistically longer in high-consumption opioid abusers who received placebo compared with group K (55 ± 13 minutes vs 44 ± 8 minutes, CIof difference 95%, 6–15; P < 0.001). The incidences of bradypnea, apnea, nausea, vomiting, and hemodynamic changes were not statistically different between the ketamine and placebo groups.Preemptive low-dose ketamine (0.1 mg/kg) as a bolus has opioid-sparing effects in opioid abusers undergoing moderate sedation.