Conclusions

Kratom-associated toxicity represents an emerging challenge in acute care because it may present with opioid-like signs despite negative routine opioid immunoassay screening and may respond incompletely or transiently to naloxone. Reported cases describe delayed or recurrent respiratory depression, particularly following high-dose exposure or polysubstance use. Clinicians should maintain a high index of suspicion for kratom toxicity, provide supportive care, administer repeat naloxone when clinically indicated, and base observation and disposition decisions on the patient's clinical course rather than the initial response to naloxone alone.

Current evidence is derived primarily from case reports, retrospective studies, and preclinical investigations, highlighting the need for prospective human studies to better define optimal diagnostic and management strategies. As kratom use continues to increase, improved clinician awareness, continued research, and evidence-based regulatory approaches will be important for enhancing patient safety and informing future clinical practice.