Case Presentation: A 23-year-old woman with type 1 diabetes mellitus, multiple previous hospitalizations for diabetic ketoacidosis (DKA), and severe gastroparesis presented with persistent nausea, vomiting, and abdominal pain. Her history included a remote gastric surgery of unclear type. CT abdomen/pelvis and esophagram with oral contrast showed no mechanical obstruction. Despite optimized antiemetic and prokinetic therapy, including ondansetron, prochlorperazine, trimethobenzamide, and metoclopramide, symptoms persisted. Adjunctive benztropine and gabapentin also failed to provide relief. Due to refractory pain and minimal oral tolerance, she required IV fluids and insulin infusion. Attempts to taper opioid analgesics led to rebound abdominal pain and recurrent DKA from dehydration and inadequate intake, raising concern for opioid-induced gastric dysmotility and prompting early pain-management consultation. A continuous subanesthetic ketamine infusion was initiated. Within 72 hours, she tolerated fluids; opioids were tapered then discontinued, and glycemic control improved. She transitioned to oral non-opioid analgesics and maintained adequate enteral intake without requiring supplemental nutritional support.
Discussion: Diabetic gastroparesis results from autonomic neuropathy, smooth muscle dysfunction, and loss of interstitial cells of Cajal (ICC). ICC are specialized pathway pacemaker cells that generate slow-wave electrical activity required for coordinated contractions. ICC injury disrupts peristalsis, leading to delayed emptying. As oral intake worsens, dehydration and hyperglycemia develop. Decreased intake makes insulin dosing unreliable and increases the risk of DKA, contributing to recurrent admissions for poor intake, nausea, and metabolic instability. Opioids intensify this instability. Peripherally, μ-opioid receptor activation suppresses acetylcholine release in the enteric nervous system, slowing peristalsis. Centrally, opioids potentiate NDMA receptor activity, creating visceral hyperalgesia, and reinforcing opioid dependence. In diabetic gastroparesis, these effects rapidly escalate pain requirements, worsen dysmotility, and undermine glycemic control. Ketamine offers an alternative. As a noncompetitive NMDA receptor antagonist, it reduces central sensitization and hyperalgesia while preserving gastric motility by maintaining cholinergic and sympathetic tone. This enables adequate analgesia without worsening dysmotility, supporting improved intake and metabolic stability. Although evidence for subanesthetic ketamine in complex pain is growing, its application in visceral dysmotility remains underrecognized. This case highlights how early coordination among hospital medicine and pain management can shift the trajectory when standard approaches fail.
Conclusions: Refractory diabetic gastroparesis often creates a destructive cycle of uncontrolled pain, increased opioid use, worsening gastric dysmotility, poor intake, dehydration, and recurrent DKA, resulting in repeated hospitalizations. In this case, ketamine provided effective analgesia while preserving motility, allowing the patient to regain oral tolerance, taper off opioids, and stabilize glycemic control. Introducing opioid-sparing pain strategies earlier in care may offer a viable path to breaking the cycle of recurrent admissions and metabolic decompensation in patients with complex dysmotility syndromes.