title: Respiratory failure following delayed intrathecal morphine pump refill: a valuable, but costly lesson.
abstract: BACKGROUND
  Spinal analgesia, mediated by opioid receptors, requires only a fraction of the opioid dose that is needed systemically. By infusing a small amount of opioid into the cerebrospinal fluid in close proximity to the receptor sites in the spinal cord, profound analgesia may be achieved while sparing some of the side effects due to systemic opioids. Intraspinal drug delivery (IDD) has been increasingly used in patients with intractable chronic pain, when these patients have developed untoward side effects with systemic opioid usage. The introduction of intrathecal opioids has been considered one of the most important breakthroughs in pain management in the past three decades. A variety of side effects associated with the long-term usage of IDD have been recognized. Among them, respiratory depression is the most feared.
  
  
  OBJECTIVE
  To describe a severe adverse event, i.e., respiratory failure, following delayed intrathecal morphine pump refill.
  
  
  METHODS
  A 65-year-old woman with intractable chronic low back pain, due to degenerative disc disease, and was referred to our clinic for an intraspinal drug delivery evaluation, after failing to respond to multidisciplinary pain treatment. Following a psychological evaluation confirming her candidacy, she underwent an outpatient patient-controlled continuous epidural morphine infusion trial. The infusion trial lasted 12 days and was beneficial in controlling her pain. The patient reported more than 90% pain reduction with improved distance for ambulation. She subsequently consented and was scheduled for permanent intrathecal morphine pump implantation. The intrathecal catheter was inserted at right paramedian L3-L4, with catheter tip advanced to L1, confirmed under fluoroscopy. Intrathecal catheter placement was confirmed by positive CSF flow and by myelogram. A non-programmable Codman 3000 constant-flow rate infusion pump was placed in the right mid quandrant between right rib cage and right iliac crest. The intrathecal infusion consisted of preservative free morphine, delivering 1.0 mg /day. Over the following 6 months, the dosage was gradually titrated up to 4 mg/day with satisfactory pain control without significant side effects. However, the patient was not able to return to the clinic for pump refill until 12 days later than the previously scheduled pump-refill date. Her pump was accessed and was noted to be empty. Her intrathecal pump was refilled with preservative free morphine, delivering 4 mg/day (the same daily dose as her previous refill). However, on the night of pump refill, 10 hours after the pump refill, the patient was found to be unresponsive by her family members. 911 was called. Upon arriving, paramedics found her in respiratory failure, with shallow breathing at a rate of 5/min, pulse oxymetry showing oxygen saturation about 55-58%. She was emergently intubated on site and rushed to local hospital ER. The on call physician for our clinic was immediately contacted, and advised the administration of intravenous Naloxone. Her respiratory effort improved dramatically after receiving a total of 0.6 mg IV Naloxone IV over 25 minutes. Her intrathecal pump was immediately accessed by clinic on call physician and the remainder of the medication in the catheter space was aspirated. The pump infusate was immediately diluted with preservative free normal saline, to deliver preservative free morphine at 1mg/day. She was transferred to the intensive care unit and extubated the next morning. She recovered fully without any sequelae.
  
  
  CONCLUSIONS
  Loss of opioid tolerance due to delayed pump refill may subject patients to the development of severe respiratory depression. Meticulous approach should be employed when refilling pumps in these patients when their pumps are completely empty. To our knowledge, this is the first reported case of this type.
authors.affiliation: Physicians' Pain Specialists of Alabama, Mobile, AL, USA. xiuluruan@yahoo.com
authors.forename: Xiulu
authors.initials: X
authors.lastname: Ruan
authors.forename: J Patrick
authors.initials: JP
authors.lastname: Couch
authors.forename: HaiNan
authors.initials: H
authors.lastname: Liu
authors.forename: Rinoo V
authors.initials: RV
authors.lastname: Shah
authors.forename: Frank
authors.initials: F
authors.lastname: Wang
authors.forename: Srinivas
authors.initials: S
authors.lastname: Chiravuri
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000506:poisoning; D000075202:Contraindications; D004334:Drug Administration Schedule; D062787:Drug Overdose / Q000209:etiology / Q000517:prevention & control; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D015918:Infusion Pumps, Implantable / Q000009:adverse effects / Q000191:economics / Q000592:standards; D007278:Injections, Spinal / Q000009:adverse effects* / Q000379:methods / Q000592:standards; D009020:Morphine / Q000506:poisoning*; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology; D012131:Respiratory Insufficiency / Q000139:chemically induced* / Q000175:diagnosis; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine