CASE STUDIES

 

A 57-year-old man with moderate chronic renal failure (plasma creatinine level of 399 µM) and hyperchloremic metabolic acidosis secondary to a chronic interstitial nephritis is admitted to the hospital following the abrupt apparence of confusion (<24 hours). A few hours after his admission, the patient presents an aggravation of his neurologic status, and becomes unconscious. Physical examination shows coma stade II-III, bilateral myosis, no other signs of central nervous system disorders, body temperature of 37°, bradycardia, but normal blood pressure. Results of laboratory studies show a creatinine level of 1060 µM, urinary ratio Na/K <1, normal liver enzymes, and renal ultrasonography reveals no evidence of obstruction. The patient’s usual treatment was epoietin alpha (2000 UIx2/week), allopurinol (200 mg/day), lansoprazole (20 mg /day), calcium bicarbonate (2 gr./day), and calcifédiol (25 mg/ day). Moreover, the patient has been taking 2 tablets of sustained-release morphine sulfate for the past two days for recent moderate and diffuse arthralgia.

Question 1 and 2

 

The diagnosis of morphine encephalopathy is confirmed by positive naloxone test, and treatment by naloxone is started (and sustained-release morphine sulfate is stopped) allowing, after repeated doses of naloxone, for obvious but slow improvement of the neurological signs since day 3 with complete healing at day 9. The renal function returns to the baseline level (plasma creatinine level of 412 µM) after adequate hydration.

Question 3 and 4

 

Selected references

1. Hanes SD, Franklin M, Kuhl DA, Headley AS. Prolonged opioid antagonism with naloxone in chronic renal failure. Pharmacotherapy. 1999 Jul;19(7):897-901. Pubmed Link

2. Lotsch J, Zimmermann M, Darimont J, Marx C, Dudziak R, Skarke C, Geisslinger G. Does the A118G polymorphism at the mu-opioid receptor gene protect against morphine-6-glucuronide toxicity? Anesthesiology. 2002 Oct;97(4):814-9. Pubmed Link

3. Milne RW, Nation RL, Reynolds GD, Somogyi AA, Van Crugten JT. High-performance liquid chromatographic determination of morphine and its 3- and 6-glucuronide metabolites: improvements to the method and application to stability studies. J Chromatogr. 1991 Apr 19;565(1-2):457-64. Pubmed Link

4. Milne RW, Nation RL, Somogyi AA, Bochner F, Griggs WM. The influence of renal function on the renal clearance of morphine and its glucuronide metabolites in intensive-care patients. Br J Clin Pharmacol. 1992 Jul;34(1):53-9. Pubmed Link

5. Sear JW, Hand CW, Moore RA, McQuay HJ. Studies on morphine disposition: influence of renal failure on the kinetics of morphine and its metabolites. Br J Anaesth. 1989 Jan;62(1):28-32 Pubmed Link

6. Van Crugten JT, Sallustio BC, Nation RL, Somogyi AA. Renal tubular transport of morphine, morphine-6-glucuronide, and morphine-3-glucuronide in the isolated perfused rat kidney. Drug Metab Dispos. 1991 Nov-Dec;19(6):1087-92. Pubmed Link

Acknowledgements: The author is indebted to Prof. Michel Andrejak, Dr Valérie Gras-Champel, Dr Martial Pannier for revising the manuscript and giving useful suggestions.