Lethal morphine intoxication in a patient with a sickle cell crisis and renal impairment: case report and a review of the literature.
Morphine-6-glucuronide, the active metabolite of morphine, and to a lesser extent morphine itself are known to accumulate in patients with renal failure. A number of cases on non-lethal morphine toxicity in patients with renal impairment report high plasma concentrations of morphine-6-glucuronide, suggesting that this metabolite achieves sufficiently high brain concentrations to cause long-lasting respiratory depression, despite its poor central nervous system penetration. We report a lethal morphine intoxication in a 61-year-old man with sickle cell disease and renal impairment, and we measured concentrations of morphine and morphine-6-glucuronide in blood, brain and cerebrospinal fluid. There were no measurable concentrations of morphine-6-glucuronide in cerebrospinal fluid or brain tissue, despite high blood concentrations. In contrast, the relatively high morphine concentration in the brain suggests that morphine itself was responsible for the cardiorespiratory arrest in this patient. Given the fatal outcome, we recommend to avoid repeated or continuous morphine administration in renal failure.
Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands. Jurjen.lagas@slz.nl
Jurjen S
JS
Lagas
Jiri F P
JF
Wagenaar
Alwin D R
AD
Huitema
Michel J X
MJ
Hillebrand
Cornelis H W
CH
Koks
Victor E A
VE
Gerdes
Desiderius P M
DP
Brandjes
Jos H
JH
Beijnen
D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D017809:Fatal Outcome; D006323:Heart Arrest / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000097:blood / Q000134:cerebrospinal fluid / Q000627:therapeutic use / Q000633:toxicity*; D009022:Morphine Derivatives / Q000097:blood / Q000134:cerebrospinal fluid; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications / Q000188:drug therapy*
D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine