Which of the following medications is likely responsible for this urine discoloration in an intubated and sedated ICU patient?

  1. Fentanyl
  2. Ketamine
  3. Lorazepam
  4. Midazolam
  5. Propofol

Answer: 5. Propofol

Propofol Induced Urine Discoloration

  • Propofol (2,6 di-isopropylphenol) is commonly used for both induction of anesthesia and prolonged sedation as well as to treat refractory status epilepticus, delirium tremens and as a sedative in severe asthma due to its effects as a bronchodilator (1,2).
  • Propofol is metabolized by cytochrome P450 in the liver producing propofol glucuronide and multiple quinol derivatives that are renally excreted (3).
  • The quinol derivatives of propofol excreted in the urine are likely responsible for the green discoloration, however the mechanism causing the green color itself is not completely understood (3,4).
  • Although the green color is striking, it is benign and rare with a reported incidence less than 1% (5).
  • The metabolites thought to be responsible for the discoloration do not affect renal function, and urine returns to normal color with cessation of propofol (6).

Is any treatment indicated?

  • Many physicians will opt to stop the propofol infusion and transition to another sedative agent when this color change is noted.
  • Green urine is not part of the life threatening propofol infusion syndrome that can occur in patients who receive prolonged high dose infusions. This syndrome is characterized by bradycardia, metabolic acidosis, rhabdomyolysis and an enlarged or fatty liver (7).

What else causes green urine?

  • Green discoloration of the urine has been noted with several other medications including (8):
    • Phenol containing compounds
    • Methylene blue
    • Amitriptyline
    • Methocarbamol
    • Indomethacin
    • Cimetidine
  • Infection with Pseudomonas aeruginosa has been associated with green urine due to the pyocyanin pigment produced by the microbe (9).
  • Food coloring additives, such as FD&C Blue #1, can be absorbed in sufficient quantities to discolor urine (10).
  • Diquat, a toxic herbicide, can be quickly identified as the toxic agent responsible for a patient’s deterioration when normal appearing urine turns green with the addition of sodium bicarbonate and sodium dithionite (11).

Clinical Pearls

  • Metabolites of the commonly used IV sedative propofol can cause green urine discoloration.
  • The discoloration is rare, benign and reversible with cessation of the drug.
  • Green urine has multiple causes, and a broad differential should be considered if this abnormality is identified.
  • There is a life-threatening syndrome of toxicity associated with propofol infusion, but green urine is not an indicator of propofol infusion syndrome

This post has been peer reviewed on behalf of ACMT by Bryan Judge, Louise Kao, Michelle Ruha, and Aaron Skolnik.

References

  1. Rai S, Drislane FW. Treatment of Refractory and Super-refractory Status Epilepticus. Neurotherapeutics. 2018 Jul;15(3):697-712. doi: 10.1007/s13311-018-0640-5. PMID: 29922905
  2. Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639-49. doi: 10.2174/1381612043382846. PMID: 15579060
  3. Shioya N, Ishibe Y, Shibata S, Makabe H, Kan S, Matsumoto N, Takahashi G, Yamada Y, Endo S. Green Urine Discoloration due to Propofol Infusion: A Case Report. Case Rep Emerg Med. 2011;2011:242514. doi: 10.1155/2011/242514. Epub 2011 Dec 27. PMID: 23326690
  4. Fujii-Abe K, Kawahara H, Fukayama H. An analysis of green discoloration of urine caused by propofol infusion. J Clin Anesth. 2016 Dec;35:358-360. doi: 10.1016/j.jclinane.2016.08.032. Epub 2016 Oct 13. PMID: 27871556
  5. Kim GE, Kim DY, Yoo DK, Lee J-H, Lee SM, Min JJ. Green urine after general anesthesia with propofol: different responses in the same patient -A case report-. Anesth Pain Med. 2017;12(1):32-36.
  6. Rawal G, Yadav S. Green Urine Due to Propofol: A Case Report with Review of Literature. J Clin Diagn Res. 2015 Nov;9(11):OD03-4. doi: 10.7860/JCDR/2015/15681.6706. Epub 2015 Nov 1. PMID: 26673613
  7. Foot CL, Fraser JF. Uroscopic rainbow: modern matula medicine. Postgrad Med J. 2006 Feb;82(964):126-9. doi: 10.1136/pgmj.2005.037598. PMID: 16461475
  8. Ananthanarayan C, Fisher JA. Why was the urine green? Can J Anaesth. 1995 Jan;42(1):87-8. doi: 10.1007/BF03010578. PMID: 7889591
  9. Kam PC, Cardone D. Propofol infusion syndrome. Anaesthesia. 2007 Jul;62(7):690-701. doi: 10.1111/j.1365-2044.2007.05055.x. PMID: 17567345
  10. Carpenito G, Kurtz I. Green urine in a critically ill patient. Am J Kidney Dis. 2002;39. DOI: 10.1053/ajkd.2002.3201. PMID: 11920362
  11. Vohra R, Salazar A, Cantrell FL, Fernando R, Clark RF. The poison pen: bedside diagnosis of urinary diquat. J Med Toxicol. 2010 Mar;6(1):35-6. doi: 10.1007/s13181-010-0033-6. PMID: 20229151
Clare Gunn, MD

Clare Gunn, MD

Emergency Medicine Resident
Carolinas Medical Center, Charlotte, NC
Kathryn T. Kopec, DO

Kathryn T. Kopec, DO

Associate Professor of Emergency Medicine
Medical Toxicologist
Carolinas Medical Center
Kathryn T. Kopec, DO

@KopecToxEM

Emergency Medicine Physician & Medical Toxicologist