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Thursday, 28 April 2016

GREEN URINE, A RARE FINDING IN THE CLINIC LABORATORY

Written by José Luis García de Veas Silva | Rocío Escobar Conesa | Carmen García Rabaneda, Posted in Volumen 2

A 60 years old patient was operated for acute abdominal pain due to purulent peritonitis. He was derived to the intensive care unit (ICU) with multiple organ failure (hemodynamic, renal and respiratory) under sedoanalgesia. Antibiotic treatment is started. During his stay in the ICU, it was observed a normalization of the inflammatory and infectious biomarkers with progressive improvement of the renal and respiratory function. The patient was under sedation based on propofol and remifentanil. An intense green coloration was observed in the urine samples from the patient in subsequent analytical tests to surgery and perfusion of sedatives (Figure 1).
Articulo4 imagen1 500x500 Figure 1. Urine sample of the patient

The presence of a greenish coloration in the urine of patients is an unusual finding in the clinical laboratory. This could be due to several underlying causes such as drugs, dyes compounds, infections and metabolic disorders. These causes can be classified into three groups1,2:

  • Drugs: due to the presence of triamterene, propofol, mitoxantrone, methocarbamol, flutamide, promethazine, phenylbutazone, cimetidine, amitriptyline and methylene blue.
  • Pathological: presence of biliverdin in urine, bacterial infection by Pseudomonas aeruginosa, enterovesical fistula with loss of bile, Hartnup disease and indicanuria.
  • Dye compounds: chlorophyll, resorcinol, indigo blue, indigo carmine and carbolic acid (phenol acid).
Therefore, the differential study of the origin of urine coloration could help us to to rule out or confirm a possible pathological origin and take appropriate measures. In our case, the study of urine was normal without presence of biliverdin or microorganisms. The coloration was attributed to the propofol dispensed as sedative to the patient with the consequent excretion of metabolites of propofol in urine3.
 
Articulo4 imagen2 500x504Figure 2. Main metabolic pathway of propofol5.
 
 
Propofol (2,6-diisopropyl-phenol) presents an extensive metabolism in liver microsomes (Figure 2). In phase I, propofol is metabolized to 2,6-diisopropyl-1,4-quinol by cytochrome P450. In phase II, the mayor metabolite is propofol-glucuronide and the minor metabolites were the 2,6-diisopropyl-1,4-quinol derivates: 1-(2,6-diisopropyl-1,4-quinol)-glucuronide, 4-(2,6-diisopropyl-1,4-quinol)-glucuronide and 4-(2,6-diisopropyl-1,4-quinol)-sulphate. Propofol metabolites presents a characteristic greenish coloration, are innocuous and do not induce nephrotoxicity. This coloration of the urine appears when clearance of propofol exceeds hepatic elimination, and extrahepatic elimination of propofol occurs4,5. In the following samples of the patient, the green coloration of urine was resolved spontaneously.

Finally, a brief summary of the causes associated to the different colours of the urine is presented in Table 1.
COLOR CAUSA CORRELACIÓN CLÍNICA / LABORATORIO
Incolora

Consumo de fluidos reciente

Observado en muestras al azar

Amarillo pálido

Poliuria o diabetes insípida

Diabetes mellitus

Muestras al azar diluidas

Incremento volumen 24 horas y descenso densidad

Aumento de densidad y valores de  glucosa elevados

Consumo de fluidos reciente

Amarillo oscuro

Muestras concentradas

Deshidratación

Bilirrubina

Puede ser normal tras ejercicio intenso o en la orina de primera hora de la mañana

Fiebre o quemaduras

Espuma de color amarillo tras agitación y valores de bilirrubina elevados

Amarillo anaranjado

Fenazopiridina

Fenindiona

Fármaco administrado para la infección del tracto urinario

Anticoagulante (naranja en orina básica e incolora en orina ácida)

Amarillo verdoso

Bilirrubina oxidada a biliverdina

Espuma coloreada en orinas ácidas y resultados falsos negativos de bilirrubina

Verde

Infección por Pseudomonas

Cultivo de orina positivo que confirma presencia de Pseudomonas

Azul verdoso

Amitriptilina

Metocarbamol

Azul de metileno

Fenoles

Antidepresivo

Relajante muscular

Antiséptico leve del tracto urinario

Oxidación de los compuestos fenólicos

Rosa

Hematíes

Orina turbia y observación de hematíes al microscopio

Rojo

Hemoglobina

Mioglobina

Rifampicina

Contaminación por menstruación

Orina de color roja clara con tira reactiva positiva para sangre; hemólisis intravascular

Orina clara con tira reactiva positiva para sangre; daño muscular

Fármaco para el tratamiento de la Tuberculosis

Orina turbia con hematíes, mucus y coágulos

Rojo vino

Porfirinas

Tira reactiva negativa para sangre y se necesitan estudios adicionales

Marrón rojizo

Hematíes oxidados a metahemoglobina

En orinas ácidas tras reposo, tira reactiva positiva para sangre

Marrón

Ácido homogentísico (alcaptonuria)

En orinas alcalinas tras reposo y se necesitan estudios adicionales

Negra

Melanoma maligno/melanina

Derivados fenólicos

Argyrol (antiséptico)

Metildopa o levodopa

Metronidazol
Orina oscura tras reposo y reaccionan con nitroprusiato y cloruro férrico

Interferencia con test de reducción de cobre

Color desaparece con cloruro férrico

Antihipertensivos

Oscurece al reposar, infecciones intestinales y vaginales.


References
  • Blakey SA, Hixson-Wallace JA. Clinical Significance of Rare and Benign Side Effects: Propofol and Green Urine. Pharmacotherapy. 2000;20(9):1120–2.
  • Ananthanarayan C, Fisher JA. Why was the urine green? Can J Anaesth J Can d’anesthésie. 1995;42(1):87–8.
  • Lee J-S, Jang H-S, Park B-J. Green discoloration of urine after propofol infusion in the intensive care unit. Korean J Anesthesiol. 2013;65(2):177–9.
  • Rawal G, Yadav S. Green Urine Due to Propofol: A Case Report with Review of Literature. J Clin Diagn Res. 2015;9(11):OD03–4
  • Shioya N, Ishibe Y, Shibata S, Makabe H, Kan S, Matsumoto N, et al. Green urine discoloration due to propofol infusion: a case report.Case Rep Emerg Med 2011; 2011: 242514.
  • Foot CL, Fraser JF. Uroscopic rainbow: modern matula medicine. Postgrad Med J 2006;82(964)126-9.

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