Correspondence
Systemic Absorption of Food Dye in Patients with Sepsis
N Engl J Med 2000; 343:1047-1048October 5, 2000
- Article
To the Editor:
Critically ill patients who are receiving enteral feeding are susceptible to pulmonary aspiration of gastric contents. Measures to enhance the early detection of aspiration include the tinting of feedings with the food dye FD&C blue no. 1.1 During sepsis, gastrointestinal permeability increases because of enterocyte death and loss of barrier function at intercellular gaps. Thus, substances that are otherwise nonabsorbable may be absorbed during sepsis.2 We report two deaths associated with the systemic absorption of blue dye no. 1 from enteral feedings; in both cases, the absorption was heralded by the appearance of blue or green skin and serum.
A 54-year-old woman with chronic renal failure was hospitalized for congestive heart failure and confusion. Hemodialysis and nasogastric feeding were initiated. Later, staphylococcal pneumonia with sepsis was attributed to aspiration, prompting the addition of blue dye no. 1 to her enteral feedings. The patient was febrile but hemodynamically stable until two days later, when her skin and serum turned green. She died of refractory hypotension and acidosis that day.
A 12-month-old boy with trisomy 21 underwent tracheostomy for obstructive apnea. Pseudomonas pneumonia with sepsis developed; aspiration was believed to have occurred. Blue dye no. 1 was added to his enteral feedings. He remained hemodynamically stable, with normal renal function, until the next day, when his skin (Figure 1Figure 1
Blue Discoloration of the Skin in a 12-Month-Old Boy Who Had Received Enteral Feedings Tinted with FD&C Blue Dye No. 1.), serum, and urine became blue and hyperthermia developed (rectal temperature, 47°C). He died of refractory hypotension and acidosis that day.Neither patient had bacteremia. Autopsies of both patients revealed green or blue discoloration of the skin and internal organs, without gastrointestinal perforation. Light-spectroscopic analysis of the child's serum and of the stock of blue dye no. 1 revealed identical, single absorption peaks at 629 nm (a peak that was absent in control serum), confirming the systemic absorption of dye. Although the blue tinting of feedings was visually titrated at our institutions, it is unlikely that oral-intake limits established by the Food and Drug Administration (FDA) for blue dye no. 1 (12 mg per kilogram of body weight per day)3 were exceeded. The adult patient had renal failure, which is notable given that this dye is cleared by the kidneys.
FD&C blue dye no. 1 was approved by the FDA for use in food after experiments showed that the dye was nontoxic and was not absorbable. However, these experiments were performed in healthy animals.3 Artificial food dyes can inhibit mitochondrial oxidative phosphorylation in vitro by acting as uncouplers (as does 2,4-dinitrophenol), by blocking electron transport (as does cyanide), or by inhibiting energy transformation by blocking the generation of ATP. Blue dye no. 1, a triphenylmethane dye, is a potent inhibitor of mitochondrial respiration in vitro4 and reduces oxygen consumption by a factor of eight in mitochondrial preparations in vitro.5 It appears to inhibit energy transformation by blocking the adenine nucleotide translocator (as is the case with atractyloside).5
Although both patients had serious underlying illnesses, their condition was improving before they received the dye and turned color. We hypothesize that the refractory hypotension and metabolic acidosis seen in these patients may be explained by the known biochemical effects of this dye, since neither patient had hypotension or severe acidosis immediately before the discoloration. The hyperthermia in the child may represent an uncoupling effect of FD&C blue dye no. 1 that is not apparent in vitro. We encourage judicious use of this food dye in patients with sepsis or other illnesses associated with increased gastrointestinal permeability.
5 ReferencesJames P. Maloney, M.D.
Medical College of Wisconsin, Milwaukee, WI 53226Ann C. Halbower, M.D.
Brian F. Fouty, M.D.
Karen A. Fagan, M.D.
Vivek Balasubramaniam, M.D.
Adrian W. Pike, Ph.D.
Paul V. Fennessey, Ph.D.
University of Colorado, Denver, CO 80262Marc Moss, M.D.
Emory University, Atlanta, GA 303221
Metheny NA ,Clouse RE . Bedside methods for detecting aspiration in tube-fed patients. Chest 1997;111:724-731
CrossRef | Web of Science | Medline2
Bjarnason I ,MacPherson A ,Hollander D . Intestinal permeability: an overview. Gastroenterology 1995;108:1566-1581
CrossRef | Web of Science | Medline3
Food and Drug Administration 4
Reyes FG ,Valim MF ,Vercesi AE . Effect of organic synthetic food colours on mitochondrial respiration. Food Addit Contam 1996;13:5-11
CrossRef | Web of Science | Medline5
Noda K ,Yoshimoto M ,Hatano S ,Watanabe T . Effect of coal tar dyes on oxygen uptake in mitochondria isolated from rat liver. J Food Hyg Soc Japan 1985;26:203-207
Web of Science
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Linda M. Lord. (2011) Minimizing tracheobronchial aspiration in the tube-fed patient part 1. The Nurse Practitioner 36:12, 12-14
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Hong-Yan Wang, Li-Min Ma, Tian Li, Ya-Lei Zhang, Hong-Wen Gao. (2009) Preparation and characterization of silver thiocyanate – tetrabromo-tetrachlorofluorescein inclusion material and its adsorption to synthetic dye. Colloids and Surfaces A: Physicochemical and Engineering Aspects 333:1-3, 126-132
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Jing Lin, Hong-Wen Gao. (2009) SDBS@BaSO4: an efficient wastewater-sorbing material. Journal of Materials Chemistry 19:22, 3598
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Hong-Wen Gao, Jing Bai, Xiao-Mei Pei, Hong-Yan Wang, Shi-Long Wang. (2008) Preparation, Characterization and Application of Silver Chloride-Eosin Y Inclusion Material. Zeitschrift für Physikalische Chemie 222:12, 1635-1650
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Norma A Metheny, Kathleen L Meert, Ray E Clouse. (2007) Complications related to feeding tube placement. Current Opinion in Gastroenterology 23:2, 178-182
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Steven B. Leder, Lynn M. Acton, Heather L. Lisitano, Joseph T. Murray. (2005) Fiberoptic Endoscopic Evaluation of Swallowing (FEES) with and without Blue-Dyed Food. Dysphagia 20:2, 157-162
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Craig M. Coopersmith, Paul E. Stromberg, Christopher G. Davis, W. Michael Dunne, Daniel M. Amiot, Irene E. Karl, Richard S. Hotchkiss, Timothy G. Buchman. (2003) Sepsis from Pseudomonas aeruginosa pneumonia decreases intestinal proliferation and induces gut epithelial cell cycle arrest*. Critical Care Medicine 31:6, 1630-1637
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Mohammad M Alsolaiman, Lyn Howard. (2003) FD&C blue dye no. 1 and blue nail discoloration:. Nutrition 19:4, 395-396
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Samuel Klein. (2002) A primer of nutritional support for gastroenterologists. Gastroenterology 122:6, 1677-1687
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Michael Czop, Daniel L. Herr. (2002) Green skin discoloration associated with multiple organ failure. Critical Care Medicine 30:3, 598-601
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Craig M. Coopersmith, Katherine C. Chang, Paul E. Swanson, Kevin W. Tinsley, Paul E. Stromberg, Timothy G. Buchman, Irene E. Karl, Richard S. Hotchkiss. (2002) Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice. Critical Care Medicine 30:1, 195-201
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Kathleen L. Meert, Kshama M. Daphtary, Norma A. Metheny. (2002) Detection of pepsin and glucose in tracheal secretions as indicators of aspiration in mechanically ventilated children. Pediatric Critical Care Medicine 3:1, 19-22
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Mark C. Blunt, Peter J. Young, Anita Patil, Alan Haddock. (2001) Gel Lubrication of the Tracheal Tube Cuff Reduces Pulmonary Aspiration. Anesthesiology 95:2, 377-381
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