CI: Blue Dye Use (2006)

Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

Review the literature on the dye method and dye pharmacology, report results of a survey on dye use and describe two recent deaths associated with blue-dye absorption in enteral feedings.

Inclusion Criteria:
  • Methods to locate and select studies and validity of original studies not described/assessed
  • However, the following information is report in this review
    • Case reports of dye absorption from enteral feedings: A cause for concern and the case was reported to the FDA
    • Other case reports of blue dye absorption (1991 to 2001): Seven other reports of blue dye absorption from enteral feedings including the first two from 1991. All reports before 1999 were published as meeting abstracts, making their existence known to relatively few.
Exclusion Criteria:
Not specified.
Description of Study Protocol:

This is a review article on food dye use in enteral feeding and its effects on patients. The following are the issues reviewed in this paper:

  • History of blue dye use in American hospitals/intensive care units since at least 1982
  • The dietitan and nursing perspective on enteral feeding and blue food dye use
  • The sensitivity and safety issues of blue dye method use in enteral feeding
  • Enteral feeding and blue food dye use: A surgical perspective
  • Evidence that the blue dye method has poor utility for aspiration detection
  • Case reports of dye absorption from enteral feedings: A cause for concern and the case was reported to the FDA
  • Other case reports of blue dye absorption: Seven other reports of blue dye absorption from enteral feedings including the first two from 1991. All reports before 1999 were published as meeting abstracts, making their existence known to relatively few.
  • Gut permeabilty in hospitalized patients: Absorption of nonabsorbable dye
  • Pharmacology: Properties of FD&C Blue No. 1 and Methylene blue
  • Emphasizing methods that prevent aspiration during enteral feeding.


Data Collection Summary:
  • Data analysis not available
  • Only case reports of the patients were reported.
Description of Actual Data Sample:
  • Seven other reports of blue dye absorption based on the available literature as five abstracts and three journal articles (1991 to 2001)
  • Two case reports based on their own observation as follows:
    • 87-year old woman with dementia, COPD, CHF, dementia, pressure ulcers, shock, sepsis: 105ml dye added to 240ml tube feeding
    • 84-year old woman with emphysema, dyspnea to hypoxemic respiratory failure; NGT feeding at 50ml per hour via commercial drip pellet dye system


Summary of Results:

 The authors reported a survey results of ICU-based dietitians as follows:

  • Results of a survey of ICU-based dietitians (N=27) regarding use of food dye for tinting enteral feeds. Dietitians responded to the seven questions by fax, telephone or email
  • The survey was first done in November 1999 before the publication of two deaths associated with blue dye absorption. The survey was repeated in April 2001. The blue dye method was used regularly by 91% of respondents.
  • All surveyed hospitals had food dye policies by April 2001, whereas only 48% had such a policy in November 1999 
  • Dietitians reported changing practice by stopping dye use, limited dye volume or duration of use and identifying patients at risk for absorption.

Case Reports

  • Patient 1: An 87-year old woman with severe kyphoscoliosis, dementia, chronic obstructive pulmonary disease and congestive heart failure had four days of vomiting, diarrhea, lethargy and confusion. She treated with IV antibiotics and fluids for dehydration and sepsis from decubitus ulcers. In advertently,15ml of FD&C Blue No.1 was added to 240ml of feedings. Six hours after the start of feedings, the patient appeared cyanotic depite arterial oxygen percent of saturation of 93%. Blue green discoloration of skin, mucus membranes and all body fluids was marked. Enteral feeding was held but patient was unresponsive with ventricular fibrallation and died. The case was reported to FDA. No autopsy procedures, photographs and fluid samples were available.
  • Patient 2: An 84-year old woman with emphysema was admitted for dyspnea that progressed to hypoxemic respiratory failure. Mechanical ventilation, IV antibiotics, corticosteroids and bronchodilators were instituted. Nasogastric feedings were begun through as commercial drip-pellet FD&C Blue No.1 delivery system. No pulmonary, infiltrates were noted. She was weaned from mechanical ventilation on day seven and urine was noted to be green. She requested do not resuscitate status and was transferred to the  ward on day nine. Enteral feedings at 50ml per hour continued to be green. On day 11, the patient complained of chest pain and a myocardial infarction was confirmed.
    On day 14, her skin turns green then blue. Patient died one hour later. Seven days after death autopsy was conducted. Autopsy revealed blue green discoloration of skin. Examination results revealed no gastrointestinal abnormalities, mild pneumonia, emphysema and no emboli and there was cardiomegaly but no CHD and no infarction. No suitable samples were obtained for dye detection. The case was reported to FDA.
Other Reported Cases of Blue-Dye Absorption

Number of patients
Aorta repair,ARF→green skin, urine serum
CABG, ARDS→green skin, urine, serum
sepsis→green urine ,serum
Sepsis,CUC→green urine
sepsis→blue green skin/urine /serum
sepsis→blue green skin,urine ,serum
sepsis→blue green skin/urine /serum
Drip pellet
COPD,Respiratory failure, MI sepsis→ blue skin/ urine /serum

*Only new reports listed.
†Dye absorption linked with death.
Abstr: Abstract report; Jrnl: Journal report; F: Female; M: Male; ARF: Acute renal failure; CABG: Coronary artery bypass graft; ARDS: Acute respiratory distress syndrome; CUC: ulcerative colitis; COPD: Chronic obstructive pulmonary disease; MI: myocardial infarction 

Intestinal permeability is increased in various conditions associated with compromised mucosal integrity.

 Conditions with Increased Gut Permeability

Severe burns
Hemorrhagic shock
Cardiac bypass
Major vascular surgery
Abdominal aortic aneurysm repair
Nonsteroidal anti-inflammatory drug use
Renal failure
Celiac sprue
Inflammatory bowel disease
Cystic fibrosis

*Most data is from infected patients.
Author Conclusion:
  • The blue-dye method should be abandoned
  • The available evidence demonstrates that tinting of enteral feedings with food dyes has poor utility as a method to detect pulmonary aspiration
  • The growing number of reports of FD&C Blue No.1 absorption from enteral feedings, the mitochondrial toxicity of this dye and related dyes and deaths attributed to dye absorption all suggest that the blue dye method is unsafe. It is a concern in patients with enhanced gut permeability.
  • Providers may implicate blue dye toxicity only in obvious cases and causes discoloration in the patient
  • Samples of serum and urine should be frozen and the FDA should be notified using the adverse reaction monitoring system
  • Evidence based methods that prevent aspiration, such as nonrecumbent positioning, should be used in all patients receiving enteral tube feeding.
Funding Source:
University/Hospital: Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, Meriter Hospital, Covenant Medical Center-Lakeside, Johns Hopkins University,Emory University
Reviewer Comments:
  • This review reported the caution of using blue dye in enteral feeding. The evidence of case reports are not very clear because of lack of data on clinical findings and histopathology reports of the autopsy. The case reports reported in this review is not providing clear findings it is based only on abstracts and three journal articles.
  • Even though it is not a systematic review, some of the clinical findings need more investigations. Further research on food blue dye for enteral feeding is important for the safety of the patients.
  • FDA toxicological studies are required to  study its physicochemical properties, dose effects, pathophysiological effects of the dye and its effects on different organs, biochemical and clinical findings
  • The 2002 Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients, JPEN2002; 26 (supplement) 39SA refer to the “lack of a truly reliable bedside method for detection of aspiration (which) makes study of this complication difficult.” No mention is made of blue dye.


Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? ???
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? ???
  4. Will the information, if true, require a change in practice? Yes
Validity Questions
  1. Was the question for the review clearly focused and appropriate? ???
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? No
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? No
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? No
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? No
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? ???
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? No
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? No
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? ???
  10. Was bias due to the review's funding or sponsorship unlikely? ???