I have already posted why your argument is flawed but it got deleted. all I can say, is you need to post more material aspects rather than abstract conclusions. Researchers all day long can say why they feel there are unknown risks with blue dye but as long as it is listed as recognized with safe limits by the FDA and IPCI stays within those limits, one will have a very difficult time to argue it cant be used.
The recommended daily limits are irrelevant because there are no supporting human studies. Those numbers are extrapolated from animal models, and healthy animals at that. Plus, many of the known deaths associated with blue dye use in gastric-tube nutritional fluids have been under the daily limits. The risk is in conditions of increased gut permeability, such as sepsis, IBS or sprue- all of which are common conditions and will be seen in Rexista users with regularity. There are no human studies that confirm the safety of concentrated doses of blue #1 in any person, but especially in those high-risk conditions. IMO, it would be unethical to try and design one because of the known risk of systemic absorption and known fact that blue #1 readily passes through the blood-brain barrier. Remember, blue #1 is a nasty biomolecule that actively inhibits aerobic energy processes in vitro. It directly inhibits mitochondrial oxygen uptake, and any cell exposed to high enough concentration of blue dye is unable to convert oxygen to energy.
These are not "unknown risks." These risks are well-known. I hope you'll take a minute to consider what Dr. Malony did in the paper I cited last week (see below). He personally is responsible for saving hundreds, maybe thousands, of lives. He was lead author on the New England Journal article from 2000 that cited the first two blue-skin deaths. There were a few subsequent reports, and he continued to hear about similar cases from colleagues. He suspected it was widespread but under-reported. He also suspected it was not a good idea to pump a coal-tar derived mitochondrial toxin down the gullets of sick people, and when they turn blue and die then maybe its not a coincidence. He knew of four blue deaths, but thought there must be more. So he sent out 100 surveys, 50 to intensivists and 50 to hospital dietitians. In doing this, he discovered 17 more cases, including 5 additional deaths, none of which had been reported to FDA. He facilitated all the cases being formally reported to the FDA, and subsequent to that, FDA issued the famous Advisory about Blue Dye #1. After the Advisory, we stopped putting blue dye in tube feeds.
To put it in perspective, he sent out just 100 surveys, which was 2.3% of dietitians and .5% of critical care docs, and this identified 5 deaths. You can't formally extrapolate from that, but it is not hard to believe that surveys sent to 100% of dietitians and CC docs could have identified hundreds of blue deaths. Dr. Maloney is hero-smart. He recognized a problem with a toxic substance, and he figured out a way to expose it and bring it to the attention of the FDA in a way they couldn't ignore. He personally prevented hundreds of deaths of people who otherwise would have been poisoned by blue dye #1. And now here we are, 14 years later and about to repeat the same failed experiment. Unless, just maybe, there's another doc out there who knows enough to put 2 + 2 together and put it in the face of the FDA in a way they can't ignore.
At our request, the 17 detailed cases identified in our survey were subsequently reported to the FDA by providers with our assistance, and were reviewed by the FDA preparatory to the drafting of their Public Health Advisory in September 2003 regarding potential hazards of this practice [40].
FDA Public Health Advisory: Subject: Reports of Blue Discoloration and Death in Patients Receiving Enteral Feedings Tinted With The Dye, FD&C Blue No. 1
September 29, 2003
Dear Health Care Professional:
The Food and Drug Administration (FDA) would like you to be aware of several reports of toxicity, including death, temporally associated with the use of FD&C Blue No. 1 (Blue 1) in enteral feeding solutions. In these reports, Blue 1 was intended to help in the detection and/or monitoring of pulmonary aspiration in patients being fed by an enteral feeding tube. Reported episodes were manifested by blue discoloration of the skin, urine, feces, or serum and some were associated with serious complications such as refractory hypotension, metabolic acidosis and death. Case reports indicate that seriously ill patients, particularly those with a likely increase in gut permeability (e.g., patients with sepsis), may be at greater risk for these complications. Because these events were reported voluntarily from a population of unknown size, it is not possible to establish the incidence of these episodes.
A causal relationship between systemic absorption of Blue 1 and the reported serious and life-threatening patient outcomes (including death) has not been definitively established. Indeed, it would be very difficult to establish a clear, causal relationship in the setting of complex medical issues often seen in patients receiving feedings via enteral tubes. However, in vitro evidence that Blue 1 can be a mitochondrial toxin lends plausibility to the idea that Blue 1 could cause these kinds of serious adverse effects if significant or persistent serum levels of the dye were to occur. From the reports, it appears that neither the concentration nor the total amount of Blue 1 used in the enteral feeding solutions was unusually high compared to other patients in whom no toxicity was observed. Thus, if there is a causal relationship between the dye and the serious outcomes, there could be underlying patient-related factor(s) that allow significant absorption of Blue 1 in some enterally fed patients.
While we are not able at this time to establish a cause-and-effect relationship between the reported serious and life-threatening patient outcomes and the use of the dye, nonetheless, given the seriousness of the potential complications, we believe health care professionals should be notified of these reports.
As background, FD&C Blue No. 1 is a water-soluble dye allowed by the FDA for use in foods, drugs and cosmetics, based on numerous studies in animals. Data from life-exposure animal studies supports an ADI (acceptable daily intake) of Blue 1 of 12.0 milligrams/kilogram body weight/day. The dye is batch certified by the FDA and is widely used in food products (candies, confections, beverages, etc.) in amounts consistent with good manufacturing practices (generally at parts per million). There have been no reports of toxicity associated with this general use. Toxicity has been reported only in association with Blue 1 tinting of enteral feedings, intended as a means of visually detecting pulmonary aspiration. This use, although a common practice for nearly 30 years, has never been evaluated by the FDA for safety or utility (i.e., there has been no evaluation by the FDA of the sensitivity and specificity of its use in this manner).
SUMMARY OF REPORTS
As of September, 2003, the FDA is aware of 20 cases from the scientific literature or in FDA post-marketing adverse event reports associating the use of blue dye in tube feedings with blue discoloration of body fluids and skin, as well as more serious complications. There have been 12 reported deaths and one case with an unknown outcome.
In more than 75% of all reported cases, patients had a reported history of sepsis (and therefore likely altered gut permeability) before or during systemic absorption of Blue 1.
Time of onset of toxicity from first use of Blue 1 varied from several hours to 20 days of continuous use in enteral feedings.
At this time, the FDA believes practitioners should be aware of the following points:
Use of Blue 1-tinted enteral feedings for detecting aspiration has been associated with several serious adverse events, including death, although a direct causal relationship has not been definitely established.
The safety of Blue 1-tinted enteral feedings for detecting aspiration has not been documented.
Based on the reports received to date, patients at risk for increased intestinal permeability, which includes those with sepsis, burns, trauma, shock, surgical interventions, renal failure, celiac sprue, or inflammatory bowel disease, appear to be at increased risk of absorbing Blue 1 from tinted enteral feedings.
In addition to the possibility of systemic toxicity, Blue 1-tinted enteral feedings may interfere with diagnostic stool examinations, such as the hemoccult test.
Other blue dyes, such as methylene blue and FD&C Blue No. 2, may have similar if not greater toxicity potential than Blue 1 and would not be appropriate replacements.
The FDA will continue to closely monitor reports for additional events. We encourage all health professionals to report any serious adverse events occurring with Blue 1-tinted enteral feedings to the FDA's MedWatch program at 1-800-FDA-1088 tel, 1-800-FDA-0178 fax, or online at www.fda.gov/medwatch/. Additional information on color additives, in general, may be accessed at http://www.cfsan.fda.gov/~dms/col-toc.html Sincerely yours,
David W. K. Acheson, MD Chief Medical Officer Center for Food Safety and Applied Nutrition Food and Drug Administration
References Systemic absorption of food dye in patients with sepsis. Maloney JP, Halbower AC, Fouty BF, Fagan KA, Balasubramaniam V, Pike AW, Fennessey PV, Moss M. N Engl J Med 2000 Oct 5;343(14):1047-8 Food Dye Use in Enteral Feedings: A Review and a Call for a Moratorium. Maloney JP, Ryan TA, Brasel KJ, Binion DG, Johnson DR, Halbower AC, Frankel EH, Nyffeler M, Moss M. Nutrition in Clinical Practice 2002 Jun 17: 168-181 Risk factors for aspiration. Metheny NA. JPEN J Parenter Enteral Nutr 2002 Nov-Dec;26(6 Suppl):S26-31; discussionS32-3 North American Summit on Aspiration in the Critically Ill Patient: consensus statement.McClave SA, DeMeo MT, DeLegge MH, DiSario JA, Heyland DK, Maloney JP, Metheny NA, Moore FA, Scolapio JS, Spain DA, Zaloga GP. JPEN J Parenter Enteral Nutr 2002 Nov-Dec;26(6 Suppl):S80-5 Pharmokinetic study of biliary secretion. II. Comparison of excretion behavior in triphenylmethane dyes. Iga T, Awazu S, Nogami H. Chem Pharm Bull (Tokyo) 1971, 19:273-81 A survey of bedside methods used to detect pulmonary aspiration of enteral formula in intubated tube-fed patients. Metheny NA, Myra AA, Wunderlich RJ. Am J Crit Care Med 1999 May;8(3):160-7 Comparison of blue dye visualization and glucose oxidase test strip methods for detecting pulmonary aspiration of enteral feedings in intubated adults. Potts RG, Zaroukian MH, Guerrero PA, Baker CD. Chest 1993 Jan;103(1):117-21 Efficacy of dye-stained enteral formula in detecting pulmonary aspiration. Metheny NA, Dahms TE, Stewart BJ, Stone KS, Edwards SJ, Defer JE, Clouse RE. Chest 2002 Jul;122(1):276-81 Effect of organic synthetic food colours on mitochondrial respiration. Reyes FG, Valim MF, Vercesi AE. Food Addit Contam 1996 Jan;13(1):5-11
Well you placed your life on credit and your lovin' days are done, The checks you signed with love and kisses later come back signed insufficient funds.
Funkadelic - Can You Get To That Maggot Brain, 1971
