Bolus Technique vs Drip Technique for DTPA chelation for GDD... and the general concept

This is a revisitation of subject matter from earlier blogs, with some expansion.

In brief terms, Gd was administered as a GBCA by power injection at a rate of 2 ml/sec in the vast majority of people, including GDD sufferers. Gd is power injected in the body at a fast rate to improve visualization of essentially all forms of disease, and to observe the normal capillary flow of organs.

.Substances that are toxic to the person, that are in part left behind, the retained material follow the pathway they were administered and also affected by the rate. I term this the mud-tracks. So for example an inhaled toxin, most of what is left behind is closely positioned within lung tissue. In the case of an iv administration, retained material is primarily in a perivascular location, mainly peri-capillary and peri-venules. Power-injection of a substance drives the material into the deep interstitial tissue, so power injection results in deposition around vessels but an additional dominant deposition in the deep interstitial tissue (AKA extracellular matrix {ECM} ). Gd distribution pattern is therefore unique among the heavy metals since almost all others enter the body by the digestive tract or inhalational.

Had the Gd been administered by drip technique, then drip infusion of DTPA would be a sufficient method of treatment, as the vast majority of the Gd in that situation would be perivascular in location. Note that both Iodine contrast and Gd contrast were originally administered by drip infusion, for CT and MRI respectively, Within a couple of years for Iodine, 1 year for Gd, this technique was realized to be a poor method, since tissues were not well enhanced, and especially cancers, so drip was rapidly abandoned in favor of power injection.

So, to chase down and remove Gd one has to emulate the manner of administration to capture the mud tracks of the retained metal. . Hence rapid injection is the most effective means, and hand bolus injection most often used.

Some practitioners have observed with drip technique that less Flare is generated, and hence based on this may be preferred. My theory why there is less Flare is that drip technique removes essentially just Gd along the vessel walls, and this is a location that generally does not result in patient symptoms, hence removal also does not result in symptoms. This however means that the most disease causing location of Gd is largely untouched. So I rarely use drip technique and rarely advise using it.

However, there are some critical issues. Bolus technique does generally require a concurrent steroid/ antihistamine approach. This is perfectly fine for the majority of people, a few not. Also since drip fundamentally results in less Flare, individuals especially sensitive to Gd may benefit from drip technique, after all some Gd removal is better than no Gd removal.

So circumstances where drip technique is advisable:

1. extreme sensitivity to Gd.

2. patient situations where steroids may pose more risk to the overall health of the patient. This would be individuals with active bacterial infection (I have never encountered this) or with active malignancy where steroids may diminish the host ability to fight the cancer (I have seen this).

Also, I have also posed the concept that over time, after a certain number of DTPA chelations, is that number 10, is it 20? the majority of the Gd in the soft tissue may now be from re-equilibration of Gd from bone, and not from the primary deposition from the GBCA injection. If it is re-equilibrated Gd, then it would not be deposited driven into the deep ECM, but likely most is then perivascular in location, that drip technique would adequately remove. This is not an unreasonable theory.

However, at the same time, starting at about the 5th chelation session, regardless if DTPA is administered by bolus technique, the Flare reaction starts to diminish substantially, so moving to a drip technique to reduce Flare may no longer be needed. The primary explanation for the lessening Flare is since a lot of Gd has already been removed, and thus there is less Gd to generate Flare. Possibly as well, using the above mentioned logic, with time more Gd is now re-equilibrated Gd in a perivascular location, and this intrinsically results in less Flare when removed.

So I prefer bolus technique. It removes the most symptom-generating Gd in the deep ECM. Also the use of steroids not only controls Flare, but I opine it also trains the immune system to diminish reacting to the presence of Gd, since steroids primarily work on calming down T cells.

A final note, a thoughtful patient proposed to me: how about comparing bolus and drip technique directly for Flare generation and for Gd removal This is an interesting concept, however... how to make a meaningful comparison? First off, the best comparison would be where you documented histologically where the Gd is located and how it changes over time. This would involve a large animal like a dog or a primate. So for me that's out, I prefer the scientific logic of an expert (me).

Secondly to look at Flare, since there is such an intrinsic heterogeneity of Flare anyways, a sufficient number of individuals would need to be studied. Also the timeline of which chelation session is done with each approach would have to be comparable.

So realistically an appropriate, meaningful study would be a crossover study involving at least 50 patients in each group, so 100 people. Cross-over would mean one group starting with drip, the other with bolus, then crossing over to the other technique. When to cross over? After each chelation? How many crossovers? Continuous cross over with alternating each approach each time? Should some cross overs be random? The subjects should be blinded, so both bolus DTPA arm, and drip DTPA arm would need to receive a bolus. The drip technique group would need a bolus of normal saline. The administrator also ideally should be blinded, so double blinded study. Suddenly now you have a $10 million study to compare bolus vs drip. I prefer my empirical reasoning, especially since I am relying on the strategy of administering the contrast to begin with- so I am using a knowledge of 2 billion doses of bolus technique iodine contrast and 600 million of blus technique of GBCA injection, and referencing it to the historic use of drip technique of 50 million doses of Iodine contrast (40-35 years ago) and 5 million of GBCA (25 years ago).

On the surface one may have some qualms of using empiric reasoning, even if it is by the world authority, but one would have to also be aware that essentially all use of all drugs is made largely on the basis of empiric reasoning, since testing strategies rigorously is exceedingly expensive.

So bolus technique is the best approach. BUT there are valid times to use a Drip technique..

Richard Semelka, MD