Tuesday, January 02, 2007

Trial and Error


# 272


As evidenced by the wording of the WHO report, released yesterday in The Lancet on antiviral recommendations for the treatment of the H5N1 virus, doctors and scientists are working with a nearly crippling lack of direct knowledge of the efficacy of the treatments used thus far.


And this, I’m quite sure, is as frustrating to them as it is to each of us.


To date, nearly all of the avian flu victims have been in countries with less than ideal surveillance and treatment facilities. Patients show up generally, only after days of illness, often on death’s door before they see a doctor. Treatments are either too little, or too late. Autopsies are rarely performed, and so we are left with many unanswered questions.


It is very difficult to draw any conclusions of what might work based on the data we have so far.


The fact that a panel of 13 doctors and scientists were able to make a strong recommendation for the use of Oseltamevir (Tamiflu), based on admittedly weak evidence, is nothing less than remarkable. Getting a room full of doctors to agree on a standardized treatment for any given condition is difficult.


This panel deserves credit for making a difficult decision with such little direct evidence.


Whether Tamiflu, or Relenza, or even the M2 ion channel inhibitors prove to be effective against the H5N1 virus remains to be seen. These doctors and scientists made no claim that these drugs would work, only that they had the best chance of working of what we currently have available.


Human H5N1 infections have an extremely high mortality rate, and given that fact, it is reasonable to use medicines even if confidence in their ability to reduce the mortality and morbidity of the disease are low, as long as the downsides are acceptable.


As more patients contract this infection, and are treated, our knowledge will expand. Hopefully we will learn more, and develop better ways to combat it.


Like it or not, medicine is a moving target. Treatments that were considered `standard’ a few years ago have been abandoned today because we discovered that they either didn’t work, or did more harm than good. Sometimes, old treatments, once abandoned, are brought back, because we discovered they actually worked.


The classic example, known to every doctor who has been in practice more than 20 years, is that prior to 1986, a patient in cardiac arrest for more than a minute was automatically given 2 amps of sodium bicarbonate intravenously to correct acidosis.


Every doctor `knew’ you couldn’t cardiovert (defibrillate) an acidotic heart. So before attempting defibrillation, 2 amps of bicarb always went in.


This practice was removed from the protocol in 1986, after it was determined that the bicarb didn’t help, and possibly did some harm.


The doctors and paramedics (including myself) that used the old protocol weren’t bad or incompetent. They were simply using the best practice of the time, based on our understanding of human physiology and the pharmacology we had available.


The advent of paramedics, and advanced mobile life support units in the early 1970’s allowed doctors more opportunities to treat cardiac arrests than they had ever had before, and that helped advance our knowledge of what worked, and what didn’t.


And in just the same way, as more doctors, and more hospitals deal with the H5N1 infection, we will learn more. The earliest patients will be treated, by necessity, by trial and error.


It’s a lousy way to learn. But it’s the only way we have.


Wulfgang said...


Interesting summary you have on antiviral recommendations from the WHO. Recently, on Dec 18th, the US HHS released their updated status progress report on the National Strategy for Pandemic Influenza: Implementation Plan, and I don’t recall any mention of this subject in their report, so one has to wonder, who is really on top of their game here – maybe I just missed any mention of it. But, I suspect the Fed’s, as they are in so many other areas of pandemic planning, have defaulted to the states to develop their own priorities and guidelines for these medicines – which is probably all over the board, in the final analysis. I would expect to have seen similar published guidelines from the HHS and CDC, but maybe they’ve made so much progress, that it just isn’t apparent.

An actual pandemic situation to me is like a war strategy: I regard a pre-pandemic vaccine as the actual superior first line-of-defense, similar to sending in the Air Force and Navy, for a first strike attack. The neuraminidase inhibitors and adamantine drugs in my mind, are the boots-on-the-ground infantry foot soldiers who will be depended upon to defeat the H5N1 enemy, during an all out ground conflict.

So, the question you raise is a good one – what’s the real dosage to be used for oseltamivir ? Single, or double - how many foot soldiers do we use ?

Good question.


maryinhawaii said...

There is another little problem with oseltamivir....not enough of it. Not nearly. If a pandemic hits, most people will never get a chance for treatment at all. A second problem is that right now every time there is a suspect outbreak they give everyone who has been exposed and/or showing symptoms massive doses of tamiflu. Great,they survive if given early enough. How? It knocks down the virus' ability to replicate. This also, incidentally, makes it virtually impossible to find the virus in the tests they do, so everyone comes back "negative" and we all breathe a sigh of relief. If all those potentially false negatives were actually positive, we'd probably be in WHO phase 4 or 5 by.

FLA_MEDIC said...

Mary you bring up two serious problems with our antiviral stockpile. We only have enough right now to treat a very small percentage of the population, currently enough for 20 million people, assuming they each only need 10 pills (a big assumption). At best, that's enough to cover 6.6% of the nation.

Tamiflu resistance is another problem we may well face, if the use of tamiflu `blankets' fail to stop the virus at its source.

Basically we're facing a viral enemy with a gun with very few bullets in it.