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Homeopathy and Sepsis

ResearchBlogging.orgIt had once been suggested in the comments section of the blog that homeopathy is useful in the treatment of diseases that are not self limited. Homeopathy is effective therapy for diseases that do not get better on their own, that homeopathy has a real effect on real diseases.

One example given was for the treatment of sepsis.

“Frass M, Linkesch, M, Banjya, S, et al. Adjunctive homeopathic treatment in patients with severe sepsis: a randomized, double-blind, placebo-controlled trial in an intensive care unit. Homeopathy 2005:94;75–80. At a University of Vienna hospital, 70 patients with severe sepsis were enrolled in a randomized double-blind, placebo-controlled clinical trial, measuring survival rates at 30 days and at 180 days. Those patients given a homeopathic medicine were prescribed it in the 200C potency only (in 12 hour intervals during their hospital stay). The survival rate at day 30 was 81.8% for homeopathic patients and 67.7% for those given a placebo. At day 180, 75.8% of homeopathic patients survived and only 50.0% of the placebo patients survived (p=0.043). One patient was saved for every four who were treated.”

I am, as I have mentioned before, but I mention again for those who might be new to the blog, an Infectious Disease physician. My job is to diagnosis and treat infectious diseases and sepsis is up there at the top of the list of diseases I take of. Sepsis butters my bread, and I consider myself knowledgeable about sepsis.

And I had never heard of this study. A therapy that saves one in four patients would be an astounding intervention for an often fatal disease, and I have never come across it all my reading. Maybe its because there are so many articles and so little time. Maybe it hasn’t been publicized. Or maybe it is a lousy article.

Sepsis is not a single disease, but a syndrome. Bacteria invade an organ, like the lung to cause pneumonia or the kidney to cause pyelonephritis. Then the bacteria enter the blood stream and cause a massive inflammatory response that results in most or all the patients organs shuting down and they die. Rapidly. The inflammatory response in sepsis is mind numbingly complicated. The medical interventions used to treat sepsis are equally complicated and multifaceted.

Sepsis is as non-self-limited a disease as one could want. Untreated, almost everyone dies. Under the best current treatment, a minimum of 30% die, but depending on the underlying medical conditions and the infecting organisms, some causes of sepsis have almost 100% mortality rates. Any therapeutic intervention that decreases the mortality of this syndrome, even a little, would be welcomed.

So why I had never heard of this study, which decreased mortality a whopping 25%? That is an impressive result, if true. If true.

Now I will admit my bias is that the underlying premise for homeopathy is ludicrous, so I would not expect any homeopathic nostrum to be effective. But who knows, maybe this is the study that will revolutionize all of medicine and prove that homeopathy alters the course of one of the most difficult to treat syndromes in medicine.

So lets go over the article and see if there is a there there.

70 patients admitted to the ICU at the University of Vienna with sepsis were included in the study.

The criteria for sepsis were reasonable:

“Patients with a known or suspected infection on the basis of clinical data at the time of screening and three or more signs of systemic inflammation (temperature <= 36 or >= 38 1C, respiratory rate  >= 20/min, heart rate >= 90/min, leukocytes  >= 12 G/L) and sepsis-induced dysfunction of at least two organ systems that lasted no longer than 48 h were included.”

The two groups were well matched by clinical criteria. Same number of underlying diseases, same distribution of infections and infecting organisms. So far, so good.

Then in a double blind, placebo trial,  patients received, within 48 hours of admission to the ICU, either placebo or an individualized homeopathic nostrum.

As I gather from the study, one homeopathic practitioner, but perhaps more, evaluated the patient and determined which nostrum best suited the patient. It was then dispensed by another who did not know if they were dispensing placebo or homeopathic nostrum. All the nostrums were 200C.  That’s 1 part in

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The known universe is not large enough to dilute one atom to that degree.

They were then given 5 globules of either placebo or the homeopathic nostrum twice a day until death or resolution of the sepsis.

What were the nostrums given? Here are the nostrums, with the indication for which it was given.

Apis mellifica: Oedema, Extreme dyspnoea.

Arsenicu malbum: Weakness, exhaustion Cardiovascular compromise, Anxiety, restlessness Cachectic appearance.

Baptisia: ARDS, Sepsis, Hot skin.

Belladonna: High temperature with sweat, Red discolouration, face.

Bryonia: Pneumonia, esp. right lung, Stitching pain in chest.

Carbo vegetabilis: Respiratory insufficiency, ARDS.

Crotalus horridus: Purpura haemorrhagica, Haemorrhages.

Lachesis muta: Septic shock, Haemorrhage High temperature, Embolism, Discolouration blue, purple.

Lycopodium clavatum: Fever, afternoon, Distension, abdominal.

Phosphorus: Pneumonia, esp. right lower lobe, Haemorrhage, Purpura haemorrhagica.

Pyrogenium: Septic fever, Offensive odour.

It is amazing, given the multitudinous signs and symptoms that you have to recognize and treat in sepsis, that the homeopath would choose offensive odor as the basis of therapy. Or hot skin. Or anxiety.

Yes, E. coli is in your blood stream, your lungs and kidneys are failing, your blood pressure cannot be maintained, you are on a respirator and dialysis and the most important symptom upon which to base the life saving therapy is offensive odor. It suggests a profound intellectual ignorance in the understanding of a severe infection.

There are several precepts underlying homeopathy. One, of course, is like cures like.

Lachesis muta is snake venom and, as best as I can tell, does not mimic septic shock. Septic shock in no way resembles death from snake venom except at the most superficial level. Carbo vegetalis is vegetable charcoal. It, as best as I can tell, does not mimic ARDS. Baptisia is derived from Wild indigo plant, and as best I can tell, when ingested does not mimic ARDS.

Prior to this study, I can find no references that ANY of these nostrums were ever used for these symptoms before, probably because without modern medical therapy everyone died before they could be tested.

Also key to homeopathic nostrums is the concept of provings. The nostrums are tested on healthy people to insure it causes the symptoms it allegedly treats. I cannot find that any of these remedies were tested with proving’s and, given the severity of the symptoms of sepsis, a proving would be fatal.

As best I can tell from perusing the homeopathic writings, there is little if any homeopathic justification (within  their therapeutic paradigm) for using these remedies under these circumstances. One wonders whether the IRB at the University of Vienna knew not only that the it was an experiment to see if homeopathy was effective, but that each remedy was being tried for the first time for these indications.

The one feature about all these nostrums is how they ignore the underlying problem and only treat the symptoms, evidently with a complete disregard of the underlying pathophysiology of sepsis.  Sepsis is fundamentally due to infections in the blood. If you don’t treat the infection, you do nothing.  The basis of chosing a homeopathic nostrum in sepsis is worse than applying a band-aid to a multiple trauma victim.

All patients were receiving standard care in addition to homeopathic nostrums. But it suggests a certain intellectual bankruptcy that when someone is admitted with bacteria in their blood stream and all the organs shutting down, actively trying to die, that the practitioner focuses on stitching pain in the chest as the diagnostic sign of importance in choosing an intervention.

The study had two end points: 30 day mortality and 180 day mortality.

30 day mortality is a standard endpoint in sepsis studies.

In this study there was a not a significant difference in 30 day mortality between the placebo and treatment groups (verum 81.8%, placebo 67.7%, P = 0.19), although the percentages look markedly different. Given the small numbers of patients in each wing of the study, I would expect insignificant differences between the two groups to show up looking greater than they are. A difference in one or two deaths would make a huge difference in the percentages. One more death in the placebo and one less in the homeopathic group and the both would be in the 70’s. With a mere 32 patients in each group, there is an insufficient number of patients to find any real significant differences. Small numbers of patients are much more likely to show spurious, random results that are clinically insignificant even if statistically significant.

Then the study becomes risible.

People die from sepsis. They die in the first day or so from the acute infection. They come in too sick to be saved. They die in the first week or so from progressive multi-organ system failure. They die in the first month from complications of medical care or underlying medical diseases. But if they make it to 30 days, they made it. If they die, it is usually not related to the sepsis.

Sepsis is, above all, a transient and completely reversible process. Once the bacteria are killed off and the immune system mops up the endotoxins, there is no disease left. The patient is cured; the disease eradicated. No further disease  pathophysiology is present. It is not like other processes, for example coronary artery disease, where the underlying disease persists.

180 days. 6 months. To think that a few days of any therapy for sepsis is going to make a difference in mortality at six months is ludicrous. It would rely upon an understanding of causality and the pathophysiology of sepsis the elude me. How a treatment of sepsis for a few days leads to a decrease in mortality months later beggars the imagination.

But that is the endpoint and they found a significant difference for mortality at 180 days.

“On day 180, survival was statistically significantly higher with verum homeopathy (75.8% vs 50.0%, P = 0.043). “

Most studies use 0.05 as the point where it is statistically significant. A p = 0.05 means that the odds are 1 in 20, or 5 % that the results are not correlated. Statistically significant does not mean clinically significant and also does not necessarily mean real. With small numbers in a trial, random variation can look significant.  A change of one death in each group would have made the p value no longer significant.

And p value is not all that significant. Why did they die? Not known. Why 6 months later as an end point? Not known. Why did homeopathy lead to an increased survival at six months, which if really true would be an important advance in sepsis? Not even hinted at in the discussion. Somehow, a few days of a 200C homeopathyic nostrum exerted some powerful medical effect on their offensive odour, increasing their chance of survival six months later.

In comparison, the biggest and best study for sepsis was the activated protein C study in the NEJM in 2001.

“A total of 1690 randomized patients were treated (840 in the placebo group and 850 in the drotrecogin alfa activated group). The mortality rate was 30.8 percent in the placebo group and 24.7 percent in the drotrecogin alfa activated group. On the basis of the prospectively defined primary analysis, treatment with drotrecogin alfa activated was associated with a reduction in the relative risk of death of 19.4 percent (95 percent confidence interval, 6.6 to 30.5) and an absolute reduction in the risk of death of 6.1 percent (P=0.005).”

This huge, multicenter study it altered how patients with severe sepsis are treated.

Note the smaller difference in effect and a much greater p value.

And they included the morality curves over time:

The discussion is of interest in that only two paragraphs are devoted to the study, mostly to comment that there are not enough homeopaths to provide the needed care for septic patient.

“Our data suggest that adjunctive homeopathic treatment may be beneficial for the survival of critically ill patients. Short-time survival showed a non-statistically significant trend in favour of homeopathy; however, this may be due to the relatively small sample size. The lack of adverse effects is an important advantage of homeopathic treatment. As a further advantage, there is no interference with traditional treatment. Dosing via the oral route is easy and possible also in intubated patients orally and patients with oral or nasal feeding tubes. Furthermore, homeopathic medicines are low cost. One constraint is the small number of trained homeopathic doctors available in this setting.

Confounding factors include that placebo patients were more seriously affected in terms of heart rate and leukocyte count. However, there was no significant difference in the means of these variables. All patients received antibiotic therapy. “

Whether it was appropriate antibiotic therapy we are not told, but why why why did it work? No thoughts from the authors.

The  rest of the discussion is a superficial tutorial on the various real ways to treat sepsis. I am guessing the average reader of Homeopathy has no understanding of sepsis, and  probably no real experience treating the disease.

Its almost as if they knew that their result was bogus.

Does homeopathy increase survival in sepsis? Only if you think that a sip of water today will decrease your chance of dying in 6 months.

This is not a lousy study; it is a joke.

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REFERENCES:

1. FRASS, M., LINKESCH, M., BANYAI, S., RESCH, G., DIELACHER, C., LOBL, T., ENDLER, C., HAIDVOGL, M., MUCHITSCH, I., & SCHUSTER, E. (2005). Adjunctive homeopathic treatment in patients with severe sepsis: a randomized, double-blind, placebo-controlled trial in an intensive care unit Homeopathy, 94 (2), 75-80 DOI: 10.1016/j.homp.2005.01.002

2. Gordon R. Bernard, Jean-Louis Vincent, Pierre-Francois Laterre, Steven P. LaRosa, Jean-Francois Dhainaut, Angel Lopez-Rodriguez, Jay S. Steingrub, Gary E. Garber, Jeffrey D. Helterbrand, E. Wesley Ely, & Charles J. Fisher (2001). Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis NEJM, 344 (10), 699-709

Posted in: Clinical Trials, Homeopathy

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