Doi:10.1016/j.homp.2005.01.002

Homeopathy (]]]]) ], ]]]–]]]r 2004 The Faculty of Homeopathy doi:10.1016/j.homp.2005.01.002, available online at ORIGINAL PAPER
Adjunctive homeopathic treatment in patients
with severe sepsis: a randomized, double-blind,
placebo-controlled trial in an intensive care unit
M Frass1,Ã, M Linkesch2, S Banyai2,3, G Resch1, C Dielacher2, T Lo¨bl2, C Endler1, M Haidvogl1, 1Ludwig Boltzmann Institute for Homeopathy, Graz, Austria 2II Department of Internal Medicine, University of Vienna, Vienna, Austria 4Department of Medical Computer Sciences, University of Vienna, Vienna, Austria Background: Mortality in patients with severe sepsis remains high despite the
development of several therapeutic strategies. The aim of this randomized, double-
blind, placebo-controlled trial was to evaluate whether homeopathy is able to influence
long-term outcome in critically ill patients suffering from severe sepsis.
Methods: Sixty-seven patients with severe sepsis received homeopathic treatment
(n ¼ 33) or placebo (n ¼ 34). Five globules in a potency of 200c were given at 12 h
interval during the stay at the intensive care unit. Survival after a 30 and 180 days was
recorded.
Results: Baseline characteristics including age, sex, BMI, prior conditions, APACHE II
score, signs of sepsis, number of organ failures, need for mechanical ventilation, need
for vasopressors or veno-venous hemofiltration, and laboratory parameters were not
significantly different between groups. On day 30, there was non-statistically
significantly trend of survival in favour of homeopathy (verum 81.8%, placebo 67.7%,
P ¼ 0.19). On day 180, survival was statistically significantly higher with verum
homeopathy (75.8% vs 50.0%, P ¼ 0.043). No adverse effects were observed.
Conclusions: Our data suggest that homeopathic treatment may be an useful
additional therapeutic measure with a long-term benefit for severely septic patients
admitted to the intensive care unit. A constraint to wider application of this method is
the limited number of trained homeopaths.
Homeopathy (]]]]) ], ]]]–]]].
Keywords: APACHE II; homeopathy; critically ill patients; intensive care unit; sepsis;
survival; double-blind; randomized prospective; placebo-controlled study
during the last decades. Recent guidelinesrecommend use of goal directed therapy, low-tidal ventilation, The incidence of severe sepsis is 70,000 to 300,000 administration of recombinant Protein C (aPC), close UNCORRECTED PROOF
monitoring of blood glucose with a target value of associated with mortality rates ranging from 40% to 80–100 mg/dl, and administration of hydrocortisone.
90%.Several new therapeutic approaches have failed Despite these therapeutic strategies, mortality hasremained almost unchanged during the last few years.
Homeopathic medicine has been used for about two ÃCorrespondence: M Frass, Ludwig Boltzmann Institute for centuries. Several studies describe its superiority above Homeopathy, Duerergasse 4, A 8010 Graz, Austria.
placebo.Experimental studies demonstrate the E-mail: michael.frass@kabsi.atReceived 3 August 2004; revised 11 January 2005; accepted 26 effect of high dilutionseven beyond Avogadro’s number.There are several case reports on the and after administration of the globules, no oral fluid or food intake or oral hygiene was allowed to avoid patients.We initiated this study to investigate the any potential interference with the globules. The effect of homeopathy on the outcome of critically ill homeopathic doctors were free to decide which patients. The aim of this prospective, randomized, homeopathic medicine should be applied. All medi- double-blind, placebo-controlled trial was to evaluate cines were prepared as a 200c (Rote Krebs Apotheke, at two time points (30 and 180 days) whether homeopathy can influence outcome in patients suffer- Patients were followed for 180 days after the start of treatment unless death occurred earlier. Base-line characteristics including demographic information and information on pre-existing conditions, organ The Ethical Committee of the University of Vienna function, markers of disease severity (APACHE II), approved the study. Seventy patients admitted to a and infection were assessed within the 24 h before Medical Intensive Care Unit (MICU) of the University starting treatment. Adverse effects were recorded of Vienna were assessed for eligibility, all were included in the study. All were randomized and treated, threehad to be excluded because of incomplete data, all of the latter survived. Written informed consent was obtained from all participants or their authorized representatives. The criteria for severe sepsis of Bone et The evaluated end point was death within 180 days.
al. were used.Patients with a known or suspected Statistical analysis was done at the Department of infection on the basis of clinical data at the time of Medical Computer Sciences, University of Vienna, screening and three or more signs of systemic using the SAS software package (Statistical Analysis System, SAS Institute Inc., Cary, NC). All statistical analyses were done before breaking the randomization code. Statistical analysis of the data was performed X12 G/L) and sepsis-induced dysfunction of at least two organ systems that lasted no longer than 48 h using Kruskal–Wallis Test for comparing the two were included. Treatment with homeopathy or placebo started within 48 h after the patients met the inclusion Within 24 h after meeting the criteria for sepsis, all No adverse effects were observed in either group.
eligible patients were sequentially randomized into two Baseline demographic characteristics including age, groups, receiving either the homeopathic medicine or sex, weight, height, and body mass index (BMI) as well placebo, according to a computer-generated code. An as prior conditions were similar between the two independent physician not involved into the study held groups (). Baseline clinical indices including the code. A person not involved in the decision and/or APACHE II score and signs of inflammation, the 101 application process for the study prepared the medica- number of organ failures, the need for mechanical ventilation, vasopressor support, veno-venous pump- 103 driven haemofiltration and positive blood cultures Start of therapy and sublingual administration of the were not significantly different between groups. Only 105 heart rate exceeding 90 beats/min differed significantly, Within 12 h after meeting the criteria for sepsis, occurring more frequently in the placebo group 107 homeopathic treatment started. A person not involved in the randomization process poured five globules into On day 30, survival showed a non-statistically 109 UNCORRECTED PROOF
the tube containing the globules, then the significant trend in favour of homeopathy (verum globules were poured from the lid directly underneath 81.8%, placebo 67.7%, P ¼ 0.19; ). On day the patient’s tongue. In patients with endotracheal 180, survival was statistically significantly higher in the tubes, the globules were administered just aside the verum group 1 (verum 75.8%, placebo 50.0%, 112 endotracheal tube. Globules were given twice daily at P ¼ 0.043; ). The most frequently prescribed an interval of 12 h until sepsis was resolved or until homeopathic medicines were Apis mellifica, Arsenicum 113 death. Patients were treated for the duration of their album, Baptisia, Bryonia, Carbo vegetabilis, Crotalus stay in the intensive care unit. Treatment stopped on horridus, Lachesis muta, Lycopodium clavatum, Phos- 114 transfer to the general ward. Fifteen minutes before ill patients. Short-time survival showed a non-statisti-cally significant trend in favour of homeopathy; Our data suggest that adjunctive homeopathic however, this may be due to the relatively small sample treatment may be beneficial for the survival of critically size. The lack of adverse effects is an important advantage of homeopathic treatment. As a furtheradvantage, 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 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 The mortality of severe sepsis, defined as sepsis with at least one organ failure, and septic shock, defined as hypotension not reversible by fluid resuscitation and associated with organ dysfunction or hypoperfusion abnormalities, remains very high despite increased Guidelines have been developed in an endeavour to improve outcome.Resuscitation of a patient in severe sepsis or sepsis-induced tissue hypoperfusion should begin as soon as the syndrome is recognized and should not be delayed pending ICU admission. During UNCORRECTED PROOF
the first 6 h, the goals should include all of the promptly. Intravenous antibiotic therapy should be following: central venous pressure 8–12 mmHg; mean started within the first hour of recognition of severe arterial pressure 465 mmHg; urine output 40.5 ml/ sepsis, after appropriate cultures have been obtained.
kg/h; and central venous or mixed venous oxygen Establishing vascular access and initiating aggressive saturation 470%. Early therapy directed towards fluid resuscitation is the first priority when managing patients with severe sepsis or septic shock. The Appropriate cultures should always be obtained antimicrobial regimen should always be reassessed before antimicrobial therapy is initiatedand tests after 48–72 h on the basis of microbiological and should be done as soon as possible to determine the clinical data with the aim of using a narrow-spectrum source of the infection and the causative organism.
antibiotic to prevent the development of resistance, to Imaging studies such as ultrasound and/or bedside reduce toxicity, and to reduce costs. Fluid challenge in computer tomography should be performed. Sources patients with suspected hypovolemia (suspected inade- of infection requiring drainage should be identified quate arterial circulation) may be given over 30 minand repeated based on response (increase in blood pressure and urine output) and tolerance (evidence of intravascular volume overload). If appropriate fluid challenge fails to restore adequate blood pressure and organ perfusion, administration with vasopressor Intravenous corticosteroids are recommended in patients with septic shock who, despite adequate fluid replacement, require vasopressor therapy to maintain Most often used homeopathic medicines and indications Anxiety, restlessnessCachectic appearance UNCORRECTED PROOF
adequate blood pressure.Recombinant activated 8 Frass M. Durch A¨hnliches Heilen—Homo¨opathie in O¨ster- protein C (rhAPC) is recommended in patients at high reich, 2nd edn. Peter Ko¨nig, Orac Verlag, Austria, in press.
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