Adjunctive homeopathic treatment in patients with severe sepsis: a randomized, double-blind, placebo-controlled trial in an intensive care unit

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available online at Adjunctive homeopathic treatment in patientswith severe sepsis: a randomized, double-blind,placebo-controlled trial in an intensive care unit* M M , S BanG Resch, C T L€, C EndlerM HaidvoglI and E Schuster 1Ludwig Boltzmann Institute for Homeopathy, Graz, Austria 2II Department of Internal Medicine, University of Vienna, Vienna, Austria 3Cantonal Hospital of Lucerne, Switzerland 4Department of Medical Computer Sciences, University of Vienna, Vienna, Austria Mortality in patients with severe sepsis remains high despite the develop- ment of several therapeutic strategies. The aim of this randomized, double-blind, pla-cebo-controlled trial was to evaluate whether homeopathy is able to influence long-term outcome in critically ill patients suffering from severe sepsis.
Methods: Seventy patients with severe sepsis received homeopathic treatment (n=35) or placebo (n=35). Five globules in a potency of 200c were given at 12 h interval duringthe stay at the intensive care unit. Survival after a 30 and 180 days was recorded.
Results: Three patients (2 homeopathy, 1 placebo) were excluded from the analyses be- cause of incomplete data. All these patients survived. Baseline characteristics includingage, 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 (verum81.8%, placebo 67.7%, P=0.19). On day 180, survival was statistically significantly higherwith verum homeopathy (75.8% vs 50.0%, P=0.043). No adverse effects were observed.
Conclusions: Our data suggest that homeopathic treatment may be an useful addi- tional therapeutic measure with a long-term benefit for severely septic patients admit-ted to the intensive care unit. A constraint to wider application of this method is thelimited number of trained homeopaths.
Keywords: APACHE II; homeopathy; critically ill patients; intensive care unit; sepsis;survival; double-blind; randomized prospective; placebo-controlled study The incidence of severe sepsis is 70,000 to 300,000 patients in the United States each year.Septic shock is associated with mortality rates ranging from 40% to Several new therapeutic approaches have failed during the last decades. Recentguidelirecommend use of goal directed therapy, low-tidal ventilation, administration of recombinant Protein C (aPC),close monitoring of blood glucose with a target value of 80e100 mg/dl, and administration of hydrocortisone. Despite thesetherapeutic strategies, mortality has remained almost unchanged during the last few years.
*Correspondence: M Frass, Ludwig Boltzmann Institute for Homeopathy, Duerergasse 4, A 8010 Graz, Austria.
E-mail: [email protected] *This article is a reprint of a previously published article. For citation purposes, please use the original publication details; Homp 2005; 94:75e80.
Received 3 August 2004; revised 11 January 2005; accepted 26 January 2005 Homeopathic medicine has been used for about two centuries. Several studies describe its superiority above placebo.
Experimental studies demonstrate the effect of high dilutionseven beyond Avogadro’s number.There are several case re-ports on the beneficial effect of homeopathy in critically ill patients.We initiated this study to investigate the effect of ho-meopathy on the outcome of critically ill patients. The aim of this prospective, randomized, double-blind, placebo-controlledtrial was to evaluate at two time points (30 and 180 days) whether homeopathy can influence outcome in patients sufferingfrom severe sepsis.
The Ethical Committee of the University of Vienna approved the study. Seventy patients admitted to a Medical Intensive Care Unit (MICU) of the University of Vienna were assessed for eligibility, all were included in the study. All were random-ized and treated, three had to be excluded because of incomplete data, all of the latter survived. Written informed consent wasobtained from all participants or their authorized representatives. The criteria for severe sepsis of Bone et al. were Pa-tients with a known or suspected infection on the basis of clinical data at the time of screening and three or more signs ofsystemic inflammation (temperature #36 or P38 C, respiratory rate P20/min, heart rate P90/min, leukocytes #4P12 G/L) and sepsis-induced dysfunction of at least two organ systems that lasted no longer than 48 h were included.
Treatment with homeopathy or placebo started within 48 h after the patients met the inclusion criteria ().
Within 24 h after meeting the criteria for sepsis, all eligible patients were sequentially randomized into two groups, receiv- ing either the homeopathic medicine or placebo, according to a computer-generated code provided by a member of the De-partment of Medical Computer Sciences. An independent physician not involved into the study held the code. A person notinvolved in the decision and/or application process for the study prepared the medication for each patient.
Start of therapy and sublingual administration of the globules Within 12 h after meeting the criteria for sepsis, homeopathic treatment started. A person not involved in the randomization process poured five globules into the lid of the tube containing the globules, then the globules were poured from the lid directlyunderneath the patient’s tongue. In patients with endotracheal tubes, the globules were administered just aside the endotra-cheal tube. Globules were given twice daily at an interval of 12 h until sepsis was resolved or until death. Patients were treatedfor the duration of their stay in the intensive care unit. Treatment stopped on transfer to the general ward. Fifteen minutesbefore and after administration of the globules, no oral fluid or food intake or oral hygiene was allowed to avoid any potentialinterference with the globules. The homeopathic doctors were free to decide which homeopathic medicine should be applied.
All medicines were prepared as a 200c (Rote Krebs Apotheke, Vienna, Austria).
Patients were followed for 180 days after the start of treatment unless death occurred earlier. Base-line characteristics in- cluding demographic information and information on pre-existing conditions, organ function, markers of disease severity(APACHE II),and infection were assessed within the 24 h before starting treatment. Adverse effects were recorded duringthe treatment period.
Figure 1 Flow of patients through the study.
Table 1 Baseline demographic characteristics The evaluated end point was death within 180 days. Statistical analysis was done at the Department of Medical Computer Sciences, University of Vienna, 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 usingKruskaleWallis Test for comparing the two groups.
No adverse effects were observed in either group. Baseline demographic characteristics including age, sex, weight, height, and body mass index (BMI) as well as prior conditions were similar between the two groups ). Baseline clinical in-dices including APACHE II score and signs of inflammation, the number of organ failures, the need for mechanical ventila-tion, vasopressor support, veno-venous pump-driven haemofiltration and positive blood cultures were not significantlydifferent between groups. Only heart rate exceeding 90 beats/min differed significantly, occurring more frequently in the pla-cebo group (P=0.033; On day 30, survival showed a non-statistically significant trend in favour of homeopathy (verum 81.8%, placebo 67.7%, P=0.19; ). On day 180, survival was statistically significantly higher in the verum group 1 (verum 75.8%, placebo50.0%, P=0.043; ). The most frequently prescribed homeopathic medicines were Apis mellifica, Arsenicum album,Baptisia, Bryonia, Carbo vegetabilis, Crotalus horridus, Lachesis muta, Lycopodium clavatum, Phosphorus, and Pyrogenium( 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 relativelysmall 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 patientsorally and patients with oral or nasal feeding tubes. Furthermore, homeopathic medicines are low cost. One constraint isthe 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.
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 highdespite increased efforts in intensive care Guidelines have been developed in an endeavour to improve outcomeResuscitation 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 ICUadmission. During the first 6 h, the goals should include all of the following: central venous pressure 8e12 mmHg; mean ar-terial pressure >65 mmHg; urine output >0.5 ml/kg/h; and central venous or mixed venous oxygen saturation >70%. Earlytherapy directed towards these goals improves surviv Appropriate cultures should always be obtained before antimicrobial therapy is initiand tests should be done as soon as possible to determine the source of the infection and the causative organism. Imaging studies such as ultrasound and/orbedside computer tomography should be performed. Sources of infection requiring drainage should be identified promptly.
Intravenous antibiotic therapy should be started within the first hour of recognition of severe sepsis, after appropriate cultureshave been obtained.
Establishing vascular access and initiating aggressive fluid resuscitation is the first priority when managing patients with severe sepsis or septic shock. The antimicrobial regimen should always be reassessed after 48e72 h on the basis of microbi-ological and clinical data with the aim of using a narrow-spectrum antibiotic to prevent the development of resistance, to re-duce toxicity, and to reduce costs. Fluid challenge in patients with suspected hypovolemia (suspected inadequate arterialcirculation) may be given over 30 min and repeated based on response (increase in blood pressure and urine output) and tol-erance (evidence of intravascular volume overload). If appropriate fluid challenge fails to restore adequate blood pressure andorgan perfusion, administration with vasopressor agents should be started.
Table 4 Most often used homeopathic medicines and indications Weakness, exhaustionCardiovascular compromiseAnxiety, restlessnessCachectic appearance High temperature with sweatRed discolouration, face Pneumonia, esp. right lungStitching pain in chest Septic shockHaemorrhageHigh temperatureEmbolismDiscolouration blue, purple Pneumonia, esp. right lowerlobeHaemorrhagePurpura haemorrhagica Intravenous corticosteroids are recommended in patients with septic shock who, despite adequate fluid replacement, require vasopressor therapy to maintain adequate blood preRecombinant activated protein C (rhAPC) is recommended inpatients at high risk of death (APACHE II >25, sepsis-induced multiple organ failure, septic shock, or sepsis-induced ARDS)and no absolute contraindication that outweighs the potential benefit of rhAPC. The inflammatory response in sepsis is pro-coagulant in the early stages. rhAPC, an endogenous anti-coagulant with anti-inflammatory properties, has been shown, toimprove survival in patients with sepsis-induced organ dysfunction.
Mechanical ventilation in sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) should be adjusted to a “low” tidal in conjunction with the goal of maintaining end-inspiratory plateau pressures less than30 cmH2Daily spontaneous breathing trials reduce the duration of mechanical ventilation.eMechanicallyventilated patients receiving continuous sedation may have a significantly longer duration of mechanical ventilation, ICUand hospital length of stay.Daily interruption or lightening of sedation may reduce the duration of mechanical ventilationand ICU stay.Following initial stabilization, blood glucose should be kept below 8.3 mmol/l using continuous infusion in-sulin if necessary Our data suggest that homeopathic treatment has a beneficial effect on the long-term survival of patients with severe sepsis, further research is required before making firm recommendations. The lack of trained homeopaths available to advise on treat-ment on ICUs is an important constraint to further research and implementation.
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