High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial.

BACKGROUND: Andes virus (ANDV)-related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial. METHODS: Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat. RESULTS: Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P = .43). We observed no significant difference in mortality between treatment groups (P = .41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P = .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load. CONCLUSIONS: Although methylprednisolone appears to be safe, it did not provide significant clinical benefit to patients. Our results do not support the use of methylprednisolone for HCPS. CLINICAL TRIALS REGISTRATION: NCT00128180.

Impacto de la obesidad en pacientes con neumonía grave por virus influenza A/H1N1: estudio multicéntrico chileno / Impact of obesity with severe pneumonia by influenza A/H1N1 virus: a Chilean multicenter study

En la primera pandemia del siglo XXI por virus influenza A/H1N1, una importante proporción de paciente que desarrollaron neumonía y Falla Respiratoria Aguda (FRA) eran obesos. La obesidad ha sido propuesta como un factor de riesgo que aumenta la morbimortalidad; sin embargo, hay controversia al respecto. Objetivo: evaluar el impacto de la obesidad en complicaciones, estadía y/o mortalidad en pacientes adultos graves por virus influenza A/H1N1. Estudio observacional y multicéntrico realizado en 17 UCIs de Chile durante el periodo mayo-agosto 2009. Fueron incluidos en el estudio solo paciente con infección por virus Influenza A/H1N1 confirmada o probable. Los paciente obesos (IMC>30) fueron comparados con pacientes no obesos. Resultados: De un total de 136 pacientes incluidos en el estudio, 64 (47 por ciento) fueron obesos y de estos 13 obesos mórbidos (BMI >40). Los pacientes obesos tienen mayor frecuencia de: comorbilidades, ventilación mecánica y complicaciones. La estadía en UCI y en el hospital fue más prolongada en pacientes obesos (18,1+/-15 vs. 10,9+/-10,2, p=0,002 y 27,2+/-24,7 vs17,7 +/- 14,6, p=0,01 respectivamente). La mortalidad fue mayor en pacientes obesos (36 por ciento vs. 19,4 por ciento; OR 2,32; IC95 por ciento 1,07-5,05, p=0.035). El estudio de regresión logística encuentra que la FOM es un factor pronóstico independiente de mortalidad en pacientes obesos. Conclusiones: Los pacientes obesos con neumonía grave por virus influenza A/H1N1 tienen una mayor morbi-mortalidad y prolongación de su estadía en UCI y en el hospital. El desarrollo de FOM en pacientes obesos es un factor de mal pronóstico.

In the first pandemic of the 21st century due to influenza A/H1N1 virus, a significant proportion of patients who developed pneumonia and acute respiratory failure (ARF) were obese. Obesity has been proposed as a risk factor that increases morbidity and mortality, however, there is controversy about it. Objective: To determine the impact of obesity on complications, stay and / or mortality in adult patients with severe influenza A/H1N1 virus. Multicenter observational study conducted in 17 ICUs of Chile during the period May to August 2009. Were included only patients with influenza A/H1N1 virus infection confirmed or probable. Obese patients (BMI> 30) were compared with non obese patients. The results: Of a total of 136 patients included in the study, 64 (47 percent) were obese and of these 13 morbidly obese (BMI> 40). Obese patients have a higher frequency of: comorbidities, mechanical ventilation and complications. The stay in ICU and hospital was longer in obese patients (18.1 +/- 15 vs. 10.9 +/- 10.2, p = 0.002 and 27.2 +/- 24.7 vs17, 7 +/- 14.6, p = 0.01 respectively). Mortality was higher in obese patients (36 percent vs. 19.4 percent, OR 2.32, 95 percent CI 1.07 to 5.05, p = 0,035). The logistic regression analysis found that the MOF is an independent predictor of mortality in obese patients. Conclusions: Obese patients with severe pneumonia due to the influenza A/H1N1 virus have a high morbidity and mortality and prolonged stay in ICU and hospital. MOF development in obese patients is a poor prognostic factor.

Hantavirus pulmonary syndrome, southern Chile.

We analyzed data from 25 consecutive patients with hantavirus pulmonary syndrome (HPS) admitted to the Puerto Montt and Osorno Regional Hospitals, southern Chile, from 1997 to 2001, emphasizing epidemiologic, clinical, radiographic, treatment, and laboratory aspects. Hemorrhage was frequent (64%), and 48% of patients showed alterations in renal function. Ten patients died (40%). We identified three groups of patients, which included the following: 1) those with the least severe form who had prodromic symptoms without pulmonary involvement; 2) those with moderate illness who had interstitial pulmonary infiltrates, usually needed supplemental nasal oxygen, were hemodynamically stable, and had an APACHE II <12 (none of whom died); and 3) those with the severe form who required mechanical ventilation, frequently had hemodynamic instability (93%), experienced a high mortality rate (77%), and had an APACHE II >12. Mild forms of HPS also exist, which are poorly known; the symptoms could be confounded with those of other viral diseases, leading to underdiagnosis.