Early identification of leptospirosis-associated pulmonary hemorrhage syndrome by use of a validated prediction model

Summary

Objective

To identify prediction factors for the development of leptospirosis-associated pulmonary hemorrhage syndrome (LPHS).

Methods

We conducted a prospective cohort study. The study comprised of 203 patients, aged ≥14 years, admitted with complications of the severe form of leptospirosis at the Emílio Ribas Institute of Infectology (Sao Paulo, Brazil) between 1998 and 2004. Laboratory and demographic data were obtained and the severity of illness score and involvement of the lungs and others organs were determined. Logistic regression was performed to identify independent predictors of LPHS. A prospective validation cohort of 97 subjects with severe form of leptospirosis admitted at the same hospital between 2004 and 2006 was used to independently evaluate the predictive value of the model.

Results

The overall mortality rate was 7.9%. Multivariate logistic regression revealed that five factors were independently associated with the development of LPHS: serum potassium (mmol/L) (OR = 2.6; 95% CI = 1.1–5.9); serum creatinine (μmol/L) (OR = 1.2; 95% CI = 1.1–1.4); respiratory rate (breaths/min) (OR = 1.1; 95% CI = 1.1–1.2); presenting shock (OR = 69.9; 95% CI = 20.1–236.4), and Glasgow Coma Scale Score (GCS) < 15 (OR = 7.7; 95% CI = 1.3–23.0). We used these findings to calculate the risk of LPHS by the use of a spreadsheet. In the validation cohort, the equation classified correctly 92% of patients (Kappa statistic = 0.80).

Conclusions

We developed and validated a multivariate model for predicting LPHS. This tool should prove useful in identifying LPHS patients, allowing earlier management and thereby reducing mortality.

Introduction

Leptospirosis, a spirochetal zoonosis, has been increasingly recognized as an important cause of pulmonary hemorrhage syndrome.1, 2, 3, 4 Five to fifteen percent of the clinical infections progresses to develop severe disease manifestations.1, 2, 3, 5 The Nicaragua outbreak in 1995 raised awareness of leptospirosis as the cause of severe pulmonary hemorrhage.⁴ Whereas case fatality is 5–15% for Weil's disease, it is more than 50% in patients who develop leptospirosis-associated pulmonary hemorrhage syndrome (LPHS).5, 6, 7, 8

Early identification and triage of patients at risk for developing LPHS is essential to reduce the high case fatality rate. LPHS patients require intensive care unit (ICU) monitoring and aggressive supportive care for concomitant acute respiratory distress syndrome (ARDS), acute kidney injury and hypotension.9, 10, 11, 12, 13, 14 Protective mechanical ventilation modalities¹⁴ and daily hemodialysis¹⁵ have been shown to provide beneficial outcomes in clinical trials which included leptospirosis patients as subjects. However, identification of patients at risk for developing LPHS is difficult10, 11, 12, 13, 14 especially during initial hospital evaluation. Therefore predictive markers (e.g. hematology-test and biochemistry-test) need to be identified such that patients at risk for developing LPHS can be effectively identified and triaged.

We herein report the findings of a study which aimed to develop and validate a predictive model which can be used to identify patients at risk for developing LPHS at the time of hospital admission.