Clinical characteristics and outcomes of pulmonary haemorrhage in leptospirosis: A retrospective cohort study from Sri Lanka

Background Leptospirosis, a tropical, spirochaetal infection presents as an acute febrile illness with organ injury. There is a paucity of data on clinical characteristics and treatment for Leptospirosis Pulmonary Haemorrhage Syndrome (LPHS). Methodology and principal findings A retrospective cohort study was conducted including all patients with LPHS treated in the medical Intensive Care Unit (ICU), at National Hospital Sri Lanka from 2019 to 2022 to describe the clinical characteristics and factors related to poor outcomes. Survival of patients who received different treatment modalities for LPHS was compared. Seventy patients were studied with a mean age of 42.69 ± 27.84 years and 61 (87.1%) males. Forty-nine (70%) were mechanically ventilated and 16 (22.9%) died. Higher heart rate, higher lactate, lower pH on admission to ICU, and requirement of blood product transfusion were associated with increased mortality. Patients were treated with plasmapheresis (PLEX), intranasal desmopressin (DDAVP), and intravenous steroids alone or in combination as the specific treatment for LPHS. Seven (10%) patients were treated with PLEX alone, 13 (18.6%) with PLEX + DDAVP, 46 (65.7%) with PLEX + DDAVP + steroids, and 4(5.7%) were treated with steroids alone. All patients who received the PLEX and DDAVP combination survived. There were 11 (23.9%) deaths in the PLEX+ DDAVP + steroids group, 3 (49.2%) in the PLEX alone group, and 2 (50%) in the steroids alone group. Mortality was least when PLEX was done for 3 days. Twenty-five (35.7%) patients developed hospital-acquired infections and risk factors were mechanical ventilation and longer ICU stay. Conclusions The presence of tachycardia, acidosis, and high lactate predicted death in LPHS. PLEX and DDAVP combination had better survival than other treatments alone or in combination for LPHS. Randomized clinical trials are urgently needed to identify the role of PLEX and DDAVP in treating LPHS. Author Summary Leptospirosis, a tropical infection causes multiple organ injury. Bleeding into the lungs (pulmonary haemorrhage) in leptospirosis is poorly studied. There is no established treatment for pulmonary haemorrhage in leptospirosis (LPHS). A large cohort of LPHS patients treated in a medical ICU in Sri Lanka was studied to identify clinical characteristics and outcomes. The presence of higher heart rate, high lactate, lower pH, need for blood product, and intravenous tranexamic acid were identified as risk factors for death. We compared different treatment modalities used for the treatment of LPHS. In addition to standard treatment with antibiotics and supportive care, a combination of steroids, plasma exchange (PLEX), and intranasal desmopressin (DDAVP) were used to treat LPHS. Mortality was least when patients were treated with DDAVP + PLEX. The optimum duration of PLEX was 3 days. Clinical trials are urgently needed to identify the benefit of PLEX and DDAVP in the treatment of LPHS. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The author(s) received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics review committee, Faculty of medicine, University of Colombo I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are available in the BioStudies database () under accession number S-BSST1368. * AKI : acute kidney injury DDAVP : desmopressin FFP : Fresh frozen plasma HR : hazard ratio ICU : intensive care unit LPHS : Leptospirosis pulmonary haemorrhage syndrome MAT : microscopic agglutination test MICU : Medical intensive unit NHSL : National Hospital of Sri Lanka OR : odds ratio PCR : polymerase chain reaction PLEX : plasma exchange RCC : Red cell concentrate RRT : renal replacement therapy ULN : upper limit of normal vWF : von Willebrand factor