Efficacy of Intravenous Amboxol Hydrochloride as an Adjunct Therapy for Severe Pneumonia in Critically Ill Patients

Ambroxol is a mucolytic containing an active N-desmethyl metabolite of bromhexine. It is approved by both the U.S. FDA and EMA to be marketed under several formulations including oral, nasal, oro-mucosal, rectal and intravenous formulations. One of ambroxol's authorized use is for the treatment of bronchopulmonary infections. In addition, it has been found over the decades to have other multi-pronged properties such as local anaesthesia, anti-inflammatory and anti-oxidant effects. It also stimulates surfactant production in Type II pneumocytes, thus preventing atelectasis in pneumonia. Ambroxol has demonstrated a wide safety profile and is an extensively studied drug in terms of safety with the commonest side effects being skin rashes, allergies, nausea, vomiting, abdominal pain and dyspepsia.Severe pneumonia is is defined by the American Thoracic Society (ATS) as pneumonia that requires ICU admission and specifically fulfils one of two major criteria, or three out of nine minor criteria as per recommended in the latest ATS guideline.This study aims to investigate the effects of using intravenous ambroxol as an adjunct therapy on the resolution of severe pneumonia. The improvements in modified Clinical Pulmonary Infection Score (CPIS) will be used as a surrogate for resolution of severe pneumonia. Modified CPIS is a clinical score of 0-12 based on 6 clinical features: volume and character of tracheal secretions, chest radiograph infiltrates, body temperature, leukocyte count, oxygenation index, and microbiology results. Traditionally, CPIS score has been used to facilitate the diagnosis of VAP where a cut-off point of >6 is used to denote possible pneumonia. Interestingly, Luna et al has found that serial improvements in CPIS score can be successfully used as a surrogate for pneumonia resolution with good correlation with eventual survivability.This study will also explore the effects of using ambroxol on other clinical outcomes of patients with severe pneumonia, including ICU mortality, duration of ICU stay, length of mechanical ventilation and incidence of reintubation within 48 hours. If this adjunct treatment is able to reduce duration of ICU stay and length of MV, it will not only directly impact the patients' short & long term outcomes but will also confer logistical benefits in terms of saving resources and reducing healthcare economic burden while optimizing ICU turnover rates.

Inclusion Criteria:Patients aged > 18 years oldMechanically ventilated due to severe community or hospital acquired pneumoniaExclusion Criteria:Patients aged <18 years oldPregnant and lactating patientsPatients with known allergies to ambroxol hydrochloridePatients with aspartate aminotransferase (AST) >5 times the upper limit of normal at the time of recruitmentMoribund patients who are expected to not survive within 24 hours of ICU admission