Mechanical Insufflation-Exsufflation Compared With CPAP in Patients Admitted to an Intermediate Care Unit With Pneumonia

Background Mechanical insufflation‐exsufflation (MIE) was invented to help mobilize secretion from the lower respiratory tract by simulating a cough [1]. It is widely used in patients who have neuromuscular disease and therefore reduced cough strength, both during hospital admissions, and in patients' homes. Delivered by a Cough Assistor device through a mask, MIE functions by delivering a positive inspiratory pressure followed immediately by a negative expiratory pressure [1]. In patients with neuromuscular disease, MIE prevents hospital admissions, improves survival rates and delay time to tracheostomy [1]. In this patient group, MIE has proven to be safe with few adverse effects, and generally well tolerated [1‐3]. In patients with neuromuscular disease and an acute respiratory‐tract infection, MIE in combination with non‐invasive ventilation (NIV) is superior to NIV alone in removing secretion from the airways in patients with respiratory tract infections [2]. In a study among patients with severe chronic obstructive pulmonary disease (COPD) and difficulties clearing airway secretions after acute respiratory failure, MIE had a significant effect on both oxygenation and dyspnea [3]. Pneumonia is, with a yearly incidence of 5‐11 per 1.000 adult population, a leading cause of morbidity worldwide [4]. Around 22‐42% of adults with community‐acquired pneumonia (CAP) require hospitalization [4]. Globally, pneumonia is the leading cause of death due to infections, and the mortality among hospitalized patients with pneumonia is 5.7‐14% [4,5]. Pneumonia is seen with increased incidence in high risk patient groups such as the elderly, smokers, patients with immunodeficiencies and co‐morbidities [6]. Early initiation of appropriate antimicrobial therapy is the cornerstone in treatment of pneumonia and has been shown to shorten the course of disease and lessen the risk of complications and mortality [7]. In the acute phase of the disease, in addition to effective antimicrobial treatment, supportive treatment is important to optimize the respiratory care of the patients. Continuous positive airway pressure (CPAP) delivered through a face mask is widely used as supportive treatment and improves oxygenation in patients with acute hypoxemic respiratory failure compared to oxygen delivered by mask [8]. CPAP also improves oxygenation in patients with pneumonia in a hospital setting compared to oxygen therapy, but the effect quickly resolves after discontinuation, and CPAP has failed to show effect on endotracheal intubation rate, hospital mortality and length of intensive care unit stay in patients with acute respiratory failure [8‐10]. There are, to the investigators knowledge, no published studies who evaluate the effect of MIE on patients with acute respiratory‐tract infections without neuromuscular disease. The aim of this study is to investigate the safety and effect of MIE on patients hospitalized due to lower respiratory‐tract infections and examine their outcome with the current standard treatment of CPAP. Hypothesis Patients receiving MIE have better mobilization of secretions from the lower airways, and thereby faster oxygenation. Patients in the MIE group will have less need of ventilator support, and have a shorter admission to the intermediate care unit. Methods Randomization In total, 30 patients will be included and undergo 1:1 randomization to receive either CPAP or CPAP followed by MIE. Study design This randomized clinical pilot study is conducted at the intermediate care unit at the Department of Infectious Diseases, Odense University Hospital, Denmark. The intermediate care unit consists of 3 beds, all served by a nurse with special training in intermediate care. Continuous monitoring of blood pressure, pulse, oxygen saturation and respiratory rate is available. The assessment of the patient and admittance to the intermediate care unit is determined by the senior infectious disease doctor on call. Interventions CPAP will be administered through MR 810 (Fisher & Paykel Healthcare, Auckland, New Zealand) with standard settings of H2O and an oxygen flow of 15L/min [11]. CPAP is given by trained physiotherapists or nurses at the intermediate care unit. MIE will be administered through the NIPPY Clearway (B&D Electromedical, Stratford‐Upon‐Avon, Warwickshire, United Kingdom) with standard settings of insufflation 20 cm H2O and exsufflation 20 cm H2O, with possible individual changes from 10/‐10 H2O up to 40/‐40 H2O, and oxygen flow up to 15 l/min [12]. The standard settings will be set to five cycles of 2 seconds insufflation, 3 seconds exsufflation with a three second pause between each cycle. Every treatment session consists of five rounds of five cycles, in all 25 insufflation/exsufflation, with time between each cycle of 30 seconds, meant used for suction. The MIE is given by trained physiotherapists or nurses at the intermediate care unit. Clinical data The following data will be registered for each patient: age, sex, comorbidities, the severity of pneumonia using the CURB‐65 score [13], chest radiograph findings, antibiotic treatment up to and during the admission, days of admission, hours admitted to the semi‐intensive unit, transfer to intensive care unit (ICU), intubation and mechanical ventilation, in‐hospital and 30‐days mortality and re‐admittance within 30 days of discharge. During the admission in the intermediate care unit, number of CPAP and MIE treatments, oxygenation and oxygen need (liters/min) every 2 hours for the first 24 hours, hereafter every 4 hours, respiratory rate every 6 hours for the first 24 hours, hereafter every day, and the daily number of suction in pharynx or trachea in each patient will be registered. Paraclinical data For each patient, microbial growth from blood and sputum cultures will be registered, as will Polymerase Chain Reaction (PCR) results from sputum samples and relevant bacterial serology during admission, C‐reactive protein (CRP), white blood cell count (WBC) and urea at time of admission, time of entering the intermediate care unit, time of discharge from the intermediate care unit and time of discharge from the hospital. Statistical analysis Fisher's exact test and Wilcoxon rank sum will be used for categorical and continuous variables, respectively. A p‐value of < 0.05 is considered statistically significant. The statistical analyses will be performed using STATA version 13.0.