Aim of the Study:The aim of this study was to evaluate the effect of a 5 days infusion of aminophylline on diaphragm contractility as measured by ultrasonographic parameters of diaphragm contraction. We hypothesize that low dose of aminophylline will be helpful in preserving diaphragmatic contractility in mechanical ventilated patients, without any significant side effect.

 Primary Objective:The goal of this study is to find out the change in diaphragmatic excursion on day 5 with respect to baseline, with the use of low dose aminophylline for 5 days.

Methodology: . Patients on mechanical ventilation who meet the inclusion criteria will be will be enrolled in the study.  After randomisation, the patients in Group A will receive aminophylline infusion of 200 mg over one hour, twice a day (Equivalent dose of 320 mg theophylline per day)^[1] for 5 days.  Group C will receive saline infusion for 1 hour, twice a day for 5 days. Rest of the treatment will be as per the patient’s clinical condition and ICU protocol. The study drug will be initiated once the patient is adequately fluid resuscitated, hemodynamically stabilized and recovered from effects of any neuromuscular blockade which may have been used to facilitate endotracheal intubation.

The baseline characteristics of all the patients will be recorded: medical diagnosis, comorbidities, age, gender, weight, height, body mass index and the Sequential Organ Function Assessment (SOFA) scores. Baseline hemodynamic parameters such as heart rate (HR), systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP), pulse pressure, oxygen saturation (SpO2) will be noted.

 Mode of mechanical ventilation during the assessment period will be adjusted to target a delivered tidal volume of 6-8 ml per kg body weight to allow for uniformity in diaphragm excursion. Weaning will be attempted as per the weaning protocol followed in the ICU and guided by patient’s clinical condition. The diaphragm evaluation will be done with the patient in supine position. In case the patient cannot be placed in supine position then the degree of incline for baseline reading will be noted and subsequent diaphragm evaluation will be done at the same degree of inclination.

On Day 1, Day 3 and Day5 diaphragmatic excursion, diaphragmatic thickening fraction, parasternal intercostal muscle thickening fraction, RSBI, maximum inspiratory pressure will be measured. Parameters measured in relation to mechanical ventilation will be: level of pressure support, PEEP and the tidal volume generated at this setting. The duration of mechanical ventilation, weaning time, success with SBT and length of stay in ICU (ICU-LOS) will be noted. A failed extubation will be defined as requirement of invasive or non-invasive mechanical ventilation within 48 hours after extubation. Extubation to NIV for prevention of weaning failure will not be considered as failed extubation. Anticipated adverse events arising out of theophylline use will also be recorded. These include- arrythmias, tremors, seizures, insomnia, hypotension and hypokalemia. On Day 3, serum sample will be sent for serum theophylline levels.