Effects of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboons

Abstract

Objective: To study diaphragmatic strength and endurance after a prolonged period of mechanical ventilation.

Design: Prospective animal study.

Setting: Animal research laboratory.

Subjects: Seven uninjured adult baboons (Papio cynocephalus) were anesthetized with ketamine, sedated, paralyzed, and mechanically ventilated. Animals were monitored with pulmonary arterial and peripheral arterial catheters.

Interventions: Mechanical ventilation was provided for 11 days with an FIO2 of 0.21 and tidal volume of 15 mL/kg. Pulmonary function tests, including lung volumes, arterial blood gases, and chest radiographs were also monitored. Nursing care procedures included frequent turning, chest physiotherapy, and endotracheal suction. Antacids and prophylactic antibiotics (intravenous penicillin, topical polymyxin B, and gentamicin sulfate) were administered. In three animals, fishhook electrodes were surgically placed around both phrenic nerves on both day 0 and after 11 days of mechanical ventilation for diaphragmatic stimulation. On day 0, the electrodes were removed after phrenic nerve stimulation studies were performed. After 11 days of mechanical ventilation, animals were electively killed and full autopsy performed.

Measurements and main results: Hemodynamic and pulmonary function parameters were measured at baseline and every day during the 11 days of mechanical ventilation. Diaphragmatic strength and endurance were measured on days 0 and 11. Diaphragmatic endurance was determined by an inspiratory resistive loading protocol. There were no significant changes in hemodynamics, lung volumes, or gas exchange during the period of mechanical ventilation. On day 7, the chest radiographs showed patchy lobar atelectasis in six animals, which cleared by day 11 in all but two of the animals. Lung pathology showed mild, focal pneumonitis. By day 11, maximum transdiaphragmatic pressure had decreased by 25% from day 0 and diaphragmatic endurance had decreased by 36%.

Conclusions: Eleven days of mechanical ventilation and neuromuscular blockade in healthy baboons resulted in nonsignificant changes in hemodynamics, oxygenation, and/or lung function. However, significant impairment in diaphragmatic endurance and strength were seen. Based on these results, it is likely that prolonged mechanical ventilation by itself impairs diaphragmatic function independent of underlying lung disease.