Influence of rhDNAse on the duration of mechanical ventilation in intensive care patients

Introduction

rhDNase is effective in the treatment of children with cystic fibrosis [1]. Significant reduction of the duration of ventilation by rhDNAse has been reported in children following cardiac surgery [2]. The goal of the present study was to investigate whether rhDNase is able to reduce the duration of ventilation in adult mechanically ventilated intensive care patients.

Methods

After approval of local ethics committees we conducted a double-blind, placebo-controlled, randomised, multicentre national trial. Patients were stratified into two subgroups depending on their status as surgical or nonsurgical. The trial was started within 48 hours after the start of mechanical ventilation and lasted until weaning was successful. Patients in the treatment group received 2.5 ml rhDNase endotracheally twice a day. Patients in the placebo group received the same amount of normal saline.

Results

One hundred and twenty-three surgical and 162 nonsurgical patients were included in the study. Factors such as gender, weight, smoking habit, chronic pre-existing diseases and prevalence of chronic obstructive pulmonary disease were distributed equally in both groups in surgical patients. In nonsurgical patients, more smokers were randomized to the rhDNase group. Acute burn patients were randomized to the rhDNase group only. Twelve patients (two surgical) died in the rhDNase group versus 16 (four surgical) in the placebo group. In surviving surgical patients, the median duration of ventilation was 16.6 days (95% CI 11.5–21 days) in the rhDNase group and 11.7 days (95% CI 8.4–15.6 days, P = 0.39) in the placebo group. In surviving nonsurgical patients, the median duration of ventilation was 7.8 days (95% CI 6–9.3 days) in the rhDNase group and 12.6 days (95% CI 7.9–16.9 days; P = 0.038) in the placebo group without adjustment for smoking habits.

Conclusion

In adult nonsurgical intensive care patients, rhDNase significantly shortens the duration of ventilation. This effect is not seen in surgical patients. The hypothesis that especially pneumonia that requires mechanical ventilation responds favourably to treatment with rhDNase should be investigated.