Moderate and prolonged hypercapnic acidosis may protect against ventilator-induced diaphragmatic dysfunction in healthy piglet: an in vivo study

Abstract

Introduction: Protective ventilation by using limited airway pressures and ventilation may result in moderate and prolonged hypercapnic acidosis, as often observed in critically ill patients. Because allowing moderate and prolonged hypercapnia may be considered protective measure for the lungs, we hypothesized that moderate and prolonged hypercapnic acidosis may protect the diaphragm against ventilator-induced diaphragmatic dysfunction (VIDD). The aim of our study was to evaluate the effects of moderate and prolonged (72 hours of mechanical ventilation) hypercapnic acidosis on in vivo diaphragmatic function.

Methods: Two groups of anesthetized piglets were ventilated during a 72-hour period. Piglets were assigned to the Normocapnia group (n = 6), ventilated in normocapnia, or to the Hypercapnia group (n = 6), ventilated with moderate hypercapnic acidosis (PaCO₂ from 55 to 70 mm Hg) during the 72-hour period of the study. Every 12 hours, we measured transdiaphragmatic pressure (Pdi) after bilateral, supramaximal transjugular stimulation of the two phrenic nerves to assess in vivo diaphragmatic contractile force. Pressure/frequency curves were drawn after stimulation from 20 to 120 Hz of the phrenic nerves. The protocol was approved by our institutional animal-care committee.

Results: Moderate and prolonged hypercapnic acidosis was well tolerated during the study period. The baseline pressure/frequency curves of the two groups were not significantly different (Pdi at 20 Hz, 32.7 ± 8.7 cm H₂O, versus 34.4 ± 8.4 cm H₂O; and at 120 Hz, 56.8 ± 8.7 cm H₂O versus 60.8 ± 5.7 cm H₂O, for Normocapnia and Hypercapnia groups, respectively). After 72 hours of ventilation, Pdi decreased by 25% of its baseline value in the Normocapnia group, whereas Pdi did not decrease in the Hypercapnia group.

Conclusions: Moderate and prolonged hypercapnic acidosis limited the occurrence of VIDD during controlled mechanical ventilation in a healthy piglet model. Consequences of moderate and prolonged hypercapnic acidosis should be better explored with further studies before being tested on patients.

Figure 1

Diaphragmatic pressure/frequency curves obtained in the Normocapnia group (A) (n = 6) and in the Hypercapnia group (B) (n = 6). Transdiaphragmatic pressure (Pdi) after supramaximal phrenic nerve stimulation at 20, 40, 60, 80, 100, and 120 Hz over a period of 72 hours of mechanical ventilation were obtained in both groups. In the Normocapnia group, Pdi significantly decreased between baseline and H72 at all frequencies (except at 20 Hz) (P < 0.05). No significant differences between baseline and H72 were observed for the values obtained at all frequencies in the Hypercapnia group. Data are expressed as mean ± SD. NS, not significant. P values refer to between H72 versus baseline.

Figure 2

Transdiaphragmatic pressure (Pdi) expressed as percentage of Pdi at normocapnia obtained at 100 Hz stimulation at each stimulation (every 12 hours) in the Normocapnia group (A) (n = 6) and in the Hypercapnia group (B) (n = 6). Pdi was significantly lower at 100 Hz compared with H0 after 48 hours of mechanical ventilation in the normocapnia group (A). Conversely, no significant decreases were noted in Pdi between the successive measures in the hypercapnia group (B). Data are expressed as percentage (mean ± SD). NS, not significant. P values refer to between H72 versus baseline.