Non-chemical inhibition of respiratory motor output during mechanical ventilation in sleeping humans

Abstract

1. To determine the magnitude and time course of changes in respiratory motor output caused by non-chemical influences, six sleeping subjects underwent assist-control mechanical ventilation (ACMV) at increased tidal volume (VT). During ACMV, end-tidal PCO2 (PET,CO2) was either held at normocapnic levels (PET,CO2, 0.6-1.1 mmHg > control) by adding CO2 to the inspirate, or it was allowed to fall (hypocapnia). 2. Each sleeping subject underwent several repeat trials of twenty-five ACMV breaths (VT, 1.3 or 2.1 times control; peak flow rate, 30-40 l min-1; inspiratory time, +/- 0.3 s of control). The end-tidal to arterial PCO2 difference throughout normocapnic ACMV at raised VT was unchanged from eupnoeic levels during studies in wakefulness. 3. Normocapnic ACMV at both the smaller and larger increases in VT decreased the amplitude of respiratory motor output, as judged by decreased maximum rate of rise of mask pressure (Pm) (mean dPm/dtmax, 46-68% of control), reduced diaphragmatic EMG (to 55% of control) and reduced VT on the first spontaneous breath after ACMV (to 70% of control). Expiratory time (TE) was slightly prolonged (13-32% > control). This inhibition of amplitude of respiratory motor output progressed over the first five to seven ventilator cycles, was maintained over the remaining 18-20 cycles and persisted for three to five spontaneous breaths immediately following cessation of ACMV. 4. Hypocapnia did not further inhibit respiratory motor output amplitude beyond the effect of normocapnic ACMV at high VT, but did cause highly variable prolongation of TE when PET,CO2 was reduced by greater than 3 mmHg for at least five ventilator cycles. 5. These data in sleeping humans support the existence of a significant, non-chemical inhibitory influence of ACMV at increased VT and positive pressure upon the amplitude of respiratory motor output; this effect is manifested both during and following normocapnic mechanical ventilation.

Figure 1. Recording of one trial of normocapnic ACMV at high ventilator volume (850 ml, 215 % baseline V_T) during stage III sleep

Note: (a) the diminution of EMG_di activity and dP_m/dt_max and slight slowing of respiratory rate during mechanical ventilation and (b) the slow recovery of spontaneous V_T after mechanical ventilation was discontinued. Dashed vertical lines indicate the start and finish of mechanical ventilation.

Figure 2. Group mean data during normocapnic ACMV

V_T, peak V_I (inspiratory flow); T_tot, respiratory cycle time; dP_m/dt_max, maximum rate of change of mask pressure; P_ET,CO2, mean area EMG_di (diaphragmatic EMG). Data represent means ±s.d. for six subjects, one to six trials per subject. A, normocapnic ACMV at low ventilator V_T (128 % baseline V_T) (n= 6). As one subject was aroused from sleep, only five subjects are represented in data beyond ventilator breath 22 (note break in horizontal lines). Mean area EMG_di data represent the means ±s.d. of one trial in each of the six subjects. B, normocapnic ACMV at high ventilator V_T (210 % baseline V_T) (n= 6). Mean area EMG_di data represent the means ±s.d. of one trial in each of five subjects (1 trial per subject). Only four subjects are represented in data beyond ventilator breath 23. Dashed vertical lines indicate start and finish of mechanical ventilation.

Figure 6. Assessment of indices of respiratory motor output

A, nadir of the changes from baseline in mean area of EMG_diversus dP_m/dt_max for 23 trials where EMG was analysed. The dotted line indicates the linear regression line (r= 0·61, P < 0·002). B, dP_m/dt_max, V_T and V_T/T_I for the first spontaneous breath after ACMV are shown for all trials. Dotted lines indicate linear regressions for dP_m/dt_maxversus V_T and V_T/T_I (r= 0·73 (P < 0·001) and 0·65 (P < 0·001), respectively). Closed symbols, normocapnic ACMV; open symbols, hypocapnic ACMV; circles, low ventilator V_T; squares, high ventilator V_T.

Figure 3. Recording of one trial of hypocapnic ACMV at high ventilator volume (870 ml, 203 % baseline V_T) during stage III sleep

Note: (a) the slowing of respiratory rate and (b) the rapid fall in EMG_di, leading to an inspiratory effort insufficient to trigger a ventilator cycle, and an irregular respiratory rhythm. The trial ends in arousal from sleep.

Figure 4. Individual subject responses (mean of 1-5 trials in each of 6 subjects) to hypocapnic ACMV

A, hypocapnic ACMV at low ventilator V_T (128 % of baseline V_T). Most subjects show a gradual fall in dP_m/dt_max and EMG_di but no apnoea. However, one subject became apnoeic following ventilator breath 8 after P_ET,CO2 fell by 4 mmHg. B, hypocapnic ACMV at high ventilator V_T (212 % of baseline V_T). Note that only half of the subjects experienced two- to fivefold prolongations in T_tot; weak inspiratory efforts ended the trials of the remaining three subjects.

Figure 5. Change in P_ET,CO2versus longest T_tot and nadir dP_m/dt_max

Change in P_ET,CO2 from baseline levels for all normocapnic and hypocapnic trials is plotted against longest T_tot during each trial (A) and nadir dP_m/dt_max occurring either at the same time as or before the breath with the longest T_tot (B). For the hypocapnic trials, the first significant prolongation of T_tot was used as the longest T_tot because following this initial T_tot prolongation P_ET,CO2 increases and both breathing pattern and P_ET,CO2 were unstable. •, trials at low ventilator V_T; ○, trials at high ventilator V_T.

Figure 7. P_CO2, pH and the arterial - end-tidal P_CO2 difference during eupnoea and ACMV

Measurements of arterial P_CO2 and pH and arterial - end-tidal P_CO2 differences (means ±s.d.) in five awake subjects during normocapnic ACMV (4 trials per subject, •) and hypocapnic ACMV (1 trial per subject, ○). Note that ACMV did not change the arterial P_ET,CO2 difference from baseline levels.