Acute renal response to changes in carbon dioxide in mechanically ventilated female pigs

Abstract

Kidney response to acute and mechanically induced variation in ventilation associated with different levels of PEEP has not been investigated. We aimed to quantify the effect of ventilatory settings on renal acid-base compensation. Forty-one pigs undergoing hypo- (<0.2 Lkg^-1 min^-1, PEEP 25 cmH₂O), intermediate (0.2-0.4 Lkg^-1 min^-1 with either PEEP 5 or 25 cmH₂O), or hyper-ventilation (>0.4 Lkg^-1 min^-1, PEEP 5 cmH₂O) for 48 h were retrospectively included. The decrease in pH paralleled the decrease in plasma strong ion difference (SID) in hyper- and intermediately ventilated groups with lower PEEP. In contrast, the plasma SID remained nearly constant in hypo- and intermediately ventilated groups with higher PEEP. Changes in plasma chloride concentration accounted for the changes in plasma SID (conditional R² = 0.86). The plasma SID changes were paralleled by mirror changes in urinary SID. Higher PEEP (25 cmH₂O), compared to lower PEEP (5 cmH₂O) dampened or abolished the renal compensation through its effect on hemodynamics (higher central venous and mean pulmonary pressures), irrespective of minute ventilation. During mechanical ventilation, the compensatory renal response to respiratory derangement is immediate and progressive but can be dampened by high PEEP levels.

Keywords: PEEP; Stewart's model; acid–base; mechanical ventilation; renal compensation.

FIGURE 1

Symbols and annotations: L_VENT‐H_PEEP, low‐minute ventilation high PEEP (blue triangles); I_VENT‐H_PEEP, intermediate‐minute ventilation high PEEP (green triangles); I_VENT‐L_PEEP, intermediate‐minute ventilation low PEEP (green circles); H_VENT‐L_PEEP, high‐minute ventilation low PEEP (red circles). The dashed and the solid lines connects groups treated with 5 or 25 cmH₂O of PEEP, respectively. Note that, for the sake of clarity, the intervals between measurements at baseline and 0.5 h has been arbitrarily equated to an interval of 6 h. Differences among groups within time were assessed by a two‐ways repeated measures ANOVA. (a) Time course of minute ventilation in the four experimental groups. Minute ventilation was significantly different among low, intermediate, and high ventilation groups (p _GROUP  <0.001) during the experimental phase (from 0.5 to 48 h) due to the experimental protocol. No significant differences were found between intermediate groups ventilated with higher and lower PEEP (p = 0.321). (b) Time course of arterial carbon dioxide partial pressure (PaCO₂) in the four experimental groups. Arterial PaCO₂ behavior was significantly different among low, intermediate, and high ventilation groups; of note, arterial PCO₂ began to be significantly different also between intermediately ventilated groups treated with higher or lower PEEP after 24 h (p < 0.050). p _GROUP  <0.001, p _TIME  = 0.615, p _INTER  <0.001. (c) Time course of arterial pH in the four experimental groups. Arterial pH behavior was significantly different among low, intermediate, and high ventilation groups within time (p _INTER  <0.001). After reaching the near‐PCO₂ steady state (0.5–6 h), arterial pH significantly decreased with time in high and intermediate ventilation groups, while it remained unchanged in the low ventilation group. p _GROUP  <0.001, p _TIME  <0.001, p _INTER  <0.001.

FIGURE 2

Symbols and annotations as in Figure 1. Differences among groups within time were assessed by a two‐ways repeated measures ANOVA. (a) Time course of plasma strong ion difference (plasma [SID]) in the four experimental groups. Plasma [SID] showed a significant interaction among groups within time, resulting in statistically different plasma SID among all the four groups at 48 h. p _GROUP  <0.001, p _TIME  <0.001, p _INTER  <0.001. (b) Time course of plasma sodium concentration (plasma [Na⁺]) in the four experimental groups. All four experimental groups showed a similar behavior within time. p _GROUP  = 0.191, p _TIME  <0.001, p _INTER  = 0.424. (c) Time course of plasma potassium concentration (plasma [K⁺]) in the four experimental groups. The lower (dashed lines) and higher (solid lines) PEEP groups showed a significantly different behavior within time. p _GROUP  <0.001, p _TIME  <0.001, p _INTER  <0.001. (d) Time course of plasma chloride concentration (plasma [Cl⁻]) in the four experimental groups. The lower (dashed lines) and higher (solid lines) PEEP groups showed a significantly different behavior within time. p _GROUP  <0.001, p _TIME  <0.001, p _INTER  <0.001.

FIGURE 3

Relationship between changes in plasma SID (ΔPlasma [SID]) and changes in plasma chloride concentration (ΔPlasma [Cl⁻]). A linear mixed effect model was used to model the relationship: $\mathrm{\Delta }\mathit{\text{Plasmatic}}\left[\mathit{SID}\right]=0.29-0.76\times \mathrm{\Delta }\mathit{\text{Plasmatic}}\left[C{l}^{-}\right]$, p < 0.001, Conditional R ² = 0.86. Dotted lines represent 0.95% confidence intervals of the model. L_VENT‐H_PEEP, low‐minute ventilation high PEEP (blue dots); I_VENT‐H_PEEP, intermediate‐minute ventilation high PEEP (green dots); I_VENT‐L_PEEP, intermediate‐minute ventilation low PEEP (green dots); H_VENT‐L_PEEP, high‐minute ventilation low PEEP (red dots).

FIGURE 4

Renal compensation ratios among experimental groups after 48 h of mechanical ventilation. L_VENT‐H_PEEP, low‐minute ventilation high PEEP (blue, solid line); I_VENT‐H_PEEP, intermediate‐minute ventilation high PEEP (green, solid line); I_VENT‐L_PEEP, intermediate‐minute ventilation low PEEP (green, dashed line); H_VENT‐L_PEEP, high‐minute ventilation low PEEP (red, dashed line). The horizontal line represents the expected compensation for chronic respiratory alkalosis (Rose & Post, 2001). Differences among groups were assessed by a one‐way ANOVA, while post hoc pairwise comparisons were performed.

FIGURE 5

Symbols and annotations as in Figure 1. Differences among groups within time were assessed by a two‐way repeated measures ANOVA. (a) Time course of central venous pressure in the four experimental groups. Central venous pressure was significantly different among groups, specially between groups ventilated with higher and lower PEEP. p _GROUP  <0.001, p _TIME  <0.001, p _INTER  = 0.401. (b) Time course of mean pulmonary arterial pressure in the four experimental groups. Mean pulmonary arterial pressure was significantly different among groups, specially between groups ventilated with higher and lower PEEP. p _GROUP  <0.001, p _TIME  = 0.077, p _INTER  = 0.131. (c) Time course of systemic vascular resistance in the four experimental groups. The hypo‐ventilated group with higher PEEP showed a significantly different behavior within time compared to other groups. p _GROUP  = 0.123, p _TIME  = 0.007, p _INTER  = 0.026. (d) Time course of cardiac output in the four experimental groups. The hypo‐ventilated group with higher PEEP showed a significantly different behavior within time compared to other groups. p _GROUP  = 0.004, p _TIME  = 0.001, p _INTER  <0.001.

FIGURE 6

Symbols and annotations as in Figure 1. Differences among groups within time were assessed by a two‐way repeated measures ANOVA. Time course of plasma creatinine in the four experimental groups. The groups ventilated with higher PEEP showed a significantly different behavior over time compared to groups with lower PEEP. p _GROUP  <0.001, p _TIME  <0.001, p _INTER  <0.001.