Restrictive Fluid Resuscitation Leads to Better Oxygenation than Non-Restrictive Fluid Resuscitation in Piglets with Pulmonary or Extrapulmonary Acute Respiratory Distress Syndrome

Abstract

Background: Early goal-directed therapy (EGDT) is used to reduce mortality from septic shock and could be used in early fluid resuscitation of acute respiratory distress syndrome (ARDS). The aim of the present study was to assess the effects of restrictive (RFR) and nonrestrictive fluid resuscitation (NRFR) on hemodynamics, oxygenation, pulmonary function, tissue perfusion, and inflammation in piglets with pulmonary or extrapulmonary ARDS (ARDSp and ARDSexp).

Material and methods: Chinese miniature piglets (6-8 weeks; 15 ± 1 kg) were randomly divided into 2 groups (n=12/group) for establishing ARDSp and ARDSexp models, and were further divided into 2 subgroups (n=6/subgroup) for performing RFR and NRFR. Piglets were anesthetized and hemodynamic, pulmonary, and oxygenation indicators were collected at different time points for 6 hours. The goal of EGDT was set for PiCCO parameters (mean arterial pressure (MAP), urine output and cardiac index (CI), and central venous oxygen saturation (ScvO2).

Results: Piglets under RFR had lower urine output compared with NRFR, as well as lower total fluid volume (P<0.05). EVLW was decreased in ARDSp+RFR and NRFR, as well as in ARDSexp+RFR, but EVLW increased in ARDSexp+NRFR (P<0.05). PaO2/FiO2 decreased in ARDSp using both methods, but was higher with RFR (P<0.05), and was increased in ARDSexp+RFR. Other pulmonary indicators were comparable. The anti-inflammatory cytokines IL-10 and LXA4 were increased in ARDSexp after RFR (P<0.05), but not in the other groups.

Conclusions: RFR led to better oxygenation in ARDSp and ARDSexp compared with NRFR, but fluid restriction improved oxygenation in ARDSexp only.

Figure 1

Postmortem pathological examination of representative piglets. (A) Lungs from ARDSexp models showed diffuse pulmonary congestion and edema, as well as flower porphyritic changes. (B) Lungs from ARDSp models showed large red edema. (C) Histopathological examination of ARDSexp lung tissues showed relatively complete alveolar damage with septal oozing, few hemorrhage and a significant accumulation of neutrophiles. (D) Histopathological examination of ARDSp lung tissues showed severe alveolar damage, alveolar fusion, alveolar exudate, severe hemorrhage, an important recruitment of inflammatory cells and focal atelectasis. (HE staining, C,D ×200).

Figure 2

Changes in oxygenation index, urine output, extravascular lung water (EVLW), and pHi during fluid resuscitation in ARDSp and ARDSexp piglets. (A) Pulmonary acute respiratory distress syndrome (ARDSp) (group A) and (B) extrapulmonary acute respiratory distress syndrome (ARDSexp) (group B) models (n=12/group). Restrictive fluid resuscitation (RFR) (group A1 and B1) and nonrestrictive fluid resuscitation (NRFR) (group A2 and B2) (n=6/subgroup). (C) Changes of urine output. (D) Changes of EVLW. (E) Changes in pHi. One piglet died in groups A2 and B1. Before modeling (T0), after modeling and before resuscitation (T1), at 2 h (T2), 4 h (T3) and 6 h (T4) after resuscitation. Data are shown as mean±standard deviation (SD). ^a P<0.05 A1 vs. A2; ^b P<0.05 B1 vs. B2; ^c P<0.05 A1 group vs. B1 group; ^e P<0.05 vs. T0 within the same group. ^f P<0.05 vs. T1 within the same group.

Figure 3

Effects of early goal-directed therapy (EGDT)-guided fluid resuscitation on inflammatory cytokines in serum and bronchoalveolar lavage fluid (BALF) in piglets with ARDSp or ARDSexp. Inflammatory cytokines levels were determined by ELISA. (A) Tumor necrosis factor-α (TNF-α) levels. (B) Interleukin-1β (IL-1β) levels. (C) Interleukin-6 (IL-6) levels. (D) Interleukin-10 (IL-10) levels. (E) Lipoxin A4 (LXA4) levels. (F) Surfactant protein A (SP-A) levels. (G) Soluble intercellular adhesion molecule-1 (sICAM-1) levels. Data are shown as mean ±SD. A1 (n=6), B1 (n=5), A2 (n=5), B2 (n=6). ^a P<0.05 A1 vs. A2; ^b P<0.05 B1 vs. B2; ^e P<0.05 vs. T1 within the same group; ^f P<0.05 BALF vs. serum.