Higher Concentration of Hypertonic Saline Shows Better Recovery Effects on Rabbits with Uncontrolled Hemorrhagic Shock

Abstract

BACKGROUND Our previous study found a novel fluid combination with better resuscitation effects under hypotensive condition at the early stage of uncontrolled hemorrhagic shock (UHS). However, the optimal recovery concentration of hypertonic saline in this fluid combination remains unknown. This experiment aimed to explore the optimal concentration. MATERIAL AND METHODS New Zealand white rabbits (n=40) were randomly divided into 5 groups, including a sham-operated group (SO), a shock non-treated group (SNT), a normal saline group (NS), and hypertonic saline groups (4.5% and 7.5%). We established an UHS model and administered various fluid combinations (dose-related sodium chloride solution+crystal-colloidal solution) to the groups followed by monitoring indexes of hemodynamic and renal function, measuring infusion volume and blood loss, and analyzing pathological morphology by hematoxylin and eosin staining. RESULTS The hypertonic saline groups showed more stable hemodynamic indexes, reduced blood loss, fewer required infusions, and milder decreases in renal function than those of control groups (SNT and NS groups), and exhibited fewer pathological changes in the heart, lung, kidney, and liver. All indexes in the 4.5% and 7.5% groups were better than those of the NS group, and the hemodynamic indexes in the 7.5% group were more stable than those of the 4.5% group (P<0.05), with reduced blood loss and infusion volume and a milder decrease in renal function. CONCLUSIONS The novel fluid combination with 7.5% hypertonic saline group had a better recovery effect at the early stage of UHS before hemostasis compared to that of the 4.5% hypertonic saline group. This result may provide guidance for clinical fluid resuscitation.

Figure 1

Protocol of establishing UHS model. Rabbits were subjected to UHS by bleeding via the femoral artery, followed by drawing additional amounts of blood to maintain MAP of 40–45 mmHg for 15 minutes. At T30, the blood was allowed to flow free. Animals were treated with the dose-related saline at 10 minutes. Then, rabbits were treated with LRS+HES (ratio of 2: 1) to maintain MAP of 50–55 mmHg (hypotensive resuscitation). UHS – uncontrolled hemorrhagic shock; MAO – mean arterial pressure; LRS – lactate Ringer’s solution; HES – 6% hydroxyethyl starch 130/0.4 solution.

Figure 2

(A, B) LVSP, CVP at T0, T15, T30, T45, T60 and T90. * P<0.05: at T15 and T30, LVSP, CVP in group SO were significantly higher than those in the SNT group, the NS group, the 4.5% group, and the 7.5% group. ^@ P<0.05: at T45, LVSP, CVP in the 7.5% group were significantly higher than those in the SNT group and the NS group. At T45, ^# P<0.05: LVSP in the 7.5% group was significantly higher than in the 4.5% group. Abbreviations: SO, sham-operated, SNT, shock non-treated group; NS, normal saline group; 4.5% – 4.5% hypertonic saline solution; 7.5% – 7.5% hypertonic saline solution; n=8 for all groups.

Figure 3

(A, B) ±dp/dt_max at T0, T15, T30, T45, T60 and T90. * P<0.05: at T15, T30, ±dp/dt_max in the SO group was significantly higher than in the SNT group, the NS group, the 4.5% group, and the 7.5% group. ^@ P<0.05: at T45, ±dp/dt_max in the 7.5% group was significantly higher than in the SNT group and the NS group. ^# P<0.05: ±dp/dt_max in the 7.5% group was significantly higher than in 4.5% group. SO – sham-operated; SNT – shock non-treated group; NS – normal saline group; 4.5% – 4.5% hypertonic saline solution; 7.5% – 7.5% hypertonic saline solution; n=8 for all groups.

Figure 4

HR at T0, T15, T30, T45, T60 and T90. * P<0.05: at T90, HR in group 7.5% were significantly higher than those in the NS group and the 4.5% group. SO – sham-operated; SNT – shock non-treated group; NS – normal saline group; 4.5% – 4.5% hypertonic saline solution; 7.5% – 7.5% hypertonic saline solution; n=8 for all groups.

Figure 5

(A, B) BUN and SCR at T0, T30, T60 and T90. * P<0.05: at T30, BUN and SCR in the SO group were significantly lower than those in the SNT group, the NS group, the 4.5% group, and the 7.5% group. ^@ P<0.05: at T60, BUN and SCR in the 7.5% group were significantly lower than in the NS group. ^# P<0.05: at T90, BUN and SCR in 7.5% group were significantly lower than those in the NS group. SO – sham-operated, SNT, shock non-treated group; NS, normal saline group; 4.5% – 4.5% hypertonic saline solution; 7.5% – 7.5% hypertonic saline solution; n=8 for all groups.

Figure 6

The changes of pathological section at heart, lung and kidney of UHS rabbits. (A) photomicrographs of heart; (B) photomicrographs of lung; (C) photomicrographs of kidney; (D) photomicrographs of liver. SO – sham-operated; SNT – shock non-treated group; NS – normal saline group; 4.5% – 4.5% hypertonic saline solution; 7.5% – 7.5% hypertonic saline solution; n=8 for all groups.

Figure 7

The histopathologic injury score in the (A) heart, (B) lung, (C) kidney, and (D) liver after uncontrolled hemorrhagic shock (UHS). * P<0.05 for the NS group compared with the 4.5% group. ^@ P<0.05 for the NS group compared with the 7.5% group. ^# P<0.05 for 4.5% group compared with the 7.5% group.