Immediate hemodynamic and metabolic effects of 7.5% sodium chloride and its association with 6% dextran 70 in hemorragic shock resuscitation: an experimental study in dogs

Abstracts

JUSTIFICATIVA E OBJETIVOS: O dextran associado à solução hipertônica de cloreto sódio a 7,5% apresenta efeitos hemodinâmicos benéficos no controle prolongado da reanimação no choque hemorrágico. O objetivo deste estudo foi verificar se a associação do dextran à solução de cloreto de sódio a 7,5% apresentaria vantagens na avaliação imediata dos parâmetros hemodinâmicos e metabólicos na reanimação em modelo de choque hemorrágico controlado em cães. MÉTODO: Foram estudados 16 cães submetidos à hemorragia controlada até que a pressão arterial média atingisse 40 mmHg e permanecesse assim por até 30 minutos. Estes foram divididos em G1, com administração de NaCI a 7,5%, e G2, com administração NaCI a 7,5% combinada com dextran 70 a 6%, no volume de 4 mL.kg-1, durante três minutos. Foram avaliados os parâmetros hemodinâmicos e metabólicos. Consideraram-se quatro momentos: M1 - 10 minutos após o preparo cirúrgico, M2 - obtido na metade da fase de choque, M3 - obtido dois minutos após o final da administração das soluções, M4 - 30 minutos após o início da reanimação. RESULTADOS: Após a reanimação, não houve diferença significativa dos valores da FC, PAM, PCP e IRVS. O G2 apresentou valores maiores do IC em M4. Os valores da SvO2 foram menores no G1, final do experimento. A C(a-v)O2 foi maior no G1 nos momentos M3 e M4. Os valores do VO2 aumentaram nos dois grupos em M4 e os valores do lactato plasmático aumentaram progressivamente até M3 e diminuíram em M4. Houve aumento dos valores do Na plasmático e redução do hematócrito nos dois grupos. CONCLUSÕES: O G2 mostrou melhor desempenho hemodinâmico principalmente após 30 minutos do início da reanimação. Observou-se, também, maior expansão plasmática e melhor perfusão tecidual na associação do dextran ao NaCl a 7,5%.

ANIMAIS; CHOQUE; VOLEMIA

SCIENTIFIC ARTICLE

Immediate hemodynamic and metabolic effects of 7.5% sodium chloride and its association with 6% dextran 70 in hemorragic shock resuscitation. An experimental study in dogs^*

Efectos hemodinámicos y metabólicos inmediatos determinados por las soluciones de cloruro de sodio a 7,5% y de su asociación con dextran 70 a 6% en la reanimación del choque hemorrágico. Estudio experimental en perros

José Fernando Amaral Meletti, TSA, M.D.^I; José Reinaldo Cerqueira Braz, TSA, M.D.^II; Norma Sueli Pinheiro Módolo, TSA, M.D.^III

^IProfessor Adjunto da Disciplina de Anestesiologia da Faculdade de Medicina de Jundiai, SP

^IIProfessor Titular do CET/SBA da FMB - UNESP

^IIIProfessora Adjunta Livre-Docente do CET/SBA da FMB - UNESP

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: Dextran associated with 7.5% sodium chloride has positive hemodynamic effects in the long term control of hemorrhagic shock. The objective of this study was to verify whether the association of dextran with 7.5% chloride solution would be advantageous in the immediate hemodynamic evaluation of controlled hemorrhagic shock in dogs.

METHODS: This study included 16 dogs submitted to controlled hemorrhage until their mean arterial blood pressure reached 40 mmHg, being maintained at this level for 30 minutes. They were divided in two groups: G1 received 7.5% NaCl and G2 received 7.5% NaCl in 6% dextran 70; in both groups, 4 mL.kg^-1 of the solutions were administered for three minutes. Hemodynamic and metabolic parameters were evaluated in four different phases: M1 – 10 minutes after preparation for surgery, M2 – obtained in the middle of the shock phase. M3 – two minutes after the administration of the IV solutions, M4 – 30 minutes after the beginning of the resuscitation.

RESULTS: After the resuscitation, there were no significant differences in HR, MAP, PCP, and SVRI. G2 presented the highest CI values in M4. G1 showed the smaller SvO₂ values at the end of the experiment; and the C_(a-v)O₂ was higher in M3 and M4. For both groups, VO₂ values increased in M4, and lactate plasma values increased progressively until M3, decreasing in M4. Both groups also presented increased Na plasma values and decreased hematocrit.

CONCLUSIONS: G2 showed the best hemodynamic performance, especially 30 minutes after the beginning of resuscitation. Plasma expansion and tissue perfusion were also better with 7.5% NaCl in dextran.

Key Words: ANIMALS: dogs; SHOCK: hypovolemic; VOLEMIA: crystalloid expansion, dextran.

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: El dextran, asociado a la solución hipertónica de cloruro sodio a 7,5% presenta efectos hemodinámicos benéficos en el control prolongado de la reanimación en el choque hemorrágico. El objetivo de este estudio fue verificar si la asociación del dextran a la solución de cloruro de sodio a 7,5% presentaría ventajas en la evaluación inmediata de los parámetros hemodinámicos y metabólicos en reanimación de modelo de choque hemorrágico controlado en perros.

MÉTODO: Se estudiaron 16 perros sometidos a la hemorragia controlada hasta que la presión arterial promedio alcanzase 40 mmHg y permaneciese así hasta 30 minutos. Ellos fueron divididos en G1 administración de NaCI a 7,5% y G2 administración NaCI a 7,5% combinada con dextran 70 a 6%, en un volumen de 4 mL.kg^-1, durante tres minutos. Se evaluaron los parámetros hemodinámicos y metabólicos. Se tuvo en cuenta cuatro momentos de estudio: (M1) 10 minutos después de la preparación quirúrgica, (M2) obtenido en la mitad de la fase de choque, (M3) obtenido dos minutos después del final de la administración de las soluciones, (M4) 30 minutos después del inicio de la reanimación.

RESULTADOS: Después de la reanimación, no hubo diferencia significativa de los valores de la FC, PAM, PCP y IRVS. El G2 presentó valores mayores del IC en M4. Los valores de la SvO₂ fueron menores en el G1, final del experimento. La C_(a-v)O₂ fue mayor en el G1 en los momentos M3 y M4. Los valores del VO₂ aumentaron en los dos grupos en M4 y los valores del lactato plasmático aumentaron progresivamente hasta llegar a M3 disminuyendo en M4. Hubo un aumento de los valores del en la plasmático y una reducción del hematócrito en los dos grupos.

CONCLUSIONES: El G2 mostró un mejor desempeño hemodinámico principalmente después de 30 minutos del inicio de la reanimación. Se observó también, una mayor expansión plasmática y una mejor perfusión de tejido en la asociación del dextran con NaCl a 7,5%.

INTRODUCTION

Hypertonic sodium chloride has been used since the beginning of the XX Century as initial or adjuvant treatment of hemorrhagic shock. Its use was first described in the treatment of American soldiers in World War I ¹. In the 1960s, it was observed that sodium chloride solutions containing 1800 mOsm.L^-1 provided temporary recovery of the blood pressure in patients with hemorrhagic shock ². That result was attributed to volume expansion and pre-capillary vasodilation ^3,4.

Velasco et al. demonstrated that the administration of 7.5% sodium chloride solution (2400 mOsm.L^-1), at a volume corresponding to 10% of the total blood loss, to dogs with hemorrhagic shock (blood loss of 40 to 50 mL.kg^-1) improved mean arterial blood pressure, cardiac output, and survival. Hemodynamic parameters did not improve in animals treated with normal saline and they all died ⁵.

The effects of 7.5% NaCl were temporary, disappearing one to two hours ^6,7 after the infusion. Associating 6% dextran 70 to the hypertonic solution ⁸ accelerated volume expansion and converted the temporary hemodynamic effects of the dextran solution into an effective increase in blood pressure and cardiac output ^9,10.

Other colloid solutions, besides dextran, were evaluated to determine whether their association was also beneficial. Hemodynamic responses were better for 7.5% NaCl in 6% dextran 70 than for 7.5% NaCl in 6% hetastarch¹¹.

Comparative evaluation of 7.5% NaCl solution and its association with 6% dextran 70 was studied in experimental models of hemorrhagic shock in pigs, in which some hemodynamic parameters were measured 5, 15, and 30 minutes after the treatment. It showed that the association with dextran was significantly superior to 7.5% NaCl alone ¹².

Prospective, randomized studies evaluated the effects of 7.5% NaCl alone or associated with 6% dextran 70 as the initial treatment of hemorrhagic shock in approximately 1,500 patients admitted to hospitals ^13-16. They demonstrated that the hypertonic solution associated with dextran was safe and free of toxic side effects. There were no renal, neurological, cardiopulmonary, or septic complications. They showed a fast and significant increase in blood pressure, longer survival, and absence of rebleeding ¹⁷.

This study was designed to determine whether 7.5% NaCl solution or its association with 6% dextran 70 presented different hemodynamic and metabolic effects in the immediate post-resuscitation period in the experimental model of controlled hemorrhagic shock in dogs, since the benefits of adding hyperoncotic solutions to hypertonic sodium chloride solutions are evident in the long-term control of hemorrhagic shock.

METHODS

After approval by the Ethics Committee on Animal Experiments of the Faculdade de Medicina da UNESP, Campus Botucatu, 16 adult, mongrel dogs, of both genders, weighing between 16 and 24 kg were studied. They were divided in two groups with 8 animals each, which underwent three experimental phases: in the preparation phase, the animals were treated with the same anesthetics and submitted to the same procedures; in the experimental resuscitation phase, the animals were divided according to the type of solution used for resuscitation:

G1: hypertonic solution: 7.5% sodium chloride solution (HS) – 4 mL.kg^-1.

G2: hypertonic solution with dextran: 7.5% sodium chloride solution 6% dextran 70 (HSD) – 4 mL.kg^-1.

After a 12-hour fasting period, animals were anesthetized with pentobarbital sodium 30 mg.kg^-1, with a maintenance anesthesia of 3.6 mg.kg^-1h^-1 (infusion pump model Anne, Abbot, USA), and placed on a Claude Bernard gutter and the following procedures were performed:

1. Tracheal intubation and controlled mechanical ventilation with a rebreather system using model 674 of the anesthesia device K. Takaoka model 2600. The settings included a tidal volume of 12 mL.kg^-1 , respiratory rate of 16 irpm, and oxygen at 1 L.min^-1; 2. Dissection and catheterization of the femoral veins, left and right, for administration of anesthetic drugs (pentobarbital sodium and 0.08 mg.kg^-1 of pancuronium chloride) and to collect blood samples, respectively; 3. Dissection and catheterization of the left femoral artery to monitor blood pressure, and right femoral artery to bleed the dog; 4. Dissection of the right external jugular artery and placement of a Swan-Ganz catheter; 5. Calibration of the Datex Engstron monitor, type D-VNC 15-00-02 s/n 763177; 6. Verification of catheter placement; 7. Monitoring with continual electrocardiogram, D_II lead derivation, pulse oxymeter on the animal's tongue, and tympanic thermometer on the left ear; 8. Laparotomy with a midline incision for splenectomy with strict homeostasis of the surgical wound; 9. Complementation of the dose of pancuronium (0.02 mg.kg^-1) and stabilization of the animal for 10 minutes; 10. Performance of the first phase of the study (control phase): drawing blood samples: arterial, venous, and mixed; and determination of baseline hemodynamic parameters (heart rate, systolic arterial pressure, mean arterial pressure, pulmonary arterial pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac output, cardiac index, systolic index, systemic vascular resistance index, pulmonary vascular resistance index, and left ventricle end-diastolic work load index); 11. Animals were bled two minutes after the control phase; 12. Bleeding 10% of the animal's calculated blood volume through the right femoral artery catheter and observation of the hemodynamic parameters for 5 minutes; 13. Bleeding of an additional 10% of the animal's calculated blood volume through the right femoral artery catheter and observation of the hemodynamic parameters for 5 minutes to determine whether the animal would need further bleeding; 14. Bleeding was discontinued when mean arterial pressure was maintained at approximately 40 mmHg for a 5-minute period; 15. Animals were stabilized for 30 minutes; 16. Drawing arterial, venous, and mixed blood samples and determination of the same hemodynamic parameters halfway the stabilization phase (M2); 17. 4 mL.kg^-1 HS (G1) or HSD (G2) were administered for 3 minutes; 18. Collection of arterial, venous, and mixed blood samples and determination of hemodynamic parameters 2 minutes after the infusion of the hypertonic solution was finished (M3); 19. The animal was stabilized for 25 minutes; 20. Drawing arterial, venous, and mixed blood samples and the measurement of hemodynamic parameters 30 minutes after the beginning of the infusion of hypertonic solution (M4); 21. End of the experiment.

Parameters Evaluated

1. Hemodynamic: heart rate (HR – beats.min^-1), mean arterial pressure (MAP – mmHg), pulmonary capillary wedge pressure (PCWP – mmHg), cardiac index (CI – L.min^-1.m^-2), systemic vascular resistance index (SVRI – dinas.seg. cm^-5.m^-2). 2. Tissue oxygenation and metabolites: mixed venous saturation (SvO₂ - %), oxygen arteriovenous difference C_(av)O₂ mL. 100 mL^-1), oxygen delivery (DO₂ mL.min^-1), oxygen consumption (VO₂ mL.min^-1), plasma lactate (Lactate mEq.L^-1). 3. Acid-base balance: pH, partial pressure of carbon dioxide (PaCO₂ mmHg). 4. Hematological: sodium plasma level (Na mEq.l^-1), hematocrit (Ht - %).

The data were measured in 4 moments: M1 – after a 10-minute stabilization period following the surgical phase, considered the baseline or control parameter; M2 – after the shock phase, 15 minutes after the beginning of the 30-minute stabilization period; M3 – 2 minutes after the infusion of the IV solution ended; M4 – 30 minutes after the beginning of the resuscitation with hypertonic solution.

Statistical Analysis

The statistical analysis of the weight, height, and volume of blood loss was done once and the comparison between both groups was done using the test t for two independent samples, calculating t and p¹⁸.

Profile Analysis was used to verify the variables through time¹⁹. F and p were calculated for each hypothesis. In every analysis, values were considered statistically significant for a p < 0.05. When 0.05 < p < 0.10 it was considered a significant tendency (p is the probability of wrongfully concluding for the significance).

RESULTS

Weight, length, body surface area, and volume of blood loss were similar in both groups (test t) (Table I).

Heart rate was lower at the end of the bleeding phase and in the beginning of the resuscitation phase in both groups, returning to baseline (control) values at the end of the experiment. Mean arterial pressure was increased in both groups after resuscitation (M3 and M4); however, these values did not return to baseline (M1). Pulmonary capillary wedge pressure was lower in G2 than in G1 at the second phase of the experiment, but values were the same in both groups during resuscitation. Even though both groups have similar profiles, CI in G2 was slightly higher than in G1 during the fourth phase. Baseline SVRI values were increased in both groups, remained elevated after bleeding, but were significantly reduced at the beginning of the resuscitation; however, SVRI returned to baseline values at the end of the experiment (Table II).

The profile of SvO₂ values was different between both groups and among the different phases. In phase four, those values were significantly higher in G2 than in G1. Regarding the oxygen content difference, values in G1 were significantly higher during resuscitation. Baseline DO₂ values were elevated in both groups. They decreased drastically during the shock, but increased after crystalloid expansion without reaching baseline values. Oxygen consumption values were higher in G1 than in G2. Plasma lactate values increased gradually until the beginning of the resuscitation; at the end of the experiment, it reduced considerably to values similar to those found during the hypovolemic shock (Table III).

As for the acid-base balance, pH values did not change with the hemorrhagic shock, decreasing after crystalloid expansion. After resuscitation, the partial pressure of carbon dioxide increased considerably in both groups (Table IV).

Both groups showed equal and pronounced elevation of sodium plasma values after volume resuscitation. On the other hand, hematocrit values reduced significantly after bleeding and immediately before resuscitation, stabilizing after the administration of IV solution in both groups (Table V).

DISCUSSION

The anesthetic technique used is recommended by most authors for this experimental model; it allows the establishment of an adequate anesthetic plane in a few minutes ^{5, 20-23}. Pentobarbital sodium was infused continuously (3.6 mg.kg^-1. h^-1) to maintain a stable plasma concentration of the drug to keep the dog anesthetized during the whole experiment ^24-26.

The experimental model of hemorrhagic shock in animals used frequently is the Wiggers, 1942 model ²⁷. Shock is induced by bleeding the animal and maintaining the mean arterial pressure between 35 and 40 mmHg. Several researchers have modified this model to suit the objectives of their work ^28-30.

It was determined that the hypertonic solution would be administered over a 3-minute period, similar to other works ^8,9,13,31, and this time was aimed at not causing histological lesions in the vascular wall ³¹. The volume infused to each group was 4 mL.kg^-1. This is the volume proposed by most studies, experimental or in human beings ^5,7,8,11,32.

We observed that the heart rate decreased significantly in the hemorrhagic shock phase. This can be explained by the Baindridge reflex in which a decrease in venous return leads to bradycardia, since the sensibility of the venous baroreceptors is greater than the arterial baroreceptors ^33,34. Therefore, in this situation, the significative reduction in venous return may have caused a reduction in heart rate.

At the time of resuscitation with both solutions used in this study, there were no changes in HR, which was also observed in other studies using rapid infusion of hypertonic solutions ^12,35. Thirty minutes after the infusion of the IV solution started, plasma osmolarity increased due to an increase in sodium concentration, leading to improved cardiac performance and HR when compared to control levels ^23,36.

The simple hypertonic solution improves hemodynamic parameters temporarily, unless a colloid solution is added to the hyperosmolar solution. While the hypertonicity of the solution is responsible for removing fluid from the intracellular space, the hyperoncotic colloid solution maintains this fluid in the intravascular space. The physiological effects of small volumes of hypertonic solutions are associated with an increase in mean arterial pressure, cardiac output, and plasma expansion. These solutions also increase oxygen consumption; dilate the pre-capillary sphincters; increase cardiac contractility, diuresis, and natriuresis; restore membrane potential and decrease the volume needed to restore blood volume in the long-term control of shock ¹¹.

In this study, both solutions had similar hemodynamic performances in the second minute after the administration of the solution finished, earlier than other reports in the literature. However, from that point until 30 minutes after the beginning of resuscitation, the superiority of the hypertonic solution in dextran is unquestionable, especially when the cardiac index in both groups is analyzed.

The effects of the 7.5% hypertonic solution on blood pressure, cardiac output, and systolic index are almost instantaneous, lasting 45 minutes for 7.5% NaCl and from 2 to 4 hours when it is combined with 6% dextran 70. The increase in cardiac contractility does not depend on preload ¹⁷.

Vasodilation is most likely secondary to an effect of the osmolarity on the arteriolar wall or to a vasodilation reflex triggered by pulmonary receptors that can detect an increase in plasma osmolarity. Characteristically, vasodilation triggered by hypertonic solutions decreases systemic vascular resistance and pulmonary vascular resistance directly, independently of the local innervation, and is observed in most vascular beds ¹⁷.

When hemodynamic parameters were analyzed, we noticed that hyperosmolar solutions at 7.5% produced immediate and peculiar cardiovascular effects. Basically, there was an important pre-capillary vasodilation, with decreased systemic vascular resistance, improved myocardial contractility, increased mean arterial pressure and pulmonary capillary wedge pressure, and increased preload indexes.

Adding the hyperoncotic solution, 6% dextran 70, to 7.5% NaCl did not produce any hemodynamic differences during the early resuscitation phase (M3). Analyzing the results 30 minutes after the resuscitation began, HSD had better vascular performance, especially in the cardiac index.

In normal physiological conditions, oxygen consumption is determined by the tissue metabolic needs, independently of oxygen transport. During periods of increased metabolism or decreased tissue perfusion, oxygen extraction, which is normally 25%, increases to 75%-80%. In these conditions, there is a drastic reduction in oxygen content in the central compartment ³⁷.

In this study, there was a 38% reduction in the mixed venous saturation with a 46% reduction in blood volume during the hemorrhagic shock phase. This result was similar to the results reported in the literature ^28,38.

Mixed venous saturation showed the same results in both groups in the resuscitation phase. However, at the end of the experiment, they remained unchanged in the HSD group, while they were significantly reduced in the HS group. These results demonstrate that 7.5% NaCl in dextran 70 was superior to the hypertonic solution alone regarding mixed venous saturation in the first 30 minutes of resuscitation. Mixed venous saturation demonstrated that blood flow in the microcirculation was even lower in the HS group, leading to an increased oxygen extraction, than in the HSD group.

Oxygen delivery (DO₂) is the result of the arterial oxygen content (CaO₂) multiplied by the cardiac output (CO). Conversely, the reduction in arterial oxygen content depends on hemoglobin oxygen concentration and saturation. Therefore, a reduction in DO₂ can be corrected with a blood transfusion or increasing cardiac output. Cardiac output tends to be increased when oxygen consumption is increased, such as in trauma ³⁹.

Oxygen consumption (VO₂) is the result of oxygen venous content multiplied by cardiac output. Reduced or inadequate oxygen consumption is the common denominator in every shock syndrome. Oxygen consumption also seems to be related with survival in patients with hemorrhagic shock ⁴⁰.

The oxygen content arteriovenous difference index (C_(av)O₂) represents the relationship between oxygen consumption and cardiac output. For this reason, it represents intrinsically an index of hemodynamic function adequacy; therefore, its elevation usually represents hypodinamic cardiovascular states secondary to cardiac dysfunction or hypovolemia ⁴¹.

With a blood loss of approximately 34 mL.kg^-1, we observed a reduction in oxygen delivery and increase in arteriovenous oxygen difference in both groups, but oxygen consumption remained unchanged. Oxygen consumption should be considered a prognostic index in hemorrhagic shock. When reduced, it indicates irreversible shock ³.

Hannon et al. ⁴² evaluated the relationship between oxygen transport and requirements during a hemorrhage of approximately 37 mL.kg^-1 in one hour and during resuscitation with 4 mL.kg^-1 of 7.5% NaCl in 6% dextran 70 in the experimental shock model in pigs. During the shock phase, there was a slight increase in VO₂, lactate plasma values were significantly increased, DO₂ values were significantly decreased, and oxygen requirements doubled. The difference between oxygen delivery and requirements was reduced by volume expansion with hypertonic solution, primarily by the suppression of the metabolic requirements and, to a lesser extent, by an increase in DO₂.

Hemodynamic and metabolic performance of HS and HSD solutions at 5, 15, and 30 minutes after resuscitation of pigs with hemorrhagic shock demonstrated that oxygen transport values were significantly higher in the dextran group throughout the experiment.

Clinically, increased lactate values presented a good correlation with oxygen deficiency and anaerobic metabolism. In humans, lactate values higher than 2 mEq.L^-1 are associated with increased mortality, and values higher than 3 and 4 mEq.L^-1 indicate profound hypoperfusion.

In aerobic conditions, carbohydrate metabolism follows the Krebs cycle; therefore, the sequential oxidation of a molecule of carbon produces 38 ATP molecules. When oxygen supply is reduced, the usual sequence is interrupted. Pyruvate is converted in lactate and the energy yield is limited to the production of just 2 ATP molecules. Lactate produced in anaerobic conditions accumulates in the body because it is used in a limited number of depurative processes that occur, basically, in the hepatocytes ³⁷.

Strecker et al. ⁴³ studied the efficacy of 6% dextran or 6% hetastarch associated with 7.5% hypertonic solutions in the resuscitation of hemorrhagic shock in rabbits. In both groups, the oxygen content difference returned to pre-shock values 2 minutes after resuscitation, similar to what happened in our study. But in his study, they were significantly increased in the hetastarch group 15 and 60 minutes after resuscitation. Serum lactate values decreased immediately in both groups, but this reduction was less prominent in the dextran group. Lactate and BE values were significantly reduced, but this reduction was greater in the dextran group than in the hetastarch group 60 minutes after resuscitation.

In Strecker's study, a reduction in circulating volume caused a reduction in cardiovascular function that led to a significant decrease in TEO₂ during the hemorrhagic shock phase. After resuscitation, CO and DO₂ were higher in the group that received hypertonic saline-dextran (HSD). Consequently, the oxygen content difference was lower in the HSD group than in the hetastarch group. The authors explained that the greater elevation of lactate values in the HSD group was secondary to an increase in tissue perfusion in areas with high lactate content caused by the shock.

In this study, C_(av)O₂ values were higher in the hypertonic solution group on both resuscitation times. The TEO₂ values showed a statistically significant difference; they were higher in G1 30 minutes after IV infusion started. It indicated that the decrease in systemic flow was greater in G1 than in G2, being responsible for the greater oxygen extraction by the cells and the smaller mixed venous saturation in G1 seen at the end of the experiment.

In this study, there were significant differences in lactate values in the study groups, which were reduced only at the end of the experiment.

Chiara et al. ⁴⁴ also compared 7.5% NaCl and its combination with 6% dextran 70 in an experimental model of hemorrhagic shock in pigs. They concluded that there were no statistically significant differences in DO₂, VO₂, and TEO₂ between both solutions in the beginning of the resuscitation. These indexes increased significantly only one hour after the administration of the solutions in the HSD group when compared to the HS group.

There was an decrease in pH and an increase in the partial pressure of carbon dioxide after the administration of the hypertonic solution of sodium chloride (1800 mOsm.L^-1) ². The same happened after the administration of 7.5% NaCl ⁵.

Arterial pH changed from 7.34 to 7.26 after removal of around 44% of the estimated blood volume for each dog ⁴⁵. In our study, pH was reduced from about 7.30 to 7.23 in both groups, and there were no statistically significant differences in the variation of pH after the removal of approximately 46% of the estimated blood volume for each dog.

In our experiment, after volume expansion, both groups presented similar behavior. The increase in pH and partial pressure of carbon dioxide was significant and sustained, both in M3 and M4, similar to what was seen in other studies^42,43.

The administration of hypertonic solution alone or in dextran increased the PaCO₂ and reduced arterial pH significantly shortly after resuscitation of hemorrhagic shock. This was due to the brief acidemia caused, mainly, by the hyperchloremia, hypokalemia, and metabolic acidosis without anion gap, secondary to respiratory acidosis caused by elevated PaCO₂^46,47.

In our study, the worsening of the acidosis in the initial stages of resuscitation was probably due to a possible hyperchloremia caused by the administration of hypertonic solution, without enough time for its recovery. The sudden increase in partial pressure of carbon dioxide indicated improvement in tissue perfusion, but also contributed to maintaining the acidemia recorded during resuscitation.

Substituting chloride for acetate in the hypertonic solution, in order to produce isochloremic resuscitation, was not effective. Plasma chloride values were not elevated and blood acidosis was quickly corrected, but its administration led to unsatisfactory cardiovascular and metabolic performances when compared with traditional solutions ⁴⁸.

There was a reduction in hematocrit immediately after resuscitation. This was explained by the acute expansion of the intravascular compartment caused by the administration of 7.5% NaCl and by the transport of fluids from the intracellular and interstitial compartments, resulting in a dramatic reduction in hematocrit immediately after resuscitation ^2,5,49.

Comparing 7.5% NaCl with its association with 6% dextran 70 in dogs submitted to hemorrhagic shock showed that volume expansion was maintained over three hours in the group that received the hypertonic saline-dextran solution, with consequent decrease in hematocrit ^52,53. This plasma expansion would be secondary to the reduction of the cellular edema caused by hemorrhagic shock ^50,51. The hypertonic solution of sodium chloride also contributed with the removal of intracellular fluid from red blood cells and endothelial cells ^52,53.

Reduction of the edema of the endothelial cells was particularly important in the capillaries, where previously settled edema reduced significantly vessel lumen, leading to an important reduction in red blood cell flow. This may explain the immediate recovery in metabolic function after the administration of hypertonic solution when compared with the same volume-expanding effect of the isotonic solution, since it recomposes the volume equally, but does not decrease endothelial edema immediately ^54-56.

The osmotic gradient of solutions with 2400 mOsm.L^-1 removed intracellular fluid, initially from the red blood cells and from endothelial cells, followed by the interstitial compartment and tissue cells. It is possible that the addition of the hyperoncotic solution of dextran was responsible for the sustained plasma expansion at the end of the experiment, seen in G2, not allowing the hematocrit to rise.

The single administration of 4 mL.kg^-1 of HS adds 5.13 mEq.L^-1 of sodium per kilogram of weight, leading to a moderate and temporary hypernatremia ⁵⁷. Since intravascular volume is approximately 40 mL.kg^-1, this sodium load would promote a theoretical increase of 128 mEq.L^-1, elevating sodium plasma values to 263-268 mEq.L^-1. However, while the solute is being administered, its osmotic force dilutes the intravascular compartment, avoiding the expected increase in plasma sodium concentration ⁵⁸.

In this study, sodium plasma values increased dramatically after resuscitation with 7.5% NaCl and its association with 6% dextran 70, reaching up to 153 mEq.L^-1. The elevation of plasma sodium values was moderate and temporary, increasing values an mean of 12 mEq.L^-1, which was not harmful for the dogs ^7,59.

We conclude that, in this experimental model in dogs, the association of a hypertonic solution, 7.5% sodium chloride, with a hyperosmolar solution, 6% dextran 70 (HSD), had a better hemodynamic performance than 7.5% NaCl alone, especially 30 minutes after the beginning of the resuscitation. Tissue perfusion, reflected by the mixed venous saturation and arterial-venous oxygen difference, was better with HSD than with HS. Plasma expansion, secondary to the increased tonicity of the solutions, was evident immediately after resuscitation in both groups, but only the association with 6% dextran 70 was capable of maintaining this effect for up to 30 minutes after the beginning of the IV administration.

REFERENCES

Submitted for publication 09 de dezembro de 2005

Accepted for publication 27 de junho de 2006

• 01. Penfield WG The treatment of severe and progressive hemorrhage by intravenous injections. Am J Physiol, 1919;48:121-128.
• 02. Baue AE, Tragus ET, Parkins WM Effects of sodium chloride and bicarbonate in shock with metabolic acidosis. Am J Physiol, 1967;212:54-60.
• 03. Gazitua S, Scott JB, Chou CC et al Effect of osmolarity on canine renal vascular resistance. Am J Physiol, 1969;217:1216-1223.
• 04. Gazitua S, Scott JB, Swindall B et al Resistance response to local changes in plasma osmolality in three vascular beds. Am J Physiol, 1971;220:384-391.
• 05. Velasco IT, Pontieri V, Rocha e Silva M Jr et al Hyperosmotic NaCl and severe hemorrhagic shock. Am J Physiol, 1980; 239: H664- H673.
• 06. Rocha e Silva M, Negraes GA, Soares AM et al Hypertonic resuscitation from severe hemorrhagic shock: patterns of regional circulation. Circ Shock, 1986;19:165-175.
• 07. Rocha e Silva M, Velasco IT, Nogueira da Silva RI et al Hyperosmotic sodium salts reverse severe hemorrhagic shock: other solutes do not. Am J Physiol, 1987;253:H751- H762.
• 08. Smith GJ, Kramer GC, Perron P et al A comparison of several hypertonic solutions for resuscitation of bled sheep. J Surg Res, 1985;39:517-528.
• 09. Kramer GC, Perron PR, Lindsey DC et al Small-volume resuscitation with hypertonic saline dextran solution. Surgery, 1986;100:239-247.
• 10. Velasco IT, Rocha e Silva M, Oliveira MA et al Hypertonic and hyperoncotic resuscitation from severe hemorrhagic shock in dogs: a comparative study. Crit Care Med, 1989;17:261-264.
• 11. Kramer GC, Walsh JC, Perron PR et al Comparison of hypertonic saline/dextran versus hypertonic saline/hetastarch for resuscitation of hypovolemia. Braz J Med Biol Res, 1989;22:279-282.
• 12. Wade C, Hannon J, Bossone C et al Superiority of hypertonic saline/dextran over hypertonic saline during the first 30 min of resuscitation following hemorrhagic hypotension in conscious swine. Resuscitation, 1990;20:49-56.
• 13. Holcroft JW, Vassar MJ, Turner J et al 3% NaCl and 7.5% Na/Cl/dextran 70 in the resuscitation of severely injured patients. Ann Surg, 1987;206:276-288.
• 14. Mattox KL, Maningas PA, Moore EE et al Prehospital hypertonic saline/dextran infusion for post-traumatic hypotension. The USA Multicenter Trial. Ann Surg, 1991;213:482-491.
• 15. Vassar MJ, Holcroft JW Use of hypertonic-hyperosncotic fluids for resuscitation of trauma patients. J Intensive Care Med, 1992; 7:189-198.
• 16. Younes RN, Ching CT, Goldenberg DC et al Hypertonic saline-dextran in the treatment of hemorrhagic shock: clinical trial in the emergency room. Proceedings of the 5^th International Conference on Hypertonic Resuscitation, 1992.
• 17. Rocha e Silva M Hypertonic saline resuscitation. Medicina (B Aires), 1998;58:393-402.
• 18. Curi PR Metodologia e Análise da Pesquisa em Ciências Biológicas. 2Ş Ed, Botucatu: Tipomic, 1998.
• 19. Morrison DF Multivariate Statistical Methods. 3Ş Ed, New York: Mc Graw Hill; 1967.
• 20. Gilmore JP Pentobarbital sodium anesthesia in the dog. Am J Physiol, 1965;209:404-408.
• 21. Olmsted F, Page IH Hemodynamic changes in dogs caused by sodium pentobarbital anesthesia. Am J Physiol, 1966;210:817-820.
• 22. Priano LL, Traber DL, Wilson RD Barbiturate anesthesia: an abnormal physiologic stimulation. J Pharmacol Exp Ther, 1969;165:126-135.
• 23. Ogino R, Suzuki K, Kohno M et al Effects of hypertonic saline and dextran 70 on cardiac contractility after hemorrhagic shock. J Trauma, 1998;44:59-69.
• 24. Hotvedt R, Platou ES, Koppang ER et al Pentobarbital plasma concentration and cardiac eletrophysiology during prolonged pentobarbital infusion anesthesia in the dog. Acta Anaesthesiol Scand, 1982;26:638-642.
• 25. Welte M, Goresch T, Frey L et al Hypertonic saline dextran does not increase cardiac contractile function during small volume resuscitation from hemorrhagic shock in anesthetized pigs. Anesth Analg, 1995;80:1099-1107.
• 26. Sato JK Efeitos hemodinâmicos da isradipina em cães submetidos a pinçamento aórtico infra renal. [dissertação]. Botucatu: Faculdade de Medicina, Universidade Estadual Paulista; 1997.
• 27. Wiggers CJ, Werle JN Exploration of a method for standarding hemorragic. Proc Soc Biol Med, 1942;49:604-606.
• 28. Dillon AR, Hankes GH, Nachreiner RF et al Experimental hemorrhage in splenectomized and nosplenectomized dogs. Am J Vet Res, 1980;41:707-711.
• 29. Scalea TM, Holman M, Fuortes M et al Central venous blood oxygen saturation: an early, accurate measurement of volume during hemorrhage. J Trauma, 1988;28:725-732.
• 30. Pianim NA, Liu SY, Dubecz S et al Tissue oxygenation in hypovolemic shock. J Surg Res, 1993;55:338-343.
• 31. Hands R, Holcroft J, Perron P et al Comparison of peripheral and central infusions of 7.5% NaCl/6% dextran 70. Surgery, 1988;103:684-689.
• 32. Onarheim H, Missavage AE, Kramer GC et al Effectiveness of hypertonic saline-dextran 70 for initial fluid resuscitation of major burns. J Trauma, 1990;30:597-603.
• 33. Epstein SE, Stampfer M, Beiser GD Role of the capacitance and resistance vessels in vasovagal syncope. Circulation, 1968; 37:524-533.
• 34. Greene NM Reports of scientific meetings. Anesthesiology, 1971;34:104-105.
• 35. De Barros LF, Baena RC, Velasco IT et al Efeitos hemodinâmicos imediatos da infusão rápida de solução hipertônica de cloreto de sódio-dextran-70 para tratamento de choque hemorrágico em cães. Arq Bras Cardiol, 1993;61:317-320.
• 36. Mouren S, Delayance S, Mion G et al Mechanisms of increased myocardial contractility with hypertonic saline solutions in isolated blood-perfused rabbit hearts. Anesth Analg, 1995;81:777-782.
• 37. Guyton AC Tratado de Fisiologia Médica. 4Ş Ed, Rio de Janeiro: Guanabara Koogan; 1992.
• 38. Kim SI, Desai JM, Shoemaker WC Sequence of cardiorespiratory alterations after gradual prolonged hemorrhage in conscious dogs. Am J Physiol, 1969;216:1044-1050.
• 39. Barash PG, Lawrence LP Clinical Anaesthesia. 5^th Ed, Philadelphia: Lippincott; 1993.
• 40. Shoemaker WC Relation of oxygen transport patterns to the pathophysiology and therapy of shock states. Intensive Care Med, 1987;13:230-243.
• 41. Terzi RGG, Araújo S Monitorização Hemodinâmica e Suporte Cardiocirculatório do Paciente Crítico. São Paulo: Atheneu; 1996.
• 42. Hannon JP, Wade CE, Bossone CA et al Blood gas and acid-base status of conscious pigs subjected to fixed-volume hemorrhage and resuscitated with hypertonic saline dextran. Circ Shock, 1990;32:19-29.
• 43. Strecker U, Dick W, Madjidi A et al The effect of type of colloid in the efficacy of hypertonic saline colloid mixture in hemorrhagic shock: dextran versus hydroxyethyl starch. Resuscitation, 1993;25:41-57.
• 44. Chiara O, Segala M, Volpi D et al Hypertonic saline solutions in resuscitation in hemorrhagic shock. An experimental study. Minerva Chir, 1997;52:753-762.
• 45. Schwartz S, Frantz RA, Shoemaker WC Sequential hemodynamic and oxygen transport responses in hypovolemia, anemia and hypoxia. Am J Physiol, 1981;241:H864-H871.
• 46. Dubick MA, Davis JM, Myers T et al Dose response effects of hypertonic saline and dextran on cardiovascular responses and plasma volume expansion in sheep. Shock, 1995;3:137-144.
• 47. Moon PF, Kramer GC Hypertonic saline-dextran resuscitation from hemorrhagic shock induces transient mixed acidosis. Crit Care Med, 1995;23:323-331.
• 48. Kramer GC, Elgjo GI, De Figueiredo LFP Hypertonic-hyperoncotic solutions. Baillieres Clin Anaesth, 1997;2:143-161.
• 49. Nakayama S, Sibley L, Gunther R et al Small-volume resuscitation with hypertonic saline (2,400 mOsm/liter) during hemorrhagic shock. Circ Shock, 1984;13:149-159.
• 50. Nakayama S, Kramer GC, Carlsen RC et al Infusion of very hypertonic saline to bled rats: membrane potentials and fluid shifts. J Surg Res, 1985;38:180-186.
• 51. Matteucci MJ, Wisner DH, Gunther RA et al Effects of hypertonic and isotonic fluid infusion on the flash evoked potential in rats: hemorrhage, resuscitation, and hypernatremia. J Trauma, 1993;34:1-7.
• 52. Mazzoni MC, Borgstrom P, Arfors KE et al Dynamic fluid redistribution in hyperosmotic resuscitation of hypovolemic hemorrhage. Am J Physiol, 1988;255:H629-H637.
• 53. Mazzoni MC, Lundgren E, Arfors KE et al Volume changes of an endothelial monolayer on exposure to anisotonic media. J Cell Res, 1989;140:272-280.
• 54. Hunter M, Lee J Determination of fluid extraction and osmotic conductance sigma K in the lung with hypertonic NaCl infusion. II. Experiments. Microvasc Res, 1992;44:319-333.
• 55. Scalia SV, Taheri PA, Force S et al Mesenteric microcirculatory changes in nonlethal hemorrhagic shock: the role of resuscitation with balanced electrolyte or hypertonic saline/dextran. J Trauma, 1992;33:321-325.
• 56. Bauer M, Marzi I, Ziegenfuss T et al Comparative effects of crystalloid and small volume hypertonic hyperoncotic fluid resuscitation on hepatic microcirculation after hemorrhagic shock. Circ Shock, 1993;40:187-193.
• 57. Shackford SR, Fortlage DA, Peters RM et al Serum osmolar and electrolyte changes associated with large infusions of hypertonic sodium lactate for intravascular volume expansion of patients undergoing aortic reconstruction. Surg Gynecol Obstet, 1987;164:127-136.
• 58. Shackford SR, Norton CH, Todd MM Renal, cerebral, and pulmonary effects of hypertonic resuscitation in a porcine model of hemorrhagic shock. Surgery, 1988;104:553-560.
• 59. Dubick MA, Wade CE A review of the efficacy and safety of 7.5% NaCl/6% dextran 70 in experimental animals and in humans. J Trauma, 1994;36:323-330.

*

Received from do Laboratório Experimental do Departamento de Anestesiologia da Faculdade de Medicina da Universidade do Estado de São Paulo (FMB – UNESP), Botucatu, SP

Publication Dates

• Publication in this collection
  22 Sept 2006
• Date of issue
  Oct 2006

History

• Received
  09 Dec 2005
• Accepted
  27 June 2006