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Anesth Analg 2004;99:536-546
© 2004 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000122639.55433.06

CRITICAL CARE AND TRAUMA

The Early Systemic and Gastrointestinal Oxygenation Effects of Hemorrhagic Shock Resuscitation with Hypertonic Saline and Hypertonic Saline 6% Dextran-70: A Comparative Study in Dogs

José Reinaldo Cerqueira Braz, MD PhD, Paulo do Nascimento, Jr., MD PhD, Odilar Paiva Filho, MD, Leandro Gobbo Braz, MD, Luiz Antonio Vane, MD PhD, Pedro Thadeu Galvão Vianna, MD PhD, and Geraldo Rolim Rodrigues, Jr., MD PhD

Department of Anesthesiology, School of Medicine, University of São Paulo State, Botucatu, São Paulo, Brazil

Address correspondence and reprint requests to José Reinaldo Cerqueira Braz, MD, PhD, Department of Anesthesiology, School of Medicine, UNESP, District of Rubião Júnior, PO Box 530, 18618-970 Botucatu, São Paulo, Brazil. Address e-mail to jbraz{at}fmb.unesp.br


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
The smaller volemic state from hypertonic (7.5%) saline (HS) solution administration in hemorrhagic shock can determine lesser systemic oxygen delivery and tissue oxygenation than conventional plasma expanders. In a model of hemorrhagic shock in dogs, we studied the systemic and gastrointestinal oxygenation effects of HS and hyperoncotic (6%) dextran-70 in combination with HS (HSD) solutions in comparison with lactated Ringer’s (LR) and (6%) hydroxyethyl starch (HES) solutions. Forty-eight mongrel dogs were anesthetized, mechanically ventilated, and subjected to splenectomy. A gastric air tonometer was placed in the stomach for intramucosal gastric CO2 (PgCO2) determination and for the calculation of intramucosal pH (pHi):



The dogs were hemorrhaged (42% of blood volume) to hold mean arterial blood pressure at 40–50 mm Hg over 30 min and were then resuscitated with LR (n = 12) in a 3:1 relation to removed blood volume; HS (n = 12), 6 mL/kg; HSD (n = 12), 6 mL/kg; and HES (mean molecular weight, 200 kDa; degree of substitution, 0.5) (n = 12) in a 1:1 relation to the removed blood volume. Hemodynamic, systemic, and gastric oxygenation variables were measured at baseline, after 30 min of hemorrhage, and 5, 60, and 120 min after intravascular fluid resuscitation. After fluid resuscitation, HS showed significantly lower arterial pH and mixed venous PO2 and higher systemic oxygen uptake index and systemic oxygenation extraction than LR and HES (P < 0.05), whereas HSD showed significantly lower arterial pH than LR and HES (P < 0.05). Only HS and HSD did not return arterial pH and pHi to control levels (P < 0.05). In conclusion, all solutions improved systemic and gastrointestinal oxygenation after hemorrhagic shock in dogs. However, the HS solution showed the worst response in comparison to LR and HES solutions in relation to systemic oxygenation, whereas HSD showed intermediate values. HS and HSD solutions did not return regional oxygenation to control values.

IMPLICATIONS: Resuscitation with hypertonic saline and hypertonic saline with dextran solutions during hemorrhagic shock in dogs may not improve the splanchnic circulation, as indicated by lower intramucosal pH values during resuscitation.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Therapy for hemorrhagic shock should be aimed not only at restoring basic hemodynamic and oxygen transport variables, but also at correcting oxygen demands for specific organs (1), such as the gastrointestinal tract. The gastrointestinal tract is one of the earliest affected by hypoperfusion and may be one of the primary triggers of multiple organ system failure. Intense vasoconstriction occurs early and frequently leads to a nonreflow phenomenon, even when the macrocirculation is restored after intravascular volume replacement (2,3). Thus, the hemodynamic and systemic oxygenation variables may not reveal splanchnic hypoperfusion, resulting in a failure to recognize inadequately treated hemorrhagic shock (1). Fiddian-Green et al. (1) developed a new method to estimate gastric intramucosal pH (pHi) by using a tonometric catheter. An automated technique using a gastric air tonometer to estimate pHi semicontinuously was proposed as a routine tool (4). The pHi is an indicator of tissue perfusion, and its usefulness has been reported in a variety of patients (4–8) and in experimental hemorrhagic shock (9–11).

The concept of resuscitation with the use of a small volume (4 to 6 mL/kg) of very hypertonic (7.5%) sodium chloride (SC) solution (HS) has been described in experimental (12,13) and clinical (14,15) conditions involving hypovolemia. Small-volume HS infusions rapidly increase cardiovascular and metabolic functions by combining plasma volume expansion through the displacement of intracellular and interstitial fluid to the vascular compartment, with systemic vasodilation, myocardial performance improvement, and increased oxygen delivery (DO2) and consumption (VO2) (12,16). The use of HS with 6% dextran-70 (HSD), which is hypertonic and hyperoncotic, is a new perspective for intravascular volume replacement because it prolongs volume expansion through an endogenous fluid redistribution (17,18). The high-molecular-weight molecules from dextran-70 remain largely intravascular, augmenting plasma volume and plasma oncotic pressure and thereby limiting transvascular fluid filtration (17,18).

Using HS and HSD solutions gives small-volume resuscitation, which may have a less important circulatory effect at the initial phase of resuscitation in relation to lactated Ringer’s (LR) and hydroxyethyl starch (HES) solutions but prevents the occurrence of side effects associated with resuscitation, such as acute pulmonary edema. However, the smaller volemic state that results from HS solution administration would determine an increase in systemic DO2 and tissue oxygenation to a lesser extent than conventional plasma expanders.

Whereas the early resuscitation hemodynamic systemic effects of HS or HSD have been largely investigated in animal studies (11–13,17), their effects on regional perfusion recovery are relatively few and controversial (11,19–24). The aim of this investigation was to compare, in a model of hemorrhagic shock in dogs, the early systemic and gastrointestinal oxygenation effects of fixed bolus injections of HS and HSD solutions in comparison with LR and HES solutions. The hypothesis was that resuscitation with HS and HSD solutions improves the gut perfusion less, as measured by tonometry, than LR and HES solutions.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
The study was approved by the University Ethical Commission in Research Animals. Forty-eight mongrel dogs of both sexes, weighing from 18 to 28 kg, were used in the study. They were considered healthy after clinical examination and a normal erythrocyte count. The animals were fasted overnight but were allowed water ad libitum. A biomonitor (AS3; Datex Engstron Instrumentarium, Helsinki, Finland) was installed for monitoring and recording ventilation, anesthetic gases, oxygenation, hemodynamic variables, automated air tonometry, and temperature. Each animal was anesthetized with 6 mg/kg of propofol and 5 µg/kg of fentanyl. The animal was then placed in dorsal recumbency on the operating table. Orotracheal intubation was performed, and the animal was maintained on mechanical ventilation by using a volume-controlled mode with a tidal volume of 20 mL/kg, a fraction of inspired oxygen of 0.50, and a respiratory rate of 12–14 breaths/min to maintain normoventilation. The inspired and expired gas samples were collected between the endotracheal tube and the Y valve of the respiratory circuit to analyze end-tidal CO2, oxygen, and isoflurane. Respiratory settings were kept constant during surgery. Anesthesia was maintained during the animal preparation at 2.0 minimum alveolar anesthetic concentration (MAC) (2.8%) isoflurane and then during the study at 1.0 MAC (1.4%) isoflurane, according to a previously published report (25). Neuromuscular blockade was provided by an initial IV dose of 0.6 mg/kg rocuronium bromide and was maintained at 10 µg · kg–1 · min–1 by using an infusion pump. An esophageal thermometer was inserted, and the animal’s temperature was maintained at 38°C by using a warming device. We installed a three-channel electrocardiograph (lead DII) and a pulse oximetry sensor placed on the animal’s tongue.

Both femoral arteries and both femoral veins were isolated by cut-down and cannulated with polyethylene catheters. The left femoral artery was used to measure mean arterial blood pressure (MAP) and to sample blood. The right femoral artery was used to perform bleeding. The right femoral vein was used for the administration of drugs and to sample blood. The left femoral vein was used for the administration of fluids. A 7.5F flow-directed thermodilution Swan-Ganz catheter was inserted into the right external jugular vein and advanced into the pulmonary artery for measurements of cardiac output and to sample blood.

After a midline laparotomy had been performed, a splenectomy was done to prevent autotransfusion. A gastric air tonometer (TonometricsTM catheter; Datex-Ohmeda, Helsinki, Finland) was placed in the stomach for intramucosal gastric CO2 (PgCO2) determination, and its position was checked manually through palpation. We used continuous gastric suctioning, but no histamine type 2 (H2) blockers were administered. After careful homeostasis, the abdomen was closed. To compensate for perspiration, each animal was given a 6 mL · kg–1 · h–1 LR infusion during animal preparation and the experimental procedure.

Cardiac index (CI = cardiac output/body surface area (BSA)) was measured in triplicate by thermodilution with 10 mL of cold 5% dextran solution. Arterial and mixed venous PO2, PCO2, and pH were measured with a gas analyzer (Chiron Diagnostics Model 865; Halstead, Essex, UK). Hemoglobin (Hb), arterial oxygen saturation. and mixed venous oxygen saturation (SvO2) were measured by using a cooximeter (Chiron Diagnostics Model 865). Plasma Na+ and Cl– were measured by using an AVL Electrolyte Analyzer Model 9180 (Roswell, GA). Arterial and mixed venous contents (CaO2 and CvO2, respectively) were calculated as



Systemic oxygen transport and uptake indexes (DO2I and VO2I, respectively) were estimated as



and



The systemic oxygen extraction ratio (O2ER) was calculated as



After the tonometer balloon was filled with a 5-mL sample of air and allowed to equilibrate for 15 min, the gas was automatically sampled and measured by infrared spectroscopy (Tonocap®; Datex) for the calculation of pHi (7):



where pHa is arterial pH. An enzymatic electrode (Chiron Diagnostics Model 865) was used to measure arterial lactate.

Baseline data collection was performed after a 15-min stabilization period and once a steady-state was achieved. Then hemorrhage of 28 mL/kg of blood (40% of blood volume) was started from the right femoral artery catheter at 10 mL · kg–1 · min–1, to keep MAP between 40 and 50 mm Hg, as reported by other studies (10,12,13,17,20) that used a similar model of controlled hemorrhage. During the next 30 min, these values were maintained by additional bleeding if necessary. The measurements were repeated after 30 min of hemorrhage. Afterward, the animals were randomly allocated, by opening a sealed envelope, to 1 of 4 groups (12 animals in each group), according to the type of solution used for resuscitation in 15 min: LR group, LR solution in a 3:1 relation to removed blood volume; HS group, HS solution (6 mL/kg); HSD group, HSD solution (6 mL/kg); and HES group, 6% hyperoncotic HES (mean molecular weight, 200 kDa; degree of substitution, 0.5) in a 1:1 relation to removed blood volume. The solutions were supplied by B. Braun Laboratories (Sorocaba, São Paulo, Brazil). The measurements were repeated after 5, 60, and 120 min of fluid resuscitation. At these same times, blood samples were collected to determine pH and blood gases, Na+ and Cl–, Hb, hematocrit, and lactate. At the conclusion of the experiment, the dogs were killed with an IV bolus injection of potassium chloride.

The sample size of the groups was estimated by using an expected difference of approximately 0.15 in the pHi variable with an SD of approximately 0.13 between the LR and HS group means. The sample size of the groups was determined to be 12 dogs. The power of the test used was 80%. In relation to the Type I and Type II statistical errors, in the calculation of the sample size of the groups, we tried to use probabilities to minimize these errors.

Anthropometric variables were compared among the four groups by analysis of variance. Sexes were compared by Fischer’s exact test. Parametric continuous data were compared among the groups by using analysis of variance for repeated measures, followed by Tukey’s test to investigate differences at different times in each group. In this case, data are reported as means ± SD. Nonparametric continuous data were compared among the groups by using the Kruskal-Wallis test for repeated measures followed by Friedman’s test to investigate differences at different times in each group. In this case, data are reported as median (25th–75th percentiles). For all analyses, P < 0.05 was used to determine statistical significance.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Four of 48 animals died of refractory hypotension after exsanguination. They were replaced with other dogs. We found no differences among the groups in anthropometric variables or sex (Table 1).


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  		Table 1. Distribution of Sex and Anthropometric Variables in the Lactated Ringer’s (LR), Hypertonic Saline (HS), Hypertonic Saline Associated with Dextran (HSD), and Hydroxyethyl Starch (HES) Groups
 
Target MAP was successfully achieved and maintained after 30 min of hemorrhage in all groups. The level of hypotension was similar in the four groups (Fig. 1). The average blood volume loss was 30 ± 1 mL/kg, corresponding to 42.8% of the circulating blood volume, and there were no significant differences among groups (P > 0.05). Hemorrhage caused marked effects on hemodynamics (Figs. 1 and 2 and Table 2) and oxygenation (Table 3 and Fig. 3) (P < 0.05), without significant differences among groups (P > 0.05). In all groups, MAP (Fig. 1), CI (Fig. 2), cardiac filling pressures (Table 2), DO2I, and SvO2 decreased significantly (P < 0.05), whereas VO2I and O2ER increased significantly (P < 0.05) (Table 3). However, signs of tissue hypoxia were evident. Thus, there were significant decreases of arterial pH (Table 4) and pHi (Fig. 3) (P < 0.05), whereas there was hyperlactatemia (P < 0.05) (Table 4). All groups showed a significant decrease in Hb concentration and hematocrit with exsanguination (P < 0.05) (Table 5).



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  		Figure 1. Mean arterial blood pressure (means ± SD) in each group at the time of measurements. LR = lactated Ringer’s solution; HS = hypertonic saline; HSD = hyperoncotic dextran-70 in combination with HS; HES = hydroxyethyl starch. *P < 0.05 vs control in the same group.

 


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  		Figure 2. Maximum, minimum, median, and 25th and 75th percentile values of the cardiac index in each group at the time of measurements. LR = lactated Ringer’s solution; HS = hypertonic saline; HSD = hyperoncotic dextran-70 in combination with HS; HES = hydroxyethyl starch. #P < 0.05: HS, HSD vs RL, HES; *P < 0.05 vs control in the same group.

 

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  		Table 2. Hemodynamic Data of the Groups During Hemorrhagic Shock and After Fluid Resuscitation with Lactated Ringer’s (LR), Hypertonic (7.5%) Saline (HS), Hypertonic Saline with Hyperoncotic (6%) Dextran-70 (HSD), and 6% Hyperoncotic Hydroxyethyl Starch (HES) Solutions
 

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  		Table 3. Systemic Oxygenation Data After 30 Minutes of Hemorrhagic Shock and After Fluid Resuscitation with Lactated Ringer’s (LR), Hypertonic (7.5%) Saline (HS), Hypertonic Saline with Hyperoncotic (6%) Dextran-70 (HSD), and 6% Hyperoncotic Hydroxyethyl Starch (HES) Solutions
 


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  		Figure 3. Gastric intramucosal pH (pHi) (means ± SD) in each group at the time of measurements. LR = lactated Ringer’s solution; HS = hypertonic saline; HSD = hyperoncotic dextran-70 in combination with HS; HES = hydroxyethyl starch. *P < 0.05 vs control in the same group.

 

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  		Table 4. Metabolic Data During Hemorrhagic Shock and After Fluid Resuscitation with Lactated Ringer’s (LR), Hypertonic (7.5%) Saline (HS), Hypertonic Saline with Hyperoncotic (6%) Dextran-70 (HSD), and 6% Hyperoncotic Hydroxyethyl Starch (HES) Solutions
 

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  		Table 5. Laboratory Data During Hemorrhagic Shock and After Fluid Resuscitation with Lactated Ringer’s (LR), Hypertonic (7.5%) Saline (HS), Hypertonic Saline with Hyperoncotic (6%) Dextran-70 (HSD), and 6% Hyperoncotic Hydroxyethyl Starch (HES) Solutions
 
After resuscitation, all four solutions induced similar MAP recoveries throughout the observation period, and no solution except HES restored MAP to the prehemorrhage levels (P < 0.05) (Fig. 1). HS and HSD produced similar responses in CI (Fig. 2), central venous pressure, pulmonary artery occlusion pressure, and stroke volume index (Table 2), but their values were significantly lower than LR and HES after 5 and 60 min (P < 0.05), but not after 120 min (P > 0.05), of fluid resuscitation. Only HS did not return CI values to prehemorrhage levels after 2 h of observation (P < 0.05) (Fig. 2), and only LR returned central venous pressure values to control levels after 2 h of fluid resuscitation (Table 2). No solutions restored stroke volume index to the prehemorrhage levels (P < 0.05) (Table 2). Mean pulmonary arterial pressure was lower with HS solution than the other solutions after 5 min of fluid resuscitation (P < 0.05); its values were higher with HES solution in comparison with the three other solutions after 5 and 60 min of fluid resuscitation (P < 0.05), but not after 120 min of fluid resuscitation (P > 0.05). Only HES solution returned mean pulmonary arterial pressure values to control levels after 120 min of fluid resuscitation (P > 0.05) (Table 2).

The effects of HS on hemodynamic variables were followed by marked alterations in systemic oxygenation variables. Then, in the HS group, after 120 min of fluid resuscitation, VO2I and O2ER values were significantly higher and SvO2 values were significantly lower than in the LR and HS groups (P < 0.05), whereas DO2I values were similar in all groups (P > 0.05). The HSD group showed intermediate VO2I and SvO2 values between the LR and HES groups and the HS group (Table 3). Signs of tissue hypoxia were evident in the HS and HSD groups. In the HS and HSD groups, after 120 min of fluid resuscitation, arterial pH values were lower than in the LR and HES groups (P < 0.05) (Table 4). Arterial pH values returned to prehemorrhage levels only in the LR and HES groups. There were no significant differences among groups in relation to pHi (P > 0.05). Only the LR and HES solutions corrected pHi to prehemorrhage levels (P > 0.05) (Fig. 3). PaCO2 levels increased significantly in all groups (P < 0.05) (Table 4). Arterial lactate levels returned to prehemorrhage levels after 120 min of fluid resuscitation in all groups (P > 0.05) (Table 4). There was no significant difference in Hb concentration and hematocrit among the groups with resuscitation (P > 0.05), and their levels maintained lower than prehemorrhage levels (P < 0.05) (Table 5). Plasma Na+ and Cl– levels increased exclusively after HS and HSD resuscitation, peaked at 5 min (9% and 18%, respectively), and then gradually declined. At 2 h, however, they were still significantly higher than control (P < 0.05) (Table 5).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
In this study, we examined, in a model of controlled hemorrhage, the short-term effects of fixed fluid bolus administration—which is usually used in clinical situations of a patient with severe hemorrhage—on hemodynamic variables and systemic and gastrointestinal oxygenation. We showed that all solutions used improved hemodynamic, systemic, and regional oxygenation. However, systemic oxygenation with HS was significantly worse than the three other resuscitative solutions. In addition, HS and HSD did not return regional oxygenation to prehemorrhage levels.

Tonometry has emerged as a useful tool with which to evaluate gut mucosal oxygen metabolism, because blood flow to the gastrointestinal tract is early and disproportionally reduced in hypovolemia and shock states (10,19,26,27). Gastrointestinal intramucosal acidosis can arise from several mechanisms (10). First, it might appear because of tissue hypoxia, when DO2I is less than its critical value. In anaerobic metabolism, CO2 increases from an imbalance between decreased aerobic CO2 production and increased anaerobic CO2 production due to proton buffering by bicarbonates (28). When DO2I is more than its critical value, ensuring constant CO2 production by oxidase phosphorylation, increased CO2 reflects a decreased CO2 washout secondary to decreased gastric blood flow (29). In both situations, tonometry identifies this CO2 excess.

After hemorrhage, we did not reach the criti- cal DO2I level required to jeopardize VO2I in the dog under anesthesia, stated as approximately 200 mL · min–1 · m–2 or 7.9 ± 1.9 mL · min–1 · kg–1 (30). Nevertheless, there was ample evidence of anaerobic metabolism, such as metabolic acidosis, hyperlactatemia, and intramucosal acidosis. In this model, tissue hypoxia by gastrointestinal vasoconstriction might have been the main mechanism responsible for intramucosal acidosis (11). Persistent regional tissue hypoperfusion results in inadequate DO2I, leading to gut barrier dysfunction. This has been thought to provoke distant organ injury. Detection and reversal of gut ischemia have been proposed as a means of limiting the development of multiple organ dysfunction syndrome and its increased morbidity and mortality (5,31).

LR and HES solutions, by different mechanisms, resulted in larger intravascular volume expansion and, consequently, better hemodynamic performance. The high-molecular-weight molecules from HES solution remain largely intravascular, augmenting plasmavolume and plasma oncotic pressure and thereby limiting transvascular fluid filtration (32). Another beneficial effect of HES solution in the treatment of hemorrhagic shock or hypovolemia is the decrease of microvascular endothelial cell swelling, restoring shock-induced microcirculatory disturbances and tissue oxygen tension; this is not seen with LR solution (32). This can explain the good results obtained in our study and in others (6,8,20) in relation to arterial pH and pHi with HES solution. However, the use of artificial colloids has been associated with adverse effects, such as impaired renal, hepatic, and hemostatic function (33,34).

However, crystalloids are not the best plasma expanders; no more than one-fifth of unexcreted fluid should remain within the plasma volume after equilibration, and, for this reason, a large volume is necessary (35). These data are in agreement with those seen in our study, which showed good hemodynamic performance and consequently good systemic oxygenation immediately after crystalloid administration, but after 120 minutes this was no longer maintained. The poor intravascular retention of balanced salt solutions supports intravascular volume transiently but later can cause tissue edema formation with impaired oxygen perfusion (36).

HS solution caused maximum intravascular volume expansion immediately at the end of infusion. Infusion of 2400 mOsm/L HS transiently increases serum osmolality by 30–50 mOsm/L, depending on the rate of infusion. Such osmolality generates large transcapillary absorptive forces of at least 50–100 mm Hg, which reverse the transendothelial pressure gradient from a small filtration force to a large absorptive force (37). Adding 6% dextran-70 to HS has been widely studied, both in clinical scenarios and in experimental research, and it has been demonstrated that there is an increase in plasmatic volume depending on the dextran solution (17,18,32,38).

Even though the infusion of HS and HSD in hemorrhaged animals quickly increases the plasmatic volume, the plasma volume remains less than the normal volume (13,17). Consequently, the initial increases in CI and cardiac filling pressures after transfusion were clearly less after HS and HSD solution administration compared with LR and HES solutions. This implies that the amount of volume infused was not equieffective. The initial smaller volume state with HS and HSD solutions may explain the results in relation to systemic and regional oxygenation. However, after 120 minutes of fluid resuscitation, all four solutions induced similar CI and cardiac filling pressures, but the HS solution showed a significant alteration of the systemic oxygenation in relation to the other groups.

In relation to regional oxygenation, LR and HES showed the best results, with both solutions correcting pHi to prehemorrhage levels, the first aided by its buffering effect on arterial pH. Lactate is rapidly converted to bicarbonate and acts as a buffer that may alleviate the preexisting metabolic acidosis of hemorrhagic shock (39). The use of chloride as the anion in HS and HSD solutions resulted in hyperchloremia and maintained the metabolic acidosis that may have affected gut mucosal acidosis. HS infusion produces metabolic acidosis by increasing the plasma chloride concentration relative to the plasma sodium concentration (39). The result is a reduction in the strong ion difference—the difference between positively and negatively charged electrolytes—which in turn produces an increase in free hydrogen ions to preserve electrical neutrality. This is measured as a decrease in pH.

The effects of hypertonic and hyperoncotic solutions on pHi have not been extensively investigated. In a model of uncontrolled hemorrhage from a vascular injury in swine and limited resuscitation with HSD, LR, or HS acetate with 6% dextran 75 (HAD) solutions, pHi was not significantly different among groups, with the gut becoming acidic in all groups with the limited resuscitation, although alkalosis was seen in the systemic arterial blood samples from the HAD group (11). In pigs submitted to two hours of occlusion of the superior mesenteric artery and resuscitation with sodium chloride (SC group) or HS associated to 10% hydroxyethyl starch (HHES group) solutions, pHi was significantly different between groups. The SC group showed that gastric pHi decreased even more (P < 0.05), whereas the HES group showed a normalization of the gastric pHi and serum lactate within 30 minutes (24).

Care is necessary in the interpretation of the pHi data. The fact that the calculated pHi depends partly on arterial pH may explain the relation observed between the two variables in our groups. However, pHi also depends on PgCO2 and PaCO2 values, which were directly determined, and the authors (11) verified low pHi values in patients with metabolic alkalosis, which was determined by resuscitation with HAD solution.

Splanchnic hypoperfusion and lactate production may influence the systemic indicators for the development of multiple organ failure, but tonometric variables may nevertheless correlate only poorly with systemic factors (40). Because hyperlactatemia-associated metabolic acidosis is prognostically unfavorable in critically ill patients, it can be questioned whether tonometry is of additive predictive value. However, a low pHi value may be superior in the prediction of morbidity that is multiple organ failure and mortality, to global hemodynamics and metabolic variables, including lactate concentration and acid-base variables in the systemic blood of critically ill patients (41–43). A subnormal gastric pHi may predict circulating markers, an inflammatory response, and a poor outcome, with postoperative complications and multiple organ failure, after major cardiac, vascular, and abdominal surgery (6–8,43).

In this study, the change in pHi was recorded during the two hours of resuscitation, not to predict the outcome but to evaluate the effectiveness of early resuscitation. It is widely accepted that the earlier adequate therapy for hemorrhagic shock is started, the better the prognosis will be (1,31). The adequacy or inadequacy of the therapy from hemorrhagic shock seems to be associated with an increase or decrease, respectively, in gut pHi during the initial resuscitation (9). In our study, the effectiveness of resuscitation for hemorrhagic shock was evaluated with pHi tonometry and simultaneous measurements of hemodynamic and systemic oxygenation variables.

Routine use of H2 blockers to reduce the error of PgCO2 measurements has been questioned (44). The recommendations are based mainly on studies in volunteers. Our study protocol did not mandate the use of H2 blockers, because we did not know whether they could improve the clinical reliability of PgCO2 measurements in dogs. We used continuous suctioning to eliminate the mixture of gastric acid with refluxed duodenal bicarbonate, which could determine false-positive increases of PgCO2.

The first limitation of the study was the short observation time after the end of resuscitation. Only the immediate response to a single bolus injection of solutions with different tonicity with or without added colloids was investigated. The medium- or long-term response might have been different. A second limitation was that the study concerns anesthetized animals. Anesthetics also cause intraoperative changes in the variables that directly or indirectly modify circulating blood volume (45). A third limitation was that a hemorrhage of 30 mL/kg was performed. This represents an important amount of blood (42.8%) of the total blood volume.

We conclude that all solutions used improved systemic and gastrointestinal oxygenation after hemorrhagic shock in dogs. However, HS solution showed the worst response in comparison to LR and HES solutions in relation to systemic oxygenation. Whereas HSD showed intermediate values, HS and HSD solutions did not return regional oxygenation to control levels. Thus, resuscitation with HS and HSD solutions during hemorrhagic shock in dogs may not have improved the splanchnic circulation, as indicated by lower pHi values during resuscitation, in comparison to control values.


   Acknowledgments
 
Supported by Fundação de Amparo à Pesquisa of São Paulo State Grant 99/12572-0.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication February 2, 2004.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press