early hemodynamic and renal effects of hemorrhagic shock

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Early Hemodynamic and Renal Effects of Hemorrhagic Shock

Resuscitation with Lactated Ringers Solution, Hydroxyethyl Starch,

and Hypertonic Saline with or without 6% Dextran-70

Paulo Nascimento, Jr, M.D., Ph.D.,*,1 Odilar de Paiva Filho, M.D., Ph.D.,* Ldia Raquel de Carvalho, Ph.D.,and Jos Reinaldo Cerqueira Braz, M.D., Ph.D.*

*Department of Anesthesiology,Sciences Institute, UNESP University of So Paulo State, Medical School of Botucatu,Botucatu/SP, Brazil

Submitted for publication February 17, 2006

Background. Considering the renal effects of fluid

resuscitation in hemorrhaged patients, the choice of

fluid has been a source of controversy. In a model of

hemorrhagic shock, we studied the early hemody-

namic and renal effects of fluid resuscitation with lac-

tated Ringers (LR), 6% hydroxyethyl starch (HES),

and 7.5% hypertonic saline (HS) with or without 6%

dextran-70 (HSD).

Materials and methods.Forty-eight dogs were anes-

thetized and submitted to splenectomy. An estimated

40% blood volume was removed to maintain mean ar-

terial pressure (MAP) at 40 mm Hg for 30 min. The dogs

were divided into four groups: LR, in a 3:1 ratio to

removed blood volume; HS, 6 mL kg1; HSD, 6 mL kg1;

and HES in a 1:1 ratio to removed blood volume. He-

modynamics and renal function were studied duringshock and 5, 60, and 120 min after fluid replacement.

Results. Shock treatment increased MAP similarly

in all groups. At 5 min, cardiac filling pressures and

cardiac performance indexes were higher for LR and

HES but, after 120 min, there were no differences

among groups. Renal blood flow and glomerular filtra-

tion rate (GFR) were higher in LR at 60 min but GFR

returned to baseline values in all groups at 120 min.

Diuresis was higher for LR at 5 min and for LR and

HES at 60 min. There were no differences among

groups in renal variables 120 min after treatment.

Conclusions.Despite the immediate differences in

hemodynamic responses, the low-volume resuscita-tion fluids, HS and HSD, are equally effective to LR

and HES in restoring renal performance 120 min

after hemorrhagic shock treatment. 2006 Elsevier Inc.

All rights reserve d.Key Words:hemorrhagic shock; renal function; crys-

talloid; colloid; hypertonic saline; dog.

INTRODUCTION

Trauma is the leading cause of death in the popula-tion under 45 years [1]. Vital organ perfusion, mostnotably, renal perfusion, is severely compromised inlow-flow states and much of the morbidity and mortal-ity associated with acute hemodynamic decompensa-tion is the result of end-organ failure[2].Under certain

circumstances, severe blood loss, massive muscle massinjury, and delayed resuscitation can lead to compart-ment syndrome and rhabdomyolysis, and up to 40% ofthese patients will develop acute renal failure [3].

Acute renal failure in patients with low-flow states isusually reversible with restoration of adequate perfu-sion. However, initial fluid management in traumapatients and in the prehospital environment is a chal-lenging and controversial issue. The available evidencedoes not clearly support any single approach, espe-cially in terms of the renal response to fluid resuscita-tion in hemorrhaged patients.

Currently, the American College of Surgeons recom-

mends crystalloids to be used as the initial resuscita-tion fluid in the treatment of hemorrhagic shock [4].However, these solutions are poor plasma volume ex-panders and less than 20% of the administered volumestays within the intravascular space[5].Consequently,infusion of large volumes of crystalloids is necessary tomaintain cardiovascular stability. Hydroxyethyl starch

1 To whom correspondence and reprint requests should be ad-dressed at Department of AnesthesiologyMedical School of Botu-catu, University of So Paulo StateUNESP., District of Rubio Jr,s/no.Postal mail 530 18618-970 Botucatu, SP, Brazil. E-mail:[email protected].

Journal of Surgical Research136, 98105 (2006)doi:10.1016/j.jss.2006.04.021

980022-4804/06 $32.00 2006 Elsevier Inc. All rights reserved.


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(HES) preparations have been used to treat hypovole-mia and shock with results equal to or even better thangelatin and albumin[6].These solutions are also moreeffective as plasma expanders than crystalloids butmay exert some adverse effects on the coagulation sys-tem [7]. Considering the logistics of the prehospitalsetting, for the patient with hemorrhagic shock and

urgent therapeutic requirements, small-volume resus-citation appeared to be a viable fluid therapy. Velascoand colleagues [8] first reported that severe hemor-rhagic shock can be effectively treated with hypertonicsaline (HS). The addition of 6% dextran-70 to HS(HSD) has been shown to enhance the duration andintensity of volume expansion that is reached by HSand several groups have treated hemorrhagic shockwith HSD[9, 10].

According to those studies that show good hemody-namic response and high survival rate after hemor-rhagic shock treatment with HS and HSD, we testedthe hypothesis that HS and HSD are as effective as LRand HES, in terms of early renal response followinghemorrhagic shock. In this set of experiments, weaimed to evaluate the early cardiovascular hemody-namic effects and the renal function related to fluidresuscitation with lactated Ringers solution (LR), 6%HES, HS, and HSD in anesthetized dogs with hemor-rhagic shock. This model simulates a trauma whereblood loss is severe and also compares the early re-sponse to four different resuscitation fluids with differ-ent mechanisms of action, as they are commonly usedin clinical practice.

MATERIALS AND METHODS

The study was approved by the Institutional Ethics Committee ofAnimal Research. After an overnight fasting period, 48 healthy adultmongrel dogs (both sexes; weighing 18 to 30 kg; body surface areabetween 0.71 and 0.90 m2) were anesthetized with propofol (6 mgkg1 i.v.) and fentanyl (5 g kg1 i.v.). The animals were placedsupine, intubated with a 8.5- to 9.0-mm inner diameter cuffed endo-tracheal tube, and mechanically ventilated at 12 to 16 breaths min1

(210 SE Excel Anesthesia Machine; Ohmeda, Madison, WI) with 20ml kg1 tidal volume and 0.5 inspired oxygen fraction to maintainend-tidal CO2 between 4.6 and 6.0 kPa and pulse oximetry at 98 to100%. Anesthesia was maintained during the animal preparation at2.0 minimum alveolar anesthetic concentration (MAC) (2.8%) isoflu-rane and then during the study at 1.0 MAC (1.4%) isoflurane. Neu-

romuscular blockade was provided by an initial i.v. dose of 0.6 mgkg1 rocuronium bromide and was maintained at 10 g kg1 min1 byusing a two-channel infusion pump (Anne; Abbott, Abbott Park, IL).

We then installed a 3-lead electrocardiogram (lead DII), an in-spired and expired gas analyzer, and a SpO 2 probe on the animalstongue. An AS3 biomonitor (Datex-Engstrom Instrumentarium,Helsinki, Finland) was used for monitoring and recording param-eters.

Both femoral arteries and both femoral veins were isolated bycut-down and cannulated. The left femoral artery was used to mea-sure mean arterial pressure (MAP) and to sample blood. The rightfemoral artery was used to perform bleeding. The right femoral veinwas used for the administration of drugs and to sample blood. Theleft femoral vein was used for the administration of fluids.

A thermistor-tip, flow-directed catheter was floated through theleft external jugular vein into a pulmonary artery to measure pul-monary artery pressure (PAP), right atrial pressure (RAP), pulmo-nary artery occlusion pressure (PAOP), and the cardiac output (CO)by thermodilution. A laparotomy was performed and the spleen wasremoved. A catheter for urinary volume measurement and samplingwas placed into the bladder. Warming of the abdomen, thorax, andhead of the animals was done by a specific blanket (Warm Touch;

Mallinckrodt, St. Louis, MO) in a temperature ranging from 36 to46C, to maintain body temperature between 37 and 38C.After surgical procedures, a priming dose of creatinine (30 mg

kg1) and para-aminohippuric acid (PAH) (4 mg kg1) was infusedfollowed by the maintenance infusion of PAH (0.24 g dL1) andcreatinine (0.6 g dL1) in LR (6 mL kg1 h1) using a two-channelinfusion pump (Anne, Abbott).

After a 30-min stabilization period, the first set of measurements(baseline) was performed. Then, hemorrhage of 28 mL kg1 of blood(40% of blood volume) was started at 5 mL kg1 min1 to keep MAPbetween 35 and 45 mm Hg, as reported by other studies that used asimilar model of controlled hemorrhage[9].For 30 min, these valueswere maintained by additional bleeding if necessary. The measure-ments were repeated after 30 min of hemorrhage. Afterward, theanimals were randomly allocated to one of four groups (12 animals ineach group),according to the type of solution used for resuscitation in

15 min: LR group, LR solution in a 3:1 ratio to removed blood volume;HS group, 7.5% hypertonic solution (6 mL kg1); HSD group, 7.5%hypertonic saline with 6% dextran-70 solution (6 mL kg1); and HESgroup, 6% HES (mean molecular weight, 200 kDa; degree of substi-tution, 0.5) in a 1:1 ratio to removed blood volume. The solutions weresupplied by B. Braun Laboratories (Sorocaba, So Paulo, Brazil). Themeasurements were repeated after 5, 60, and 120 min of fluid resus-citation.

In each period of study, excluding the shock period, the procedurewas as follows: emptying the bladder; collecting the urine for 15 min;and, halfway through this 15-min period, measurement of heart rate(HR), MAP, PAP, RAP, PAOP, and CO, besides blood collection foranalysis. During shock period, the urine was not collected and renalfunction was not studied because of the insufficient urinary volumefor analysis. At the end of the study, the animals were killed using

saturated potassium chloride.The following variables were studied to control the experiment:weight, length, body surface area, sex of the animals, and hematocrit(Hct).

The cardiovascular recorded variables were as follows: HR, MAP,PAP, RAP, PAOP, systemic vascular resistance index (SVRI), strokeindex (SI), and left ventricular stroke work index (LVSWI). Addition-ally, renal blood flow, measured by PAH clearance (C PAH) [RBF CPAH/1 (Hct/100)]; glomerular filtration rate, measured by creati-nine clearance (CCr); urinary output (UO); renal vascular resistance(MAP/RBF); sodium fractional excretion (CNa 100/CCr); urinary os-molality (Uosm); osmolar clearance (C osm Uosm UO/plasma osmola-lity); and free-water clearance (UO-Cosm) were measured. Standardformulas were used to calculate hemodynamic variables.

Data were compared among groups by analysis of variance forrepeated measures, followed by Tukeys test to investigate differ-ences at different times in each group. Data were expressed asmean standard error of the mean. Demographic data were sub-mitted to analysis of variance and Fishers exact test. Differenceswere considered significant when P 0.05.

RESULTS

Four of 48 animals died of refractory hypotensionafter exsanguination, but before randomization andtreatment. Additional dogs were used for replacementto achieve equal nvalues for each group. No differenceswere found among groups in anthropometric variablesor sex (P 0.05).

99NASCIMENTO ET AL.: RENAL FUNCTION AFTER HEMORRHAGIC SHOCK


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Target MAP was successfully achieved and main-tained after 30 min of hemorrhage in all groups. Thelevel of hypotension was similar in the four groups(Table 1). The average blood volume loss was 30 1 mL kg1, corresponding to 42.8% of the circulatingblood volume, and there were no significant differencesamong groups (P 0.05). Hemorrhage caused markedeffects on hemodynamics (Fig. 1and Table 1) withoutsignificant differences among groups (P 0.05). In allgroups, MAP, cardiac filling pressures, CI, PAP, SI,

SVRI, and LVSWI decreased during hemorrhage with-out significant differences among groups. HR increasedduring shock and remained higher than baseline afterfluid replacement in all groups.

After resuscitation, MAP was similarly increased inall groups and there were no significant differencesamong groups throughout the observation period (P 0.05), but only HES restored MAP to prehemorrhage

values (P 0.05) (Table 1). Five minutes after fluidreplacement, LR and HES produced similar responses

TABLE 1

Hemodynamic Variables of the Groups During Hemorrhagic Shock and After Resuscitation with LactatedRingers (LR), Hypertonic (7.5%) Saline (HS), Hypertonic Saline with 6% Dextran-70 (HSD), and HydroxyethylStarch (HES)

Variable Baseline Hemorrhagic shock

After fluid resuscitation

5 min 60 min 120 min

Heart rate (beats min1)LR 112 4 151 9 146 7 140 8 146 9HS 124 4 167 10 161 6 168 7 162 8HSD 126 7 152 7 153 5 157 5 158 5HES 123 8 142 7 149 6 146 7 141 7

Mean arterial pressure (mm Hg)LR 105 6 42 2 93 5 89 4 90 4HS 99 5 39 3 73 2 70 5 74 5HSD 107 5 41 3 79 4 80 5 90 6HES 96 5 38 3 89 5 93 4 94 4

Right atrium pressure (mm Hg)LR 3.8 0.4 1.8 0.3 5.7 0.6 3.3 0.3 3.3 0.3HS 4.2 0.3 1.9 0.4 3.1 0.5* 2.8 0.4 2.7 0.4HSD 3.6 0.4 1.4 0.4 3.0 0.4* 2.3 0.4 2.4 0.3HES 3.6 0.3 1.8 0.2 5.7 0.2 3.9 0.2 3.1 0.2

Mean pulmonary arterial pressure(mm Hg)

LR 13.5 0.6 9.0 0.5 16.4 0.9 11.1 0.6 12.3 0.6HS 14.2 0.5 9.2 0.4 13.4 0.7* 11.8 0.6 11.3 0.4HSD 13.9 0.8 9.2 0.6 14.5 0.7* 12.5 1.0 12.9 1.1HES 14.6 0.7 9.3 0.4 19.5 0.6 14.9 0.6 13.8 1.0

Stroke index (mL m2)LR 35.0 2.7 12.5 1.4 56.4 4.7 32.5 3.3 27.5 3.2HS 31.3 3.6 10.6 1.2 32.6 3.8* 20.3 1.8* 20.1 2.4HSD 31.1 2.0 12.8 1.5 40.2 2.6* 24.3 2.0* 22.4 1.4HES 31.5 3.2 11.9 1.3 56.6 3.8 38.5 4.0 28.7 3.5

Systemic vascular resistanceindex (dyne s/cm5 m2)

LR 2,186 198 1,932 199 945 120 1,713 197 1,982 193

HS 2,132 177 1,796 103 1,161 70* 1,698 138 1,890 135HSD 2,267 219 1,748 150 1,056 114 1,758 199 1,905 207HES 2,100 197 1,777 90 820 56 1,380 107 1,955 130

Left ventricular stroke work index(g m/m2)

LR 49 6 7 1 65 7 38 5 33 5HS 41 6 6 1 31 4* 19 2* 21 4HSD 43 4 7 1 40 3* 25 3* 27 3HES 40 5 6 1 62 6 46 6 33 5

Note.Values are mean SE.*P 0.05: HS, HSD versusLR.P 0.05: HS, HSD versusHES.P 0.05: LR versus HES.P 0.05: HS versusHSD.

P

0.05: versuscontrol in the same group.

100 JOURNAL OF SURGICAL RESEARCH: VOL. 136, NO. 1, NOVEMBER 2006


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in RAP, PAOP, CI, SVRI, and LVSWI (P 0.05). Atthis set of measurements, HS resulted in the lowest

values for CI, PAP, SI, and LVSWI and in the highestvalues for SVRI (P 0.05). At 60 min, cardiac fillingpressures, CI, SI, and PAP were significantly higherfor HES than the other three groups (P 0.05). Strokeindex and LVSWI remained lower for HS than theother three groups at this set of measurements (P 0.05). With the exception of MAP, HR, and SVRI, he-modynamic variables progressively decreased duringthe resuscitation period. No significant differencesamong groups occurred 120 min after resuscitation in

any hemodynamic variable (P 0.05).Renal function is shown inFig. 2andTable 2.Renal

blood flow returned to baseline values 5 min afterresuscitation, similarly in LR, HSD, and HES (P 0.05). Glomerular filtration rate failed to return tobaseline values 5 min after fluid replacement in anygroup, but it did return to baseline values in LR at 60min and in all groups at 120 min. For both renal bloodflow and glomerular filtration rate, significantly higher

values were seen with LR 60 min after resuscitation(P 0.05). A robust and significantly higher diuresisdeveloped immediately after LR resuscitation (P

0.05). After 60 min, LR and HES presented similardiuresis values that were significantly higher thanthose of HS and HSD (P 0.05). Sixty minutes afterfluid replacement, osmolar clearance values in LR weresignificantly higher than those in the other groups (P0.05). Sodium fractional excretion was significantlyhigher than baseline 5 min after LR, HS, and HSD

administration (P 0.05) and significantly higher inthese groups than in HES (P 0.05). Free-water clear-ance was increased to above baseline values in allgroups after fluid replacement (P 0.05). All solutionsdecreased urinary osmolality to values lower thanbaseline, and immediately after fluid replacement, LRresulted in significantly lower values than the othersolutions (P 0.05). Renal vascular resistance washigher than baseline after HS resuscitation, but therewas an increase in its values to above baseline in allgroups 120 min after shock treatment (P 0.05). Nosignificant differences were seen in renal variablesamong groups 120 min after fluid resuscitation (P 0.05).

FIG. 2. Renal blood flow (top), glomerular filtration rate (mid-dle), and urinary output (bottom). Values are mean SE for lactatedRingers (LR), hypertonic (7.5%) saline (HS), hypertonic saline with6% Dextran-70 (HSD), and hydroxyethyl starch (HES). *P 0.05:HS, HSDversusLR; P 0.05: HS, HSD versusHES; P 0.05: LRversusHES; #P 0.05: versus control in the same group.

FIG. 1. Pulmonary artery occlusion pressure (top) and cardiacindex (bottom). Values are mean SE for lactated Ringers (LR),hypertonic (7.5%) saline (HS), hypertonic saline with 6% Dextran-70(HSD), and hydroxyethyl starch (HES). *P 0.05: HS, HSD versusLR; P 0.05: HS, HSD versus HES; P 0.05: LR versus HES;P 0.05 HS versus HSD; #P 0.05: versus control in the samegroup.



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Hematocrit values, shown inFig. 3,presented a sim-ilar decrease with shock in all groups. Significantlylower values were seen in LR and HES groups 5 min

after fluid replacement (P 0.05). HES had signifi-cantly lower values than the other groups 60 min afterplasma volume expansion, but the values were similarin all groups in the last set of measurements (P 0.05).

DISCUSSION

Hemodynamic Variables

In a model of pressure-controlled hemorrhagic shock,

we studied the short-term effects of fixed fluid bolusadministration on hemodynamics and renal variables.Four different fluids with distinct mechanisms of ac-tion were used to resuscitate the animals, and the

volume of the solutions as well as the way they wereinfused simulate the initial approach for fluid resusci-tation in trauma and hemorrhagic shock patients inprehospital environments, emergency rooms, and op-erating rooms. We showed that all solutions used im-proved hemodynamics, and renal variables. Large vol-umes of LR and HES initially resulted in significantlybetter performance than that seen with the small-

TABLE 2

Renal Variables of the Groups During Hemorrhagic Shock and After Resuscitation with Lactated Ringers(LR), Hypertonic (7.5%) Saline (HS), Hypertonic Saline with 6% Dextran-70 (HSD), and HydroxyethylStarch (HES)

Variable Baseline

After fluid resuscitation

5 min 60 min 120 min

Renal vascular resistance (mm Hg/mL/min)LR 0.28 0.04 0.28 0.05 0.35 0.07 0.38 0.05HS 0.30 0.05 0.40 0.09 0.41 0.06 0.37 0.06HSD 0.31 0.03 0.25 0.04 0.33 0.02 0.40 0.06HES 0.29 0.04 0.28 0.05 0.41 0.06 0.36 0.04

Osmolar clearance (mL min1)LR 2.5 0.3 2.2 0.5 2.2 0.3* 1.8 02HS 2.4 0.2 1.7 0.4 1.1 0.2 1.4 0.3HSD 2.0 0.2 1.4 0.3 1.4 0.2 1.6 0.2HES 2.1 0.3 1.5 0.3 1.7 0.2 1.7 0.2

Free-water clearance (mL min1)LR 1.3 0.2 0.2 0.3 0.4 0.3 0.6 0.2HS 1.3 0.2 0.5 0.2 0.3 0.1 0.4 0.2HSD 1.2 0.1 0.5 0.1 0.6 0.2 0.7 0.1HES 1.1 0.2 0.5 0.1 0.4 0.3 0.4 0.2

Sodium fractional excretion (%)LR 1.2 0.3 2.6 0.6 1.1 0.2 0.7 0.1HS 1.4 0.2 2.3 0.4 0.8 0.2 0.7 0.2HSD 0.7 0.2 1.9 0.2 0.9 0.3 0.5 0.1HES 1.1 0.3 0.8 0.2 0.8 0.2 0.6 0.2

Urinary osmolality (mosm L1)LR 743 97 371 36* 466 72 481 59HS 693 77 473 38 525 58 550 67HSD 852 69 508 45 572 66 607 44HES 695 65 489 34 514 88 506 73

Note.Values are mean SE.*P 0.05: LR versus HS, HSD, HES.P 0.05: HES versusLR, HS, HSD.

P 0.05: versus control in the same group.

FIG. 3. Hematocrit. Values are mean SE for lactated Ringers(LR), hypertonic (7.5%) saline (HS), hypertonic saline with 6%Dextran-70 (HSD), and hydroxyethyl starch (HES). *P 0.05: HS,HSD versus LR; P 0.05: HS, HSD versus HES; P 0.05: LRversus HES; #P 0.05: versus control in the same group.



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volume solutions, HS and HSD. Besides, for some ofthe variables, HSD resulted in significantly higher val-ues than those in HS. Nevertheless, during the resus-citation phase, for all groups, hemodynamic variablesprogressively decreased, and 120 min after treatment,there were no significant differences among groups.

LR and HES solutions, by different mechanisms, re-

sulted in larger intravascular volume expansion thanHS and HSD and, consequently, better hemodynamicperformance. The high-molecular-weight moleculesfrom HES solution remain largely intravascular, in-creasing colloid oncotic pressure and plasma volume,and thereby limiting transvascular fluid filtration[11].However, crystalloids are not the best plasma expand-ers; no more than one-fifth of unexcreted fluid shouldremain within the plasma volume after equilibrationand, for this reason, a large volume is necessary [5].Especially in high doses, LR dilutes plasma protein,reducing colloid oncotic pressure, and favors capillaryfiltration[12]. Our data are in agreement with thoseseen in the literature. There was a good hemodynamicperformance immediately after crystalloid administra-tion, but after 120 min, this was no longer maintained.HS solution caused maximum intravascular volumeexpansion immediately at the end of infusion. Infusionof 2400 mOsm L1 HS transiently increases serumosmolality by 3050 mOsm L1, depending on the rateof infusion. Such osmolality generates large transcap-illary absorptive forces of at least 50100 mm Hg,which reverse the transendothelial pressure gradientfrom a small filtration force to a large absorptive force[13]. Adding 6% dextran-70 to HS has been widely

studied, both in clinical scenarios and in experimentalresearch, and it has been demonstrated that there is anincrease in plasma volume depending on the dextransolution[14].Even though the infusion of HS and HSDin hemorrhaged animals quickly increases plasma vol-ume, the blood volume remains less than the normal

volume[10, 15].Consequently, the initial increases inCI and cardiac filling pressures after treatment wereclearly less after HS and HSD solution administrationcompared with LR and HES solutions.

Renal Function

Renal response to low-flow states includes reductionof glomerular filtration rate and urinary output. Res-toration of the volemic status and cardiac output arepivotal for recovery of renal blood flow after hemor-rhagic shock [16]. Thus, the hemodynamic beneficialeffects of fluid expansion induced by all of the solutionsin this study were reflected in the renal system. The

volume expansion and the increase in cardiac outputresulted in an increase in renal blood flow that was notmaintained over the 2-h observation period. Baseline

values of renal blood flow were reached 5 min after LR,HSD, and HES administration. Comparing groups, the

highest values were obtained 60 min after Ringerssolution resuscitation. Renal function, if analyzed byglomerular filtration rate, was equally restored by allstudied solutions 120 min after shock treatment.

All of the solutions in this research, probably by pro-ducing plasma expansion and raising blood pressure,resulted in an increase in the glomerular hydrostaticpressure and in the glomerular filtration rate. Theincrease in the renal blood flow may also originate froma precapillary dilation by a direct action of the hyper-tonic solutions on the capillary smooth muscles. Thisaction is even more significant in capillaries with swol-len endothelium, as in the hemorrhagic shock[17].

The diuresis induced by volume replacement is par-tially explained by the fast volume expansion and gen-eral improvement of the cardiovascular hemodynamic.However, the increase in renal blood flow is not pro-portional to the magnitude of the urinary output,mainly in LR. The absorption and the secretion of

substances by renal tubules are also factors that deter-mine an increase or a decrease in diuresis, and they areinfluenced by some serum hormones. LR led to a sig-nificant increase in sodium excretion immediately af-ter its administration, as well as a significantly higherosmolar clearance at the 60-min observation period,compared to the other groups. This fact indicates ahigher loss of osmotically active substances throughurine and natriuresis, probably caused by the inhibi-tion of aldosterone secretion that occurred due to thequick plasma expansion [18, 19]. In several animalspecies, including dog, vasopressin may also play a role

in sodium excretion and diuresis[20].During isotoniccrystalloid infusion, vasopressin secretion is probablysuppressed by increments in central blood volume thatleads to an increase in diuresis. Normally, during hy-pertonic saline loading, the osmotic stimulus domi-nates over the volumetric stimuli, and vasopressin lev-els increase substantially[21].On the other hand, thetreatment of hemorrhagic shock with hypertonic solu-tions can result in an acute decrease in serum vaso-pressin, renin, and angiotensin levels[22].This reduc-tion of the vasopressin levels appears despite theincrease in osmolality that normally is responsible for

its secretion. In this situation, the response to osmola-lity is superposed by the correction of hypovolemia [23].Even though, in the present study, diuresis was mod-est after HS and HSD infusion as compared to LRgroup, hypertonic solutions can determine a significantincrease in diuresis that may be maintained for hoursafter the initial administration[24, 25].Although Rich-ards and colleagues[26]also suggested that the atrialnatriuretic factor would possibly be responsible for thenatriuresis, no rise was observed in atrial natriureticfactor level in response to HS or HSD administration[27, 28].



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The initial copious volume expansion caused byRingers solution collaborated with the production ofurine, justifying our results. Otherwise, there was alsoan increase in the free-water clearance in the HS andHSD groups, indicating a satisfactory plasma volumeexpansion in these groups. Besides, the glomerularfiltration of hyperoncotic dextran molecules is also ca-

pable of producing osmotic diuresis, free of solutes, asverified by other groups [16, 29]. Cox and colleagues[30]found close correlation between the slight increasein renal perfusion and substantial increase in free-water clearance due to high levels of vasopressin. Ac-cording to the authors, this hormone presents a bipha-sic effect. At normal and physiological levels, it wouldact as an anti-diuretic and would concentrate theurine, but at high levels it would act as a diuretic,promoting loss of water and electrolytes.

The HES solutions, besides their copious volemic ex-pansion, are also capable of producing osmotic diuresissince the low-molecular-weight molecules are quicklyeliminated by glomerular filtration from the beginningof their administration [31]. These solutions can in-crease diuresis and do not impair renal function eitherin normal kidneys[32]or in transplanted ones[33].

We conclude that all solutions used in this studyimproved hemodynamics and renal function in a short-term period after hemorrhagic shock. Although a goodhemodynamic performance and a copious diuresis werethe immediate result of the treatment of hemorrhagicshock with LR, no differences were seen 120 min afterresuscitation among the four different fluids. None ofthe studied solutions maintained hemodynamics and

renal blood flow 2 h after their administration. Consid-ering glomerular filtration rate as an index of renalperformance after fluid replacement following hemor-rhagic shock, the low-volume resuscitation fluids, HSand HSD, are equally effective to LR and HES inrestoring renal function in a 2-h period.

Limitations

This study shows the short-term hemodynamic andrenal effects of four different fluids used as a singlebolus to treat hemorrhagic shock. The medium- orlong-term response might have been different. Besides,

in a grade IV hemorrhage, additional fluid therapyshould be necessary. These considerations would beimportant in case of either delayed resuscitation ordelayed definitive treatment after the initial approachto a trauma patient. This is not a model of primaryrenal injury or renal failure. Different performancescould be expected if the kidneys were damaged or in-sufficient already prior to the hemorrhage. Nonethe-less, further investigation on renal performance afterhemorrhagic shock should consider our results, espe-cially if other additional aggression, as muscle massinjury, is associated. If any of the solutions studied had

not recovered renal performance, the supposed solutionprobably would not have been useful in a more severerenal injury associated with the hemorrhage. Thiswould be important considering the higher mortalityrates associated with renal failure after hypovolemiastates [34]. Finally, we are aware of the differencesbetween the four studied solutions (oncocity, osmolal-

ity, electrolyte content, and buffering capacity) andthe different plasma effects caused by their infusion(plasma Na and Cl, plasma osmolality, and colloidoncotic pressure)[35]. We did not intend to comparethe effects of equal volumes of different solutions or toadjust the volumes infused according to sodium load,but we do compare solutions as they are used in clinicalpractice or suggested to be used from other experimen-tal studies.

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Anesth Analg 2004;99:536.


early hemodynamic and renal effects of hemorrhagic shock

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