Effects of intravenous administration of lactated Ringer's solution on hematologic, serum biochemical, rheological, hemodynamic, and renal measurements in healthy isoflurane-anesthetized dogs

William W. Muir III QTest Laboratories, 6456 Fiesta Dr, Columbus, OH 43235.

Search for other papers by William W. Muir III in
Current site
Google Scholar
PubMed
Close
 DVM, PhD, DACVA, DACVECC
,
Anusak Kijtawornrat QTest Laboratories, 6456 Fiesta Dr, Columbus, OH 43235.

Search for other papers by Anusak Kijtawornrat in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Yukie Ueyama QTest Laboratories, 6456 Fiesta Dr, Columbus, OH 43235.

Search for other papers by Yukie Ueyama in
Current site
Google Scholar
PubMed
Close
 DVM
,
Steven V. Radecki QTest Laboratories, 6456 Fiesta Dr, Columbus, OH 43235.

Search for other papers by Steven V. Radecki in
Current site
Google Scholar
PubMed
Close
 PhD
, and
Robert L. Hamlin QTest Laboratories, 6456 Fiesta Dr, Columbus, OH 43235.

Search for other papers by Robert L. Hamlin in
Current site
Google Scholar
PubMed
Close
 DVM, PhD, DACVIM

Click on author name to view affiliation information

Abstract

Objective—To determine the hematologic, serum biochemical, rheological, hemodynamic, and renal effects of IV administration of lactated Ringer's solution (LRS) to healthy anesthetized dogs.

Design—4-period, 4-treatment cross-over study.

Animals—8 healthy mixed-breed dogs.

Procedures—Each dog was anesthetized, mechanically ventilated, instrumented, and randomly assigned to receive LRS (0, 10, 20, or 30 mL/kg/h [0, 4.5, 9.1, or 13.6 mL/lb/h]), IV, on 4 occasions separated by at least 7 days. Blood hemoglobin concentration and serum total protein, albumin, lactate, and electrolyte concentrations; PCV; colloid osmotic pressure; arterial and venous pH and blood gases (Po2; Pco2); whole blood and plasma viscosity; arterial and venous blood pressures; cardiac output; results of urinalysis; urine production; glomerular filtration rate; and anesthetic recovery times were monitored. Oxygen delivery, vascular resistance, stroke volume, pulse pressure, and blood and plasma volume were calculated.

Results—Increasing rates of LRS administration resulted in dose-dependent decreases in PCV; blood hemoglobin concentration and serum total protein and albumin concentrations; colloid osmotic pressure; and whole blood viscosity. Plasma viscosity; serum electrolyte concentrations; data from arterial and venous blood gas analysis; glomerular filtration rate; urine production; heart rate; pulse, central venous, and arterial blood pressures; pulmonary vascular resistance; and oxygen delivery did not change. Pulmonary artery pressure, stroke volume, and cardiac output increased, and systemic vascular resistance decreased.

Conclusions and Clinical Relevance—Conventional IV infusion rates of LRS to isoflurane-anesthetized dogs decreased colligative blood components; increased plasma volume, pulmonary artery pressure, and cardiac output; and did not change urine production or oxygen delivery to tissues.

Abstract

Objective—To determine the hematologic, serum biochemical, rheological, hemodynamic, and renal effects of IV administration of lactated Ringer's solution (LRS) to healthy anesthetized dogs.

Design—4-period, 4-treatment cross-over study.

Animals—8 healthy mixed-breed dogs.

Procedures—Each dog was anesthetized, mechanically ventilated, instrumented, and randomly assigned to receive LRS (0, 10, 20, or 30 mL/kg/h [0, 4.5, 9.1, or 13.6 mL/lb/h]), IV, on 4 occasions separated by at least 7 days. Blood hemoglobin concentration and serum total protein, albumin, lactate, and electrolyte concentrations; PCV; colloid osmotic pressure; arterial and venous pH and blood gases (Po2; Pco2); whole blood and plasma viscosity; arterial and venous blood pressures; cardiac output; results of urinalysis; urine production; glomerular filtration rate; and anesthetic recovery times were monitored. Oxygen delivery, vascular resistance, stroke volume, pulse pressure, and blood and plasma volume were calculated.

Results—Increasing rates of LRS administration resulted in dose-dependent decreases in PCV; blood hemoglobin concentration and serum total protein and albumin concentrations; colloid osmotic pressure; and whole blood viscosity. Plasma viscosity; serum electrolyte concentrations; data from arterial and venous blood gas analysis; glomerular filtration rate; urine production; heart rate; pulse, central venous, and arterial blood pressures; pulmonary vascular resistance; and oxygen delivery did not change. Pulmonary artery pressure, stroke volume, and cardiac output increased, and systemic vascular resistance decreased.

Conclusions and Clinical Relevance—Conventional IV infusion rates of LRS to isoflurane-anesthetized dogs decreased colligative blood components; increased plasma volume, pulmonary artery pressure, and cardiac output; and did not change urine production or oxygen delivery to tissues.

Intravenous fluid therapy is generally considered an important component of anesthetic practice. The American Animal Hospital Association mandates peri-operative administration of fluids as a standard of care for anesthetized animals. Reasons for perioperative fluid administration include offsetting anesthetic-induced vasodilatation; prevention and treatment of hypotension, hypovolemia, and poor tissue perfusion; and maintenance of normal renal function.1 In 1 study,2 hypotension (mean arterial blood pressure < 60 mm Hg) was the most frequent anesthetic complication in dogs (ie, 39.7% of complications) during general anesthesia.2

The primary goals of fluid therapy are to optimize cardiac preload, increase cardiac output, and maintain adequate oxygen delivery to tissues. However, optimal regimens of perioperative administration of fluids (crystalloid vs colloid) remain empirical and reflect biases focused on the rationale for fluid selection and uncertainties regarding individual patient fluid requirements.3,4 Several fluids, including 5% dextrose in water, saline (0.9% NaCl) solution, polyionic crystalloid solutions, and hetastarch, have been advocated as replacement fluids for the treatment of anesthesia-associated hypotension in anesthetized dogs.5–8 However, evidence to support perioperative fluid administration in dogs remains contentious or extrapolated from human trials. Furthermore, the clinical efficacy of various recipe-based protocols (vol/wt) or heuristic (ie, so-called rule of thumb) fluid administration formulas for the treatment of anesthesia-associated hypotension has not been thoroughly investigated. A clinical study5 that examined the effects of IV administration of 5% dextrose in water (5 to 15 mL/kg/h [2.3 to 6.8 mL/lb/h]) and a polyionic crystalloid solution (0 to 15 mL/kg/h) on serum biochemical and arterial blood pressures in healthy halothane-anesthetized dogs during routine elective surgical procedures lasting < 2 hours did not identify any fluid therapy–associated changes in PCV, serum total protein concentration, or systolic arterial blood pressure among treatment groups. The authors concluded that that IV administration of dextrose or crystalloid solutions did not produce a substantial effect on PCV or serum total protein concentration and was not necessary to maintain adequate blood pressure. The authors postulated that adequate arterial blood pressure may not correlate with cardiac output, which was not monitored in the study.5 Findings of recent studies3,9–13 suggest that central venous pressure and arterial blood pressures are poor indicators of cardiac output and tissue perfusion and question the various recipe-based approaches to perioperative administration of fluids in favor of goal-directed approaches. Other studies10,14,15 suggest that nontraditional (ie, goal-directed) methods should be used to monitor fluid administration, including assessment of pulse pressure variation and mixed venous oxygen saturation, and that these indices provide more meaningful and reliable data for assessing the status of the microcirculation.

Isoflurane is the most common inhalant anesthetic used in veterinary practice, and LRS (5 to 15 mL/kg/h) is the most frequently prescribed fluid for maintaining homeostasis.1,7 Nevertheless, no studies have comprehensively investigated the hematologic, rheological, hemodynamic, or acid-base effects of serially increasing rates of LRS administration in isoflurane-anesthetized dogs.5,16–18 The purpose of the study reported here was to determine the effects of LRS administered IV at rates that encompass and exceed those used clinically on hematologic, serum biochemical, and hemodynamic measurements and urine production in healthy isoflurane-anesthetized dogs.

Materials and Methods

Animals—All procedures were reviewed and approved by the Institutional Animal Care and Use Committee of QTest Labs and complied with federal guidelines for the care and use of laboratory animals. Eight purpose-bred young adult mixed-breed dogs (4 males and 4 females) weighing 12.2 to 18.9 kg (26.84 to 41.58 lb) were acclimated for at least 14 days prior to the start of the study. Dogs were individually housed in a temperature-controlled facility with a 12-hour light-dark cycle and provided commercial dry dog food and water ad libitum. A health examination was performed on each dog 7 and 1 days before being studied. The health examination included a physical examination, fecal flotation test, ophthalmologic assessment, auscultation of the heart and lungs, ECG, hemogram, and serum biochemical analysis.

Design—Dogs were randomly assigned to receive 0, 10, 20, or 30 mL of LRSa/kg/h (0, 4.5, 9.1, or 13.6 mL/lb/h) in a 4-period, 4-treatment crossover study with repeated measures. A block randomization method was used to randomize subjects into groups of equal size for each treatment. All possible balanced treatment combinations within a block were calculated and then blocks were randomly chosen. All 8 dogs received each treatment for 60 minutes during isoflurane anesthesia with a minimum of 7 days between treatments. The study was not conducted in a blinded fashion.

Animal preparation and procedures—Blood and urine samples were collected 24 hours before (day −1), during (day 0), and 24 hours after (day 1) treatment for each experiment. Urine samples were collected aseptically via cystocentesis by use of a 23-gauge needle and a 10-mL syringe (days −1 and 1) and bladder catheterization (day 0). The glomerular filtration rate was determined on the basis of exogenous creatinine clearance on days −1 and 1.19

On the day that the dog was assigned to receive LRS (0, 10, 20, or 30 mL/kg/h), a 20-gauge IV catheter was inserted into the cephalic vein. All dogs received acepromazine (0.025 mg/kg [0.0114 mg/lb], IV) and butorphanol (0.1 mg/kg [0.05 mg/lb], IV) 10 minutes before receiving propofol (approx 4 to 6 mg/kg [1.82 to 2.7 mg/lb], IV, to effect). The dogs were orotracheally intubated and mechanically ventilated by use of an ascending-bellows, volume-cycled, pressure-regulated ventilator.b The ventilator was set to deliver a tidal volume of 10 to 15 mL/kg (maximum allowed pressure, 16 to 20 cm H2O) at a rate of 8 to 12 breaths/min to maintain end-tidal partial pressure of carbon dioxidec between 35 and 45 mm Hg. The endotracheal tube was connected to a circle anesthetic rebreathing circuit, and anesthesia was maintained with isoflurane in oxygen delivered by use of an out-of-circuit precision vaporizer.d The end-tidal inhalant concentrationc was maintained between 1.4% and 1.6%. A warm air blankete was used to maintain body temperature between 36.5° and 37°C (97.7° and 98.6°F). The ECG, hemoglobin oxygen saturation, and arterial blood pressure (oscillometric techniquef) were continuously monitored throughout induction and maintenance of isoflurane anesthesia.

A flow-directed, balloon-tipped 5F thermodilution catheterg was percutaneously and aseptically inserted into the jugular vein and advanced into the pulmonary artery to permit continuous monitoring of central venous and pulmonary artery pressure and intermittent determination of cardiac output by use of thermodilution.h The mean of 3 thermodilution cardiac output determinations was calculated to obtain a cardiac output value at each recording time point. A catheter-tipped pressure-sensing catheter with a fluid-filled sampling porti was aseptically inserted into the right femoral artery and the tip advanced into the thoracic aorta. This catheter was used to record arterial blood pressure and to collect anerobic blood samples for determination of arterial pHj and blood gases (Pao2 and Paco2).j Mixed venous blood samples were obtained from the pulmonary artery catheter for determination of mixed venous pH,j venous blood gases (Pvo2 and Pvco2),j and hematologic and serum biochemical data. Each dog was in a stabilized anesthetic state for approximately 30 minutes before recording baseline data (time 0), collection of blood samples, and initiation of fluid administration (0, 10, 20, and 30 mL/kg/hk). All dogs were allowed to recover from anesthesia, and the times to tracheal tube removal, sternal recumbency, and standing were recorded.

Experimental data—Urine samples were evaluated for color, clarity, bilirubin, blood, protein, glucose, ketones, urobilinogen, microscopic sediment, nitrites, occult blood, leukocytes, pH, specific gravity, and electrolytes (Na+, K+, and Cl). The plasma BUN and serum creatinine concentrations were determined on days −1, 0, and 1. The glomerular filtration rate (reference range, 2.5 to 5.5 mL/kg/min [1.14 to 2.5 mL/lb/min]) was assessed on days −1 and 1.20

Blood hemoglobin concentrationj and serum total protein,l albumin,m lactate,j and electrolyte (Na+, K+, Cl, and ionized Ca2+)j concentrations; COPn; and PCV were determined from mixed venous blood samples at time 0 (baseline) and 30 and 60 minutes. Arterial and mixed venous pH,j Po2,j and Pco2j were determined from anaerobic blood samples collected at baseline and at 30 and 60 minutes. Whole blood and plasma viscositieso were determined from mixed venous blood samples obtained at baseline and 60 minutes at a shear rate of 150 s−1 and temperature of 37°C. Heart ratep; respiration rate; systolic, mean, and diastolic arterial blood pressuresp; thermodilution cardiac output (0 and 60 minutes only); central venousp and mean pulmonary artery pressurep; and body temperaturep were recorded at 0 (baseline), 15, 30, and 60 minutes. Systemic and pulmonary vascular resistance, stroke volume, pulse pressure, and oxygen delivery were calculated at 0 and 60 minutes from standard formulas. The bladder was emptied, and urine output was recorded from time 0 for 60 minutes.

Blood volume and PV changes over time were calculated from estimated baseline values of blood volume (81.5 mL/kg [37.05 mL/lb]) and PV (49 mL/kg [22.3 mL/lb]) for clinically normal dogs.21 Preinfusion and subsequent estimates of blood volume and PV were determined by use of previously described mass balance equations.22,23 Preinfusion calculation of blood volume (PVt/[1 – PCV × 0.95 × 0.92]) was corrected for known errors in large vessel Hct (0.92) and plasma trapped in erythrocyte column of the Hct tube (0.95).24 Changes in PV expansion were calculated as ΔPV = PVt – PVt−1. Volume expansion efficiency was calculated as the net change in PV divided by the cumulative volume of LRS infused (ΣFt) such that VEEt = PV/ΣFt.24

Statistical analysis—An ANOVA appropriate for a 4-period, 4-treatment crossover study with repeated measures was used to evaluate the effect of fluid administration on the outcomes of interest. The assumption of normality was evaluated through the use of normal probability plots. The statistical model included treatment sequence, period, treatment (0, 10, 20, or 30 mL/kg/h), time, and the time by treatment interaction as fixed effects. Dog nested in sequence was included as a random effect. Given only 2 to 4 generally equally spaced time intervals, the structure of the covariance matrix was assumed to be compound symmetric. The repeated measures associated with period were ignored. If the time by treatment interaction was significant, an all-pairwise comparison of treatment effects within time was conducted. Additionally, given a time by treatment interaction, within treatment, time effects were assessed by comparing time 0 values to values collected after time 0. If no interaction existed, the main effect of time was investigated and again an all-pairwise approach was used. Where there were no repeated measures, the same approach was taken but the time and time by treatment interactions were excluded from the model. Values of P < 0.05 were considered significant.

Results

Urine pH ranged from 5.0 to 9.0 and urine specific gravity from 1.018 to 1.042 on days −1, 0, and 1. The plasma BUN concentration ranged from 13 to 35 mg/dL and serum creatinine concentration from 0.5 to 1.2 mg/dL on days −1, 0, and 1. The glomerular filtration rate ranged from 3.0 to 5.4 mL/kg/min (1.4 to 2.45 mL/lb/min) and was within reference limits for dogs on days −1 and 1.

Induction of anesthesia and transition to isoflurane anesthesia were uneventful. No dog became excited or had uncharacteristic changes in heart rate or rhythm, oxygen saturation (< 90%), or oscillometric blood pressure measurements (systolic arterial blood pressure < 90 mm Hg). The normal probability plots did not identify deviations from normal, and thus, all outcomes were analyzed under the assumption of normality. The IV administration of LRS produced dose-dependent decreases in PCV; blood hemoglobin concentration and serum total protein and albumin concentrations; COP; and whole blood viscosity, compared with baseline values (Table 1). Plasma viscosity did not change. These responses were greater for administration at 30 mL/kg/h, compared with administration at 20 and 10 mL/kg/h and baseline. Serum Na+ (140 to 145 mEq/L), K+ (3.3 to 4.8 mEq/L), Cl (109 to 116 mEq/L), and ionized Ca2+ (1.36 to 1.51 mmol/L) concentrations did not change during fluid administration and were not different among treatment groups. Arterial and mixed venous pH, blood gas variables (Po2, and Pco2), and lactate concentrations did not change during LRS administration (Table 2). Increasing rates of LRS administration did not change heart rate (Table 3). Systemic arterial pressures increased minimally but not significantly during LRS administration and were not different among treatment groups. However, mean central venous pressure apparently increased with LRS administration but not significantly (P = 0.089). Increasing rates of LRS administration increased pulmonary artery pressure and CO. The increases in pulmonary artery pressure were greatest during LRS administration at 30 mL/kg/h, followed by administration at 20 mL/kg/h, and were not observed at baseline or during LRS administration at 10 mL/kg/h. The increases in cardiac output were greatest during LRS administration at 30 mL/kg/h, followed by LRS administration at 20 and 10 mL/kg/h, and were not observed at baseline. The rate of urine production did not change and was not different among treatment groups (0.7 ± 0.4 mL/kg/h to 1.1 ± 0.8 mL/kg/h [0.32 ± 0.18 mL/lb/h to 0.5 ± 0.36 mL/lb/h]). Stroke volume increased and systemic vascular resistance decreased during LRS administration (Table 4). The increases in stroke volume and decreases in systemic vascular resistance were greatest during administration at 30 mL/kg/h, followed by administration at 20 mL/kg/h, and were not observed at baseline or during LRS administration at 10 mL/kg/h. Pulmonary vascular resistance and pulse pressure were not changed by LRS administration. Body temperature ranged from 35.1° to 37.9°C (95.18° to 100.22°F) and did not change with LRS administration. Increasing rates of LRS administration increased PV (Figure 1). The 60-minute increase in PV was greatest during LRS administration at 30 mL/kg/h, followed by LRS administration at 20 mL/kg/h, and was not significant for baseline measurements and LRS administration at 10 mL/kg/h. The VEE (vol/vol of LRS infused) ranged from 37% to 50% for the 20 and 30 mL/kg/h infusion rates immediately at the end of infusion.

Figure 1—
Figure 1—

Mean ± SD change in PV produced by LRS infusion to isoflurane-anesthetized dogs. *Values within a treatment group are significantly (P < 0.05) different from time 0. a–cValues within a time point with no common superscripts are significantly (P < 0.05) different from each other (n = 8 dogs in a 4-treatment cross-over study).

Citation: Journal of the American Veterinary Medical Association 239, 5; 10.2460/javma.239.5.630

Table 1—

Effects of LRS administration on blood variables in 8 healthy mixed-breed dogs.

  Time point (min)
VariableInfusion rate (mL/kg)03060
PCV (%)037 ± 437 ± 4a35 ± 3a
 1037 ± 335 ± 4a,b35 ± 3a,b
 2037 ± 335 ± 3b*34 ± 4b,c*
 3037 ± 334 ± 4b*32 ± 4c*
Blood hemoglobin concentration (g/dL)011.1 ± 1.311.1 ± 1.3a11.0 ± 1.1a
 1011.1 ± 1.60.5 ± 1.1b*10.1 ± 1.2b*
 2011.0 ± 1.09.9 ± 1.2c*9.5 ± 1.1c*
 3011.3 ± 1.19.7 ± 1.3c*9.2 ± 1.5c*
Serum total protein concentration (g/dL)05.6 ± 0.35.4 ± 0.3a5.3 ± 0.3a
 105.4 ± 0.45.2 ± 0.2b*4.9 ± 0.3b*
 205.3 ± 0.24.9 ± 0.2c*4.7 ± 0.3c*
 305.4 ± 0.34.7 ± 0.3d*4.5 ± 0.4d*
COP (mm Hg)016 ± 216 ± 1a16 ± 2a
 1017 ± 315 ± 2a,b16 ± 3a
 2017 ± 415 ± 2b,c*13 ± 1b*
 3016 ± 213 ± 2c*13 ± 1b*
Serum albumin concentration (g/dL)02.8 ± 0.22.7 ± 0.2a2.7 ± 0.2a*
 102.7 ± 0.32.6 ± 0.3a*2.5 ± 0.2b*
 202.8 ± 0.32.5 ± 0.2b*2.4 ± 0.2c*
 302.7 ± 0.32.4 ± 0.2c*2.3 ± 0.2c*
Blood viscosity (cP)03.2 ± 0.3NA3.2 ± 0.3a
 103.3 ± 0.5NA2.9 ± 0.4b*
 203.2 ± 0.2NA2.8 ± 0.3b,c*
 303.3 ± 0.3NA2.7 ± 0.3c*
Plasma viscosity (cP)01.1 ± 0.1NA1.1 ± 0.1
 101.2 ± 0.2NA1.1 ± 0.1
 201.2 ± 0.1NA1.1 ± 0.1
 301.2 ± 0.1NA 1.0± 0.1

Values are presented as mean 6 SD.

Values within a treatment group are significantly (P < 0.05) different from time 0.

Values within a time point with no common superscripts are significantly (P < 0.05) different from each other.

cP = Centipoise. NA = Not applicable.

Table 2—

Effects of LRS administration on arterial and venous pH and blood gas variables in the same dogs as in Table 1.

  Time point (min)
VariableInfusion rate (mL/kg)03060
Arterial pH07.30 ± 0.037.31 ± 0.037.31 ± 0.02
 107.31 ± 0.037.31 ± 0.037.32 ± 0.07
 207.30 ± 0.047.32 ± 0.037.33 ± 0.03
 307.32 ± 0.037.34 ± 0.027.35 ± 0.03
Pao2 (mm Hg)0561 ± 55576 ± 29542 ± 51
 10583 ± 38574 ± 45553 ± 49
 20578 ± 66572 ± 39570 ± 39
 30587 ± 36569 ± 46564 ± 38
Paco2 (mm Hg)044 ± 343 ± 243 ± 3
 1046 ± 445 ± 444 ± 2
 2045 ± 444 ± 243 ± 5
 3045 ± 344 ± 242 ± 4
Venous pH07.28 ± 0.047.29 ± 0.037.29 ± 0.02
 107.28 ± 0.047.30 ± 0.057.31 ± 0.03
 207.27 ± 0.037.29 ± 0.037.29 ± 0.06
 307.29 ± 0.027.31 ± 0.027.32 ± 0.02
Pvco2 (mm Hg)044 ± 445 ± 245 ± 2
 1046 ± 245 ± 444 ± 2
 2047 ± 346 ± 346 ± 6
 3047 ± 244 ± 243 ± 3
Serum lactate concentration (mmol/L)01.7 ± 0.41.6 ± 0.41.6 ± 0.2
 101.5 ± 0.61.7 ± 0.61.7 ± 0.6
 201.4 ± 0.61.5 ± 0.61.3 ± 0.5
 301.1 ± 0.51.4 ± 0.31.4 ± 0.3

See Table 1 for key.

Table 3—

Effects of LRS administration on physiologic variables in the same dogs as in Table 1.

  Time point (min)
VariableInfusion rate (mL/kg)0153060
Heart rate (beats/min)085 ± 887 ± 487 ± 689 ± 5
 1082 ± 986 ± 589 ± 688 ± 12
 2083 ± 1483 ± 1184 ± 786 ± 8
 3077 ± 1282 ± 1384 ± 1388 ± 13
Mean central venous pressure (mm Hg)08 ± 18 ± 18 ± 17 ± 1
 108 ± 38 ± 38 ± 38 ± 2
 207 ± 38 ± 37 ± 38 ± 3
 308 ± 29 ± 29 ± 210 ± 2
Mean pulmonary artery pressure (mm Hg)017 ± 117 ± 117 ± 1a17 ± 1a
 1016 ± 216 ± 117 ± 2a17 ± 3a
 2017 ± 118 ± 218 ± 2a,b18 ± 2b*
 3016 ± 218 ± 3*19 ± 3b*20 ± 3c*
Systolic arterial blood pressure (mm Hg)0110 ± 12117 ± 13118 ± 12118 ± 14
 10101 ± 17111 ± 12116 ± 10117 ± 10
 2098 ± 18107 ± 18109 ± 18111 ± 16
 3099 ± 17107 ± 15109 ± 16111 ± 16
Diastolic arterial blood pressure (mm Hg)083 ± 1088 ± 1089 ± 986 ± 10
 1075 ± 1482 ± 984 ± 985 ± 8
 2073 ± 1677 ± 1678 ± 1577 ± 14
 3073 ± 1577 ± 1478 ± 1478 ± 14
Mean arterial blood pressure (mm Hg)096 ± 10102 ± 10103 ± 10102 ± 14
 1088 ± 1596 ± 9100 ± 96101 ± 8
 2086 ± 1792 ± 1793 ± 1694 ± 15
 3086 ± 1692 ± 1494 ± 1592 ± 17
Cardiac output (mL/kg/min)0171 ± 22NANA187 ± 25a
 10155 ± 21NANA195 ± 28a,b*
 20161 ± 41NANA226 ± 44b,c*
 30150 ± 25NANA243 ± 42c*
Urine output (mL/kg/h)0NANANA0.7 ± 0.4
 10NANANA0.7 ± 0.3
 20NANANA0.8 ± 0.5
 30NANANA1.1 ± 0.8

See Table 1 for key.

Table 4—

Effects of LRS administration on calculated variables in the same dogs as in Table 1.

VariableInfusion rate (mL/kg)0 min60 min
Systemic vascular resistance (dynes/s/cm5)03792,973 ± 459a
 103,201 ± 6742,779 ± 500a
 202,816 ± 8042,316 ± 778b*
 303,213 ± 2102,105 ± 744b*
Pulmonary vascular resistance (dynes/s/cm5)0313 ± 73301 ± 37
 10320 ± 103264 ± 76
 20345 ± 100265 ± 75
 30336 ± 140250 ± 57
Stroke volume (mL)028 ± 429 ± 4a
 1025 ± 732 ± 5a
 2028 ± 637 ± 7b*
 3027 ± 738 ± 8b*
Pulse pressure (mm Hg)027 ± 332 ± 4
 1026 ± 432 ± 5
 2025 ± 433 ± 3
 3026 ± 333 ± 3
Oxygen delivery (mL/min)0351 ± 67381 ± 68
 10318 ± 95372 ± 70
 20347 ± 95394 ± 83
 30319 ± 61381 ± 88

See Table 1 for key.

Mean times to extubation (13 to 19 minutes), sternal recumbency (26 to 36 minutes), and standing (39 to 49 minutes) were not different among treatment groups. All dogs recovered from anesthesia uneventfully and were returned to their kennels.

Discussion

We investigated the effects of increasing infusion rates of LRS on hematologic, serum biochemical, rheological, hemodynamic, and renal variables in isoflurane-anesthetized dogs. Our results support and extend those of previous studies16–18,25,26 in anesthetized dogs, pigs, sheep, and humans and confirm that the administration of an acellular, albumin-free, minimally hypotonic (273 mOsm/L) crystalloid solution (LRS) to isoflurane-anesthetized dogs decreases PCV; serum total protein and albumin concentrations and blood hemoglobin concentration; COP; and whole blood viscosity. Heart rate, mean central venous pressure, and systemic arterial blood pressure did not change. However, as a result of an increase in stroke volume, cardiac output increased from that measured at either baseline or after the infusion of LRS at 10 mL/kg/h; it increased significantly after infusions of 20 or 30 mL/kg/h. The increase in stroke volume may be attributed to increased preload, positive cardiac contractile effects, decreases in aortic input impedance, or a decrease in blood viscosity; however, considering it followed fluid replacement, changes in blood viscosity or preload appear to be the most reasonable explanations.25,26 The pulmonary artery pressure increased at the highest fluid infusion rate, suggesting compensatory rheological effects and intravascular volume expansion. The rate of urine production did not change among treatment groups during isoflurane anesthesia despite an increasing rate of fluid infusion, suggesting fluid retention during anesthesia and an anesthesia-associated decrease in urine production.

The results of the present study agree with those of other studies10,25–28 that found that mean central venous and systemic arterial blood pressures are relatively poor monitors of fluid administration when LRS is administered at a rate of 10 mL/kg/h. Cardiac output increases at rates of fluid administration exceeding 20 mL/kg/h, dogs retain large amounts of fluid during isoflurane anesthesia, and urine production is not an adequate indicator of fluid balance in isoflurane-anesthetized dogs. A previous study27 investigated the hematologic and hemodynamic effects of rapid infusion of LRS (90, 225, and 360 mL/kg/h [40.9, 102.3, and 163.6 mL/lb/h]) for 1 hour to mildly dehydrated, conscious dogs. The investigators in that study27 observed that an infusion rate of 90 mL/kg/h was well tolerated, and signs of fluid excess (profuse nasal serous discharge, restlessness, coughing, abdominal distention, vomiting, and diarrhea) were not observed until an infusion rate of 360 mL/kg/h was obtained. These adverse effects resolved quickly after cessation of fluid administration, suggesting that relatively rapid rates of fluid administration (90 mL/kg/h) are tolerated, at least in conscious dogs.27 In agreement with results of the present study, that previous study27 revealed that systemic arterial blood pressure increased minimally and inconsistently and that central venous pressure did not change when LRS was administered at 90 mL/kg/h. More recent studies8 investigating the hemodynamic effects of IV infusion of LRS at a rate of 80 mL/kg/h (36.4 mL/lb/h) for 1 hour during isoflurane-induced hypotension (systolic arterial blood pressure, 80 mm Hg) in dogs demonstrated decreases in PCV, COP, whole blood viscosity, and serum total protein and albumin concentrations and no change in arterial blood pressure. Central venous and pulmonary artery pressures, stroke volume, cardiac output, and blood volume increased and systemic vascular resistance decreased 15 minutes after beginning fluid infusion. Urine production was not measured. A clinical study5 revealed that the administration of 5, 10, or 15 mL of polyionic crystalloid solution/kg/h, IV, to halothane-anesthetized dogs produced no effect on PCV, serum total protein concentration, or systolic arterial blood pressure. However, subsequent studies16 in isoflurane- or sevoflurane-anesthetized dogs demonstrated that administration of 10 mL of LRS/kg/h, IV, for 1 hour was associated with a decrease in PCV and blood hemoglobin and serum total protein concentrations. Others have reported similar decreases in PCV, serum total protein concentration, and COP but cautioned that anesthesia alone can decrease serum total protein concentration and COP.17 A recent clinical study28 conducted in isoflurane-anesthetized dogs administered 10 mg of LRS/kg/h, IV, and subjected to an orthopedic surgical procedure concluded that a large amount of IV fluid is retained as indicated by increased body weight, positive fluid balance, increased total body water volume, and increased extracellular fluid volume. Collectively, the results of our investigation and data provided by others provide evidence that conventional rates of IV administration of LRS dilute blood components and that the fluids are distributed to extravascular fluid depots.

Acid-base abnormalities are common during anesthesia, and the IV administration of crystalloids has the potential to alter acid-base balance. Crystalloids with a strong ion difference of 24 mEq/L maintain base excess near zero and are considered balanced.29 Alternatively, physiologic saline solution has a strong ion difference of 0 mEq/L and the potential to produce hyperchloremic metabolic acidosis regardless of dilution of plasma proteins (weak acids).29–32 Lactated Ringer's solution is minimally hypotonic and has a strong ion difference of 27 mEq/L, suggesting that it produces minimal effects on strong ion difference and base excess when administered to normovolemic dogs. We did not observe or expect any changes in arterial or venous acid-base status (pH and Pco2). Our data and those of others16–18,29,32,33 confirm that the IV administration of moderate to large amounts of LRS to normovolemic, isoflurane-anesthetized dogs is unlikely to exacerbate acid-base abnormalities.

The rate and duration of fluid administration are key factors in restoring blood volume and hemodynamics. However, higher fluid infusion rates than are currently recommended (> 10 to 15 mL/kg/h) may not have the desired effect upon PV but do increase interstitial fluid volume.34–37 We estimated the VEE (ΔPV/total cumulative fluid volume) following IV administration of LRS at rates of 20 and 30 mL/kg/h to be approximately 40%, similar to that of a previous study,24 and did not determine the rate of return of vascular volume to baseline. A study24 in isoflurane-anesthetized sheep revealed that the VEE at the end of a 20-minute infusion of saline solution (25 mL/kg [11.4 mL/lb]) was approximately 40% but rapidly decreased to approximately 14% by 30 minutes after infusion. A recent investigation in isoflurane-anesthetized dogs subjected to an orthopedic surgical procedure and administered 10 mL of LRS/kg/h, IV, suggested relatively rapid loss of fluid from the vascular space and retention of large amounts of fluid in the extracellular space.28 Although the experimental methods used in each of the previous studies varied considerably, they emphasize that the rate and duration of fluid administration affect VEE, larger fluid volumes and faster rates of crystalloid administration increase VEE, and crystalloids are not retained within the vascular fluid compartment for extended periods. Furthermore, the increase in VEE may not be associated with an increase in oxygen delivery, regardless of increases in cardiac output, because blood hemoglobin concentration decreased (dilutional effect). Furthermore, our data support the finding that elimination of the infused volume of LRS from the vascular compartment in isoflurane-anesthetized dogs cannot be accounted for by urinary excretion because urine production did not change. This finding supports the contention that most of the infused fluid must accumulate in a peripheral or extravascular site. Additional studies are required to determine the optimal blood hemoglobin concentration relative to cardiac output to maintain an adequate oxygen delivery during LRS infusion in isoflurane-anesthetized dogs.

We attempted to design our study to include and mimic the clinical conditions encountered during isoflurane anesthesia in otherwise healthy dogs. The results of our study must be interpreted carefully. Our study may have been underpowered regarding several hemodynamic variables, including mean central venous and arterial blood pressures, which may have resulted in significant changes had we included more dogs. Our dogs were ventilated, and a specific anesthetic protocol was selected. Anesthesia is known to alter homeostasis and the rate of elimination of infused crystalloids from the intravascular space through changes in their distribution and alterations in urinary excretion.24 None of our dogs were subjected to major surgery or became hypotensive, effects that are known to increase the amount of fluid that accumulates in extravascular body fluid compartment and delays fluid elimination, respectively.36,37 Our dogs were not splenectomized, which may have altered our calculation of PV and VEE. Furthermore, we may have overestimated the VEE due to alterations in the large-vessel whole-body PCV ratio.24,36 Finally, we administered a range of fluid rates that encompassed conventional recommendations but may not represent universal clinical practice. Larger infusion rates administered over shorter periods are generally recommended for the acute treatment of hypotension or hemorrhage and likely would have produced different results.

In conclusion, findings in our study indicate that conventional rates of LRS administration to healthy isoflurane-anesthetized dogs increase PV and cardiac output and decrease blood viscosity and the colligative properties of blood but do not increase the rate of urine production or produce consistent and significant alterations in mean central venous or arterial blood pressures.

ABBREVIATIONS

COP

Colloid osmotic pressure

LRS

Lactated Ringer's solution

PV

Plasma volume

VEE

Volume expansion efficiency

a.

Veterinary Lactated Ringer's Injection USP, Abbott Laboratories, North Chicago, Ill.

b.

Hallowell EMC 2KIE, Hallowell, Pittsfield, Mass.

c.

Gas module SE, Datascope, Montvale, NJ.

d.

MSS Isoflurane, Highland Medical Equipment, Tamecula, Calif.

e.

Bair Hugger, Arizant Inc, Prairie, Minn.

f.

Passport 2, Datascope, Montvale, NJ.

g.

Swan-Ganz, Edwards Lifesciences, Irvine, Calif.

h.

Edwards Com-2 Cardiac Output Computer, Edwards Life-sciences, Irvine, Calif.

i.

MIKRO-TIP Catheter Transducer, Millar Instruments Inc, Houston, Tex.

j.

i-STAT, Abbott Point of Care Inc, Princeton, NJ.

k.

Heska Vet IV 2.2, Sensor Devices Inc, Waukesha, Wis.

l.

Clinical refractometer J-351, Jorgensen Laboratories Inc, Love-land, Colo.

m.

Olympus AU2700 Chemistry Analyzer, Olympus America Inc, Melville, NY.

n.

Colloid Osmometer, model 4420, Wescor, Logan, Utah.

o.

Brookfield Engineering Laboratories, Middleboro, Mass.

p.

IOX and EC Gauto, EMKA Technologies, Fall Church, Va.

References

  • 1. Kudnig ST, Mama K. Perioperative fluid therapy. J Am Vet Med Assoc 2002; 221: 11121121.

  • 2. Redondo JI, Rubio M, Soler G, et al. Normal values and incidence of cardiorespiratory complications in dogs during general anaesthesia. A review of 1281 cases. J Vet Med 2007; 54: 470477.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Chapell D, Mathias J, Hofmann-Klefer K, et al. A rational approach to perioperative fluid management. Anesthesiology 2009; 109: 723740.

    • Search Google Scholar
    • Export Citation
  • 4. Roche AM, James MF. Colloids and crystalloids: does it matter to the kidney? Curr Opin Crit Care 2009; 15: 520524.

  • 5. Gaynor JS, Wertz EM, Kesel LM, et al. Effect of intravenous administration of fluids on packed cell volume, blood pressure, and total protein and blood glucose concentrations in healthy halothane-anesthetized dogs. J Am Vet Med Assoc 1996; 203: 20132015.

    • Search Google Scholar
    • Export Citation
  • 6. Muir WW, Wiese AJ. Comparison of lactated Ringer's solution and a physiologically balanced 6% hetastarch plasma expander for the treatment of hypotension induced via blood withdrawal in isoflurane-anesthetized dogs. Am J Vet Res 2004; 65: 11891194.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Mensack S. Fluid therapy: options and rational administration. Vet Clin North Am Small Anim Pract 2008; 38: 575586.

  • 8. Aarnes TK, Bednarski RM, Lerche P, et al. Effect of intravenous administration of lactated Ringer's solution or hetastarch for the treatment of isoflurane-induced hypotension in dogs. Am J Vet Res 2009; 70: 13451353.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Magder S. Central venous pressure: a useful but not so simple measurement. Crit Care Med 2006; 34: 22242227.

  • 10. Renner J, Scholz J, Bein B. Monitoring fluid therapy. Best Pract Res Clin Anaesthesiol 2009; 23: 159171

  • 11. Hilterbrand LB, Kinberger O, Anrberger M, et al. Crystalloids versus colloids for goal-directed fluid therapy in major surgery. Crit Care 2009; 13: R40.

  • 12. Kehlet H. Goal-directed perioperative fluid management. Anesthesiology 2009; 110: 453455.

  • 13. Kimberger O, Arnberger M, Brandt S, et al. Goal-directed colloid administration improves the microcirculation of healthy and perianastomotic colon. Anesthesiology 2009; 110: 496504.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. De Backer D, Heenan S, Piagnerelli M, et al. Pulse pressure variations to predict fluid responsiveness: influence of tidal volume. Intensive Care Med 2005; 31: 517523.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15. Magder S. Clinical usefulness of respiratory variations in arterial pressure. Am J Crit Care Med 2004; 169: 151155.

  • 16. Valverde A, Hatcher E, Stampfli HR. Effects of fluid therapy on total protein and its influence on calculated unmeasured anions in the anesthetized dog. J Vet Emerg Crit Care 2008; 18: 480487.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Wright BD, Hopkins A. Changes in colloid osmotic pressure as a function of anesthesia and surgery in the presence and absence of isotonic fluid administration in dogs. Vet Anaesth Analg 2008; 15: 282288.

    • Search Google Scholar
    • Export Citation
  • 18. Dismukes DI, Thomovsky EJ, Mann FA. et al. Effects of general anesthesia on plasma colloid oncotic pressure in dogs. J Am Vet Med Assoc 2010; 236: 309311.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Finco DR, Brown SA, Crowell WA. et al. Exogenous creatinine clearance as a measure of glomerular filtration rate in dogs with reduced renal mass. Am J Vet Res 1991; 52: 10291032.

    • Search Google Scholar
    • Export Citation
  • 20. Chew DJ. Fluid therapy during intrinsic renal failure. In: Di-Bartola SP, ed. Fluid therapy in small animal practice. 2nd ed. Philadephia: WB Saunders Co, 2000; 410427.

    • Search Google Scholar
    • Export Citation
  • 21. Wamberg S, Sandgaard NCF, Bie P. Simultaneous determination of total body water and plasma volume in conscious dogs by the indicator dilution principle. J Nutr 2002; 132: 1711817138.

    • Search Google Scholar
    • Export Citation
  • 22. Tølløfsrud S, Elgjo GI, Prough DS, et al. The dynamics of vascular volume and fluid shifts of infused lactated Ringer's and hypertonic saline dextran (HSD) in normovolemic sheep. Anesth Analg 2001; 93: 823831.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23. Svenson CH, Rodhe PM, Prough DS. Pharmacokinetic aspects of fluid therapy. Best Pract Res Clin Anaesthesiol 2009; 23: 213224.

  • 24. Connolly CM, Kramer GC, Hahn RG, et al. Isoflurane but not mechanical ventilation promotes extravascular fluid accumulation during crystalloid volume loading. Anesthesiology 2003; 98: 670681.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25. Hiltebrand LB, Pestel G, Hager H, et al. Perioperative fluid management: comparison of high, medium and low fluid volume on tissue oxygen pressure in the small bowel and colon. Eur J Anaesthesiol 2007; 24: 927933.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Johansen LB, Bie P, Warberg J, et al. Hemodilution, central blood volume, and responses after an isotonic saline infusion in humans. Am J Physiol 1997; 272: R549R556.

    • Search Google Scholar
    • Export Citation
  • 27. Cornelius LM, Finco DR, Culver DH. Physiologic effects of rapid infusion of Ringer's lactate solution into dogs. Am J Vet Res 1978; 39: 11851190.

    • Search Google Scholar
    • Export Citation
  • 28. Boscan P, Pypendop BH, Siao KT, et al. Fluid balance, glomerular filtration rate, and urine output in dogs anesthetized for an orthopedic surgical procedure. Am J Vet Res 2010; 71: 501507

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Morgan TJ, Venkatesh B. Designing “balanced” crystalloids. Crit Care Resusc 2003; 5: 284291.

  • 30. Kellum JA. Disorders of acid-base balance. Crit Care Med 2007; 35: 26302636.

  • 31. Constable PD. Clinical assessment of acid-base status: comparison of the Henderson-Hasselbalch and strong ion approaches. Vet Clin Pathol 2000; 29: 115128.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Boldt J. The balanced concept of fluid resuscitation. Br J Anaesth 2007; 99: 312315.

  • 33. Morgan TJ. Clinical review: the meaning of acid-base abnormalities in the intensive care unit: part III—effects of fluid administration. Crit Care 2005; 9: 204211.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34. Hahn RG, Svensen C. Plasma dilution and the rate of infusion of Ringer's solution. Br J Anaesth 1997; 79: 6467.

  • 35. Tatara T, Tashiro C. Quatitative analysis of fluid balance during abdominal surgery. Anesth Analg 2007; 104: 347354.

  • 36. Drobin D, Hahn RG. Volume kinetics of Ringer's solution in hypotensive volunteers. Anesthesiology 1999; 90: 8191.

  • 37. Jacob M, Chappell D, Rehm M. The ‘third space’—fact or fiction. Best Pract Res Clin Anaesthesiol 2009; 23: 145157.

All Time Past Year Past 30 Days
Abstract Views 286 0 0
Full Text Views 894 750 81
PDF Downloads 313 181 17
Advertisement