SUMMARY

Changes in blood gases, pH, and plasma electrolyteconcentrations in response to intravenously infusedsodium bicarbonate (NaHCO3) and sodium acetate(NaCH3CO2) solutions (1.34 mEq/mL) in 5 light breedmares were investigated. Jugular venous blood sampleswere collected before and after completion of the infu-sions in 20-minute intervals for 200 minutes. Infusion ofsodium bicarbonate and sodium acetate caused significant(P < .00l) increases in blood pH and bicarbonate ion con-centration that persisted throughout the collection period.The elevation in blood pH and bicarbonate ion concentra-tions was greater (P < .01) for sodium bicarbonate thanfor sodium acetate immediately after the completion ofthe infusions but was not different (P > .05) thereafter.There were significant reductions (P < .01) in plasma-ion-ized calcium and potassium after infusion of both sodiumbicarbonate and sodium acetate. This study found that sig-nificant metabolic alkalosis in horses and correspondingshifts in electrolyte concentrations can be induced by in-travenous infusion of solutions of either sodium bicarbon-ate or sodium acetate, and they persist for at least 3 hours.These data show that the short-term elevation in pH andbicarbonate ion concentration is momentarily higher afterinfusion of sodium bicarbonate. This is likely due to thedirect infusion of bicarbonate ions in the sodium bicar-bonate treatment, such that further metabolism is not re-quired to be effective. However, the longer-term alkalosisdid not differ between isomolar solutions of sodium bi-carbonate and sodium acetate.

INTRODUCTION

The effects of oral administration of sodium bicar-bonate on acid-base changes and athletic performance

From the Departments of Animal Sciences and Veterinary ClinicalMedicine, University of Illinois, Urbana.0737-0806/$ - see front matter© 2005 Elsevier Inc. All rights reserved.doi:10.1016/j.jevs.2005.07.003

Volume 25, Number 8 349

Effects of Intravenous Sodium Bicarbonateand Sodium Acetate on Equine Acid-Base StatusKevin Kline, PhD; Leonard P. Frey, PhD; Jonathan H. Foreman, DVM, MS; Joseph T. Lyman, DVM, MS

Scientific Papers

have been investigated in both equine and human ath-letes. Metabolic alkalosis has been consistently observed;however, conclusive evidence of consistent ergogenicbenefits to horses given oral solutions of sodium bicar-bonate or other alkalinizing compounds (“milk shakes”)has yet to be found. The potential for sodium bicarbonateto influence athletic performance may depend on dosage,time of administration before exercise, and intensity andduration of exercise. The literature, however, contains lit-tle data comparing the effects of intravenous administra-tion to horses of sodium bicarbonate with other com-pounds such as sodium acetate, which has the potential tobe used for its alkalinizing effect, similar to that of thetraditional orally administered “milk shake” or sodiumbicarbonate solution. The blood gas and electrolyte datafrom this experiment are relevant for Standardbred andThoroughbred racing jurisdictions to refine proceduresused to detect and deter the unlawful administration of al-kali or buffers, via any route, to horses before racing.

MATERIALS AND METHODS

Experimental Design

Changes in acid-base and electrolyte status after in-travenous infusion of isomolar (1.34 mEq/mL) sodiumbicarbonate or sodium acetate solutions or a control solu-tion of 0.9% sodium chloride were determined in 5 mares(1 Thoroughbred, 2 Quarter Horse, and 2 Standardbred),6 to 8 years old weighing 503 to 610 kg, in a switchbackstudy. Each mare participated in 3 trials whereby in eachtrial a different treatment was administered. The order inwhich each trial was performed in each mare was ran-domized. Trials were no fewer than 3 days apart. Thesodium bicarbonate and sodium acetate treatments wereprepared using sterile techniques in laboratory. The con-centrations of sodium bicarbonate and sodium acetatewere chosen on the basis of our laboratory’s previous useof an 11.25% solution of sodium bicarbonate that was de-termined to induce significant metabolic alkalosis butpose little health risk to horses. Each mare was adminis-

REFEREED

350 Journal of Equine Veterinary Science August 2005

tered 1 L of each treatment. Mares were kept in confinedareas with shelter and received an invariable diet ofmedium-quality alfalfa hay ad libitum for 12 weeks be-fore and between all trials. Mares were placed in individ-ual box stalls and denied hay and water during blood col-lection times after administering treatments. Each trialwas performed beginning the same time each day. TheInstitutional Animal Care and Use Committee of theUniversity of Illinois approved the protocol.

Sampling Protocol

Blood was collected after placing mares in familiar-ized stocks. A 16-gauge, 31/4- inch Teflon catheter(Angiocath, Becton Dickinson Vascular Access, Sandy,UT) was placed aseptically in the right jugular vein.Blood samples were collected from the left jugular byvenipuncture before infusion (time 0), within 10 secondsafter the cessation of infusion, and in 20-minute intervalsfor 200 minutes. Infusion of treatments was started afterinsertion of the catheter at a constant rate of 50 mL perminute, and infusion duration time was 20 minutes.Blood samples (7 mL) for determination of blood gasesand pH were collected in sodium heparinized evacuatedglass tubes (Vacutainer, Becton Dickinson and Company,Franklin Lakes, NJ), placed on ice, and analyzed within1 hour of collection. An additional blood sample wastaken at each time for determination of serum electrolyteconcentrations. These samples were collected in un-treated evacuated glass tubes (Monoject, SherwoodMedical, St. Louis, MO), centrifuged after clotting, andthe serum removed and frozen until analysis.

Measurement of Variables

Blood pH and PCO2 were measured, and blood bicar-bonate (HCO3

-) was calculated by a Ciba-Corning 238blood gas analyzer (Ciba-Corning Diagnostics Ltd,Model No. M238, Haistead, Essex, England), whichmeasures the aqueous phase of the blood sample. Theserum electrolytes, sodium (Na+), potassium (K+), chlo-ride (Cl-), and calcium (Ca++) were determined by aHitachi 911 Automatic analyzer (Hitachi Instruments,Inc., Boehringer Mannheim Corporation, Indianapolis,IN) using a direct ion selective electrode. The blood gasand serum electrolyte analyzers were manually calibrateddaily and within each day on an automatic, hourly basis,using standard solutions supplied by each machine man-ufacturer. The intra-assay coefficients of variation (CV)for determinations of pH and PCO2 made on the Ciba-Corning 238 blood gas analyzer for 20 replicate samplesof equine blood were 0.04% and 1.5%, respectively. Themean inter-assay CV for determinations of pH and PCO2

for 20 samples each of normal, acidic, and alkalotic stan-dard solutions measured on 20 separate days were 0.1%and 2.1%, respectively. The intra-assay CV for determi-nations of Na+, K+, Cl- ,and Ca++ made on the Hitachi911 analyzer for 20 replicate samples of equine bloodwere 0.7%, 0.9%, 1.5%, and 0.9%, respectively. Themean inter-assay CV for determinations of Na+, K+, andCl- for 20 samples each of normal (PrecitrolN, Boeh-ringer Mannheim Corporation, Indianapolis, IN) and ab-normal (PrecitrolA, Boehringer Mannheim Corporation,Indianapolis, IN) control serum measured on 20 separatedays were 1.0%, 1.2%, and 1.2%, respectively. The inter-assay CV for Ca++, using a single 10.7 mmol/L standardsolution (Boehringer Mannheim Corporation, Indianapo-lis, IN) measured on 20 separate days was 1.6%.

Statistical Analysis

Least square means differences for pH, HCO3-, PCO2,Na+, Cl-, K+, and Ca++ were determined using analysis ofvariance for repeated measures in the General LinearModels procedure of Statistical Analysis Systems.1 Eachvalue plotted in the figures represents the estimated valueof y at each determination point.

RESULTS

Blood Gas Changes

At 20 minutes after initiating the infusion of sodiumbicarbonate and sodium acetate (within 10 seconds ofcompletion of the infusion), and at all sampling timesthereafter, blood plasma pH and HCO3

- concentrationswere elevated significantly (P < .01) above the controltreatment (Fig 1). The NaHCO3 treatment caused greaterincreases (P < .01) for both blood pH and HCO3

- than thesodium acetate treatment at 20 minutes after infusion.Blood pH and HCO3

- levels declined gradually through-out the blood collection period for these 2 treatmentsafter 20 minutes post-infusion. No differences (P > .05)between the bicarbonate and acetate treatments were de-tected at 40 minutes after infusion and thereafter.

Immediately after infusion of NaHCO3, venous PCO2(P < .01) increased significantly (Fig 1). The hypercap-nia produced from the NaHCO3 treatment remainedhigher than for the other treatments throughout blood col-lection, although not significantly greater (P > .05) at alltimes. The sodium acetate treatment did not induce sig-nificant (P > .05) changes in venous PCO2.

Serum ElectrolytesSerum sodium was increased (P < .01) in the sodium

bicarbonate and sodium acetate treatments immediately

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Figure 1. Venous blood pH (A), bicarbonate (B), and PCO2 (C) after intravenous infusion of 1.34 mEq/mL sodium acetate,1.34 mEq/mL sodium bicarbonate, or 0.9% sodium chloride. Values in parentheses are pooled standard errors for esti-mated values of y at each determination point.

352 Journal of Equine Veterinary Science August 2005

after infusion but did not always remain significantlyhigher (P > .05) than the control treatment beyond 1 hourafter infusion (Fig 2). Sodium acetate significantly de-creased (P < .05) blood calcium for up to 2 hours afterinfusion, and levels remained consistently lower thanother treatments throughout blood collection (Fig 2).

Immediately after infusion of sodium acetate andsodium bicarbonate, potassium concentration decreased(P < .05). Potassium concentration tended to be more de-pressed by the sodium acetate treatment 1 hour after in-fusion (Fig 2).

DISCUSSION

Intravenous administration of sodium bicarbonateresulted in changes in blood constituents characterizedby distinct and persistent metabolic alkalosis. The re-

sponse peaked immediately, as it did in 2 other studies inhorses after infusion.2,3 The effects found in these stud-ies were reported to be persistent for 8 to 12 hours insome horses. The duration of blood collection in the cur-rent study was just over 3 hours. However, blood sam-pling was more frequent with sampling intervals of 20minutes versus hourly, as reported by the other stud-ies.2,3 The purpose of this more frequent sampling was tomore closely document the immediate changes occur-ring in blood constituents owing to intravenous adminis-tration of sodium bicarbonate and sodium acetate. It wasfound in this study that venous blood pH and bicarbon-ate concentrations for the sodium bicarbonate andsodium acetate treatments were indeed higher before the60-minute post-infusion blood sample. This suggeststhat studies with blood sampling intervals of 1 hour after

Figure 2. Serum sodium (a), calcium (b), potassium (c), and chloride (d) after intravenous infusion of 1.34 mEq/mLsodium acetate, 1.34 mEq/mL sodium bicarbonate, or 0.9% sodium chloride. Values in parentheses are pooled standarderrors for estimated values of y at each determination point.

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infusion may not identify peak responses to infusedbasic solutions.

Sodium acetate is commonly used as a buffer inhemodialysis and is also used as a substrate in total par-enteral nutrition to correct eventual metabolic acidosis.4

To this author’s knowledge, sodium acetate has not beenevaluated extensively in performance studies as an er-gogenic aid; however, it has the potential to be used assuch owing to its alkalinizing effects. Sodium bicarbon-ate, on the other hand, has been studied extensively inboth human5,6 and equine athletes.7,8,9 Sodium citrate so-lutions administered orally have also been found to im-prove athletic performance in human humans,10,11 al-though that compound has yet to be examined in equinesubjects, and it was felt that the danger of excessive ion-ized calcium binding, possibly leading to muscle tetany

precluded the use of intravenous citrate in the currentstudy.

In a study of acidotic calves,12 the authors reported thatintravenous administration of bicarbonate characteristicallyinduces an immediate increase in blood pH, because bicar-bonate does not require cellular metabolism to exert an al-kalinizing effect. They reported that sodium acetate,whether oxidized or metabolized, reacts with carbon diox-ide and water to produce acetic acid and sodium bicarbon-ate. In addition, they calculated that 1 mol of bicarbonate isgenerated from 1 mol of acetate metabolized. The findingsof our current study are consistent with these observations.In our study, sodium acetate had a lower peak pH andHCO3

- immediately after cessation of infusion compared tosodium bicarbonate, probably because of the delay in theproduction of bicarbonate anions from the sodium acetate

Figure 2. (continued) Serum sodium (a), calcium (b), potassium (c), and chloride (d) after intravenous infusion of 1.34mEq/mL sodium acetate, 1.34 mEq/mL sodium bicarbonate, or 0.9% sodium chloride. Values in parentheses are pooledstandard errors for estimated values of y at each determination point.

354 Journal of Equine Veterinary Science August 2005

treatment. However, pH and HCO3- concentrations were

not different after an additional 20 minutes had elapsed, al-lowing for metabolism of the acetate anion.

Results of studies8,13,14 have found that sodium bicar-bonate administration causes blood plasma electrolyte im-balances such as hypokalemia, hypocalcemia, and hyper-natremia. Our group,8 in accordance with another,15 haspreviously found that neuromuscular problems may occurwhen horses are administered large doses of sodium bi-carbonate or when doses are used in conjunction withfurosemide, a common pre-race diuretic. An observationin the current study was that the infusion of sodium ac-etate decreased venous blood calcium and potassium to agreater extent than the infusion of sodium bicarbonate.This observation should be considered in future studiesusing sodium acetate, especially when determiningdosage levels. Metabolic alkalosis caused by infusion ofsodium bicarbonate or acetate solutions would be ex-pected to cause increased binding of plasma proteins toionized calcium, and intracellular potassium (K+) wouldbe expected to be exchanged for intracellular hydrogenions (H+) . In addition, however, part of the reduction inthe concentration of the plasma ions calcium and potas-sium noted in the current study may be explained by fluidshifts. The hypertonic sodium bicarbonate and sodium ac-etate solutions would also be expected to increase the ex-tracellular fluid volume to a greater degree than the iso-tonic control treatment of sodium chloride.

In conclusion, the intravenous administration ofsodium bicarbonate and sodium acetate caused signifi-cant changes in acid-base and electrolyte status of horses,consistent with profound metabolic alkalosis. The infu-sion of sodium acetate resulted in similar acid-basedchanges as compared with sodium bicarbonate. Racingjurisdictions should be aware that alkalinizing com-pounds, when administered intravenously, increase bloodpH and bicarbonate ion concentration faster as comparedwith oral administration.

Supported by the United States Trotting Association and theIllinois Department of Agriculture.

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