Use of multifrequency bioelectrical impedance analysis for estimation of total body water and extracellular and intracellular fluid volumes in horses

OBJECTIVE: To evaluate the use of multifrequency bioelectrical impedance analysis (MF-BIA) for estimating total body water (TBW), extracellular fluid volume (ECFV), and intracellular fluid volume (ICFV) in horses. ANIMALS: 9 healthy mares. PROCEDURE: TBW and ECFV were measured by use of deuterium oxide and sodium bromide dilution techniques, respectively. Intracellular fluid volume was calculated as the difference between TBW and ECFV. Concurrently, MF-BIA recordings were obtained by use of 4 anatomic electrode positions and 3 measurements of length. Models for MF-BIA data were created for all combinations of length and anatomic electrode position. Models were evaluated to determine the position-length configuration that provided the most consistent estimates of TBW, ECFV, and ICFV, compared with values determined by use of the dilution techniques. RESULTS: Positioning electrodes over the ipsilateral carpus and tarsus and use of height at the tuber sacrale for length provided the closest estimate between values for TBW, ECFV, and ICFV predicted by use of MF-BIA and measured values obtained by dilutional techniques. This model had the narrowest 95% limits of agreement. CONCLUSIONS AND CLINICAL RELEVANCE: MF-BIA techniques have been used to predict changes in TBW, ECFV, and ICFV in healthy and diseased humans. Results reported in this study provide an equine-specific model to serve as the basis for further evaluation of MF-BIA in horses with altered fluid states. The MF-BIA techniques have a number of potential applications for use in horses, including evaluation of exercise physiology, pharmacologic studies, and critical-care management.     

Effect of endotoxin administration on body fluid compartments in the horse

Plasma volume, extracellular fluid volume (ECFV), and total body water (TBW) were measured before and after endotoxin (Escherichia coli) administration in 6 conscious adult horses. Evan's blue dye, sodium thiocyanate, and antipyrine were the test substances used to estimate plasma volume, ECFV, and TBW, respectively. Pharmacokinetic analysis of plasma concentration vs time was used to determine changes in body fluid compartments. The pathophysiologic effects of endotoxin were monitored by clinical evaluation, blood chemical changes, and blood gas determinations. All horses became dyspneic within 15 minutes of endotoxin administration and clinical signs of colic were evident 30 to 45 minutes after endotoxin administration. After endotoxin administration, serum glucose and creatinine concentrations were significantly (P less than 0.05) elevated, and all horses became hypoxic and developed marked metabolic acidosis, and plasma volume decreased approximately 15% (P less than 0.05). A significant change in ECFV or TBW during the 300-minute experimental period was not observed.     

Pharmacokinetics and clinical utility of sodium bromide (NaBr) as an estimator of extracellular fluid volume in horses

The purpose of this study was to describe the pharmacokinetics of bromide in horses and to evaluate the corrected bromide space as an indicator of extracellular fluid volume (ECFV) in horses after the administration of a single dose of bromide by intravenous infusion. Sodium bromide (30 mg/kg of body weight, IV) was administered to 6 clinically healthy mares over a period of 3 minutes. Blood samples were collected before infusion and at intervals between 0.5 hours and 53 days after infusion. Mean elimination half-life (harmonic mean) was 126 hours (5.2 days), clearance was 1.4 +/- 0.09 mL/(kg x h), area under the curve was 17,520 +/- 1,100 microg x h/mL. and volume of distribution (steady state) was 0.255 +/- 0.015 L/kg. The mean corrected bromide space was determined from the volume of distribution (steady state) and the serum concentrations of bromide at equilibration. Corrected bromide space, an estimate of ECFV, was 0.218 +/- 0.01 L/kg. The conclusion was made that ECFV of horses can be estimated by measuring bromide concentrations in a preinfusion serum sample and a sample obtained 5 hours after the administration of bromide.     

Evaluation of Equine Albumin Solution in Fluid Therapy in Horses with Colic

Equine albumin solution can be a good therapeutic option in fluid replacement for treatment of horses with colic. The purpose of this study was to evaluate the effects of initial fluid therapy with equine albumin solution in horses presenting with colic and mild-to-moderate dehydration, and to compare this therapy with fluid therapy based on crystalloids alone. Nineteen horses of both genders presenting with colic and mild-to-moderate dehydration were used. Animals were randomly assigned to one of two groups (control: fluid therapy based on crystalloid solutions; experimental: fluid therapy based on equine albumin and crystalloid solutions). Physical examination, hematocrit determination, blood gas analysis, serum biochemistry, blood and peritoneal lactate assessment, and measurement of colloid osmotic and arterial pressure were performed at predetermined times. Good results were obtained with equine albumin solution. More fluid is attracted into and maintained in the intravascular compartment, despite infusion of small volumes, as indicated by higher arterial pressure, lower capillary refill time, lower hematocrit and serum protein concentrations, lower colloid osmotic pressure, and better skin turgor. Equine albumin solution has good oncotic action and is a safe fluid therapy option for horses with colic and mild-to-moderate dehydration. Our results suggest it can be a good choice of fluid for correction of severe dehydration, although further research is necessary to determine the adequate dose in such cases.     

Assessment of changes in blood volume in response to resuscitative fluid administration in dogs

Objective: To determine the continuous changes in blood volume in response to fluid administration using an in‐line hematocrit monitor. Design: Prospective study. Setting: Research laboratory. Animals: Four healthy dogs. Interventions: Each dog received intravenous boluses of 80 mL/kg of 0.9% saline (S), 4 mL/kg of 7.5% saline (HS), 20 mL/kg of dextran 70 (D), 20 mL/kg of hetastarch (HES), or no fluids (control, C) on separate occasions. Fluids were administered at 150 mL/min in the S, D, and HES groups, and at 1 mL/kg/min in the HS group. Measurements and main results: Blood volume changes were measured every 20 seconds for 240 minutes using an in‐line hematocrit monitor. There was a rapid rise in blood volume during all infusions. Immediately after the administration of crystalloid fluids, the rapid rise in blood volume ceased. Subsequently, there was a steep decline in blood volume for 10 minutes, and a slower decline thereafter. In contrast, the rise in blood volume continued for at least 10 minutes after the infusion of the colloids was complete, and a plateau was observed for the remainder of the experiment. The blood volume effect, as measured by area under the curve, was significantly greater in the saline group than the other groups during the infusion time and for the 0–240 minutes time period. The areas under the curve for the two colloid solutions were not significantly different from each other during any time periods. The percent increase in blood volume immediately following the infusions was 76.4±10.0 in the S group, 17.1±3.2 in the HS group, 23.0±10.5 in the D group, and 27.2±6.4 in the HES group. At 30 minutes from the start of the infusion, the mean percent increases in blood volumes were 35.2±9.3 in the S group, 12.3±0.9 in the HS group, 35.9±7.3 in the D group, and 36.8±6.5 in the HES group. At 240 h post‐infusion, the mean percent increases in blood volume were 18.0±9.7 in the S group, 2.9±6.1 in the HS group, 25.6±16.1 in the D group, and 26.6±8.6 in the HES group. The C group had a mean percent change in blood volume of ?3.7±3.4 at the end of the experiment. Conclusions: This study indicates that the rapid administration of saline at clinically relevant doses leads to the largest immediate increase in blood volume, although this change is transient because of rapid redistribution of the fluid. Despite a brief increase in blood volume that was almost 3 times the volume administered, hypertonic saline led to the smallest increase in blood volume post‐infusion. The synthetic colloid solutions increased the blood volume by an amount greater than that infused and the effect was sustained for a longer period of time than seen following crystalloid administration, but the maximum increase in blood volume was significantly less than saline. The measurement of continuous changes in blood volume, using an in‐line hematocrit monitor, was a useful means of assessing the dynamic effects of fluid administration in dogs in a research setting.     

Cardiovascular and pulmonary effects of hetastarch plus hypertonic saline solutions during experimental endotoxemia in anesthetized horses

BACKGROUND: Small volume resuscitation has been advocated as a beneficial therapy for endotoxemia in horses but this therapy has not been investigated in a prospective manner. The objective of this study was to determine the cardiopulmonary effects of small-volume resuscitation using hypertonic saline solution (HSS) plus Hetastarch (HES) during experimental endotoxemia in anesthetized horses. HYPOTHESIS: Treatment of horses with induced endotoxemia using HES-HSS does not alter the response of various cardiopulmonary indices when compared to treatment with either small- or large-volume isotonic crystalloid solutions. ANIMALS: Eighteen healthy horses were randomly assigned to 1 of 3 groups. Anesthesia was maintained with halothane. Endotoxemia was induced by administering 50 microg/kg of Escherichia coli endotoxin IV. The horses were treated over 30 minutes with 15 mL/kg of balanced polyionic crystalloid solution (control), 60 mL/kg of balanced polyionic crystalloid solution (ISO), or 5 mL/kg of HSS followed by 10 mL/kg of HES (HSS-HES). METHODS: Prospective randomized trial. RESULTS: Cardiac output (CO) after endotoxin infusion increased significantly (P < .05) from baseline in all groups, whereas mean central venous pressure increased significantly (P < .05) in the ISO group only. Mean pulmonary artery pressure increased from baseline (P < .05) in horses treated with isotonic fluids and HSS-HES. There was no effect of treatment with HSS-HES on CO, systemic vascular resistance (SVR), mean arterial pressure, blood lactate concentrations, or arterial oxygenation. CONCLUSIONS AND CLINICAL IMPORTANCE: The use of HSS-HES failed to ameliorate the deleterious hemodynamic responses associated with endotoxemia in horses. The clinical value of this treatment in horses with endotoxemia remains unconfirmed.     

Use of a three-blood-sample plasma clearance technique to measure GFR in horses

Measurement of renal function in horses poses a particular challenge because plasma creatinine is influenced by muscle mass which is highly developed and variable between individuals, while conventional clearance methods involve potentially daunting problems, particularly urine collection and bladder washout. This paper provides data which enable technetium-diethyleneaminopentacetic acid (Tc-DTPA) clearance to be used to calculate glomerular filtration rate (GFR)/extracellular fluid volume (ECFV) as an expression of GFR in horses, as previously validated in humans, dogs and calves. Apart from being arguably a more physiological expression of GFR than using derivatives of body weight, the use of GFR/ECFV eliminates a source of delay and error, namely measurement of the injected dose, and offers the convenience of requiring only three blood samples. It therefore has advantages for both research and clinical applications.     

Effects of intravenous administration of dimethyl sulfoxide on cardiopulmonary and clinicopathologic variables in awake or halothane-anesthetized horses

OBJECTIVE: To evaluate the cardiopulmonary and clinicopathologic effects of rapid IV administration of dimethyl sulfoxide (DMSO) in awake and halothane-anesthetized horses. DESIGN: Prospective study. ANIMALS: 6 adult horses. PROCEDURES: Horses received IV infusion of 5 L of a balanced electrolyte solution with and without 1 g/kg (0.45 g/lb) of 10% DMSO solution when they were awake and anesthetized with halothane (4 treatments/horse). Arterial and venous blood samples were collected immediately before and at intervals during or after fluid administration and analyzed for blood gases and hematologic and serum biochemical variables, respectively. Heart rate, respiratory rate, and arterial blood pressure variables were recorded prior to, during, and after fluid administration. RESULTS: After administration of fluid with or without DMSO, changes in measured variables were detected immediately, but most variables returned to baseline values within 4 hours. One awake control horse had signs of anxiety; agitation and tachycardia were detected in 2 awake horses administered DMSO. These clinical signs disappeared when the rate of infusion was reduced. In anesthetized horses, increased concentrations of WBCs and plasma fibrinogen and serum creatine kinase activity persisted for 24 hours, which was related to the stress of anesthesia more than the effects of fluid administration. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of 5 L of balanced electrolyte solution with or without 10% DMSO induced minimal changes in cardiopulmonary function and clinicopathologic variables in either awake or halothane-anesthetized horses. Stress associated with anesthesia and recovery had a greater influence on measured variables in anesthetized horses than fluid administration.     

Cardiovascular effects of rapid infusion of crystalloid in the hypovolaemic cat

The effects of rapidly infused lactated Ringer's solution were studied in ten cats made hypovolaemic by acute bleeding and subsequently given, intravenously, crystalloid in an amount approximately equal to 1 blood volume (five cats) or 2 blood volumes (five cats). Fluid administration was begun approximately 30 min after the cats were bled and completed in 1 hour. A control group of three cats was instrumented but not bled or treated. Cardiovascular haemodynamics were measured before bleeding, 30 min after bleeding, at the half-way point of fluid administration, and immediately after total fluid administration. While the catheterization and vessel ligation had minimal effects, both blood removal and fluid administration had marked effects on haemodynamics. Cats which received fluids equal to 2 blood volumes were severely affected by hypervolaemia. Central venous pressures in these cats were significantly higher during and after fluid administration. Seventy per cent of the experimental cats survived long term; however, several surviving cats had complicated or prolonged recoveries in which clinical signs consistent with acute pulmonary oedema were seen during the treatment and recovery period.     

Comparison of fluid types for resuscitation after acute blood loss in mallard ducks (Anas platyrhynchos)

Objective – The purpose of this study was to determine the LD₅₀ for acute blood loss in mallard ducks ( Anas platyrhynchos ), compare the mortality rate among 3 fluid resuscitation groups, and determine the time required for a regenerative RBC response.
Design – Prospective study.
Setting – Medical College of Wisconsin Research facility.
Animals – Eighteen mallard ducks were included for the LD₅₀ study and 28 for the fluid resuscitation study.
Interventions – Phlebotomy was performed during both the LD₅₀ and fluid resuscitation studies. Ducks in the fluid resuscitation study received a 5 mL/kg intravenous bolus of crystalloids, hetastarch (HES), or a hemoglobin-based oxygen-carrying solution (HBOCS).
Measurements and Main Results – The LD₅₀ for acute blood loss was 60% of total blood volume. This blood volume was removed in the fluid resuscitation study to create a model of acute blood loss. Following fluid administration, 6 birds in the crystalloid group (66%), 4 birds in the HES group (40%), and 2 birds in the HBOCS group (20%) died. No statistical difference in mortality rate was seen among the 3 fluid resuscitation groups. Relative polychromasia evaluated post-phlebotomy demonstrated regeneration starting at 24 hours and continuing through 48 hours.
Conclusions – The LD₅₀ for acute blood loss in mallard ducks was 60% of their total blood volume. Although no statistical difference in mortality rate was appreciated among the 3 fluid resuscitation groups, a trend of decreased mortality rate was observed in the HBOCS group. An early regenerative response was apparent following acute blood loss.     

An evaluation of an oral glucose-glycine-electrolyte solution for the treatment of experimentally induced dehydration in the horse

Five standardbred geldings were given 1 mg/kg bodyweight of frusemide by intramuscular injection to induce mild dehydration. After food and water deprivation overnight, the mean weight loss was 24.4 +/- 1.8 kg (5.5 per cent of bodyweight). The horses were then given an equivalent volume of an oral glucose-glycine-electrolyte solution by stomach tube. No more than 10 litres was given every 30 minutes until the calculated bodyweight loss had been replaced. Measurements made before, during and after the fluid administration included bodyweight, arterial blood haematocrit, PCO2, pH, standard bicarbonate, base excess and plasma concentrations of sodium, potassium, chloride, total protein, glucose, urea and creatinine. The final measurement was taken eight hours after the last dose of fluid and no food or water was offered to the horses during this time. Administration of the solution caused a rapid correction of the frusemide-induced dehydration and metabolic alkalosis. Absorption of the fluid from the gastrointestinal tract appeared to be very rapid because by 30 minutes after the last dose of the solution, plasma protein values were not significantly different from those before administration of frusemide. Plasma glucose concentrations became significantly increased for up to three hours after the fluid was given and an increase in creatinine and urea concentrations, which was observed after the administration of frusemide, was still evident at eight hours. The glucose-glycine-electrolyte solution was well retained, there being a mean bodyweight loss of 2.8 kg at three hours and 6.2 kg at eight hours after the last dose of fluid.     

Physiologic alterations in the horse produced by food and water deprivation during periods of high environmental temperatures

Eight normal horses were held without access to food or water for 72 hours during a period of high environmental temperatures. During this period, the horses had an average weight loss of 51.6 kg (10.7% of body weight). Highly significant (P less than 0.001) decreases in extracellular fluid volume (18.6 L) and plasma volume (5 L) were observed during this period as compared with base-line values. Plasma protein, sodium, chloride, and osmolality progressively increased in response to the dehydration, whereas packed cell volume, plasma potassium, calcium, magnesium, and phosphate were not significantly altered. The dehydration and clinicopathologic alterations produced were similar to those observed in other species in which the principal problem was a water deficit. After the end of the experimental dehydration period, the horses replaced 62% of the weight loss during a 1-hour period with access to water only.     

Erythrogram and red cell distribution width of Equidae with experimentally induced anemia

The erythrogram (erythrocyte histogram) and red cell distribution width (RDW) were evaluated in 5 purebred horses and 1 pony of mixed breeding with experimentally induced anemia. Four horses were studied for 6 weeks after 20% of their estimated blood volume was removed on each of 2 consecutive days (40% total blood loss; acute blood-loss group). Two horses were given acetylphenyl hydrazine IV daily, until acute Heinz body hemolytic anemia was induced; the 2 horses were then evaluated for 6 weeks. One horse and the pony had 20% of their estimated blood volume removed via phlebotomy once each week for 8 weeks to induce iron-deficiency anemia (chronic blood-loss group); the horse had been partially depleted of iron before the study began. Weekly blood samples were examined for changes in the erythrogram, RDW, mean cell volume (MCV), and erythrocyte glucose-6-phosphate dehydrogenase activity. Fourteen days after acute blood loss, mild increases were seen in the MCV, which persisted to day 42. The RDW was increased at day 14 and remained increased until day 42; however, the percentage increase was double that of the MCV at days 14, 21, and 28. Erythrograms had mild extensions of the right slope at days 14 to 28. Mean erythrocyte glucose-6-phosphate dehydrogenase activity increased in all 3 groups, but individual concentrations were erratic. In the 2 horses with acute hemolytic anemia, modest increases of similar magnitude were seen in RDW and MCV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses

OBJECTIVE: To determine effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. ANIMALS: 6 adult Standardbreds. PROCEDURES: In a balanced crossover study, horses received dexamethasone (0.08 mg/ kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment) during a 21-day period. Horses underwent a 3-hour frequently sampled IV glucose tolerance test (FSIGT) 2 days after treatment. Minimal model analysis of glucose and insulin data from FSIGTs were used to estimate insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg), and disposition index. Proxies for Si (reciprocal of the inverse square of basal insulin concentration [RISQI]) and beta-cell responsiveness (modified insulin-to-glucose ratio [MIRG]) were calculated from basal plasma glucose and serum insulin concentrations. RESULTS: Mean serum insulin concentration was significantly higher in dexamethasone-treated horses than control horses on days 7, 14, and 21. Similarly, mean plasma glucose concentration was higher in dexamethasone-treated horses on days 7, 14, and 21; this value differed significantly on day 14 but not on days 7 or 21. Minimal model analysis of FSIGT data revealed a significant decrease in Si and a significant increase in AIRg after dexamethasone treatment, with no change in Sg or disposition index. Mean RISQI was significantly lower, whereas MIRG was higher, in dexamethasone-treated horses than control horses on days 7, 14, and 21. CONCLUSIONS AND CLINICAL RELEVANCE: The study revealed marked insulin resistance in healthy horses after 21 days of dexamethasone administration. Because insulin resistance has been associated with a predisposition to laminitis, a glucocorticoid-induced decrease in insulin sensitivity may increase risk for development of laminitis in some horses and ponies.     

Pulsed-wave Doppler ultrasonographic evaluation of hepatic veins during variable hemodynamic states in healthy anesthetized dogs

OBJECTIVES: To quantify direction and velocity of blood flow in hepatic veins in dogs under different hemodynamic conditions by use of pulsed-wave Doppler ultrasonography. ANIMALS: 10 healthy dogs. PROCEDURE: Dogs were anesthetized, and venous flow velocities in the quadrate lobe were measured. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and cardiac output were measured simultaneously. The timing of each waveform during the cardiac cycle was used to identify velocity profiles. Peak waveform velocities were measured during conditions of light anesthesia with isoflurane (baseline; period 1), cardiovascular depression following administration of high-dose isoflurane and esmolol i.v. (period 2), cardiovascular depression with crystalloid volume expansion (period 3), and high cardiac output induced with dobutamine (period 4). Hemodynamic measurements and maximum waveform velocities were compared among the 4 periods by use of an ANOVA and univariate and multivariate linear regression. RESULTS: During each study period, 4 distinct, low-velocity waves were identified. Mean velocities recorded during period 1 were as follows: retrograde atrial contraction a-wave, 7.3 cm/s; antegrade systolic S-wave, 15.0 cm/s; retrograde venous return v-wave, 2.7 cm/s; and antegrade diastolic D-wave, 11.4 cm/s. Mean S:D ratio was 1.27. During periods 3 and 4, S-wave velocity increased; D-wave velocity was highest during period 4. CONCLUSIONS AND CLINICAL RELEVANCE: Consistent hepatic venous velocity profiles were observed in healthy dogs under different hemodynamic conditions. These findings provide baseline values that may be useful in evaluating clinical cases, but further study involving healthy, awake dogs and dogs with cardiac and hepatic diseases is required.     

Comparison of Hematologic and Biochemical Results on Blood Obtained by Jugular Venipuncture as Compared with Intravenous Catheter in Adult Horses

Background: During hospitalization, horses typically undergo frequent blood sampling for diagnostic testing and monitoring. The need for numerous samples in hospitalized horses makes acquisition from an intravenous catheter (IVC) both convenient and less stressful to the patient. Hypothesis: We hypothesized that there would be no significant difference in the plasma chemistry and CBC variables from blood samples obtained from a jugular catheter as compared with direct jugular venipuncture. Animals: Fifty adult hospitalized horses; 25 receiving constant rate crystalloid therapy, and 25 receiving low volume IV medication. Methods: This study was conducted using a prospective, blinded, cross‐over design. Samples were obtained sequentially by direct venipuncture of the jugular vein and aspiration from an IVC in the contralateral vein after an appropriate presample of blood was obtained and discarded. Samples were submitted for blinded analysis including CBC, plasma chemistry analysis, stall side plasma glucose concentration, PCV, and total protein concentration. Data obtained were analyzed using a Student's t‐test with compensation for unequal variances between the 2 groups. Analyses were Bonferroni corrected for a 5% 2‐tailed hypothesis test. Results: There were no statistically significant or clinically relevant differences associated with sampling method (venipuncture versus catheter) regardless of fluid administration status in any of the 24 analytes measured. Conclusions and Clinical Importance: Blood samples obtained by IVC have clinically equivalent values to those taken by direct venipuncture in commonly performed analyses. Additional investigation is warranted to establish if this technique is associated with increased complications such as phlebitis or bacteremia.     

Relationship between hydration estimate and body weight change after fluid therapy in critically ill dogs and cats

Objective: To characterize the relationship between clinical estimates of hydration in dogs and cats admitted to an intensive care unit (ICU) and changes in their body weight following 24–48 hours of fluid therapy. Design: Outcome study. Setting: ICU at a veterinary teaching hospital (VTH). Animals: A total of 151 dogs and 42 cats with various medical disorders that had not had surgery within 48 hours of admission into the ICU were consecutively admitted into the study. Animals with any condition predisposing to excess fluid loss or retention were excluded: heart disease, sepsis, trauma, pancreatitis, pleural or pericardial effusion, ascites, and pathologic oliguria. Animals that acquired any of the following during the observation period were excluded: gastrointestinal fluid loss, edema or diseases predisposing to edema, oliguria, diuretic therapy, and body fluid drainage or hemorrhage. Fluid therapy was ordered based on estimate of hydration at admission. Other treatments were not modified or withheld. Interventions: Physiologic data were collected at the time of admission and 24–48 hours later. Measurements and main results: Hydration was estimated on admission to the ICU using clinical judgement with no supporting laboratory data. Each admitting clinician used this estimate to plan fluid therapy. Fluid therapy was defined as the administration of any enteral or parenteral fluids as well as any decision to withhold fluids. Paired measurements taken on admission and at 24–48 hours included packed cell volume (PCV), total plasma solids (TS), and body weight. Amount and type of fluids or blood products administered were noted. Neither clinician estimates of dehydration nor baseline PCV or TS predicted clinically significant changes in body weight following fluid therapy, and there was no relationship between weight change and changes in PCV or TS. Conclusions: A clinical diagnosis of dehydration in our ICU does not predict weight gain following fluid therapy. Neither baseline PCV/TS nor changes in these measurements following 24–48 hours of fluid therapy predicted changes in body weight.     

Pharmacokinetics of voriconazole following intravenous and oral administration and body fluid concentrations of voriconazole following repeated oral administration in horses

OBJECTIVE: To determine the pharmacokinetics of voriconazole following IV and PO administration and assess the distribution of voriconazole into body fluids following repeated PO administration in horses. ANIMALS: 6 clinically normal adult horses. PROCEDURES: All horses received voriconazole (10 mg/kg) IV and PO (2-week interval between treatments). Plasma voriconazole concentrations were determined prior to and at intervals following administration. Subsequently, voriconazole was administered PO (3 mg/kg) twice daily for 10 days to all horses; plasma, synovial fluid, CSF, urine, and preocular tear film concentrations of voriconazole were then assessed. RESULTS: Mean +/- SD volume of distribution at steady state was 1,604.9 +/- 406.4 mL/kg. Systemic bioavailability of voriconazole following PO administration was 95 +/- 19%; the highest plasma concentration of 6.1 +/- 1.4 microg/mL was attained at 0.6 to 2.3 hours. Mean peak plasma concentration was 2.57 microg/mL, and mean trough plasma concentration was 1.32 microg/mL. Mean plasma, CSF, synovial fluid, urine, and preocular tear film concentrations of voriconazole after long-term PO administration were 5.163 +/- 1.594 microg/mL, 2.508 +/- 1.616 microg/mL, 3.073 +/- 2.093 microg/mL, 4.422 +/- 0.8095 microg/mL, and 3.376 +/- 1.297 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole distributed quickly and widely in the body; following a single IV dose, initial plasma concentrations were high with a steady and early decrease in plasma concentration. Absorption of voriconazole after PO administration was excellent, compared with absorption after IV administration. Voriconazole appears to be another option for the treatment of fungal infections in horses.     

Haemodynamic effects of small volume hypertonic saline in experimentally induced haemorrhagic shock

A comparison of the haemodynamic benefits of small volume hypertonic saline (2,400 mOsm/litre) versus isotonic saline (300 mOsm/litre) was conducted in 12 adult horses using a haemorrhagic shock model. The horses were anaesthetised and intravascular catheters placed for the measurement of haemodynamic data. Mean systemic arterial pressure was then reduced to 50 to 60 mmHg by controlled haemorrhage and maintained at that level for 40 mins. Cardiac output, stroke volume, mean systemic arterial pressure, plasma volume and urine production decreased significantly following blood loss. Hypertonic or isotonic saline was administered randomly by intravenous infusion and haemodynamic data recorded for a 2 h period. Treatment with hypertonic saline produced rapid elevations in cardiac output, stroke volume, mean systemic and pulmonary arterial pressures, cardiac contractility and urine output, and was accompanied by expansion of the plasma volume. The changes in cardiac output and stroke volume were maintained for the duration of the recording period, whereas increases in mean systemic arterial pressure were not as remarkable. Infusion of isotonic saline caused only transient increases in cardiac output and mean systemic and pulmonary arterial pressure, and cardiac output; urine output and plasma volume did not change. This study indicates that hypertonic saline produces haemodynamic improvements in experimentally induced haemorrhagic shock in horses.     

IOHEXOL PLASMA CLEARANCE IN HEALTHY DOGS AND CATS

Iohexol plasma clearance as a measure of glomerular filtration was determined in 31 dogs and 19 cats after an intravenous (i.v.) bolus injection. All animals were healthy and privately owned. Serial blood samples were taken before and up to 4 h after tracer injection. Iohexol plasma concentration was determined using X-ray fluorescence. A plasma tracer elimination curve was generated and clearance was calculated by dividing the injected dose by the area under the curve estimated using a two-compartment pharmacological model. Clearance was normalized to body weight (BW), body surface area (BSA), and extracellular fluid volume (ECFV). Mean, SD, and coefficient of variation of plasma clearance, before and after normalization, were calculated. Linear regression analyses were performed between body size and normalized plasma clearances. No significant linear relation was found between BSA and clearance normalized to BSA in dogs, and between BSA, BW, ECFV and clearance normalized to BSA, BW, and ECFV in cats. The optimal method for normalization of iohexol plasma clearance in dogs was by using BSA. In cats, all three methods tested were considered satisfactory. Normalization to BSA appears to be superior to normalization to BW and ECFV in dogs, and can be recommended for clinical use.