Systemic,Renal, and Colonic Effects of Intravenous and Enteral Rehydration in Horses

Background

Intravenous (IV) and intragastric (IG) administration of fluid therapy are commonly used in equine practice, but there are limited data on the systemic, renal, and enteric effects.

Hypothesis

IV fluid administration will increase intestinal and fecal hydration in a rate‐dependent manner after hypertonic dehydration, but will be associated with significant urinary water and electrolyte loss. Equivalent volumes of IG plain water will result in comparatively greater intestinal hydration with less renal loss.

Animals

Six Thoroughbred geldings.

Methods

Experimental study. 6 by 6 Latin square design investigating constant rate IV administration at 50, 100, and 150 mL/kg/d over 24 hours in horses dehydrated by water deprivation. Equivalent volumes of IG plain water were administered by 4 bolus doses over 24 hours.

Results

Water deprivation resulted in a significant decrease in the percentage of fecal water, and increases in serum and urine osmolality. IV fluids administered at 100 and 150 mL/kg/d restored fecal hydration, but increasing the rate from 100 to 150 mL/kg/d did not confer any additional intestinal benefit, but did result in significantly greater urine production and sodium loss. Equivalent 24‐hour volumes of plain water resulted in greater intestinal water and less urine output.

Conclusions and Clinical Importance

IV polyionic isotonic fluids can be used to hydrate intestinal contents in situations where enteral fluids are impractical. IV fluids administered at three times maintenance are no more efficacious and might be associated with adverse physiological findings after withdrawal. Bolus dosing of IG water can be used to restore intestinal water with minimal adverse effects.     

Pharmacokinetics of marbofloxacin in blue and gold macaws (Ara ararauna)

OBJECTIVE: To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws. ANIMALS: 10 healthy blue and gold macaws. PROCEDURES: In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography-mass spectrometry assay. RESULTS: After oral administration, mean +/- SD area under the curve was 7.94 +/- 2.08 microg.h/mL, maximum plasma concentration was 1.08 +/- 0.316 microg/mL, and bioavailability was 90.0 +/- 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 +/- 0.32 L/kg, plasma clearance was 0.29 +/- 0.078 L/h/kg, area under the curve was 9.41 +/- 2.84 microg.h/mL, and the harmonic mean terminal half-life was 4.3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.     

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 and pharmacodynamics of furosemide after oral administration to horses

Furosemide is the most common diuretic drug used in horses. Furosemide is routinely administered as IV or IM bolus doses 3-4 times a day. Administration PO is often suggested as an alternative, even though documentation of absorption and efficacy in horses is lacking. This study was carried out in a randomized, crossover design and compared 8-hour urine volume among control horses that received placebo, horses that received furosemide at 1 mg/kg PO, and horses that received furosemide at 1 mg/kg IV. Blood samples for analysis of plasma furosemide concentrations, PCV, and total solids were obtained at specific time points from treated horses. Furosemide concentrations were determined by reversed-phase high-performance liquid chromatography with fluorescent detection. Systemic availability of furosemide PO was poor, erratic, and variable among horses. Median systemic bioavailability was 5.4% (25th percentile, 75th percentile: 3.5, 9.6). Horses that received furosemide IV produced 7.4 L (7.1, 7.7) of urine over the 8-hour period. The maximum plasma concentration of 0.03 microg/mL after administration PO was not sufficient to increase urine volume compared with control horses (1.2 L [1.0, 1.4] PO versus 1.2 L [1.0, 1.4] control). There was a mild decrease in urine specific gravity within 1-2 hours after administration of furosemide PO, and urine specific gravity was significantly lower in horses treated with furosemide PO compared with control horses at the 2-hour time point. Systemic availability of furosemide PO was poor and variable. Furosemide at 1 mg/kg PO did not induce diuresis in horses.     

Pharmacokinetics of single-dose intravenous levetiracetam administration in normal dogs

Objective: To determine plasma pharmacokinetics of levetiracetam after a single intravenous dose (60 mg/kg) in normal dogs using a high‐performance liquid chromatography assay validated for canine plasma. Design: Pharmacokinetic study. Setting: A university‐based canine research facility. Animals: Six healthy adult dogs. Interventions: Intravenous drug administration, multiple blood sample procurement. Measurements and main results: There were no obvious adverse effects associated with the intravenous (IV) bolus administration of levetiracetam in any of the dogs. Plasma levetiracetam concentrations remained above or within the reported therapeutic range for humans (5–45 μg/mL) for all dogs, for all time periods evaluated. Mean and median (in parentheses) values for pharmacokinetic parameters included the following: maximum plasma concentration, 254 μg/mL (254 μg/mL); half‐life, 4.0 hours (4.0 hours); volume of distribution at steady state, 0.48 L/kg (0.48 L/kg); clearance, 1.4 mL/kg/min (1.5 mL/kg/min); and median residence time, 6.0 hours (6.0 hours). Conclusions: In normal dogs, a 60 mg/kg IV bolus dose of levetiracetam is well tolerated and achieves plasma drug concentrations within or above the therapeutic range reported for humans for at least 8 hours after administration. Based on the favorable pharmacokinetics and tolerability demonstrated for IV levetiracetam in this study, in addition to previously demonstrated efficacy of oral levetiracetam, IV levetiracetam may be a useful treatment option for emergency management of canine seizure activity.     

Hemostatic defects associated with two infusion rates of dextran 70 in dogs.

We investigated changes in hemostatic function after infusion of 6% dextran 70 (high molecular weight dextran) at 2 rates. Six healthy dogs underwent 3 regimens: 20 ml of dextran/kg of body weight administered in 1 hour (trial A), 20 ml of dextran/kg administered in 30 minutes (trial B), and 0.9% sodium chloride solution as a control administered over 1 hour to achieve hemodilution equivalent to that for 20 ml of dextran/kg (trial C). Before and at 2, 4, 8, and 24 hours after the start of trials A and B, we measured PCV, total solids (TS) concentration, amount of von Willebrand factor antigen (vWf:Ag), factor VIII coagulant activity (VIII:C), prothrombin time, activated partial thromboplastin time (APTT), platelet retention in a glass bead column, and buccal mucosa bleeding time (BMBT). Values were not obtained at 8 and 24 hours for trial C. Saline-induced changes in hemostasis were significant (P less than 0.05) from baseline throughout the sample collection period. Significant differences (P less than 0.05) between trial A and control were observed for vWf:Ag, VIII:C, BMBT, APTT, TS, and PCV values at 2 hours, and for VIII:C at 4 hours. Significant differences (P less than 0.05) between trial B and control were observed for APTT, TS, and PCV values at 2 hours, and for vWf:Ag, VIII:C, BMBT, APTT, TS, and PCV values at 4 hours. During trials A and B, mean values of analytes infrequently deviated from reference intervals, and clinical signs of bleeding were not observed in any dog.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effects of xylazine,romifidine, or detomidine on hematology,biochemistry, and splenic thickness in healthy horses

Alpha-2 agonist-induced changes in packed cell volume (PCV), total solids (TS), selected biochemical parameters, and splenic thickness were investigated in horses. Four healthy mares were treated in a blinded, randomized, cross-over design with a dose of xylazine (0.5 mg/kg), romifidine (0.04 mg/kg), or detomidine (0.01 mg/kg) IV, and detomidine (0.02 mg/kg) IM. Hematology, TS, colloid osmotic pressure (COP), plasma osmolality; glucose, lactate, urea (BUN) and electrolyte concentrations; venous blood pH and ultrasonographic splenic thickness were evaluated at intervals for 300 min. Repeated measures analysis of variance (ANOVA) were performed with P < 0.05. There was a significant change over time in PCV and TS following each treatment (P < 0.001), with median (range) reductions of 20.9% (12.9% to 27.3%) and 5.8% (3.0% to 10.3%), respectively. Red blood cell count, BUN, and COP decreased while osmolality, glucose, Na⁺, and splenic thickness increased. Treatments induced clinically significant transient changes in PCV, TS, and other biochemical parameters, which should be considered when assessing horses that received these drugs.     

Effects of 6% hetastarch (600/0.75) or lactated Ringer's solution on hemostatic variables and clinical bleeding in healthy dogs anesthetized for orthopedic surgery

ObjectiveTo evaluate and compare hemostatic variables and clinical bleeding following the administration of 6% hetastarch (600/0.75) or lactated Ringer’s solution (LRS) to dogs anesthetized for orthopedic surgery.Study designRandomized blinded prospective study.AnimalsFourteen, healthy adult mixed-breed hound dogs of either sex, aged 11–13 months, and weighing 20.8 ± 1.2 kg.MethodsThe dogs were randomly assigned to receive a 10 mL kg^?1 intravenous (IV) bolus of either 6% hetastarch (600/0.75) or LRS over 20 minutes followed by a maintenance infusion of LRS (10 mL kg^?1hour^?1) during anesthesia. Before (Baseline) and at 1 and 24 hours after bolus administration, packed cell volume (PCV), total protein concentration (TP), prothrombin time (PT), activated partial thromboplastin time (APTT), von Willebrand’s factor antigen concentration (vWF:Ag), factor VIII coagulant activity (F VIII:C), platelet count, platelet aggregation, colloid osmotic pressure (COP) and buccal mucosal bleeding time (BMBT) were measured. In addition a surgeon who was blinded to the treatments assessed bleeding from the incision site during the procedure and at 1 and 24 hours after the bolus administration.ResultsFollowing hetastarch or LRS administration, the PCV and TP decreased significantly 1-hour post-infusion. APTT did not change significantly compared to baseline in either treatment group, but the PT was significantly longer at 1-hour post-infusion than at 24 hours in both groups. No significant change was detected for vWF:Ag, FVIII:C, platelet aggregation or clinical bleeding in either group. The BMBT increased while platelet count decreased significantly at 1-hour post-infusion in both groups. The COP decreased significantly in both treatment groups 1-hour post-infusion but was significantly higher 1-hour post-infusion in the hetastarch group compared to the LRS group.Conclusions and clinical relevanceAt the doses administered, both hetastarch and LRS can alter hemostatic variables in healthy dogs. However, in these dogs undergoing orthopedic surgery, neither fluid was associated with increased clinical bleeding.     

Endotoxemia in horses: protection provided by antiserum to core lipopolysaccharide

An equine antiserum to core lipopolysaccharide was produced by inoculation of 6 horses with a boiled cell bacterin made from the J-5 mutant of Escherichia coli O111:B4. The antiserum immunoglobulin G titer to J-5 mutant E coli, as determined by enzyme-linked immunosorbent assay, was 1:15,006. Pooled serum prepared before inoculation (preimmune serum) had a J-5 immunoglobulin G titer of 1:350. The J-5 antiserum was tested for its protective efficacy in sublethal endotoxemia in 14 horses. Four horses served as nontreated controls and were given nothing before endotoxin challenge exposure (10 micrograms/kg of body weight, IV). Pooled preimmune serum (3 ml/kg, IV) was administered to 5 horses and J-5 antiserum (3 ml/kg, IV) was administered to 5 other horses 2 to 15 hours before endotoxin challenge exposure. During the 24 hours postendotoxin challenge exposure, endotoxemia was accompanied by significant (P less than 0.05) time-related changes in temperature, heart rate, pulse character, respiratory rate and character, capillary refill time, mucous membrane color, fecal composition, attitude, PCV, total plasma protein, WBC count, platelet count, plasma fibrinogen, prothrombin time, activated partial thromboplastin time, fibrinolytic degradation products, plasma glucose, and plasma lactate in all horses. There were no apparent treatment vs time interactions (P greater than 0.05). Two horses (1 control and 1 given J-5 antiserum) died suddenly from unknown causes immediately after endotoxin challenge exposure. Seemingly, equine antiserum to core lipopolysaccharide did not provide protection from the adverse effects of experimental endotoxemia produced by bolus IV infusion of 10 micrograms of endotoxin/kg.     

The effects of hypohydration on central venous pressure and splenic volume in adult horses

Background: Central venous pressure (CVP) is used in many species to monitor right‐sided intravascular volume status, especially in critical care medicine. Hypothesis: That hypohydration in adult horses is associated with a proportional reduction in CVP. Animals: Ten healthy adult horses from the university teaching herd. Methods: In this experimental study, horses underwent central venous catheter placement and CVP readings were obtained by water manometry. The horses were then deprived of water and administered furosemide (1 mg/kg IV q6h) for up to 36 hours. Weight, CVP, vital signs, PCV, total protein (TP), and serum lactate were monitored at baseline and every 6 hours until a target of 5% decrease in body weight loss was achieved. The spleen volume was estimated sonographically at baseline and peak volume depletion. Linear regression analysis was used to assess the association of CVP and other clinical parameters with degree of body weight loss over time. Results: There was a significant association between CVP and decline in body weight (P < .001), with a decrease in CVP of 2.2 cmH₂O for every percentage point decrease in body weight. Other significant associations between volume depletion and parameters measured included increased TP (P= .007), increased serum lactate concentration (P= .048), and decreased splenic volume (P= .046). There was no significant association between CVP and vital signs or PCV. Conclusions and Clinical Importance: These findings suggest that CVP monitoring might be a useful addition to the clinical evaluation of hydration status in adult horses.     

Use of a von Frey device for evaluation of pharmacokinetics and pharmacodynamics of morphine after intravenous administration as an infusion or multiple doses in dogs

OBJECTIVE: To evaluate the pharmacokinetics and pharmacodynamics of morphine after IV administration as an infusion or multiple doses in dogs by use of a von Frey (vF) device. ANIMALS: 6 dogs. PROCEDURE: In the first 2 crossover experiments of a 3-way crossover study, morphine or saline (0.9%) solution was administered via IV infusion. Loading doses and infusion rates were administered to attain targeted plasma concentrations of 10, 20, 30, and 40 ng/mL. In the third experiment, morphine (0.5 mg/kg) was administered IV every 2 hours for 3 doses. The vF thresholds were measured hourly for 8 hours. Plasma concentrations of morphine were measured by high-pressure liquid chromatography. RESULTS: No significant changes in vF thresholds were observed during infusion of saline solution. The vF thresholds were significantly increased from 5 to 8 hours during the infusion phase, corresponding to targeted morphine plasma concentrations > 30 ng/mL and infusion rates > or = 0.15 +/- 0.02 mg/kg/h.The maximal effect (EMAX) was 78 +/- 11% (percentage change from baseline), and the effective concentration to attain a 50% maximal response (EC50) was 29.5 +/- 5.4 ng/mL. The vF thresholds were significantly increased from 1 to 7 hours during the multiple-dose phase; the EC50 and EMAX were 23.9 +/- 4.7 ng/mL and 173 +/- 58%, respectively. No significant differences in half-life, volume of distribution, or clearance between the first and last dose of morphine were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine administered via IV infusion (0.15 +/- 0.02 mg/kg/h) and multiple doses (0.5 mg/kg, IV, every 2 hours for 3 doses) maintained significant antinociception in dogs.     

The association of lung function and plasma volume expansion in neonatal alpaca crias following plasma transfusion for failure of passive transfer

Objective– Failure of passive transfer in neonatal alpacas is often corrected by IV administration of commercial camelid plasma. The goal of this study was to characterize changes in pulmonary function, gas exchange, and cardiovascular parameters associated with IV plasma transfusion. Design– Prospective clinical study. Setting– A university‐based referral hospital. Animals– Eleven clinically healthy alpaca crias (age: 1–18 days) with failure of passive transfer (IgG<8 g/L [800 mg/dL]). Interventions– Thirty milliliters per kilogram of commercial camelid plasma was administered IV over 90 minutes. Before and after the transfusion, the following cardiopulmonary measurements were obtained: arterial blood gas analysis, pulmonary functional residual capacity (FRC), PCV, total plasma protein and echocardiographic M‐mode measures. Additionally, central venous pressure and indirect arterial blood pressure were monitored throughout the plasma transfusion. Measurements and Main Results– The IV plasma transfusion resulted in significantly reduced PCV (−5.4±5.1%), increased total plasma protein (+4±4 g/L [0.4±0.4 g/dL]), elevated central venous pressure and changes in left and right ventricular M‐mode indices, consistent with plasma volume expansion. Transfusion was further associated with a significant increase in arterial oxygen pressure (PaO₂) (+11.2±15 mm Hg) and decrease in FRC (−5.6±8.3 mL/kg). Conclusions– IV administration of 30 mL/kg camelid plasma to neonatal crias resulted in measurable plasma volume expansion and a concurrent reduction in FRC. Administration of this quantity of plasma appeared to be safe in healthy neonatal crias. However, changes in lung volume associated with plasma administration may create risks for crias with underlying cardiopulmonary or systemic disease.     

Intravenous infusion of electrolyte solution changes pharmacokinetics of drugs: pharmacokinetics of ampicillin

The pharmacokinetics of ampicillin in dogs was determined after intravenous (i.v.) bolus and constant rate infusion. Ampicillin was administered to six beagle dogs as an i.v. bolus at 20 mg/kg and as a constant rate i.v. infusion (CRI) at 20 mg/kg during 8 h (0.042 mL/min/kg) in Ringer's lactate (Hartmann's) solution. The concentrations were determined by an LC/MS/MS method. After i.v. bolus, ampicillin total body clearance, apparent volume of distribution at steady‐state, mean residence time (MRT), and half‐life were 4.53 ± 0.70 mL/min/kg, 0.275 ± 0.044 L/kg, 61 ± 13 min, and 111 (85–169) min, respectively. The corresponding parameters calculated after CRI were 13.5 ± 1.06 mL/min/kg, 0.993 ± 0.415 L/kg, 73 ± 27 min, and 49 (31–69) min. Ampicillin concentration decreased by 30% in the Ringer's lactate infusion solution mostly during the first hour after preparation of the solution. Constant rate infusion of Ringer's lactate solution during 8 h caused significant changes in ampicillin pharmacokinetics. The results suggested that special attention should be given to drug pharmacokinetics when co‐administered intravenously with electrolyte solutions.     

The use of 25% human serum albumin: outcome and efficacy in raising serum albumin and systemic blood pressure in critically ill dogs and cats

Objective: To report on the use of 25% human serum albumin (25% HSA) (Plasbumin®), associated outcome, and efficacy in raising serum albumin and systemic blood pressure (BP) in critically ill dogs and cats. Design: Retrospective clinical study. Animals: Client‐owned cats and dogs. Interventions: Administration of 25% HSA. Measurements and main results: The medical records of 66 animals (64 dogs, 2 cats) at the Ontario Veterinary College, which received 25% HSA (Plasbumin®) from June 1997 to December 2001 were reviewed for age, body weight, clinical problems, albumin and globulin (g/L) levels pre‐ and within 18‐hour post‐transfusion and upon discharge from hospital, total solids (TS), systolic and diastolic BP pre‐ and post‐transfusion total volume administered, adverse reactions, blood products and synthetic colloids used, and outcome. Twenty‐five percent HSA was prescribed for a range of clinical problems, which were grouped into 6 categories for analysis. The age range was 4 months–12 years and body weight range 1.4–65 kg. The maximum volume administered to any dog was 25 mL/kg, mean volume administered was 5 mL/kg, maximum volume given as a slow push or bolus was 4 mL/kg with a mean of 2 mL/kg volume. The range for a constant rate infusion (CRI) was 0.1–1.7 mL/kg/hr over 4–72 hours. Forty‐seven (71%) animals survived to discharge; 11(16%) were euthanized, and 8 (12%) died. Serum albumin and TS increased significantly (P<0.0001) above pre‐transfusion levels as did systolic BP (P<0.01). Conclusions: Twenty‐five percent HSA can be safely administered to critically ill animals, and an increase in albumin levels and systemic BP can be expected.     

Effects of subanesthetic doses of ketamine on hemodynamic and immunologic variables in dogs with experimentally induced endotoxemia

OBJECTIVE: To determine the effects of ketamine hydrochloride on hemodynamic and immunologic alterations associated with experimentally induced endotoxemia in dogs. ANIMALS: 9 mixed-breed dogs. PROCEDURES: In a crossover study, dogs were randomly allocated to receive ketamine (0.5 mg/kg, IV, followed by IV infusion at a rate of 0.12 mg/kg/h for 2.5 hours) or control solution (saline [0.9% NaCl] solution, 0.25 mL, IV, followed by IV infusion at a rate of 0.5 mL/h for 2.5 hours). Onset of infusion was time 0. At 30 minutes, lipopolysaccharide (LPS; 1 microg/kg, IV) was administered. Heart rate (HR), systolic arterial blood pressure (SAP), plasma tumor necrosis factor (TNF)-alpha activity, and a CBC were evaluated. RESULTS: Mean SAP was significantly reduced in dogs administered ketamine or saline solution at 2 and 2.5 hours, compared with values at time 0. However, there was no significant difference between treatments. At 1, 2, and 2.5 hours, dogs administered ketamine had a significantly lower HR than dogs administered saline solution. Although plasma TNF-alpha activity significantly increased, compared with values at time 0 for both groups, ketamine-treated dogs had significantly lower peak plasma TNF-alpha activity 1.5 hours after LPS administration. All dogs had significant leukopenia and neutropenia after LPS administration, with no differences detected between ketamine and saline solution treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a subanesthetic dose of ketamine had immunomodulating effects in dogs with experimentally induced endotoxemia (namely, blunting of plasma TNF-alpha activity). However, it had little effect on hemodynamic stability and no effect on WBC counts.     

Effects of fluid therapy on total protein and its influence on calculated unmeasured anions in the anesthetized dog

Objective – To determine the effects of IV lactated Ringer's solution at a rate of 10 mL/kg/h in anesthetized dogs on total protein (TP) measurement and calculation of unmeasured anions (UAs) using 2 quantitative methods of acid‐base status determination, strong ion gap, and modified base deficit. Design – Prospective clinical study. Animals – Forty‐three dogs, anesthetic health status I or II according to the American Society of Anesthesiologists, undergoing surgery under general anesthesia. Interventions – Arterial blood analyses for gas tensions, acid‐base balance, electrolytes, lactate, hemoglobin (Hb), PCV, and TP were performed under general anesthesia immediately after induction and again after administration of approximately 10 mL/kg of lactated Ringer's solution (given over 1 h). UAs were determined using strong ion gap and modified base deficit. Measurements and Main Results – Fluid replacement for 1 hour decreased TP, Hb, and PCV by 8%, 7.8%, and 8.6%, respectively. The degree of decrease in TP did not impact the calculation of UAs by quantitative methods when the prefluid administration TP value was used instead of the postfluid TP value in the calculation. Comparison of the two methods showed a low correlation (r≤0.68) and marked differences in the precision (1.96 SD). Conclusions: The degree of decrease in TP after 1 hour of fluid replacement at approximately 10 mL/kg does not affect determination of UAs when prefluid TP is used within that time period.     

Moxidectin toxicosis in a puppy successfully treated with intravenous lipids

Objective – To describe successful treatment of canine moxidectin toxicosis with the novel therapy of IV lipid administration.
Case Summary – A 16-week-old female Jack Russell Terrier was presented with acute onset of seizures followed by paralysis and coma shortly following suspected exposure to an equine formulation of moxidectin. Moxidectin toxicity was later confirmed. Initial therapy consisted of diazepam, glycopyrrolate, and IV fluids. Mechanical ventilation and supportive nursing care were provided as needed. An emulsion of 20% soybean oil in water, commonly used as the fat component of parenteral nutrition, was administered intravenously as a bolus of 2 mL/kg followed by 4 mL/kg/h for 4 hours beginning 10 hours after exposure and was administered again at a rate of 0.5 mL/kg/min for 30 minutes beginning 25.5 hours post-exposure. Mild improvement was seen after the first dose, and dramatic improvement was noted within 30 minutes of the second dose. The puppy's neurologic status returned to normal within 6 hours of the second administration, with no relapses.
Unique Information Provided – IV lipid therapy is a novel treatment approach for moxidectin toxicity. Its use is supported by recent research and case studies involving IV lipid administration for bupivacaine and other fat-soluble toxins. Lipid administration appeared to reverse the signs of toxicity and may prove to be a highly effective therapy for moxidectin and other fat-soluble toxins.     

Pharmacokinetics of intravenously and intramuscularly administered ticarcillin and clavulanic acid in foals

Serum concentrations of ticarcillin and clavulanic acid were measured in healthy foals (2 to 6 months old) given the drugs in combination by intravenous and intramuscular routes of administration. Five foals were administered 50 mg of ticarcillin/kg of body weight and 1.67 mg of clavulanic acid/kg, IV. Five foals were administered 100 mg of ticarcillin/kg and 3.33 mg of clavulanic acid/kg, IV, and 4 of those 5 were given the same combined dose IM. The elimination half-life of ticarcillin for intravenous administration was 0.83 hour for the low dosage and 0.96 hour for the high dosage. After intramuscular administration, the half-life of elimination was 2.9 hours, with bioavailability of 54.6%. For IV administered clavulanic acid, the elimination half-life was 0.65 hour for the low dosage and 0.74 hour for the high dosage. After intramuscular administration, the elimination half-life was 0.92 hour, and bioavailability was 68.1%. A combined dosage, 50 mg of ticarcillin/kg and 1.67 mg of clavulanic acid/kg, given every 6 hours is recommended.     

Effect of Manually Preheparinized Syringes on Packed Cell Volume and Total Solids in Blood Samples Collected from American Alligators (Alligator mississippiensis)

The hemodilution effect of manually preheparinized syringes was determined by evaluating the packed cell volume (PCV) and total solids (TS) from blood samples collected from 50 American alligators (Alligator mississippiensis). A volume of 0.2 mL of blood was drawn into 3 syringes of 1 mL: control with no heparin sodium, heparin sodium drawn to 0.1 mL and then expelled, and heparin sodium drawn to 0.2 mL and then expelled. PCV and TS values were determined from each syringe immediately after collection. Mean PCV and TS values were compared between the control and heparin groups using linear mixed modeling. The syringes coated with heparin resulted in a significantly lower mean PCV and TS values when compared with controls, with no significant difference between the heparin groups. This dilution effect was also found to be inconsistent and not accurate from one syringe to another. An adjunct method of obtaining 0.5 mL from already-collected blood samples into 1-mL syringes that were coated with heparin drawn to 0.2 mL and then expelled also showed a significant decrease in PCV and TS values when compared with the control samples, although to a lesser extent. As a result, it cannot be recommended to manually preheparinize syringes when collecting small volume of blood samples from American alligators because significant and unpredictable hemodilution is likely to occur.