Severe reaction to intravenous administration of an ionic iodinated contrast agent in two anesthetized dogs

CASE DESCRIPTION: Acute severe systemic reactions developed during i.v. administration of an ionic iodinated contrast agent (iothalamate meglumine) in 2 dogs undergoing contrast-enhanced computed tomography. CLINICAL FINDINGS: Both dogs developed marked changes in heart rate and systolic arterial blood pressure during or immediately after i.v. administration of the contrast agent. The first dog became profoundly hypertensive and bradycardic with poor oxygenation, apparent bronchospasm, and prolonged diarrhea. The second dog became hypotensive and tachycardic with erythema on the ventral aspect of the abdomen and pelvic limbs, periocular edema, and diarrhea. TREATMENT AND OUTCOME: Both dogs were treated for shock by means of i.v. fluid administration, and anesthesia was discontinued. The first dog was placed on a ventilator to improve oxygenation but was hypertensive and unresponsive for 6.5 hours following contrast agent administration. Bloody diarrhea persisted once consciousness was regained. The dog was discharged 3 days after contrast agent administration, and diarrhea resolved 15 days later. The second dog responded to phenylephrine administration, but urine output appeared low immediately following recovery from anesthesia. Urine output was normal the following day, and the dog was released 36 hours after contrast administration with no residual adverse effects. CLINICAL RELEVANCE: Findings highlighted the potential risk for severe reactions associated with i.v. administration of ionic iodinated contrast agents in dogs. Both hypertensive and hypotensive responses were seen. Supportive care for systemic manifestations was effective in these 2 dogs, and extended hospitalization was not necessary.     

Comparison of excretory urographic contrast effects of dimeric and monomeric non-ionic iodinated contrast media in dogs

In excretory urography, the osmolarity of contrast media has rarely been treated as important in veterinary medicine. In this study, the contrast effect of two contrast media (monomeric iohexol and dimeric iodixanol) in the renal cortex and aorta were compared using computed tomography (CT). Five beagle dogs were used and the study employed a cross-over method for each contrast media. The results showed that there was no difference between the media in the aorta, but iodixanol showed higher CT value and a longer contrast effect than iohexol in the renal cortex, in spite of having the same iodine dosage. It is believed that iodixanol, with its low osmolarity, is diluted less by osmotic diuresis than monomeric iohexol. It is important to consider the osmolarity of the contrast media when evaluating the contrast effect, and it is essential to use the same contrast media for each examination, or the renal excretory speed will be under/overestimated.     

Hemodynamic and serum biochemical alterations associated with intravenous administration of three types of contrast media in anesthetized dogs

OBJECTIVE: To determine the incidence and type of alterations in heart rate (HR), peak systolic blood pressure (PSBP), and serum biochemical variables (total bilirubin, BUN, and creatinine concentrations) associated with IV administration of ionic-iodinated contrast (IIC), nonionic-iodinated contrast (NIC), and gadolinium dimeglumine (GD) contrast media in anesthetized dogs. ANIMALS: 280 anesthetized dogs undergoing cross-sectional imaging. PROCEDURES: HR and PSBP were recorded at 5-minute intervals for 20 minutes for untreated control dogs and dogs that received IIC, NIC, or GD contrast medium. The development of an HR of < 60 beats/min or > 130 beats/min that included a > or = 20% change from baseline was considered a response. The development of PSBP of < 90 mm Hg or > 160 mm Hg that included a > or = 20% change from baseline was considered a response. Pre- and postcontrast serum biochemical values were recorded. Results-Of dogs receiving IIC medium, 3% (3/91) had a response in HR and 4% (4/91) had a response in PSBP at > or = 1 time points. None of the dogs receiving NIC medium had a response in HR; 1 of 16 had a response in PSBP. Of dogs receiving GD contrast medium, 1% (1/92) had a response in HR and 4% (4/92) had a response in PSBP. Of control dogs, 2% (2/81) had a response in HR and 4% (3/81) had a response in PSBP. No serum biochemical alterations were observed. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of contrast media in anesthetized dogs caused moderate bradycardia, tachycardia, hypotension, or hypertension.     

Hemodynamic and serum biochemical alterations associated with intravenous administration of three types of contrast media in anesthetized cats

OBJECTIVE: To determine the incidence and type of alterations in heart rate (HR), peak systolic blood pressure (PSBP), and serum biochemical variables (serum total bilirubin, BUN, and creatinine concentrations) associated with IV administration of ionic-iodinated contrast (IIC), nonionic-iodinated contrast (NIC), and gadolinium (GD) contrast media in anesthetized cats. ANIMALS: 220 anesthetized cats undergoing cross-sectional imaging. PROCEDURES: HR and PSBP were recorded at 5-minute intervals for 20 minutes for untreated control cats and cats that received IIC, NIC, or GD contrast medium. The development of HR < 100 beats/min or > 200 beats/min that included a > or = 20% change from baseline was considered a response. The development of PSBP of < 90 mm Hg or > 170 mm Hg that included a > or = 20% change from baseline was considered a response. Pre- and postcontrast serum biochemical values were recorded. Results-Of cats receiving IIC medium, 2% (1/60) had a response in HR at > or = 1 time point. Of cats receiving IIC medium, 7% (4/60) had a response in PSBP. None of the cats receiving NIC medium had a response in HR; 2 of 12 had a response in PSBP. Of cats receiving GD contrast medium, 6% (5/83) had a response in HR and 8% (7/83) had a response in PSBP. None of the control cats had a response in HR or PSBP. No serum biochemical alterations were observed. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of iodine and GD contrast media in anesthetized cats was associated with changes in HR and PSBP.     

Cardiovascular effects of butorphanol administration in isoflurane-O2 anesthetized healthy dogs

Cardiovascular consequences of butorphanol tartrate (0.2 mg/kg of body weight, IV) administration during isoflurane (1.7% end-tidal concentration) anesthesia were determined in mechanically ventilated healthy dogs. Butorphanol administration caused significant (P less than or equal to 0.05) reductions in mean, systolic, and diastolic arterial blood pressures; cardiac output; and rate-pressure product.     

Effects of hyperosmolar ionic and low osmolar non-ionic contrast media on coagulation times and some blood parameters in dogs: an in vivo study

The purpose of this study is to evaluate the effects of hyperosmolar ionic contrast media (CM) (diatrizoate) and low osmolar non-ionic CM (iohexol and ioxilan) on coagulation time and some blood parameters in dogs in vivo. The animals were divided into three groups in equal numbers. The dogs in groups I, II and III received diatrizoate, iohexol and ioxilan at the dose of 700 mgI/kg intravenously (IV) as a bolus, respectively. Administration of contrast media and blood samples were collected from vena cephalica antebrachii prior to CM administration and thereafter at 3, 15, 30, 60, 90 and 180 min and 24 h to measure the coagulation factors [activated partial thromboplastin time (APTT), prothorombin time (PT), fibrinogen and fibrinogen degradation products] and some other blood parameters [red blood cells, platelet, white blood cells, haematocrit (Ht) and haemoglobin (Hb)]. While a statistically significant decrease was observed on APTT at 15 min in group III, no significant differences were found in groups I and II. All the groups had insignificant alterations for PT, fibrinogen and fibrinogen degradation product, following CM administration. Significant decreases were observed for platelet at 3 min in all groups. This decrease was also significant at 15- and 30- min intervals in group I. There were significant decreases for erythrocytes, Ht and Hb measurements within 30 min, and no significant alterations were observed for leucocytes within 60 min in all groups compared with baseline values. No differences were observed with regard to coagulation times and some blood parameters as far as long-lasting and major effects of each CM are concerned.     

Adverse events diagnosed within three days of vaccine administration in dogs

OBJECTIVE: To determine incidence rates and potential risk factors for vaccine-associated adverse events (VAAEs) diagnosed within 3 days of administration in dogs. DESIGN: Retrospective cohort study. ANIMALS: 1,226,159 dogs vaccinated at 360 veterinary hospitals. PROCEDURE: Electronic records from January 1, 2002, through December 31, 2003, were searched for possible VAAEs (nonspecific vaccine reaction, allergic reaction, urticaria, or anaphylaxis) diagnosed within 3 days of vaccine administration. Information included age, weight, sex, neuter status, and breed. Specific clinical signs and treatments were reviewed in a random sample of 400 affected dogs. The association between potential risk factors and a VAAE was estimated by use of multivariate logistic regression. RESULTS: 4,678 adverse events (38.2/10,000 dogs vaccinated) were associated with administration of 3,439,576 doses of vaccine to 1,226,159 dogs. The VAAE rate decreased significantly as body weight increased. Risk was 27% to 38% greater for neutered versus sexually intact dogs and 35% to 64% greater for dogs approximately 1 to 3 years old versus 2 to 9 months old. The risk of a VAAE significantly increased as the number of vaccine doses administered per office visit increased; each additional vaccine significantly increased risk of an adverse event by 27% in dogs < or = 10 kg (22 lb) and 12% in dogs > 10 kg. CONCLUSIONS AND CLINICAL RELEVANCE: Young adult small-breed neutered dogs that received multiple vaccines per office visit were at greatest risk of a VAAE within 72 hours after vaccination. These factors should be considered in risk assessment and risk communication with clients regarding vaccination.     

Pharmacokinetics of buprenorphine following intravenous administration in dogs

OBJECTIVE: To determine pharmacokinetics of buprenorphine in dogs after i.v. administration. ANIMALS: 6 healthy adult dogs. PROCEDURES: 6 dogs received buprenorphine at 0.015 mg/kg, i.v. Blood samples were collected at time 0 prior to drug administration and at 2, 5, 10, 15, 20, 30, 40, 60, 90, 120, 180, 240, 360, 540, 720, 1,080, and 1,440 minutes after drug administration. Serum buprenorphine concentrations were determined by use of double-antibody radioimmunoassay. Data were subjected to noncompartmental analysis with area under the time-concentration curve to infinity (AUC) and area under the first moment curve calculated to infinity by use of a log-linear trapezoidal model. Other kinetic variables included terminal rate constant (k(el)) and elimination half-life (t(1/2)), plasma clearance (Cl), volume of distribution at steady state (Vd(ss)), and mean residence time (MRT). Time to maximal concentration (T(max)) and maximal serum concentration (C(max)) were measured. RESULTS: Median (range) values for T(max) and MRT were 2 minutes (2 to 5 minutes) and 264 minutes (199 to 600 minutes), respectively. Harmonic mean and pseudo SD for t(1/2) were 270+/-130 minutes; mean +/- SD values for remaining pharmacokinetic variables were as follows: C(max), 14+/-2.6 ng/mL; AUC, 3,082+/-1,047 ng x min/mL; Vd(ss), 1.59+/-0.285 L/kg; Cl, 5.4+/-1.9 mL/min/kg; and, k(el), 0.0026+/-0.0,012. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetic variables of buprenorphine reported here differed from those previously reported for dogs. Wide variations in individual t(1/2) values suggested that dosing intervals be based on assessment of pain status rather than prescribed dosing intervals.     

Disposition of ciprofloxacin following intravenous administration in dogs

The pharmacokinetics of ciprofloxacin (CIP) following intravenous administration m dogs nave been mvestisated. The drug was administered at three doses (2.5,5 and 10 mg/kg body weight) and was assayed in biological fluid samples (plasma and urine) by an HPLC method. The plasma concentration-time curves ere best described by a two-compartment open pharmacokinetic model. The was widely distributed (V_d(area) almost 3 1/kg), being distributed in the dog more rapidly than in other species (t_1/2(λ1) 3 min approximately). The elimination half-life (t_1/2λ2)) was 129–180 min which is similar to values obtaine in other species. The unchanged drug eliminated in urine was less than 37% of the administered dose, which is less than the values obtained in humans, calves and pigs. The glomerular filtration rate and the renal clearance of CIP in the dog suggest that renal elimination probably occurs mainly by glomerular filtration. The results showed that the pharmacokinetics of CIP, as in other species, was linear in dogs in the dose range studied.     

Prevention of adverse reactions following milbemycin D administration to microfilaremic dogs infected with Dirofilaria immitis

Some adverse reactions such as shock-like reaction and dirofilarial hemoglobinuria (caval syndrome) occasionally occurred in microfilaremic dogs following milbemycin D (Milbe) administration. This study was carried out to seek the prevention of these adverse reactions. In two groups containing 16 and 9 dogs respectively which were administered either chlorpheniramine maleate (1 mg/kg) or indomethacin (2.5 mg/kg) simultaneously with Milbe (1 mg/kg), the incidence of clinical signs such as the pale color of the visible mucous membranes, respiratory disorders, caval syndrome and shock-like reaction as well as changes in clinical parameters such as RBC and WBC counts, WBC profile and serum total protein, were almost equal to that observed in the group administered Milbe alone. In 41 dogs administered prednisolone (1 mg/kg) simultaneously with Milbe (1 mg/kg), no shock-like reaction was observed. Changes in clinical parameters were different from those in the group administered Milbe alone, whereas some clinical signs of adverse reactions, including caval syndrome, were observed. These results indicated that prednisolone was effective for prevention of the shock-like reaction in microfilaremic dogs induced by Milbe.     

Effects of hyperosmolar ionic and low osmolar non-ionic contrast media on acid base, blood gas and electrolyte status in dogs

The dogs in groups I, II and III in equal numbers received diatrizoate, iohexol and ioxilan at a dose of 700 mgI/kg intravenously (i.v.) as a bolus, respectively. Blood samples were collected prior to contrast media (CM) administration and thereafter at 3, 15, 30, 60, 90 and 180 min to evaluate acid-base, venous blood gas status (pH, PCO2, PO2, HCO, BE, O2) and electrolytes (Na+, Ca++, K+). Values of pH, PCO2, BE, HCO, Na+ and K+ remained unchanged or within non-significant fluctuations compared with the baseline values. PO2 was significantly different from the baseline values in group 1 up to 90 min after administration, significant alterations were found for O2 saturation in group 1 up to 90 min, and in group II at 3, 60 and 180 min; and for Ca++ in group 1 at all time points except at 90 min, and groups II and II at 3 and 15 min post administration. It was concluded that none of the CM are considered to cause long-lasting and major effects on acid-base, blood gas and electrolyte status.     

Cardiorespiratory effects of epidural administration of morphine and fentanyl in dogs anesthetized with sevoflurane

OBJECTIVE: To determine the cardiorespiratory effects of epidural administration of morphine alone and in combination with fentanyl in dogs anesthetized with sevoflurane. DESIGN: Prospective study. ANIMALS: 6 dogs. PROCEDURE: Dogs were anesthetized with sevoflurane and allowed to breathe spontaneously. After a stable plane of anesthesia was achieved, morphine (0.1 mg/kg [0.045 mg/lb]) or a combination of morphine and fentanyl (10 microg/kg [4.5 microg/lb]) was administered through an epidural catheter, the tip of which was positioned at the level of L6 or L7. Cardiorespiratory variables were measured for 90 minutes. RESULTS: Epidural administration of morphine alone did not cause any significant changes in cardiorespiratory measurements. However, epidural administration of morphine and fentanyl induced significant decreases in diastolic and mean arterial blood pressures and total peripheral resistance. Stroke volume was unchanged, PaCO2 was significantly increased, and arterial pH and base excess were significantly decreased. Heart rate was significantly lower after epidural administration of morphine and fentanyl than after administration of morphine alone. None of the dogs had any evidence of urine retention, vomiting, or pruritus after recovery from anesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that epidural administration of morphine at a dose of 0.1 mg/kg in combination with fentanyl at a dose of 10 microg/kg can cause cardiorespiratory depression in dogs anesthetized with sevoflurane.     

Respiratory reflexes in response to nasal administration of halothane to anesthetized, spontaneously breathing dogs

OBJECTIVE: To characterize and determine the sensory innervation of respiratory reflexes elicited by nasal administration of halothane to dogs. ANIMALS: 10 healthy Beagles. PROCEDURE: Dogs underwent permanent tracheostomy and, 2 to 3 weeks later, were anesthetized with thiopental and alpha-chloralose administered IV. The nasal passages were functionally isolated so that halothane could be administered to the nasal passages while dogs were breathing 100% O2 via the tracheostomy. Respiratory reflexes in response to administration of halothane at concentrations of 1.25, 1.75, and 2.5 times the minimum alveolar concentration (MAC), and 5% (administered in 100% O2 at a flow rate of 5 L/min) were recorded. Reflexes in response to administration of 5% halothane were also recorded following transection of the infraorbital nerve, transection of the caudal nasal nerve, and nasal administration of lidocaine. RESULTS: Nasal administration of halothane induced an inhibition of breathing characterized by a dose-dependent increase in expiratory time and a resultant decrease in expired volume per unit time. Effects were noticeable immediately after the onset of halothane administration and lasted until its cessation. Reflex responses to halothane administration were attenuated by transection of the caudal nasal nerve and by nasal administration of lidocaine, but transection of the infraorbital nerve had no effect. CONCLUSIONS AND CLINICAL RELEVANCE: Nasal administration of halothane at concentrations generally used for mask induction of anesthesia induces reflex inhibition of breathing. Afferent fibers in the caudal nasal nerve appear to play an important role in the reflex inhibition of breathing induced by halothane administration.     

Effect of intravenous administration of ketamine on the minimum alveolar concentration of isoflurane in anesthetized dogs

OBJECTIVE: To determine the effect of 6 plasma ketamine concentrations on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 dogs. PROCEDURE: In experiment 1, the MAC of isoflurane was measured in each dog and the pharmacokinetics of ketamine were determined in isoflurane-anesthetized dogs after IV administration of a bolus (3 mg/kg) of ketamine. In experiment 2, the same dogs were anesthetized with isoflurane in oxygen. A target-controlled IV infusion device was used to administer ketamine and to achieve plasma ketamine concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL by use of parameters obtained from experiment 1. The MAC of isoflurane was determined at each plasma ketamine concentration, and blood samples were collected for ketamine and norketamine concentration determination. RESULTS: Actual mean +/- SD plasma ketamine concentrations were 1.07 +/- 0.42 microg/mL, 1.62 +/- 0.98 microg/mL, 3.32 +/- 0.59 microg/mL, 4.92 +/- 2.64 microg/mL, 13.03 +/- 10.49 microg/mL, and 22.80 +/- 25.56 microg/mL for target plasma concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL, respectively. At these plasma concentrations, isoflurane MAC was reduced by 10.89% to 39.48%, 26.77% to 43.74%, 25.24% to 84.89%, 44.34% to 78.16%, 69.62% to 92.31%, and 71.97% to 95.42%, respectively. The reduction in isoflurane MAC was significant, and the response had a linear and quadratic component. Salivation, regurgitation, mydriasis, increased body temperature, and spontaneous movements were some of the adverse effects associated with the high plasma ketamine concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine appears to have a potential role for balanced anesthesia in dogs.     

Suspected anaphylactoid reaction following intravenous administration of a gadolinium‐based contrast agent in three dogs undergoing magnetic resonance imaging

ObservationsAnaphylactoid reactions were suspected in three dogs following the intravenous administration of the contrast agent gadobenate dimeglumine 0.05 mmol kg^?1 (Multihance^®).Case 1: A 14 kg 6–year–old atopic female dog was anaesthetized for brain magnetic resonance imaging (MRI). All monitored parameters remained stable during the procedure. Fifteen minutes following MR completion; facial, peri–orbital and sublingual oedema were noted. Resolution of the oedema was rapid and uneventful following treatment of clinical signs over 2 hours.Case 2: A 16 kg 10–month–old male dog was anaesthetized for brain and neck MRI. Ten minutes after MR contrast intravenous (IV) injection; heart rate (HR) increased (85–120 beats minute^?1), mean arterial blood pressure (MAP) decreased (from 70 to 43 mmHg) and Pe′CO₂ decreased (from 4.66 to 3.19 kPa). Labial, periorbital and lingual oedema were noted. Clinical signs responded to fluid bolus administration. The dog vomited in recovery but oedema resolved within one hour.Case 3: A 34 kg 2–year–old atopic male dog was anaesthetized for head MRI. Within 5 minutes of MR contrast IV injection; the dog suffered severe cardiovascular collapse. MRI procedure was aborted and administration of anaesthetics discontinued. Aggressive IV fluid resuscitation and IV epinephrine administration were necessary to re–establish cardiovascular stability. Some periorbital and labial oedema were noted. The dog vomited once and had soft faeces but made a complete recovery.ConclusionsThe administration of contrast medium may result in mild to severe anaphylactoid reactions.     

Adverse reactions suggestive of type III hypersensitivity in six healthy dogs given human albumin

CASE DESCRIPTION:6 healthy dogs given human albumin solution as part of a study were examined following development of an immediate hypersensitivity reaction (1 dog) and signs suggestive of a type III hypersensitivity reaction (all 6 dogs). CLINICAL FINDINGS: All 6 dogs were healthy prior to administration of human albumin solution. One dog developed signs of an immediate hypersensitivity reaction, characterized by vomiting and facial edema, during administration of human albumin solution. All 6 dogs developed signs of a delayed adverse reaction 5 to 13 days after administration of human albumin solution. Initial clinical signs included lethargy, lameness, edema, cutaneous lesions indicative of vasculitis, vomiting, and inappetance. TREATMENT AND OUTCOME: In the dog with signs of immediate hypersensitivity, signs resolved after administration of human albumin solution was discontinued and diphenhydramine was administered. Supportive treatment was provided after dogs developed signs of a delayed adverse reaction. Four dogs recovered, but 2 dogs died despite treatment. All 6 dogs were found to have antihuman albumin antibodies. There was no evidence of contamination of the human albumin solution. CLINICAL RELEVANCE: Findings suggest that administration of human albumin solution in healthy dogs with normal serum albumin concentrations may result in signs of a type III hypersensitivity reaction.     

Plasma salicylate concentrations in immature dogs following aspirin administration: comparison with adult dogs

Aspirin disposition in immature and adult dogs, assessed by plasma salicylate concentrations following single doses of aspirin given orally (p.o.) and intravenously (i.v.), was compared. Using a cross-over design, four immature (12–16-weeks-old) and eight adult (1– 2-years-old) dogs were given a single dose of aspirin at 17.5 mg/kg body weight i.v. and a single dose of buffered aspirin at 35 mg/kg body weight p.o. Blood was collected from the jugular vein for 24 h following each dose. A fluorescence polarization immunoassay was used for determination of salicylate in plasma. Significant differences in aspirin disposition were identified between the two groups. Immature dogs had significantly shorter salicylate half-life, lower mean residence time, and more rapid salicylate clearance than adult dogs. The difference in volume of distribution between the two groups was not significantly different. Immature dogs had lower mean (± SD) peak plasma salicylate concentrations (64.5 ± 2.38 mg/L) than adult dogs (95.9 ± 12.2 mg/L) following a single oral dose of buffered aspirin at 35 mg/kg body weight. Predicted plasma salicylate concentration-time curves were constructed for various aspirin dosage regimens. This analysis showed that the previously recommended buffered aspirin dose for adult dogs of 25 mg/kg body weight p.o. every 8 h would be ineffective in maintaining plasma salicylate concentrations > 50 mg/L in immature dogs.     

Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs

Pharmacokinetic analysis of buprenorphine administered to six healthy dogs via the oral transmucosal (OTM) route at doses of 20 and 120 microg/kg was conducted using liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS). Bioavailability was 38% plus or minus 12% for the 20 microg/kg dose and 47%+/-16% for the 120 microg/kg dose. Maximum plasma concentrations were similar for buprenorphine doses of 20 microg/kg IV and 120 microg/kg OTM. Sedation and salivation were common side effects, but no bradycardia, apnea, or cardiorespiratory depressive effects were seen. When the two OTM dosing rates were normalized to dose, LC-ESI-MS/MS analysis of buprenorphine and its metabolites detected no significant difference (P>.05), indicating dose proportionality. The results of this study suggest that OTM buprenorphine may be an alternative for pain management in dogs.