Veterinary Clinical Sciences Publications Veterinary Clinical Sciences

11-1-2014

Effect of dosing interval on efficacy of maropitantfor prevention of hydromorphone-inducedvomiting and signs of nausea in dogsBonnie L. Hay KrausIowa State University, bhkraus@iastate.edu

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Effect of dosing interval on efficacy of maropitant for prevention ofhydromorphone-induced vomiting and signs of nausea in dogs

AbstractObjective—To evaluate the effect of dosing interval on the efficacy of maropitant for prevention of opioid-induced vomiting and signs of nausea in dogs.

Design—Randomized prospective clinical study.

Animals—50 client-owned dogs that underwent an elective surgical procedure.

Procedures—Dogs were randomly assigned to receive maropitant (1 mg/kg [0.45 mg/lb], SC), thenhydromorphone (0.1 mg/kg [0.045 mg/lb], IM) at 0 (simultaneously; group 0; n = 10), 15 (group 15; 10),30 (group 30; 10), 45 (group 45; 10), or 60 (group 60; 10) minutes later. Dogs were monitored for vomitingand signs of nausea for 30 minutes after hydromorphone administration. A historical control group of similardogs (n = 9) that were administered hydromorphone (0.1 mg/kg, IM) but not maropitant served as thereferent for comparison purposes.

Results—Vomiting was recorded for 6 dogs in group 0 and 2 dogs in group 15. Signs of nausea were recordedfor 10 dogs in group 0, 9 dogs in group 15, 8 dogs in group 30, 6 dogs in group 45, and 1 dog in group 60.Compared with dogs in the historical control group, vomiting was significantly decreased and prevented whenmaropitant was administered 15 and 30 minutes, respectively, before hydromorphone; signs of nausea weresignificantly decreased only when maropitant was administered 60 minutes before hydromorphone.

Conclusions and Clinical Relevance—Results indicated that vomiting was significantly decreased and thenprevented when maropitant was administered to dogs 15 and 30 minutes before hydromorphone. However,signs of nausea were significantly decreased only when the dosing interval was 60 minutes.

DisciplinesComparative and Laboratory Animal Medicine | Small or Companion Animal Medicine | VeterinaryToxicology and Pharmacology

CommentsThis article is published as Kraus, Bonnie L. Hay. "Effect of dosing interval on efficacy of maropitant forprevention of hydromorphone-induced vomiting and signs of nausea in dogs." Journal of the AmericanVeterinary Medical Association 245, no. 9 (2014): 1015-1020. doi: 10.2460/javma.245.9.1015. Posted withpermission.

This article is available at Iowa State University Digital Repository: http://lib.dr.iastate.edu/vcs_pubs/13

This material has been provided by the publisher for your convenience. It may not be further reproduced in any manner, including (but not limited to) reprinting, photocopying, electronic storage or transmission, or uploading onto the Internet. It may not be redistributed, amended, or overprinted. Reproduction of this material without permission of the publisher violates federal law and is punishable under Title 17 of the United States Code (Copyright Act) and various international treaties. Reprints or permission to reprint may be ordered by contacting dfaqen@avma.org .

Effect of dosing interval on efficacy of maropitant for prevention of hydromorphone­

induced vomiting and signs of nausea in dogs

Bonnie L. Hay Kraus, DVM

Objective-To evaluate the effect of dosing interval on the efficacy of ma ropitant for pre­vention of opioid-induced vomiting and signs of nausea in dogs.

Design-Randomized prospective clinical study.

Animals-50 client-owned dogs that underwent an elective surgical procedure.

Procedures-Dogs were randomly assigned to receive maropitant (1 mg/kg [0.45 mg/lb], SC). then hydromorphone (0.1 mg/kg [0.045 mg/lb], IM) at 0 (simultaneously; group O; n = 10). 15 (group 15; 10), 30 (group 30; 10). 45 (group 45; 10), or 60 (group 60; 10) minutes later. Dogs were monitored for vomiting and signs of nausea for 30 minutes after hydro­morphone administration. A historical control group of similar dogs (n = 9) that were ad­ministered hydromorphone (0.1 mg/kg, IM) but not maropitant served as the referent for comparison purposes. Results- Vomiting was recorded for 6 dogs in group 0 and 2 dogs in group 15. Signs of nausea were recorded for 10 dogs in group 0, 9 dogs in group 15, 8 dogs in group 30, 6 dogs in group 45, and 1 dog in group 60. Compared with dogs in the historical control group, vomiting was significantly decreased and prevented when maropitant was administered 15 and 30 minutes, respectively, before hydromorphone; signs of nausea were significantly decreased only when maropitant was administered 60 minutes before hydromorphone.

Conclusions and Clinical Relevance-Results indicated that vomiting was significantly decreased and then prevented when maropitant was administered to dogs 15 and 30 min­utes before hydromorphone. However, signs of nausea were signif icantly decreased only when the dosing interval was 60 minutes. (J Am Vet Med Assoc 2014;245:1015-1020)

H ydromorphone is a synthetic µ-opioid receptor agonist that is commonly used alone or in combi­

nation with tranquilizers or sedatives as an anesthetic premedication, as part of an anesthesia induction regi­men for high-risk patients, and as an intraoperative and postoperative analgesic. Hydromorphone does not cause histamine-induced vasodilation and hypotension following IV administration, and that property, along with its low cost, has contributed to the widespread use of hydromorphone for pain management in dogs. 1

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In dogs, opioid administration frequently results in unwanted adverse effects, including bradycardia, re­spiratory depression, behavior changes (eg, sedation, dysphoria, or excitement) , urine retention or decreased urine production, and gastrointestinal abnormalities (eg, signs of nausea, vomiting, and defecation). 4

-6 Signs of nausea and vomiting occur frequently in dogs after administration of morphine, hydromorphone, and oxy­morphone. The incidence of vomiting associated with hydromorphone administration ranges from 0% to 100% and is dependent on the dose and route of admin­istration, study conditions, population, duration that

From th e Department of Veterinary Clinical Sciences, College of Vet­erinary Medicine , Iowa State University, Ames, IA 500ll.

Maropitant was provided by Zoetis , Florham, NJ. No other external funding was provided for this smdy.

Presented in abstract form at the American College of Veterinary An­esthesia and Analgesia Meeting, San Diego, September 2013.

The author thanks Mollie Jacobs for technical assistance. Address correspondence to Dr. Hay Kraus (bhkraus@iastate.edu) .

JAVMA. Vol 245. No. 9. November 1, 2014

ASA Cm ax NK1 VAS

ABBREVIATIONS

American Society of Anesthesiologists Peak plasma concentration Neurokinin 1 Visual analogue scale

food was withheld prior to administration, and concur­rent administration of acepromazine.3.7- JO

Vomiting during the perioperative period can result in aspiration of gastric contents, esophagitis and subsequent esophageal stricture, unnecessary tension on sutures, and increases in intracranial and intraocular pressures. Pro­fuse or prolonged vomiting can cause dehydration, electrolyte and acid-base imbalances, and prolonged hospitalization.11 Thus, the avoidance and prevention of nausea and vomiting during the perioperative pe­riod are important objectives in human medicine. Both human patients and anesthesiologists rate nausea and vomiting among the top anesthesia-associated adverse effects to be avoided.12 In fact, many human patients consider nausea and vomiting to be more distressing than postsurgical pain.12·13 In dogs, vomiting and re­gurgitation, especially when associated with anesthesia and hydromorphone administration, are risk factors for the development of aspiration pneumonia. 14-18 Under­lying gastrointestinal dysfunction, upper airway abnor­malities, and surgical interventions put brachycephalic breeds of dogs at an increased risk of vomiting, regurgi­tation, aspiration, and death during the perianesthetic

Scientific Reports 1015

period, compared with those risks in the general canine population. 19

•20

Prevention of signs of nausea and vomiting during the perioperative period is garnering attention in vet­erinary medicine. Maropitant is a highly selective NKl antagonist that was developed and approved for the treatment and prevention of vomiting in dogs. Clini­cally, it is used to treat vomiting resulting from various causes and to prevent vomiting subsequent to a broad spectrum of emetic stimuli including motion sickness and administration of cisplatin, apomorphine, hydro­morphone, morphine, or copper sulfate. 10·21- 27

Results of a recent study10 indicate that maropitant (1.0 mg/kg [0.45 mg/lb], SC) effectively prevents signs of nausea and vomiting in dogs when administered 1 hour prior to hydromorphone (O.l mg/kg [0.045 mg/ lb], IM). In another study,27 maropitant (1.0 mg/kg, SC) administered to dogs 20 minutes prior to mor­phine (1.0 mg/kg IM) significantly decreased, but did not eliminate, vomiting and retching and had no effect on the incidence of signs of nausea, compared with those incidences for dogs that were administered saline (0 .9% NaCl) solution instead of maropitant prior to morphine. The objective of the study reported here was to evaluate the effect of dosing interval on the efficacy of maropitant for the prevention of hydromorphone­induced vomiting and retching and signs of nausea.

Materials and Methods

Animals-Client-owned dogs~ 6 months old that were admitted to the Lloyd Veterinary Medical Center at Iowa State University between January and August 2012 for elective surgery or advanced imaging that required anesthesia were considered for study enrollment. To be included in the study; each dog had to be classified as ASA28 status I (healthy with no evidence of systemic dis­ease) or status II (mild systemic disease with no func­tional limitations) on the basis of results of a complete physical examination, CBC, and serum biochemical analysis. The final study population consisted of 50 dogs (18 spayed females, 4 sexually intact females, 22 castrated males, and 6 sexually intact males) that ranged in age from 6 months to 10.9 years and weight from 1.3 to 57.3 kg (2.9 to 126.1 lb) and included a mixture of purebred and mixed-breed dogs. Owner consent was obtained for each dog prior to study enrollment, and all study procedures were approved by the Iowa State University Institutional Animal Care and Use Committee.

Study design-A card-draw technique29 was used to randomly assign each dog to 1 of 5 treatment groups. All dogs were premedicated with maropitant citrate• (1.0 mg/kg, SC) and then hydromorphone (0.1 mg/kg, IM) at 0 (ie, the same time; group O; n = 10), 15 (group 15; 10), 30 (group 30; 10), 45 (group 45 ; 10), or 60 (group 60; 10) minutes later.

Food, but not water, was withheld from all dogs be­ginning at 10:00 PM the night before anesthesia, which resulted in food being withheld from dogs for 8.5 to 15 hours prior to maropitant administration. All SC injec­tions were administered under the loose skin on the dor­sal midline between the scapulae, and all IM injections were administered in the lumbar epaxial muscles. A

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trained observer (BHK) monitored each dog for 30 min­u tes after hydromorphone administration and recorded emetic events (vomiting and retching) and whether the dog had signs of nausea. This observer was aware of the treatment group assignment for each dog. Vomiting was defined as the expulsion of stomach contents from the mouth. Retching was defined as forceful contraction of abdominal muscles without expulsion of stomach con­tents from the mouth. Each discrete vomiting or retching event was recorded. Signs of nausea were defined as sali­vation and increased frequency of or exaggerated swal­lowing motions and licking of lips; the presence of any of those signs was considered positive for signs of nausea. Dogs that vomited or retched were considered to have signs of nausea regardless of whether the other signs of nausea were observed because it is generally assumed that nausea is a prodromal sign of vomiting or retching.

Historical control group-A group of dogs (n = 9) that were administered saline (0.9% NaCl) solution 1 hour prior to hydromorphone during another study10

was used as a historical control group to serve as a refer­ent for comparison with treatment groups of the present study. That study10 was approved by the Iowa State Uni­versity Institutional Animal Care and Use Committee, and owner consent was obtained for each dog prior to study enrollment. Those dogs were similar to the dogs of the present study in that they were admitted to the Lloyd Veterinary Medical Center for an elective surgery and were classified as ASA status I or status II on the basis of results of a complete physical examination, CBC, and se­rum biochemical analysis. The group consisted of a mix­ture of purebred and mixed-breed dogs (6 females and 3 males) with a mean± SD age of 5.3 ± 2.75 years and weight of 27 ± 16.5 kg (59.4 ± 36.3 lb) . All dogs were administered saline solution (O.l mUkg, SC) under the loose skin on the dorsal midline between the scapulae 1 hour before hydromorphone (O.l mg/kg, IM) , which was injected in the lumbar epaxial muscles. The trained observer (BHK) that monitored the dogs of the present study also monitored each dog of that study10 for 30 min­utes after hydromorphone administration and recorded emetic events (vomiting and retching) and whether the dog had signs of nausea. The definitions of vomiting, retching, and signs of nausea used in that study10 were the same as those used in the present study.

Statistical analysis-A 1-way ANOVA was used to compare the mean age and weight among the treatment groups (groups 0, 15, 30, 45, and 60) and the historical control group. A X2 test was used to assess differences in the sex distribution between the respective treatment groups and the historical control group. The outcomes of interest were the incidence of emetic events (vomit­ing or retching) and signs of nausea. A 2-tailed Fisher exact test was used compare the incidence of each out­come between the respective treatment groups and the historical control group. For all analyses, values of P ~ 0.05 were considered significant.

Results

The mean age (P = 0.589) and weight (P = 0.322) and sex distribution (P = 0.158) of dogs did not dif-

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Table 1-Number of dogs that vomited or retched and had signs of nausea within 30 minutes after hydromorphone (0.1 mg/kg [0.045 mg/lb]. IM) administration following premedication with saline (0.9% NaCl) solution (0.1 mUkg, SC) 1 hour previously (historical control group) or maropitant (1.0 mg/kg [0.45 mg/lb]. SC) at 0 (ie, same time; group 0), 15 (group 15). 30 (group 30). 45 (group 45), or 60 (group 60) minutes previously.

No. of dogs Vomiting Signs of Treatment group in group or retching nausea

Historical control 9 7 9 0 10 6 10 15 10 2* 9 30 10 O* 8 45 10 O* 6 60 10 O* 1*

All dogs were classified as ASA status I or status II on the basis of results of a physical examination, CBC, and serum biochemical analy­sis. Vomiting was defined as the expulsion of stomach contents from the mouth. Retching was defined as forceful contraction of abdominal muscles without expulsion of stomach contents from the mouth. Signs of nausea were defined as salivation and increased frequency of or exag­gerated swallowing motions and licking of lips; the presence of any of those signs was considered positive for signs of nausea. Dogs that vom­ited or retched were considered to have signs of nausea regardless of whether the other signs of nausea were observed because it is generally assumed that nausea is a prodromal sign of vomiting or retching.

*Within a column, value differs significantly (P~ 0.05) from that for the historical control group.

fer significantly among the treatment groups and the historical control group. The number of dogs that vomited or retched and had signs of nausea within 30 minutes after hydromorphone administration for each treatment group and the historical control group was summarized (Table 1) . The incidence of vomiting or retching was significantly (P = 0.023) less for group 15, compared with that for the historical control group. None of the dogs in groups 30, 45, and 60 vomited or retched within 30 minutes after hydromorphone administration, which suggested that administration of maropitant at least 30 minutes prior to hydromor­phone prevented vomiting and retching. The respective incidences of signs of nausea for groups 0, 15, 30, and 45 did not differ significantly from that for the histori­cal control group. The incidence of signs of nausea for group 60 was significantly (P < 0.001) less than that for the historical control group, which suggested that administration of maropitant at least 60 minutes prior to hydromorphone reduced the occurrence of signs of nausea .

Discussion

Results of the present study indicated that admin­istration of maropitant (1.0 mg/kg, SC) to dogs 1 hour prior to administration of hydromorphone (O.l mg/kg, IM) was effective in preventing vomiting and retch­ing and reducing the incidence of signs of nausea and confirmed the findings of another study. 10 Further, in the present study, administration of maropitant as little as 15 minutes prior to hydromorphone administration was effective in reducing the incidence of vomiting and retching. This time frame was substantially shorter than that required for maropitant to reduce (30 min­utes) and cease (39 minutes) cisplatin-induced emesis in dogs .2J Maropitant (1.0 mg/kg, SC) administration to

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dogs achieves a Cmax of 92 ng/mL at 0.75 hours after injection.21 On the basis of the results of the present study, it appears that the antiemetic activity of maropi­tant can be achieved well before the time required for the drug to reach its Cmax, especially when maropitant is administered before the emetic challenge (ie , before opioid administration) . However, the pharmacokinetic­pharmacodynamic relationship of the NKl-antagonist activity of maropitant remains relatively unexplored.

Neurokinin 1 antagonists (eg, maropitant) and their active metabolites have highly potent receptor­binding affinity and are thought to penetrate the blood­brain barrier and mediate their biological effect through occupation of NKl receptors in the brain.21 Because maropitant is highly protein bound, only a small frac­tion of the total dose remains unbound to protein after injection and available to cross the blood-brain barrier to elicit pharmacological activity. 21 Results of 1 study2J indicate that the antiemetic activity of maropitant in dogs lasts for 19 hours following oral administration of 2.0 mg of maropitant/kg, even when the mean plasma concentration of maropitant or its active metabolites is assumed to be < 40 ng/mL. In the present study, SC administration of maropitant to dogs 15 minutes before hydromorphone resulted in a significant reduction in the incidence of opioid-induced vomiting or retching, which provided further evidence that the in vivo activ­ity of maropitant for prevention of opioid-induced em­esis was achieved at plasma or CSF drug concentrations less than the Cmax. Additional research is warranted to determine the ability of maropitant and its active me­tabolites to penetrate the blood-brain barrier and the concentration of maropitant in the plasma or CSF nec­essary to induce its antiemetic effects.

Although maropitant administration at least 15 minutes before hydromorphone administration effec­tively reduced or prevented vomiting or retching in the present study, a significant decrease in the incidence of signs of nausea was apparent only when maropitant was administered 60 minutes prior to hydromorphone. In human patients, nausea is subjectively described as an unpleasant sensation associated with the awareness of the urge to vomit.Jo The mechanisms that cause nausea remain unclear but are thought to be associated with stimuli from high brain centers that disrupt the normal contraction and relaxation patterns of the stomach,Jo which changes gastrointestinal motility and gastric acid secretion and causes reverse peristalsis.Jo Clinical signs associated with nausea in human patients include in­creased salivation, pallor, tachycardia, hot and cold sen­sations, and diaphoresis .J0 In dogs, nausea is described as a sensation that precedes vomiting and may or may not lead to vomiting, and the clinical signs of nausea in dogs include depression, salivation, licking of lips, and increased swallowing.J I Visual analogue scale scores for signs of nausea in dogs treated with apomorphine (ie, a centrally acting emetic) 1 hour after maropitant admin­istration were lower than those for placebo-treated dogs during the first 12 minutes after apomorphine adminis­tration. J2 However, when dogs were treated with syrup of ipecac (ie, a peripherally acting emetic), the VAS scores for signs of nausea for dogs that were premedi­cated with maropitant, compared with those for dogs

Scientific Reports 1017

that were premedicated with a placebo, did not differ significantly within the first 33 minutes after syrup of ipecac administration but were significantly lower be­tween 36 and 60 minutes after syrup of ipecac admin­istration.32 In both instances,32 maropitant significantly decreased but did not eliminate emesis, compared with a placebo, and it was more effective for reducing the in­cidence of emesis than it was for reducing the incidence of signs of nausea. Healthy dogs that were administered maropitant immediately after cisplatin had significantly decreased VAS scores for signs of nausea for up to 80 minutes, compared with control dogs that were admin­istered saline solution instead of maropitant.23 Results of a recent study33 in which dogs were orally adminis­tered maropitant (2.0 to 4.0 mg/kg [0.9 to 1.8 mg/lb]) or a lactose monohydrate placebo 2 hours prior to hydro­morphone (0.1 mg/kg, IM) indicate that, although ma­ropitant effectively prevented vomiting, 12 of 20 (60%) maropitant-treated dogs developed signs of nausea . In that study,33 of the 12 maropitant-treated dogs that de­veloped signs of nausea, 10 had signs that were subjec­tively classified as moderate or severe, whereas only 2 of 16 placebo-treated dogs that developed signs of nau­sea had signs that were classified as moderate or severe. Findings of the present study indicated that the inject­able formulation of maropitant has a clear advantage over the oral formulation for the prevention of signs of nausea in dogs, although it must be administered at least 1 hour before opioid administration for this effect to be realized.

A limitation of the present study was the failure to obtain VAS scores for signs of nausea for dogs in each of the treatment groups. This data would have allowed the severity of signs of nausea to be correlated with the dos­ing interval between administration of maropitant and hydromorphone. The obvious advantage of maropitant administration to veterinary patients is the prevention of vomiting during the perioperative period and the as­sociated decrease in patient morbidity and death; how­ever, another advantage of maropitant administration is the reduction in patient discomfort caused by nausea. Human patients widely report that nausea causes dis­comfort and distress. It should be assumed that nau­sea may affect veterinary patients similarly, and steps should be taken to prevent or treat signs of nausea in those patients.34

Another limitation of the present study is that the observer that recorded emetic events and the presence of signs of nausea was aware of (ie, not blinded to) the treatment group assignment for each dog, and that ob­server's conscious or unconscious predisposition might have generated bias. In both human and veterinary medicine, many randomized clinical trials are conduct­ed without the outcome assessor being blinded. Blind­ing of outcome assessors can increase the time, cost, and logistic complexity of clinical trials and does not guarantee that the results will not be biased. However, results of multiple systematic reviews3S-37 indicate that observer bias tends to occur when nonblinded asses­sors record measurement of scale, time-to-event, and binary outcomes. For randomized clinical trials with binary outcomes, use of nonblinded assessors biased treatment effect estimates and exaggerated ORs by

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36%.37 However, in that systematic review,37 the pooled OR for blinded versus nonblinded assessors (ie, ob­server bias) was 0.55 for randomized trials with subjec­tive outcomes and 0.93 for randomized trials with less subjective outcomes, which suggested that there was very little difference between blinded and nonblinded observers. Bias is more likely to occur in trials with subjective measures than it is in trials with objective outcomes. The outcomes assessed in the present study were considered to be categorical and objective (ie, ei­ther the dogs vomited, retched, or had signs of nausea or they did not during the 30 minutes after hydromor­phone administration); subjective outcomes such as the measurement of the severity of the signs of nausea were not assessed. Therefore, blinding the observer was not considered necessary and likely would not have substantially affected the results or conclusions of this study; however, the presence of observer bias cannot be ruled out.

The use of a historical control group from a study10

performed by the same investigator at the same institu­tion as the present study might also be considered a limi­tation. Use of data from a historical control group has several advantages, including a reduction in the number of patients required for a clinical trial, which decreases the cost and shortens the duration of the trial. When the historical control group consists of subjects that received an ineffective treatment (ie, a placebo), use of data from those subjects may have an ethical advantage because fewer subjects receive the ineffective treatment. Addi­tionally, reduced allocation of subjects to a placebo group might make recruitment easier and increase the feasibil­ity of study completion.38 For those reasons, the use of historical control data has become increasingly impor­tant in human clinical trials and has been used to some extent in veterinary medicine.39-

43 In a seminal paper,43

Pocock outlined the conditions for the acceptable use of data from a historical control group, which include the same criteria for subject enrollment, same methods for treatment evaluation, and comparable distribution of subject characteristics. Pocock's final condition is that the study for which use of a historical control group is being considered should be performed by the same or­ganization with most of the same clinical investigators as the study that is providing the data for the historical control group. The present study fulfilled all the require­ments for use of a historical control group.

Maropitant administration to dogs and cats has gar­nered the interest of clinicians because of its analgesic as well as its antiemetic properties. Neurokinin 1 recep­tors and substance P are involved in pain perception via central and peripheral pathways that include sensory afferent fibers, dorsal root ganglia, the dorsal horn of the spinal cord, ascending spinal cord projections, and higher nerve centers.44 During a surgical procedure in which traction was applied to the ovarian ligament of female dogs and cats, administration of maropitant to the anesthetized animals caused a significant decrease in the minimum alveolar concentration of sevoflurane, compared with the minimum alveolar concentration of sevoflurane required for animals that did not receive maropitantH.45 The antiemetic, antinausea , and pos­sible adjunct analgesic properties of maropitant make

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it an attractive, cost-effective addition to sedatives and opioid analgesics in anesthetic premedication protocols for veterinary patients.

In the present study, administration of maropitant to dogs at least 15 minutes before hydromorphone sig­nificantly decreased the incidence of vomiting or retch­ing during the first 30 minutes after hydromorphone administration, compared with that for dogs that did not receive maropitant prior to hydromorphone. How­ever, maropitant had to be administered at least 60 min­utes before hydromorphone to significantly decrease signs of nausea. Thus, for dogs in which the avoidance of vomiting and signs of nausea is imperative, maropi­tant should be administered 1 hour prior to an opioid analgesic. The antiemetic, antinausea, and adjunct an­algesic properties of maropitant make it an attractive alternative for inclusion in veterinary preanesthetic protocols.

a. Cerenia, Zoetis, Florham Park, NJ.

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From this month's AJVR ----------------

Multivoxel proton magnetic resonance spectroscopy of inflammatory and neoplastic lesions of the canine brain at 3.0 T

Krystina L. Stad ler et al

Objective-To describe findings of 3.0-T mu ltivoxe l proton magnetic reso nance spectroscopy ('H­MRS) in dogs with inflammatory and neoplastic intracrania l disease and to determine the appli­cab il ity of 'H-MRS for differentiating between inflammatory and neoplastic les ions and between meningiomas and gliomas.

Animals-33 dogs wi th intracranial disease (19 neoplastic (10 meningioma, 7 glioma, and 2 other] and 14 inflammatory) .

Procedures-3.0-T multivoxel 'H-MRS was performed on neoplastic or inflammatory intracranial lesions identifi ed with conventional MRI. N-acetylaspartate (NAA), choline, and creatine concentra ­tions were obtained retrospectively, and metabolite ratios were calculated. Values were compared for metabolites separate ly, between lesion categories (neopl astic or inflammatory), and between neoplastic lesion types (meningioma or glioma) by means of discriminant analysis and 1-way ANOVA.

Results- Th e NAA-to-choline ratio was 82.7% (62/75) accurate for differentiating neoplastic from inflammatory intracranial lesions. Adding the NAA-to-creatine ratio or cho line-to-creatine rati o did not affect the accuracy of differentiation. Neoplastic lesions had lower NAA concentrations and higher choline concentrations than did inflammatory lesions. resu lting in a lower NAA-to-choline ra­tio, lower NAA-to-creatine ratio, and higher choline-to-creatine ratio for neoplasia re lative to inflam­mation . No significant metabolite differences between meningiomas and gliomas were detected.

Conclusions and Clinical Relevance-'H-MRS was effective for differentiating inflammatory lesions from neoplastic lesions in dogs. Metabol ite alterations for 'H-MRS in neoplasia and in­flammation were simi lar to changes described for humans. Use of 'H-MRS provided no additional information for differentiating between meningiomas and gliomas. Proton MRS may be a beneficia l adjunct to conventiona l MRI in patients with high clinical suspicion of inflammatory or neop lastic intracranial lesions. (Am J Vet Res 2014;75:982-989)

AJVR

November 201 4

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1020 Scientific Reports JAVMA, Vol 245, No. 9, November 1, 2014