Evaluation of Diphenhydramine As a Sedative for Dogs EXOTIC Erik H
Total Page：16
File Type：pdf, Size：1020Kb
04-03-0142.qxp 3/11/2005 11:40 AM Page 1092 Evaluation of diphenhydramine as a sedative for dogs EXOTIC Erik H. Hofmeister, DVM, and Christine M. Egger, DVM, MVSc, DACVA SMALL ANIMALS/ slows physical reaction time.3,4 It is indicated for use in allergic conditions, motion sickness, and Parkinson’s Objective—To determine and compare levels of disease.5 In a survey6 of 19,108 patients after conscious sedation achieved by IM administration of diphenhy- surgery for cataract removal, inclusion of diphenhy- dramine, saline (0.9% NaCl) solution, and acepro- dramine in the preanesthetic protocol resulted in sub- mazine in dogs. stantial reduction in incidence of pain during surgery; Design—Prospective randomized study. reduction in dissatisfaction with pain management; Animals—56 dogs. and reduction in incidence of postoperative drowsi- Procedure—Dogs were randomly assigned to ness, nausea, and vomiting. If diphenhydramine had receive diphenhydramine at 2, 4, or 8 mg/kg (0.9, 1.8, similar effects in dogs, its routine inclusion as part of a or 3.6 mg/lb, respectively) IM; acepromazine at 0.1 preanesthetic medication would be warranted. mg/kg (0.05 mg/lb) IM; or saline solution at 0.05 The sedative effects of diphenhydramine in dogs mL/kg (0.02 mL/lb) IM. Sedation was assessed by have been reported only in a secondary reference7 and use of a 6-category descriptive system based on have not been specifically studied in a prospective, ran- observation and interaction. domized, controlled research trial. The purpose of the Results—Dogs in the acepromazine group had signif- study reported here was to determine the sedative icantly higher sedation scores than did dogs in the effects of administration of diphenhydramine in dogs. saline solution or diphenhydramine groups at 30 min- utes. Dogs in the diphenhydramine groups did not have significantly different sedation scores from dogs Materials and Methods in the saline solution group at any time point. Fifty-six random-source (obtained from municipal shel- Conclusions and Clinical Relevance—Diphenhydra- ters), mixed-breed dogs that were anesthetized for a surgical mine did not cause clinically appreciable sedation in exercises laboratory were used in the study. There were 8 healthy dogs. Diphenhydramine is not suitable as a sole dogs in a negative control group that received only saline sedative prior to general anesthesia in dogs. (J Am Vet (0.9% NaCl) solution and 12 dogs in each of 4 other groups. Med Assoc 2005;226:1092–1094) The protocol was approved by the University of Georgia Animal Care and Use Committee, and husbandry was pro- vided according to established institutional guidelines. Any dog deemed unhealthy because of results of physical exami- iphenhydramine is an H1 receptor antagonist used in 1 nation or with an abnormal PCV or total protein concentra- Da variety of allergic conditions. Because of its antihis- tion was excluded. Body condition score (BCS) was assessed taminic and anticholinergic properties, it may cause seda- by use of a previously published system.8 Dogs were ran- tion as an adverse effect in humans.2 Because of this effect, domly assigned to groups that received saline solution (0.05 many practitioners use diphenhydramine for mild seda- mL/kg [0.02 mL/lb], IM), diphenhydraminea (2, 4, or 8 tion in dogs, including sedation for travel, during stress- mg/kg [0.9, 1.8, or 3.6 mg/lb, respectively] IM), or acepro- ful experiences, or before anesthetic induction. Diphen- mazineb (0.1 mg/kg [0.05 mg/lb], IM [positive control hydramine is frequently used in our hospital as a pre- group]). All IM injections were made in the caudal epaxial medication agent before anesthesia in patients with mast musculature by an experienced individual. A single individual (EHH), blinded to treatment group, cell tumors in an attempt to decrease histamine effects performed all sedation scoring. Dogs were housed individual- that result from degranulation of mast cells associated ly during sedation scoring and for at least 12 hours before ini- with tumor manipulation. Diphenhydramine is inexpen- tiation of the study. Dogs were acclimated to the presence of sive, is not a controlled substance, causes minimal cardio- the observer for approximately 10 minutes before administra- vascular suppression, and is readily accessible to general tion of a test substance. During data collection, the dogs were practitioners. All these qualities make it a potentially valu- allowed to move freely in their cages. Sedation scores were able drug for use as a sedative before anesthesia. obtained before administration and at 10, 20, and 30 minutes after administration by use of a modification of a previously In humans, diphenhydramine causes drowsiness, 9 impedes performance on mental cognition tests, and published objective scoring system. A score for analgesia was removed from the original system because none of the drugs administered in this study would be expected to provide anal- From the Departments of Large Animal Medicine (Hofmeister) and Small Animal Medicine and Surgery (Egger), College of Veterinary gesia. The total sedation score for each dog at each time point Medicine, University of Georgia, Athens, GA 30602. Dr. Hofmeister’s was calculated by adding all values for all 6 categories togeth- present address is Department of Small Animal Medicine and er. Any adverse effects were recorded. Between recordings, the Surgery, College of Veterinary Medicine, University of Georgia, observer walked between dog cages, further acclimating the Athens, GA 30602. Dr. Egger’s present address is Department of dogs to the observer’s presence. Small Animal Clinical Sciences, College of Veterinary Medicine, The sedation data were analyzed for normality, and para- University of Tennessee, Knoxville, TN 37996. metric statistics were used for data analysis. For sedation scores, The authors thank Dr. C. Rawlings for technical assistance. weight in kilograms, and BCS, a 1-way ANOVA was used for Address correspondence to Dr. Hofmeister. comparisons among groups. Post hoc analysis was performed by 1092 Scientific Reports: Original Study JAVMA, Vol 226, No. 7, April 1, 2005 04-03-0142.qxp 3/11/2005 11:40 AM Page 1093 Table 1—Mean ± SD sedation scores in dogs given diphenhy- to-5 scoring systems to systems as detailed as the one SMALL ANIMALS/ dramine (2, 4, or 8 mg/kg [0.9, 1.8, or 3.6 mg/lb, respectively], 10-12 IM, [D2, D4, and D8, respectively]), acepromazine (0.1 mg/kg used in the study reported here. None of the seda- [0.05 mg/lb], IM [ACE]), or saline (0.9% NaCl) solution (0.05 tion scoring systems reviewed in the veterinary litera- EXOTIC mL/kg [0.02 mL/lb], IM [SAL]) before (time 0) and 10, 20, and 30 ture has been fully validated. A more detailed scoring minutes after administration. system could not be located in the literature or inde- Time (min) pendently derived, so we believe that the system we used was as sensitive as possible in a clinical setting. Group 0 10 20 30 It is possible that diphenhydramine causes seda- D2 –3.25 Ϯ 3.33 –0.67 Ϯ 2.77a 0.0 Ϯ 2.89a 1.0 Ϯ 2.89a tion only after oral administration. The pharmacoki- D4 –0.58 Ϯ 3.37 0.25 Ϯ 2.8 1.0 Ϯ 2.95 1.75 Ϯ 3.86a D8 –1.08 Ϯ 2.54 1.83 Ϯ 2.25a 2.0 Ϯ 2.80a 3.08 Ϯ 2.15a netics of diphenhydramine in dogs have been evaluat- ACE –2.33 Ϯ 4.14 1.17 Ϯ 2.95a 3.17 Ϯ 3.16a 6.08 Ϯ 2.97a,b ed only in 1 publication, which reported data from SAL –2.13 Ϯ 4.91 –0.63 Ϯ 3.58 1.13 Ϯ 4.32a 1.5 Ϯ 3.89a only 2 dogs.13 Thus, we cannot comment on the Maximum possible sedation score is 14. bioavailability or plasma concentrations of diphenhy- aSignificantly (P Ͻ 0.05) different from value at time 0. dramine after administration PO or IM, and we cannot bSignificantly (P Ͻ 0.05) different from SAL, D2, D4, and D8 at this correlate sedation levels with plasma concentrations of time point. the drug because this was not investigated. We recorded sedation scores for 30 minutes after use of the Tukey multiple-comparison test. A 1-way ANOVA for administration, which may have been inadequate for repeated measures was used to test for changes within a treat- ment group over time. When significance was found, post hoc efficacious plasma concentrations to be reached. analysis was performed by use of the Tukey multiple-compari- However, in cats, behavior changes were observed as son test. A commercial statistical software package was used for early as 30 minutes after oral administration of diphen- all analyses.c Statistical significance was set at P < 0.05. hydramine at 3 mg/kg (1.4 mg/lb).14 We chose to stop recording sedation at 30 minutes because, when evalu- Results ated for use as a sedative before anesthesia, an onset There were no significant differences among time > 30 minutes is not likely to be clinically useful. groups for weight or BCS. There were no significant However, if sedation occurs at a later time point, the differences among groups for sedation scores at 0, 10, drug may contribute to increased anesthetic depth or and 20 minutes. At 30 minutes, mean sedation score in prolonged recovery time after general anesthesia. the acepromazine group was significantly higher than The dogs in the present study were all random- that in the saline solution or diphenhydramine groups. source, healthy young dogs. Many were either quite agi- Sedation scores increased over time for all groups tated and energetic or somewhat frightened and timid.