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A retrospective study of fecal output and postprocedure colic in 246 horses undergoing standing sedation with detomidine, or general anesthesia with or without detomidine
Veterinary Anaesthesia and Analgesia 2019, 46, 458e465
https://doi.org/10.1016/j.vaa.2019.03.006
RESEARCH PAPER
A retrospective study of fecal output and postprocedure colic in 246 horses undergoing standing sedation with detomidine, or general anesthesia with or without detomidine Christopher J Thibaulta, Deborah V Wilsona, Sheilah A Robertsonb, Dhruv Sharmac & Marc A Kinsleyd a b
Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA Lap of Love Veterinary Hospice, Lutz, FL, USA
c
Center for Statistical Training and Consulting, Michigan State University, East Lansing, MI, USA
d
Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA
Correspondence: Deborah V Wilson, Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI, USA. E-mail: [email protected]
Abstract Objective To determine time to first passage of feces, total fecal piles and incidence of colic in the first 24 hours postprocedure in horses undergoing standing sedation with detomidine, or general anesthesia with or without detomidine. Study design Retrospective cohort study. Animals A total of 246 horses. Methods Records of all horses that underwent standing sedation or general anesthesia between December 2012 and March 2016 were reviewed. Horses aged <6 months, admitted for colic or cesarean section, with inadequate data, and those not administered xylazine and/or detomidine were excluded. Records included patient signalment, fasting duration, procedure performed, drugs administered, time to first feces, number of fecal piles during 24 hours postprocedure and mention of colic. Chi-square, Fisher’s exact and Tukey’s post hoc comparison tests were used. Parametric data were reported as mean ± standard deviation with significance defined as p <0.05. Results In total, 116 and 57 horses underwent general anesthesia without detomidine (group GA) and with detomidine (group GAeD), respectively, and remaining 73 horses underwent standing sedation with detomidine (group SeD). Detomidine dose was significantly higher in group SeD than in group GAeD. Time to first feces was longer (7.1 ± 4.2 hours), and group SeD horses passed one fewer fecal pile (6.3 ± 2.4) than group GA horses. There was no interaction between detomidine treatment and preprocedure food withholding and the time to first feces or 458
the number of fecal piles in the first 24 hours postprocedure. Overall, seven horses (2.8%) showed signs of colic (five, one and one in GA, GAeD and SeD, respectively). Conclusions and clinical relevance Detomidine administration, as part of an anesthetic protocol or for standing sedation procedures, should not be expected to contribute to postprocedural colic. Keywords detomidine, fasting, fecal output, horse, postprocedure colic, sedation. Introduction Gastrointestinal (GI) dysfunction induced by pain, stress, changes in management or drugs can manifest as reduced GI motility, delayed intestinal transit times and reduced postprocedural fecal output, and contributes to the development of postprocedural colic (PPC) in horses (Roger & Ruckebusch 1987; Little et al. 2001; Roussel et al. 2001; Cohen et al. 2004; Senior et al. 2004, 2006; Andersen et al. 2006; Boscan et al. 2006; Nelson et al. 2013; Scherrer et al. 2016; Curto et al. 2018). One study reported abdominal pain in 2.8% (12 out of 416) of horses after anesthesia, with risk factors for developing signs of abdominal pain including time to passage of first feces 7 hours and production of less than four fecal piles in the first 24 hours (Nelson et al. 2013). Routine monitoring of these variables in horses after anesthesia should allow early identification of a problem and therapeutic intervention. PPC increases morbidity, mortality, hospitalization time and cost of treatment in affected horses. Colic has been reported following general anesthesia in 1.5e12% of horses (Little et al.
Retrospective study of postanesthetic colic CJ Thibault et al.
2001; Mircica et al. 2003; Senior et al. 2004, 2006; Andersen et al. 2006; Nelson et al. 2013; Bailey et al. 2016; Scherrer et al. 2016; Secor et al. 2018). Since 1987, there have been over 20 studies published evaluating the risk factors associated with PPC. Perioperative administration of specific medications, including non-steroidal anti-inflammatory drugs (NSAIDs), sodium benzylpenicillin, ceftiofur sodium and anesthesia with isoflurane, have been reported to increase the risk of PPC, whereas romifidine administration is associated with a reduced risk (Mircica et al. 2003; Andersen et al. 2006; Boscan et al. 2006; Jago et al. 2015; Scherrer et al. 2016). Suppression of GI motility is a well-recognized side effect of a2-adrenergic agonist drugs (Daunt & Steffey 2002; Elfenbein et al. 2009). Studies have demonstrated decreases in gastric emptying, duodenal contractions, cecal motility and colonic activity following administration of these drugs (Roger & Ruckebusch 1987; Merritt et al. 1998; Sutton et al. 2002; Elfenbein et al. 2009). Xylazine, an a2-adrenergic agonist, reduced the spike burst duration of smooth muscle contraction in the ileum, right ventral colon and small colon, and decreased the cecal emptying rate of radiolabeled markers (Lester et al. 1998). Xylazine reduced intestinal motor activity in a dose-dependent manner, especially in the left ventral colon (Roger & Ruckebusch 1987). Detomidine produces a dose-dependent slowing of gastric emptying that is not reported with xylazine; the addition of butorphanol increases this delay (Sutton et al. 2002). An intravenous (IV) detomidine bolus produced a non-doseedependent decrease in the amplitude of duodenal contractions for 50 minutes after administration, and based on real-time volumetric movement, the effects were both immediate and profound (Elfenbein et al. 2009). Activity in the entire large intestine was inhibited for 60e180 minutes following detomidine (0.1 mg kg1) IV and abolished cecal electrophysiologic activity for 10e15 minutes (Roger & Ruckebusch 1987). After detomidine (0.02 mg kg1) administration, motility resumed within 120 minutes (Elfenbein et al. 2009). The left dorsal colon, left ventral colon and cecum have a greater sensitivity than the jejunum to a2-adrenergic agonist drugs, with detomidine being a more potent inhibitor of motility than xylazine (Adams et al. 1984; Sasaki et al. 2000). Detomidine is used as a bolus or infusion in many clinical scenarios; because of its potency and duration of action on the GI tract, investigation of its impact on PPC and fecal production in horses seems warranted. Within our hospital, there was a clinical impression that detomidine administration was a cause of PPC. In a literature search, no published clinical studies were found on the relationship between detomidine and development of PPC. The aim of this retrospective study was to determine the time to passage of feces, total fecal piles observed in the first 24 hours postprocedure and the incidence of colic in horses
undergoing standing sedation with detomidine or general anesthesia with or without detomidine. Our hypotheses were 1) that detomidine administration by infusion for standing sedation or as part of an anesthetic protocol was associated with increased time to passage of feces and a reduction of total observed fecal piles, and 2) that detomidine was associated with an increased risk for developing PPC. The objectives were to calculate time to passage of first feces postprocedure, record total observed fecal piles in the 24 hours postprocedure and the risk of PPC in three groups of horsesdthose undergoing general anesthesia without detomidine (group GA), and those undergoing general anesthesia with detomidine administration (group GAeD) and those undergoing standing sedation with detomidine infusion (group SeD). Materials and methods The study was designed as a retrospective, cohort study. Clinical records of horses at the College of Veterinary Medicine, Michigan State University, MI, USA, that underwent general anesthesia or sedation between December 2012 and March 2016 (40 months) were electronically searched and manually reviewed. Institutional approval was not required for medical records review. Any horse aged <6 months, that underwent emergency abdominal surgery, was admitted for colic as the primary complaint, not administered xylazine and/or detomidine and records with inadequate data were excluded. Horses treated with topical ophthalmic atropine were excluded from statistical analysis. All included horses were American Society of Anesthesiologists (ASA) physical status I or II. Data collected from the patient records included signalment (age, breed and sex), ASA status, type of procedure, preanesthetic weight, heart rate (HR), respiratory rate (fR), temperature, duration of food (hay) withholding prior to the procedure, time of first feces and number of fecal piles observed during the first 24 hours postprocedure. Every medical record was manually checked for the word colic after the procedure. Details of medical and surgical treatment of colic were extracted. All periprocedural sedatives, tranquillizers, opioids, NSAIDs, antibiotics and lidocaine infusions were recorded. Normal practice management within the hospital is that grain is withheld from all horses starting 24 hours prior to anesthesia or sedation. Hay is always provided until the time of surgery (0 hour food withholding) unless otherwise directed by the primary clinician, and this was noted in the record. Based upon clinician preferences, some horses have hay withheld for different periods before a procedure. Access to water is never restricted. The duration of fasting was calculated as the interval between the time during which all food was withheld until the time of induction of anesthesia or sedation. Feeding after anesthesia or sedation follows a standard protocol. At 30 minutes after the horse is returned to its stall, a handful of hay
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Retrospective study of postanesthetic colic CJ Thibault et al.
is initially offered, followed by a one-half flake (approximately 0.71 kg) every 2 hours for two feedings, and finally one flake of hay every 4 hours until discharge from the hospital. When a part of the individual’s normal diet, grain is reintroduced after discharge from the hospital. Neither total food nor water intake is quantified. Antibiotics and NSAIDs were administered to all horses prior to surgery. The standard premedication for all horses undergoing general anesthesia is xylazine (XylaMed; MWI Animal Health, ID, USA) IV or detomidine (Dormosedan; Zoetis Inc., MI, USA) intramuscularly. Additional xylazine IV is administered to any horse immediately before induction of general anesthesia if not adequately sedate. This means the majority of horses (170/173) were administered xylazine IV. Before recovery from anesthesia, small doses of xylazine, or occasionally detomidine, are administered IV. A combination of ketamine (VetaKet; Akorn Animal Health Inc., IL, USA) and diazepam (Diazepam; Hospira Inc., IL, USA) or midazolam (Midazolam Injection USP; West-Ward Pharmaceutical Corp., NJ, USA) IV was used to induce general anesthesia, and anesthesia was maintained with isoflurane (Isoflurane Inhalation Agent USP; Akorn Animal Heath Inc.) and oxygen with intermittent positive pressure ventilation. During general anesthesia, horses were administered lactated Ringer’s solution (Vetivex; Dechra Veterinary Products LLC, KS, USA) at 5 mL kge1 houre1. For procedures performed standing, detomidine was diluted to a concentration of 0.05 mg mLe1 in 0.9% saline, quantitated based on graduated markings on the bag, which was administered through IV administration tubing delivering lactated Ringer’s solution during the procedure. The sedation protocol was administration of detomidine (0.006 mg kge1) IV as a bolus, followed by an infusion (0.003e0.024 mg kge1 houre1) with the rate adjusted by the anesthetist as needed (Van Dijk et al. 2003). Horses with PPC all had specific mention of colic in the medical record. The medical records of the horses with PPC were reviewed by two clinicians (MAK and CJT) to confirm their inclusion. Hospital protocol requires that all animals are closely monitored postoperatively: observation every hour by a licensed veterinary technician who records HR, fR, presence/ absence by auscultation of GI sounds in any/all four quadrants, animal behavior indicating abdominal discomfort and the number of fecal piles in the stall, after which the stall is cleaned. Neither fecal weight nor volume is quantified. Horses are also routinely assessed by a clinician after the procedure when returned to the stall, again the next morning before 08:00 hours and at any other time as required. Rectal temperature is measured and recorded every morning. The duration of anesthesia was defined as the time from induction until the horse was extubated. Duration of standing sedation was the time from bolus administration of detomidine until the detomidine infusion was stopped. Interval between 460
extubation, or discontinuation of detomidine infusion and the first fecal pile was calculated, and the number of fecal piles in the 24 hours postprocedure was recorded. Statistical analysis All data management and analysis were performed using R statistical software Version 3.5.0 for Windows [R Core Team (2018) R Foundation for Statistical Computing, Austria]. The distribution of continuous variables was assessed with skewness and kurtosis tests for normality. Chi-squared (or Fisher small sample size exact) tests were used to study the association between two categorical variables, and analysis of variance models were used to test the effects of treatment on continuous outcomes. Where significant differences were present, Tukey’s post hoc comparison was used. For analysis, fasting duration was categorized as none (0 hours), short (12 hours), or extended (>12 hours) (Senior et al. 2004, 2006; Schoster et al. 2016). Parametric data were reported as mean ± standard deviation. The level of significance was defined as p-value of <0.05. Overall, three groups were identified; general anesthesia without (group GA) and with detomidine administration (group GAeD) and standing sedation with detomidine (group SeD). Descriptive data from seven horses treated with topical ophthalmic atropine were retained in the case series, but their data were excluded from analysis. Results The preliminary electronic medical search identified 364 horses that underwent general anesthesia or standing sedation for procedures during the selected study period. Of these, 118 horses did not meet the criteria for inclusion in the study: 75 were presented to the hospital with colic, 25 were discharged the same day or did not have enough data for inclusion, nine were aged <6 months, one required caesarean section, seven were euthanized under general anesthesia and one was administered romifidine only. During the study period, 225 horses had 246 general anesthesia or sedation events; two procedures on 13 horses and three procedures on four horses. Median time between procedures on these 17 horses was 30 days (range, 1e455 days), and 10 horses were discharged from the hospital between procedures. Of the 246 procedures performed, there were 116 horses in GA, 57 horses in GAeD and 73 horses in SeD. Breeds represented were 62 Warmbloods, 55 Quarter Horses, 39 Thoroughbreds, 18 Arabians, 13 Standardbreds and 59 mixed breed horses. The age and weight were 9.1 ± 6.0 years and 539 ± 135 kg, respectively. Procedures included soft tissue surgery (GA: 23, GAeD: 24, SeD: 61), orthopedic surgery (GA: 58, GAeD: 26, SeD: 1), advanced imaging (computerized tomography or magnetic resonance imaging; GA: 31, GAeD: 4, SeD: 0) and ophthalmic surgery (GA: 4,
© 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., 46, 458e465
Retrospective study of postanesthetic colic CJ Thibault et al.
GAeD: 3, SeD: 11). The procedure duration was significantly longer in SeD (2.05 ± 0.83 hours) versus GA (1.70 ± 0.50; p < 0.01) and GAeD (1.81 ± 0.51 hours; p ¼ 0.07). The time to first passage of feces was longer in SeD (p ¼ 0.03) and fewer total fecal piles were recorded during the first 24 hours postoperatively (p < 0.01) than in GA (Table 1). PPC was observed in seven out of 246 horses (2.8%; Table 2). Of these horses, two had been administered detomidine (one each in SeD and GAeD). All horses survived to hospital discharge; six horses responded to medical management, and in one horse, exploratory laparotomy revealed gas distension and no mechanical obstruction. Hay was not withheld before the procedure for 157 out of 246 horses, 55 horses had a short fast and 34 had an extended fast. Duration of food withholding was not correlated with the time to first feces (p ¼ 0.10). There was also no correlation between detomidine administration and food withholding on the time to first feces or the number of fecal piles in the first 24 hours postprocedure. Where results of abdominal auscultation were reported, borborygmi were present in all four quadrants in 85% of horses (GA, 100/112 horses; GAeD, 46/56 horses; SeD, 59/72 horses) when evaluated 5.6 ± 2.6 hours either after tracheal extubation or stopping the detomidine infusion. Borborygmi were present in all four quadrants in 90% of horses on the following morning (GA, 104/111 horses; GAeD, 50/57 horses; SeD, 63/73 horses). Results of auscultation were missing at the first time point from four horses in GA and from one horse in both GAeD and SeD. Results of auscultation were missing at the second time point from five horses in GA. Cumulative detomidine dose in SeD was 0.030 ± 0.030 mg kge1, significantly higher than that in GAeD (0.019 ± 0.007 mg kge1; p < 0.01). Total detomidine dose was not reported for 15 horses in SeD, but all 15 horses underwent a prolonged detomidine infusion to facilitate their surgical procedure. Detomidine was administered prior to recovery in an unspecified dose in one horse in GAeD. Xylazine IV was administered to every horse in GA (0.95 ± 0.31 mg kge1), to 54 horses in GAeD (0.62 ± 0.31 mg kge1)
and to 12 horses in SeD (0.38 ± 0.24 mg kge1). Xylazine dose differed significantly among groups with all pairwise comparisons significantly different from each other (p < 0.01). A total of 164 horses (67%) were administered an opioid during the procedure. In GA, 68 horses were administered butorphanol (Butorphic; Akorn Animal Health Inc.) and one was administered morphine (Morphine Sulfate Injection USP; West-Ward Pharmaceutical Corp.). In GAeD, 30 horses were administered butorphanol, one morphine and four methadone (Methadone Hydrochloride Injection USP; Akorn Animal Health Inc.). In SeD, 22 horses were administered butorphanol, 26 morphine and nine methadone. Multiple opioids were administered to three horses during the same procedure: two horses were administered morphine and butorphanol and one horse methadone and butorphanol. Of the seven PPC horses, five horses were administered butorphanol and two horses were administered no opioid. Lidocaine (Lidocaine 2%; MWI Animal Health) was administered as an infusion to 61 horses; 31 (26.9%) in GA, 20 (35.7%) in GAeD and 10 (14.7%) in SeD. Of the seven horses with PPC, three were administered a lidocaine infusion during the procedure. Of the 18 horses undergoing ophthalmologic procedures, 17 were enucleations with bilateral enucleations in two horses, and one horse underwent third eyelid removal. Ocular disease resulting in enucleation included corneal diseases in 12 horses, intraocular disease in four horses and exophthalmos in one horse. During the procedure, 10 horses were administered peribulbar bupivacaine (Bupivacaine Hydrochloride Injection USP; AuroMedics Pharma LLC, NJ, USA). Topical ophthalmic atropine (ISOPTO Atropine 1%, Alcon, TX, USA) was administered to seven of 12 horses with corneal disease (1 mg per horse) every 12e24 hours, and only one eye was treated in each case. Treatment was for 4 days in two horses, 7 days in four horses and for 3 weeks in one horse before the surgical procedure. In the latter horse, topical ophthalmic atropine was administered prior to unilateral enucleation and continued postoperatively in the other eye with no PPC. No atropine-treated horses displayed signs of colic
Table 1 Observed fecal piles in 239 horses after general anesthesia without detomidine (group GA), after general anesthesia that included detomidine (group GAeD) and after sedation with detomidine (group SeD). Data from seven horses treated with topical ophthalmologic atropine were excluded from statistical analysis Variable
Time to first feces (hours) Fecal piles in 24 hours
Group GA (n ¼ 115)
GAeD (n ¼ 56)
SeD (n ¼ 68)
5.5 ± 3.9* 7.7 ± 3.3*
6.3 ± 3.2 7.0 ± 3.2
6.8 ± 4.1 6.3 ± 2.4
n, number of horses. Data are mean ± standard deviation. * GA significantly different from SeD (p < 0.01).
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Retrospective study of postanesthetic colic CJ Thibault et al. Table 2 Descriptive information from seven horses that underwent general anesthesia or sedation procedures that developed postprocedural colic (PPC) Horse number
Group
Procedure
Food withholding (hours)
Adjunctive drugs
Time to first feces (hours)
Fecal piles/24 hours
1 2* 3 4 5 6 7
GA GAeD GA SeD GA GA GA
P1 Fracture Enucleation Arthroscopy Sinusotomy Bursoscopy Enucleation P1 Fracture
0 0 0 5 2 0 0
B B None B L B, L B, L
5 13 3 2 3 6 5
6 5 8 9 8 9 6
Group: GA, general anesthesia; GAeD, general anesthesia including detomidine; SeD, sedation with detomidine. Procedure: P1, first phalanx. Food withholding: 0, hay was provided until the time of surgery (horses 1e3, 6, 7); 2, 5, hay withheld for 2 hours (horse 5) or 5 hours (horse 4) before surgery. Adjunctive drugs, drugs administered during procedure; B, butorphanol; L, lidocaine. *Horse 2 required medical and surgical treatment for PPC.
before anesthesia; one developed PPC after enucleation (Table 2). Of the atropine-treated horses, six were also administered topical ophthalmic voriconazole (Voriconazole; Alvogen Inc., NJ, USA); no other antifungals were administered. Discussion The results of this retrospective study indicate that when added to an anesthetic protocol, detomidine administration does not influence the time to first fecal passage or number of piles in the first 24 hours. Detomidine infusion for standing sedation was associated with prolonged time to first fecal passage and approximately one less fecal pile in 24 hours. The number of horses developing PPC was at the low end of previously published incidence (Little et al. 2001; Mircica et al. 2003; Senior et al. 2004, 2006; Andersen et al. 2006; Nelson et al. 2013; Bailey et al. 2016; Scherrer et al. 2016; Secor et al. 2018). The hypothesis that administration of detomidine would be associated with an increased incidence of PPC was not supported. Detomidine is commonly used for its analgesic properties in horses (Daunt & Steffey 2002). Despite profound effects on gastric emptying, duodenal contractions, cecal and colonic activity (Roger & Ruckebusch 1987; Merritt et al. 1998; Sutton et al. 2002; Elfenbein et al. 2009), the duration of these effects appears to be dose-dependent and unlikely to extend much beyond the period of drug administration. A single bolus of detomidine (0.005 mg kge1) IV in horses provided sedation for 30 minutes and reduced intestinal motility for up to 75 minutes (Gozalo-Marcilla et al. 2017). In another study, a single bolus dose of detomidine (0.02 mg kge1) reduced intestinal motility for 4 hours (Pimenta et al. 2011). Standing procedures avoid administration of general anesthesia but require higher doses of sedative agents administered over a longer period, potentiating increases in dose-dependent side effects. The cumulative detomidine dose was high in the 462
sedation group, and approximately double than that administered to horses during general anesthesia. In the present study, time to passage of the first feces postprocedure was approximately 6 hours. This is similar to that previously reported in 376 horses (Nelson et al. 2013). However, horses in all groups in the present study produced three to four more fecal piles in the first 24 hours after a procedure than those in previously published studies (Little et al. 2001; Nelson et al. 2013). This is likely the result of differences in dietary management among institutions. Results of two other retrospective studies reporting data from horses that fasted for either 6 hours (Nelson et al. 2013) or over 12 hours (Little et al. 2001) suggested that increased time of food withholding prior to a procedure would be associated with reduced fecal output in the first 24 hours. However, results of the present study suggest that withholding hay for up to 24 hours did not impact time to first fecal passage or number of piles produced in 24 hours postprocedure, particularly when combined with the specific and regimented refeeding protocol in our hospital. An opioid was administered to 68% of the horses in the present study during the procedure. None of the PPC horses in this study were administered morphine, which is the drug most investigated regarding its contribution to colic in horses. Several studies have shown that morphine (0.5e1.0 mg kge1) IV is linked to delays in GI transit and increased incidence of colic (Kohn & Muir 1988; Senior et al. 2004; Boscan et al. 2006). However, morphine administered in the dose used in this study (0.1 mg kge1 IV) has been reported to have no effect on the incidence of PPC (Mircica et al. 2003; Andersen et al. 2006; Senior et al. 2006). Lidocaine exerts an anti-inflammatory (Cook & Blikslager 2008), anesthetic-sparing and mild analgesic effect in horses (Robertson et al. 2005; Doherty & Seddighi 2010), but does not act as an intestinal prokinetic (Milligan et al. 2007; Cook & Blikslager 2008; Okamura et al. 2009) and may even reduce
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Retrospective study of postanesthetic colic CJ Thibault et al.
intestinal motility (Salem et al. 2016). In the present study, lidocaine was administered during the procedure to 25% of all horses, 30% of horses during general anesthesia and 43% of horses that developed PPC. The administration of this drug is a confounder and highlights the limitations of a retrospective study. Between 8% (Scherrer et al. 2016) and 21% (Patipa et al. 2012) of horses hospitalized for ophthalmologic procedures have been reported to manifest PPC. Horses hospitalized for ophthalmic disease may experience pain, stress and administration of drugs decreasing GI motility. In the present study, the incidence of PPC in the horses undergoing ophthalmologic procedures was 11% (two/18), similar to the incidence published in earlier studies. Some controversy persists regarding the role of topical ophthalmologic atropine and PPC in horses, perhaps owing to differences in dosing between institutions and over the years. An early study reports colic in four out of six (60%) horses when high doses of topical ophthalmologic atropine (1 mg houre1 per horse for 24 hours) were administered (Williams et al. 2000). For this reason, and despite the low doses of topical ophthalmologic atropine administered, in the present study, descriptive data from seven atropinetreated horses were reported but were removed from data analysis. Multivariate analysis in three studies reporting data from 299 atropine-treated horses undergoing ophthalmologic procedures determined that atropine treatment was not a risk factor for PPC (Little et al. 2001; Patipa et al. 2012; Scherrer et al. 2016). Only one of these studies (Scherrer et al. 2016) reported the dose of topical ophthalmologic atropine administered, namely 1 mg per horse every 12 hours. A separate study reported that double this dose administered to horses induced no delay in the passage of ingesta, no ileus and no measurable serum levels of atropine (Wehrman et al. 2017). In the present study, topical ophthalmologic antifungal treatment was used in six horses, including one PPC horse. Systemic, but not topical, administration of fluconazole reduces GI motility and results in PPC in horses (Curto et al. 2018). Most of the horses in the present study had borborygmi present when assessed. It should be noted, however, that intensity and presence or absence of borborygmi are subjective assessments and have been shown to poorly predict GI function (Little et al. 2001; Roussel et al. 2001; Cohen et al. 2004; Boscan et al. 2006; Naylor et al. 2006). Previous studies have reported that increased procedure duration is associated with either an increased risk (Little et al. 2001; Roussel et al. 2001; Cohen et al. 2004), no association (Senior et al. 2004; Nelson et al. 2013; Bailey et al. 2016) or a decreased risk (Andersen et al. 2006) of PPC. Procedure duration in the SeD group in the present study was
approximately 0.3 hours longer than that in the GA and GAeD groups, contributing to the increased total dose of detomidine administered. This difference in procedure duration was statistically but not clinically significant. Retrospective studies are associated with several inevitable biases related to collection of historical data, use of clinical patients with confounding conditions and accuracy of reporting. Additional highly-powered prospective studies, ideally placebo-controlled or paired group observational studies are recommended to better understand the impact of detomidine administration on PPC and postprocedural fecal output. Potential confounding factors, such as surgical pain, the duration of fasting and adjunct drug administration, including lidocaine and atropine, could then be controlled. Another limitation of the present study is that fecal output of these horses was not accurately quantified because fecal piles were counted but fecal mass, volume or water content were not measured. Use of a fecal collection device (Elfenbein et al. 2011, 2014) would allow accurate weighing of fecal output. Pain scoring is not routinely performed within our hospital, and implementation of a recognized pain scoring system would enhance animal care and allow assessment of the effects of pain on many variables including colic (van Loon & Van Dierendonck 2018). Conclusion Detomidine administration for sedation for standing procedures prolonged the time to first feces and reduced fecal output by one pile during the 24 hours postprocedure. However, associated with our described refeeding protocol, this is not associated with PPC and has little clinical relevance. Detomidine administration, as part of an anesthetic protocol or for standing sedation procedures, should not be expected to contribute to PPC. The results of this study can be used to support sample size calculations and design issues for future studies. Acknowledgements The authors thank Dr Joe G Hauptman for early statistical and study design advice. Authors' contributions CJT: study design, data acquisition and interpretation. DVW: study design, data interpretation. SAR and MAK: study design. DS: statistical analysis. All authors contributed to preparation of the manuscript and approved the final submission. Conflict of interest statement The authors report no conflict of interest.
© 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., 46, 458e465
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References Adams SB, Lamar CH, Masty J (1984) Motility of the distal portion of the jejunum and pelvic flexure in ponies: effects of six drugs. Am J Vet Res 45, 795e799. Andersen MS, Clark L, Dyson SJ, Newton JR (2006) Risk factors for colic in horses after general anaesthesia for MRI or nonabdominal surgery: absence of evidence of effect from perianaesthetic morphine. Equine Vet J 38, 368e374. Bailey PA, Hague BA, Davis M et al. (2016) Incidence of postanesthetic colic in non-fasted adult equine patients. Can Vet J 57, 1263e1266. Boscan P, Van Hoogmoed LM, Farver TB, Snyder JR (2006) Evaluation of the effects of the opioid agonist morphine on gastrointestinal tract function in horses. Am J Vet Res 67, 992e997. Cohen ND, Lester GD, Sanchez LC et al. (2004) Evaluation of risk factors associated with development of postoperative ileus in horses. J Am Vet Med Assoc 225, 1070e1078. Cook VL, Blikslager AT (2008) Use of systemically administered lidocaine in horses with gastrointestinal tract disease. J Am Vet Med Assoc 232, 1144e1148. Curto EM, Griffith EH, Posner LP et al. (2018) Factors associated with postoperative complications in healthy horses after general anesthesia for ophthalmic versus non-ophthalmic procedures: 556 cases (2012e2014). J Am Vet Med Assoc 252, 1113e1119. Daunt DA, Steffey EP (2002) Alpha-2 adrenergic agonists as analgesics in horses. Vet Clin North Am Equine Pract 18, 39e46. Doherty TJ, Seddighi MR (2010) Local anesthetics as pain therapy in horses. Vet Clin North Am Equine Pract 26, 533e549. Elfenbein JR, Sanchez LC, Robertson SA et al. (2009) Effect of detomidine on visceral and somatic nociception and duodenal motility in conscious adult horses. Vet Anaesth Analg 36, 162e172. Elfenbein JR, Robertson SA, Corser AA et al. (2011) Systemic effects of a prolonged continuous infusion of ketamine in healthy horses. J Vet Intern Med 25, 1134e1137. Elfenbein JR, Robertson SA, MacKay RJ et al. (2014) Systemic and anti-nociceptive effects of prolonged lidocaine, ketamine, and butorphanol infusions alone and in combination in healthy horses. BMC Vet Res 10 (Suppl 1), S6. Gozalo-Marcilla M, Luna SP, Crosignani N et al. (2017) Sedative and antinociceptive effects of different combinations of detomidine and methadone in standing horses. Vet Anaesth Analg 44, 1116e1127. Jago RC, Corletto F, Wright IM (2015) Peri-anaesthetic complications in an equine referral hospital: risk factors for post anaesthetic colic. Equine Vet J 47, 635e640. Kohn CW, Muir WW (1988) Selected aspects of the clinical pharmacology of visceral analgesics and gut motility modifying drugs in the horse. J Vet Intern Med 2, 85e91. Lester GD, Merritt AM, Neuwirth L et al. (1998) Effect of alpha 2adrenergic, cholinergic, and nonsteroidal anti-inflammatory drugs on myoelectric activity of ileum, cecum, and right ventral colon and on cecal emptying of radiolabeled markers in clinically normal ponies. Am J Vet Res 59, 320e327. 464
Little D, Redding WR, Blikslager AT (2001) Risk factors for reduced postoperative fecal output in horses: 37 cases (1997e1998). J Am Vet Med Assoc 218, 414e420. Merritt AM, Burrow JA, Hartless CS (1998) Effect of xylazine, detomidine, and a combination of xylazine and butorphanol on equine duodenal motility. Am J Vet Res 59, 619e623. Milligan M, Beard W, Kukanich B et al. (2007) The effect of lidocaine on postoperative jejunal motility in normal horses. Vet Surg 36, 214e220. Mircica E, Clutton RE, Kyles KW, Blissitt KJ (2003) Problems associated with perioperative morphine in horses: a retrospective case analysis. Vet Anaesth Analg 30, 147e155. Naylor JM, Poirier KL, Hamilton DL, Dowling PM (2006) The effects of feeding and fasting on gastrointestinal sounds in adult horses. J Vet Intern Med 20, 1408e1413. Nelson BB, Lordan EE, Hassel DM (2013) Risk factors associated with gastrointestinal dysfunction in horses undergoing elective procedures under general anaesthesia. Equine Vet J Suppl, 8e14. Okamura K, Sasaki N, Yamada M et al. (2009) Effects of mosapride citrate, metoclopramide hydrochloride, lidocaine hydrochloride, and cisapride citrate on equine gastric emptying, small intestinal and caecal motility. Res Vet Sci 86, 302e308. Patipa LA, Sherlock CE, Witte SH et al. (2012) Risk factors for colic in equids hospitalized for ocular disease. J Am Vet Med Assoc 240, 1488e1493. Pimenta EL, Teixeira Neto FJ, S a PA et al. (2011) Comparative study between atropine and hyoscine-N-butylbromide for reversal of detomidine induced bradycardia in horses. Equine Vet J 43, 332e340. Robertson SA, Sanchez LC, Merritt AM, Doherty TJ (2005) Effect of systemic lidocaine on visceral and somatic nociception in conscious horses. Equine Vet J 37, 122e127. Roger T, Ruckebusch Y (1987) Colonic alpha 2-adrenoceptormediated responses in the pony. J Vet Pharmacol Ther 10, 310e318. Roussel AJ, Cohen ND, Hooper RN, Rakestraw PC (2001) Risk factors associated with development of postoperative ileus in horses. J Am Vet Med Assoc 219, 72e78. Salem SE, Proudman CJ, Archer DC (2016) Has intravenous lidocaine improved the outcome in horses following surgical management of small intestinal lesions in a UK hospital population? BMC Vet Res 12, 157. Sasaki N, Yoshihara T, Hara S (2000) Difference in the motile reactivity of jejunum, cecum, and right ventral colon to xylazine and medetomidine in conscious horses. J Equine Sci 11, 63e68. Scherrer NM, Lassaline M, Richardson DW, Stefanovski D (2016) Interval prevalence of and factors associated with colic in horses hospitalized for ocular or orthopedic disease. J Am Vet Med Assoc 249, 90e95. Schoster A, Mosing M, Jalali M et al. (2016) Effects of transport, fasting and anaesthesia on the faecal microbiota of healthy adult horses. Equine Vet J 48, 595e602. Secor EJ, Gutierrez-Nibeyro SD, Clark-Price SC (2018) Comparison of complication rates following elective arthroscopy performed as inpatient versus outpatient surgery in horses. J Am Vet Med Assoc 253, 346e354.
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Retrospective study of postanesthetic colic CJ Thibault et al. Senior JM, Pinchbeck GL, Dugdale AH, Clegg PD (2004) Retrospective study of the risk factors and prevalence of colic in horses after orthopaedic surgery. Vet Rec 155, 321e325. Senior JM, Pinchbeck GL, Allister R et al. (2006) Post anaesthetic colic in horses: a preventable complication? Equine Vet J 38, 479e484. Sutton DG, Preston T, Christley RM et al. (2002) The effects of xylazine, detomidine, acepromazine and butorphanol on equine solid phase gastric emptying rate. Equine Vet J 34, 486e492. Van Dijk P, Lankveld D, Rijkenhuizen A, Jonker FH (2003) Hormonal, metabolic and physiological effects of laparoscopic surgery using a detomidine-buprenorphine combination in standing horses. Vet Anaesth Analg 30, 71e79.
van Loon JPAM, Van Dierendonck MC (2018) Objective pain assessment in horses (2014e2018). Vet J 242, 1e7. Wehrman RF, Gemensky-Metzler AJ, Zibura AE et al. (2017) Objective evaluation of the systemic effects of topical application of 1% atropine sulfate ophthalmic solution in healthy horses. J Am Vet Med Assoc 251, 1324e1330. Williams MM, Spiess BM, Pascoe PJ, O'Grady M (2000) Systemic effects of topical and subconjunctival ophthalmic atropine in the horse. Vet Ophthalmol 3, 193e199. Received 28 August 2018; accepted 25 March 2019. Available online 4 May 2019
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https://doi.org/10.1016/j.vaa.2019.03.006
RESEARCH PAPER
A retrospective study of fecal output and postprocedure colic in 246 horses undergoing standing sedation with detomidine, or general anesthesia with or without detomidine Christopher J Thibaulta, Deborah V Wilsona, Sheilah A Robertsonb, Dhruv Sharmac & Marc A Kinsleyd a b
Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA Lap of Love Veterinary Hospice, Lutz, FL, USA
c
Center for Statistical Training and Consulting, Michigan State University, East Lansing, MI, USA
d
Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA
Correspondence: Deborah V Wilson, Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, 784 Wilson Road, East Lansing, MI, USA. E-mail: [email protected]
Abstract Objective To determine time to first passage of feces, total fecal piles and incidence of colic in the first 24 hours postprocedure in horses undergoing standing sedation with detomidine, or general anesthesia with or without detomidine. Study design Retrospective cohort study. Animals A total of 246 horses. Methods Records of all horses that underwent standing sedation or general anesthesia between December 2012 and March 2016 were reviewed. Horses aged <6 months, admitted for colic or cesarean section, with inadequate data, and those not administered xylazine and/or detomidine were excluded. Records included patient signalment, fasting duration, procedure performed, drugs administered, time to first feces, number of fecal piles during 24 hours postprocedure and mention of colic. Chi-square, Fisher’s exact and Tukey’s post hoc comparison tests were used. Parametric data were reported as mean ± standard deviation with significance defined as p <0.05. Results In total, 116 and 57 horses underwent general anesthesia without detomidine (group GA) and with detomidine (group GAeD), respectively, and remaining 73 horses underwent standing sedation with detomidine (group SeD). Detomidine dose was significantly higher in group SeD than in group GAeD. Time to first feces was longer (7.1 ± 4.2 hours), and group SeD horses passed one fewer fecal pile (6.3 ± 2.4) than group GA horses. There was no interaction between detomidine treatment and preprocedure food withholding and the time to first feces or 458
the number of fecal piles in the first 24 hours postprocedure. Overall, seven horses (2.8%) showed signs of colic (five, one and one in GA, GAeD and SeD, respectively). Conclusions and clinical relevance Detomidine administration, as part of an anesthetic protocol or for standing sedation procedures, should not be expected to contribute to postprocedural colic. Keywords detomidine, fasting, fecal output, horse, postprocedure colic, sedation. Introduction Gastrointestinal (GI) dysfunction induced by pain, stress, changes in management or drugs can manifest as reduced GI motility, delayed intestinal transit times and reduced postprocedural fecal output, and contributes to the development of postprocedural colic (PPC) in horses (Roger & Ruckebusch 1987; Little et al. 2001; Roussel et al. 2001; Cohen et al. 2004; Senior et al. 2004, 2006; Andersen et al. 2006; Boscan et al. 2006; Nelson et al. 2013; Scherrer et al. 2016; Curto et al. 2018). One study reported abdominal pain in 2.8% (12 out of 416) of horses after anesthesia, with risk factors for developing signs of abdominal pain including time to passage of first feces 7 hours and production of less than four fecal piles in the first 24 hours (Nelson et al. 2013). Routine monitoring of these variables in horses after anesthesia should allow early identification of a problem and therapeutic intervention. PPC increases morbidity, mortality, hospitalization time and cost of treatment in affected horses. Colic has been reported following general anesthesia in 1.5e12% of horses (Little et al.
Retrospective study of postanesthetic colic CJ Thibault et al.
2001; Mircica et al. 2003; Senior et al. 2004, 2006; Andersen et al. 2006; Nelson et al. 2013; Bailey et al. 2016; Scherrer et al. 2016; Secor et al. 2018). Since 1987, there have been over 20 studies published evaluating the risk factors associated with PPC. Perioperative administration of specific medications, including non-steroidal anti-inflammatory drugs (NSAIDs), sodium benzylpenicillin, ceftiofur sodium and anesthesia with isoflurane, have been reported to increase the risk of PPC, whereas romifidine administration is associated with a reduced risk (Mircica et al. 2003; Andersen et al. 2006; Boscan et al. 2006; Jago et al. 2015; Scherrer et al. 2016). Suppression of GI motility is a well-recognized side effect of a2-adrenergic agonist drugs (Daunt & Steffey 2002; Elfenbein et al. 2009). Studies have demonstrated decreases in gastric emptying, duodenal contractions, cecal motility and colonic activity following administration of these drugs (Roger & Ruckebusch 1987; Merritt et al. 1998; Sutton et al. 2002; Elfenbein et al. 2009). Xylazine, an a2-adrenergic agonist, reduced the spike burst duration of smooth muscle contraction in the ileum, right ventral colon and small colon, and decreased the cecal emptying rate of radiolabeled markers (Lester et al. 1998). Xylazine reduced intestinal motor activity in a dose-dependent manner, especially in the left ventral colon (Roger & Ruckebusch 1987). Detomidine produces a dose-dependent slowing of gastric emptying that is not reported with xylazine; the addition of butorphanol increases this delay (Sutton et al. 2002). An intravenous (IV) detomidine bolus produced a non-doseedependent decrease in the amplitude of duodenal contractions for 50 minutes after administration, and based on real-time volumetric movement, the effects were both immediate and profound (Elfenbein et al. 2009). Activity in the entire large intestine was inhibited for 60e180 minutes following detomidine (0.1 mg kg1) IV and abolished cecal electrophysiologic activity for 10e15 minutes (Roger & Ruckebusch 1987). After detomidine (0.02 mg kg1) administration, motility resumed within 120 minutes (Elfenbein et al. 2009). The left dorsal colon, left ventral colon and cecum have a greater sensitivity than the jejunum to a2-adrenergic agonist drugs, with detomidine being a more potent inhibitor of motility than xylazine (Adams et al. 1984; Sasaki et al. 2000). Detomidine is used as a bolus or infusion in many clinical scenarios; because of its potency and duration of action on the GI tract, investigation of its impact on PPC and fecal production in horses seems warranted. Within our hospital, there was a clinical impression that detomidine administration was a cause of PPC. In a literature search, no published clinical studies were found on the relationship between detomidine and development of PPC. The aim of this retrospective study was to determine the time to passage of feces, total fecal piles observed in the first 24 hours postprocedure and the incidence of colic in horses
undergoing standing sedation with detomidine or general anesthesia with or without detomidine. Our hypotheses were 1) that detomidine administration by infusion for standing sedation or as part of an anesthetic protocol was associated with increased time to passage of feces and a reduction of total observed fecal piles, and 2) that detomidine was associated with an increased risk for developing PPC. The objectives were to calculate time to passage of first feces postprocedure, record total observed fecal piles in the 24 hours postprocedure and the risk of PPC in three groups of horsesdthose undergoing general anesthesia without detomidine (group GA), and those undergoing general anesthesia with detomidine administration (group GAeD) and those undergoing standing sedation with detomidine infusion (group SeD). Materials and methods The study was designed as a retrospective, cohort study. Clinical records of horses at the College of Veterinary Medicine, Michigan State University, MI, USA, that underwent general anesthesia or sedation between December 2012 and March 2016 (40 months) were electronically searched and manually reviewed. Institutional approval was not required for medical records review. Any horse aged <6 months, that underwent emergency abdominal surgery, was admitted for colic as the primary complaint, not administered xylazine and/or detomidine and records with inadequate data were excluded. Horses treated with topical ophthalmic atropine were excluded from statistical analysis. All included horses were American Society of Anesthesiologists (ASA) physical status I or II. Data collected from the patient records included signalment (age, breed and sex), ASA status, type of procedure, preanesthetic weight, heart rate (HR), respiratory rate (fR), temperature, duration of food (hay) withholding prior to the procedure, time of first feces and number of fecal piles observed during the first 24 hours postprocedure. Every medical record was manually checked for the word colic after the procedure. Details of medical and surgical treatment of colic were extracted. All periprocedural sedatives, tranquillizers, opioids, NSAIDs, antibiotics and lidocaine infusions were recorded. Normal practice management within the hospital is that grain is withheld from all horses starting 24 hours prior to anesthesia or sedation. Hay is always provided until the time of surgery (0 hour food withholding) unless otherwise directed by the primary clinician, and this was noted in the record. Based upon clinician preferences, some horses have hay withheld for different periods before a procedure. Access to water is never restricted. The duration of fasting was calculated as the interval between the time during which all food was withheld until the time of induction of anesthesia or sedation. Feeding after anesthesia or sedation follows a standard protocol. At 30 minutes after the horse is returned to its stall, a handful of hay
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Retrospective study of postanesthetic colic CJ Thibault et al.
is initially offered, followed by a one-half flake (approximately 0.71 kg) every 2 hours for two feedings, and finally one flake of hay every 4 hours until discharge from the hospital. When a part of the individual’s normal diet, grain is reintroduced after discharge from the hospital. Neither total food nor water intake is quantified. Antibiotics and NSAIDs were administered to all horses prior to surgery. The standard premedication for all horses undergoing general anesthesia is xylazine (XylaMed; MWI Animal Health, ID, USA) IV or detomidine (Dormosedan; Zoetis Inc., MI, USA) intramuscularly. Additional xylazine IV is administered to any horse immediately before induction of general anesthesia if not adequately sedate. This means the majority of horses (170/173) were administered xylazine IV. Before recovery from anesthesia, small doses of xylazine, or occasionally detomidine, are administered IV. A combination of ketamine (VetaKet; Akorn Animal Health Inc., IL, USA) and diazepam (Diazepam; Hospira Inc., IL, USA) or midazolam (Midazolam Injection USP; West-Ward Pharmaceutical Corp., NJ, USA) IV was used to induce general anesthesia, and anesthesia was maintained with isoflurane (Isoflurane Inhalation Agent USP; Akorn Animal Heath Inc.) and oxygen with intermittent positive pressure ventilation. During general anesthesia, horses were administered lactated Ringer’s solution (Vetivex; Dechra Veterinary Products LLC, KS, USA) at 5 mL kge1 houre1. For procedures performed standing, detomidine was diluted to a concentration of 0.05 mg mLe1 in 0.9% saline, quantitated based on graduated markings on the bag, which was administered through IV administration tubing delivering lactated Ringer’s solution during the procedure. The sedation protocol was administration of detomidine (0.006 mg kge1) IV as a bolus, followed by an infusion (0.003e0.024 mg kge1 houre1) with the rate adjusted by the anesthetist as needed (Van Dijk et al. 2003). Horses with PPC all had specific mention of colic in the medical record. The medical records of the horses with PPC were reviewed by two clinicians (MAK and CJT) to confirm their inclusion. Hospital protocol requires that all animals are closely monitored postoperatively: observation every hour by a licensed veterinary technician who records HR, fR, presence/ absence by auscultation of GI sounds in any/all four quadrants, animal behavior indicating abdominal discomfort and the number of fecal piles in the stall, after which the stall is cleaned. Neither fecal weight nor volume is quantified. Horses are also routinely assessed by a clinician after the procedure when returned to the stall, again the next morning before 08:00 hours and at any other time as required. Rectal temperature is measured and recorded every morning. The duration of anesthesia was defined as the time from induction until the horse was extubated. Duration of standing sedation was the time from bolus administration of detomidine until the detomidine infusion was stopped. Interval between 460
extubation, or discontinuation of detomidine infusion and the first fecal pile was calculated, and the number of fecal piles in the 24 hours postprocedure was recorded. Statistical analysis All data management and analysis were performed using R statistical software Version 3.5.0 for Windows [R Core Team (2018) R Foundation for Statistical Computing, Austria]. The distribution of continuous variables was assessed with skewness and kurtosis tests for normality. Chi-squared (or Fisher small sample size exact) tests were used to study the association between two categorical variables, and analysis of variance models were used to test the effects of treatment on continuous outcomes. Where significant differences were present, Tukey’s post hoc comparison was used. For analysis, fasting duration was categorized as none (0 hours), short (12 hours), or extended (>12 hours) (Senior et al. 2004, 2006; Schoster et al. 2016). Parametric data were reported as mean ± standard deviation. The level of significance was defined as p-value of <0.05. Overall, three groups were identified; general anesthesia without (group GA) and with detomidine administration (group GAeD) and standing sedation with detomidine (group SeD). Descriptive data from seven horses treated with topical ophthalmic atropine were retained in the case series, but their data were excluded from analysis. Results The preliminary electronic medical search identified 364 horses that underwent general anesthesia or standing sedation for procedures during the selected study period. Of these, 118 horses did not meet the criteria for inclusion in the study: 75 were presented to the hospital with colic, 25 were discharged the same day or did not have enough data for inclusion, nine were aged <6 months, one required caesarean section, seven were euthanized under general anesthesia and one was administered romifidine only. During the study period, 225 horses had 246 general anesthesia or sedation events; two procedures on 13 horses and three procedures on four horses. Median time between procedures on these 17 horses was 30 days (range, 1e455 days), and 10 horses were discharged from the hospital between procedures. Of the 246 procedures performed, there were 116 horses in GA, 57 horses in GAeD and 73 horses in SeD. Breeds represented were 62 Warmbloods, 55 Quarter Horses, 39 Thoroughbreds, 18 Arabians, 13 Standardbreds and 59 mixed breed horses. The age and weight were 9.1 ± 6.0 years and 539 ± 135 kg, respectively. Procedures included soft tissue surgery (GA: 23, GAeD: 24, SeD: 61), orthopedic surgery (GA: 58, GAeD: 26, SeD: 1), advanced imaging (computerized tomography or magnetic resonance imaging; GA: 31, GAeD: 4, SeD: 0) and ophthalmic surgery (GA: 4,
© 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., 46, 458e465
Retrospective study of postanesthetic colic CJ Thibault et al.
GAeD: 3, SeD: 11). The procedure duration was significantly longer in SeD (2.05 ± 0.83 hours) versus GA (1.70 ± 0.50; p < 0.01) and GAeD (1.81 ± 0.51 hours; p ¼ 0.07). The time to first passage of feces was longer in SeD (p ¼ 0.03) and fewer total fecal piles were recorded during the first 24 hours postoperatively (p < 0.01) than in GA (Table 1). PPC was observed in seven out of 246 horses (2.8%; Table 2). Of these horses, two had been administered detomidine (one each in SeD and GAeD). All horses survived to hospital discharge; six horses responded to medical management, and in one horse, exploratory laparotomy revealed gas distension and no mechanical obstruction. Hay was not withheld before the procedure for 157 out of 246 horses, 55 horses had a short fast and 34 had an extended fast. Duration of food withholding was not correlated with the time to first feces (p ¼ 0.10). There was also no correlation between detomidine administration and food withholding on the time to first feces or the number of fecal piles in the first 24 hours postprocedure. Where results of abdominal auscultation were reported, borborygmi were present in all four quadrants in 85% of horses (GA, 100/112 horses; GAeD, 46/56 horses; SeD, 59/72 horses) when evaluated 5.6 ± 2.6 hours either after tracheal extubation or stopping the detomidine infusion. Borborygmi were present in all four quadrants in 90% of horses on the following morning (GA, 104/111 horses; GAeD, 50/57 horses; SeD, 63/73 horses). Results of auscultation were missing at the first time point from four horses in GA and from one horse in both GAeD and SeD. Results of auscultation were missing at the second time point from five horses in GA. Cumulative detomidine dose in SeD was 0.030 ± 0.030 mg kge1, significantly higher than that in GAeD (0.019 ± 0.007 mg kge1; p < 0.01). Total detomidine dose was not reported for 15 horses in SeD, but all 15 horses underwent a prolonged detomidine infusion to facilitate their surgical procedure. Detomidine was administered prior to recovery in an unspecified dose in one horse in GAeD. Xylazine IV was administered to every horse in GA (0.95 ± 0.31 mg kge1), to 54 horses in GAeD (0.62 ± 0.31 mg kge1)
and to 12 horses in SeD (0.38 ± 0.24 mg kge1). Xylazine dose differed significantly among groups with all pairwise comparisons significantly different from each other (p < 0.01). A total of 164 horses (67%) were administered an opioid during the procedure. In GA, 68 horses were administered butorphanol (Butorphic; Akorn Animal Health Inc.) and one was administered morphine (Morphine Sulfate Injection USP; West-Ward Pharmaceutical Corp.). In GAeD, 30 horses were administered butorphanol, one morphine and four methadone (Methadone Hydrochloride Injection USP; Akorn Animal Health Inc.). In SeD, 22 horses were administered butorphanol, 26 morphine and nine methadone. Multiple opioids were administered to three horses during the same procedure: two horses were administered morphine and butorphanol and one horse methadone and butorphanol. Of the seven PPC horses, five horses were administered butorphanol and two horses were administered no opioid. Lidocaine (Lidocaine 2%; MWI Animal Health) was administered as an infusion to 61 horses; 31 (26.9%) in GA, 20 (35.7%) in GAeD and 10 (14.7%) in SeD. Of the seven horses with PPC, three were administered a lidocaine infusion during the procedure. Of the 18 horses undergoing ophthalmologic procedures, 17 were enucleations with bilateral enucleations in two horses, and one horse underwent third eyelid removal. Ocular disease resulting in enucleation included corneal diseases in 12 horses, intraocular disease in four horses and exophthalmos in one horse. During the procedure, 10 horses were administered peribulbar bupivacaine (Bupivacaine Hydrochloride Injection USP; AuroMedics Pharma LLC, NJ, USA). Topical ophthalmic atropine (ISOPTO Atropine 1%, Alcon, TX, USA) was administered to seven of 12 horses with corneal disease (1 mg per horse) every 12e24 hours, and only one eye was treated in each case. Treatment was for 4 days in two horses, 7 days in four horses and for 3 weeks in one horse before the surgical procedure. In the latter horse, topical ophthalmic atropine was administered prior to unilateral enucleation and continued postoperatively in the other eye with no PPC. No atropine-treated horses displayed signs of colic
Table 1 Observed fecal piles in 239 horses after general anesthesia without detomidine (group GA), after general anesthesia that included detomidine (group GAeD) and after sedation with detomidine (group SeD). Data from seven horses treated with topical ophthalmologic atropine were excluded from statistical analysis Variable
Time to first feces (hours) Fecal piles in 24 hours
Group GA (n ¼ 115)
GAeD (n ¼ 56)
SeD (n ¼ 68)
5.5 ± 3.9* 7.7 ± 3.3*
6.3 ± 3.2 7.0 ± 3.2
6.8 ± 4.1 6.3 ± 2.4
n, number of horses. Data are mean ± standard deviation. * GA significantly different from SeD (p < 0.01).
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Retrospective study of postanesthetic colic CJ Thibault et al. Table 2 Descriptive information from seven horses that underwent general anesthesia or sedation procedures that developed postprocedural colic (PPC) Horse number
Group
Procedure
Food withholding (hours)
Adjunctive drugs
Time to first feces (hours)
Fecal piles/24 hours
1 2* 3 4 5 6 7
GA GAeD GA SeD GA GA GA
P1 Fracture Enucleation Arthroscopy Sinusotomy Bursoscopy Enucleation P1 Fracture
0 0 0 5 2 0 0
B B None B L B, L B, L
5 13 3 2 3 6 5
6 5 8 9 8 9 6
Group: GA, general anesthesia; GAeD, general anesthesia including detomidine; SeD, sedation with detomidine. Procedure: P1, first phalanx. Food withholding: 0, hay was provided until the time of surgery (horses 1e3, 6, 7); 2, 5, hay withheld for 2 hours (horse 5) or 5 hours (horse 4) before surgery. Adjunctive drugs, drugs administered during procedure; B, butorphanol; L, lidocaine. *Horse 2 required medical and surgical treatment for PPC.
before anesthesia; one developed PPC after enucleation (Table 2). Of the atropine-treated horses, six were also administered topical ophthalmic voriconazole (Voriconazole; Alvogen Inc., NJ, USA); no other antifungals were administered. Discussion The results of this retrospective study indicate that when added to an anesthetic protocol, detomidine administration does not influence the time to first fecal passage or number of piles in the first 24 hours. Detomidine infusion for standing sedation was associated with prolonged time to first fecal passage and approximately one less fecal pile in 24 hours. The number of horses developing PPC was at the low end of previously published incidence (Little et al. 2001; Mircica et al. 2003; Senior et al. 2004, 2006; Andersen et al. 2006; Nelson et al. 2013; Bailey et al. 2016; Scherrer et al. 2016; Secor et al. 2018). The hypothesis that administration of detomidine would be associated with an increased incidence of PPC was not supported. Detomidine is commonly used for its analgesic properties in horses (Daunt & Steffey 2002). Despite profound effects on gastric emptying, duodenal contractions, cecal and colonic activity (Roger & Ruckebusch 1987; Merritt et al. 1998; Sutton et al. 2002; Elfenbein et al. 2009), the duration of these effects appears to be dose-dependent and unlikely to extend much beyond the period of drug administration. A single bolus of detomidine (0.005 mg kge1) IV in horses provided sedation for 30 minutes and reduced intestinal motility for up to 75 minutes (Gozalo-Marcilla et al. 2017). In another study, a single bolus dose of detomidine (0.02 mg kge1) reduced intestinal motility for 4 hours (Pimenta et al. 2011). Standing procedures avoid administration of general anesthesia but require higher doses of sedative agents administered over a longer period, potentiating increases in dose-dependent side effects. The cumulative detomidine dose was high in the 462
sedation group, and approximately double than that administered to horses during general anesthesia. In the present study, time to passage of the first feces postprocedure was approximately 6 hours. This is similar to that previously reported in 376 horses (Nelson et al. 2013). However, horses in all groups in the present study produced three to four more fecal piles in the first 24 hours after a procedure than those in previously published studies (Little et al. 2001; Nelson et al. 2013). This is likely the result of differences in dietary management among institutions. Results of two other retrospective studies reporting data from horses that fasted for either 6 hours (Nelson et al. 2013) or over 12 hours (Little et al. 2001) suggested that increased time of food withholding prior to a procedure would be associated with reduced fecal output in the first 24 hours. However, results of the present study suggest that withholding hay for up to 24 hours did not impact time to first fecal passage or number of piles produced in 24 hours postprocedure, particularly when combined with the specific and regimented refeeding protocol in our hospital. An opioid was administered to 68% of the horses in the present study during the procedure. None of the PPC horses in this study were administered morphine, which is the drug most investigated regarding its contribution to colic in horses. Several studies have shown that morphine (0.5e1.0 mg kge1) IV is linked to delays in GI transit and increased incidence of colic (Kohn & Muir 1988; Senior et al. 2004; Boscan et al. 2006). However, morphine administered in the dose used in this study (0.1 mg kge1 IV) has been reported to have no effect on the incidence of PPC (Mircica et al. 2003; Andersen et al. 2006; Senior et al. 2006). Lidocaine exerts an anti-inflammatory (Cook & Blikslager 2008), anesthetic-sparing and mild analgesic effect in horses (Robertson et al. 2005; Doherty & Seddighi 2010), but does not act as an intestinal prokinetic (Milligan et al. 2007; Cook & Blikslager 2008; Okamura et al. 2009) and may even reduce
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Retrospective study of postanesthetic colic CJ Thibault et al.
intestinal motility (Salem et al. 2016). In the present study, lidocaine was administered during the procedure to 25% of all horses, 30% of horses during general anesthesia and 43% of horses that developed PPC. The administration of this drug is a confounder and highlights the limitations of a retrospective study. Between 8% (Scherrer et al. 2016) and 21% (Patipa et al. 2012) of horses hospitalized for ophthalmologic procedures have been reported to manifest PPC. Horses hospitalized for ophthalmic disease may experience pain, stress and administration of drugs decreasing GI motility. In the present study, the incidence of PPC in the horses undergoing ophthalmologic procedures was 11% (two/18), similar to the incidence published in earlier studies. Some controversy persists regarding the role of topical ophthalmologic atropine and PPC in horses, perhaps owing to differences in dosing between institutions and over the years. An early study reports colic in four out of six (60%) horses when high doses of topical ophthalmologic atropine (1 mg houre1 per horse for 24 hours) were administered (Williams et al. 2000). For this reason, and despite the low doses of topical ophthalmologic atropine administered, in the present study, descriptive data from seven atropinetreated horses were reported but were removed from data analysis. Multivariate analysis in three studies reporting data from 299 atropine-treated horses undergoing ophthalmologic procedures determined that atropine treatment was not a risk factor for PPC (Little et al. 2001; Patipa et al. 2012; Scherrer et al. 2016). Only one of these studies (Scherrer et al. 2016) reported the dose of topical ophthalmologic atropine administered, namely 1 mg per horse every 12 hours. A separate study reported that double this dose administered to horses induced no delay in the passage of ingesta, no ileus and no measurable serum levels of atropine (Wehrman et al. 2017). In the present study, topical ophthalmologic antifungal treatment was used in six horses, including one PPC horse. Systemic, but not topical, administration of fluconazole reduces GI motility and results in PPC in horses (Curto et al. 2018). Most of the horses in the present study had borborygmi present when assessed. It should be noted, however, that intensity and presence or absence of borborygmi are subjective assessments and have been shown to poorly predict GI function (Little et al. 2001; Roussel et al. 2001; Cohen et al. 2004; Boscan et al. 2006; Naylor et al. 2006). Previous studies have reported that increased procedure duration is associated with either an increased risk (Little et al. 2001; Roussel et al. 2001; Cohen et al. 2004), no association (Senior et al. 2004; Nelson et al. 2013; Bailey et al. 2016) or a decreased risk (Andersen et al. 2006) of PPC. Procedure duration in the SeD group in the present study was
approximately 0.3 hours longer than that in the GA and GAeD groups, contributing to the increased total dose of detomidine administered. This difference in procedure duration was statistically but not clinically significant. Retrospective studies are associated with several inevitable biases related to collection of historical data, use of clinical patients with confounding conditions and accuracy of reporting. Additional highly-powered prospective studies, ideally placebo-controlled or paired group observational studies are recommended to better understand the impact of detomidine administration on PPC and postprocedural fecal output. Potential confounding factors, such as surgical pain, the duration of fasting and adjunct drug administration, including lidocaine and atropine, could then be controlled. Another limitation of the present study is that fecal output of these horses was not accurately quantified because fecal piles were counted but fecal mass, volume or water content were not measured. Use of a fecal collection device (Elfenbein et al. 2011, 2014) would allow accurate weighing of fecal output. Pain scoring is not routinely performed within our hospital, and implementation of a recognized pain scoring system would enhance animal care and allow assessment of the effects of pain on many variables including colic (van Loon & Van Dierendonck 2018). Conclusion Detomidine administration for sedation for standing procedures prolonged the time to first feces and reduced fecal output by one pile during the 24 hours postprocedure. However, associated with our described refeeding protocol, this is not associated with PPC and has little clinical relevance. Detomidine administration, as part of an anesthetic protocol or for standing sedation procedures, should not be expected to contribute to PPC. The results of this study can be used to support sample size calculations and design issues for future studies. Acknowledgements The authors thank Dr Joe G Hauptman for early statistical and study design advice. Authors' contributions CJT: study design, data acquisition and interpretation. DVW: study design, data interpretation. SAR and MAK: study design. DS: statistical analysis. All authors contributed to preparation of the manuscript and approved the final submission. Conflict of interest statement The authors report no conflict of interest.
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References Adams SB, Lamar CH, Masty J (1984) Motility of the distal portion of the jejunum and pelvic flexure in ponies: effects of six drugs. Am J Vet Res 45, 795e799. Andersen MS, Clark L, Dyson SJ, Newton JR (2006) Risk factors for colic in horses after general anaesthesia for MRI or nonabdominal surgery: absence of evidence of effect from perianaesthetic morphine. Equine Vet J 38, 368e374. Bailey PA, Hague BA, Davis M et al. (2016) Incidence of postanesthetic colic in non-fasted adult equine patients. Can Vet J 57, 1263e1266. Boscan P, Van Hoogmoed LM, Farver TB, Snyder JR (2006) Evaluation of the effects of the opioid agonist morphine on gastrointestinal tract function in horses. Am J Vet Res 67, 992e997. Cohen ND, Lester GD, Sanchez LC et al. (2004) Evaluation of risk factors associated with development of postoperative ileus in horses. J Am Vet Med Assoc 225, 1070e1078. Cook VL, Blikslager AT (2008) Use of systemically administered lidocaine in horses with gastrointestinal tract disease. J Am Vet Med Assoc 232, 1144e1148. Curto EM, Griffith EH, Posner LP et al. (2018) Factors associated with postoperative complications in healthy horses after general anesthesia for ophthalmic versus non-ophthalmic procedures: 556 cases (2012e2014). J Am Vet Med Assoc 252, 1113e1119. Daunt DA, Steffey EP (2002) Alpha-2 adrenergic agonists as analgesics in horses. Vet Clin North Am Equine Pract 18, 39e46. Doherty TJ, Seddighi MR (2010) Local anesthetics as pain therapy in horses. Vet Clin North Am Equine Pract 26, 533e549. Elfenbein JR, Sanchez LC, Robertson SA et al. (2009) Effect of detomidine on visceral and somatic nociception and duodenal motility in conscious adult horses. Vet Anaesth Analg 36, 162e172. Elfenbein JR, Robertson SA, Corser AA et al. (2011) Systemic effects of a prolonged continuous infusion of ketamine in healthy horses. J Vet Intern Med 25, 1134e1137. Elfenbein JR, Robertson SA, MacKay RJ et al. (2014) Systemic and anti-nociceptive effects of prolonged lidocaine, ketamine, and butorphanol infusions alone and in combination in healthy horses. BMC Vet Res 10 (Suppl 1), S6. Gozalo-Marcilla M, Luna SP, Crosignani N et al. (2017) Sedative and antinociceptive effects of different combinations of detomidine and methadone in standing horses. Vet Anaesth Analg 44, 1116e1127. Jago RC, Corletto F, Wright IM (2015) Peri-anaesthetic complications in an equine referral hospital: risk factors for post anaesthetic colic. Equine Vet J 47, 635e640. Kohn CW, Muir WW (1988) Selected aspects of the clinical pharmacology of visceral analgesics and gut motility modifying drugs in the horse. J Vet Intern Med 2, 85e91. Lester GD, Merritt AM, Neuwirth L et al. (1998) Effect of alpha 2adrenergic, cholinergic, and nonsteroidal anti-inflammatory drugs on myoelectric activity of ileum, cecum, and right ventral colon and on cecal emptying of radiolabeled markers in clinically normal ponies. Am J Vet Res 59, 320e327. 464
Little D, Redding WR, Blikslager AT (2001) Risk factors for reduced postoperative fecal output in horses: 37 cases (1997e1998). J Am Vet Med Assoc 218, 414e420. Merritt AM, Burrow JA, Hartless CS (1998) Effect of xylazine, detomidine, and a combination of xylazine and butorphanol on equine duodenal motility. Am J Vet Res 59, 619e623. Milligan M, Beard W, Kukanich B et al. (2007) The effect of lidocaine on postoperative jejunal motility in normal horses. Vet Surg 36, 214e220. Mircica E, Clutton RE, Kyles KW, Blissitt KJ (2003) Problems associated with perioperative morphine in horses: a retrospective case analysis. Vet Anaesth Analg 30, 147e155. Naylor JM, Poirier KL, Hamilton DL, Dowling PM (2006) The effects of feeding and fasting on gastrointestinal sounds in adult horses. J Vet Intern Med 20, 1408e1413. Nelson BB, Lordan EE, Hassel DM (2013) Risk factors associated with gastrointestinal dysfunction in horses undergoing elective procedures under general anaesthesia. Equine Vet J Suppl, 8e14. Okamura K, Sasaki N, Yamada M et al. (2009) Effects of mosapride citrate, metoclopramide hydrochloride, lidocaine hydrochloride, and cisapride citrate on equine gastric emptying, small intestinal and caecal motility. Res Vet Sci 86, 302e308. Patipa LA, Sherlock CE, Witte SH et al. (2012) Risk factors for colic in equids hospitalized for ocular disease. J Am Vet Med Assoc 240, 1488e1493. Pimenta EL, Teixeira Neto FJ, S a PA et al. (2011) Comparative study between atropine and hyoscine-N-butylbromide for reversal of detomidine induced bradycardia in horses. Equine Vet J 43, 332e340. Robertson SA, Sanchez LC, Merritt AM, Doherty TJ (2005) Effect of systemic lidocaine on visceral and somatic nociception in conscious horses. Equine Vet J 37, 122e127. Roger T, Ruckebusch Y (1987) Colonic alpha 2-adrenoceptormediated responses in the pony. J Vet Pharmacol Ther 10, 310e318. Roussel AJ, Cohen ND, Hooper RN, Rakestraw PC (2001) Risk factors associated with development of postoperative ileus in horses. J Am Vet Med Assoc 219, 72e78. Salem SE, Proudman CJ, Archer DC (2016) Has intravenous lidocaine improved the outcome in horses following surgical management of small intestinal lesions in a UK hospital population? BMC Vet Res 12, 157. Sasaki N, Yoshihara T, Hara S (2000) Difference in the motile reactivity of jejunum, cecum, and right ventral colon to xylazine and medetomidine in conscious horses. J Equine Sci 11, 63e68. Scherrer NM, Lassaline M, Richardson DW, Stefanovski D (2016) Interval prevalence of and factors associated with colic in horses hospitalized for ocular or orthopedic disease. J Am Vet Med Assoc 249, 90e95. Schoster A, Mosing M, Jalali M et al. (2016) Effects of transport, fasting and anaesthesia on the faecal microbiota of healthy adult horses. Equine Vet J 48, 595e602. Secor EJ, Gutierrez-Nibeyro SD, Clark-Price SC (2018) Comparison of complication rates following elective arthroscopy performed as inpatient versus outpatient surgery in horses. J Am Vet Med Assoc 253, 346e354.
© 2019 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved., 46, 458e465
Retrospective study of postanesthetic colic CJ Thibault et al. Senior JM, Pinchbeck GL, Dugdale AH, Clegg PD (2004) Retrospective study of the risk factors and prevalence of colic in horses after orthopaedic surgery. Vet Rec 155, 321e325. Senior JM, Pinchbeck GL, Allister R et al. (2006) Post anaesthetic colic in horses: a preventable complication? Equine Vet J 38, 479e484. Sutton DG, Preston T, Christley RM et al. (2002) The effects of xylazine, detomidine, acepromazine and butorphanol on equine solid phase gastric emptying rate. Equine Vet J 34, 486e492. Van Dijk P, Lankveld D, Rijkenhuizen A, Jonker FH (2003) Hormonal, metabolic and physiological effects of laparoscopic surgery using a detomidine-buprenorphine combination in standing horses. Vet Anaesth Analg 30, 71e79.
van Loon JPAM, Van Dierendonck MC (2018) Objective pain assessment in horses (2014e2018). Vet J 242, 1e7. Wehrman RF, Gemensky-Metzler AJ, Zibura AE et al. (2017) Objective evaluation of the systemic effects of topical application of 1% atropine sulfate ophthalmic solution in healthy horses. J Am Vet Med Assoc 251, 1324e1330. Williams MM, Spiess BM, Pascoe PJ, O'Grady M (2000) Systemic effects of topical and subconjunctival ophthalmic atropine in the horse. Vet Ophthalmol 3, 193e199. Received 28 August 2018; accepted 25 March 2019. Available online 4 May 2019
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