Pharmacokinetics and pharmacodynamics of hydromorphone hydrochloride in healthy horses

ObjectivesTo determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses.Study designProspective, randomized, crossover study.AnimalsA group of six adult healthy horses weighing 585.2 ± 58.7 kg.MethodsEach horse was administered IV hydromorphone (0.025 mg kg^–1; treatment H0.025), hydromorphone (0.05 mg kg^–1; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was totaled over 24 hours. Data were analyzed using repeated measures anova with significance at p < 0.05. Blood samples were collected in treatment H0.05 for quantification of plasma hydromorphone and hydromorphone-3-glucuronide and subsequent pharmacokinetic parameter calculation.ResultsHydromorphone administration resulted in a dose-dependent increase in heart rate (HR) and systolic arterial pressure (SAP). HR and SAP were 59 ± 17 beats minute^–1 and 230 ± 27 mmHg, respectively, in treatment H0.05 at 5 minutes after administration. No clinically relevant changes in respiratory rate, arterial gases or temperature were observed. The borborygmi scores in both hydromorphone treatments were lower than baseline values for 2 hours. Fecal output did not differ among treatments and no evidence of abdominal discomfort was observed. Recorded behaviors did not differ among treatments. For hydromorphone, mean ± standard deviation for volume of distribution at steady state, total systemic clearance and area under the curve until the last measured concentration were 1.00 ± 0.29 L kg^–1, 106 ± 21 mL minute^–1 kg^–1 and 8.0 ± 1.5 ng hour mL^–1, respectively.Conclusions and clinical relevanceHydromorphone administered IV to healthy horses increased HR and SAP, decreased abdominal borborygmi and did not affect fecal output.     

Initial investigation of mortality rates and prognostic indicators in horses with colic in Israel: A retrospective study

Reasons for performing study: Initial assessment of the mortality rates and prognostic indicators in horses with colic presented to a referral hospital in Israel. Objectives: To determine mortality rates and to identify potential prognostic indicators in horses undergoing treatment for colic. Methods: The medical records of 208 colic cases were reviewed and mortality rates calculated including 95% confidence intervals. Mortality rates in surgical cases were calculated separately for strangulating and nonstrangulating lesions as well as for lesions of the large and small intestines. Potential prognostic indicators were identified and evaluated by Student's t test or X² test, where appropriate. Those found to be significant (P<0.05) were evaluated in 2 logistic regression models; one including all horses with colic and one for surgical cases only. Results: The overall mortality rate was 51/208 (25%); 5/72 (7%) in medically treated cases, 46/136 (34%) in surgical cases, 30/50 (60%) in strangulating lesions and 15/85 (18%) in nonstrangulating lesions, 17/27 (63%) in cases involving small intestinal lesions and 28/108 (26%) in cases with large intestinal lesions. Clinical parameters found to be significantly associated with death by univariate analysis were medical/surgical treatment, location of lesion, severity of lesion, mucous membrane colour (MM), capillary refill time (CRT) and heart rate. Using a multivariate logistic regression model, including all cases, medical/surgical treatment, CRT and MM were found to be prognostic indicators and when using the surgical cases alone, only CRT and lesion severity remained related to mortality. Conclusions: Mortality rates were similar or better than those previously reported in most cases, however, studies from the USA and the UK published better success rates for small intestinal surgeries. Cultural attitudes toward euthanasia may be associated with mortality rates. Potential relevance: These results assist clinicians in providing an immediate prognosis based on clinical findings at presentation and contribute to an international database that may aid future research in improving treatment of colic.     

Surgical colic in racing endurance horses

A retrospective study was performed of horses that developed colic during endurance racing, and subsequently required surgery. Fifteen horses met the inclusion criteria, of which 13 (87%) had small intestinal volvulus. Nine of the 15 horses (60%) had a small intestinal resection and anastomosis performed. Post operative ileus, particularly in those horses that had a resection performed, was a common complication. Eleven of the 15 (73%) survived, and 4 (27%) have since raced.     

Cardiorespiratory effects of enoximone in anaesthetised colic horses

Reasons for performing study: No studies have been reported on the effects of enoximone in anaesthetised colic horses. Objective: To examine whether enoximone improves cardiovascular function and reduces dobutamine requirement in anaesthetised colic horses. Methods: Forty‐eight mature colic horses were enrolled in this prospective, randomised clinical trial. After sedation (xylazine 0.7 mg/kg bwt) and induction (midazolam 0.06 mg/kg bwt, ketamine 2.2 mg/kg bwt), anaesthesia was maintained with isoflurane in oxygen and a lidocaine constant rate infusion (1.5 mg/kg bwt, 2 mg/kg/h). Horses were ventilated (PaCO₂<8.00 kPa). If hypotension occurred, dobutamine and/or colloids were administered. Ten minutes after skin incision, horses randomly received an i.v. bolus of enoximone (0.5 mg/kg bwt) or saline. Monitoring included respiratory and arterial blood gases, heart rate (HR), arterial pressure and cardiac index (CI). Systemic vascular resistance (SVR), stroke index (SI) and oxygen delivery index (DO₂I) were calculated. For each variable, changes between baseline and T10 within each treatment group and/or colic type (small intestines, large intestines or mixed) were analysed and compared between treatments in a fixed effects model. Differences between treatments until T30 were investigated using a mixed model (α= 0.05). Results: Ten minutes after enoximone treatment, CI (P = 0.0010), HR (P = 0.0033) and DO₂I (P = 0.0007) were higher and SVR lower (P = 0.0043) than at baseline. The changes in CI, HR and SVR were significantly different from those after saline treatment. During the first 30 min after enoximone treatment, DO₂I (P = 0.0224) and HR (P = 0.0003) were higher than after saline administration. Because the difference in HR between treatments was much clearer in large intestine colic cases, an interaction was detected between treatment and colic type in both analyses (P = 0.0076 and 0.0038, respectively). Conclusions: Enoximone produced significant, but short lasting, cardiovascular effects in colic horses. Potential relevance: Enoximone's cardiovascular effects in colic horses were of shorter duration than in healthy ponies.     

Postoperative pharmacokinetics of meloxicam in horses after surgery for colic syndrome

NSAID s are often used in horses with colic syndrome during the postoperative period, due to their ability to contrast endotoxemia and to promote an analgesic and anti‐inflammatory effect. As the pharmacokinetics of a drug are often modified in unhealthy animals compared to healthy subjects, the aim of this study was to evaluate the pharmacokinetic profile of meloxicam after i.v. administration in horses undergoing laparotomy for colic syndrome. Eight horses received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples were taken at scheduled time points during the following 24 hr. The serum concentration of the drug was determined by HPLC . Terminal half‐life (6.88 ± 2.96 hr), volume of distribution at steady‐state (186.53 ± 61.20 ml/Kg) and clearance (27.91 ± 5.72 ml kg^?1 hr^?1) were similar to those reported in literature for healthy horses. This result suggests that no adjustment of the approved dose should be necessary when meloxicam is used to treat horses in the immediate postoperative period after surgery for colic syndrome.     

Risk factors of colic in horses in Austria

A hospital‐based case study was conducted at the University of Veterinary Medicine Vienna for a 1‐year period. The purpose of this study was to determine possible alterable and non‐alterable risk factors of equine colic in Austria. The investigated parameters were obtained from hospital medical records (individual factors, duty of the horse, deworming, change in diet and water intake), from questionnaires (feed intake, watering types, housing and pasture practices) and from http://www.orf.at (weather‐related factors). Moreover, 221 collected feed samples were investigated through hygienic quality sensory evaluation and mould, yeast and bacteria presumptive samples were confirmed by microbiological investigation. Variables that were observed from the hospital medical records and found to be significantly associated with colic in a univariate analysis were included in multivariate analysis and the only remaining risk factor was decreased water consumption (p < 0.001, OR = 5.025). Consequently, a total of 2743 horses and 366 cases of colic were observed during the study period. The risk factors for colic in Austria were identified for the first time in this study and these increased risk factors were decreased water consumption, high amount of concentrate intake (p = 0.037), low hygienic quality of hay (p = 0.027) and high temperature on the arrival date (p = 0.003). Results suggest that the occurence of colic may not stop, but may decrease with better feed management practices in Austria.     

A farm-based prospective study of equine colic incidence and associated risk factors

Abdominal pain (colic) in the horse is one of the most acute problems facing equine practitioners. Several causes and risk factors are associated with colic. The current study evaluated the incidence and associated risk factors of colic during a 1-year evaluation in horse farms of Kerman, Iran. The study investigated age, sex, breed, anthelmintic control program, and nutritional status of 128 horses of four breeds on six farms that took part in the study. The mean incidence density rate of colic in the horse population was 8.6% (11/128) in a year. Crossbred horses had more chance of developing colic (P < .05). Horses between the ages of 2 and 10 years also had more risk of developing colic (P < .05). There was no significant difference between sexes (P < .05), and nutritional factors were the most associated risk factors in the cases under study.     

Clinical comparison of two regimens of lidocaine infusion in horses undergoing laparotomy for colic

ObjectiveTo compare, in horses undergoing laparotomy for colic, the effects of administering or not administering a loading intravenous (IV) bolus of lidocaine prior to its constant rate infusion (CRI). Effects investigated during isoflurane anaesthesia were end-tidal isoflurane concentration (Fe’ISO), cardiovascular function, anaesthetic stability and the quality of recovery.Study designProspective, randomized clinical study.AnimalsThirty-six client-owned horses.MethodsHorses were assigned randomly to receive lidocaine as a CRI (50 μg kg⁻¹ minute⁻¹) either preceded (LB) or not preceded (L) by a loading dose (1.5 mg kg⁻¹ IV over 15 minutes). Lidocaine infusion (LInf) was started (T0) within 20 minutes after induction of general anaesthesia and discontinued approximately 30 minutes before the end of surgery. Anaesthetic depth, Fe’ISO, intra-operative physiological parameters and quality of recovery were assessed or measured. Data were analysed using one-way anova, t-test, Fisher test, Wilcoxon and Kruskal–Wallis tests as appropriate (p < 0.05).ResultsMean ± SD Fe’ISO was 1.21 ± 0.08% in group LB and 1.23 ± 0.06% in group L. Heart rate was significantly higher in group L than in group LB at times T5-T15, T25, T35 and T95. No difference was found between groups in other measured physiological values, nor in any measure taken to improve these parameters. Recovery phase was comparable and satisfactory in all but one full term pregnant horse in group L which fractured a femur during recovery.ConclusionPreloading with a lidocaine bolus prior to a CRI of lidocaine did not influence isoflurane requirements, cardiopulmonary effects (other than a reduction in heart rate at some time points) or recovery compared to no preloading bolus.Clinical relevanceA loading dose of lidocaine prior to CRI does not confer any advantage in horses undergoing laparotomy for colic.     

Extraperitoneal incisional abscess formation after colic surgery in 3 horses

In this article we report 3 horses that developed an extraperitoneal abscess after colic surgery at the incision site. All 3 horses presented with nonspecific clinical signs and extraperitoneal abscess was diagnosed from ultrasound evaluations and cytological examination of abscess aspirates. One horse developed dehiscence of the incision after drainage of the abscess through the incision. In 2 cases a small standing paramedian incision was performed through which the abscess was drained and lavaged; complete resolution of the abscess and healing of the incision was achieved in both cases. Extraperitoneal abscess is a previously unreported incisional complication after colic surgery in horses. Early and careful ultrasonographic examination of the abdominal incision is required for diagnosis in cases with nonspecific clinical signs. A paramedian incision through the rectus abdominis muscle into the abscess cavity permitted adequate drainage and debridement of the abscess in 2 cases.     

Surgical treatment of colic in the miniature horse: a retrospective study of 57 cases (1993-2006)

REASONS FOR PERFORMING STUDY: It has been suggested that the rate of post operative abdominal adhesions in miniature horses is higher than that for other breeds. However, few reports exist in the veterinary literature describing complications and long-term survival following surgical treatment of colic in these horses. OBJECTIVES: To determine the prevalence of surgical lesions in miniature horses with acute abdominal disease in terms of clinical signs, surgical management, post operative treatment and complications, as well as short- and long-term survival. METHODS: Medical records of 57 American Miniature Horses undergoing surgical treatment for acute abdominal pain at the Michigan State University Large Animal Veterinary Teaching Hospital 1993-2006 were evaluated for clinical information. Owners and trainers were contacted to gain information regarding long-term survival. RESULTS: The most common surgical lesion was a faecalith (38/57 cases) located primarily within the descending colon and most frequently diagnosed in horses age <6 months (19/38 cases). Short-term survival to hospital discharge for horses recovered from anaesthesia was 98% (55/56) with the most common post operative complications being diarrhoea and inappetance. Intra-abdominal adhesions were identified in 2/8 horses requiring a second celiotomy. Long-term follow-up was available for 45 horses and 87% (39/45) were alive at least 12 months after surgery. CONCLUSIONS: As previously reported, faecalith obstruction is a frequent surgical lesion in the miniature horse and is most common in miniature horses age <6 months. The incidence of adhesion formation may be lower than previously reported.     

Pulsed inhaled nitric oxide improves arterial oxygenation in colic horses undergoing abdominal surgery

Objective

To evaluate the effect of pulsed inhaled nitric oxide (INO) on arterial oxygenation in horses during abdominal surgery.

Clinical observations surrounding an increased incidence of postanesthetic myopathy in halothane-anesthetized horses

BACKGROUND: During an 8-year period of clinic improvements, an increased incidence of postanesthetic myopathy (PAM) was observed in horses undergoing anesthesia. A request was made for an independent anesthesiologist to examine possible reasons for this increase. Routine methods used for anesthesia were then compared with new methods introduced by the anesthesiologist. OBSERVATIONS: Investigative observations were conducted from October 1999 to April 2000. Following premedication with xylazine or detomidine, anesthesia was induced with diazepam or guiaifenesin followed by ketamine. Maintenance of anesthesia was with halothane/O(2) with mechanical ventilation. Information was gathered from observing routine anesthetics. Seventeen horses were designated group A (October-December 1999) for which hypotension was defined as mean arterial pressure (MAP) <60 mmHg and managed using low-volume crystalloid fluid therapy, etilefrine, or dopamine. In the next 18 horses (group B), hypotension was redefined as MAP <70 mmHg, and was managed using high-volume fluid therapy and dobutamine (January-April 2000). No other changes were made. In both groups, creatine kinase (CK) and aspartate transaminase (AST) concentrations were measured before induction, 1 and 25 hours after standing. Occurrence of PAM was defined as CK and/or AST concentrations above 1000 IU L(-1) and analyzed with Fisher's exact test between groups. Muscle enzymes increased in five horses in group A (two with clinical signs) and in one horse in group B (difference between groups: p = 0.088). CONCLUSIONS: Maintaining MAP >70 mmHg with high-volume fluid therapy and dobutamine may help to reduce the severity of myopathy.     

Colon constipation in horses after sustained-release buprenorphine administration

Objective

To investigate the pharmacological profile and side effects of buprenorphine administered as a sustained-release formulation in horses.

Surgical management of sand colic impactions in horses: a retrospective study of 41 cases

OBJECTIVE: A retrospective review of the medical records of 41 horses requiring abdominal surgery for sand colic. RESULTS: The diagnosis of sand colic was made when sand was found to be the cause of impaction of the gastrointestinal tract during surgical exploration. The most common clinical signs at presentation were abdominal pain, abdominal distension and diarrhoea. A statistically significant association was found between the respiratory rate on arrival and short-term survival. Sand impaction at multiple locations was detected in one-third of the horses. Concurrent pathology was detected in half of the horses. Four horses were euthanased during surgery; of those that recovered from surgery, 35/37 (95%) were discharged from hospital. Short- and long-term complications were similar to those previously reported. Long-term (1 year) survival of the horses discharged was 100%. CONCLUSION: The good prognosis for horses undergoing surgery for the treatment of sand impaction supports early surgical intervention in cases where large amounts of sand are suspected.     

Pharmacokinetics and pharmacodynamics of hydromorphone after intravenous and intramuscular administration in horses

ObjectiveTo compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration.Study designRandomized, masked, crossover design.AnimalsA total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg.MethodsHorses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg^⁻1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg^⁻1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (f_R), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant.ResultsThe mean ± SD hydromorphone terminal half-life (t_1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute^⁻1 kg^⁻1 and 1125 ± 309 mL kg^⁻1. The t_1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL^⁻1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p < 0.0001 for both) and baseline (p = 0.006). There was no difference in thermal threshold between H-IV and H-IM. No difference was found in physical examination variables among groups or in comparison to baseline. Fecal weight was significantly less than P for H-IV and H-IM (p = 0.02).Conclusions and clinical relevanceIM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration.IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration.     

Sparing the gut: COX-2 inhibitors herald a new era for treatment of horses with surgical colic

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage a wide variety of conditions in horses, including management of colic. Flunixin meglumine is by far the most commonly used drug in the control of colic pain and inflammation and has become a go-to for not only veterinarians but also horse-owners and nonmedical equine professionals. NSAID use, however, has always been controversial in critical cases due to a high risk of adverse effects associated with their potent cyclo-oxygenase (COX) inhibition. There are two important COX isoenzymes: COX-1 is generally beneficial for normal renal and gastrointestinal functions and COX-2 is associated with the pain and inflammation of disease. Newer selective NSAIDs can target COX-2-driven pathology while sparing important COX-1-driven physiology, which is of critical importance in horses with severe gastrointestinal disease. Emerging research suggests that firocoxib, a COX-2-selective NSAID labelled for use in horses, may be preferable for use in colic cases in spite of the decades-long dogma that flunixin saves lives.     

Changes in intraocular pressure and pupil size following intramuscular administration of hydromorphone hydrochloride and acepromazine in clinically normal dogs

Objective To investigate the effects of intramuscularly administered hydromorphone hydrochloride and acepromazine on intraocular pressure (IOP) and pupil size (PS). Animals studied Seventeen dogs free of clinically relevant ocular abnormalities. Procedure Measurements of IOP and PS were obtained and the dogs were injected intramuscularly with hydromorphone (0.04–0.08 mg/kg) and acepromazine (0.04 mg/kg). Measurements of IOP and PS were repeated 10 min and 25 min later. Results Though a decreasing trend in IOP values was demonstrated, no significant difference was noted in IOP from the initial examination to examination following intramuscular administration of hydromorphone and acepromazine. Significant miosis was present in 16 of 17 dogs at 10 min and 25 min following administration of hydromorphone and acepromazine. Conclusion Hydromorphone (0.04–0.08 mg/kg) and acepromazine (0.04 mg/kg) cause significant miosis in dogs at 10 and 25 min following intramuscular administration.