- Email: [email protected]
Prolonged anesthesia using sevoflurane, remifentanil and dexmedetomidine in a horse
Veterinary Anaesthesia and Analgesia, 2013, 40, 521–526
doi:10.1111/vaa.12048
CASE REPORT
Prolonged anesthesia using sevoflurane, remifentanil and dexmedetomidine in a horse Perrine Benmansour* & Tanya Duke-Novakovski* *Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
Correspondence: Perrine Benmansour, Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N5B4, Canada. E-mail: [email protected]
Follow-up Seven months later, the mare was doing well.
Abstract History A 10-year old Arabian mare had a slowgrowing mass on the lower right mandible and required a large partial mandibulectomy. Physical examination No abnormalities detected apart from the mass.
were
Management A temporary tracheostomy was performed pre-operatively. Anesthesia was induced with xylazine followed by ketamine and diazepam. For 13 hours, anesthesia was maintained using sevoflurane, dexmedetomidine and remifentanil infusions, with the exception of surgical preparation time. Intra-operatively, ventilation was delivered through the cuffed tracheotomy tube. Heart and respiratory rates, ECG, arterial pressures, inspired and expired gases, pulse oximetry values and body temperature were monitored. Dobutamine and whole blood were necessary, and romifidine was used to control recovery. Postoperatively, phenylbutazone and buprenorphine given systemically and bupivacaine administered through a wound soaker catheter were used to provide analgesia. Head-shaking from buprenorphine was controlled with acepromazine and detomidine once standing after 87 minutes in recovery. For 3 days after surgery, analgesia was provided with butorphanol, phenylbutazone and bupivacaine. The mare recovered well, appeared comfortable and started eating the following day with no signs of ileus.
Conclusions Sevoflurane, dexmedetomidine and remifentanil infusions were suitable for a long and invasive procedure. Keywords dexmedetomidine, horse, partial intravenous anesthesia, prolonged anesthesia, remifentanil, sevoflurane.
Introduction Duration of anesthesia and prolonged periods of hypotension can increase the incidence of postanesthetic myopathy (PAM) even when protective padding is used (Grandy et al. 1987; Lindsay et al. 1989; Richey et al. 1990). However, well-managed anesthetic periods of 7 and 18 hours in horses using sevoflurane have been reported to have few detrimental effects on body systems and during recovery (Mizuno et al. 1996; Driessen et al. 2002). Balanced anesthesia is a technique of general anesthesia whereby several drugs are given to achieve specific components of anesthesia (unconsciousness, muscle relaxation, analgesia, immobility). This usually results in lower doses of these drugs and the result is a better quality of anesthesia with fewer detrimental side-effects. When infusions of analgesic and/or sedative drugs are used alongside inhalational anesthesia, the term partial intravenous anesthesia (PIVA) is often used (BettschartWolfensberger & Larenza 2007). 521
Sevoflurane/remifentanil anaesthesia in a horse P Benmansour and T Duke-Novakovski
Fentanyl and remifentanil have been used in horses for analgesia and PIVA as part of a balanced anesthesia technique, but their long-term use has not been reported (Ohta et al. 2010; Benmansour et al. 2011). Alpha2-adrenergic agonists are also used for their analgesic and anesthetic sparing properties in horses (Marcilla et al. 2010). The use of dexmedetomidine infusions for a long-term anesthetic period has not been reported. History A 10 year old Arabian mare, weighing 393 kg, was referred for excision of a high grade, soft tissue sarcoma on her right mandible. The mass had been steadily growing for the previous 5 years, but she appeared to be healthy with a body condition score of 5/9 (Henneke et al. 1983). She was able to eat and drink without apparent difficulty. No evidence of metastases were found on thoracic radiographic examination. Ultrasound guided fine needle aspirates of the right sub-mandibular and retropharyngeal lymph nodes revealed severely reactive inflammatory tissue. A computed tomography scan of the head revealed an expansive osteolytic mass in the body and ramus of the right mandible displacing the pharynx to the left side, with soft tissue involvement and loss of alveolar bone. The larynx did not appear to be involved. Management A radical segmental excision of the right mandible was performed from a site 4 cm distal to the temporo-mandibular joint, up to a site between teeth 407 and 408. The mandibular lymph nodes were also excised. Pre-anesthetic preparation The day of surgery, whole blood (total 6.3 L) was obtained from two compatible donor mares after being cross-matched with this mare. A 14-gauge 133 mm catheter (BD Angiocath; Becton Dickinson, UT) was placed in each jugular vein. The mare was sedated with 150 mg intravenous (IV) xylazine hydrochloride (Rompun; Bayer Healthcare, ON, Canada) and after local infiltration of 10 mL lidocaine 2% (Lurocaine; Vetoquinol N.-A. Inc., QC, Canada) a temporary tracheostomy was performed and a metal tracheostomy tube was placed. Ten million IU of penicillin (Penicillin G Sodium; 522
Novopharm Limited, ON, Canada) and 2 g of phenylbutazone (Phenylbutazone Injection, USP; Vetoquinol N.-A. Inc.,) were administered IV. Anesthetic management Thirty minutes post-tracheostomy, the mare was premedicated with xylazine hydrochloride (1 mg kg 1, IV). Anesthesia was induced with ketamine hydrochloride (Vetalar; Bioniche Animal Health Canada Inc., ON, Canada: 2 mg kg 1, IV) and diazepam (Diazepam Injection USP; Sandoz Canada Incorporated, QC, Canada: 0.1 mg kg 1, IV). The metal tracheostomy tube was replaced with a 24 mm cuffed tracheostomy tube and oxygen insufflated through the tube (10 L minute 1). The mare was hoisted and positioned in left lateral recumbency on a 30 cm thick pad, and the legs supported using stands. During the 20 minutes of surgical preparation in the induction room, anesthesia was maintained with a ‘triple drip’ combination (ketamine hydrochloride 1000 mg and xylazine hydrochloride 500 mg in 1 L of 5% guaifenesin in 5% dextrose [Guaifenesin USP and Dextrose USP Anhydrous, PCCA ON, Canada]) given to effect as is standard practice at this institution. The mare received a total dose of 15 g of guaifenesin, 300 mg of ketamine and 150 mg of xylazine. A 20-gauge 48 mm catheter (BD Insyte, Becton Dickinson) was percutaneously placed in the right metatarsal artery to monitor pressure and for blood gas sampling. Once in the surgical suite, the tracheostomy tube was attached to the circle breathing system, and anesthesia maintained with sevoflurane (Sojourn, MINRAD Inc., PA, USA) in oxygen. The end-tidal sevoflurane (E′Sevo) concentration was adjusted to maintain sluggish anal reflexes and hemodynamic stability in an attempt to block autonomic responses while preserving arterial pressure. Intermittent positive pressure ventilation was started once connected to the breathing circuit using a respiratory rate (fR) of 7 breaths minute 1, a tidal volume of 5 L (12.7 mL kg 1) and a positive end-expiratory pressure of 0.7 kPa (5 cm H2O). Dexmedetomidine hydrochloride (Dexdomitor; Pfizer Animal Health Canada Inc., QC, Canada: 1.5 lg kg 1 hour 1) and remifentanil hydrochloride (Ultiva; Abbott Laboratories, Limited, QC, Canada: 3 lg kg 1 hour 1) infusions were started before surgery commenced, and maintained until the horse was moved into the recovery box. Dobutamine hydrochloride (Dobutamine Injection USP;
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 40, 521–526
Sevoflurane/remifentanil anaesthesia in a horse P Benmansour and T Duke-Novakovski Sandoz Inc.) was infused as needed to maintain mean arterial pressure (MAP) above 70 mmHg. Cefazolin (Cefazolin Injection USP; Novopharm Limited, ON, Canada: 22 mg kg 1 IV) was administered every 90 minutes throughout surgery. A total of 70 L (13.7 mL kg 1 hour 1) of balanced electrolyte solution (Lactated Ringer’s Solution; Hospira Healthcare Corps., QC, Canada) was administered throughout the procedure. Additionally, 3.6 L of blood was transfused to replace blood loss during surgery. The blood loss was estimated at 4 L from the suction jar and visual assessment of the blood on surgical drapes and on the floor. A urinary catheter was placed and a total of 85 L of urine (approximately 16.6 mL kg 1 hour 1) was collected. Rectal body temperature was measured and maintained within normal physiological limits using blankets. Heart rate (HR), electrocardiogram, systolic, diastolic and mean arterial pressure, fR and E′Sevo were recorded every 5 minutes. PE′CO2, pulse oximetry (SpO2) and body temperature (Temp) were recorded every 15 minutes. Arterial blood was sampled periodically for arterial blood gas, electrolyte and lactate measurement. All variables remained within physiologically normal limits. HR oscillated around 40 beats minute 1; MAP remained above 70 mmHg throughout surgery; E′Sevo fluctuated between 2.1% and 3.2%. The lowest SpO2 recorded was 97%. Body temperature remained between 36.9 and 37.5 °C. PE′CO2 and PaCO2 fluctuated between 6.3 and 7.5 kPa (47 and 56 mmHg); and 7.3 and 8 kPa (54.4 and 59.9 mmHg), respectively. The lowest and highest PaO2 were 55.1 kPa (413.3 mmHg) and 62.8 kPa (470.8 mmHg), respectively. The lowest and highest pH values were 7.34 and 7.37, respectively. Minor problems occurred during the anesthetic period. Firstly, a mild leak occurred because the tracheostomy tube cuff was unreliable. Over the first 4 hours of surgery, the oxygen flow was increased from 3 to 7 L minute 1 despite attempts to seal the leak. Replacing the tracheostomy tube would have solved the problem however, there was no other appropriately sized tracheostomy tube available. Ventilation in the room was increased to minimize workspace contamination. Secondly, after 12 hours of anesthesia, the CO2 absorber granules were fully exhausted leading to rebreathing of CO2. At this point, surgery was due to finish, so the CO2 absorber granules were not replaced. PE′CO2 values remained around 6.7 kPa (50 mmHg). Since the PE′CO2 – PaCO2 gradient was approximately 10 mmHg
(1.3 kPa), ventilation settings were not immediately adjusted. However, the inspired CO2 eventually increased to 2 kPa (15 mmHg). When PE′CO2 reached 7.3 kPa (55 mmHg), fR was increased, because increasing tidal volume aggravated the leak. Total surgical time was 12 hours and total anesthesia time from induction to end of sevoflurane administration was 13 hours. Recovery Once surgery had finished, 10 mL bupivacaine 0.5% (Marcaine 0.50%; Hospira Healthcare Corps.) was administered through a wound soaker catheter (Diffusion/Wound catheter – 9in (22.5 cm) Dispersion Area; MILA International, Inc., KY) placed within the wound during closure, and 2 g phenylbutazone given IV. Dexmedetomidine and remifentanil infusions were discontinued before transportation to the recovery stall. In the stall, the mare was positioned in left lateral recumbency on a padded mattress. The tracheostomy tube was left in place and tied around the neck. Oxygen was insufflated through the tracheostomy tube (15 L minute 1). Romifidine hydrochloride (Sedivet; Boehringer Ingelheim, ON, Canada: 25 lg kg 1 IV) was administered intravenously, and buprenorphine (Vetergesic; Alstoe Limited, Yorks, UK: 5 lg kg 1) was placed on the buccal mucosa. Sternal position was attained 75 minutes after stopping sevoflurane. The mare stood up on her fifth attempt 12 minutes later. A recovery score of 3 was given (1: Very poor, 5: Excellent). During the recovery period, increased excitement behaviors were observed including paddling and twitching in recumbency, and head-nodding and circling once standing, when acepromazine (Acevet; Vetoquinol N.-A. Inc.: 0.05 mg kg 1, IV) and detomidine (Domosedan; Pfizer Animal Health Inc.: 0.01 mg kg 1, IV) were administered to control the head-nodding. The mare was returned to her stall 30 minutes later and a lidocaine infusion (1.3 mg kg 1 followed by 50 lg kg 1 minute 1 to prevent post-operative ileus). After 4 hours, the mare began to have further excitement signs that resolved after discontinuation of the lidocaine infusion. Twelve hours after surgery, intestinal sounds were present in all four quadrants and normal feces were produced. No signs of PAM were observed. Bupivacaine 0.75% was instilled through the wound catheter four times a day during the first 48 hours, twice daily on day 3, and discontinued on day 4. Phenylbutazone was given
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 40, 521–526
523
Sevoflurane/remifentanil anaesthesia in a horse P Benmansour and T Duke-Novakovski
IV at 2 g daily for 4 days, then 1 g twice daily for 2 days, followed by oral phenylbutazone (Butequine; Bioniche Animal Health, ON, Canada) 1 g twice daily for 7 days. Ten million I.U. of IV penicillin four times a day, and gentamicin daily (Gentocin; Schering-Plough, QC, Canada: 6.6 mg kg 1 IV) were administered for 5 days post-surgery. Lactated Ringer’s solution with potassium chloride 10 mEq L 1 and calcium gluconate 11 mEq L 1 were administered at 8 mL kg 1 hour 1 post-surgery. The fluid rate was reduced to 5 mL kg 1 hour 1 after 24 hours, and discontinued after 36 hours. Creatine phosphokinase (CPK) and aspartate aminotransferase (AST) values were mildly increased (746 U L 1[laboratory reference interval 88– 439 U L 1] and 762 U L 1 [laboratory reference interval 6–347 U L 1], respectively) 81 hours after standing. Over the next few days, the mare recovered well from surgery. Seven months later (at time of writing), the mare continues to do well. Discussion The aim was to maintain an appropriate level of analgesia for intense surgical stimulation while attempting to minimize the volatile agent requirement and any side effects that might result in PAM. A partial intravenous anesthesia technique was considered the best option. Sevoflurane was chosen because of previous reports of its use for prolonged anesthesia (Mizuno et al. 1996). Although common clinical practice, there are no reports of dexmedetomidine used with opioid infusions in anesthetized horses, although dexmedetomidine infusion alone has been studied (Marcilla et al. 2010). Dexmedetomidine with remifentanil infusions for research horses was found to produce no detrimental effects during a 1 hour period (Benmansour et al. 2011). There was no concurrent surgical procedure performed in the research study and using this combination of drugs for the mare in this case report allowed us to examine their utility for a surgically invasive and long procedure. A loading dose of dexmedetomidine should have been administered because the elimination half-life in ponies is reported to be 29 minutes (BettschartWolfensberger et al. 2005), and only 20 minutes had elapsed between the start of the infusions and the first incision. The pharmacokinetics of remifentanil in horses are unknown, but elimination half-life has been reported to be 3–5 minutes and 15.7 minutes in dogs and cats, respectively (Chism & Rickert 1996; 524
Ferreira et al. 2009). It is therefore unknown whether true steady state was achieved at the time of first incision. However, the most stimulatory and painful events occurred later in the procedure. Due to rapid elimination of dexmedetomidine (Bettschart-Wolfensberger et al. 2005) and remifentanil (Chism & Rickert 1996), postoperative analgesia had to be provided through other means. Phenylbutazone, buprenorphine and wound infiltration using bupivacaine were initially used. Administration of local anesthetics through wound catheters is an important part of a multi-modal approach to analgesic therapy, especially in humans and dogs (Abelson et al. 2009). Despite use of romifidine in our case, the mare had signs of excitement and increased locomotor activity in recovery, and this was assumed to be due to buprenorphine. Buprenorphine was administered through the buccal mucosa to provide a long-lasting analgesia. The antinociception to a thermal stimulus produced by a combination of acepromazine and buprenorphine at 5, 7.5 or 10 lg kg 1 IV was significantly longer compared to a combination of acepromazine and butorphanol 100 lg kg 1 IV in horses (Love et al. 2012). Sublingual buprenorphine (6 lg kg 1) was successfully used to treat pain in a foal with spinal canal stenosis and suspected cervical fracture. The analgesic effect for a single dose lasted 12 hours without signs of excitement (Walker 2007). Others have reported moderate excitement after administration of 5 lg kg 1 IV buprenorphine with increased locomotor activity and head shaking for up to 6 hours in non-painful horses (Carregaro et al. 2007). In our case, detomidine and acepromazine appeared to alleviate the head-shaking. The head-shaking could have also been due to pain. However, the mare appeared comfortable and did not show any clinical sign of discomfort such as pawing or sweating (van Loon et al. 2010) in recovery. Acepromazine administration before or at the time of buprenorphine administration may have prevented excitement behaviors. After weighing the potential benefits for analgesia with increased risk of locomotor activity that might be controllable through use of sedatives, it is the authors’ opinion that buprenorphine should still be considered for pain management. Despite the laterally recumbent position for 13 hours, no marked gas exchange disturbances were observed in arterial blood. The mare’s small stature, body position, and well maintained _ Q_ hemodynamics contributed to preservation of V=
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 40, 521–526
Sevoflurane/remifentanil anaesthesia in a horse P Benmansour and T Duke-Novakovski matching (Mitchell & Littlejohn 1974; Moens et al. 1995). Oxygen carrying capacity was preserved by replacement of surgical blood losses. A more objective blood loss assessment and more tailored blood replacement therapy could have been achieved by also weighing surgical sponges and drapes soaked in blood. Increased urine output was probably due to reduction of anti-diuretic hormone from the dexmedetomidine infusion (Gasthuys et al. 1987). However, the discrepancy in fluid replacement and urine production did not appear to produce any perioperative clinical problems. Because of the risk of PAM, an assisted recovery using head and tail ropes was considered. However, the position of the surgical site precluded the use of a head halter and so recovery was left unassisted. Mizuno et al. (1996) reported use of sevoflurane in a dorsally recumbent horse undergoing a 7-hour long orthopaedic repair. In their case, the recovery was also unassisted and there was no reported lameness, despite increased CK concentrations 12 hours after standing, and swelling in the musculus longissimus suggestive of subclinical PAM. In our case, CK and AST concentrations were mildly increased 81 hours post-standing, suggesting muscle damage either from the surgical procedure itself and/or subclinical PAM. CK and AST concentrations can peak at 6 and 24 hours after the insult, respectively, therefore we missed peak blood concentrations (Hennig & Court 1991). In several studies a significantly lower incidence of PAM occurred in normotensive horses compared to hypotensive horses (Grandy et al. 1987; Richey et al. 1990). Significant differences between hypotensive and normotensive halothane-anesthetized horses positioned in left lateral recumbency have been demonstrated for PAM as well as for enzyme alterations (Lindsay et al. 1989). However, the occurrence of PAM is multifactorial. Causative factors include hypotension, local hypoxia, positioning and type of padding (Lindsay et al. 1980, 1985, 1989). In our case, maintaining MAP above 70 mmHg, providing intravenous fluid therapy and maintaining oxygen carrying capacity with whole blood replacement therapy, as well as careful positioning were important determining factors in preventing PAM. The PIVA technique used also helped to maintain the observed hemodynamic stability. Conflict of interest No conflicts of interest have been declared.
References Abelson AL, McCobb EC, Shaw S et al. (2009) Use of wound soaker catheters for the administration of local anesthetic for post-operative analgesia: 56 cases. Vet Anaesth Analg 36, 597–602. Benmansour P, Graham M, Bracamonte J et al. (2011) Cardiopulmonary effects of dexmedetomidine with remifentanil or morphine infusions in isoflurane anaesthetized horses. Proceedings of the AVA Spring Meeting, Bari, Italy. p. 70 (abstract). Bettschart-Wolfensberger R, Larenza MP (2007) Balanced anesthesia in the equine. Clin Tech Equine Pract 6, 104– 110. Bettschart-Wolfensberger R, Freeman SL, Bowen IM et al. (2005) Cardiopulmonary effects and pharmacokinetics of i.v. dexmedetomidine in ponies. Equine Vet J 37, 60–64. Carregaro AB, Luna SPL, Mataqueiro MI et al. (2007) Effects of buprenorphrine on nociception and spontaneous locomotor activity in horses. Am J Vet Res 68, 246–250. Chism JP, Rickert DE (1996) The pharmacokinetics and extra-hepatic clearance of remifentanil, a short acting opioid agonist, in male beagle dogs during constant rate infusions. Drug Metab Dispos 24, 34–40. Driessen B, Zarucco L, Steffey EP et al. (2002) Serum fluoride concentrations, biochemical and histopathological changes associated with prolonged sevoflurane anaesthesia in horses. J Vet Med A Physiol Pathol Clin Med 49, 337–347. Ferreira TH, Aguiar AJA, Valverde A et al. (2009) Effect of remifentanil hydrochloride administered via constant rate infusion on the minimum alveolar concentration of isoflurane in cats. Am J Vet Res 70, 581–588. Gasthuys F, Terpstra P, Van den Hende C et al. (1987) Hyperglycaemia and diuresis during sedation with detomidine in the horse. J Vet Med A Physiol Pathol Clin Med 34, 641–648. Grandy JL, Steffey EP, Hodgson DS et al. (1987) Arterial hypotention and the development of postanesthetic myopathy in halothane-anesthetized horses. Am J Vet Res 48, 192–197. Henneke DR, Potter GD, Kreider JL et al. (1983) Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet J 15, 371–372. Hennig GE, Court MH (1991) Equine postanesthetic myopathy – an update. Compend Cont Ed Pract Vet 13, 1709–1715. Lindsay WA, McDonell W, Bignell W (1980) Equine postanesthetic forelimb lameness: intracompartmental muscle pressure changes and biochemical patterns. Am J Vet Res 41, 1919–1924. Lindsay WA, Pascoe PJ, McDonell WN et al. (1985) Effect of protective padding on forelimb intracompartmental muscle pressures in anesthetized horses. Am J Vet Res 46, 688–691.
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 40, 521–526
525
Sevoflurane/remifentanil anaesthesia in a horse P Benmansour and T Duke-Novakovski
Lindsay WA, Ribonson GM, Brunson DB et al. (1989) Induction of equine postanesthetic myositis after halothane-induced hypotension. Am J Vet Res 50, 404–410. van Loon JPAM, Back W, Hellebrekers LJ et al. (2010) Application of a composite pain scale to objectively monitor horses with somatic and visceral pain under hospital conditions. J Equine Vet Sci 30, 641–649. Love EJ, Taylor PM, Murrell J et al. (2012) Effects of acepromazine, butorphanol and buprenorphine on thermal and mechanical nociceptive thresholds in horses. Equine Vet J 44, 221–225. Marcilla MG, Schauvliege S, Duchateau L et al. (2010) Cardiopulmonary effects of two constant rate infusions of dexmedetomidine in isoflurane anaesthetized ponies. Vet Anaesth Analg 37, 311–321. Mitchell B, Littlejohn A (1974) The effect of anaesthesia and posture on the exchange of respiratory gases and on the heart rate. Equine Vet J 6, 177–178.
526
Mizuno Y, Ohashi N, Aida H (1996) Anesthetic management with sevoflurane for internal fixation of long bone fracture in a horse. J Equine Vet Sci 7, 47–50. Moens Y, Lagerweij E, Gootjes P et al. (1995) Distribution of inspired gas to each lung in the anaesthetised horse and influence of body shape. Equine Vet J 27, 110–116. Ohta M, Wakuno A, Okada J et al. (2010) Effects of intravenous fentanyl administration on end-tidal sevoflurane concentrations in thoroughbred racehorses undergoing orthopedic surgery. J Vet Med Sci 72, 1107– 1111. Richey MT, Holland MS, McGrath CJ et al. (1990) Equine post-anesthetic lameness. A retrospective study. Vet Surg 19, 392–397. Walker AF (2007) Sublingual administration of buprenorphine for long-term analgesia in the horse. Vet Rec 160, 808–809. Received 18 January 2012; accepted 8 June 2012.
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 40, 521–526
doi:10.1111/vaa.12048
CASE REPORT
Prolonged anesthesia using sevoflurane, remifentanil and dexmedetomidine in a horse Perrine Benmansour* & Tanya Duke-Novakovski* *Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
Correspondence: Perrine Benmansour, Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N5B4, Canada. E-mail: [email protected]
Follow-up Seven months later, the mare was doing well.
Abstract History A 10-year old Arabian mare had a slowgrowing mass on the lower right mandible and required a large partial mandibulectomy. Physical examination No abnormalities detected apart from the mass.
were
Management A temporary tracheostomy was performed pre-operatively. Anesthesia was induced with xylazine followed by ketamine and diazepam. For 13 hours, anesthesia was maintained using sevoflurane, dexmedetomidine and remifentanil infusions, with the exception of surgical preparation time. Intra-operatively, ventilation was delivered through the cuffed tracheotomy tube. Heart and respiratory rates, ECG, arterial pressures, inspired and expired gases, pulse oximetry values and body temperature were monitored. Dobutamine and whole blood were necessary, and romifidine was used to control recovery. Postoperatively, phenylbutazone and buprenorphine given systemically and bupivacaine administered through a wound soaker catheter were used to provide analgesia. Head-shaking from buprenorphine was controlled with acepromazine and detomidine once standing after 87 minutes in recovery. For 3 days after surgery, analgesia was provided with butorphanol, phenylbutazone and bupivacaine. The mare recovered well, appeared comfortable and started eating the following day with no signs of ileus.
Conclusions Sevoflurane, dexmedetomidine and remifentanil infusions were suitable for a long and invasive procedure. Keywords dexmedetomidine, horse, partial intravenous anesthesia, prolonged anesthesia, remifentanil, sevoflurane.
Introduction Duration of anesthesia and prolonged periods of hypotension can increase the incidence of postanesthetic myopathy (PAM) even when protective padding is used (Grandy et al. 1987; Lindsay et al. 1989; Richey et al. 1990). However, well-managed anesthetic periods of 7 and 18 hours in horses using sevoflurane have been reported to have few detrimental effects on body systems and during recovery (Mizuno et al. 1996; Driessen et al. 2002). Balanced anesthesia is a technique of general anesthesia whereby several drugs are given to achieve specific components of anesthesia (unconsciousness, muscle relaxation, analgesia, immobility). This usually results in lower doses of these drugs and the result is a better quality of anesthesia with fewer detrimental side-effects. When infusions of analgesic and/or sedative drugs are used alongside inhalational anesthesia, the term partial intravenous anesthesia (PIVA) is often used (BettschartWolfensberger & Larenza 2007). 521
Sevoflurane/remifentanil anaesthesia in a horse P Benmansour and T Duke-Novakovski
Fentanyl and remifentanil have been used in horses for analgesia and PIVA as part of a balanced anesthesia technique, but their long-term use has not been reported (Ohta et al. 2010; Benmansour et al. 2011). Alpha2-adrenergic agonists are also used for their analgesic and anesthetic sparing properties in horses (Marcilla et al. 2010). The use of dexmedetomidine infusions for a long-term anesthetic period has not been reported. History A 10 year old Arabian mare, weighing 393 kg, was referred for excision of a high grade, soft tissue sarcoma on her right mandible. The mass had been steadily growing for the previous 5 years, but she appeared to be healthy with a body condition score of 5/9 (Henneke et al. 1983). She was able to eat and drink without apparent difficulty. No evidence of metastases were found on thoracic radiographic examination. Ultrasound guided fine needle aspirates of the right sub-mandibular and retropharyngeal lymph nodes revealed severely reactive inflammatory tissue. A computed tomography scan of the head revealed an expansive osteolytic mass in the body and ramus of the right mandible displacing the pharynx to the left side, with soft tissue involvement and loss of alveolar bone. The larynx did not appear to be involved. Management A radical segmental excision of the right mandible was performed from a site 4 cm distal to the temporo-mandibular joint, up to a site between teeth 407 and 408. The mandibular lymph nodes were also excised. Pre-anesthetic preparation The day of surgery, whole blood (total 6.3 L) was obtained from two compatible donor mares after being cross-matched with this mare. A 14-gauge 133 mm catheter (BD Angiocath; Becton Dickinson, UT) was placed in each jugular vein. The mare was sedated with 150 mg intravenous (IV) xylazine hydrochloride (Rompun; Bayer Healthcare, ON, Canada) and after local infiltration of 10 mL lidocaine 2% (Lurocaine; Vetoquinol N.-A. Inc., QC, Canada) a temporary tracheostomy was performed and a metal tracheostomy tube was placed. Ten million IU of penicillin (Penicillin G Sodium; 522
Novopharm Limited, ON, Canada) and 2 g of phenylbutazone (Phenylbutazone Injection, USP; Vetoquinol N.-A. Inc.,) were administered IV. Anesthetic management Thirty minutes post-tracheostomy, the mare was premedicated with xylazine hydrochloride (1 mg kg 1, IV). Anesthesia was induced with ketamine hydrochloride (Vetalar; Bioniche Animal Health Canada Inc., ON, Canada: 2 mg kg 1, IV) and diazepam (Diazepam Injection USP; Sandoz Canada Incorporated, QC, Canada: 0.1 mg kg 1, IV). The metal tracheostomy tube was replaced with a 24 mm cuffed tracheostomy tube and oxygen insufflated through the tube (10 L minute 1). The mare was hoisted and positioned in left lateral recumbency on a 30 cm thick pad, and the legs supported using stands. During the 20 minutes of surgical preparation in the induction room, anesthesia was maintained with a ‘triple drip’ combination (ketamine hydrochloride 1000 mg and xylazine hydrochloride 500 mg in 1 L of 5% guaifenesin in 5% dextrose [Guaifenesin USP and Dextrose USP Anhydrous, PCCA ON, Canada]) given to effect as is standard practice at this institution. The mare received a total dose of 15 g of guaifenesin, 300 mg of ketamine and 150 mg of xylazine. A 20-gauge 48 mm catheter (BD Insyte, Becton Dickinson) was percutaneously placed in the right metatarsal artery to monitor pressure and for blood gas sampling. Once in the surgical suite, the tracheostomy tube was attached to the circle breathing system, and anesthesia maintained with sevoflurane (Sojourn, MINRAD Inc., PA, USA) in oxygen. The end-tidal sevoflurane (E′Sevo) concentration was adjusted to maintain sluggish anal reflexes and hemodynamic stability in an attempt to block autonomic responses while preserving arterial pressure. Intermittent positive pressure ventilation was started once connected to the breathing circuit using a respiratory rate (fR) of 7 breaths minute 1, a tidal volume of 5 L (12.7 mL kg 1) and a positive end-expiratory pressure of 0.7 kPa (5 cm H2O). Dexmedetomidine hydrochloride (Dexdomitor; Pfizer Animal Health Canada Inc., QC, Canada: 1.5 lg kg 1 hour 1) and remifentanil hydrochloride (Ultiva; Abbott Laboratories, Limited, QC, Canada: 3 lg kg 1 hour 1) infusions were started before surgery commenced, and maintained until the horse was moved into the recovery box. Dobutamine hydrochloride (Dobutamine Injection USP;
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 40, 521–526
Sevoflurane/remifentanil anaesthesia in a horse P Benmansour and T Duke-Novakovski Sandoz Inc.) was infused as needed to maintain mean arterial pressure (MAP) above 70 mmHg. Cefazolin (Cefazolin Injection USP; Novopharm Limited, ON, Canada: 22 mg kg 1 IV) was administered every 90 minutes throughout surgery. A total of 70 L (13.7 mL kg 1 hour 1) of balanced electrolyte solution (Lactated Ringer’s Solution; Hospira Healthcare Corps., QC, Canada) was administered throughout the procedure. Additionally, 3.6 L of blood was transfused to replace blood loss during surgery. The blood loss was estimated at 4 L from the suction jar and visual assessment of the blood on surgical drapes and on the floor. A urinary catheter was placed and a total of 85 L of urine (approximately 16.6 mL kg 1 hour 1) was collected. Rectal body temperature was measured and maintained within normal physiological limits using blankets. Heart rate (HR), electrocardiogram, systolic, diastolic and mean arterial pressure, fR and E′Sevo were recorded every 5 minutes. PE′CO2, pulse oximetry (SpO2) and body temperature (Temp) were recorded every 15 minutes. Arterial blood was sampled periodically for arterial blood gas, electrolyte and lactate measurement. All variables remained within physiologically normal limits. HR oscillated around 40 beats minute 1; MAP remained above 70 mmHg throughout surgery; E′Sevo fluctuated between 2.1% and 3.2%. The lowest SpO2 recorded was 97%. Body temperature remained between 36.9 and 37.5 °C. PE′CO2 and PaCO2 fluctuated between 6.3 and 7.5 kPa (47 and 56 mmHg); and 7.3 and 8 kPa (54.4 and 59.9 mmHg), respectively. The lowest and highest PaO2 were 55.1 kPa (413.3 mmHg) and 62.8 kPa (470.8 mmHg), respectively. The lowest and highest pH values were 7.34 and 7.37, respectively. Minor problems occurred during the anesthetic period. Firstly, a mild leak occurred because the tracheostomy tube cuff was unreliable. Over the first 4 hours of surgery, the oxygen flow was increased from 3 to 7 L minute 1 despite attempts to seal the leak. Replacing the tracheostomy tube would have solved the problem however, there was no other appropriately sized tracheostomy tube available. Ventilation in the room was increased to minimize workspace contamination. Secondly, after 12 hours of anesthesia, the CO2 absorber granules were fully exhausted leading to rebreathing of CO2. At this point, surgery was due to finish, so the CO2 absorber granules were not replaced. PE′CO2 values remained around 6.7 kPa (50 mmHg). Since the PE′CO2 – PaCO2 gradient was approximately 10 mmHg
(1.3 kPa), ventilation settings were not immediately adjusted. However, the inspired CO2 eventually increased to 2 kPa (15 mmHg). When PE′CO2 reached 7.3 kPa (55 mmHg), fR was increased, because increasing tidal volume aggravated the leak. Total surgical time was 12 hours and total anesthesia time from induction to end of sevoflurane administration was 13 hours. Recovery Once surgery had finished, 10 mL bupivacaine 0.5% (Marcaine 0.50%; Hospira Healthcare Corps.) was administered through a wound soaker catheter (Diffusion/Wound catheter – 9in (22.5 cm) Dispersion Area; MILA International, Inc., KY) placed within the wound during closure, and 2 g phenylbutazone given IV. Dexmedetomidine and remifentanil infusions were discontinued before transportation to the recovery stall. In the stall, the mare was positioned in left lateral recumbency on a padded mattress. The tracheostomy tube was left in place and tied around the neck. Oxygen was insufflated through the tracheostomy tube (15 L minute 1). Romifidine hydrochloride (Sedivet; Boehringer Ingelheim, ON, Canada: 25 lg kg 1 IV) was administered intravenously, and buprenorphine (Vetergesic; Alstoe Limited, Yorks, UK: 5 lg kg 1) was placed on the buccal mucosa. Sternal position was attained 75 minutes after stopping sevoflurane. The mare stood up on her fifth attempt 12 minutes later. A recovery score of 3 was given (1: Very poor, 5: Excellent). During the recovery period, increased excitement behaviors were observed including paddling and twitching in recumbency, and head-nodding and circling once standing, when acepromazine (Acevet; Vetoquinol N.-A. Inc.: 0.05 mg kg 1, IV) and detomidine (Domosedan; Pfizer Animal Health Inc.: 0.01 mg kg 1, IV) were administered to control the head-nodding. The mare was returned to her stall 30 minutes later and a lidocaine infusion (1.3 mg kg 1 followed by 50 lg kg 1 minute 1 to prevent post-operative ileus). After 4 hours, the mare began to have further excitement signs that resolved after discontinuation of the lidocaine infusion. Twelve hours after surgery, intestinal sounds were present in all four quadrants and normal feces were produced. No signs of PAM were observed. Bupivacaine 0.75% was instilled through the wound catheter four times a day during the first 48 hours, twice daily on day 3, and discontinued on day 4. Phenylbutazone was given
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 40, 521–526
523
Sevoflurane/remifentanil anaesthesia in a horse P Benmansour and T Duke-Novakovski
IV at 2 g daily for 4 days, then 1 g twice daily for 2 days, followed by oral phenylbutazone (Butequine; Bioniche Animal Health, ON, Canada) 1 g twice daily for 7 days. Ten million I.U. of IV penicillin four times a day, and gentamicin daily (Gentocin; Schering-Plough, QC, Canada: 6.6 mg kg 1 IV) were administered for 5 days post-surgery. Lactated Ringer’s solution with potassium chloride 10 mEq L 1 and calcium gluconate 11 mEq L 1 were administered at 8 mL kg 1 hour 1 post-surgery. The fluid rate was reduced to 5 mL kg 1 hour 1 after 24 hours, and discontinued after 36 hours. Creatine phosphokinase (CPK) and aspartate aminotransferase (AST) values were mildly increased (746 U L 1[laboratory reference interval 88– 439 U L 1] and 762 U L 1 [laboratory reference interval 6–347 U L 1], respectively) 81 hours after standing. Over the next few days, the mare recovered well from surgery. Seven months later (at time of writing), the mare continues to do well. Discussion The aim was to maintain an appropriate level of analgesia for intense surgical stimulation while attempting to minimize the volatile agent requirement and any side effects that might result in PAM. A partial intravenous anesthesia technique was considered the best option. Sevoflurane was chosen because of previous reports of its use for prolonged anesthesia (Mizuno et al. 1996). Although common clinical practice, there are no reports of dexmedetomidine used with opioid infusions in anesthetized horses, although dexmedetomidine infusion alone has been studied (Marcilla et al. 2010). Dexmedetomidine with remifentanil infusions for research horses was found to produce no detrimental effects during a 1 hour period (Benmansour et al. 2011). There was no concurrent surgical procedure performed in the research study and using this combination of drugs for the mare in this case report allowed us to examine their utility for a surgically invasive and long procedure. A loading dose of dexmedetomidine should have been administered because the elimination half-life in ponies is reported to be 29 minutes (BettschartWolfensberger et al. 2005), and only 20 minutes had elapsed between the start of the infusions and the first incision. The pharmacokinetics of remifentanil in horses are unknown, but elimination half-life has been reported to be 3–5 minutes and 15.7 minutes in dogs and cats, respectively (Chism & Rickert 1996; 524
Ferreira et al. 2009). It is therefore unknown whether true steady state was achieved at the time of first incision. However, the most stimulatory and painful events occurred later in the procedure. Due to rapid elimination of dexmedetomidine (Bettschart-Wolfensberger et al. 2005) and remifentanil (Chism & Rickert 1996), postoperative analgesia had to be provided through other means. Phenylbutazone, buprenorphine and wound infiltration using bupivacaine were initially used. Administration of local anesthetics through wound catheters is an important part of a multi-modal approach to analgesic therapy, especially in humans and dogs (Abelson et al. 2009). Despite use of romifidine in our case, the mare had signs of excitement and increased locomotor activity in recovery, and this was assumed to be due to buprenorphine. Buprenorphine was administered through the buccal mucosa to provide a long-lasting analgesia. The antinociception to a thermal stimulus produced by a combination of acepromazine and buprenorphine at 5, 7.5 or 10 lg kg 1 IV was significantly longer compared to a combination of acepromazine and butorphanol 100 lg kg 1 IV in horses (Love et al. 2012). Sublingual buprenorphine (6 lg kg 1) was successfully used to treat pain in a foal with spinal canal stenosis and suspected cervical fracture. The analgesic effect for a single dose lasted 12 hours without signs of excitement (Walker 2007). Others have reported moderate excitement after administration of 5 lg kg 1 IV buprenorphine with increased locomotor activity and head shaking for up to 6 hours in non-painful horses (Carregaro et al. 2007). In our case, detomidine and acepromazine appeared to alleviate the head-shaking. The head-shaking could have also been due to pain. However, the mare appeared comfortable and did not show any clinical sign of discomfort such as pawing or sweating (van Loon et al. 2010) in recovery. Acepromazine administration before or at the time of buprenorphine administration may have prevented excitement behaviors. After weighing the potential benefits for analgesia with increased risk of locomotor activity that might be controllable through use of sedatives, it is the authors’ opinion that buprenorphine should still be considered for pain management. Despite the laterally recumbent position for 13 hours, no marked gas exchange disturbances were observed in arterial blood. The mare’s small stature, body position, and well maintained _ Q_ hemodynamics contributed to preservation of V=
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 40, 521–526
Sevoflurane/remifentanil anaesthesia in a horse P Benmansour and T Duke-Novakovski matching (Mitchell & Littlejohn 1974; Moens et al. 1995). Oxygen carrying capacity was preserved by replacement of surgical blood losses. A more objective blood loss assessment and more tailored blood replacement therapy could have been achieved by also weighing surgical sponges and drapes soaked in blood. Increased urine output was probably due to reduction of anti-diuretic hormone from the dexmedetomidine infusion (Gasthuys et al. 1987). However, the discrepancy in fluid replacement and urine production did not appear to produce any perioperative clinical problems. Because of the risk of PAM, an assisted recovery using head and tail ropes was considered. However, the position of the surgical site precluded the use of a head halter and so recovery was left unassisted. Mizuno et al. (1996) reported use of sevoflurane in a dorsally recumbent horse undergoing a 7-hour long orthopaedic repair. In their case, the recovery was also unassisted and there was no reported lameness, despite increased CK concentrations 12 hours after standing, and swelling in the musculus longissimus suggestive of subclinical PAM. In our case, CK and AST concentrations were mildly increased 81 hours post-standing, suggesting muscle damage either from the surgical procedure itself and/or subclinical PAM. CK and AST concentrations can peak at 6 and 24 hours after the insult, respectively, therefore we missed peak blood concentrations (Hennig & Court 1991). In several studies a significantly lower incidence of PAM occurred in normotensive horses compared to hypotensive horses (Grandy et al. 1987; Richey et al. 1990). Significant differences between hypotensive and normotensive halothane-anesthetized horses positioned in left lateral recumbency have been demonstrated for PAM as well as for enzyme alterations (Lindsay et al. 1989). However, the occurrence of PAM is multifactorial. Causative factors include hypotension, local hypoxia, positioning and type of padding (Lindsay et al. 1980, 1985, 1989). In our case, maintaining MAP above 70 mmHg, providing intravenous fluid therapy and maintaining oxygen carrying capacity with whole blood replacement therapy, as well as careful positioning were important determining factors in preventing PAM. The PIVA technique used also helped to maintain the observed hemodynamic stability. Conflict of interest No conflicts of interest have been declared.
References Abelson AL, McCobb EC, Shaw S et al. (2009) Use of wound soaker catheters for the administration of local anesthetic for post-operative analgesia: 56 cases. Vet Anaesth Analg 36, 597–602. Benmansour P, Graham M, Bracamonte J et al. (2011) Cardiopulmonary effects of dexmedetomidine with remifentanil or morphine infusions in isoflurane anaesthetized horses. Proceedings of the AVA Spring Meeting, Bari, Italy. p. 70 (abstract). Bettschart-Wolfensberger R, Larenza MP (2007) Balanced anesthesia in the equine. Clin Tech Equine Pract 6, 104– 110. Bettschart-Wolfensberger R, Freeman SL, Bowen IM et al. (2005) Cardiopulmonary effects and pharmacokinetics of i.v. dexmedetomidine in ponies. Equine Vet J 37, 60–64. Carregaro AB, Luna SPL, Mataqueiro MI et al. (2007) Effects of buprenorphrine on nociception and spontaneous locomotor activity in horses. Am J Vet Res 68, 246–250. Chism JP, Rickert DE (1996) The pharmacokinetics and extra-hepatic clearance of remifentanil, a short acting opioid agonist, in male beagle dogs during constant rate infusions. Drug Metab Dispos 24, 34–40. Driessen B, Zarucco L, Steffey EP et al. (2002) Serum fluoride concentrations, biochemical and histopathological changes associated with prolonged sevoflurane anaesthesia in horses. J Vet Med A Physiol Pathol Clin Med 49, 337–347. Ferreira TH, Aguiar AJA, Valverde A et al. (2009) Effect of remifentanil hydrochloride administered via constant rate infusion on the minimum alveolar concentration of isoflurane in cats. Am J Vet Res 70, 581–588. Gasthuys F, Terpstra P, Van den Hende C et al. (1987) Hyperglycaemia and diuresis during sedation with detomidine in the horse. J Vet Med A Physiol Pathol Clin Med 34, 641–648. Grandy JL, Steffey EP, Hodgson DS et al. (1987) Arterial hypotention and the development of postanesthetic myopathy in halothane-anesthetized horses. Am J Vet Res 48, 192–197. Henneke DR, Potter GD, Kreider JL et al. (1983) Relationship between condition score, physical measurements and body fat percentage in mares. Equine Vet J 15, 371–372. Hennig GE, Court MH (1991) Equine postanesthetic myopathy – an update. Compend Cont Ed Pract Vet 13, 1709–1715. Lindsay WA, McDonell W, Bignell W (1980) Equine postanesthetic forelimb lameness: intracompartmental muscle pressure changes and biochemical patterns. Am J Vet Res 41, 1919–1924. Lindsay WA, Pascoe PJ, McDonell WN et al. (1985) Effect of protective padding on forelimb intracompartmental muscle pressures in anesthetized horses. Am J Vet Res 46, 688–691.
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 40, 521–526
525
Sevoflurane/remifentanil anaesthesia in a horse P Benmansour and T Duke-Novakovski
Lindsay WA, Ribonson GM, Brunson DB et al. (1989) Induction of equine postanesthetic myositis after halothane-induced hypotension. Am J Vet Res 50, 404–410. van Loon JPAM, Back W, Hellebrekers LJ et al. (2010) Application of a composite pain scale to objectively monitor horses with somatic and visceral pain under hospital conditions. J Equine Vet Sci 30, 641–649. Love EJ, Taylor PM, Murrell J et al. (2012) Effects of acepromazine, butorphanol and buprenorphine on thermal and mechanical nociceptive thresholds in horses. Equine Vet J 44, 221–225. Marcilla MG, Schauvliege S, Duchateau L et al. (2010) Cardiopulmonary effects of two constant rate infusions of dexmedetomidine in isoflurane anaesthetized ponies. Vet Anaesth Analg 37, 311–321. Mitchell B, Littlejohn A (1974) The effect of anaesthesia and posture on the exchange of respiratory gases and on the heart rate. Equine Vet J 6, 177–178.
526
Mizuno Y, Ohashi N, Aida H (1996) Anesthetic management with sevoflurane for internal fixation of long bone fracture in a horse. J Equine Vet Sci 7, 47–50. Moens Y, Lagerweij E, Gootjes P et al. (1995) Distribution of inspired gas to each lung in the anaesthetised horse and influence of body shape. Equine Vet J 27, 110–116. Ohta M, Wakuno A, Okada J et al. (2010) Effects of intravenous fentanyl administration on end-tidal sevoflurane concentrations in thoroughbred racehorses undergoing orthopedic surgery. J Vet Med Sci 72, 1107– 1111. Richey MT, Holland MS, McGrath CJ et al. (1990) Equine post-anesthetic lameness. A retrospective study. Vet Surg 19, 392–397. Walker AF (2007) Sublingual administration of buprenorphine for long-term analgesia in the horse. Vet Rec 160, 808–809. Received 18 January 2012; accepted 8 June 2012.
© 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia, 40, 521–526