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Postoperative complications in a lamb after major surgery
Veterinary Anaesthesia and Analgesia, 2011, 38, 63–69
doi:10.1111/j.1467-2995.2010.00578.x
CASE REPORT
Postoperative complications in a lamb after major surgery Enzo Vettorato, Gudrun Schoeffmann, Philippa Beard & R Eddie Clutton Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, EH25 9RG, UK
Correspondence: Enzo Vettorato, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, EH25 9RG, UK. E-mail: [email protected] Current address: Dick White Referrais, Station Farm, London Road, Six Mile Bottom, Suffolk, CB8 0UH
Abstract Intoduction Anaesthesia in lambs undergoing experimental surgery may develop problems associated with age-related immune incompetency: a postoperative complication in a 3 week old Scottish blackface lamb after spinal surgery is presented. Case history and management Both lamb and ewe were in good condition. The ewe was vaccinated against Clostridium perfringens and Clostridium tetani 5 weeks pre-partum. There were no apparent problems with the lamb’s intake of colostrum. Preanaesthetic medication was intramuscular medetomidine (10 lg kg)1). Anaesthesia was induced and maintained with sevoflurane in oxygen. Morphine (0.5 mg kg)1), meloxicam (0.6 mg kg)1) and ketamine (1 mg kg)1 followed by 10 lg kg)1 minute)1) were administered intravenously (IV) for perioperative analgesia. Atracurium (0.5 mg kg)1 IV, followed by 0.17 mg kg)1 injected when the first twitch of the four, train-of four count was palpated) was used to improve muscle relaxation. The lamb’s trachea was intubated and the lungs mechanically ventilated to maintain normocapnia. Intrathecal morphine (0.2 mg kg)1), IV meloxicam (0.3 mg kg)1) and edrophonium (0.5 mg kg)1) were administered before recovery. Operative and initial recovery periods were unremarkable. Three hours after surgery the lamb became depressed. Tachycardia (180–250 beats minute)1), tachypnoea (30 breaths minute)1), poor peripheral perfusion and cold
pelvic limb extremities were present mimicking severe pain, and/or hypovolaemic shock. Analgesics – morphine (total dose 1.3 mg kg)1) - and IV fluid therapy boluses – crystalloids (300 mL), colloids (120 mL) and fresh whole blood (60 mL) – failed to ameliorate clinical signs and so the lamb was euthanized 10 hours after surgery. Post-mortem findings supported a possible diagnosis of peracute Clostridium perfringens enterotoxaemia. Conclusion Clostridium perfringens enterotoxaemia should be considered when clinical signs of severe pain and/or hypovolaemic shock fail to respond to analgesics and fluid resuscitation in lambs after major surgery. Keywords anaesthesia, Clostridium perfringens, enterotoxaemia, lamb.
Introduction Problems with anaesthetizing lambs for biomedical research arise from the animals’ high metabolic rate, high body water content, low body fat and poorly developed thermoregulatory and cardiovascular reflexes compared with adult sheep (Clutton et al. 1998). Immature hepatic enzyme systems and an incomplete blood-brain barrier aggravate these problems (Jenkins 1986). Restoring body temperature and physical activity, specifically the ability to stand and suck, are imperative in the postoperative period. Depressed sucking activity may irretrievably break the ewe-lamb bond, particularly in sheep 63
Postoperative complications in a lamb E Vettorato et al.
breeds where good mothering is not a characteristic trait (Nowak et al. 2008). For approximately the first 3 months of a lamb’s life, immunity depends on passive immunity conferred by post-partum colostrum imbibition (De la Rosa et al. 1997). This protects most lambs against infectious agents to which their dams have been previously exposed, but depends on the strength of the ewe’s immune system and the quantity of colostrum imbibed. Anaesthesia – and more importantly surgery – cause immune suppression in human neonates and may therefore increase morbidity and mortality associated with systemic infections (Kurosawa & Kato 2008). Clostridum perfringens is an important cause of enteric disease in domestic animals and human beings (Hatheway 1990; Sorger 1996). Five serotypes have been isolated (A to E), with types A, B, C and D being most common in lambs. The clinical signs of infection are dysentery, abdominal pain, collapse and sudden death (Songer 1998). Mortality in unvaccinated flocks can reach 30% (Montgomerie 1961). Treatment of affected individuals is usually ineffective, thus prevention is essential. Administration of antibiotics, e.g. penicillin, is frequently futile once clinical signs have appeared. The main risk factors for field outbreaks are poor management, improperly timed and balanced food rations (in particular, the intake of an excessively energy dense diet), immunosuppression or inappropriate scheduling of dam vaccinations (Songer 1998). This case report describes a fatal case most probably due to Cl. perfringens enterotoxaemia which developed acutely within 10 hours of an otherwise uncomplicated recovery from general anaesthesia and orthopaedic surgery in a lamb. The animal’s demise resulted from: 1) a failure to recognize enterotoxaemia as a postsurgical complication in lambs; and 2) the similarity between signs of peracute enterotoxaemia, pain and hypovolaemic shock. Material and methods A 3 week old, Scottish blackface ewe-lamb, weighing 12.3 kg, was anaesthetized in the course of a study necessitating major orthopaedic surgery (PIL 60/3832). The animal and its dam were from a group purchased from a commercial flock. Both were acclimatized for 10 days before surgery. Housing was indoors and consisted of two opposite lines of five hurdled pens (1.5 · 2 m) littered with either barley or wheat straw. The lamb and its dam 64
were confined in a single pen: water and hay were available ad libitum and the ewe was provided with commercial pellets ration (0.5 kg day)1 divided in 2 aliquots). Lambs were allowed to suckle ewes until after pre-anaesthetic medication and immediately before induction of anaesthesia, at which time they were separated. Artificial lighting was maintained from 08:00 until 23:30 each day. Preoperative physical examination indicated that both the lamb and ewe were healthy. Two days before surgery, the lamb’s thoracic wall was clipped, the underlying skin disinfected with povidone-iodine, and the body wall bandaged with elasticated bandage. This measure was taken to acclimatize the ewe to the lamb’s anticipated postoperative (visual and olfactory) characteristics in an attempt to prevent rejection. On the day of the surgery the lamb received an intramuscular (IM) injection of medetomidine (10 lg kg)1, Domitor; Pfizer, UK) and was separated from the ewe 15 minutes later, when profound sedation was present. Anaesthesia was induced using sevoflurane (Sevoflo; Abbott Laboratories, UK) delivered by mask using a Bain breathing system; fresh gas flow was 3 L minute)1. After tracheal intubation had been performed under laryngoscopy with a 6.5 mm OD cuffed endotracheal tube, anaesthesia was maintained with sevoflurane carried in oxygen and delivered using a circle system. End-tidal concentration of sevoflurane (FE´Sevo) was held at 2.8%. Intermittent positive pressure ventilation (Penlon Nuffield 200 Ventilator, InterMed, UK) was applied throughout the procedure in order to maintain normocapnia (4.8– 6.0 kPa) [36–45 mmHg]. After jugular venous cannulation using an 18-gauge cannula, Ringer’s lactate solution was infused (10 mL kg)1 hour)1). Morphine (0.5 mg kg)1, Morphine sulphate injection BP 1%; Martinadale Pharmaceuticals, UK), meloxicam (0.6 mg kg)1, Metacam; Boehringer Ingelheim, UK) and ketamine (1 mg kg)1, followed by a constant rate infusion of 10 lg kg)1 minute)1, Vetalar V 10%; Pharmacia & Upjohn, UK) were administered intravenously (IV) before surgery began. Neuromuscular blockade was achieved with atracurium (0.5 mg kg)1 IV, Tracrium; GlaxoSmithKline, UK) and monitored by counting the responses to train-of-four stimulation (Bard Biomedical, MA, USA) of the common peroneal nerve. Additional atracurium doses (0.17 mg kg)1 IV) were given whenever the first twitch of the trainof-four count returned. A 22-gauge cannula was
2011 The Authors. Veterinary Anaesthesia and Analgesia 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists, 38, 63–69
Postoperative complications in a lamb E Vettorato et al.
placed in the auricular artery for pressure measurement and blood-gas analysis (i-STAT; Abbott Point of Care Inc, UK). A heat pad, a heat and moisture exchange filter (Hydro-Therm II HME; Intersurgical Ltd, UK) and an ambient temperature of 22–24 C were used to maintain normothermia. The electrocardiogram (lead II), invasive blood pressure, end-expiratory partial pressure of carbon dioxide (PE´CO2), FE´Sevo, rectal temperature and spirometry were monitored and recorded every five minutes (Datex AS/3; Datex-Engstrom, Finland) throughout surgery. Venous blood glucose concentrations were assessed hourly (One-Touch Ultra 2; LifeScan Inc, CA, USA). Ephedrine (0.1 mg kg)1 IV) was administered when mean arterial pressure (MAP) was <55 mmHg. Surgery (which involved deep dissection of the epaxial muscles to the ribs, exposure of the transverse processes of T5 to L2, the resection of the proximal extremities of six ribs and the implantation of two prosthetic tethers anchoring the transverse processes of vertebrae T5 to L1) lasted 3 hours and involved the loss of 70 mL blood. During this time, physiological variables were maintained within prescribed limits and anaesthesia was uneventful. Median and range of the anaesthetic variables monitored are reported in Table 1; ephedrine was administered on 5 occasions. At the end of surgery, a second dose of meloxicam (0.3 mg kg)1) was injected IV. Morphine (0.2 mg kg)1 in 1.5 mL NaCl 0.9%) was injected intrathecally at the L6 – S1 interface using a 22 gauge 1.50 inch spinal needle (BD Spinal Needle; Becton Dickinson S.A., Spain). Neuromuscular blockade was antagonized with edrophonium (0.5 mg kg)1 IV, Camsilon; Cambridge Laboratories, UK). Perioperative antibiosis was begun 24 hours before surgery with oxytetracycline (20 mg kg)1,
IM, Engemycin; Intervet Ltd, UK) administered daily and cefuroxime (20 mg kg)1, IV, Zinacev; GlaxoSmithKline, UK) injected every 8 hours, with the first dose given shortly after induction. For the first part of recovery the lamb was positioned in a sling designed to facilitate postoperative nursing and minimize discomfort. Seven minutes after the discontinuation of sevoflurane, returning pharyngeal and laryngeal reflexes prompted tracheal extubation. Rectal temperature at this time was 37.9 C and blood glucose was 4.1 mmol L)1. Ten minutes later the lamb was able to stand and maintain an SpO2 > 0.95% breathing room air. Consequently she was reunited with the ewe. Throughout the first 2 hours of recovery, lamb and ewe behaviours were monitored every 10 minutes by CCTV and recorded digitally. The lamb spent much of this time in lateral recumbency, but was seen to stand on several occasions when it appeared to be ‘‘subdued’’. Three hours after tracheal extubation, the lamb was recumbent and depressed; the respiratory rate was 30 breaths minute)1. The rectal temperature was 39.2 C and the heart rate was 180 beats minute)1. Active sucking reflexes were present and so 60 mL of milk were collected from the ewe and offered by bottle. The lamb drank this enthusiastically and completely. A physical examination performed at this time revealed the lamb was able to move spontaneously from lateral to sternal recumbency. Two hours later, the lamb was still recumbent and depressed but moved to sternal recumbency when approached. Physical examination revealed cooling of the pelvic limb extremities. At this time another 100 mL of milk were given by mouth and morphine (0.3 mg kg)1, IV) by injection. By the seventh postoperative hour, the lamb was profoundly depressed and unresponsive to external
Table 1 Median, minimum and maximum of the cardiopulmonary variables recorded in a sevoflurane anaesthetized and mechanical ventilated lamb undergoing orthopaedic surgery
Median Range
FE¢Sevo
HR
SAP
DAP
MAP
fR
PE¢CO2
Compl
Paw
T
2.7 2.5–3
124 109–157
87 62–102
55 41–74
66 51–83
15 15–15
5.9 [44] 4.8–6.8 [36–51]
8 6–9
23 22–28
39 38.9–39.3
FE¢Sevo, end-expiratory fraction of sevoflurane (%); HR, heart rate (beats minute)1); SAP, systolic arterial pressure (mmHg); DAP, diastolic arterial pressure (mmHg); MAP, mean arterial pressure (mmHg); fR, respiratory rate (breaths minute)1); PE¢CO2, end– expiratory partial pressure of carbon dioxide (kPa [mmHg]); Compl, compliance (mL cmH2O)1); Paw, airway pressure (cmH2O); T, temperature (C). 2011 The Authors. Veterinary Anaesthesia and Analgesia 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists, 38, 63–69
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stimuli: the heart rate was 250 beats minute)1, fR was 30 breaths minute)1, and peripheral (a. dorsalis pedis) pulses were poor. Rectal temperature was 40 C, haematocrit was 0.43 L L)1 and blood glucose was 3.2 mmol L)1. Morphine (1 mg kg)1, IV) and 300 mL of Ringer’s lactate solution supplemented with 1.5 g glucose were administered. As no improvement was noticed, Pentastarch (10 mL kg)1 bolus) and 60 mL of whole maternal blood were infused IV. However, tachycardia, tachypnoea, poor peripheral pulses, and prolonged capillary refill time persisted and the lamb began teeth grinding. No abnormalities were detected on the ECG. The arterial catheter was removed at the initial reunion between lamb and ewe so blood pressure values were unknown. Despite the apparent failure of fluid therapy, the diagnosis of hypovolaemic shock was maintained. Inadequate pain management was also considered even though the lamb had received intrathecal and IV morphine (total dose = 1.3 mg kg)1) and IV meloxicam (total dose = 0.9 mg kg)1). No improvement in demeanour or cardiovascular status was detected over the following 4 hours so, in accordance with Home Office regulations, the animal was euthanized with pentobarbital (Euthatal; Merial Animal Health Ltd, UK). Post-mortem examination Gross examination revealed the serosa and mucosa of the caudal two-thirds of the small intestine and the cranial three quarters of the large intestine, including the caecum, were diffusely dark red to black and friable. No torsion was noted. The mesenteric lymph nodes were prominent, dark red to black. There was a 10 · 5 cm full thickness rupture of the pyloric part of the abomasal wall with gastrointestinal contents free in the abdominal cavity. Clostridium perfringens was isolated from the jejunum and from the spinal cord. No pathogens were isolated from the ileum or abdominal contents. Histopathological examination revealed severe, regionally extensive, necro-haemorrhagic, fibrinous enteritis with intralesional bacteria detected in both small and large intestine. The post-mortem findings supported a diagnosis of peracute clostridial enterotoxaemia. The abomasal perforation most likely occurred either immediately ante mortem or post-mortem, as there was no evidence of an inflammatory or healing responses at the rupture site or evidence of peritonitis. 66
Discussion Clostridium perfringens is a Gram-positive, spore forming, anaerobic and ubiquitous bacteria found in soil, water and poorly preserved feeds. It is a commensal organism of the intestinal tract of domestic animals and humans (Hatheway 1990; Sorger 1996). There are 5 types (A, B, C, D and E) classified on the production of 4 major toxins: alpha (a), beta (b), epsilon (e) and iota (i) (Uzal & Songer 2008). Enteric Cl. perfringens disease is initiated by a change in the intestinal environment which permits overgrowth of the clostridial organism. It can result in localised effects (necrotising enteritis and diarrhoea), and systemic effects (particularly associated with types A and D) when toxins produced by the bacteria in the intestine are absorbed systemically. Cl. perfringens types A, B, C and D are the most common causes of enterotoxaemia in lambs and sheep and are associated with peracute disease in which death may occur within a few hours. Periodic muscular tremor, depression, grinding of the teeth and convulsions are the commonest clinical signs. Diarrhoea may also be present (Uzal & Songer 2008). The lamb described here showed depression, tachycardia and teeth grinding but diarrhoea and neurological signs were absent. As the signs are non-specific and can indicate pain (Molony & Kent 1997) the animal was initially given morphine which was without effect. The organism may proliferate when large quantities of carbohydrate and protein are ingested or when the diet is changed abruptly. Overeating or mild indigestion, as well as anaesthesia and surgical stress, may cause intestinal stasis, which prevents the normal flushing of toxins from the tract (Weissmann 1980; Niilo 1988). Small intestinal mucosal injuries may also predispose to changes in bacterial flora and promote clostridial overgrowth, thereby facilitating toxin absorption and enterotoxaemia (Barker et al. 1993). The lamb’s apparent normality during the first part of recovery was based on the presence and strength of the sucking reflexes observed. As it had been deprived of food for 7 hours, a total of 160 mL of milk divided in 2 aliquots was administered over the first hour. The administered milk may have contributed to the development of the enterotoxaemia: pyloric sphincter relaxation leading to milk passage into the proximal ileum may have produced the favourable conditions for bacterial proliferation (Niilo 1988). However, stress caused by prolonged anaesthesia
2011 The Authors. Veterinary Anaesthesia and Analgesia 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists, 38, 63–69
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and surgery may also have contributed to intestinal stasis (Weissmann 1980). Surgical stress suppresses immunity in human beings (Faist et al. 1996) and may have played a role in this case. In surgical subjects, extensive tissue injury in conjunction with hemorrhagic shock and pain impair immune reactivity, attenuate the up-regulation of cytokine secretion while decreasing lymphocyte count and function (Kurosawa & Kato 2008). These disturbances correlate positively with the duration of surgery and the circulating volume lost (Dietz et al. 2000). In the case described here, surgery lasted 3 hours and intraoperative blood lost was estimated at 70 mL. Anaesthetics modulate the stress response and impair immune function. The resultant dysfunction predisposes postoperative and intensive-care patients to infection, severe sepsis, multiple organ failure and death (Kelbel & Weiss 2001; Kurosawa & Kato 2008). The stress response is characterised by activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis producing tachycardia, hypertension, tachypnoea, vasoconstriction, hyperglycaemia and an elevated catabolic state (Molony & Kent 1997; Desborough 2000). In the lamb reported here, HR ranged between 200–250 beats minute)1, fR was 30 breaths minute)1 and glucose ranged between 3–4 mmol L)1; signs consistent with the stress response. The effect of l-opioid receptors on gastrointestinal motility is of particular concern in humans and horses (Boscan et al. 2006; DeHaven-Hudkins et al. 2008). The stimulation of l receptors of the submucosal Meissner’s plexus, myenteric Auerbach’s ganglia and longitudinal muscle of the ileum alter intestinal motility, secretion, absorption and blood flow causing constipation and ileus (De Luca & Coupar 1996). Morphine’s inhibitory effect on propulsive gut motility in association with surgical stress and periodic gut hypoperfusion might have created the environment for Clostridium proliferation. Moreover, ephedrine, a post-synaptic a- and b-receptor agonist, may have further decreased gut perfusion by increasing splanchnic vascular resistance. When administered to adult dogs anaesthetized with isoflurane (Chen et al. 2007) and ponies anaesthetized with halothane (Lee et al. 2002), ephedrine reduced total peripheral resistance and improved arterial blood pressure and oxygen delivery by increasing cardiac output. However, the author is not aware of any study investigating the effect of ephedrine on the splanchnic vasculature in lambs.
The potency of sevoflurane, expressed as minimum alveolar concentration (MAC), in lambs is unknown. In adult sheep MAC-Sevo ranges between 1.52 (Okutomi et al. 2009) and 3.3% (Lukasik et al. 1998). In our study FE´Sevo was maintained at 2.8%. In a recent study of sheep undergoing orthopaedic surgery the mean FE´Sevo used to provide adequate and stable anaesthesia ranged between 1.96 and 2.28% (Mohamadnia et al. 2008). The drugs used in the lamb described here (medetomidine, ketamine CRI, morphine and atracurium) should have reduced the MAC of sevoflurane. However, because atracurium had been administered it was decided to maintain the FE´Sevo in order to avoid awareness. This strategy may have produced relative overdose with vasodilatation, hypotension and hypoperfusion. If this were the case, then pre-emptive meloxicam may have impaired gastrointestinal homeostasis despite the prompt recognition and treatment of hypotension with ephedrine. Bleeding and ulceration of the gastric and intestinal mucosa, the principal side-effects of NSAIDs in humans, occur because they suppress gastric prostacyclin and prostaglandins PGI2 and PGE2 production, which participate in wound healing. Ulceration is usually asymptomatic but can cause severe haemorrhage and full thickness perforation (Hollander 1994). However, meloxicam is considered to have low ulcerogenic potential and its therapeutic index is relatively high compared with other NSAIDs (Engelhardt et al. 1996). Recently, the pharmacokinetics of meloxicam (0.5 mg kg)1, IV) has been studied in adult sheep (Shukla et al. 2007). The authors concluded that the dose used may be appropriate to maintain the effective plasma concentration above 0.73 lg mL)1 up to 12 hours. The high dose of meloxicam used here (0.9 mg kg)1, IV) and the immature hepatic enzyme systems of the lamb may have maintained more elevated plasma concentrations compared with adults. However, no gastrointestinal ulcerations were found in the lamb. Furthermore, post-mortem examination revealed abomasal perforation which probably occurred immediately ante mortem, or at death, because no evidence of an inflammatory or healing responses at the rupture site, or of peritonitis, were found. In horses, non-specific histological changes of the intestinal mucosa, such as swollen and necrotic blood vessels, were found 48 hours after the administration of phenylbutazone (13.46 mg kg)1 IV) (Meschter et al. 1990). In the lamb reported here, the endothelial cells of some blood vessels were
2011 The Authors. Veterinary Anaesthesia and Analgesia 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists, 38, 63–69
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swollen but the severity of the inflammatory changes (necrohaemorrhagic, fibrinous enteritis) make meloxicam over-dosage an unlikely explanation for abomasal perforation. In order to improve the lamb’s postoperative comfort, morphine was administered spinally (0.2 mg kg)1) at the end of the surgery despite Wagner et al. (1996) showing that subarachnoid morphine (0.1 mg kg)1) produces no apparent benefit in sheep after stifle surgery. Spinal cord contamination and meningitis are theoretical complications of neuraxial injection (Skarda & Tranquilli 2007). In the lamb reported here Cl. perfringes was also isolated from the spinal cord. As the injection was made aseptically and after surgical preparation of the skin it is possible that spinal cord contamination was iatrogenic and occurred during the post-mortem examination. Alternatively, the lamb may have been bacteraemic. The diagnosis of hypovolaemic shock was based on the history and signs of depression, tachycardia, weak pulse and cold extremities. Acute haemorrhage is common in children undergoing spinal surgeries, particularly during recovery (Soundararajan & Cunliffe 2007). However, aggressive fluid therapy with crystalloids, followed by colloid and whole fresh maternal blood was unsuccessful. Given that the infusion of 860 mL should have increased its effective circulating blood volume (ECBV) by 30% - assuming an ECBV of 7% body mass (Moritz et al. 1994) - the absence of response should have prompted the search for an alternative diagnosis, or forced the conclusion of continuing volume losses. A purified toxoid solution of Cl. perfringens types B, C and D and Clostridium tetani (Lambivac; Intervet, UK) was administered to the ewe described here 5 weeks pre-partum and problems with colostrum uptake were not recorded after birth. Lamb vaccination may have provided higher levels of protection after colostral immunity wanes (De la Rosa et al. 1997) and may have been preventative in the case described. Perioperative antibiosis consisted of oxytetracycline and cefuroxime. The former is routinely used in sheep as a broad-spectrum antimicrobial (Fajt & Pugh 2002) as it is effective against gram-positive and negative bacteria including Rickettsia, Chlamydia, Myoplasma and Ehrlichia. It is bacteriostatic at normal, and bactericidal at high concentrations. In horses exposed to stress, surgery, transportation and multiple antimicrobial agents, oxytetracycline promotes Clostridium and Salmonella spp overgrowth, 68
causing fatal colitis (Andersson et al. 1971; Baker & Leyland 1973). Cefuroxime, a second generation cephalosporin that inhibits bacterial cell-wall synthesis in a way similar to that of penicillin (Petri 2001) has been previously used in sheep undergoing spinal surgery without complication (Clutton et al. 1998). However, in humans, cephalosporins are associated with Cl. difficile over-growth (Ambrose et al. 1985). Therefore, it is possible that the antimicrobials chosen, together with other risk factors, produced a favourable environment for the proliferation of Cl. perfringens and subsequent enterotoxaemia. Tetracycline is an effective suppressor of a toxin production in vitro, but is less potent than metronidazole (Stevens et al. 1987). For this reason, metronidazole was also given to the sheep in this study. Conclusion In lambs undergoing major surgery, the possibility of postoperative Cl. perfringens enterotoxaemia should be considered when clinical signs of hypovolaemic shock and, or pain fail to respond to fluid resuscitation and analgesics respectively. References Ambrose NS, Johnson M, Burdon DW et al. (1985) The influence of single dose intravenous antibiotics on faecal flora and emergence of Clostridium difficile. J Antimicrob Chemother 15, 319–326. Andersson G, Ekman L, Mansson I et al. (1971) Lethal complication following administration of oxytetracycline in the horse. Nordic Vet Med 23, 9–22. Baker JR, Leyland A (1973) Diarrhoea in the horse associated with stress and tetracycline therapy. Vet Rec 93, 583–584. Barker IK, Van Dreumel AA, Palmer N (1993) The alimentary system. In: Pathology of domestic animals (6th edn). Jubb KVF, Kennedy PC, Palmer NC (eds). Academic Press, Inc, London, UK. pp. 1–317. Boscan P, Van Hoogmoed LM, Pypendop BH et al. (2006) Pharmacokinetic of the opioid antagonist N-methylnaltrexone and evaluation of its effects on gastrointestinal tract function in horses treated or not treated with morphine. Am J Vet Res 67, 998–1004. Chen HC, Sinclair MD, Dyson DH (2007) Use of ephedrine and dopamine in dogs for the management of hypotension in routine clinical cases under isoflurane anesthesia. Vet Anaesth Analg 34, 301–311. Clutton RE, Murison PJ, Funnel OD (1998) Anaesthesia for lambs undergoing spinal surgery: a case series. Lab Anim 32, 414–421.
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Molony V, Kent JE (1997) Assessment of acute pain in farm animals using behavioural and physiological measurements. J Anim Sci 75, 266–272. Montgomerie RF (1961) Clostridium perfringens (Cl. Welchii) enterotoxaemia in the ruminant. Can Vet Jour 2, 439–450. Moritz KM, Potocnik SJ, Tangalakis K et al. (1994) Blood volume measurements in the neonatal lamb: validation of a method using [51Cr]-labelled red cells. Clin Exp Pharmacol Physiol 21, 577–581. Niilo L (1988) Clostridium perfringens Type C enterotoxaemia. Can Vet J 29, 658–664. Nowak R, Porter RH, Blache D et al. (2008) Behaviour and welfare of the sheep. In: The welfare of the sheep. Dwyer CM (ed). Springer Science, UK. pp. 81–135. Okutomi T, Whittington RA, Stein DJ et al. (2009) Comparison of the effects of sevoflurane and isoflurane anesthesia on the maternal-fetal unit in sheep. J Anesth 23, 392–398. Petri WA Jr (2001) Antimicrobial Agents: penicillins, cephalosporins and other b-lactam antibiotics. In: Goodman & Gilman’s The pharmacological basis of therapeutics (10th edn). Hardman JG, Limbird LE, Goodman Gilman A (eds). The McGraw-Hill Company, Inc, USA. pp. 1189–1218. Shukla M, Singh G, Sindhura BG et al. (2007) Comparative plasma pharmacokinetics of meloxicam in sheep and goats following intravenous administration. Comp Biochem Physiol C Toxicol Pharmacol 145, 528–532. Skarda RT, Tranquilli WJ (2007) Local and regional anesthetic and analgesic techniques: ruminants and swine. In: Lumb & Jones’ veterinary anesthesia (4th edn). Thurmon JC, Tranquilli WJ, Benson GJ (eds). Williams & Wilkins, Baltimore, MD. pp. 643–681. Songer JG (1998) Clostridial diseases of small ruminants. Vet Res 29, 219–232. Sorger JG (1996) Clostridial enteric diseases of domestic animals. Clin Microbiol Rev 9, 216–234. Soundararajan N, Cunliffe M (2007) Anaesthesia for spinal surgery in children. Br J Anaesth 99, 86–94. Stevens DL, Maier KA, Mitten JE (1987) Effect of antibiotic on toxin production and viability of Clostridium perfringens. Antimicrob Agents Chemother 31, 213–218. Uzal FA, Songer JG (2008) Diagnosis of Clostridium perfringens intestinal infection in sheep and goats. J Vet Diagn Invest 20, 253–265. Wagner AE, Dunlop CI, Turner AS (1996) Experiences with morphine injected into the subarachnoid space in sheep. Vet Surg 25, 256–260. Weissmann C (1980) The metabolic response to stress: an overview and update. Anesthesiology 73, 308–327. Received 28 January 2010; accepted 23 April 2010.
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doi:10.1111/j.1467-2995.2010.00578.x
CASE REPORT
Postoperative complications in a lamb after major surgery Enzo Vettorato, Gudrun Schoeffmann, Philippa Beard & R Eddie Clutton Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, EH25 9RG, UK
Correspondence: Enzo Vettorato, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, EH25 9RG, UK. E-mail: [email protected] Current address: Dick White Referrais, Station Farm, London Road, Six Mile Bottom, Suffolk, CB8 0UH
Abstract Intoduction Anaesthesia in lambs undergoing experimental surgery may develop problems associated with age-related immune incompetency: a postoperative complication in a 3 week old Scottish blackface lamb after spinal surgery is presented. Case history and management Both lamb and ewe were in good condition. The ewe was vaccinated against Clostridium perfringens and Clostridium tetani 5 weeks pre-partum. There were no apparent problems with the lamb’s intake of colostrum. Preanaesthetic medication was intramuscular medetomidine (10 lg kg)1). Anaesthesia was induced and maintained with sevoflurane in oxygen. Morphine (0.5 mg kg)1), meloxicam (0.6 mg kg)1) and ketamine (1 mg kg)1 followed by 10 lg kg)1 minute)1) were administered intravenously (IV) for perioperative analgesia. Atracurium (0.5 mg kg)1 IV, followed by 0.17 mg kg)1 injected when the first twitch of the four, train-of four count was palpated) was used to improve muscle relaxation. The lamb’s trachea was intubated and the lungs mechanically ventilated to maintain normocapnia. Intrathecal morphine (0.2 mg kg)1), IV meloxicam (0.3 mg kg)1) and edrophonium (0.5 mg kg)1) were administered before recovery. Operative and initial recovery periods were unremarkable. Three hours after surgery the lamb became depressed. Tachycardia (180–250 beats minute)1), tachypnoea (30 breaths minute)1), poor peripheral perfusion and cold
pelvic limb extremities were present mimicking severe pain, and/or hypovolaemic shock. Analgesics – morphine (total dose 1.3 mg kg)1) - and IV fluid therapy boluses – crystalloids (300 mL), colloids (120 mL) and fresh whole blood (60 mL) – failed to ameliorate clinical signs and so the lamb was euthanized 10 hours after surgery. Post-mortem findings supported a possible diagnosis of peracute Clostridium perfringens enterotoxaemia. Conclusion Clostridium perfringens enterotoxaemia should be considered when clinical signs of severe pain and/or hypovolaemic shock fail to respond to analgesics and fluid resuscitation in lambs after major surgery. Keywords anaesthesia, Clostridium perfringens, enterotoxaemia, lamb.
Introduction Problems with anaesthetizing lambs for biomedical research arise from the animals’ high metabolic rate, high body water content, low body fat and poorly developed thermoregulatory and cardiovascular reflexes compared with adult sheep (Clutton et al. 1998). Immature hepatic enzyme systems and an incomplete blood-brain barrier aggravate these problems (Jenkins 1986). Restoring body temperature and physical activity, specifically the ability to stand and suck, are imperative in the postoperative period. Depressed sucking activity may irretrievably break the ewe-lamb bond, particularly in sheep 63
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breeds where good mothering is not a characteristic trait (Nowak et al. 2008). For approximately the first 3 months of a lamb’s life, immunity depends on passive immunity conferred by post-partum colostrum imbibition (De la Rosa et al. 1997). This protects most lambs against infectious agents to which their dams have been previously exposed, but depends on the strength of the ewe’s immune system and the quantity of colostrum imbibed. Anaesthesia – and more importantly surgery – cause immune suppression in human neonates and may therefore increase morbidity and mortality associated with systemic infections (Kurosawa & Kato 2008). Clostridum perfringens is an important cause of enteric disease in domestic animals and human beings (Hatheway 1990; Sorger 1996). Five serotypes have been isolated (A to E), with types A, B, C and D being most common in lambs. The clinical signs of infection are dysentery, abdominal pain, collapse and sudden death (Songer 1998). Mortality in unvaccinated flocks can reach 30% (Montgomerie 1961). Treatment of affected individuals is usually ineffective, thus prevention is essential. Administration of antibiotics, e.g. penicillin, is frequently futile once clinical signs have appeared. The main risk factors for field outbreaks are poor management, improperly timed and balanced food rations (in particular, the intake of an excessively energy dense diet), immunosuppression or inappropriate scheduling of dam vaccinations (Songer 1998). This case report describes a fatal case most probably due to Cl. perfringens enterotoxaemia which developed acutely within 10 hours of an otherwise uncomplicated recovery from general anaesthesia and orthopaedic surgery in a lamb. The animal’s demise resulted from: 1) a failure to recognize enterotoxaemia as a postsurgical complication in lambs; and 2) the similarity between signs of peracute enterotoxaemia, pain and hypovolaemic shock. Material and methods A 3 week old, Scottish blackface ewe-lamb, weighing 12.3 kg, was anaesthetized in the course of a study necessitating major orthopaedic surgery (PIL 60/3832). The animal and its dam were from a group purchased from a commercial flock. Both were acclimatized for 10 days before surgery. Housing was indoors and consisted of two opposite lines of five hurdled pens (1.5 · 2 m) littered with either barley or wheat straw. The lamb and its dam 64
were confined in a single pen: water and hay were available ad libitum and the ewe was provided with commercial pellets ration (0.5 kg day)1 divided in 2 aliquots). Lambs were allowed to suckle ewes until after pre-anaesthetic medication and immediately before induction of anaesthesia, at which time they were separated. Artificial lighting was maintained from 08:00 until 23:30 each day. Preoperative physical examination indicated that both the lamb and ewe were healthy. Two days before surgery, the lamb’s thoracic wall was clipped, the underlying skin disinfected with povidone-iodine, and the body wall bandaged with elasticated bandage. This measure was taken to acclimatize the ewe to the lamb’s anticipated postoperative (visual and olfactory) characteristics in an attempt to prevent rejection. On the day of the surgery the lamb received an intramuscular (IM) injection of medetomidine (10 lg kg)1, Domitor; Pfizer, UK) and was separated from the ewe 15 minutes later, when profound sedation was present. Anaesthesia was induced using sevoflurane (Sevoflo; Abbott Laboratories, UK) delivered by mask using a Bain breathing system; fresh gas flow was 3 L minute)1. After tracheal intubation had been performed under laryngoscopy with a 6.5 mm OD cuffed endotracheal tube, anaesthesia was maintained with sevoflurane carried in oxygen and delivered using a circle system. End-tidal concentration of sevoflurane (FE´Sevo) was held at 2.8%. Intermittent positive pressure ventilation (Penlon Nuffield 200 Ventilator, InterMed, UK) was applied throughout the procedure in order to maintain normocapnia (4.8– 6.0 kPa) [36–45 mmHg]. After jugular venous cannulation using an 18-gauge cannula, Ringer’s lactate solution was infused (10 mL kg)1 hour)1). Morphine (0.5 mg kg)1, Morphine sulphate injection BP 1%; Martinadale Pharmaceuticals, UK), meloxicam (0.6 mg kg)1, Metacam; Boehringer Ingelheim, UK) and ketamine (1 mg kg)1, followed by a constant rate infusion of 10 lg kg)1 minute)1, Vetalar V 10%; Pharmacia & Upjohn, UK) were administered intravenously (IV) before surgery began. Neuromuscular blockade was achieved with atracurium (0.5 mg kg)1 IV, Tracrium; GlaxoSmithKline, UK) and monitored by counting the responses to train-of-four stimulation (Bard Biomedical, MA, USA) of the common peroneal nerve. Additional atracurium doses (0.17 mg kg)1 IV) were given whenever the first twitch of the trainof-four count returned. A 22-gauge cannula was
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placed in the auricular artery for pressure measurement and blood-gas analysis (i-STAT; Abbott Point of Care Inc, UK). A heat pad, a heat and moisture exchange filter (Hydro-Therm II HME; Intersurgical Ltd, UK) and an ambient temperature of 22–24 C were used to maintain normothermia. The electrocardiogram (lead II), invasive blood pressure, end-expiratory partial pressure of carbon dioxide (PE´CO2), FE´Sevo, rectal temperature and spirometry were monitored and recorded every five minutes (Datex AS/3; Datex-Engstrom, Finland) throughout surgery. Venous blood glucose concentrations were assessed hourly (One-Touch Ultra 2; LifeScan Inc, CA, USA). Ephedrine (0.1 mg kg)1 IV) was administered when mean arterial pressure (MAP) was <55 mmHg. Surgery (which involved deep dissection of the epaxial muscles to the ribs, exposure of the transverse processes of T5 to L2, the resection of the proximal extremities of six ribs and the implantation of two prosthetic tethers anchoring the transverse processes of vertebrae T5 to L1) lasted 3 hours and involved the loss of 70 mL blood. During this time, physiological variables were maintained within prescribed limits and anaesthesia was uneventful. Median and range of the anaesthetic variables monitored are reported in Table 1; ephedrine was administered on 5 occasions. At the end of surgery, a second dose of meloxicam (0.3 mg kg)1) was injected IV. Morphine (0.2 mg kg)1 in 1.5 mL NaCl 0.9%) was injected intrathecally at the L6 – S1 interface using a 22 gauge 1.50 inch spinal needle (BD Spinal Needle; Becton Dickinson S.A., Spain). Neuromuscular blockade was antagonized with edrophonium (0.5 mg kg)1 IV, Camsilon; Cambridge Laboratories, UK). Perioperative antibiosis was begun 24 hours before surgery with oxytetracycline (20 mg kg)1,
IM, Engemycin; Intervet Ltd, UK) administered daily and cefuroxime (20 mg kg)1, IV, Zinacev; GlaxoSmithKline, UK) injected every 8 hours, with the first dose given shortly after induction. For the first part of recovery the lamb was positioned in a sling designed to facilitate postoperative nursing and minimize discomfort. Seven minutes after the discontinuation of sevoflurane, returning pharyngeal and laryngeal reflexes prompted tracheal extubation. Rectal temperature at this time was 37.9 C and blood glucose was 4.1 mmol L)1. Ten minutes later the lamb was able to stand and maintain an SpO2 > 0.95% breathing room air. Consequently she was reunited with the ewe. Throughout the first 2 hours of recovery, lamb and ewe behaviours were monitored every 10 minutes by CCTV and recorded digitally. The lamb spent much of this time in lateral recumbency, but was seen to stand on several occasions when it appeared to be ‘‘subdued’’. Three hours after tracheal extubation, the lamb was recumbent and depressed; the respiratory rate was 30 breaths minute)1. The rectal temperature was 39.2 C and the heart rate was 180 beats minute)1. Active sucking reflexes were present and so 60 mL of milk were collected from the ewe and offered by bottle. The lamb drank this enthusiastically and completely. A physical examination performed at this time revealed the lamb was able to move spontaneously from lateral to sternal recumbency. Two hours later, the lamb was still recumbent and depressed but moved to sternal recumbency when approached. Physical examination revealed cooling of the pelvic limb extremities. At this time another 100 mL of milk were given by mouth and morphine (0.3 mg kg)1, IV) by injection. By the seventh postoperative hour, the lamb was profoundly depressed and unresponsive to external
Table 1 Median, minimum and maximum of the cardiopulmonary variables recorded in a sevoflurane anaesthetized and mechanical ventilated lamb undergoing orthopaedic surgery
Median Range
FE¢Sevo
HR
SAP
DAP
MAP
fR
PE¢CO2
Compl
Paw
T
2.7 2.5–3
124 109–157
87 62–102
55 41–74
66 51–83
15 15–15
5.9 [44] 4.8–6.8 [36–51]
8 6–9
23 22–28
39 38.9–39.3
FE¢Sevo, end-expiratory fraction of sevoflurane (%); HR, heart rate (beats minute)1); SAP, systolic arterial pressure (mmHg); DAP, diastolic arterial pressure (mmHg); MAP, mean arterial pressure (mmHg); fR, respiratory rate (breaths minute)1); PE¢CO2, end– expiratory partial pressure of carbon dioxide (kPa [mmHg]); Compl, compliance (mL cmH2O)1); Paw, airway pressure (cmH2O); T, temperature (C). 2011 The Authors. Veterinary Anaesthesia and Analgesia 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists, 38, 63–69
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stimuli: the heart rate was 250 beats minute)1, fR was 30 breaths minute)1, and peripheral (a. dorsalis pedis) pulses were poor. Rectal temperature was 40 C, haematocrit was 0.43 L L)1 and blood glucose was 3.2 mmol L)1. Morphine (1 mg kg)1, IV) and 300 mL of Ringer’s lactate solution supplemented with 1.5 g glucose were administered. As no improvement was noticed, Pentastarch (10 mL kg)1 bolus) and 60 mL of whole maternal blood were infused IV. However, tachycardia, tachypnoea, poor peripheral pulses, and prolonged capillary refill time persisted and the lamb began teeth grinding. No abnormalities were detected on the ECG. The arterial catheter was removed at the initial reunion between lamb and ewe so blood pressure values were unknown. Despite the apparent failure of fluid therapy, the diagnosis of hypovolaemic shock was maintained. Inadequate pain management was also considered even though the lamb had received intrathecal and IV morphine (total dose = 1.3 mg kg)1) and IV meloxicam (total dose = 0.9 mg kg)1). No improvement in demeanour or cardiovascular status was detected over the following 4 hours so, in accordance with Home Office regulations, the animal was euthanized with pentobarbital (Euthatal; Merial Animal Health Ltd, UK). Post-mortem examination Gross examination revealed the serosa and mucosa of the caudal two-thirds of the small intestine and the cranial three quarters of the large intestine, including the caecum, were diffusely dark red to black and friable. No torsion was noted. The mesenteric lymph nodes were prominent, dark red to black. There was a 10 · 5 cm full thickness rupture of the pyloric part of the abomasal wall with gastrointestinal contents free in the abdominal cavity. Clostridium perfringens was isolated from the jejunum and from the spinal cord. No pathogens were isolated from the ileum or abdominal contents. Histopathological examination revealed severe, regionally extensive, necro-haemorrhagic, fibrinous enteritis with intralesional bacteria detected in both small and large intestine. The post-mortem findings supported a diagnosis of peracute clostridial enterotoxaemia. The abomasal perforation most likely occurred either immediately ante mortem or post-mortem, as there was no evidence of an inflammatory or healing responses at the rupture site or evidence of peritonitis. 66
Discussion Clostridium perfringens is a Gram-positive, spore forming, anaerobic and ubiquitous bacteria found in soil, water and poorly preserved feeds. It is a commensal organism of the intestinal tract of domestic animals and humans (Hatheway 1990; Sorger 1996). There are 5 types (A, B, C, D and E) classified on the production of 4 major toxins: alpha (a), beta (b), epsilon (e) and iota (i) (Uzal & Songer 2008). Enteric Cl. perfringens disease is initiated by a change in the intestinal environment which permits overgrowth of the clostridial organism. It can result in localised effects (necrotising enteritis and diarrhoea), and systemic effects (particularly associated with types A and D) when toxins produced by the bacteria in the intestine are absorbed systemically. Cl. perfringens types A, B, C and D are the most common causes of enterotoxaemia in lambs and sheep and are associated with peracute disease in which death may occur within a few hours. Periodic muscular tremor, depression, grinding of the teeth and convulsions are the commonest clinical signs. Diarrhoea may also be present (Uzal & Songer 2008). The lamb described here showed depression, tachycardia and teeth grinding but diarrhoea and neurological signs were absent. As the signs are non-specific and can indicate pain (Molony & Kent 1997) the animal was initially given morphine which was without effect. The organism may proliferate when large quantities of carbohydrate and protein are ingested or when the diet is changed abruptly. Overeating or mild indigestion, as well as anaesthesia and surgical stress, may cause intestinal stasis, which prevents the normal flushing of toxins from the tract (Weissmann 1980; Niilo 1988). Small intestinal mucosal injuries may also predispose to changes in bacterial flora and promote clostridial overgrowth, thereby facilitating toxin absorption and enterotoxaemia (Barker et al. 1993). The lamb’s apparent normality during the first part of recovery was based on the presence and strength of the sucking reflexes observed. As it had been deprived of food for 7 hours, a total of 160 mL of milk divided in 2 aliquots was administered over the first hour. The administered milk may have contributed to the development of the enterotoxaemia: pyloric sphincter relaxation leading to milk passage into the proximal ileum may have produced the favourable conditions for bacterial proliferation (Niilo 1988). However, stress caused by prolonged anaesthesia
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and surgery may also have contributed to intestinal stasis (Weissmann 1980). Surgical stress suppresses immunity in human beings (Faist et al. 1996) and may have played a role in this case. In surgical subjects, extensive tissue injury in conjunction with hemorrhagic shock and pain impair immune reactivity, attenuate the up-regulation of cytokine secretion while decreasing lymphocyte count and function (Kurosawa & Kato 2008). These disturbances correlate positively with the duration of surgery and the circulating volume lost (Dietz et al. 2000). In the case described here, surgery lasted 3 hours and intraoperative blood lost was estimated at 70 mL. Anaesthetics modulate the stress response and impair immune function. The resultant dysfunction predisposes postoperative and intensive-care patients to infection, severe sepsis, multiple organ failure and death (Kelbel & Weiss 2001; Kurosawa & Kato 2008). The stress response is characterised by activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis producing tachycardia, hypertension, tachypnoea, vasoconstriction, hyperglycaemia and an elevated catabolic state (Molony & Kent 1997; Desborough 2000). In the lamb reported here, HR ranged between 200–250 beats minute)1, fR was 30 breaths minute)1 and glucose ranged between 3–4 mmol L)1; signs consistent with the stress response. The effect of l-opioid receptors on gastrointestinal motility is of particular concern in humans and horses (Boscan et al. 2006; DeHaven-Hudkins et al. 2008). The stimulation of l receptors of the submucosal Meissner’s plexus, myenteric Auerbach’s ganglia and longitudinal muscle of the ileum alter intestinal motility, secretion, absorption and blood flow causing constipation and ileus (De Luca & Coupar 1996). Morphine’s inhibitory effect on propulsive gut motility in association with surgical stress and periodic gut hypoperfusion might have created the environment for Clostridium proliferation. Moreover, ephedrine, a post-synaptic a- and b-receptor agonist, may have further decreased gut perfusion by increasing splanchnic vascular resistance. When administered to adult dogs anaesthetized with isoflurane (Chen et al. 2007) and ponies anaesthetized with halothane (Lee et al. 2002), ephedrine reduced total peripheral resistance and improved arterial blood pressure and oxygen delivery by increasing cardiac output. However, the author is not aware of any study investigating the effect of ephedrine on the splanchnic vasculature in lambs.
The potency of sevoflurane, expressed as minimum alveolar concentration (MAC), in lambs is unknown. In adult sheep MAC-Sevo ranges between 1.52 (Okutomi et al. 2009) and 3.3% (Lukasik et al. 1998). In our study FE´Sevo was maintained at 2.8%. In a recent study of sheep undergoing orthopaedic surgery the mean FE´Sevo used to provide adequate and stable anaesthesia ranged between 1.96 and 2.28% (Mohamadnia et al. 2008). The drugs used in the lamb described here (medetomidine, ketamine CRI, morphine and atracurium) should have reduced the MAC of sevoflurane. However, because atracurium had been administered it was decided to maintain the FE´Sevo in order to avoid awareness. This strategy may have produced relative overdose with vasodilatation, hypotension and hypoperfusion. If this were the case, then pre-emptive meloxicam may have impaired gastrointestinal homeostasis despite the prompt recognition and treatment of hypotension with ephedrine. Bleeding and ulceration of the gastric and intestinal mucosa, the principal side-effects of NSAIDs in humans, occur because they suppress gastric prostacyclin and prostaglandins PGI2 and PGE2 production, which participate in wound healing. Ulceration is usually asymptomatic but can cause severe haemorrhage and full thickness perforation (Hollander 1994). However, meloxicam is considered to have low ulcerogenic potential and its therapeutic index is relatively high compared with other NSAIDs (Engelhardt et al. 1996). Recently, the pharmacokinetics of meloxicam (0.5 mg kg)1, IV) has been studied in adult sheep (Shukla et al. 2007). The authors concluded that the dose used may be appropriate to maintain the effective plasma concentration above 0.73 lg mL)1 up to 12 hours. The high dose of meloxicam used here (0.9 mg kg)1, IV) and the immature hepatic enzyme systems of the lamb may have maintained more elevated plasma concentrations compared with adults. However, no gastrointestinal ulcerations were found in the lamb. Furthermore, post-mortem examination revealed abomasal perforation which probably occurred immediately ante mortem, or at death, because no evidence of an inflammatory or healing responses at the rupture site, or of peritonitis, were found. In horses, non-specific histological changes of the intestinal mucosa, such as swollen and necrotic blood vessels, were found 48 hours after the administration of phenylbutazone (13.46 mg kg)1 IV) (Meschter et al. 1990). In the lamb reported here, the endothelial cells of some blood vessels were
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swollen but the severity of the inflammatory changes (necrohaemorrhagic, fibrinous enteritis) make meloxicam over-dosage an unlikely explanation for abomasal perforation. In order to improve the lamb’s postoperative comfort, morphine was administered spinally (0.2 mg kg)1) at the end of the surgery despite Wagner et al. (1996) showing that subarachnoid morphine (0.1 mg kg)1) produces no apparent benefit in sheep after stifle surgery. Spinal cord contamination and meningitis are theoretical complications of neuraxial injection (Skarda & Tranquilli 2007). In the lamb reported here Cl. perfringes was also isolated from the spinal cord. As the injection was made aseptically and after surgical preparation of the skin it is possible that spinal cord contamination was iatrogenic and occurred during the post-mortem examination. Alternatively, the lamb may have been bacteraemic. The diagnosis of hypovolaemic shock was based on the history and signs of depression, tachycardia, weak pulse and cold extremities. Acute haemorrhage is common in children undergoing spinal surgeries, particularly during recovery (Soundararajan & Cunliffe 2007). However, aggressive fluid therapy with crystalloids, followed by colloid and whole fresh maternal blood was unsuccessful. Given that the infusion of 860 mL should have increased its effective circulating blood volume (ECBV) by 30% - assuming an ECBV of 7% body mass (Moritz et al. 1994) - the absence of response should have prompted the search for an alternative diagnosis, or forced the conclusion of continuing volume losses. A purified toxoid solution of Cl. perfringens types B, C and D and Clostridium tetani (Lambivac; Intervet, UK) was administered to the ewe described here 5 weeks pre-partum and problems with colostrum uptake were not recorded after birth. Lamb vaccination may have provided higher levels of protection after colostral immunity wanes (De la Rosa et al. 1997) and may have been preventative in the case described. Perioperative antibiosis consisted of oxytetracycline and cefuroxime. The former is routinely used in sheep as a broad-spectrum antimicrobial (Fajt & Pugh 2002) as it is effective against gram-positive and negative bacteria including Rickettsia, Chlamydia, Myoplasma and Ehrlichia. It is bacteriostatic at normal, and bactericidal at high concentrations. In horses exposed to stress, surgery, transportation and multiple antimicrobial agents, oxytetracycline promotes Clostridium and Salmonella spp overgrowth, 68
causing fatal colitis (Andersson et al. 1971; Baker & Leyland 1973). Cefuroxime, a second generation cephalosporin that inhibits bacterial cell-wall synthesis in a way similar to that of penicillin (Petri 2001) has been previously used in sheep undergoing spinal surgery without complication (Clutton et al. 1998). However, in humans, cephalosporins are associated with Cl. difficile over-growth (Ambrose et al. 1985). Therefore, it is possible that the antimicrobials chosen, together with other risk factors, produced a favourable environment for the proliferation of Cl. perfringens and subsequent enterotoxaemia. Tetracycline is an effective suppressor of a toxin production in vitro, but is less potent than metronidazole (Stevens et al. 1987). For this reason, metronidazole was also given to the sheep in this study. Conclusion In lambs undergoing major surgery, the possibility of postoperative Cl. perfringens enterotoxaemia should be considered when clinical signs of hypovolaemic shock and, or pain fail to respond to fluid resuscitation and analgesics respectively. References Ambrose NS, Johnson M, Burdon DW et al. (1985) The influence of single dose intravenous antibiotics on faecal flora and emergence of Clostridium difficile. J Antimicrob Chemother 15, 319–326. Andersson G, Ekman L, Mansson I et al. (1971) Lethal complication following administration of oxytetracycline in the horse. Nordic Vet Med 23, 9–22. Baker JR, Leyland A (1973) Diarrhoea in the horse associated with stress and tetracycline therapy. Vet Rec 93, 583–584. Barker IK, Van Dreumel AA, Palmer N (1993) The alimentary system. In: Pathology of domestic animals (6th edn). Jubb KVF, Kennedy PC, Palmer NC (eds). Academic Press, Inc, London, UK. pp. 1–317. Boscan P, Van Hoogmoed LM, Pypendop BH et al. (2006) Pharmacokinetic of the opioid antagonist N-methylnaltrexone and evaluation of its effects on gastrointestinal tract function in horses treated or not treated with morphine. Am J Vet Res 67, 998–1004. Chen HC, Sinclair MD, Dyson DH (2007) Use of ephedrine and dopamine in dogs for the management of hypotension in routine clinical cases under isoflurane anesthesia. Vet Anaesth Analg 34, 301–311. Clutton RE, Murison PJ, Funnel OD (1998) Anaesthesia for lambs undergoing spinal surgery: a case series. Lab Anim 32, 414–421.
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