Analgesia.

Critical to reducing patient morbidity as well as heightened ethical awareness, alleviation of pain in animals has become integral to medical case management and surgical procedures. Pharmacotherapy is directed at peripheral nociceptors, primary and secondary spinal neurons, and pain-processing areas in the CNS. Accordingly, three primary pharmacologic strategies have evolved: drugs that bind to and activate opioid receptors, drugs that bind to and activate alpha 2 receptors, and drugs that reduce de novo prostaglandin synthesis. In horses, the two predominant types of pain encountered are musculoskeletal and visceral pain. Several factors must be considered when devising a therapeutic strategy, including the etiology of the painful event, desired duration of therapy (acute vs chronic), desire for sedation, and potential side effects and toxicity. Opioids and alpha 2 agonists are particularly effective for visceral pain associated with colic. Butorphanol remains the only commercially available opioid and provides superior visceral analgesia compared with pentazocine or flunixin meglumine but not compared with the alpha 2 agonists. The behavioral changes such the sedative effects of alpha 2 agonists and the increased locomotion and CNS excitability seen with some opioids are important considerations when these agents are used as analgesics. NSAIDs may be considered for visceral pain therapy also, especially pain associated with an inflammatory component or endotoxemia. In particular, flunixin meglumine and ketoprofen provide prolonged analgesia and suppress the effects of endotoxin. Long-term therapy of musculoskeletal diseases usually necessitates chronic NSAID use. Although many NSAIDs are now available in approved equine formulations, there remain some important differences among NSAIDs for the practitioner to consider when choosing an analgesic. NSAIDs differ in their ability to ameliorate pyrexia, affect platelet function, alleviate pain, and reduce inflammation. For ease of administration, those available for oral use include phenylbutazone, meclofenamic acid, flunixin meglumine, and naproxen. All are potentially ulcerogenic, and poor tolerance to one may necessitate switching to another with a better toleration profile or to drug from a different analgesic class.     

Comparison of the analgesic effects of xylazine in sheep via three different administration routes

OBJECTIVE: To examine the influence of administration route on the analgesic effects of identical doses of xylazine in sheep. A prospective, linear, randomised laboratory study. PROCEDURE: The analgesic response to the administration of 2.5 mg of the alpha2 agonist xylazine either intravenously, intramuscularly or subcutaneously was assessed using an analgesia testing method based upon a learned response to a painful electrical stimulus. RESULTS: Intravenous administration achieved the most rapid onset and highest peak analgesic values of all administration methods, but was characterised by a shorter duration of action (25 min). Intramuscular and subcutaneous administration resulted in a longer duration of action (40 min) and a greater total analgesic response. CONCLUSION: For the routine management of acute pain, intramuscular administration provided the best combination of onset, duration and total analgesic response of the routes examined. The absence of adverse side effects, such as sedation, normally associated with the administration of alpha2 agonists should also encourage the use of this method as a simple and effective means of providing significant analgesia in the sheep.     

Anatomy of the spinal cord and how the spinal cord is affected by local anesthetics and other drugs.

The spinal cord can be affected by several categories of drugs: local anesthetics, opiate agonist, alpha 2 adrenergic agonists, and ketamine. The mechanism of action, side effects, and usefulness of these injections vary with the type of drug used.     

Sedation and chemical restraint of deer

This review examines the properties of chemical immobilising agents of use or potential use in deer for velvet antler removal. The alpha-2-adrenergic agonist, xylazine, is the most commonly used agent for chemical restraint of stags for this purpose in New Zealand. This compound is often combined with an opioid or ketamine to enhance its effectiveness. Concerns about the carcinogenic potential of a xylazine metabolite have led to a call by the deer industry to limit the use of this drug and stimulated enquiry into alternatives. The potent pure opioid agonists, fentanyl, carfentanil and etorphine, are less effective than xylazine when used alone, and their use presents greater risk to operators and animals and is subject to more stringent legal restrictions. Newer alpha-2-adrenergic agonists, detomidine and medetomidine, are more potent than xylazine and unlikely to result in carcinogenic metabolites. Availability of specific alpha-2-adrenergic antagonists further enhances the usefulness of these drugs. The dissociative agent, ketamine, has proven useful for immobilisation of various domestic and wildlife species and captive species of deer but undesirable side effects and the low concentration, relative to the effective dose, of currently available formulations limit its usefulness. Combination of a dissociative agent with an alpha-2-adrenergic agent reduces the required dose of both and enhances their efficacy. A commercially available combination of the dissociative anaesthetic agent, tiletamine, and the benzodiazepine, zolazepam, is more potent than ketamine and induction times are faster. This combination can be manipulated to varying concentrations by dissolution with alpha-2-adrenergic agents. A long-acting neuroleptic agent, zuclopenthixol, has recently been investigated for calming deer and may be an alternative to classical sedative-immobilising agents. Most chemical immobilisation agents used alone or in combination produce respiratory depression and supplemental oxygen has been recommended. All would likely result in some form of chemical residues in velvet antler.     

Narcotic analgesics, their detection and pain measurement in the horse: a review

Narcotic analgesics produce pharmacological effects by interacting with specific opiate receptors. At least five major types of opiate receptors have been recognised. These include mu (morphine) and kappa (ethylketazocine) receptor types. Narcotic analgesics which interact with mu receptors produce locomotor and autonomic stimulation at doses that produce little or no analgesia. Therefore, use of these drugs as analgesics in equine medicine has not been very satisfactory. Theoretical considerations suggested that the role of kappa agonists in equine analgesia be investigated. Using a pure kappa agonist, U-50, 488H, good analgesia was produced in the horse with little or no locomotor stimulation or autonomic effects. These data suggest that kappa agonists may be superior analgesics for clinical use in the horse. On the other hand, the locomotor stimulant effects of mu agonist analgesics enable their use as illegal medications. Specifically, these agents produce a good running response, signs of central nervous stimulation and analgesia, all potentially useful effects in a racehorse. Regulatory control of most narcotic analgesics can be obtained by high performance thin layer chromatographic screening. However, effective screening for the fentanyls and small doses of etorphine can only be achieved by use of immunoassay.     

Cannabinoids CB2 Receptors,One New Promising Drug Target for Chronic and Degenerative Pain Conditions in Equine Veterinary Patients

Osteoarticular equine disease is a common cause of malady; in general, its therapy is supported on steroids and nonsteroidal anti-inflammatories. Nevertheless, many side effects may develop when these drugs are administered. Nowadays, the use of new alternatives for this pathology attention is demanded; in that sense, cannabinoid CB2 agonists may represent a novel alternative. Cannabinoid belongs to a group of molecules known by their psychoactive properties; they are synthetized by the Cannabis sativa plant, better known as marijuana. The aim of this study was to contribute to understand the pharmacology of cannabinoid CB2 receptors and its potential utilization on equine veterinary patients with a chronic degenerative painful condition. In animals, two main receptors for cannabinoids are recognized, the cannabinoid receptor type 1 and the cannabinoid receptor type 2. Once they are activated, both receptors exert a wide range of physiological responses, as nociception modulation. Recently, it has been proposed the use of synthetic cannabinoid type 2 receptor agonists; those receptors looks to confer antinociceptive properties but without the undesired psychoactive side effects; for that reason, veterinary patients, whit chronical degenerative diseases as osteoarthritis may alleviate one of the most common symptom, the pain, which in some cases for several reasons, as patient individualities, or side effects produced for more conventional treatments cannot be attended in the best way.     

A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice

Medetomidine is a relatively new sedative analgesic drug that is approved for use in dogs in Canada. It is the most potent alpha2-adrenoreceptor available for clinical use in veterinary medicine and stimulates receptors centrally to produce dose-dependent sedation and analgesia. Significant dose sparing properties occur when medetomidine is combined with other anesthetic agents correlating with the high affinity of this drug to the alpha2-adrenoreceptor. Hypoventilation occurs with medetomidine sedation in dogs; however, respiratory depression becomes most significant when given in combination with other sedative or injectable agents. The typical negative cardiovascular effects produced with other alpha2-agonists (bradycardia, bradyarrhythmias, a reduction in cardiac output, hypertension +/- hypotension) are also produced with medetomidine, warranting precautions when it is used and necessitating appropriate patient selection (young, middle-aged healthy animals). While hypotension may occur, sedative doses of medetomidine typically raise the blood pressure, due to the effect on peripheral alpha2-adrenoreceptors. Anticholinergic premedication has been recommended with alpha2-agonists to prevent bradyarrhythmias and, potentially, the reduction in cardiac output produced by these agents; however, current research does not demonstrate a clear improvement in cardiovascular function. Negatively, the anticholinergic induced increase in heart rate potentiates the alpha2-agonist mediated hypertension and may increase myocardial oxygen tension, demand, and workload. Overall, reversal with the specific antagonist atipamezole is recommended when significant cardiorespiratory complications occur. Other physiological effects of medetomidine sedation include; vomiting, increased urine volumes, changes to endocrine function and uterine activity, decreased intestinal motility, decreased intraocular pressure and potentially hypothermia, muscle twitching, and cyanosis. Decreased doses of medetomidine, compared with the recommended label dose, should be considered in combination with other sedatives to enhance sedation and analgesia and lower the duration and potential severity of the negative cardiovascular side effects. The literature was searched in Pubmed, Medline, Agricola, CAB direct, and Biological Sciences.     

Alpha-2 adrenergic agonists as analgesics in horses.

Administration of alpha-2 agonists to horses produces a variety of behavioral effects (sedation, somnolence, analgesia), and physiological effects. One of the most significant beneficial effects of administering alpha-2 agonists is the degree of analgesia they provide. Alpha-2 agonists have been the mainstay of analgesia for colic pain in horses since their introduction to clinical veterinary medicine. The increased potency of the more recently introduced alpha-2 agonists allows the provision of analgesia for conditions not previously relieved by other drugs. Unfortunately, there are significant side effects associated with alpha-2 agonist administration. Studies are underway to identify the physiologic effects associated with the stimulation of each alpha-2 receptor subtype, in hopes of developing subtype-specific alpha-2 agonists and antagonists.     

Perioperative use of selective alpha-2 agonists and antagonists in small animals

Alpha-2 agonists are the only single class of anesthetic drugs that induce reliable, dose-dependent sedation, analgesia, and muscle relaxation in dogs and cats. Used at low doses, as adjuncts to injectable and inhalational anesthetics, selective alpha-2 agonists dramatically reduce the amount of anesthetic drug required to induce and maintain anesthesia. This reduction in anesthetic requirements is achieved without significant depression of pulmonary function and with limited effects on cardiovascular function. Selective alpha-2 agonists can also be used postoperatively to potentiate the analgesic effects of opioids and other drugs. Given the nearly ideal pharmacodynamic profile and reversibility of alpha-2 agonists, these drugs will play a central role in balanced approaches to anesthesia and the management of perioperative pain in healthy dogs and cats.     

Effectiveness of a two-dose regimen of prostaglandin administration in inducing luteolysis without adverse side effects in mares

Our objectives were to determine whether repeated administration of prostaglandin F2alpha (PGF2alpha) to simulate the endogenous mode of secretion would be more effective than a single injection in inducing luteolysis and enable use of smaller doses less likely to cause adverse side effects. The main study comprised 43 dioestrous mares, who were given im. either a single 10 mg dose of natural PGF2alpha (n = 22) or 2 doses of 0.5 mg PGF2, 24 h apart (n = 21). The intensity of side effects was assessed in 8 dioestrous mares given 5, 1.5, 0.5 or 0 mg PGF2alpha in consecutive cycles. Two doses of 0.5 mg PGF2alpha 24 h apart caused lysis of the corpus luteum in all mares, whether this was determined from a fall in plasma progesterone concentrations or reproductive tract/behavioural changes; and when 10 mg PGF2, was given, the corpus luteum was lysed in 17 of 22 mares i.e. a lower proportion (P = 0.0485). A single dose of 0.5 mg PGF2a was no more effective than saline in inducing luteolysis.The intensity of side effects of PGF2alpha increased with dose. Although the 0.5 mg dose was no more likely than saline to cause sweating or muscle spasms, it raised plasma cortisol concentrations and prevented the decline in heart rate seen after saline. We conclude that a 2 dose regimen of administration increases the luteolytic efficacy of PGF2alpha and thereby provides a way to minimise adverse side effects.     

A review of clinical approaches to antagonism of alpha2‐adrenoreceptor agonists in the horse

Alpha₂‐adrenoceptor agonists xylazine, romifidine, detomidine and, in some cases, medetomidine and dexmedetomidine, are fundamental drugs used in equine practice. There are situations where the undesirable pharmacodynamic effects (ataxia, prolonged sedation, bradycardia and ileus) or accidental overdose of these drugs may need to be antagonised. The α₂‐adrenoceptor antagonists tolazoline, yohimbine and atipamezole can be used to antagonise undesirable effects. However, despite being effective, α₂‐adrenoceptor antagonists are also not without undesirable pharmacodynamic effects. Excitement, muscle trembling and triggered inappropriate stress responses are a few of the more serious undesirable effects. Horses demonstrate a variable response to the antagonists thus recommending dose rates become fraught with difficulty. It is therefore recommended that the α₂‐adrenoceptor antagonist should be titrated to the desired clinical effect. Consequently, other reversal agents, such as anticholinergics (atropine, glycopyrrolate and hyoscine), have been administered for the treatment of α₂‐adrenoceptor agonist‐induced bradycardia. Anticholinergics cannot be recommended for routine use in horses due to the undesirable cardiovascular effects and potentiation of α₂‐adrenoceptor agonist‐induced gastrointestinal hypomotility. Novel peripheral acting α₂‐adrenoceptor antagonists, such as MK‐467, are currently under scrutiny in veterinary anaesthesia in an effort to antagonise the undesirable effects of α₂‐adrenoceptor agonists without compromising on the level of sedation. This review examines the current literature on the α₂‐adrenoceptor antagonists used in horses and makes recommendations on how to use these drugs safely in an attempt to prevent undesirable pharmacodynamic effects.     

Renal actions of the alpha2-adrenoceptor agonist, xylazine, in the anaesthetised rat

AIMS: The aims of the present study were to characterise the renal effects of the alpha2-adrenergic agonist, xylazine, in the rat and to test the role of changes in glomerular filtration rate, glucosuria, and arginine vasopressin (AVP) in its mechanism of action. METHODS: Male Wistar rats were anaesthetised with pentobarbitone sodium (50 mg/kg), and polyethylene cannulae were surgically placed for blood pressure measurement and for blood and urine collection. Rats were given xylazine and other alpha2 agonists by bolus intravenous dose, and the effects of the drugs were monitored in the presence and absence of the selective alpha2 antagonist, yohimbine, the alpha1, alpha2B antagonist, prazosin, and the V2-receptor antagonist, d(CH2)5 [D-Ile2,Ile4,Ala-NH29]AVP. RESULTS: Xylazine at 2.5 mg/kg caused a significant and prolonged dose-dependent increase in urine flow rate and sodium excretion but had only short-lasting effects on blood pressure, heart rate, and glomerular filtration rate. Prazosin had no effect on the measured responses. Although plasma glucose concentration and glucose excretion rate were increased by xylazine, the magnitudes of these increases were insufficient to account for the diuresis observed. Xylazine, and 2 other alpha2 agonists, clonidine and oxymetazoline, increased urine flow and/or sodium excretion despite the presence of d(CH2)5 [D-Ile2,Ile4,Ala-NH29]AVP. CONCLUSIONS: Xylazine causes a diuretic and natriuretic alpha2A-adrenergic response in the rat that is independent of changes in glomerular filtration rate, the development of glucosuria, or AVP action on the distal nephron of the kidney. CLINICAL RELEVANCE: The adverse effects of xylazine on salt and water balance need to be considered and possibly compensated for by fluid replacement or post-surgical administration of alpha2-receptor antagonists.     

Effects of adrenergic agonists and antagonists on the blood pressure and heart rate of the pig fetus

The effects of adrenergic agonists and antagonists on blood pressure and heart rate were investigated in 18 chronically catheterised pig fetuses aged between 102 and 109 days of gestation (term is 114 days). One fetus had been decapitated in utero at 42 days of gestation. The alpha adrenergic agonist methoxamine produced a small but dose dependent hypertension and a dose related slowing in heart rate. The beta adrenergic agonist isoprenaline decreased mean arterial pressure in a dose related manner and produced tachycardia. Propranolol, a beta adrenergic blocker, increased mean arterial pressure and decreased heart rate. The response to subsequent alpha adrenergic blockade with phentolamine was hypotension and a slight bradycardia. Decapitation at 42 days of gestation did not seem to change the fetal responsiveness to adrenergic agonists but removed the blood pressure response to beta blockade. These observations indicate that the heart and circulation of the pig fetus are under adrenergic vasomotor control during late gestation.     

Pharmacological characterization of alpha1-adrenoceptors in equine digital veins

Alpha-adrenoceptors mediate contractile responses in equine digital veins (EDVs) and arteries. Vascular smooth muscle alpha(1)-adrenoceptor subtypes have been implicated in a number of conditions, such as acute equine laminitis, and are therapeutic targets for the treatment of this condition. Digital veins, rather than arteries, were investigated in the present study because they have been specifically implicated in the pathophysiology of acute laminitis. The order of potency of a series of alpha(1)-adrenoceptor-selective agonists and antagonists was determined in isolated rings of EDVs under conditions of isometric tension. A61603 was the most potent agonist, with a higher potency (76-fold greater) than phenylephrine (PHE), suggesting the presence of the alpha(1A)-adrenoceptor subtype. Prazosin (30 nm) caused competitive inhibition of the responses to A61603 and PHE, with pK(b) values of 8.05 +/- 0.28 and 8.20 +/- 0.27, respectively. In addition, the alpha(1A)-adrenoceptor antagonist, WB4101 (10 nm), also caused competitive inhibition of the responses to the two agonists, with pK(b) values of 8.37 +/- 0.16 and 8.54 +/- 0.23, respectively, confirming the presence of the alpha(1A)-adrenoceptor subtype in EDVs. The selective alpha(1D)-adrenoceptor antagonist, BMY7378 (100 nm) did not cause a significant change in the response to the agonists, giving lower pK(b) values (6.97 +/- 0.27 and 6.88 +/- 0.17 vs. A61603 and PHE, respectively). Chloroethylclonidine dihydrochloride (45 microm, 30 min), used to produce selective inactivation of alpha(1B)-adrenoceptors, caused noncompetitive inhibition of the response to PHE, but was without effect on the response to A61603. These findings indicate that EDVs possess at least two different alpha(1)-adrenoceptor populations, which are predominantly of the alpha(1A) and alpha(1B) subtypes. These data may assist in the development of more selective antagonists for therapeutic use in horses.     

Pharmacokinetics of yohimbine following intravenous administration to horses

DiMaio Knych, H.K., Steffey, E.P., Deuel, J.L., Shepard, R.A., Stanley, S.D. Pharmacokinetics of yohimbine following intravenous administration to horses. J. vet. Pharmacol. Therap. 34 , 58–63. Yohimbine is an alpha 2 adrenergic receptor antagonist used most commonly in veterinary medicine to reverse the effects of the alpha 2 receptor agonists, xylazine and detomidine. Most notably, yohimbine has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. The recent identification of a yohimbine positive urine sample collected from a horse racing in California has led to the investigation of the pharmacokinetics of this compound. Eight healthy adult horses received a single intravenous dose of 0.12 mg/kg yohimbine. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 72 h post drug administration. Plasma samples were analyzed using liquid chromatography–mass spectrometry (LC‐MS) and data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentration was 114.5 + 31.8 ng/mL and occurred at 0.09 + 0.03 h. Mean ± SD systemic clearance (Cls) and steady‐state volume of distribution (Vdss) were 13.5 + 2.1 mL/min/kg and 3.3 + 1.3 L/kg following noncompartmental analysis. For compartmental analysis, plasma yohimbine vs. time data were best fitted to a two compartment model. Mean ± SD Cls and Vdss of yohimbine were 13.6 ± 2.0 mL/min/kg and 3.2 ± 1.1 L/kg, respectively. Mean ± SD terminal elimination half‐life was 4.4 ± 0.9 h following noncompartmental analysis. Immediately following administration, two horses showed signs of sedation, while the other six appeared behaviorally unaffected. Gastrointestinal sounds were moderately increased compared to baseline while fecal consistency appeared normal.     

重组猪干扰素α1冻干粉针剂对猪的安全性试验研究简

试验旨在观察自行研制的重组猪干扰素α1冻干粉针剂对猪的安全性。将20头健康仔猪随机分为4组（3组试验组和1组对照组）,每组5只,3组试验组分别肌肉注射低、中和高剂量重组猪干扰素α1冻干粉针剂,连续注射7 d,对照组同时肌肉注射生理盐水。对动物基本生命体征、血常规、血液生化指标、组织标本病理学指标进行观察。各试验组仔猪的外表及行为特征均正常;体温、体重的变化也在正常范围之内;重要脏器如脑、肺脏、肝脏、心脏和脾脏病理解剖HE染色结果显示无器质性病变发生;血常规、血液生化指标均正常。试验结果表明本项目研制的重组猪干扰素α1冻干粉针剂对仔猪无明显毒副作用,使用安全。     

Epidural injection of xylazine for perineal analgesia in horses

Local anesthetics given in the epidural space of a horse may cause hind limb weakness in addition to analgesia. Because alpha 2 agonists given by epidural injection cause sensory blockade without motor effects in human beings and other species, their use in veterinary anesthesia is appealing. This study was designed to examine the effectiveness of xylazine HCl, an alpha 2 agonist commonly used in horses. Xylazine, 0.9% NaCl, and lidocaine were given by epidural injection to horses subjected to perineal electrical stimulation. Administration of xylazine (0.17 mg/kg of body weight, diluted to a 10-ml volume, using 0.9% NaCl) induced approximately 2.5 hours of local analgesia without apparent side effects. Higher doses of xylazine caused mild hind limb ataxia. Administration of lidocaine induced a similar duration of analgesia, with severe hind limb ataxia (100% incidence). We concluded that xylazine given by epidural injection results in safe, effective perineal analgesia in horses.     

New perspectives in cardiopulmonary therapeutics: receptor-selective adrenergic drugs

Recent advances in basic biomedical research have led to the development of clinically useful drugs known as "second generation" adrenergic receptor stimulants (agonists) and blockers (antagonists). Adrenergic receptors are now differentiated into 4 distinct subtypes: alpha 1, alpha 2, beta 1, and beta 2. The new drugs are more receptor-selective and tissue-specific than older ones and, hence, have increased potential for directed therapeutic action, with relatively less side effects on nontargeted organs. The beta 2-selective agonist terbutaline, eg, causes bronchodilation with less beta 1-cardiac excitation than does the beta 1-beta 2 nonselective agonist isoproterenol. Compared with the latter, the beta 1-selective agonist dobutamine increases myocardial contractile force and cardiac output with less beta 2-mediated vasodilation and hypotension. The beta 1-selective antagonist metoprolol has advantage over the beta 1-beta 2 nonselective blocker propranolol for controlling beta 1-cardiac excitation in patients with compromised pulmonary function. Prazosin, an alpha 1-selective blocking agent, evokes peripheral vasodilation with less reflex tachycardia than does the nonselective alpha 1-alpha 2 blocker phentolamine, probably because the former spares the prejunctional alpha 2-receptors that subserve autoinhibition of norepinephrine release from the sympathetic neuron. The contemporary practice of internal medicine will no doubt include an understanding of the pharmacologic properties associated with the various adrenergic receptor subtypes.     

Propofol anesthesia.

Although questions may still remain regarding the use of this unique sedative-hypnotic drug with anesthetic properties in high-risk patients, our studies have provided cardiopulmonary and neurological evidence of the efficacy and safety of propofol when used as an anesthetic under normal and selected impaired conditions in the dog. 1. Propofol can be safely and effectively used for the induction and maintenance of anesthesia in normal healthy dogs. Propofol is also a reliable and safe anesthetic agent when used during induced cardiovascular and pulmonary-impaired conditions without surgery. The propofol requirements to induce the safe and prompt induction of anesthesia prior to inhalant anesthesia with and without surgery have been determined. 2. The favorable recovery profile associated with propofol offers advantages over traditional anesthetics in clinical situations in which rapid recovery is important. Also, propofol compatibility with a large variety of preanesthetics may increase its use as a safe and reliable i.v. anesthetic for the induction and maintenance of general anesthesia and sedation in small animal veterinary practice. Although propofol has proven to be a valuable adjuvant during short ambulatory procedures, its use for the maintenance of general anesthesia has been questioned for surgery lasting more than 1 hour because of increased cost and marginal differences in recovery times compared with those of standard inhalant or balanced anesthetic techniques. When propofol is used for the maintenance of anesthesia in combination with a sedative/analgesic, the quality of anesthesia is improved as well as the ease with which the practitioner can titrate propofol; therefore, practitioners are able to use i.v. anesthetic techniques more effectively in their clinical practices. 3. Propofol can induce significant depression of respiratory function, characterized by a reduction in the rate of respiration. Potent alpha 2 sedative/analgesics (e.g., xylazine, medetomidine) or opioids (e.g., oxymorphone, butorphanol) increase the probability of respiratory depression during anesthesia. Appropriate consideration of dose reduction and speed of administration of propofol reduces the degree of depression. Cardiovascular changes induced by propofol administration consist of a slight decrease in arterial blood pressures (systolic, mean, diastolic) without a compensatory increase in heart rate. Selective premedicants markedly modify this characteristic response. 4. When coupled with subjective responses to painful stimuli, EEG responses during propofol anesthesia provide clear evidence that satisfactory anesthesia has been achieved in experimental dogs. When propofol is used as the only anesthetic agent, a higher dose is required to induce an equipotent level of CNS depression compared with the situation when dogs are premedicated. 5. The propofol induction dose requirement should be appropriately decreased by 20% to 80% when propofol is administered in combination with sedative or analgesic agents as part of a balanced technique as well as in elderly and debilitated patients. As a general recommendation, the dose of propofol should always be carefully titrated against the needs and responses of the individual patient, as there is considerable variability in anesthetic requirements among patients. Because propofol does not have marked analgesic effects and its metabolism is rapid, the use of local anesthetics, nonsteroidal anti-inflammatory agents, and opioids to provide postoperative analgesia improves the quality of recovery after propofol anesthesia. 6. The cardiovascular depressant effects of propofol are well tolerated in healthy animals, but these effects may be more problematic in high-risk patients with intrinsic cardiac disease as well as in those with systemic disease. In hypovolemic patients and those with limited cardiac reserve, even small induction doses of propofol (0.75-1.5 mg/kg i.v.) can produce profound hypotens     

Epidural analgesia in the dog and cat

SUMMARY: A brief outline of the history of epidural analgesia is followed by a review of the anatomy of the epidural space with particular reference to epidural block. The technique of epidural injection in the dog is described as are the indications for the technique. These include the provision of anaesthesia for such procedures as orthopaedic surgery of the hind limb and caesarian section. The cardiovascular effects of epidural block are discussed and suggestions are made for the prevention of hypotension. The various drugs and their combinations which may be used for epidural administration are outlined. The commonest used local anaesthetic agents are bupivacaine and lidocaine. Epidural administration of opioid drugs is a relatively new technique which is used to provide intra- and post-operative analgesia. Morphine is the drug of choice for this indication.The use of other classes of drugs, such as the alpha 2 agonists and ketamine, are also considered. A variety of side-effects, contra-indications and complications are described together with methods for reducing their incidence and effects.