analgesia for anesthetized patients

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TOPICAL REVIEW

Analgesia for Anesthetized Patients

Kip A. Lemke, DVM, MSc, Dipl. ACVA, and Catherine M. Creighton, DVM

Many perioperative pain management protocols for cats and dogs are overly complex, some are ineffective, andstill others expose patients to unnecessary risk. The purpose of this article is to provide clinicians with a basicunderstanding of the pathophysiology of perioperative pain and a working knowledge of the principles of effective therapy. First, the concept of multimodal analgesic therapy is discussed. Next, the pathophysiology of perioperative pain and the clinical pharmacology of the major classes of analgesic drugs are reviewed. And last,a simplified approach to managing perioperative pain in cats and dogs is presented.© 2010 Elsevier Inc. All rights reserved.

Keywords: analgesia, anesthesia, pain, dogs, cats

Multimodal analgesic therapy has gained widespreadacceptance in the management of perioperative pain

in both dogs and cats.1-3 In recent years, a clearer understand-ing of the pathophysiology of perioperative pain has pro-vided the conceptual framework for a more rational use of analgesic drugs and techniques. Surgical trauma and inflam-mation produce sensitization of the peripheral nervous sys-tem, and the subsequent barrage of nociceptive input pro-duces sensitization of neurons in the dorsal horn of the spinalcord. Blockade or attenuation of ascending nociceptive path-ways or activation of descending antinociceptive pathwaysby different classes of analgesic drugs usually provides better

analgesia with fewer side effects than unimodal therapy witha single class of analgesic drugs. Because peripheral and cen-tral neural blockade with local anesthetics are the only anal-gesic techniques that can produce complete blockade of pe-ripheral nociceptive input, these techniques are the mosteffective way to attenuate sensitization of the central nervoussystem and the development of pathological pain.4,5 Clini-cians should also remember that atraumatic surgical tech-nique is always the most effective method to prevent periph-eral and central sensitization and the development of painpostoperatively.

The neuroendocrine or stress response to surgical traumacompromises hemostatic, metabolic, and immunological

function, which increases perioperative morbidity and mor-tality.6,7 Early studies in human infants undergoing cardiacsurgery demonstrated that the neuroendocrine response wassignificantly reduced by intraoperative administration of halothane and fentanyl when compared with administrationof halothane alone.8 In a subsequent clinical study, the mor-

tality rate dropped from 25% to 0% in a similar group of infants when sufentanil was given intraoperatively and addi-tional opioids were given postoperatively.9 Perioperative useof neural blockade, in particular central neural blockade,also attenuates the neuroendocrine response and dramati-cally reduces mortality and the incidence of major complica-tions in human patients undergoing a wide variety of surgicalprocedures.10 In this analysis of 141 clinical trials, patientswith central neural blockade had a 30% reduction in mor-tality and a 40% to 60% reduction in major complications(thromboembolism, hemorrhage, respiratory depression,pneumonia) when compared with those without central neu-

ral blockade. Intraoperative use of multimodal analgesictherapy also reduces inhalation anesthetic requirements andautonomic responses to noxious surgical stimuli. These re-ductions improve cardiopulmonary function intraopera-tively and facilitate a rapid, smooth recovery from anesthesiapostoperatively.

Alpha-2 agonists, opioids, N-methyl-D-aspartate (NMDA) an-tagonists, cyclooxygenase (COX) inhibitors, and neuralblockade with local anesthetics are often used perioperativelyas part of a multimodal strategy to manage pain.1-3 Theseclasses of analgesic drugs can be incorporated easily intoanesthetic and pain management plans for cats and dogsundergoing most types of surgical procedures. Alpha-2 ago-nists can be used preoperatively and postoperatively to pro-vide sedation and analgesia. Opioids can be used throughoutthe perioperative period to reduce anesthetic requirementsand to manage pain. NMDA antagonists (ketamine) can beused throughout the perioperative period to manage pain inpatients with significant central sensitization and pathologi-cal pain. COX inhibitors can be used postoperatively to re-duce opioid requirements and provide more effective analge-sia with fewer side effects. Peripheral and central neuralblockade with local anesthetics can be used intraoperativelyto reduce anesthetic requirements and attenuate the develop-ment of central sensitization. Neural blockade can also be

used postoperatively to manage pain in selected patients. Aclear understanding of the pathophysiology of pain and the

From the Atlantic Veterinary College, University of Prince Edward Island,

Charlottetown, Prince Edward Island, Canada.Address reprint requests to: Kip A. Lemke, DVM, MSc, Dipl. ACVA, At-

lantic Veterinary College, University of Prince Edward Island, 550 Univer-

sity Ave, Charlottetown, PE, Canada, C1A 4P3. E-mail: [email protected].

© 2010 Elsevier Inc. All rights reserved.

1527-3369/06/0604-0171\.00/0doi:10.1053/j.tcam.2009.12.003

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clinical pharmacology of the major classes of analgesic drugsis required to use multimodal analgesic therapy safely andeffectively in anesthetized patients.

Pathophysiology

The terminology used to describe the pathophysiology of pain is confusing, so defining a few terms relevant to themanagement of perioperative pain is important. Nociceptionis defined as the neural response to a noxious stimulus. Spe-cifically, nociception includes signal transduction and nerveconduction in the peripheral nervous system, and synaptictransmission, projection, and modulation of nociceptive in-put in the central nervous system (Fig 1). Pain, on the otherhand, is a complex sensation that requires integration of nociceptive and other sensory input at the cortical level. Painis defined as an unpleasant sensory or emotional experiencethat is associated with actual or potential tissue damage. Paincan be further classified anatomically as somatic or visceralpain, or temporally as acute or chronic pain. Recent neuro-anatomical and functional imaging studies suggest that painis one component of an interoceptive system that is primarilyresponsible for maintaining internal homeostasis, and thatthere are significant differences among species in the neuralcomponents that make up this system.11

Most perioperative pain is due to surgical trauma and in-flammation. Some patients may have preexisting tissuetrauma and inflammation, and others may have pain associ-ated with nerve injury. Although a small number of surgical

patients may experience both inflammatory and neuropathicpain, inflammatory pain is by far the most common type of perioperative pain. The mechanisms of inflammatory painare reasonably well understood and form the basis for ratio-nal, effective, multimodal analgesic therapy. Neuropathicpain is relatively uncommon in surgical patients, and themechanisms of neuropathic pain are similar to those of in-flammatory pain.12,13 Consequently, clinicians should focuson understanding the pathophysiology and management of inflammatory pain.

Nociceptive Pathways

Ascending nociceptive pathways begin in the peripheraltissues and project to the dorsal horn of the spinal cord, brainstem, thalamus, and cerebral cortex (Fig 1). The nociceptivepathways are composed of 3 general types of neurons. Thefirst-order neurons are primary afferent neurons, and theseneurons are responsible for transduction of noxious stimuliand conduction of electrical signals to the dorsal horn of thespinal cord. The second-order neurons are projection neu-rons, and these neurons receive input from the primary affer-ent neurons and project to the medulla, pons, midbrain, thal-amus, and hypothalamus. Third-order supraspinal neuronsintegrate input from spinal neurons and project to subcorti-

cal and cortical areas where pain is finally perceived. Su-praspinal processing of afferent nociceptive input is also

Figure 1. Overview of nociceptive and antinociceptive path-ways. Surgical trauma activates mechanical, chemical, andthermal nociceptors. Action potentials are conducted to thedorsal horn of the spinal cord by primary afferent nervefibers. Second-order projection neurons encode and relay sig-nals to the brainstem and thalamus. Third-order neurons inthe thalamus project to the limbic system and somatosensorycortex where pain is perceived. Descending antinociceptivepathways modulate nociceptive processing at the level of thethalamus, brainstem, and spinal cord. Different classes of analgesic drugs act at different sites in the nociceptive andantinociceptive pathways. Multimodal analgesic therapy in-

hibits processing of nociceptive input at 2 or more sites. PAG,periaqueductal gray; RVM, rostroventral medulla.

Volume 25, Number 2, May 2010 71



closely integrated with regulation of the autonomic nervoussystem.

Primary afferent neurons are bipolar neurons. The cellbodies of these bipolar neurons are located in the trigeminal

and dorsal root ganglia, and their axons project peripherallyto somatic and visceral tissues and centrally to the dorsalhorn of the spinal cord. Some primary afferent neurons re-spond to noxious or high-threshold stimuli, and others re-spond to non-noxious or low-threshold stimuli (touch). Af-ferent nociceptive neurons have free nerve endings thatchange or “transduce” noxious mechanical, thermal, orchemical stimuli into electrical signals. Somatic tissues have ahigher density of nociceptive nerve fibers and smaller recep-tive fields, whereas visceral tissues have a lower density of nociceptive nerve fibers and larger receptive fields. These an-atomical differences may account for some of the qualitativedifferences between somatic (discrete) and visceral (diffuse)

pain.Primary afferent neurons are classified by axon diameter,

the presence or absence of myelination, and their response tomechanical, thermal, and chemical stimuli. A afferent neu-rons have large, myelinated axons that conduct impulses at avelocity of greater than 30 m/sec. The free nerve endings of these fibers respond to non-noxious mechanical stimuli(touch) but do not respond to noxious stimuli directly. A

nociceptive neurons have small, myelinated axons that con-duct impulses at a velocity of 3 to 30 m/sec. The free nerveendings of these fibers contain membrane-bound receptorsthat respond primarily to intense mechanical and thermalstimuli and are called mechanothermal nociceptors. C noci-

ceptive neurons have small, unmyelinated axons that con-duct nerve impulses at a velocity of less than 3 m/sec. The freenerve endings of these fibers contain membrane-bound recep-tors that respond to chemical as well as thermal and mechan-ical stimuli and are called polymodal nociceptors. Small, my-elinated A fibers carry the nociceptive input responsible forthe fast, sharp pain that occurs immediately after injury. Thenociceptive input responsible for the prolonged dull pain thatoccurs several seconds later is carried by small, unmyelinatedC fibers. Silent nociceptive neurons are also present in so-matic tissues. The free nerve endings of these neurons onlyrespond to mechanical and thermal stimuli after they are

activated by chemical (inflammatory) mediators. This classi-fication scheme is derived from analysis of fibers that inner-vate the somatic tissues (skin). Visceral pain is qualitativelydifferent from somatic pain and is typically dull and poorlylocalized. Visceral pain also lacks the fast and slow compo-nents that are characteristic of somatic pain.

Transduction of mechanical, thermal, and chemical stim-uli by the free nerve endings of A and C nociceptive fibers ismediated by membrane-bound receptors.13-15 Most of thesereceptors are nonselective cation channels that are gatedby temperature, chemical ligands, or mechanical shearingforces. Activation of these channels increases inward conduc-tion of Na and Ca2 ions, which ultimately depolarizes the

membrane and generates a burst of action potentials. Themechanisms of mechanical signal transduction are not well

defined. Noxious mechanical stimuli may activate a mechan-ically gated ion channel directly, or shearing forces may re-lease adenosine triphosphate, which acts on purine receptors(P2X). Noxious chemical stimuli (H) activate acid-sensing

ion channels and transient receptor potential vanilloid(TRPV1) channels. Noxious heat also activates TRPV1 chan-nels as well as related channels (TRPV2), and noxious coldactivates transient receptor potential menthol (TRPM8)channels.

Nociceptive afferent neurons synapse with second-orderneurons in the dorsal horn of the spinal cord. Projectionneurons and interneurons are the 2 major types of nocicep-tive neurons in the dorsal horn, and these neurons are orga-nized in layers or laminae. Neurons that mediate nociceptionare located in laminae I, II, and V. Projection neurons arelocated in laminae I and V, and they have axons that crossmidline and project to third-order supraspinal neurons. Pro-

jection neurons located in lamina I receive input directly fromA and C nociceptive fibers and are classified as nociceptive-specific and polymodal nociceptive neurons, respectively.Projection neurons in lamina V receive input from both no-ciceptive and non-nociceptive (A) fibers and are classified aswide, dynamic-range neurons. Interneurons are located inlamina II and also receive input from nociceptive and non-nociceptive (A) fibers. Inhibitory and excitatory interneu-rons play a central role in gating and modulating nociceptiveinput. Propriospinal neurons that project across several der-matomes are also present in the dorsal horn and are respon-sible for segmental reflexes associated with nociception.

Glutamate is the primary excitatory neurotransmitter in

the dorsal horn of the spinal cord. Nociceptive as well asnon-nociceptive fibers co-release glutamate and neuropep-tides (substance P, neurokinin A, calcitonin gene–relatedpeptide). With normal afferent input, glutamate bindsto -amino-3-hydroxy-5-methyl-4-isoxazolepropionoic acid(AMPA) receptors located on the postsynaptic membrane of projection neurons. Neuropeptides bind to several types of receptors on the postsynaptic membrane. With intensive af-ferent input, prolonged activation of AMPA and neuropep-tide receptors leads to progressive depolarization of thepostsynaptic membrane and activation of additional types of glutamate receptors. Activation of a specific type of gluta-

mate receptor, the NMDA receptor, plays a key role in thedevelopment of central sensitization.The spinothalamic tract (STT) is the major ascending no-

ciceptive pathway in carnivores and primates.11,16 LaminaI, nociceptive (nociceptive-specific, polymodal nociceptive)neurons are somatotopically organized, modality-selectiveneurons with small receptive fields that convey discrete nox-ious mechanical, thermal, and chemical afferent input. Theseneurons project to the ventromedial nucleus of the lateralthalamus, which projects to the insular cortex and the sec-ondary somatosensory cortex. These neurons also project tothe mediodorsal nucleus of the medial thalamus, whichprojects to the anterior cingulate cortex. Like the dorsal

horn, glutamate is an important excitatory neurotransmitterwithin the thalamic nuclei. Lamina V, wide, dynamic-range

72 Topics in Companion Animal Medicine



neurons have large receptive fields, are not somatotopicallyorganized or modality selective, and are responsible for inte-gration of all afferent input to the dorsal horn. These neuronsproject to the motor thalamus (ventrodorsal and ventrolat-

eral nuclei), which projects to the basal ganglia and the pri-mary somatosensory cortex. Axons from lamina I are con-centrated in the lateral STT, and axons from lamina V areconcentrated in the ventral STT. The thalamus relays afferentinput from the STT and integrates this information with af-ferent input from the autonomic nervous system. Projectionfrom neurons in the lateral thalamus to neurons in the insularand secondary somatosensory cortex appears to be responsi-ble for the sensory-discriminative aspects of pain. Projectionfrom neurons in the medial thalamus to neurons in the ante-rior cingulate cortex appears to be responsible for the moti-vational-affective aspects of pain. Projection from neurons inthe motor thalamus to neurons in the primary somatosensory

cortex appears to be responsible for sensory and motor inte-gration. Direct connections between the lateral thalamus andthe dorsal margin of the insular cortex (interoceptive cortex)are more developed in primates than in carnivores.

Antinociceptive Pathways

Mammals also have descending antinociceptive pathwaysthat modulate nociceptive input at spinal and supraspinallevels (Fig 1). The antinociceptive pathways begin at the su-praspinal level and project to neurons in the dorsal horn of the spinal cord. The periaqueductal gray matter (midbrain),locus ceruleus (pons), and nucleus raphe magnus (medulla)

are all important structures in the modulation of nociceptiveinput. The periaqueductal gray matter receives direct inputfrom the thalamus and the hypothalamus, and indirect inputfrom the insular cortex and the anterior cingulate cortex.These neurons in the periaqueductal gray matter send projec-tions to neurons in the nucleus raphe magnus, which projectto the dorsal horn of the spinal cord. Neurons in the locusceruleus project directly to the dorsal horn, and they may alsoreceive input from the periaqueductal gray matter.

Endogenous opioids (endorphins, enkephalins, dynor-phins), serotonin, and norepinephrine are the primary neu-rotransmitters in the descending antinociceptive pathways.

Axons that originate in the nucleus raphe magnus releaseserotonin in the dorsal horn of the spinal cord and are called“serotonergic” neurons. Similarly, neurons that originate inthe locus ceruleus release norepinephrine in the dorsal hornand are called “noradrenergic” neurons. Supraspinal releaseof endogenous opioid peptides activates both types of neu-rons, whereas supraspinal release of release of -aminobu-tyric acid (GABA) inhibits both types of neurons. Supraspinalinhibition of descending antinociceptive pathways is medi-ated by GABAA receptors. At the supraspinal level, endoge-nous opioids not only activate descending antinociceptivepathways, but inhibit GABA-mediated inhibition of thesesame pathways, which is called “disinhibition.”

Release of norepinephrine and serotonin in the dorsal hornof the spinal cord, and subsequent release of enkephalins and

GABA by local interneurons, inhibit presynaptic calciumchannels that modulate neurotransmitter release. This inhi-bition, mediated by presynaptic noradrenergic (2), opioid(), and GABAB receptors, limits release of glutamate and

neuropeptides from primary afferent neurons, which inhibitsnociceptive transmission. Release of norepinephrine, en-kephalins, and GABA in the dorsal horn hyperpolarizes pro-jection neurons, which also inhibits nociceptive trans-mission. This inhibition is mediated by postsynapticnoradrenergic (2) and opioid () receptors that activatepotassium channels, which leads to an outward flux of potassium ions and hyperpolarization of the postsynapticmembrane. This inhibition is also mediated by postsynap-tic GABAA receptors that activate chloride channels,which leads to an inward flux of chloride ions and hyper-polarization of the postsynaptic membrane. In summary,release of norepinephrine, endogenous opioids, and GABA

inhibits synaptic transmission between primary afferentneurons and projection neurons by inhibiting neurotrans-mitter release and hyperpolarizing the postsynaptic mem-brane, which effectively shuts down the key synapse in thedorsal horn.

Peripheral and Central Sensitization

Neural plasticity is defined as the ability of the nervoussystem to modify its function in response to different envi-ronmental stimuli. Surgical trauma and inflammation pro-duce sensitization of the peripheral nervous system, and thesubsequent barrage of nociceptive input produces sensitiza-

tion of neurons in the dorsal horn of the spinal cord. Periph-eral and central sensitization of nociceptive pathways plays acentral role in the development of pathological pain. 17 Pa-tients with no preexisting tissue trauma and inflammationexperience pain that is physiological or protective in nature(Table 1). This type of inflammatory pain is well localized,proportionate to the peripheral stimulus, and subsides oncethe inflammatory process resolves. Patients with significanttissue trauma and inflammation experience pain that ispathological or debilitating in nature (Table 2). This type of inflammatory pain is diffuse, disproportionate to the periph-eral stimulus, and continues beyond resolution of the inflam-matory process. A key concept that is often lost when trying

to understand the clinical relevance of neural plasticity is thatcentral sensitization occurs secondary to surgical trauma,inflammation, and the development of peripheral sensitiza-

Table 1. Characteristics of Physiological Pain

● Protective● Discrete or well localized● No peripheral or central sensitization● Proportionate to the peripheral stimulus● Subsides once the inflammatory response resolves● Pain can be differentiated from touch● Responds well to conventional analgesic therapy




tion. Consequently, atraumatic surgical technique and neuralblockade are far more effective than other types of analgesictherapy in limiting the development of pathological pain,

blunting the stress response, preventing major complications,and reducing mortality.18,19

Peripheral sensitization occurs as a direct consequence of tissue trauma and inflammation. Tissue trauma leads to therelease of inflammatory mediators from damaged cells (H,K, prostaglandins), plasma (bradykinin), platelets (seroto-nin), mast cells (histamine), and macrophages (cytokines).Some inflammatory mediators activate nociceptors directly(bradykinin), whereas others sensitize nociceptors (prosta-glandins). Activation of nociceptors also leads to antidromalor retrograde activation of nociceptive nerve fibers and re-lease of substance P and other neuropeptides. Release of these neuropeptides leads to mast cell degranulation, vasodi-

lation, edema, and further activation and sensitization of nociceptors. Peripheral sympathetic nerve terminals alsocontribute to activation and sensitization of nerve terminalsby releasing norepinephrine and prostaglandins. Ultimately,tissue trauma and inflammation produce a “sensitizing soup”of chemical mediators that convert high-threshold nocicep-tors to low-threshold nociceptors. In other words, peripheralsensitization is characterized by a reduction in the activationthreshold of peripheral nociceptors.

Central sensitization occurs as an indirect consequence of tissue trauma and inflammation and is contingent to a largedegree on the development of peripheral sensitization. Con-

stant activation of sensitized peripheral nociceptors leads tosustained release of glutamate and neuropeptides from affer-ent fibers. Constant activation of AMPA and neuropeptidereceptors on dorsal horn projection neurons leads to progres-sive cellular depolarization and activation of additional typesof glutamate receptors (NMDA, metabotropic). Normally,the channel of NMDA receptor complex is blocked by amagnesium plug. Progressive depolarization of the postsyn-aptic membrane releases this plug, activates the receptorcomplex, and increases inward conduction of Ca2 ions. Thisinflux of calcium, along with activation of other types of receptors, leads to activation of phospholipases, polyphos-phoinosites, kinases, and other intracellular messengers.

These activity-dependent changes lead to an increase in theexcitability of dorsal horn projection neurons. This initial

phase of central sensitization is called short-term sensitiza-tion. If the inflammatory process continues for several days,gene regulatory proteins are activated, new types receptorsare expressed, and dorsal horn projection neurons become

even more reactive to subsequent nociceptive input. Thisphase of central sensitization is called long-term sensitiza-tion. Activation of NMDA receptors and the subsequent in-flux of Ca2 also leads to the release of arachidonic acid,which is converted to prostaglandins by COX. Prostaglan-dins act presynaptically and postsynaptically to facilitate thedevelopment of central sensitization. Glial cells also appearto facilitate the development of central sensitization. Micro-glia and astrocytes normally play a supportive role in neuro-transmission, but they are also activated by glutamate andneuropeptides released from primary afferent fibers. Acti-vated glial cells release adenosine triphosphate, glutamate,nitric oxide, and cytokines, which facilitate release of neuro-

transmitters from afferent fibers and further sensitization of projection neurons.

Clinical Pharmacology

The primary goal of perioperative multimodal analgesic ther-apy is to limit the development of peripheral and centralsensitization, and prevent the development of pathologicalpain. Effective analgesic therapy also blunts the neuroendo-crine response, reduces major complications, and improvesoutcome. There are 5 major classes of analgesic drugs, andeach class blocks or modulates nociceptive input at one ormore sites of action (Fig 1). Alpha-2 agonists and opioidsalter the central perception of pain. Activation of supraspinaland spinal alpha-2 receptors and opioid receptors also inhib-its synaptic transmission in the dorsal horn of the spinal cord.Dissociative anesthetics (ketamine) block NMDA receptorson projection neurons, which inhibit the development of cen-tral sensitization. Peripheral and central neural blockadewith local anesthetics also inhibits the development of centralsensitization. COX inhibitors reduce inflammation, whichlimits the development of peripheral sensitization. COX in-hibitors also reduce the synthesis of prostaglandins in thedorsal horn of the spinal cord, which limits the developmentof central sensitization.

Selective Alpha-2 Agonists

Norepinephrine is the endogenous ligand for spinal andsupraspinal alpha-2 adrenergic receptors. Medetomidine anddexmedetomidine are the selective alpha-2 agonists currentlyavailable in North America. Medetomidine is supplied as aracemic mixture of 2 optical enantiomers. Dexmedetomidineis the active enantiomer, whereas levomedetomidine has noapparent pharmacological activity. As a result, dexmedeto-midine is approximately twice as potent as medetomidine.The clinical effects of medetomidine and dexmedetomidineare comparable when equivalent sedative doses are adminis-

tered to cats and dogs. Medetomidine has a rapid onset afterparenteral injection, and the drug has a duration of action of

Table 2. Characteristics of Pathological Pain

● Debilitating● Diffuse or poorly localized●

Significant peripheral and central sensitization● Disproportionate or exaggerated response to the periph-

eral stimulus● Continues beyond resolution of the inflammatory re-

sponse● Pain cannot be differentiated from touch● Does not respond well to conventional analgesic therapy




approximately 1 hour in dogs. The alpha-2 to alpha-1 adren-ergic receptor selectively ratios for medetomidine and xyla-zine are 1620:1 and 160:1, respectively.20 Medetomidine anddexmedetomidine are approved for use in dogs in Canada

and the United States, and studies evaluating the use of thesedrugs in cats have been completed.21-24

Selective alpha-2 agonists induce reliable dose-dependentsedation, analgesia, and muscle relaxation in cats anddogs.25,26 The sedative and analgesic effects of selective al-pha-2 agonists are mediated by activation of alpha-2 adren-ergic receptors located in the pons (locus ceruleus) and thedorsal horn of the spinal cord, respectively. In addition toproviding sedation and analgesia, preoperative administra-tion of medetomidine reduces the amount of intravenous andinhalation anesthetic required to induce and maintain anes-thesia.27-29 Perioperative administration of selective alpha-2agonists also blunts the neuroendocrine response and reduces

catecholamine and cortisol levels.30,31 Blood pressure in-creases, and heart rate and cardiac output decrease after me-detomidine administration. Bradycardia and atrioventricularblockade are potential complications, and heart rate andrhythm should be monitored closely. Medetomidine does notsensitize the myocardium to catecholamines or facilitate de-velopment of ventricular arrhythmias in patients anes-thetized with isoflurane.32,33 Respiratory rate and minuteventilation are well maintained after administration of medetomidine or dexmedetomidine in conscious and anes-thetized dogs.34,35 Blood glucose and urine production in-crease significantly after administration of medetomidine.

Selective alpha-2 agonists are used perioperatively to se-

date and calm patients, provide muscle relaxation, and po-tentiate the analgesic and anesthetic effects of other drugs.Medetomidine and dexmedetomidine are administered atrelatively low doses, and the use of these drugs is usuallylimited to healthy, hemodynamically stable patients. Preop-eratively, selective alpha-2 agonists are often given in combi-nation with opioids. The preanesthetic intramuscular doseranges for medetomidine in healthy dogs and cats are 0.005to 0.01 mg/kg and 0.01 to 0.02 mg/kg, respectively. Ultra-low doses of medetomidine can be given postoperatively toprovide sedation. The postanesthetic intramuscular doseranges for medetomidine in healthy for healthy dogs and cats

are 0.001 to 0.002 mg/kg and 0.002 to 0.004 mg/kg, respec-tively. Dexmedetomidine can be given at approximately half of the medetomidine dose. Atropine or glycopyrrolate can beused to manage bradycardia associated with administrationof low and ultra-low doses of selective alpha-2 agonists.

Opioids

Endorphins, enkephalins, and dynorphins are the endoge-nous ligands for spinal and supraspinal opioid receptors.Currently, 3 major classes of opioid receptors have beencloned: OP1 (), OP2 () and OP3 (). OP1, OP2, and OP3receptors modulate supraspinal and spinal analgesia, as well

as sedation, bradycardia, respiratory depression, and gastro-intestinal motility. Receptor subtypes of each of these classes

have been identified, and expression of these subtypes variesamong tissues. There are also significant differences in theexpression of opioid receptors among species. Parenteral ad-ministration of opioids usually causes sedation in dogs,

whereas administration of high doses of opioids can causeexcitation and dysphoria in cats. Respiratory depression is asignificant side effect in human patients, but ventilation isbetter maintained in cats and dogs. Butorphanol, morphine,hydromorphone, and fentanyl are the opioids used mostcommonly in small animals. Buprenorphine and tramadolhave also been used perioperatively to a limited extent.

Opioid agonists are the safest and most effective class of analgesic drugs used for the management of perioperativepain in cats and dogs. Morphine, hydromorphone, and fen-tanyl are the opioid agonists used most commonly in smallanimals. These analgesic drugs are agonists at all 3 types of opioid receptors. Opioid agonists are equally efficacious in

treating moderate to severe pain, but differ in potency andduration of action. Intraoperative administration of mor-phine, hydromorphone, or fentanyl reduces isoflurane re-quirements by 30% to 50% in cats and dogs. 36-39 Significantrespiratory depression can occur intraoperatively and post-operatively if the additive effects of opioid agonists and gen-eral anesthetics are not considered. Morphine and hydro-morphone are often administered as preanesthetics, andvomiting can occur with either drug. High doses of hydro-morphone ( 0.1 mg/kg) can also cause significant postop-erative hyperthermia in cats.40-42 Morphine and hydromor-phone have an intermediate duration of action (2-4 hours)after parenteral administration. The preanesthetic intramus-

cular dose range for morphine in cats and dogs is 0.2 to 0.4mg/kg. Hydromorphone is approximately 5 times more po-tent than morphine, and the preanesthetic intramusculardose range for hydromorphone in cats and dogs is 0.05 to 0.1mg/kg. Approximately half of the preanesthetic dose of mor-phine or hydromorphone can be given intraoperatively orpostoperatively. Morphine can also be given epidurally aloneor in combination with local anesthetics. The dose range forpreoperative or postoperative epidural administration of morphine is 0.1-0.3 mg/kg. At this dose range, the onset timeis slow (1-2 h), but the duration of action in long (12-24 h).Morphine can also be given postoperatively as an intrave-

nous constant-rate infusion at a dose range of 0.1 to 0.2mg/kg/h. Morphine has a relatively long duration of actionand the drug will accumulate over time. As a result, patientsshould be monitored closely, and the infusion rate should bereduced as needed. Fentanyl can also be given intravenouslyas a preanesthetic. The drug is approximately 100 times morepotent than morphine and has a relatively short duration of action (0.5 hour). The preanesthetic intravenous dose rangefor fentanyl in cats and dogs is 0.001 to 0.005 mg/kg. Fent-anyl is less likely to accumulate over time, and the drug isoften given intraoperatively to dogs as an intravenous con-stant rate infusion. The amount of inhalation anesthetic re-quired to maintain adequate anesthetic depth is reduced by

30% to 50%, which improves cardiovascular function.Minute ventilation may decrease, and positive-pressure ven-




tilation may be required to prevent significant hypoventila-tion (PaCO2 60 mm Hg). Intraoperatively, the dose rangefor fentanyl in dogs is 0.005 to 0.01 mg/kg/h. Fentanyl canalso be given postoperatively as an intravenous constant-rate

infusion at a dose range of 0.001 to 0.005 mg/kg/h. Objectiveclinical data on the use of intraoperative and postoperativefentanyl infusions in cats are limited.

Fentanyl patches were designed to be applied to humanskin. Even in healthy cats and dogs, systemic absorption of fentanyl from transdermal patches is erratic.43,44 In surgicalpatients, altered body temperature, peripheral circulation,and hydration can all compromise transdermal absorption of fentanyl. On the other hand, heating pads and forced-airwarmers can dramatically increase fentanyl absorption intra-operatively and postoperatively. Consequently, preoperativeand intraoperative use of fentanyl patches should be avoided.Once normal body temperature, peripheral circulation, and

hydration are restored, fentanyl patches can be used postop-eratively with reasonable efficacy. Onset time is very slow,and there is a 12- to 24-hour lag before effective plasmaconcentrations are reached. If the patch stays properly ad-hered to on the patient, plasma fentanyl concentrations aremaintained for 3 to 5 days. Transdermal fentanyl is dosed ata rate of 0.003 to 0.005 mg/kg/h in cats and dogs.

Opioid agonist-antagonists are also used to manage peri-operative pain in cats and dogs. Butorphanol is the opioidagonist-antagonist used most commonly in small animals.Butorphanol is an agonist at the OP2 () receptor and anantagonist or partial agonist at the OP3 () receptor. Theanalgesia produced by butorphanol is not as profound as that

produced by opioid agonists, and its duration of action isrelatively short (1-2 hours). However, side effects (vomiting,respiratory depression, bradycardia) are less likely to occurafter administration of butorphanol than after administra-tion of morphine, hydromorphone, or fentanyl. Intraopera-tive administration of butorphanol also reduces isofluranerequirements by 10% to 20% in cats and dogs. 36,45 Butor-phanol can be used perioperatively to manage mild to mod-erate pain. The preanesthetic intramuscular dose range forbutorphanol in cats and dogs is 0.2 to 0.4 mg/kg. Approxi-mately half of the preanesthetic dose can be given intraoper-atively or postoperatively. Butorphanol can be given postop-

eratively as an intravenous constant-rate infusion at a doserange of 0.1 to 0.2 mg/kg/h. Small intravenous doses of bu-torphanol (0.1 mg/kg) can also be given postoperatively toreverse sedation and respiratory depression caused by admin-istration of excessive doses of opioid agonists.

NMDA Antagonists

Glutamate is the endogenous agonist for spinal and su-praspinal NMDA receptors. Blockade of NMDA receptors inthe dorsal horn of the spinal cord prevents windup and thedevelopment of central sensitization. Ketamine is the mostwidely used NMDA antagonist in veterinary medicine. Ket-

amine is supplied as a racemic mixture of 2 optical enanti-omers. S() ketamine has 4 times the affinity of L() ket-

amine for the NMDA receptor and has a shorter duration of action. The clinical analgesic potency of S() ketamine isapproximately twice that of the racemic mixture. Nonrace-mic mixtures of ketamine may be available for use in small

animals in the near future.Ketamine can be used to manage pain throughout the peri-operative period at anesthetic and subanesthetic doses.46 In-travenous or intramuscular administration of anestheticdoses produces “dissociative” anesthesia with poor musclerelaxation in both cats and dogs. Cardiovascular effects arelimited, and ventilation is better maintained than with otheranesthetic drugs. Dysphoria and seizures can also occur afteradministration of high doses of ketamine, but dysphoria isless severe or absent at low subanesthetic or analgesic doses.The anesthetic effects of ketamine last for approximately 30minutes, but motor effects can persist for several hours. In-travenous administration of ketamine at an infusion rate of

0.6 mg/kg/h decreases isoflurane requirements by 25%.37 In-traoperative and postoperative administration of ketaminealso reduces pain scores in dogs after forelimb amputation.47

Because of the potential for dysphoria, opioid infusions are abetter choice for most patients than opioid-ketamine infu-sions or ketamine infusions alone. However, patients withsignificant preexisting central sensitization or those undergo-ing major procedures with significant surgical trauma maybenefit from intraoperative and postoperative opioid-ket-amine infusions. Intraoperatively, the intravenous infusiondose range for cats and dogs is 0.4 to 0.6 mg/kg/h. Postoper-atively, a lower intravenous infusion dose range of 0.2 to 0.3mg/kg/h is used to avoid dysphoria and motor effects. An

intravenous bolus of 0.5 to 1.0 mg/kg can be given as aloading dose or to provide short-term analgesia.

Local Anesthetics

Local anesthetics have the unique ability to produce com-plete blockade of sensory nerve fibers and prevent the devel-opment of central sensitization. Consequently, peripheraland central neural blockade are often used in combinationwith other analgesic and anesthetic drugs to manage periop-erative pain. Local anesthetics block the generation and con-duction of nerve impulses by inhibiting voltage-gated sodium

channels in nerve fibers. Lidocaine is also given systemicallyto manage pain and to reduce ileus after abdominal surgery.The mechanism of action of systemic administration of lido-caine is unclear, but peripheral, central, and antiinflamma-tory mechanisms have been proposed.48

Lidocaine, mepivacaine, and bupivacaine are the local an-esthetics used most commonly in cats and dogs. Lidocainehas a fast onset (10 minutes) and a short duration of action(1-2 hours) and is used for short diagnostic and surgicalprocedures. Mepivacaine is similar to lidocaine in potencyand onset, but has a longer duration of action (2-3 hours),causes less tissue irritation, and has a higher therapeutic in-dex. Bupivacaine is approximately 4 times the potency of

lidocaine and mepivacaine, has a slow onset (20 minutes),and a long duration of action (4-6 hours) and is used for most




surgical procedures. Aminoamide local anesthetics are highlyprotein-bound and are metabolized primarily by the liver.Consequently, anemic and hypoproteinemic patients aremore susceptible to local anesthetic toxicity. In most patients,

the clearance of lidocaine is dependent on blood flow ratherthan hepatic metabolism. As a result, the clearance of lido-caine is significantly reduced in patients with low cardiacoutput. Local anesthetics are relatively safe if they are usedcorrectly. Administration of an excessive dose and accidentalintravenous administration are the most common causes of systemic toxicity in small animals. As a general rule, the totaldose of lidocaine or bupivacaine should not exceed 8 mg/kgor 2 mg/kg, respectively. Clinicians should always considerincluding peripheral or central neural blockade in their peri-operative pain management plans. These techniques reduceinhalation anesthetic requirements, attenuate the neuroendo-crine response to surgical trauma, and improve outcome.

Local anesthetic techniques for cats and dogs are described indetail in several recent articles.4,49,50

Systemic administration of lidocaine can be used periop-eratively to reduce inhalation anesthetic requirements, toprovide analgesia, to control ventricular arrhythmias, and tomanage postoperative ileus. Intravenous administration of lidocaine at a rate of 3 mg/kg/h reduces isoflurane require-ments by 20% to 30%.37,51 Intravenous loading doses of 1 to2 mg/kg are appropriate for most dogs. Intraoperatively, theintravenous infusion dose range for dogs is 4 to 6 mg/kg/h.Postoperatively, a lower intravenous infusion dose range of 2to 3 mg/kg/h is used to provide analgesia and to improvegastrointestinal motility. Objective clinical data on the use of

intraoperative and postoperative lidocaine infusions in catsare limited.

COX Inhibitors

Prostaglandins play a central role in inflammation and thedevelopment of peripheral sensitization. Production of pros-taglandins in the dorsal horn of the spinal cord also contrib-utes to the development of central sensitization. Inhibition of constitutive (COX-1) and inducible (COX-2) cyclooxygen-ase inhibits the conversion of arachadonic acid to prostaglan-dins and thromboxanes and produces a peripheral antiin-

flammatory effect. In the dorsal horn, inhibition of COXproduces a central analgesic effect. COX inhibitors vary intheir selectivity for the different isoenzymes, as well as theirability to produce central analgesic and antiinflammatoryeffects.52,53

Several COX inhibitors are approved for perioperative usein cats and dogs. COX inhibitors are usually given postoper-atively alone or in combination with opioids. Parenteral for-mulations of ketoprofen, meloxicam, and carprofen areavailable in Canada and the United States and are bettersuited for perioperative administration. Ketoprofen has arapid onset (0.5 hour), a short half-life, and an intermediateduration of action (12 hours). The drug inhibits platelet func-

tion but does not appear to prolong bleeding time in healthyanimals undergoing elective surgery.54 Ketoprofen can be

given subcutaneously to cats and dogs immediately after sur-gery at a dose of 2 mg/kg. Therapy with ketoprofen can becontinued at a dose of 0.5 mg/kg twice daily for 3 to 5 days.Meloxicam and carprofen have a slow onset time (1-2 hours)

and a long duration of action (24 hours). These drugs do notappear to inhibit platelet function and do not prolong bleed-ing time in healthy animals. Meloxicam can be given subcu-taneously to dogs immediately after surgery at a dose of 0.2mg/kg. Therapy with meloxicam can be continued at a doseof 0.1 mg/kg once daily for 3 to 5 days. Carprofen can begiven subcutaneously to dogs immediately after surgery at adose of 4 mg/kg. Therapy with carprofen can be continued ata dose of 4 mg/kg once daily for 3 to5 days. Deracoxib is alsolabeled for perioperative use in dogs, but no parenteral for-mulation is available. Side effects are not usually a problem inhealthy animals with normal platelet, gastrointestinal, andrenal function. There is little benefit to preoperative admin-

istration of COX inhibitors, and there is significant risk forpatients with compromised platelet and renal function.

Figure 2. Components of balanced anesthesia. General an-esthetics (propofol, isoflurane) are used to induce hypnosis ora loss of consciousness, but these drugs have very low thera-peutic indices and produce significant cardiopulmonary de-pression at clinically relevant doses. Concurrent administra-tion of analgesic drugs not only attenuates autonomicresponses (increased heart rate and arterial pressure, in-creased respiratory rate) to surgical trauma, but reduces theamount of intravenous and inhalation anesthetics required toinduce and maintain anesthesia. Administration of alpha-2

agonists and local anesthetics can also improve muscle relax-ation.




T a b l e 3 . E x a m p l e s o f A n e s t h e t i c a n d

P a i n M a n a g e m e n t P r o t o c o l s f o r H e

a l t h y C a t s *

S u r g i c a l P r o c e d u r e

P r e o p e r a t i v e M

a n a g e m e n t

I n t r a o p e r a t i v e M

a n a g e m e n t

P o s t o p e r a t i v e M a n a g e m e n t

C o m m e n t s

C a

s t r a t i o n

( P r

o t o c o l 1 )

P r e m e d i c a t i o n

A c e p r o m a z i n e

: 0 . 1 - 0 . 2

m g / k g , I M

B u t o r p h a n o l : 0 . 2 - 0 . 4

m g / k g , I M

I n d u c t i o n a n d m

a i n t e n a n c e

K e t a m i n e : 1 0 - 1 5 m g / k g , I M

K e t o p r o f e n : 2 . 0 m g / k g , S C

i m m e d i a t e l y a f t e r r e c o v e r y f r o m

a n e s t h e s i a

M i l d p a i n

C a

s t r a t i o n

( P r

o t o c o l 2 )


M e d e t o m i d i n e : 0 . 0 1 - 0 . 0 2

m g / k g , I M †

B u t o r p h a n o l : 0 . 2 - 0 . 4

m g / k g , I M

I n d u c t i o n a n d m

a i n t e n a n c e

K e t a m i n e : 5 - 1 0

m g / k g , I M



a n e s t h e s i a

M i l d p a i n

O v

a r i o h y s t e r e c t o m y

( P r

o t o c o l 1 )



: 0 . 1 - 0 . 2

m g / k g , I M

H y d r o m o r p h o

n e : 0 . 0 5 - 0 . 1

m g / k g , I M

I n d u c t i o n

T h i o p e n t a l : 8 - 1

2 m g / k g , I V t o

e f f e c t

I s o fl u r a n e : 3 %

M a i n t e n a n c e

I s o fl u r a n e : 1 . 5 %

- 2 . 5 %

K e t o p r o f e n : 2 . 0 m g / k g ,

S C


a n e s t h e s i a

K e t o p r o f e n : 1 . 0 m g / k g ,

P O

o n c e d a i l y f o r 2 - 3 d a y s

M o d e r a t e p a i n

S o m e p a t i e n t s m

a y r e q u i r e

a d d i t i o n a l h y d r o

m o r p h o n e

p o s t o p e r a t i v e l y .

O v


( P r

o t o c o l 2 )


M e d e t o m i d i n e : 0 . 0 1 - 0 . 0 2

m g / k g , I M †


n e : 0 . 0 5 - 0 . 1

m g / k g , I M

G l y c o p y r r o

l a t e : 0 . 0 1 m g /

k g , I M

I n d u c t i o n

T h i o p e n t a l : 4 - 6

m g / k g , I V t o

e f f e c t



I s o fl u r a n e : 1 . 0 %

- 2 . 0 %

K e t o p r o f e n : 2 . 0 m g / k g ,

S C


a n e s t h e s i a

K e t o p r o f e n : 1 . 0 m g / k g ,

P O



S o m e p a t i e n t s m

a y r e q u i r e

a d d i t i o n a l h y d r o

m o r p h o n e


O n

y c h e c t o m y

( P r

o t o c o l 1 )



: 0 . 1 - 0 . 2

m g / k g , I M


n e : 0 . 0 5 - 0 . 1

m g / k g , I M

I n d u c t i o n

P r o p o f o l : 4 - 6 m

g / k g , I V t o

e f f e c t



I s o fl u r a n e : 1 . 5 %

- 2 . 5 %

D i g i t a l n e r v e b l o c k

0 . 5 %

b u p i v a c a i n e :

0 . 5 - 1 . 0 m L

D o n o t e x c e e d a t o t a l d o s e o f

2 m g / k g .

K e t o p r o f e n : 2 . 0 m g / k g ,

S C


a n e s t h e s i a

K e t o p r o f e n : 1 . 0 m g / k g ,

P O



D i g i t a l n e r v e b l o

c k r e d u c e s

a n e s t h e t i c r e q u i r e m e n t s

a n d i m p r o v e s a n

a l g e s i a





Clinical Management

Multimodal analgesia is not a difficult concept to understand,nor is it a difficult concept to put into practice. In the perioper-ative setting, a multimodal analgesic protocol is simply a bal-anced anesthetic and pain management protocol (Fig 2). At firstglance, the notion that analgesic drugs should be given to anes-thetized patients that are unable to consciously perceive painseems irrational. However, most intravenous (propofol) andinhalation (isoflurane, sevoflurane) anesthetics simply produceunconsciousness and do not substantially alter nociceptive pro-cessing. In fact, autonomic responses (sudden changes in respi-ratory rate, heart rate, and blood pressure) that occur duringsurgery as a result of noxious stimulation usually reflect inade-quate analgesia rather than insufficient anesthetic depth. Thesafest approach for most patients is to limit the amount of in-halation anesthetic required by providing supplemental intra-

operative analgesic therapy with opioids and local anesthetictechniques.After initial assessment of analgesic requirements and

identification of major anesthetic risk factors, drugs are se-lected to minimize risk and to provide optimal anesthetic andpain management throughout the perioperative period. Pa-tient monitoring and supportive care are also selected to op-timize cardiopulmonary function and to minimize anestheticrisk. Hypoventilation (PaCO2 60 mm Hg), hypotension(mean arterial pressure 60 mm Hg), and bradycardia arecommon perioperative complications. Care should be takento avoid or reduce doses of anesthetic and analgesic drugsthat have similar side effects. Opioids and inhalation anes-

thetics can induce significant respiratory depression. Ace-promazine, inhalation anesthetics, and epidural anesthesiacan cause significant hypotension. Alpha-2 agonists and opi-oids can cause bradycardia and enhance oculovagal and vis-cerovagal reflexes triggered by surgical manipulation. Giventhe potential for significant intraoperative complications,there is no substitute for diligent patient monitoring by aqualified, experienced anesthetist.

The type of surgery (invasive vs minimally invasive) andthe surgical site (somatic vs visceral) should also be consid-ered when developing anesthetic and pain managementplans. Pain must be managed aggressively throughout theperioperative period in patients scheduled for invasive surgi-cal procedures, whereas postoperative administration of COX inhibitors may be appropriate for patients scheduledfor minimally invasive procedures. Peripheral or central neu-ral blockade is appropriate for most patients scheduled forsurgical procedures of the front or hind limbs and for thosescheduled for dental procedures. Conversely, completeblockade of nociceptive input from somatic and visceral af-ferents may be impossible to achieve in patients scheduled forthoracic or abdominal surgical procedures.

Perioperative use of analgesic drugs and techniques re-duces the doses of intravenous and inhalation anestheticsrequired to induce and maintain anesthesia, improves cardio-

pulmonary function during surgery, and promotes a smoothrecovery from anesthesia after surgery. These analgesic drugs T

a b l e 3 . C o n t i n u e d


P r e o p e r a t i v e M

a n a g e m e n t

I n t r a o p e r a t i v e M

a n a g e m e n t


C o m m e n t s

O n

y c h e c t o m y

( P r

o t o c o l 2 )


M e d e t o m i d i n e : 0 . 0 1 - 0 . 0 2

m g / k g , I M †


n e : 0 . 0 5 - 0 . 1

m g / k g , I M

G l y c o p y r r o

l a t e : 0 . 0 1 m g /

k g , I M

I n d u c t i o n

P r o p o f o l : 2 - 3 m

g / k g , I V t o

e f f e c t



I s o fl u r a n e : 1 . 0 %

- 2 . 0 %

D i g i t a l n e r v e b l o c k

0 . 5 %

B u p i v a c a i n e :

0 . 5 - 1 . 0 m L

D o n o t e x c e e d a t o t a l d o s e o f

2 m g / k g .

K e t o p r o f e n : 2 . 0 m g / k g ,

S C


a n e s t h e s i a

K e t o p r o f e n : 1 . 0 m g / k g ,

P O



D i g i t a l n e r v e b l o

c k r e d u c e s

a n e s t h e t i c r e q u i r e m e n t s

a n d i m p r o v e s a n

a l g e s i a


A b

b r e v i a t i o n s : I M ,

I n t r a m u s c u l a r l y ; I V ,

i n t r a v e n o u s l y ; S C , s u b c u t a n e o u s l y ; P O ,

b y m o u t h .

* S o

m e o f t h e s e d r u g s a r e n o t a p p r o v e d f o r u s e i n c a t s i n C a n a d a o r t h e U n i t e d S t a t e s .

† D

e x m e d e t o m i d i n e c a n b e s u b s t i t u t e d a t a p p r o

x i m a t e l y h a l f t h e m e d e t o m i d i n e d o s e .




T a b l e 4 . E x a m p l e s o f A n e s t h e t i c a n d

P a i n M a n a g e m e n t P r o t o c o l s f o r H e

a l t h y D o g s *


P r e o p e r a t i v e M a n a g e m e n t

I n t r a o p e r a t i v e M a n a g e m e n t


C o m m e n t s

C a

s t r a t i o n

( P r

o t o c o l 1 )


A c e p r o m a z i n e : 0 . 0 5 - 0 . 1 m g / k g ,

I M B u t o r p h a n o l : 0 . 2 - 0 . 4 m g / k g ,

I M

I n d u c t i o n

P r o p o f o l : 4 - 6 m g / k g , I V t o e f f e c t



I s o fl u r a n e : 1 . 5 % - 2 . 5 %



a n e s t h e s i a

M i l d p a i n

C a

s t r a t i o n

( P r

o t o c o l 2 )


M e d e t o m i d i n e :

0 . 0 0 5 - 0 . 0 1 m g /

k g , I M †

B u t o r p h a n o l : 0 . 2 - 0 . 4 m g / k g ,

I M G l y c o p y r r o l a

t e : 0 . 0 0 5 - 0 . 0 1

m g / k g , I M

I n d u c t i o n



M a i n t e n a n c e :

I s o fl u r a n e : 1 . 0 % - 2 . 0 %



a n e s t h e s i a

M i l d p a i n

O v


( P r

o t o c o l 1 )


A c e p r o m a z i n e : 0 . 0 5 - 0 . 1 m g / k g ,

I M H y d r o m o r p h o n

e : 0 . 0 5 - 0 . 1 m g /

k g , I M

I n d u c t i o n

T h i o p e n t a l : 8 - 1 2 m g / k g , I V t o

e f f e c t



I s o fl u r a n e : 1 . 5 % - 2 . 5 %

M e l o x i c a m : 0 . 2 m g / k g ,

S C


a n e s t h e s i a

M e l o x i c a m : 0 . 1 m g / k g ,

P O



S o m e p a t i e n t s m a y r e q u i r e

a d d i t i o n a l h y d r o m

o r p h o n e


O v


( P r

o t o c o l 2 )


M e d e t o m i d i n e :

0 . 0 0 5 - 0 . 0 1 m g /

k g , I M †

H y d r o m o r p h o n

e : 0 . 0 5 - 0 . 1 m g /

k g , I M

G l y c o p y r r o l a t e :

0 . 0 0 5 - 0 . 0 1

m g / k g , I M

I n d u c t i o n

T h i o p e n t a l : 4 - 6 m

g / k g , I V t o

e f f e c t




I s o fl u r a n e : 1 . 0 % - 2 . 0 %

M e l o x i c a m : 0 . 2 m g / k g ,

S C


a n e s t h e s i a

M e l o x i c a m : 0 . 1 m g / k g ,

P O



S o m e p a t i e n t s m a y r e q u i r e

a d d i t i o n a l h y d r o m

o r p h o n e


D e

n t i s t r y w i t h a n

u p p e r c a n i n e

e x t r a c t i o n


M i d a z o l a m : 0 . 1

- 0 . 2 m g / k g , I M


e : 0 . 0 5 - 0 . 1 m g /

k g , I M

I n d u c t i o n




I s o fl u r a n e : 1 . 0 % - 2 . 0 %

I n f r a o r b i t a l n e r v e

b l o c k

0 . 5 %

B u p i v a c a i n e : 0 . 5 - 1 . 0 m L

K e t o p r o f e n : 2 . 0 m g / k g ,

S C


a n e s t h e s i a

K e t o p r o f e n : 1 . 0 m g / k g ,

P O



I n f r a o r b i t a l n e r v e

b l o c k

r e d u c e s a n e s t h e t i c

r e q u i r e m e n t s a n d

i m p r o v e s

a n a l g e s i a p o s t o p e r a t i v e l y .




and techniques also have the potential to reduce major com-plications and improve outcome. In a busy practice setting,simple, straightforward anesthetic and pain managementprotocols are the best choice for most patients. Pain can be

managed safely and effectively in the vast majority of surgicalpatients with opioids, COX inhibitors, and peripheral orcentral neural blockade. Alpha-2 agonists, NMDA antago-nists, and other adjunctive drugs are helpful in patients withsignificant short-term or long-term central sensitization. Andlast, atraumatic surgical technique is the first, and most im-portant, step in the prevention of peripheral and central sen-sitization and the development of pathological pain. Exam-ples of balanced anesthetic and pain management protocolsfor routine surgical procedures in healthy cats and dogs areoutlined in Tables 3 and 4, respectively.

References1. Muir WW, Woolf CJ: Mechanisms of pain and their therapeu-

tic implications. J Am Vet Med Assoc 219:1346-1356, 20012. Lemke KA: Understanding the pathophysiology of periopera-

tive pain. Can Vet J 45:405-413, 20043. Lamont LA: Multimodal pain management in veterinary med-

icine: the physiologic basis of pharmacologic therapies. VetClin North Am (Small Anim Pract) 38:1173-1186, 2008

4. Lemke KA, Dawson SD: Local and regional anesthesia. VetClin North Am (Small Anim Pract) 30:839-857, 2000

5. Siddall PJ, Cousins MJ: Introduction to pain mechanisms: im-plications for neural blockade, in Cousins MJ, Carr DB, Hor-locker TT, Bridenbaugh PO (eds): Neural Blockade in Clinical

Anesthesia and Pain Medicine (ed 4). Philadelphia, LippincottWilliams & Wilkins, 2009, pp 661-6926. Kehlet H: Multimodal approach to control postoperative

pathophysiology and rehabilitation. Br J Anaesth 78:606-617,1997

7. Kehlet H, Wilmore DW: Multimodal strategies to improve sur-gical outcome. Am J Surg 183:630-641, 2002

8. Anand KJ, Sippell WG, Aynsley-Green A: Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: ef-fects on the stress response. Lancet 329:62-66, 1987

9. Anand KJ, Hickey PR: Halothane-morphine compared withhigh-dose sufentanil for anesthesia and postoperative analgesiain neonatal cardiac surgery. N Engl J Med 326:1-9, 1992

10. Rodgers A, Walker N, Schug S, et al: Reduction of postopera-

tive mortality and morbidity with epidural or spinal anaesthe-sia: results from overview of randomised trials. BMJ 321:1493-1497, 2000

11. Craig AD: Pain mechanisms: labeled lines versus convergencein central processing. Annu Rev Neurosci 26:1-30, 2003

12. Truini A, Cruccu G: Pathophysiological mechanisms of neuro-pathic pain. Neurol Sci 27:S179-S182, 2006 (Suppl 2)

13. Yaksh TL: Physiologic and pharmacologic substrates of noci-ception after tissue and nerve injury, in Cousins MJ, Carr DB,Horlocker TT, Bridenbaugh PO (eds): Neural Blockade in Clin-ical Anesthesia and Pain Medicine (ed 4). Philadelphia, Lippin-cott Williams & Wilkins, 2009, pp 693-751

14. Julius D, Basbaum AI: Molecular mechanisms of nociception.Nature 413:203-210, 2001

15. Woolf CJ, Ma Q: Nociceptors—noxious stimulus detectors.Neuron 55:353-364, 2007 T

a b l e 4 . C o n t i n u e d


P r e o p e r a t i v e M a n a g e m e n t

I n t r a o p e r a t i v e M a n a g e m e n t


C o m m e n t s

C r u c i a t e r e p a i r


M i d a z o l a m : 0 . 1

- 0 . 2 m g / k g , I M


e : 0 . 0 5 - 0 . 1 m g /

k g , I M

I n d u c t i o n

T h i o p e n t a l : 8 - 1 2 m g / k g , I V t o

e f f e c t



I s o fl u r a n e : 1 . 0 % - 2 . 0 %

E p i d u r a l a n e s t h e s

i a ( l u m b o s a c r a l )

0 . 5 %

B u p i v a c a i n e : 1 . 0 m L / 5 k g

2 . 5 %

M o r p h i n e : 0 . 2 m g / k g

M e l o x i c a m : 0 . 2 m g / k g ,

S C


a n e s t h e s i a

M e l o x i c a m : 0 . 1 m g / k g ,

P O



E p i d u r a l a n e s t h e s i a r e d u c e s

a n e s t h e t i c r e q u i r e m e n t s a n d

i m p r o v e s a n a l g e s i a


A b

b r e v i a t i o n s : I M ,

I n t r a m u s c u l a r l y ; I V ,

i n t r a v e n o u s l y ; S C , s u b c u t a n e o u s l y ; P O ,

b y m o u t h .

* S o

m e o f t h e s e d r u g s a r e n o t a p p r o v e d f o r u s e i n d o g s i n C a n a d a o r t h e U n i t e d S t a t e s .

† D

e x m e d e t o m i d i n e c a n b e s u b s t i t u t e d a t a p p r o

x i m a t e l y h a l f t h e m e d e t o m i d i n e d o s e .




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