The perianesthetic drugs covered in this chapter are commonly used in anesthetic protocols during the anesthetic process or are medications that are used in the perianesthetic period. Each drug is listed in detail, alphabetically, and drug tables comparing common, categorical medications such as common induction agents, nonopioid sedatives, opioids, and blood pressure support are provided.
All phenothiazines have a wide range of central and peripheral effects. In human medicine, they are classified as antipsychotic drugs or neuroleptics and are still used in the treatment of psychiatric disturbances. In veterinary medicine, they are widely used for sedation and premedication
Because the drug is long‐lasting, postoperative recoveries are often smooth
Provides antiemetic action against opioid‐induced emesis
No analgesic properties
Antihistamine
Exerts a significant dose‐dependent MAC‐sparing effect on inhalant anesthetics (up to 48%) [1]
Acepromazine possesses antiarrhythmic, antispasmodic, and hypothermic properties
Causes a reduction in platelet aggregation but hemostasis is not altered
Splenic engorgement after alpha‐1‐adrenergic receptor blockade, shortly after acepromazine administration, results in a reduction of the HCT [2]
Healthy patients in combination with opioid: 0.01–0.05 mg/kg IM 0.01–0.03 mg/kg is routinely given IV preoperatively, and 0.005 mg/kg postoperatively for sedation
Slow onset (after IV injection it make take up to 15 min, up to 30 min when given IM). Peak effects are seen at 30–60 min. Clinical sedation lasts for 4–6 h but episodes of animals, especially dogs of giant breeds, depressed for several days are reported. This drug may last substantially longer in patients with hepatic dysfunction
Dexmedetomidine
Alpha‐2 agonist
Premedication: 0.002–0.01 mg/kg IV, 0.003–0.015 mg/kg IM CRI 1 μg/kg/h IV for sedation and analgesia
Relatively short onset when given IM (10–20 min), duration of up to 2–3 h
Diazepam
Benzodiazepine
Premedication: dogs and cats 0.1–0.4 mg/kg IV, IM Seizures: 0.5–1 mg/kg IV or rectally CRI: 0.2–0.5 mg/kg/h
In dogs half‐life is less than 1 h In cats half‐life can be up to 5 h
Midazolam
Benzodiazepine
Premedication [193]/sedation: 0.1–0.3 mg/kg IM, IV Seizures: 0.5–1 mg/kg IV
Rapid onset with a duration clinically of 30–45 min, although as dose is increased, behavioral effects may last up to 2 h in the dog [194] As usual, cats are unpredictable with their pharmacokinetics; while hepatic clearance may be so rapid elimination could not be accurately assessed [195], there is also huge variability amongst felines in this regard [196]
Xylazine
Alpha‐2 agonist
0.5–2 mg/kg IM, 0.2–1 mg/kg IV
Quick onset when given IM (10–15 min) with duration of 30–120 min depending on dose and route
CRI, constant‐rate infusion; IM, intramuscular; IV, intravenous.
.
C. PHARMACOLOGY
Acepromazine acts predominantly by blocking dopamine D2 receptors, but other effects derive from the ability to block alpha‐1‐adrenergic, muscarinic, serotoninergic, and histamine (H1) receptors
Inhibition of dopaminergic receptors of the brain causes sedation and, in combination with opioids, produces a state characterized by sedation and analgesia, known as neuroleptanalgesia [3,4]
Increase in doses may cause extrapyramidal signs
Alpha‐1‐adrenergic blockade results in decrease in SVR, peripheral vasodilation and decrease in blood pressure [5]. Healthy animals rarely display severe decreases in blood pressure but the impact on hemodynamics must be taken into account and caution is warranted in cardiovascularly unstable patients [6]
Heart rate is usually unchanged but following the reductions in SV, CO, and afterload that result in hypotension, periods of mild tachycardia may be observed [2]
Clinical doses of acepromazine may cause a mild decrease in respiratory rate, but this is often associated with an increase in tidal volume with minute ventilation usually unchanged
Metabolized in the liver; conjugated and nonconjugated metabolites are excreted in the urine
D. CONTRAINDICATIONS/PRECAUTIONS
Hypovolemic or hypotensive patients
Patients with severe liver dysfunction
Splenectomy
Caution in patients with HCM, valvular stenosis or DCM
E. PRACTICAL NOTES
Commonly diluted to 1 mg/mL with 0.9% saline or sterile water
Tablets for oral use are also available
No reversal agent available
Commonly used via OTM route in the chill protocol at 0.01–0.05 mg/kg to be given 30–60 min before hospital visit by owner [7]
II. Albuterol intermediate acting beta‐2‐adrenergic agonist
A. DOSE AND DURATION
Two puffs of 90 μg/puff by metered dose inhaler (inhalation), separated by 1–5 min
Peak effect is 30–60 min after administration
4 h duration
B. CLINICAL APPLICATIONS
Bronchodilator, helpful in reducing V/Q mismatch
C. PHARMACOLOGY
Selective beta‐2‐agonist which will relax smooth muscle tissue (both bronchiole and uterine) without stimulating the heart via beta‐1 receptor effects
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with cardiac disease (such as preexisting tachyarrhythmia) as it may cause increases in HR at higher plasma concentrations
Caution in patients at end‐stage pregnancy
Can cause a decrease in K+ and hyperglycemia
Muscle tremors may result from beta receptor stimulation
E. PRACTICAL NOTES
Use a chamber that facilitates proper particle dispersion for full effect
When administering to an intubated patient, a significant amount of the drug (50–70%) will reside within the ET tube [8]. Therefore, the doses delivered may be increased when administering albuterol to an intubated patient
Protect from light
III. Alfaxalone synthetic neuroactive steroid with anesthetic properties
1–4 mg/kg IV to effect (over 60 seconds) as a single bolus CRI: 4.2–6 mg/kg/h [197,198]
Single bolus duration is dependent on dose. In dogs a single dose of 2 mg/kg IV is reported to last about 6 min, 10 mg/kg about 26 min [199,200]
Etomidate
Imidazole derivative
0.5–2.0 mg/kg IV to effect
Promptly redistributed away from the brain, although metabolism may take 2–5 h
Ketamine
NMDA antagonist and dissociative anesthetic
Induction dosage in sedated patient: 3–5 mg/kg IV IM induction dosage of 5–10 mg/kg Buccal dose 5–20 mg/kg for sedation/immobilization Loading dose for CRI: 0.5–1 mg/kg, CRI: 0.12–1.8 mg/kg/h
Duration is dependent on route of administration, but single IV boluses are expected to last less than 15 min with an onset of 60–90 sec
Pentobarbital
Barbiturate
Anesthetic dose: 20–30 mg/kg IV To control seizures: 3–15 mg/kg IV slowly Manufactured at 390 mg/mL as euthanasia agent; dose for euthanasia is 120 mg/kg IV
Effect terminates rapidly, but may take up to 8 h to clear from the body
Propofol
Injectable sedative‐hypnotic anesthetic
2.0–6.0 mg/kg IV 2–4 mg/kg IV to effect in patients with appropriate premedication TIVA: 6–24 mg/kg/h IV
10–20 min as a single bolus; prolonged exposure to propofol (e.g., as a CRI) can result in prolonged duration of sedation, especially in cats [201]
Tiletamine and zolazepam (Telazol®)
Injectable anesthetic combination of dissociative agent and benzodiazepine
For induction of anesthesia: 2–4 mg/kg IV; 6–10 mg/kg IM For maintenance of anesthesia: 6–13 mg/kg IM
Surgical anesthesia <30 min, but it may take up to 4 h before drug effect subsides completely
CRI, constant‐rate infusion; IM, intramuscular; IV, intravenous; NMDA, N‐methyl‐D‐aspartate; TIVA, total intravenous anesthesia.
B. CLINICAL APPLICATIONS
Because it is relatively short‐acting and noncumulative, it is used for intravenous induction of anesthesia and maintenance by bolus injection or constant‐rate infusion
It is commonly used IM in association with other sedatives, benzodiazepines, or dissociative agents for chemical restraint of aggressive or noncompliant animals. However, due to low concentration, large volumes may be necessary and, therefore, the IM route is often limited to small patients
Premedication with sedatives, opioids, and benzodiazepine results in significant dose reductions [9,10], enhancement of sedation and prolongation of recumbency [11], and allows smoother intubation in both dogs and cats [12]
Recovery is variable; incidences of agitation and noise sensitivity are reported, especially in cats, and seem to be more common than with propofol anesthesia [13]
Alfaxalone is used without complication in young animals (under 12 weeks of age) [14] and to induce anesthesia in dogs prior to cesarean section [15]
Dose‐dependent cardiovascular depression with decrease in arterial blood pressure, cardiac output and systemic vascular resistance may occur with dose‐dependent delivery [18]. However, clinically used doses do not elicit hypotension when given slowly to effect [19] and result in a cardiovascular stable anesthesia
Alfaxalone causes dose‐dependent respiratory depression. Apnea is the most common side‐effect, especially when administered quickly [20]
Alfaxalone administration was evaluated to be appropriate for allowing assessment of laryngeal motion in nonbrachycephalic and brachycephalic dogs [21]
An overdose of 10 times prolonged recovery with obtunded mentation and cardiorespiratory depression for several hours without being lethal [22]
C. PHARMACOLOGY
Acts primarily on the GABA receptors. The hyperpolarization of the postsynaptic membrane that follows is responsible for altering the pathways responsible for arousal and awareness
Alfaxalone is rapidly metabolized in the liver and the metabolites are then eliminated by the hepatic/fecal and renal routes
Plasma clearance is rapid with no accumulation after repeated administration [23]
In contrast to the previous version (Saffan®, which was formulated with castor oil as vehicle and withdrawn from the market due to hyperemia and histamine release), the current formulation is diluted in cyclodextrins (HPCD) and does not cause anaphylactoid reactions
Administration of repetitive doses in cats does not appear to result in plasma accumulation or increase in recovery times
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with known sensitivity to this drug
E. PRACTICAL NOTES
Half of premedicated cats can be intubated with a coinduction technique using 0.5 mg/kg IV alfaxalone, followed by 0.08 mg/kg midazolam IV [24]. If one is not able to intubate, additional alfaxalone is administered
Often in small patients, volumes of alfaxalone are minimal. Alfaxalone is diluted with saline for reasonable dose delivery
IV. Amantadine oral NMDA antagonist analgesic
A. DOSE AND DURATION
3–5 mg/kg PO every 24 h; however, newer pharmacokinetic studies suggest that administrations every 12 h may be needed [25]
B. CLINICAL APPLICATIONS
Generally ineffective when used alone, but in combination with an opioid or NSAID, may be useful as an adjunctive therapy for chronic pain, such as osteoarthritis [26]
NMDA antagonist with oral bioavailability
It is expected to produce analgesia when pain and central sensitization are already present; therefore, it may be ineffective in the treatment of acute pain
C. PHARMACOLOGY
Acts as an NMDA antagonist to block modulation of pain
Amantadine seems to have potentiating effects on dopaminergic and anticholinergic activity
Local anesthetic properties are reported through blockage of the sodium channels
Amantadine is primarily eliminated via renal mechanisms
D. CONTRAINDICATIONS/PRECAUTIONS
Due to amantadine’s effects on release and reuptake of dopamine, caution is warranted for use in patients receiving other drugs that may alter neurotransmitter release (e.g., tramadol). These combinations could lead to development of the serotonin syndrome, a fatal syndrome characterized by CNS stimulation, tremors, tachycardia, tachypnea, and hypertension
Amantadine’s half‐life may be increased in patients with renal impairment
E. PRACTICAL NOTES
Several weeks of treatment may be required to obtain results in pain relief
V. Aminocaproic acid
A. DOSE AND DURATION
27 mg/kg diluted in 15 mL saline; give this over 30 min postoperatively
B. CLINICAL APPLICATIONS
Traditionally, this drug is used for greyhounds to decrease postoperative bleeding after sedation or anesthesia [27,28]
C. PHARMACOLOGY
Synthetic antifibrinolytic
Effect is likely due to the formation of a reversible complex with plasminogen (which would otherwise activate to plasmin); halting this activation prevents fibrin lysis and results in a more stable clot formation [29]
D. CONTRAINDICATIONS/PRECAUTIONS
In theory, this drug might result in thrombosis
E. PRACTICAL NOTES
Conventionally, oral therapy at 100 mg/kg is also sent home with owners for the next 3–5 days
Antiarrhythmic drug used for treatment of tachyarrhythmias; specifically ventricular tachycardia and ventricular fibrillation during CPR when unresponsive to other therapies [31]
C. PHARMACOLOGY
Exact mechanism of action is unknown but it is believed to increase the action potential duration
D. CONTRAINDICATIONS/PRECAUTIONS
Risk of toxicity is documented in humans at 2.2 g in 24 h [32,33]. Dose of toxicity for veterinary species is unknown
Allergic reactions as well as hypotension possible in dogs
E. PRACTICAL NOTES
The price of this drug has fallen considerably, but it is not without side‐effects
Antiarrhythmic agents are considered as adjunctive therapy in refractory cases of ventricular fibrillation or pulseless VT, but electrical defibrillation is the recommended primary treatment of choice
VII. Atenolol beta‐1‐adrendergic antagonist
A. DOSE AND DURATION
0.1–0.5 mg/kg IV slowly (over 5 min) q 12 h
B. CLINICAL APPLICATIONS
Slows sinus rate and acts as an antihypertensive
Negative inotrope and negative chronotrope
May cause bradycardia and bradyarrhythmias
C. PHARMACOLOGY
Little to no hepatic metabolism; eliminated by the kidneys
D. CONTRAINDICATIONS/PRECAUTIONS
Uncontrolled heart failure patients
Patients with existing bradyarrhythmias
Use conservatively in patients with renal failure
Asthmatic patients
E. PRACTICAL NOTES
Commonly used in patients with HCM or hyperthyroidism
This drug is not typically used under anesthesia to decrease the sinus HR
When the 0.5 mg/mL formulation of dexmedetomidine is reversed, atipamezole IM is used as a reversal at equal volume to the dexmedetomidine administered in dogs. In cats, atipamezole IM, at equal to ½ volume of the dexmedetomidine (0.5 mg/mL) solution is administered for reversal Without the alpha‐2 agonist administered, doses of 0.1–0.25 mg/kg are reported
Peak effect is reached within 25 min when used to reverse alpha‐2 agonists, and duration is 2–3 h
Flumazenil
Reversal of benzodiazepines
0.02–0.1 mg/kg IV
Quick onset; 30–60 min duration
Naloxone
Used to reverse opioids
0.01–0.04 mg/kg IV CRI to reverse long‐duration opioids: 0.005 mg/kg/h
Quick onset, 45–60 min duration
Neostigmine
Reversal of nondepolarizing NMBA (atracurium, cisatracurium, pancuronium)
0.01–0.03 mg/kg IV given slowly over 20 min
Onset is within 5–10 min Duration is 4–6 h
Yohimbine
Reversal of alpha‐2 agonists; specific for xylazine
Causes vasodilation and may result in hypotension, especially when administered IV
May result in excitement or rapid arousal
May produce gastrointestinal side‐effects, such as vomiting or diarrhea
C. PHARMACOLOGY
A highly selective antagonist of alpha‐2 agonists by binding to the alpha‐2 receptors
There appears to be no effect at other receptor sites, including benzodiazepine, opioid, beta‐adrenergic, dopaminergic, GABA, histaminergic, and muscarinic receptors [34]
Onset of peak effect is quicker when this drug is used without an alpha‐2 agonist
D. CONTRAINDICATIONS/PRECAUTIONS
IV injection results in severe hypotension due to action at the peripheral alpha‐2 agonist receptors
E. PRACTICAL NOTES
If alpha‐2 agonists are the sole means of analgesia and pain is anticipated after recovery, consider administering other analgesics prior to reversal
Signs of reversal occur in 5–10 min following IM injection, although peak effect is longer
IX. Atracurium nondepolarizing neuromuscular blocking agent
Onset occurs within 3–5 min; effect lasts 20–30 min
Cisatracurium
Short‐acting nondepolarizing NMBA
0.1 mg/kg IV bolus, CRI 0.03–0.24 mg/kg/h IV
Rapid onset; effects last 20–35 min
Pancuronium
Nondepolarizing NMBA
0.022–0.1 mg/kg IV
Onset is within 5 min, and duration is 40–60 min [202]
NMB are indicated where muscle paralysis is required. They are most commonly used for ophthalmology procedures when the eyes must remain central.
CRI, constant‐rate infusion; IV, intravenous.
B. CLINICAL APPLICATIONS
Administered to paralyze a patient generally for a procedural purpose, such as an ophthalmological procedure where the ocular globe needs to be central
C. PHARMACOLOGY
Exerts actions at the neuromuscular junction, where this drug competes with acetylcholine to bind the nicotinic receptor without depolarizing it. This prevents muscle contractions of skeletal muscle (paralysis)
Metabolized by Hoffman elimination and ester hydrolysis in plasma (metabolism is dependent upon patient’s pH and body temperature); therefore, multiple doses do not become cumulative
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with a history of adverse reactions (histamine release)
E. PRACTICAL NOTES
Before administration, a mechanical ventilator is appropriately set to maintain ventilation for the patient. Diligent monitoring of the patient to ensure adequate ventilation prior to extubation is also required
Monitor paralysis with a train of four (TOF) on a peripheral nerve stimulator; during recovery, at least two twitches should be present before reversal of the drug (see Table 3 for reversal agents)
Recovery – monitoring with a capnograph and pulse oximeter is beneficial during recovery. Patients may relapse or have residual paralytic effects and are continuously monitored until completely recovered
Results in histamine release when given rapidly in high doses (resulting in hypotension and tachycardia)
Some anesthetists will administer this drug as a CRI
30–45 min for cardiovascular effects, although with a slower onset (may take up to 5–10 min)
CPR, cardiopulmonary resuscitation; IM, intramuscular; IV, intravenous; SC, subcutaneous.
B. CLINICAL APPLICATIONS
Prevent or treat perianesthetic bradycardia, sinoatrial arrest or incomplete AV block
IM and IV are the preferred routes because of the faster absorption and shorter onset
Bronchodilation
Prevent the cardiovascular effect of cholinergic drugs used when reversing neuromuscular blockade such as neostigmine and edrophonium
May cause sedation, when administered systemically, as it crosses the blood–brain barrier. Effect is negligible when clinical doses are administered. Ataxia, seizures stimulation or drowsiness can occur
Topical administration in the eye induces mydriasis and, in cats, can increase intraocular pressure (IOP) caused by drainage angle closure. Blurred vision, photophobia, cycloplegia, and pupillary dilation are possible
The blockade of M3 receptors causes inhibition of salivation
C. PHARMACOLOGY
Competitive, reversible antagonist of the muscarinic acetylcholine receptors types M1, M2, M3, M4, and M5 at the postganglionic parasympathetic neuroeffector sites
Antagonizing the parasympathetic nervous system helps to prevent bradycardia, but also decreases GI motility and salivation, and causes mydriasis. The blockade of M3 receptors causes a decrease in gastrointestinal and urinary tract motility resulting in ileus and urinary retention
D. CONTRAINDICATIONS/PRECAUTIONS
May increase the incidence of arrhythmias, tachycardia, increased myocardial workload, and oxygen consumption
Caution using anticholinergics following the administration of alpha‐2 agonists during the hyperdynamic phase. Increasing the heart rate during the period of vasoconstriction and reflexive bradycardia will cause an increase in myocardial oxygen consumption, predisposing the patient to potential life‐threatening arrhythmias
Narrow angle glaucoma
Thyrotoxicosis‐induced tachycardia
Cardiac insufficiency‐associated tachycardia
Gastrointestinal obstruction
Paralytic ileus
Myasthenia gravis (unless used to reverse adverse muscarinic effects)
Gastrointestinal infections
Autonomic neuropathy
Atropine and glycopyrrolate may enhance the actions of sympathomimetics and may antagonize the actions of metoclopramide
Very high doses can inhibit gastric acid secretion
Overall, this drug can result in a dry mouth, dysphagia, constipation, and vomiting
E. PRACTICAL NOTES
For bradycardia under anesthesia, start with 0.02 mg/kg IV to avoid excessive tachycardia
Paradoxical parasympathomimetic activity (bradyarrhythmias such as second‐degree AV block Mobitz I) can develop in the first phase after the administration or when low doses are administered. The proposed cause is an initial blockade of presynaptic peripheral M1 receptors that normally inhibit acetylcholine release. This causes a transient increase in acetylcholine prior to the postsynaptic M2 receptor blockade
Greater increases in heart rate (excess tachycardia) may be observed in patients with high preexisting vagal tone
Antihistamines, procainamide, quinidine, meperidine, benzodiazepines, and phenothiazines may enhance the activity of atropine (and glycopyrrolate)
XI. Bupivacaine (standard formulation) local anesthetic
Regional: 2 mg/kg in dogs, 1 mg/kg in cats Epidural dosage: 0.5–1.0 mg/kg Liposomal encapsulated bupivacaine: Dog: recommended dose is 5.3 mg/kg or 0.4 mL/kg Cat: the approved dose for onychectomy is 5.3 mg/kg per forelimb (0.4 mL/kg per forelimb), for a total dose of 10.6 mg/kg per cat
5–20 min onset (in human patients, epidural analgesia has an onset of about 10 min [203], regionally 5–20 min [204]). Duration 4–6 h Liposomal encapsulated bupivacaine: duration up to 72 h from a single dose administration
Lidocaine
Dogs: 0.5–2 mg/kg IV (which may be repeated) or as regional/infiltrative block CRI: 1–6 mg/kg/h (often 1–3 mg/kg/h for analgesic benefit, 3+ mg/kg/h for antiarrhythmic benefit) Cats: regional/infiltrative block 0.5–1.5 mg/kg
Dogs: 6 mg/kg Cats: 3 mg/kg
Regional effects: 60–90 min, quick onset (2–5 min regionally) IV bolus effects: up to 45 min, which may be increased in anesthetized compared to awake animals [205]
Mepivacaine
Dogs: do not exceed 3 mg/kg Cats: do not exceed 1.5 mg/kg
Dogs: 6 mg/kg Cats: 3 mg/kg
1.5–3 h duration with quick onset (2–5 min regionally)
Proparacaine 0.5%
Two drops administered 1 min apart
Unknown
Dogs: up to 55 min Cats: up to 30 min [206]
Ropivacaine
Dog maximum dose: 3 mg/kg Cat maximum dose: 1.5 mg/kg Epidural: 1 mg/kg of 0.5% sol. (0.2 mL/kg)
Unknown
Slow onset of action and duration, similar to bupivacaine, when low concentrations are used (0.25–0.5%) Onset is faster, similar to mepivacaine, when higher concentrations are used (0.75%)
Toxic signs for doses are as follows, and gradually progress with increasing toxic dose: first signs of toxicity are usually GI in nature (nausea, vomiting). As the toxicity worsens, neurologic signs evolve (tremors, twitches, seizures). As toxicity progresses, cardiovascular depression and arrest will follow. These later signs occur at much higher doses than what is listed.
CRI, constant‐rate infusion; IV, intravenous.
B. CLINICAL APPLICATIONS
Used for local regional analgesia blocks
C. PHARMACOLOGY
All local anesthetics share a common chemical structure that includes a lipophilic, benzene ring and a hydrophilic amine group. This compound is then linked to either an ester or an amide
pKa8.1. pKa determines the amount of ionized and unionized fraction of drug present in the plasma. At high pKa, the proportion of local anesthetic is greater as the ionized, charged hydrophilic form at physiologic pH (7.4), and the onset of action will be slower. In contrast, at low pKa, a greater proportion of the nonionized lipid‐soluble form is present at physiologic pH. Onset of action is more rapid at a low pKa
% Ionized at physiological pH: 83
Lipid solubility (the main determinant of potency and onset of action) is 30
% Protein binding 95; protein binding influences the duration of action. Only the unbound fraction of drug is pharmacologically active. The higher protein binding, the longer the duration of action
Baricity is the property affecting the distribution and spread of the local anesthetic solution after intrathecal administration. When injected into the subarachnoid space, hypobaric solutions will migrate to nondependent areas, while hyperbaric solutions will migrate to dependent areas. Isobaric solutions will migrate to both sides of the spinal cord, causing bilateral spinal block. Bupivacaine routinely used in veterinary medicine is isobaric but hypo‐ and hyperbaric solutions are available
D. CONTRAINDICATIONS/PRECAUTIONS
IV administration, as this medication has high cardiotoxicity potential
Local anesthetic toxicity generally affects first the gastrointestinal system, causing nausea, vomiting, and inappetence, then the musculoskeletal system, causing muscle weakness and ataxia; continued dosing will lead to CNS toxicity, resulting in seizures and obtundation. As dosing continues, cardiovascular toxicity ensues, including hypotension, bradycardia or even ventricular arrthmias, and possible cardiovascular collapse. It is important to recognize that many of these toxic effects would go unnoticed (outside the cardiovascular effects) in the anesthetized patient.
E. PRACTICAL NOTES
Loss of motor function when used in epidural or brachial plexus block
Highly protein bound (caution with dosage in hypoalbuminemic animals)
If multiple blocks are used, ensure total dosage for patient does not exceed the toxic dose
In an epidural, preservative‐free formulations are recommended
Do not dilute concentration to less than 2.5 mg/mL or block may lose effectiveness
The addition of dexmedetomidine at 0.5 μg/mL of the volume for the local block volume will extend the duration of bupivacaine
NaCO3 can be added to local anesthetic solutions to increase the pH, resulting in less sting upon injection when administering to conscious patients. Increasing the pH may also increase the lipid‐soluble fraction, providing a more rapid onset of action and prolonged duration of sensory blockage
For many years, mixing lidocaine and bupivacaine was recommended, but this methodology was based on erroneous assumptions for the onset of action of bupivacaine, and is starting to lose favor [35,36]. The authors do not mix lidocaine and bupivacaine
XII. Bupivacaine (liposomal encapsulated) local anesthetic
Prolonged‐release liposomal encapsulated bupivacaine formulation approved by the FDA in 2016 for postoperative analgesia lasting up to 72 h for cranial cruciate ligament surgery in dogs by applying into the tissue layers during closure
Drug is often diluted 1:1 with 0.9% saline to increase volume
Useful off‐label in practically any surgical wound closure, respecting the labeled dose
Useful in TAP blocks at the labeled dose (see Chapter 7, p.261)
C. PHARMACOLOGY
Liposomal encapsulated bupivacaine is a sterile, preservative‐free, white to off‐white aqueous suspension that comes in a concentration of 13.3 mg/mL
Full prescribing summary as reference found at: www.elancolabels.com/us/nocita
D. CONTRAINDICATIONS/PRECAUTIONS
At this time, it is recommended to avoid laser therapy following administration of liposomal encapsulated bupivacaine, due to concerns over destruction of the liposomal encapsulation
E. PRACTICAL NOTES
Liposomal encapsulated bupivacaine is infiltrated in the tissues surrounding the surgical site using a moving‐needle injection technique in order to infiltrate deep and superficial layers of the surgical site
Before withdrawing the product into a syringe, the vial should be inverted several times (avoid shaking) to resuspend the particles
According to the manufacturer, unopened vials should be stored in the refrigerator at a temperature of 36–46 °F, or at room temperature of 68–77 °F for up to 4 h after withdrawal from vial. However, off‐label reports suggest storage up to 4 days after puncture of the vial at room temperature or refrigerated [37]
XIII. Buprenorphine (standard formulation) partial mu agonist opioid
Standard preparation 0.01–0.03 mg/kg IM, IV, or in cats, oral transmucosal (OTM) Epidural 0.003–0.006 mg/kg; preservative‐free formulations are recommended when available High concentration formulation buprenorphine (HCFB) (1.8 mg/mL) is labeled for cats at 0.24 mg/kg q 24 h for up to 3 days SC for the control of postoperative pain associated with surgical procedures [207,208] Sustained‐release (SR) buprenorphine: 0.12 mg/kg cats, 0.2 mg/kg dogs [209,210]
Onset varies by route of administration, but due to its pharmacologic profile, onset is generally considered delayed [211] Duration of traditional formulation (0.3 mg/mL): while duration is also affected by route of administration, generally buprenorphine is thought to last 6–8 h. When administered epidurally, duration has been reported as up to 24 h Onset of HCFB is delayed; the drug should be administered at least 1 h prior to desired effect Onset time of SR buprenorphine has not been studied. Buprenorphine SR is reported to provide 72 h worth of analgesia
Butorphanol
Kappa agonist, mu antagonist
0.1–0.4 mg/kg IM, SC, IV
Duration of 30–90 min (canine) [212] –300 min (feline) [213]
Fentanyl
Full mu agonist
IV: bolus 2–10 μg/kg CRI: 2–42 μg/kg/h Postoperative CRI: 2–5 μg/kg/h Transdermal delivery: 25 μg/h for patients under 10 kg, 50 μg/h for patients 10–20 kg, 75 μg/h for patients 20–30 kg, and 100 μg/h for patients greater than 30 kg
Duration of IV bolus in dogs and cats: 20–45 min
Transdermal onset takes up to 12–24 h; duration of 48 h or more after onset. Plasma concentrations start to decline at 72 h after application in dogs [214]
Hydromorphone
Full mu agonist
0.05–0.1 mg/kg IV 0.1–0.2 mg/kg IM CRI: 0.02–0.04 mg/kg/h
Duration of 4 h
Meperedine
Full mu agonist
Canine: 5–10 mg/kg IM Feline: 3–5 mg/kg IM
Duration of 45 min
Methadone
Full mu agonist opioid but also possesses NMDA antagonist properties
0.1–0.5 mg/kg IV, IM, SC
Duration of 4–6 h
Morphine
Prototype mu agonist opioid, to which all other opioids are compared. Morphine also works at delta and kappa receptors
0.1–1.0 mg/kg SC, IM CRI: 0.1–0.3 mg/kg/h IV Epidural: 0.1 mg/kg preservative‐free formulation
Onset of action may take up to 30 min Duration of IM systemic, single dose administration is 2–4 h; epidural duration is 12–24 h
Remifentanil
Full mu agonist
IV: bolus 0.002–0.005 mg/kg CRI: 2–42 μg/kg/h,with one dose‐finding study suggesting 24 μg/kg/h may be most suitable for cats undergoing routine OHE [215]
Duration is seconds regardless of duration of exposure; must be given as a CRI
Sufentanil
Full mu agonist
Loading dose of 0.1–0.7 μg/kg, followed by an infusion at 0.5–0.72 μg/kg/h IV [216,217]
Sufentanil has a more rapid onset and shorter duration of action than fentanyl in people [218]
Tramadol
Central acting analgesic with weak mu opioid receptor agonist
Canine: 2.5–5 mg/kg PO Feline: 2 mg/kg PO
4–12 h
CRI, constant‐rate infusion; IM, intramuscular; IV, intravenous; NMDA, N‐methyl‐D‐aspartate; OHE, ovariohysterectomy; PO, per os (by mouth); SC, subcutaneous.
B. CLINICAL APPLICATIONS
Provides mild to moderate analgesia and sedation or euphoria, especially in cats, making them more cooperative; however, has minimal sedation in dogs when used alone
Does not cause vomiting or histamine release
Has a ceiling effect
C. PHARMACOLOGY
Potent semisynthetic and highly lipophilic opioid derivative of thebaine
The authors agree with the statement made by Steagall et al: “Some authors consider buprenorphine a unique drug with a complex pharmacologic profile. The drug binds avidly to, and dissociates slowly from, opioid receptors, but does not elicit a maximal clinical response, because it is not a classic ‘full agonist’ like morphine” [38]
Metabolized by the liver
Reversible with naloxone
D. CONTRAINDICATIONS/PRECAUTIONS
Patients which are hypersensitive to buprenorphine
Causes miosis in the canine and mydriasis in the feline
E. PRACTICAL NOTES
Controlled, Schedule III
OTM is ideal for fractious cats especially when combined with ketamine. This route is questionable in dogs, due to the low bioavailability of the drug
In cats, buprenorphine has been shown to be as effective as morphine in treating moderate to severe pain [39]
Difficult to reverse due to extremely high affinity for mu receptor
Protect from light
XIV. Buprenorphine high‐concentration formulation of buprenorphine [1.8 mg/mL]
Reliable analgesia with subcutaneous route of administration, once daily, for cats
C. PHARMACOLOGY
High‐concentration formulation buprenorphine is still a potent semisynthetic and highly lipophilic opioid derivative, but concentration is higher at 1.8 mg/mL
Biphasic rapid and slow absorption kinetics, which account for its prolonged duration of effect when given SC [40]
Available as a multi‐use 10 mL vial, stored at room temperature, offering 28 days shelf‐life from first broach
D. CONTRAINDICATIONS/PRECAUTIONS
Patients which are hypersensitive to buprenorphine
Patients acutely painful and requiring immediate analgesia (this drug takes approximately 60 min for onset)
E. PRACTICAL NOTES
This drug may last longer than 24 h in some feline patients [41]
Studies have examined intravenous and OTM routes of administration, but neither route has the prolonged duration found with SC administration of the drug [40]
FDA‐approved buprenorphine injection for long‐lasting pain relief in cats
Off‐label applications are occurring. Dose in dogs appears to be 0.12 mg/kg SC or IV with an onset of greater than 60 min and duration of up to 6 (IV)–16 h (SC) [41]
XV. Buprenorphine SR sustained‐release (SR) buprenorphine
It is reported to provide up to 72 h of analgesia [42,43]. In previous studies, antinociception produced by 0.12 mg/kg of buprenorphine SR was similar to that produced by buccal administration of the regular formulation of buprenorphine [44]
C. PHARMACOLOGY
Formulation consists of buprenorphine hydrochloride in an SR delivery matrix of a water‐insoluble polymer that precipitates in body fluids and forms a depot for SR of the active drug after SC administration
D. CONTRAINDICATIONS/PRECAUTIONS
Patients which are hypersensitive to buprenorphine
Patients acutely painful and requiring immediate analgesia as onset is likely slow
E. PRACTICAL NOTES
Non‐FDA‐approved formulation of buprenorphine
XVI. Butorphanol mu antagonist, kappa agonist opioid
Dog: 2.2 mg/kg BID or 4.4 mg/kg SID PO, SC, IV The authors cannot recommend carprofen in cats due to its unpredictable metabolism in this species
12–24 h
Deracoxib
Selective COX‐2 inhibitor
Postoperative pain in dogs: 3–4 mg/kg Osteoarthritis pain in dogs: 1–2 mg/kg
24 h
Grapiprant
Antagonist of the prostaglandin E2 receptor 4
Dogs: 2 mg/kg PO SID Cats: not approved for use in cats; however, pharmacokinetics of 2 mg/kg PO and safety/toxicokinetic profiles at 3, 9, 15 mg/kg have been evaluated [219,220], with dosages of less than 15 mg/kg resulting in no adverse effects
24 h
Ketoprofen
Nonselectively inhibits both COX‐1 and COX‐2
Cats and dogs: initial dose 2 mg/kg followed by 1.0 mg/kg for up to 5 days
24 h
Meloxicam
COX‐2 preferential
Dog: 0.2 mg/kg SC as the first dose, following doses 0.1 mg/kg PO Cats: 0.1 mg/kg SC or PO once. This dosage is recommended in compliance with the FDA’s black box warning about repeated dosing of meloxicam in this species
24 h
Robenacoxib
Selective COX‐2 inhibitor
Dog: 2 mg/kg SC SID for maximum 3 days; tablet dose 2 mg/kg PO for maximum 3 days Cats: 2 mg/kg SC SID for maximum 3 days; tablet dose 1 mg/kg PO for maximum 3 days
24 h
NSAIDs are used for decreasing inflammation and pain due to inflammatory mediators and osteoarthritis. It is important to allow 3–5 days’ “wash out” between NSAIDs or following administration of steroids.
BID, bis in die (twice a day); COX, cyclooxygenase; FDA, Food and Drug Administration; IV, intravenous; PO, per os (by mouth); SC, subcutaneous; SID, semel in die (once a day).
B. CLINICAL APPLICATIONS
Used to manage pain and inflammation associated with osteoarthritis and acute pain associated with soft tissue and orthopedic surgery in dogs
Carprofen is recognized for its analgesic efficacy for up to 72 h postoperatively in canine ovariohysterectomies [47]
C. PHARMACOLOGY
Highly selective for COX‐2 inhibition
COX‐2 inhibition by NSAIDs is thought to be responsible for the antipyretic, analgesic, and antiinflammatory actions of NSAIDs. However, concurrent inhibition of COX‐1 may result in many of the unwanted effects of NSAIDs, including gastric ulceration and renal toxicity
Carprofen acts primarily to reduce the biosynthesis of prostaglandins by inhibiting cyclooxygenase (COX‐1, and preferentially COX‐2). Inhibition of prostaglandins that regulate blood flow to the gastric mucosa and stimulate bicarbonate and mucus production may result in loss of GI protective mechanisms
NSAIDs are biotransformed in the liver to inactive metabolites that are excreted either by the kidney via glomerular filtration and tubular secretion or by the bile
D. CONTRAINDICATIONS/PRECAUTIONS
Although carprofen’s use as part of a premedication prior to the inflammatory event (as opposed to postoperative administration) provides preemptive and better analgesia, caution is advised if using this drug preoperatively
Carprofen may reduce the diuretic effects of furosemide and increase serum levels of digoxin. Use with caution in patients with severe cardiac failure
Laboratory interactions – in dogs, carprofen may lower total T4 and TSH levels in dogs, but apparently does not affect free concentrations of T4
The risk or severity of hypotension may be increased when carprofen is combined with acepromazine
GI ulceration is the most common life‐threatening effect while vomiting is the most common adverse effect
May compromise renal blood flow
Potentially serious idiosyncratic hepatopathies, characterized by acute hepatic necrosis, have been reported in some dogs [48]
Avoid use of NSAIDs, especially those that are COX‐2 selective, in patients with GI surgical incisions or suspected ulcers, as they may inhibit GI healing [49]
Use with caution in patients already receiving highly protein‐bound drugs (e.g., warfarin, heparin)
E. PRACTICAL NOTES
Injectable and oral formulation are available
The authors cannot recommend carprofen in cats due to its unpredictable metabolism in this species
XIX. Cisatracurium nondepolarizing neuromuscular blocking agent
The drug is a refined form of one of the 10 stereoisomers of atracurium
Has action at the neuromuscular junction where it competes with ACh to bind the cholinergic receptor, preventing muscle contractions of skeletal muscle (paralysis)
Cleared primarily by Hoffmann elimination (metabolism is dependent upon patient’s pH and body temperature)
D. CONTRAINDICATIONS/PRECAUTIONS
Before administration, a mechanical ventilator is appropriately set to maintain ventilation for the patient. Diligent monitoring of the patient to ensure adequate ventilation prior to extubation is also required
Monitor paralysis with a train of four (TOF) on a peripheral nerve stimulator; during recovery, at least two twitches should be present before reversal of the drug (see Table 3 for reversal agents)
E. PRACTICAL NOTES
Often used for ophthalmological procedures so the eye remains central
Recovery – monitoring with a capnograph and pulse oximeter is beneficial during recovery. Patients may relapse or have residual paralytic effects and are continuously monitored until completely recovered
Some anesthetists will administer this drug as a CRI
Protect from light and refrigerate drug
Minimal cardiovascular side‐effects (cisatracurium does not induce histamine release)
XX. Dantrolene muscle relaxant
A. DOSE AND DURATION
0.5–2 mg/kg IV
Duration 8 h
B. CLINICAL APPLICATIONS
Treatment of malignant hyperthermia (MH)
Used in feline urethral spasm (0.5–2 mg/kg q 12 h)
C. PHARMACOLOGY
Skeletal muscle relaxant which works by binding to the ryanodine receptor, depressing the intrinsic mechanisms of contraction potentially by decreasing intracellular calcium concentration
Poor water solubility
D. CONTRAINDICATIONS/PRECAUTIONS
Can cause drowsiness and dizziness
Hepatoxicity is possible; use with caution in patients with hepatic disease
Results in muscle weakness
E. PRACTICAL NOTES
No discernible effects on respiratory and cardiovascular systems
Protect from light
Once reconstituted per manufacturer’s instructions, only stable for 6 h
Frequency of MH is rare, and the drug is moderately expensive. If there is preemptive suspicion that a patient may have an MH episode, this drug is obtained by an internet search
Used for controlling pain and inflammation of osteoarthritis
Used for postoperative pain from surgical procedures, specifically dentals and orthopedic procedures
C. PHARMACOLOGY
Highly selective for COX‐2 inhibition
COX‐2 inhibition by NSAIDs is thought to be responsible for the antipyretic, analgesic, and antiinflammatory actions of NSAIDs. However, concurrent inhibition of COX‐1 may result in many of the unwanted effects of NSAIDs, including gastric ulceration and renal toxicity
Inhibits one or more steps in the metabolism of arachidonic acid (AA) and possesses both analgesic and antiinflammatory properties
Deracoxib acts primarily to reduce the biosynthesis of prostaglandins by inhibiting cyclooxygenase (COX‐1 and COX‐2). Inhibition of prostaglandins that regulate blood flow to the gastric mucosa and stimulate bicarbonate and mucus production may result in loss of GI protective mechanisms
NSAIDs are biotransformed in the liver to inactive metabolites that are excreted either by the kidney via glomerular filtration and tubular secretion or by the bile
D. CONTRAINDICATIONS/PRECAUTIONS
Use with caution in patients already receiving highly protein‐bound drugs (e.g., warfarin, heparin)
For patients with renal failure, use at the lowest effective dose or avoid
Preemptive evaluation of liver function and liver enzymes, as well as periodic rechecks of liver values, are warranted in any patient where long‐term use is indicated. Rare side‐effect of hepatic toxicity can occur in dogs
Patients predisposed to or experiencing intraoperative hypotension may have compromised renal blood flow. It is the authors’ recommendation to avoid this drug for the first 24 h post anesthesia in these patients
Avoid use of NSAIDs, especially those that are COX‐2 selective, in patients with gastrointestinal surgical incisions or suspected ulcers, as they may inhibit GI healing [49]
NSAIDs may antagonize the antihypertensive effects of ACE inhibitors
E. PRACTICAL NOTES
Vomiting is the most common adverse effect
GI ulceration is the most common life‐threatening adverse effect
Short (i.e., shorter than isoflurane and sevoflurance)
0.42
18.70
700
Isoflurane
Well conserved between species at 1.2 (canine)–1.4% (feline)
Based on exposure (longer duration than sevoflurane or desflurane)
1.4
91
240
Sevoflurane
Well conserved between species at 2.3 (canine)–2.6% (feline)
Based on exposure (shorter acting than isoflurane)
0.68
47
160
MAC, minimum alveolar concentration.
B. CLINICAL APPLICATIONS
Desflurane is characterized by a more rapid induction due to its very low solubility in the blood. This characteristic also means there are rapid changes in anesthetic depth when the vaporizer is adjusted, and recovery is quicker than with isoflurane and sevoflurane
Suitable for anesthesia induction via facemask or induction chamber
Inhalant maintenance of anesthesia
C. PHARMACOLOGY
Desflurane is a clear, colorless, and odorless liquid with a boiling point close to room temperature
The exact mechanism of action by which inhalant anesthetic agents cause general anesthesia is not precisely known, but they seem to influence the electrical activity of the CNS by acting on the lipid bilayer of the cell membrane, altering cerebral metabolism and perfusion
Most important effects include prevention of movement, which is likely mediated at the level of the spinal cord, dose‐dependent cardiovascular and respiratory depression, decreased systemic vascular resistance (thus vasodilation and hypotension), increased cerebral blood flow (and therefore possible increase in intracranial pressure), depression of body temperature regulating centers, and muscular relaxation
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with preexisting extreme hypotension, cardiovascular derangements or reason for inability to handle vasodilation
In susceptible individuals, inhalant anesthesia may trigger a clinical syndrome known as malignant hyperthermia (MH). MH is a cellular hypermetabolic state that, if not treated quickly, causes death. Although it is mostly reported in human patients and pigs, other species have also been reported to be affected
The National Institute for Occupational Safety and Health Administration (NIOSH) recommends that no worker should be exposed to ceiling concentrations greater than 2 ppm of any halogenated anesthetic agent over a sampling period not to exceed 1 h
Caution in patients with increased intracranial pressure or head trauma
E. PRACTICAL NOTES
Desflurane requires a precision vaporizer with an external heat source and electricity to function
Duration of 2–4 h; additional dosage within 12–24 h will not result in a greater effect
B. CLINICAL APPLICATIONS
Although this drug is used to treat central diabetes insipidus, it is also useful in patients with von Willebrand disease to increase the release of von Willebrand factor (factor VIII)
C. PHARMACOLOGY
Synthetic analogue of AVP with minimal pressor effects (V1), but significant antidiuretic effects (V2), causing reabsorption of water in the kidney
The V2 effects are what triggers endothelial cells to release von Willebrand factor
Results in less vasoconstriction than vasopressin
D. CONTRAINDICATIONS/PRECAUTIONS
Hypercoagulable patients
Monitor blood pressure in hypertensive patients after administration (although pressor activity is minimal, it is still present)
E. PRACTICAL NOTES
Effects are short‐lived but drug is useful for administration prior to a surgical event in a patient with von Willebrand disease
Used as an injectable alternative for a patient who missed their oral dosage of corticosteroids (i.e., prior to anesthesia)
C. PHARMACOLOGY
Fluorinated derivative of prednisolone
Water soluble, allowing for a variety of routes of administration
While this drug technically has no mineralocorticoid activity, it does appear to result in a clinical effect when administered at 1/7th the dose of glucocorticoids, in animals presently on oral glucocorticoid supplementation
D. CONTRAINDICATIONS/PRECAUTIONS
Do not use in patients currently receiving NSAIDs
Caution in diabetics and patients with renal insufficiencies
Do not use in patients with GI ulcers or GI compromise, as it may cause GI ulcers
Long‐term use results in adrenocortical dependency; if a patient has received dexamethasone, especially at high doses, an Addisonian crisis may manifest under anesthesia (see Chapter 5) if this drug is abruptly withdrawn prior to the anesthetic event. Patients tapered slowly off the drug are unlikely to have this effect
Immunosuppressive features may precipitate delayed wound healing and promote secondary infections
E. PRACTICAL NOTES
Protect from light
An increase in urination and water consumption may result from a high dosage of this drug
Intranasal: a study showed that 0.02 mg/kg dexmedetomidine produced effective sedation with less bradycardia and more profound sedation compared to IM administration in healthy dogs and may be considered as an alternative route for administration in dogs [51], similar to previous studies in rabbits [52]
125 μg/m2 of dexmedetomidine oromucosal gel is useful (potentially for administration by owners), prior to veterinary visits, in reducing signs of stress (vocalizations, avoidance behaviors, panting, trembling, urination, defecation) in dogs [53]
B. CLINICAL APPLICATIONS
Dexmedetomidine is commonly used both as a sole sedative for minor procedure and in combination with opioids as a premedication for general anesthesia or to improve the quality of sedation
Dexmedetomidine has multiple routes and modalities of administration (including epidurally or as a constant‐rate infusion), is not controlled, provides substantial analgesia and moderate to profound sedation (especially when combined with opioids), making it one of the most versatile drugs for anesthesia a veterinarian has available
This drug is often used with the intent of extending the duration of a local regional block, when added to the local anesthetic solution used for regional anesthesia at 0.001mg/kg. However, efficacy of this varies by study [54–56]
C. PHARMACOLOGY
Dexmedetomidine is the active enantiomer of the racemic mixture medetomidine, and a potent sedative and analgesic drug
Dexmedetomidine is the most selective alpha‐2‐adrenergic receptor agonist and has almost completely replaced xylazine for the same purposes. The selectivity for alpha‐2‐adrenergic receptors is higher (1620:1) than xylazine, making dexmedetomidine more potent than xylazine
Presynaptic alpha‐2‐adrenergic receptors: inhibits release of norepinephrine and attenuates the sympathetic drive from the CNS
Postsynaptic alpha‐2‐adrenergic receptors: effect similar to alpha‐1‐adrenergic receptor actions resulting in vasoconstriction
After IV, IM, SC routes and across transmucosal membranes, the bioavailability is high and the onset of sedation rapid
Analgesic and sedative effects have the same duration
The action on the alpha‐2 receptors in the CNS causes dose‐dependent degree of sedation up to a plateau, after which higher doses only increase length of sedation and side‐effects. Animals deeply sedated can abruptly arise and demonstrate responses to external stimuli. The combination with opioids reduces these responses and produces deep sedation; indeed, these drugs may be synergistic when given together [57]
Analgesia is exerted by dampening the afferent inputs at various point of the nociceptive pathway. When administered epidurally or intrathecally (preservative‐free formulations preferred for this purpose), it provides excellent analgesia for a direct action on the receptors in the dorsal horn of the spinal cord
Metabolized by the liver
D. CONTRAINDICATIONS/PRECAUTIONS
Cardiovascular (CV) diseases including valvular regurgitation or arrhythmias are by far the most pressing contraindication to use of dexmedetomidine (see “Alfaxalone,” p.280 in this formulary, as an alternative IM injectable for sedation in the patient with valvular disease)
Cardiovascular effects are marked and biphasic: blood pressure is initially markedly increased, with profound bradycardia caused by a baroceptor reflex following peripheral vasoconstriction. In the second phase, a less profound bradycardia is evident and due to the suppression of the central cardiovascular center, followed by possible hypotension due to a decrease in CO
Bradyarrhythmias, including second‐degree AV block, escape rhythms and accelerated idioventricular rhythms (AIVR) are frequent in both dogs and cats. In practice, the authors use anticholinergic to treat the bradycardia related to alpha‐2‐adrenergic receptor agonists only when hypotension exists (i.e., the second phase of the cardiovascular effects). If the patient is within the first phase of cardiovascular effects (i.e., blood pressure is normal to high), administration is often reversed when hypotension or bradyarrhythmias are present. Alternatively, recent work suggests that lidocaine, initially as a 2 mg/kg bolus IV and followed with a constant‐rate infusion (CRI) of 3–6 mg/kg/h for 30 min, may counteract dexmedetomidine‐induced bradycardia [58]
Respiratory effects are related to the depth of sedation achieved and, unless the sedation is very deep, the reduction in respiratory rate is compensated by the increase in tidal volume, allowing the maintenance of a normal minute ventilation
Increase in urine output is caused by central inhibition of ADH secretion and hyperglycemia as a result of the decrease in serum level of insulin
Dexmedetomidine is contraindicated in patients with renal insufficiencies, anuria, or a blocked urinary system
Dexmedetomidine is contraindicated in patients with liver function disease
Avoid in geriatric, pregnant, pediatric, sick, or debilitated patients
E. PRACTICAL NOTES
Patients will often develop a transient hyperglycemia after administration
Most effective when administered to a patient that is allowed 5–10 min in a quiet, darkened room, with minimal stimulus
Monitor the patient after premedication and ensure reversal dose has been calculated and is available if needed
The reversal, atipamezole (see p. 285 in this formulary), is given IM, to avoid rapid vasodilation
Vasoconstriction may cause pale or blue MMC, and the pulse oximeter may have difficulty obtaining a measurement
Low doses work nicely as premedication in cats with HCM
In a study comparing the two, dexmedetomidine was more likely to cause vomiting than xylazine in cats [59]. If vomiting is undesirable, consider premedication with maropitant (see p. 337 in this formulary) [60]
XXVI. Dextrose supplement
A. DOSE AND DURATION
IV bolus for profound hypoglycemia 250 mg/kg or 0.5 mL/kg of 50% dextrose (diluted 1:4 with isotonic fluids)
Fluid additives: add appropriate amount to fluids, to yield a 2.5 5% solution (see Appendix D, Dilution equations, p.397)
Often given as a component of a CRI to prolong duration of supplementation
B. CLINICAL APPLICATIONS
Increases serum blood glucose, providing energy stores for cellular metabolism
Prevention of hypoglycemia in prone patients such as neonates
Treatment of diabetic ketoacidosis
Adjunctive treatment for hyperkalemia (see Chapter 3, p.78)
C. PHARMACOLOGY
Dextrose is a molecule made from corn identical to blood glucose (C6H12O6), a monosaccharide, and type of carbohydrate
D. CONTRAINDICATIONS/PRECAUTIONS
Extremely hypertonic, requiring dilution prior to administration
Hyperglycemic patients
E. PRACTICAL NOTES
Common dilutions for anesthesia are 2.5–5% in crystalloid solutions
Monitor blood glucose from an independent catheter
High concentrations of dextrose cause tissue irritation (especially when given perivascular) due to its hypertonic nature. 1:3 or 1:4 dilutions are recommended when administered via peripheral veins
Unreliable sedative in healthy animals but useful as central muscle relaxant and anticonvulsant
Used as coinduction agent to reduce the dose of primary induction drug needed [61]
Appetite stimulant, especially in cats
Administered in combination with ketamine or tiletamine to counteract the muscle rigidity of the dissociative agents
Antianxiety effects
C. PHARMACOLOGY
Sedative effects occur by enhancing the GABAA receptor’s affinity for the inhibitory neurotransmitter GABA within the CNS. Benzodiazepines are considered to have an indirect effect by potentiating the activity of endogenous GABA neurotransmitter, leading to a wide safety margin and minimal depression of ventilation, cardiac output, and oxygen delivery
Muscle relaxant and anticonvulsant properties derive from action on spinal interneurons
Highly protein bound
Metabolized by the liver with production of active metabolites that can persist for several hours after administration
Poorly water soluble; is supplied for injection in a solution that contains organic solvents such as propylene glycol and ethanol
D. CONTRAINDICATIONS/PRECAUTIONS
Can cause pain on IM injection and thrombophlebitis after intravenous injection [62]
Muscle tissue necrosis can develop following IM injection [63]
Crosses the placental barrier and may result in respiratory depression in neonates
Patients with liver function insufficiencies may have prolonged effect
Avoid in patients with hepatic encephalopathy
In contrast to humans and dogs, diazepam has been reported to induce severe hepatic side‐effects in cats, particularly after repeated doses [64]
E. PRACTICAL NOTES
Propylene glycol‐based and highly lipid soluble, making it incompatible with many drugs and painful on IM or SC injection as well as inconsistently absorbed
Is light sensitive and will bind to soft plastics, such as infusion lines
Part of the premedication for conditions that predispose the patient to histamine release: mast cell tumors, anaphylaxis, and heart worm extractions
Some clinicians administer preemptively before blood transfusions
C. PHARMACOLOGY
Blockade of histamine1 (H1) receptors
D. CONTRAINDICATIONS/PRECAUTIONS
May result in sedation but this is unpredictable
E. PRACTICAL NOTES
In patients with histamine release, there are decreased symptoms of reaction; however, this will not reverse a reaction. It will simply prevent histamine molecules released from binding to the receptor sites. In life‐threatening histamine release that occurs with a severe allergic reaction, diphenhydramine alone will be insufficient
For CPR (see Appendix B, p.393): Low dose: 0.01 mg/kg IV High dose: 0.1 mg/kg IV IT dose: 10× standard low IV dose is recommended For intraoperative hypotension in CRI: 0.006–0.06 mg/kg/h IV For anaphylaxis treatment: 0.02 mg/kg IM or IN [221]
Very quick onset and short duration due to rapid metabolism (less than 2 min when administered IV). Need frequent redosing or CRI for a prolonged effect
+++
+++
Nitroprusside
Peripheral vasodilator
0.1–2 μg/kg/min (ideal to use less than 0.5 mg/kg/h)
1–3 min
––
––
Norepinephrine
Catecholamine and vasopressor
0.006–0.09 μg/kg/min
1–2 min
+
+++
Phenylephrine
Vasopressor
0.002–0.005 mg/kg IV, CRI 0.5–2 μg/kg/min
A single bolus may last up to 20 min
–
+++
Vasopressin
Vasopressor
Bolus 0.2–0.8 units/kg IV with the higher dose appropriate for CPR; CRI 0.02–0.04 units/kg/h
10–20 min
–
+++
CPR, cardiopulmonary resuscitation; CRI, constant‐rate infusion; IM, intramuscular; IN, intranasal; IV, intravenous.
B. CLINICAL APPLICATIONS
Patients with weak cardiac contractility
C. PHARMACOLOGY
Beta‐1 stimulation increases myocardial contractility to improve SV and CO [65]
Mild beta‐2 agonist stimulation results in some smooth muscle relaxation (this may cause decrease in BP although CO is likely increased), although its affinity for beta‐2 receptors is approximately 10‐fold less than that of beta‐1 [65]
Short‐acting, so typically administered as a CRI
Sympathomimetic
Mild chronotropic, arrhythmogenic and vasodilator effects which increase oxygen consumption [65]
C. CONTRAINDICATIONS/PRECAUTIONS
High doses may cause hypertension, tachycardia, and arrhythmias
Contraindicated in patients with HCM, ventricular hypertrophy, ventricular arrhythmias, endogenous catecholamine overproduction
Beta‐blockers (e.g., propranolol) may antagonize the cardiac effects of dobutamine
D. PRACTICAL NOTES
Common dilution for administration is 1–2 mg/mL
Refrigeration is recommended after broaching vial
XXX. Dopamine endogenous catecholamine and positive inotrope
Used to improve blood pressure through increased contractility of the heart and to provide mild vasoconstriction
C. PHARMACOLOGY
Dopamine, which is also present as an endogenous catecholamine, is an immediate precursor to norepinephrine [65]
Action at various receptors, including alpha, beta, and dopaminergic, depends on dose (although exact doses are controversial)
Low doses (<3 μg/kg/min) provide higher affinity for dopaminergic receptors D1 and D2. This may improve hemodynamics by vasodilating capillary beds in renal, mesenteric, coronary, and cerebral regions. Because of this, outside the OR it is sometimes used as adjunctive therapy for treatment of oliguric renal failure or acute heart failure
At mid‐range doses (3–10 μg/kg/min), beta‐1 and beta‐2 receptors are the most stimulated, often maximizing myocardial contractility and increasing organ perfusion, renal blood flow, and urine production
At higher doses, vasoconstriction and increase in SVR caused by alpha‐1‐adrenergic receptor stimulation. Blood pressure increases and renal and peripheral blood flow may decrease
Dopamine has an indirect sympathomimetic activity in stimulating the release of endogenous norepinephrine from adrenergic receptors
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with endogenous catecholamine overproduction (e.g., pheochromocytomas)
Patients with ventricular tachyarrhythmias, HCM, ventricular hypertrophy
Severe hypertension develops when dopamine is used in conjunction with oxytocin [66]
The effects of dopamine may be prolonged and enhanced in patients in which monoamine oxidase (MAO) inhibitors (i.e., selegiline) were administered
Concomitant use of ephedrine with beta‐blockers may decrease the effects of both drugs
Tachycardia, tachyarrhythmias, and hypertension may occur from the coadministration of anticholinergic and dopamine
E. PRACTICAL NOTES
Note that it is controversial as to whether cats express dopaminergic receptors; while there is some evidence to support putative D1‐like or D1 receptor existence in feline kidneys [67], its use in feline renal failure patients is less reliable than in canine renal failure patients
Common dilutions are 1–2 mg/mL
Dilutions are used within 24 h and discarded if solution changes color
Refrigerate bottle after first broaching
Protect bottle and dilutions from light
High doses or administration of undiluted product can cause arrhythmias, hypertension, and tachycardia
Extravasation can cause necrosis of perivascular tissue [68]
XXXI. Doxapram respiratory stimulant
A. DOSE AND DURATION
2–5 mg/kg IV or 1–2 drops under tongue of newborn
Usually administered only once, as additional dosages may have decreased effectiveness
B. CLINICAL APPLICATIONS
Used to stimulate respiration typically in neonates or for laryngeal examination
May increase CO
C. PHARMACOLOGY
Stimulates respiration by action on the carotid chemoreceptors, resulting in an increase in tidal volume rather than respiratory rate
Contains benzyl alcohol (cautious use in cats)
D. CONTRAINDICATIONS/PRECAUTIONS
Repeated dosages may result in undesirable CNS stimulation
Protect from light
E. PRACTICAL NOTES
Authors’ preference is to avoid unnecessary use of doxapram as it causes undesirable CNS stimulation
XXXII. Ephedrine synthetic noncatecholamine inotropic and vasopressor agent
Used to temporarily increase blood pressure and heart rate
Vasoconstriction and increases in heart rate, coronary blood flow, and blood pressure result in increase in CO
Presumed splenic contraction may increase hemoglobin concentration and thus oxygen‐carrying capacity
C. PHARMACOLOGY
Directly stimulates alpha and beta receptors to increase vascular tone through mild vasoconstriction and an increase in myocardial contractility, thus increasing CO and stroke volume
Indirectly stimulates alpha, beta‐1‐ and beta‐2‐adrenergic receptors by causing the release of endogenous norepinephrine. Tachyphylaxis is observed due to depletion of norepinephrine stores [69]
Similar to other adrenergic agents, bronchodilation derives from the beta‐2 stimulation
Sympathomimetic
D. CONTRAINDICATIONS/PRECAUTIONS
When used at higher doses, more profound bradycardia may result reflexively from the significant and prolonged increase in arterial blood pressure
Crosses the blood–brain barrier and acts as a CNS stimulant; adequate anesthesia of the patient should be ensured prior to administration
The drug is excreted in milk and may have deleterious effects on nursing animals
Ephedrine may reduce renal blood flow and glomerular filtration rate due to regional vasoconstriction
Patients with heart disease where increasing myocardial workload would be detrimental, such as HCM
Increased effects can derive from the coadministration of multiple sympathomimetics
The effects of ephedrine can be prolonged and enhanced in patients where MAO inhibitors (i.e., selegiline) are previously administered
The urinary excretion of ephedrine and its duration of activity can be prolonged when urinary alkalinizers (e.g., sodium bicarbonate, citrates, carbonic anhydrase inhibitors) are administered
Concomitant use of ephedrine with beta‐blockers may decrease the effects of both drugs
E. PRACTICAL NOTES
This drug has an advantage for locations which cannot provide constant rate infusions, as it is easily administered as a single bolus
Repeating the dose once is acceptable; repeat bolus (e.g., more than twice) or a CRI is not recommended
Drug is relatively short‐acting with an appreciable clinical effect
Protect from light
Effect is dependent on norepinephrine stores; in patients with depleted norepinephrine stores, there is less of an effect
Adjunct to local anesthetics (LA) to extend the duration of the local block by causing vasoconstriction and therefore decreasing the systemic absorption of the LA, which decreases the dose of LA required, prolongs its effect and decreases the probability of systemic toxicity. Used in this manner, it may also decrease bleeding in the area blocked
C. PHARMACOLOGY
Naturally occurring catecholamine
Prototype sympathomimetic
Direct stimulation of beta‐ and alpha‐adrenergic receptor results in cardiac chronotropic, inotropic and vasopressor dose‐dependent effects
Has action on alpha and beta receptors, resulting in increased blood pressure and systemic vascular resistance, decreased airway resistance, bronchodilation, tachycardia and possible ventricular arrhythmias
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with hypertension and tachycardia
Can cause ventricular fibrillation
Caution should be exercised in cases of hypovolemia
Caution when using as a CRI, as healthy human volunteers demonstrated increased heart rate, plasma insulin, and glucose levels, and decreased mean arterial pressure and diastolic pressure [70]
Do not use as an adjuvant for a local block performed in a distal region, as it may cause necrosis or sloughing of tissue
Increased effects can derive from the coadministration of multiple sympathomimetics
The effects of epinephrine can be prolonged and enhanced in patients where MAO inhibitors (i.e., selegiline) are previously administered
Effect can be potentiated by certain antihistamines (diphenhydramine)
Beta‐blockers (propranolol) can reverse the effects of smooth muscle relaxation in the bronchi and alveoli that epinephrine exerts through stimulation of beta‐receptors and exacerbate the vasoconstrictive and hypertensive effects caused by alpha‐receptor stimulation
E. PRACTICAL NOTES
Low doses, given slowly IV, can lead to a smoother rise in systolic pressure and a decrease in diastolic pressure and decrease in SVR, due to beta‐2 stimulation
High doses will result in vasoconstriction, hypertension, tachycardia, and possibly ventricular arrhythmias. Also, increases in pulmonary vascular resistance reflect the agonism at level of pulmonary vascular alpha‐1‐adrenergic receptors that predominates over beta effects
Decreased airway resistance, bronchodilation, and reversal of hypotension are the main characteristics that make this catecholamine effective in reducing anaphylactic symptoms
The 2012 RECOVER guidelines suggest 0.01 mg/kg for cardiac arrest every 2–5 min and 0.1 mg/kg only after prolonged periods of nonresponsive resuscitation efforts [30]
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XXXIV. Eutectic mixture of lidocaine and prilocaine topical local anesthetic
A. DOSE AND DURATION
Dosage: minimal amount to cover area of anticipated insult
Duration: dependent on contact time, but may exceed 2 h [71]
Onset of action depends on contact with skin, generally 45–60 min. Heat may decrease onset time
B. CLINICAL APPLICATIONS
Topical anesthetic used for desensitization of skin often for IV catheter placement or blood draw
C. PHARMACOLOGY
Contains lidocaine 2.5% and prilocaine 2.5% (both local anesthetics) which penetrate the skin’s full thickness
Recommendations for application include clipping hair first
Authors find that covering area where cream is applied with plastic such as an examination glove to “trap” body heat may decrease onset up to a total time of 10–20 min
Works well to assist in the placement of IV catheters or drawing of blood in neonates or critical patients to avoid or minimize sedation
XXXV. Esmolol beta receptor antagonist
A. DOSE AND DURATION
0.2–0.5 mg/kg IV, CRI 0.5–10 mg/kg/h
Duration of 10 min or less as a bolus
B. CLINICAL APPLICATIONS
Prevention of tachycardia and hypertension
C. PHARMACOLOGY
Beta‐1 antagonist which is rapid in onset, resulting in decreased HR, of a short duration, unless given as a CRI
Metabolized by plasma esterase
D. CONTRAINDICATIONS/PRECAUTIONS
High doses result in myocardial depression, reduction in CO, and bradycardia
Bradyarrhythmias such as AV blocks and escape rhythms
Beta antagonists are not used if there is a suspected catecholamine‐induced nidus for hypertension or tachycardia (e.g., pheochromocytoma), unless appropriate alpha blockade is already present; unopposed alpha stimulation may prove fatal
E. PRACTICAL NOTES
IV administration only
May cause pain on injection
Useful in cases of thyrotoxicosis
Used for pheochromocytomas where α blockade is already achieved
Induction agent ideal for patient with structural or arrhythmogenic cardiovascular disease due to its minimal cardiovascular and respiratory depression characterized by absent changes in HR, SV, MAP or CO after administration
Ideal induction agent for neurologic or neurosurgical patients because of a reduction in cerebral blood flow, ICP and decreased CMRO2 consumption
C. PHARMACOLOGY
Imidazole derivative used for hypnotic properties in cats and dogs
GABAA agonist, resulting in CNS depression and hypnosis
Contains propylene glycol which can cause pain during intravenous administration
Water soluble
Rapidly metabolized both in the liver and by plasma esterases
Highly protein bound
D. CONTRAINDICATIONS/PRECAUTIONS
Avoid in critically ill patients due to suspected adrenal exhaustion. Inhibits adrenal steroidogenesis and stress response to surgery at 1/100th of the dose required to induce anesthesia, due to a dose‐dependent inhibition of cholesterol conversion to cortisol. This effect may last 4–8 h
Patients with Addison disease
Etomidate is hyperosmotic when compared to plasma and causes hemolysis. For this reason, prolonged administration of etomidate is avoided. May also cause irritation upon injection and if accidental perivascular administration occurs
Does not provide analgesia
Patients (especially cats) with renal failure, due to propylene glycol and resultant hemolysis
E. PRACTICAL NOTES
Minimal effects on ventilation
When given without sedation or in a healthy patient, etomidate can cause myoclonus and vomiting at induction and requires high doses
Best when given in sedated patients or with a dose of midazolam 0.2 mg/kg IV
XXXVII. Famotidine H2 receptor antagonist
A. DOSE AND DURATION
Dogs and cats: 0.5–1.0 mg/kg IV, SC, IM, oral formulations available
Duration: 8–12 h
B. CLINICAL APPLICATIONS
Premedication in patients with mast cell tumors (MCT), patients prone to histamine release or gastric ulcers, patients at risk of regurgitation or irritation of the gastrointestinal tract
Routine and indiscriminate use of gastroprotectants in clinical practice is discouraged by the ACVIM [74]; however, the goal with use prior to general anesthesia is to neutralize the pH of stomach contents, in case of possible regurgitation and aspiration. Due to the remarkably common occurrence of regurgitation [75–77], use prior to anesthesia may be common especially in certain procedures
While pantoprazole (see p.349) may result in more effective neutralization of gastric pH [78], it takes up to 36 h to reach effective concentrations, as opposed to 60 min for famotidine [79]. Therefore, famotidine is often utilized in emergency procedures where the patient has not been on a proton pump inhibitor and requires gastrointestinal protection
C. PHARMACOLOGY
Blocks H2 receptors
Minimizes occupation of H2 receptors in cases of histamine release
Multidose vial contains benzyl alcohol as a preservative
Intraoperative management of noxious stimuli, postoperative analgesic
Common component of a neuroleptic induction
MAC‐sparing agent when used as a CRI during anesthesia for canine patients
C. PHARMACOLOGY
Short‐acting synthetic mu‐agonist opioid; it is more potent than morphine but considered to have equal efficacy to morphine
Metabolized by the liver
Controlled, Schedule II
D. CONTRAINDICATIONS/PRECAUTIONS
May cause bradycardia and hypoventilation (caution in patients with head trauma or increased ICP if not supporting ventilation)
May cause sedation and nausea
Causes miosis in the canine and mydriasis in the feline
Heat can increase the rate of delivery and absorption of transdermal fentanyl patches and may result in skin irritation
Some formulations of transdermal fentanyl patches cannot be cut. If patch is dispensing more fentanyl than the patient requires, cover half the patch (allow half the patch to have contact with the skin)
E. PRACTICAL NOTES
Ideal for older or cardiovascular compromised canine patients to reduce MAC
While the canine patient experiences considerable MAC‐sparing effects from fentanyl, the feline does not consistently have MAC reduction. Studies done in cats with a chemical derivative of fentanyl (remifentanil; see p. 357) clearly demonstrate an analgesic benefit for cats in spite of lack of MAC reduction in the same population [80]
“Wooden chest” phenomena are described in human patients subsequent to the use of fentanyl and other opioids. This refers to muscle rigidity of the thorax and abdomen, preventing adequate ventilation. While not commonly seen in veterinary species, should this occur, reversal of the opioid, neuromuscular blockade, and mechanical ventilation may be necessary
Reversible with naloxone (opioid antagonist; see p.344)
For fentanyl patches, hair must be shaved over the area where the patch will be attached and the skin cleaned
Benzodiazepine competitive antagonist at the GABA receptor
D. CONTRAINDICATIONS/PRECAUTIONS
Can result in rapid arousal when reversing benzodiazepines
E. PRACTICAL NOTES
Some feline patients experience prolonged sedation from benzodiazepines, and require reversal with flumazenil. At time of publication, flumazenil is relatively inexpensive and suggested to keep on hand for any practice handling felines
To reverse benzodiazepines, calculate full dose of reversal and dilute 10‐fold. Give slowly IV until desired reversal effect is achieved
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XL. Furosemide diuretic
A. DOSE AND DURATION
0.5–2.0 mg/kg IM or IV
Variable depending on formulation, but generally considered to have a duration of 1 (canine) [81]–2.5 (feline) [82] h (note: in some patients with altered physiology, this drug may last longer)
Inhibits the Na‐K‐2Cl cotransporter (NKCC)‐2 in the ascending limb of the loop of Henle, reducing extracellular fluid volume expansion [83]
Precipitates in acidic solutions
D. CONTRAINDICATIONS/PRECAUTIONS
Dehydrated patients; monitor patient hydration when using this drug
Patients with electrolyte imbalances (such as hyponatremia)
Do not use in patients which are anuric
High dosages in the feline may result in ototoxicity [84]
Electrolyte imbalances, constipation, dehydration, and eventually lack of urine production are possible complications of repeated administration of furosemide
E. PRACTICAL NOTES
Slight vasodilation occurs, which will increase renal perfusion and decrease preload, although the mechanism behind this is not fully understood [83]
Cats: while doses of 10–30 mg/kg PO q 8–12 h doses are reported [85], it is common to give a 100 mg/capsule (often mixed with a small amount of wet food) orally [86]
B. CLINICAL APPLICATIONS
Adjunctive therapy for refractory seizures
Used for the treatment of chronic and neuropathic pain
Used as an adjunctive analgesic for postoperative pain management
Sedation, specifically beneficial for reducing fear responses associated with handling and examination in cats and dogs
C. PHARMACOLOGY
The exact mechanism of analgesia is not fully understood, but is believed to involve inhibition of presynaptic GABA release, action at the locus coeruleus, and effects on spinal noradrenaline [87]
Gabapentin’s main effect is attributed to the inhibition of the N‐type voltage‐dependent neuronal calcium channels. Calcium influx into the neurons is reduced and therefore also the action potential propagation and the release of excitatory neurotransmitters, such as glutamate and substance P. Through this mechanism gabapentin is thought to prevent allodynia and hyperalgesia
Gabapentin is structurally similar to GABA but does not appear to interfere with GABA receptors
While often dosed every 12–24 h, pharmacokinetic studies in the canine suggest that the dosage frequency may more suitably be every 4–6 h [88]
Gabapentin has a high bioavailability after oral administration and the peak of action is achieved after 2 h [88]
It is not significantly metabolized, with minimal hepatic metabolism, and is eliminated by the kidney largely unchanged
D. CONTRAINDICATIONS/PRECAUTIONS
Sedation can be a side‐effect
Seizures may result with abrupt discontinuation of the drug after chronic treatments. Therefore, it is recommended when withdrawing to taper the dose
Caution in animals with renal disfunction and reduction of dose may be indicated
Avoid human formulations that contain xylitol
E. PRACTICAL NOTES
Protect from light
Transdermal gabapentin is under investigation and may show promise for easier administration as an analgesic in cats but varies greatly based on preparation [89,90]
May act as an appetite stimulant in cats comparable to mirtazapine [91]
Effects are produced via potent and specific antagonism of the prostaglandin E2 receptor 4
It does not inhibit the production of other prostanoids, nor does it interfere with the maintenance of normal homeostatic function [92]
D. CONTRAINDICATIONS/PRECAUTIONS
Common clinical side‐effects include mild diarrhea, appetite loss, and vomiting
E. PRACTICAL NOTES
Suitable for chronic but not acute pain [92]; do not administer for postoperative surgical pain and select another NSAID if surgery remains a possibility (i.e., for control of pain for a ruptured cruciate with a surgical repair option)
In cats, pharmacokinetic studies show that this drug has potential to reach comparable plasma levels to that of the dog, effective for analgesia, at 2 mg/kg BID PO [93]. More studies are required before analgesic efficacy in this species is determined
Work in MDR‐1‐positive collies suggests grapiprant is well tolerated, although the pharmacokinetics suggested increased drug exposure compared to dogs without this mutation [94]
Feeding reduces oral absorption of grapiprant [93]
Used to treat or prevent bradycardia in the perioperative period
Used to counteract the cholinergic effects of neuromuscular blockade antagonists such as neostigmine [95]
Used to reduce salivation
C. PHARMACOLOGY
Synthetic quaternary ammonium compound
Glycopyrrolate is an antimuscarinic with similar actions to atropine, but has four times the potency of atropine
Glycopyrrolate is completely ionized and has poor lipid solubility. For this reason, it does not cross, or crosses only marginally, the blood–brain or blood–placenta barriers or penetrate into the eye [96]
Rapidly eliminated from the serum after IV administration and virtually no drug remains in the serum 30 min to 3 h after dosing
Only a small amount is metabolized, with most being excreted unchanged in the urine
Promotes bronchodilation and smooth muscle relaxation via M2 and M3 receptor antagonism
D. CONTRAINDICATIONS/PRECAUTIONS
Caution using anticholinergics following the administration of alpha‐2 agonists during the hyperdynamic phase [97]. Increasing the heart rate during the period of vasoconstriction and reflexive bradycardia will cause an increase in myocardial oxygen consumption, predisposing the patient to potential life‐threatening arrhythmias.
In dogs, the LD50 for glycopyrrolate is reported to be 25 mg/kg IV. In the cat, the LD50 after IM injection is reported to be 283 mg/kg. Because of its quaternary structure, minimal CNS effects should occur after an overdose of glycopyrrolate, when compared to atropine
Low doses may cause an idiosyncratic bradyarrhythmia and second‐degree AV block Mobitz I followed by sinus tachycardia
Systemic administration of glycopyrrolate has not been associated with changes in pupil diameter or IOP. In contrast, it resulted in a clinically relevant transient decrease in aqueous tear production [96]
Gastrointestinal motility has been shown to be decreased after glycopyrrolate administration in dogs
E. PRACTICAL NOTES
The authors prefer using glycopyrrolate as premedication IM in patients with high vagal tone over atropine when available
The onset of action of glycopyrrolate is slightly slower than that of atropine, usually occurring within a few minutes. However, glycopyrrolate has a longer duration of effects than atropine
Dogs: IV bolus 2–5 mL/kg, total volume delivered not to exceed 10–20 mL/kg/day
Cats: IV bolus 2–3 mL/kg, total volume delivered not to exceed 5–10 mL/kg/day
Hypoproteinemic patient fluid rate: 1–3 mL/kg/h
Duration: 12–24 h
B. CLINICAL APPLICATIONS
Used when plasma is not available in patient that are hypoproteinemic
Used as a volume expander to treat hypotension under anesthesia, although routine and indiscriminate use is falling out of favor
C. PHARMACOLOGY
Polysaccharide with an average molecular weight of 450,000 daltons
Most commonly available as a 6% aqueous solution for veterinary use
Large molecular structure allows retainment in vasculature with a long elimination half‐life to expand intravascular volume
Removed by renal excretion as well as redistribution
D. CONTRAINDICATIONS/PRECAUTIONS
Use results in hemodilution, which is associated with hypercoagulable effects at low dilutions and hypocoagulable effects at higher dilutions [102]. Additionally, there is a decrease in factor VII, von Willebrand factor and fibrongen, as well as decreased platelet function [103,104]. All these factors contribute to potential coagulopathy
The role of hetastarch in acute kidney injury (AKI) is actively being investigated. Recent work suggests that in a clinical setting for dogs requiring a fluid bolus, there were no changes over time of urine AKI biomarkers in dogs [105], in contrast to work with gelatin colloid solutions, which produced greater increases in urine biomarkers of AKI and more frequent histopathologic changes in the kidneys when used in hemorrhagic shock model patients [106,107]. In humans with renal insufficiency or sepsis, hydroxyethyl starch is avoided [108]. Until more conclusive large‐scale work is available, it is best to avoid in oliguric or anuric renal failure patients, as well as to avoid indiscriminate use of this fluid
Avoid in patients with pulmonary edema or congestive heart failure
Avoid in normo‐ or hypervolemic patients, as it may contribute to volume overload
Total protein value in patients that received hydroxyethyl starch may decrease but oncotic pressure is generally maintained
E. PRACTICAL NOTES
Anaphylactoid reactions are low, compared to natural colloid products
Monitoring colloid oncotic pressure (COP) is advised when hydroxyethyl starch is used
The authors prefer fresh frozen plasma in patients with renal disease and sepsis
Generally, this fluid is not suitable as a substitute for maintenance fluids
Anesthesia induction via facemask or induction chamber (authors do not recommend mask or chamber inductions)
C. PHARMACOLOGY
Isoflurane is a clear, colorless, and volatile liquid at room temperature and sea level
The exact mechanism of action by which inhalant anesthetic agents cause general anesthesia is not precisely known, but it is likely their influence on the electrical activity of the CNS, mediated at the level of the spinal cord, through actions at the lipid bilayer of the cell membrane
Most important effects cause CNS depression, prevention of movement likely mediated at the level of the spinal cord, dose‐dependent cardiovascular and respiratory depression, decreased systemic vascular resistance (vasodilation) and hypotension, increased cerebral blood flow and intracranial pressure, depression of body temperature regulating centers, and muscular relaxation
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with preexisting extreme hypotension, cardiovascular derangements or reason for inability to handle vasodilation (i.e., the unstable septic patient)
Caution in patients with increased intracranial pressure or head trauma
In susceptible individuals, inhalant anesthesia may trigger a clinical syndrome known as malignant hyperthermia, a cellular hypermetabolic state that if not treated quickly causes death. Although mostly reported in human patients and pigs, other species have also been reported to be affected
E. PRACTICAL NOTES
Requires a precision vaporizer
The National Institute for Occupational Safety and Health Administration (NIOSH) recommends that no worker should be exposed to ceiling concentrations greater than 2 ppm of any halogenated anesthetic agent over a sampling period not to exceed 1 h
Dosing in dogs: Routine anesthetic maintenance fluid rates for dogs start at 5 mL/kg/h, with incremental dose reduction following the first hour until maintenance fluid rates are achieved (2–3 mL/kg/h) [222] Shock bolus: 80–90 mL/kg IV; often administered in ¼ dose increments under continuous monitoring and reassessment Treatment of anesthetic hypotension: 5–10 mL/kg IV bolus, which may be repeated Dosing in cats: routine anesthetic maintenance fluid rates for cats start at 3 mL/kg/h, with incremental dose reduction following first hour until maintenance fluid rates are achieved (1–3 mL/kg/h) [222] Shock 60–70 mL/kg IV, often given in ¼ dose increments under continual monitoring and reassessment Treatment of anesthetic hypotension: 3–5 mL/kg IV bolus; repeated up to two times As this fluid approximates extracellular solution, only 20–25% will remain in the intravascular space after an hour or so
Canine: 3–5 mL/kg Feline: 1–3 mL/kg To reduce intracranial pressure, hypertonic saline can be given at 4 mL/kg over 5 min 7.5% hypertonic saline has a duration of 30–60 min
B. CLINICAL APPLICATIONS
Preoperative fluid resuscitation
Intraoperative fluid administration
Treatment of hypotension due to ineffective circulating volume during anesthesia
C. PHARMACOLOGY
Crystalloid fluid
Balanced electrolyte solution
Replacement solution
Acetate buffer
D. CONTRAINDICATIONS/PRECAUTIONS
Caution using high volumes or boluses in patients with congestive heart failure, as excessive volumes may result in pulmonary edema; consider reduced rates and avoid bolus
E. PRACTICAL NOTES
Safe to administer with blood products
XLVIII. Isoproterenol beta agonist
A. DOSE AND DURATION
0.01–0.08 μg/kg/min IV
Duration is short‐lived if not given as a CRI
B. CLINICAL APPLICATIONS
Chronotropic; “pharmacologic pacemaker” for patients with sick sinus syndrome or third‐degree AV block
C. PHARMACOLOGY
Sympathomimetic at beta‐1 and beta‐2 receptors which increases myocardial contractility and HR, causes bronchodilation and reduces bronchial spasms
Of all sympathomimetics, isoproterenol is the most potent. It is 2–3 times more potent than epinephrine and 100 times more active than norepinephrine [109]
No alpha agonist effects
Metabolized in the liver
D. CONTRAINDICATIONS/PRECAUTIONS
Causes vasodilation via beta‐2 receptors in skeletal muscles
May result in tachycardia and tachyarrhythmias
Do not use in conjunction with other catecholamines (e.g., epinephrine); effects may be additive
Coronary blood flow may be reduced due to a decrease in diastolic blood pressure at the same time as myocardial oxygen consumption increases; caution in patients with known coronary artery disease
E. PRACTICAL NOTES
Protect vial and dilutions from light
When diluted with 5% dextrose, stable for 24 h
XLIX. Ketamine NMDA antagonist and dissociative anesthetic
Used in cats and dogs as a general anesthetic for induction
Used as part of multidrug combinations for chemical restraint or anesthesia
Used as a coinduction agent to reduce primary induction drug (often propofol or alfaxalone) requirement
Used as an adjunctive analgesic
Has been used in local regional techniques such as epidurals or in regional blocks
Used as a CRI for MAC reduction (up to 40%) of inhalants in dogs [110] and cats [111]
C. PHARMACOLOGY
Phencyclidine derivative
Primary action occurs by antagonism of the NMDA receptors leading to a dissociation of the limbic and thalamocortical systems. Induces a cataleptic state in which the patient does not respond to external stimuli
Causes indirect stimulation of cardiovascular system through catecholamine reuptake inhibition (increases BP and HR and thus CO, increases myocardial O2 requirements)
Canines completely metabolize ketamine; however, the feline metabolizes ketamine to norketamine, an active metabolite which may contribute to altered feline recovery
D. CONTRAINDICATIONS/PRECAUTIONS
Patients induced with ketamine alone exhibit a catatonic state (mydriasis, nystagmus, swallowing, muscle movement/rigidity). For this reason, administration with a muscle relaxant is recommended
In privileged sites such as the CNS (secondary to protection of the blood–brain barrier), vasodilation and thus an increase in ICP occurs secondary to ketamine. In patients where increases in ICP are a concern (those with seizures or suspected space‐occupying diseases of the cranium), ketamine is avoided
Increased extraocular muscle tone results in an increase in intraocular pressure (IOP) [112]. Often ketamine is avoided in patients where increased IOP is a concern unless no other induction agent is available, in which case ketamine is administered with a benzodiazepine. Avoid in patients with ocular injuries and glaucoma
May result in hyperthermia due to increased muscle tone. This is often not an issue in patients where inhalant anesthetics are used for maintenance anesthesia, due to the concurrent hypothermia that inhalant anesthesia induces
Cats with hypertrophic cardiomyopathy
Cats with significant renal insufficiency
E. PRACTICAL NOTES
May result in apneustic breathing pattern
Painful on IM injection due to low pH
Administer with a muscle relaxant such as benzodiazepine or alpha‐2 agonist
Induction dose can act as the loading dose for a CRI provided there is not a significant delay in beginning the CRI
When using ketamine as a coinduction technique, the authors’ preference is to administer ketamine about 30 sec before titrating the primary induction agent to effect, due to the slightly longer onset time of ketamine
“Ketofol” is the combination of ketamine and propofol at 1:1 mixture, traditionally 2 mg of each agent. This combination improves the cardiovascular stability of propofol [113] and the induction quality of ketamine alone. Indeed, there were improved tracheal intubation and induction qualities using ketofol compared to propofol [114]
Recommended for acute pain (up to 5 days) in both dogs and cats
C. PHARMACOLOGY
Nonselective, potent inhibitor of COX‐1 and COX‐2
Inhibits one or more steps in the metabolism of arachidonic acid (AA) and possesses both analgesic and antiinflammatory properties
Acts primarily to reduce the biosynthesis of prostaglandins by inhibiting cyclooxygenase (COX‐1 and COX‐2). Inhibition of prostaglandins that regulate blood flow to the gastric mucosa and stimulate bicarbonate and mucus production may result in loss of GI protective mechanisms
COX‐2 inhibition by NSAIDs is thought to be responsible for the antipyretic, analgesic, and antiinflammatory actions of NSAIDs. However, concurrent inhibition of COX‐1 may result in many of the unwanted effects of NSAIDs, including gastric ulceration and renal toxicity
NSAIDs are biotransformed in the liver to inactive metabolites that are excreted either by the kidney via glomerular filtration and tubular secretion or by the bile
D. CONTRAINDICATIONS/PRECAUTIONS
Although use as part of the premedication prior to the inflammatory event, as opposed to postoperative administration, provides preemptive and better analgesia, caution is advised if using this drug preoperatively
Caution in patients that are hypoproteinemic
Because of potential antiplatelet effects, care should be exercised when using ketoprofen perioperatively
Treatment of hypotension due to ineffective circulating volume during anesthesia
C. PHARMACOLOGY
Crystalloid fluid
Balanced electrolyte solution
Replacement solution
Lactate buffer; lactate is broken down by the liver to bicarbonate, resulting in an alkalinizing effect
D. CONTRAINDICATIONS/PRECAUTIONS
Caution using high volumes or boluses in patients with congestive heart failure, as excessive volumes may result in pulmonary edema; consider reduced rates and avoid bolus
Contains Ca++: best practice is to avoid administering in the same catheter as blood products, as Ca++ will chelate with anticoagulant in blood products
E. PRACTICAL NOTES
In hypocalcemic patients, this may be a fluid of choice; however, it is unlikely to increase serum Ca++ of patient
In hyperkalemic patients, some do not recommend administering LRS as it contains K+; however, content of K+ is unlikely to clinically affect patient [115]
LII. Lidocaine Na+ channel blocker, local anesthetic
Used systemically to control ventricular arrhythmias and as a MAC reducer in dogs [116]
Antinociceptive effects when used as an intraoperative CRI in dogs [117]
Used as IV bolus at 1–1.5 mg/kg prior to intubation to reduce laryngeal response to orotracheal intubation [118]
Used during CPR for ventricular arrhythmias such as sustained ventricular tachycardia
Used for topical laryngeal splash block to ease orotracheal intubation in species prone to laryngeal spasms [119] (cats, pigs, and various exotic species)
C. PHARMACOLOGY
All local anesthetics share a common chemical structure that includes a lipophilic, benzene ring and a hydrophilic amine group. This compound is then linked to either an ester or an amide; in the case of lidocaine, it is an amide
pKa 7.8. pKa determines the amount of ionized and unionized fraction of drug present in the plasma. At high pKa, greater will be the proportion of local anesthetic in the ionized, charged hydrophilic form at physiologic pH (7.4), and the onset of action will be slower. In contrast, at low pKa, a greater proportion of the nonionized lipid‐soluble form will be present at physiologic pH and the onset of action will be more rapid
% Ionized at physiological pH: 76
Lipid solubility 3.6. Lipid solubility is the main determinant of potency and onset of action.
% Protein binding: 64. Protein binding influences the duration of action. Only the unbound fraction of drug is pharmacologically active. The higher the protein binding, the longer the duration of action
D. CONTRAINDICATIONS/PRECAUTIONS
Cats have increased sensitivity to local anesthetics [120], although the use of lidocaine to desensitize arytenoids prior to intubation and local administration of lidocaine appears safe [121]
Avoid IV use in patients with bradyarrhythmias such as AV block, sick sinus syndrome, or escape rhythms which are not secondary to dexmedetomidine (see “Practical notes”)
Patients with liver dysfunction or hypoproteinemia may have prolonged effect when given lidocaine IV
E. PRACTICAL NOTES
Used for regional and epidural (use preservative‐free) anesthesia; see Chapter 7
New evidence suggests that systemic lidocaine may reverse dexmedetomidine‐induced bradycardia [58]
Often preparations for regional blocks contain epinephrine, which will prolong the duration of a lidocaine block [122]. Epinephrine is added to lidocaine to cause vasoconstriction and therefore decrease systemic absorption of the local anesthetic when used as a local block. This technique can decrease the total dose of local anesthetic required, prolong the effect and decrease the potential for systemic toxicity. This combination is commercially available or frequently is mixed in‐house. This combination should never be administered IV. Use with caution in peripheral limbs
Sodium bicarbonate can be added to local anesthetic solutions to increase the pH, resulting in less sting upon injection when administering to conscious patients
Mixture of long‐acting (bupivacaine or ropivacaine) and short‐acting (lidocaine) local anesthetics is no longer recommended; while there is faster onset of blocks, there is also decreased duration [123]
LIII. Mannitol osmotic diuretic
A. DOSE AND DURATION
Reduction of ICP or IOP: 0.25–2.0 g/kg administered slow over 20 min IV (commonly 0.5 g/kg)
For renal support [124,125]: 0.25–1 g/kg/h as a CRI during anesthesia
Duration: often given once as a single bolus; elimination half‐life is around 70–90 min [126]
B. CLINICAL APPLICATIONS
Used to reduce ICP following cerebral injury. Commonly given in neurologic patients which demonstrate indications of increased ICP (Cushing reflex, cerebral edema)
Reduces IOP in cases of glaucoma
Used as a CRI to increase urinary output
Used to increase plasma osmolarity
C. PHARMACOLOGY
Hyperosmotic diuretic which promotes water loss via the kidneys and blocks reabsorption of water by the kidney tubules
Only means of clearance is by glomerular filtration [109]
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with intracranial hemorrhage
Dehydrated patients
Patient with congestive heart failure
Anuric renal failure patients
Use with caution in hypertensive patients
E. PRACTICAL NOTES
In single‐dose vials, at room temperature, crystals form quickly; keep solution in a warmer or run under warm water prior to administration. For this reason, a filter is used when administering this drug
When administering this drug, ensure appropriate fluid therapy and monitor urine output
May be used topically for pharyngeal swelling following brachiocephalic surgeries or a traumatic intubation. Place on cotton tip applicators and swab inflamed tissue prior to extubation
LIV. Maropitant neurokinin‐1 receptor antagonist
A. DOSE AND DURATION
1 mg/kg SC or IV slow, 2 mg/kg PO
Duration of 24 h with peak plasma concentration reached after minutes of IV injection, 1 h after SC injections, and 2 h following PO administration
B. CLINICAL APPLICATIONS
Approved by the FDA as antiemetic for dogs and cats [127], although this does not translate to an increase in postoperative appetite [128]
In addition, maropitant may provide adjunctive analgesia for visceral pain [129]
MAC‐sparing effect (15–25% reduction) is reported in dogs and cats in which general anesthesia was maintained with sevoflurane [130–132]
C. PHARMACOLOGY
The antinociceptive action is thought to be dependent on the antagonism of NK1 receptors located in the central and peripheral nervous system (specifically in the brain, spinal cord, and viscera) [133]
Blocks the binding of the endogenous neurotransmitter substance P that is known to cause emesis [133]
The drug is highly protein bound and caution should be exercised in animals receiving drugs that are also protein bound (e.g., NSAIDs). It is metabolized primarily by the liver and less than 1% is eliminated unchanged in urine or feces
Novel work suggests there may be a role for NK‐1 and associated substance P antagonism in pain modulation, as substance P is found in multiple areas of the pain pathways, including sensory afferents, dorsal root ganglia, dorsal horn, and ascending projections of the spinal cord and higher brain centers involved in pain perception [133,134]
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with possible gastrointestinal outflow obstruction when not going immediately to surgery or endoscopy
Caution in patients with liver failure; it is appropriate to reduce the dose if used in these patients
May cause hypotension, which was more significant for patients who were anesthetized than those who were not [135]
E. PRACTICAL NOTES
While some clinicians use maropitant to reduce nausea, only 25% of canine patients experience this result, as opposed to 90% of patients receiving ondansetron [136]
Pain on injection appears to be related to drug formulation [137]. Pain is primarily with SC injection; refrigerating the solution ensures more active ingredient remains bound in the cyclodextrin carrier, effectively reducing pain during injection
While undocumented in the literature, the authors note that patients with mechanical obstruction to outflow of the GI tract may profusely regurgitate during induction, when maropitant has been used to prevent vomiting (i.e., patients retain fluid in the GI tract which would have otherwise been expelled). As the airway is typically unprotected while induction is occurring, this can lead to aspiration pneumonia. Emptying the stomach with a nasogastric tube and neutralizing gastric pH are appropriate in patients who have been administered maropitant but ultimately will have surgery for obstruction of the GI tract
LV. Meloxicam NSAID
A. DOSE AND DURATION
Dog: 0.2 mg/kg SC as the first dose, following doses 0.1 mg/kg PO
Cats: 0.1 mg/kg SC or PO once. This dosage is recommended in compliance with the FDA’s black box warning about repeated dosing of meloxicam in this species
Single dose duration of 24 h
B. CLINICAL APPLICATIONS
Common NSAID for small‐breed dogs and cats
Used perioperatively and has been recognized for its analgesic efficacy for up to 20 h post surgery, including following canine ovariohysterectomies
C. PHARMACOLOGY
Blocks the action of cyclooxygenase to provide antiinflammatory, analgesic, and antipyretic effects
COX‐2 preferential
Metabolized by oxidation in cats; this is the preferred route of metabolism for drugs used in this species, as cats do not glucuronidate effectively
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with gastrointestinal disease, bleeding disorders, and renal insufficiencies
Patients who have undergone a surgery where the GI tract was breached
E. PRACTICAL NOTES
If given prior to anesthesia (either with the premedication or orally in the morning), ensure the patient is normotensive throughout the anesthetic period. If one cannot be certain, do not administer meloxicam until the animal is stabilized in the postoperative period
Injectable and oral formulations and a transmucosal spray are available
LVI. Meperidine full agonist opioid
A. DOSE AND DURATION
Dog: 3–5 mg/kg IM
Cat: 3–5 mg/kg IM
Duration of 45–60 min
B. CLINICAL APPLICATIONS
Mild analgesia and sedation
Useful as premedication specifically in young patients
C. PHARMACOLOGY
Full mu agonist
Synthetic
Metabolized by the liver
Has anticholinergic‐like effects (e.g., increase in HR)
May block sodium channels, similar to local anesthetics
May also possess alpha‐2 agonist receptor activity
D. CONTRAINDICATIONS/PRECAUTIONS
Histamine release possible (especially when given IV), which may result in hypotension and facial edema (for this reason, it is limited to IM administration)
Vomiting may occur
Avoid in patients prone to histamine release (MCT, heart worm extractions)
Patients with head trauma or increased ICP if ventilation is not supported
E. PRACTICAL NOTES
Causes miosis in the canine and mydriasis in the feline
Reversible with naloxone
Synergistic action with sedatives may cause profound sedation
Excitement possible when used alone
Ideal for young patients with patent ductus arteriosus (PDA) or portosystemic shunt (PSS) as premedication as it provides analgesia while helping to maintain heart rate
This drug is extremely short‐acting and thus has limited usefulness in most veterinary practices; a longer acting opioid should be included postoperatively
In human patients, the combination of a meperidine and an MAOI has reportedly caused serotonin syndrome – a potentially fatal reaction. While this is not documented in veterinary medicine, the possibility exists
Used for regional and epidural (use preservative‐free) anesthesia
C. PHARMACOLOGY
All local anesthetics share a common chemical structure that includes a lipophilic, benzene ring and a hydrophilic amine group. This compound is then linked to either an ester or an amide; in the case of mepivacaine, it is an amide
pKa 7.72. pKa determines the amount of ionized and unionized fraction of drug present in the plasma. At high pKa, greater will be the proportion of local anesthetic in the ionized, charged hydrophilic form at physiologic pH (7.4), and the onset of action will be slower. In contrast, at low pKa, a greater proportion of the nonionized lipid‐soluble form will be present at physiologic pH and the onset of action will be more rapid
% Ionized at physiological pH: 61
Lipid solubility 2; lipid solubility is the main determinant of potency and onset of action
% Protein binding: 77; protein binding influences the duration of action. Only the unbound fraction of drug is pharmacologically active. The higher the protein binding, the longer the duration of action
D. CONTRAINDICATIONS/PRECAUTIONS
Avoid IV use due to potential for cardiotoxicity
Cats have increased sensitivity to local anesthetics
E. PRACTICAL NOTES
Slightly longer lasting than lidocaine, shorter duration than bupivacaine
Useful for dental blocks due to quick onset and length of duration
Sodium bicarbonate can be added to local anesthetic solutions to increase the pH, resulting in less sting upon injection when administering to conscious patients
Mixture of long‐acting (bupivacaine or ropivacaine) and short‐acting (lidocaine or mepivacaine) local anesthetics is no longer recommended because they produce unpredictable clinical results [123]
Used as a premedication; most predictable in sick, calm, geriatric or neonatal patients
Commonly mixed with other sedatives or anesthetics for the chemical restraint of uncooperative animals [138]
Used as an anticonvulsant in the treatment of seizures (IV, rectal; however, multicenter work has documented superiority of intranasal administration during canine status epilepticus, as opposed to rectal diazepam administration [139])
Coinduction agent used to reduce doses of other injectable anesthetics [140–142] and provide muscle relaxation
Antianxiety action
Appetite stimulant in some laboratory species [143] and cats [144]. Although this has not been documented in the dog, it stands to reason that, like diazepam, it may result in appetite stimulation [145]
C. PHARMACOLOGY
Aqueous solution with a pH of 3.5. Not painful on IV injection. Does not cause thrombophlebitis. Once administered, at physiologic pH, the drug becomes lipid soluble and able to cross the blood–brain barrier to cause its central effects. This unique solubility characteristic provides a very rapid onset of action after administration
High bioavailability after enteral and parenteral administration due to high lipophilicity results in a very rapid onset of action
Highly protein bound. Because only the unbound portion of the drug crosses the blood–brain barrier, changes in plasma protein concentrations may affect response to a given dose
Sedative effects occur by enhancing the GABAA receptor’s affinity for the inhibitory neurotransmitter GABA within the CNS. Benzodiazepines are considered to have an indirect effect by potentiating the activity of endogenous GABA neurotransmitter, leading to a wide safety margin and minimal depression of ventilation, CO, and oxygen delivery
Muscle relaxant and anticonvulsant properties derive from action on spinal interneurons
Metabolized by the liver
The impact on the cardiovascular system is minimal [146]
Rapidly absorbed after IM administration
D. CONTRAINDICATIONS/PRECAUTIONS
Unpredictable sedative properties if used alone in healthy patients where agitation or excitement may become evident
Avoid in patients with hepatic encephalopathy or PSS
Avoid use for cesarean sections; crosses the placental barrier and may result in respiratory depression in neonates
Use with other CNS depressant may increase the risk of respiratory depression
E. PRACTICAL NOTES
Reduces the dose of propofol needed for total intravenous anesthesia (TIVA) [142]
Can be administered a variety of routes: intranasal [138,147], oral, and rectal, in addition to the traditional IM and IV routes
Effective sedation for most small mammals and avian species
Undergoes photodegradation and should be kept protected from the light
Works well intranasal in a variety of small exotic animal species [52,147]
Some cats experience profound sedation from midazolam. It is suspected that cats may eliminate 1‐hydroxymidazolam more slowly than expected [148]. While traditionally flumazenil is used to reverse this drug, one case report documents the necessity for intravenous lipid emulsion to resolve the overt sedation of one cat [148]
Engages presynaptic and postsynaptic receptor sites in the CNS, as well as on primary afferent neurons
Prototype mu agonist opioid, to which all other opioids are compared. Morphine also works at delta and kappa receptors
Metabolized in the liver to several metabolites; the active metabolite (which results in analgesia) is morphine‐6‐glucuronide
D. CONTRAINDICATIONS/PRECAUTIONS
Vomiting and panting, as well as other signs of nausea (excessive salivation), likely when given IM. Often avoided in patients where vomiting and retching will increase ICP and IOP. However, maropitant administered prior to morphine was successful in reducing incidence of vomiting [150,151]
May result in histamine release, especially with high doses given rapidly IV
Respiratory depression and bradycardia are possible at high doses
Initially increases peristaltic motility followed by prolonged period of GI stasis, which may result in constipation
Morphine, among other opioids, causes contracture of the sphincter of Oddi (common biliary duct), increasing gall bladder pressure [152]
Causes miosis in the canine and mydriasis in the feline. For this reason, in some ophthalmological procedures (lens luxation), morphine is avoided
Patients predisposed to histamine release (MCT, heart worm extraction)
E. PRACTICAL NOTES
The highly overstated phenomenon of excitement in cats has been reported. The study responsible for this rumor used doses of up to 20 mg/kg to cause dysphoria [153]. Most cats actually experience euphoria secondary to morphine administration at clinical doses
Systemic and epidural morphine results in release of antidiuretic hormone. The authors advise gentle bladder expression or catheterization of any animal which receives morphine epidurally prior to recovery, as well as good nursing care documenting normal urination
When given alone, possible dysphoria, excitement, and increased responsiveness to noise may result
Commonly used to reverse opioid effects when they contribute to a prolonged or dysphoric recovery
C. PHARMACOLOGY
Nonselective opioid antagonist
Antagonizes both exogenous and endogenous opioids
Metabolized by the liver
D. CONTRAINDICATIONS/PRECAUTIONS
Use could result in inadequate analgesia
May result in hypertension and excitement
Short duration may necessitate repeated dosing, depending on duration of the opioid reversed
E. PRACTICAL NOTES
Reversal of opioid agonists may leave the patient painful! Always have alternative analgesia on board prior to beginning reversal
Calculate dose and dilute 1:10 with saline; give in increments until desired reversal is achieved for nonemergent situations
Emergency situation or anesthetic arrest: full dose of naloxone is given IV when an opioid was administered and repeated every hour for the duration of opioid agonist
Reversal of nondepolarizing NMB agents (atracurium, cisatracurium, and pancuronium)
C. PHARMACOLOGY
Inhibits acetylcholinesterase, to increase the amount of the neurotransmitter acetylcholine at the neuromuscular junction (favoring binding of acetylcholine)
If a nondepolarizing neuromuscular blocking agent is not on board prior to administration of neostigmine, there will be presynaptic effects (resulting in muscle fasciculations)
Inhibition is reversible, as the drug acts as a competitive substrate substitute for acetylcholine and acetylcholinesterase interactions [109]
Poorly lipid soluble
D. CONTRAINDICATIONS/PRECAUTIONS
May result in bradycardia
Increases smooth muscle tone of the bladder; for this reason, it is often avoided, when possible, in patients with urinary or GI obstruction
Results in peristalsis (diarrhea) and increased secretions
E. PRACTICAL NOTES
Does not cross the blood–brain barrier or placenta
Give anticholinergic (atropine or glycopyrrolate) prior to giving neostigmine to prevent the muscarinic effects which may otherwise result in bradycardia
LXIII. Nitroprusside alpha antagonist
A. DOSE AND DURATION
CRI 0.03–0.3 mg/kg/h (ideal to use less than 0.03 mg/kg/h) IV
Duration of a single dose is 1–3 min, short half‐life
B. CLINICAL APPLICATIONS
Vascular smooth muscle relaxant used as a peripheral vasodilator for acute/severe hypertension
Used in patients with acute heart failure secondary to mitral regurgitation and in patients with refractory congestive heart failure (CHF)
Used to treat hypertension secondary to unmanaged pheochromocytoma
C. PHARMACOLOGY
Causes peripheral vasodilation (arterial and venous) through liberation of nitric oxide (NO) at the level of the vascular endothelium and underlying smooth muscle, resulting in a significant reduction of total peripheral resistance and a decrease in blood pressure. The HR increases in response to the hypotension. Finally, CO mildly decreases
Metabolized to cyanogen, which results in cyanide or thiocyanate toxicity after prolonged therapy
D. CONTRAINDICATIONS/PRECAUTIONS
Renal insufficiencies and failure (which prolong drug duration)
Risk of cyanide and thiocyanate toxicity
Signs of toxicity are tachycardia, hyperventilation, metabolic acidosis, and seizures
Toxicity is treated with thiosulfate [154] (6 mg/kg/h IV in dogs)
Avoid in patients with raised ICP
Avoid in patients whose hypertension is compensatory (such as with a Cushing reflex)
The hypotensive effects of nitroprusside may be enhanced by concomitant administration of general anesthetics or other hypotensive agents (e.g., beta‐blockers, ACE inhibitors, etc.)
Synergistic effects (increased CO and reduced wedge pressure) may result if dobutamine is used with nitroprusside
E. PRACTICAL NOTES
To administer this drug, dilute with D5W. See Appendix D for dilution equations
Being remarkably light sensitive, dilutions are only stable for 24 h if protected from all light. Wrap entire dilution and delivery line with light‐blocking material such as aluminum foil, vet wrap or brown plastic bags
Pressor treatment of choice for patients with sepsis
Helpful for nonresponsive hypotension as a result of vasodilation
C. PHARMACOLOGY
Endogenous neurotransmitter released from postganglionic sympathetic nerves
Agonist at alpha‐1‐, alpha‐2‐, and beta‐1‐adrenergic receptors with predominating alpha‐1 receptor‐mediated effects when used at clinical doses
Potent and results in profound arterial and venous vasoconstriction
D. CONTRAINDICATIONS/PRECAUTIONS
Conflicting opinions exist about administration of this drug during pregnancy, as vasoconstriction of uterine vessels may decrease perfusion to the fetus
Patients with hypertension
E. PRACTICAL NOTES
Very low doses (0.025 μg/kg/min), beta‐1‐adrenergic receptor‐mediated effects predominate, resulting in increases in HR and CO and decreases in systemic vascular resistance
At higher dose rates (greater than 0.5–1.5 μg/kg/min), norepinephrine causes dose‐dependent increases in systolic, diastolic, and mean arterial blood pressures, CO, and systemic and pulmonary vascular resistance. This may ultimately reduce CO and increase myocardial oxygen consumption due to the increase in afterload
Vasoconstriction may result in decreased perfusion. Increasing lactate levels may indicate that the drug is worsening perfusion in spite of improved BP
Tachycardia is less likely when compared with administration of epinephrine; indeed, bradycardia may result from profound vasoconstriction
Extravasation of the drug can cause necrosis due to regional vasoconstriction and ischemia. Monitor the patency of the intravenous catheter before administration. Ideally, the drug should be given through a central line
Treatment of hypotension due to ineffective circulating volume during anesthesia
C. PHARMACOLOGY
Crystalloid fluid
Balanced electrolyte solution
Replacement solution
Acetate buffer
D. CONTRAINDICATIONS/PRECAUTIONS
Caution if using high volumes or boluses in patients with congestive heart failure, as excessive volumes may result in pulmonary edema; consider reduced rates and avoid bolus
There is a report of a single dog becoming hypotensive secondary to bolus of Normosol‐R
Provides paralysis so often used to implement mechanical ventilation or ophthalmic procedures to keep the pupil central
C. PHARMACOLOGY
Original NMBA with a steroid molecule base
Exerts action at the neuromuscular junction where it competes with ACh to bind the cholinergic receptor, preventing contractions of skeletal muscle (paralysis)
Repeated doses will accumulate, so redosing is discouraged
Dependent on renal excretion, as most is eliminated unchanged in the urine (>80%)
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with renal insufficiency or failure
Inhibition of cardiac muscarinic receptors (especially those of the sinoatrial node) may result in an increase in HR, blood pressure, and CO; although this is rarely of clinical concern, alternative NMBAs may be selected for a patient with underlying cardiac disease
E. PRACTICAL NOTES
Longer duration of action than atracurium
Does not result in histamine release
Must be refrigerated
LXVII. Pantoprazole proton pump inhibitor
A. DOSE AND DURATION
0.7–1 mg/kg IV slow every 12–24 h
B. CLINICAL APPLICATIONS
Used to increase pH of gastric acid to decrease incidence of esophagitis, should regurgitation occur during anesthesia or sedation
Used to increase pH of gastric acid for treatment of gastroesophageal reflux disease
C. PHARMACOLOGY
Irreversible inhibitor of the hydrogen‐potassium adenosine triphosphatase proton pump [155]
Weak base that becomes unprotonated in the presence of physiologic pH of blood and suppresses gastric acid production
Requires reconstitution, after which stability is pH dependent (degradation increases as pH decreases)
98% serum protein bound, primary binding to albumin
Metabolized via the liver through the cytochrome P450 system
Eliminated via excretion in the urine and feces through the biliary system
D. CONTRAINDICATIONS/PRECAUTIONS
Caution if coadministering oral medications that require targeted gastric pH ranges for effectiveness (i.e., slow release, protective coated drugs) as PPIs increase gastric pH. These drugs may need to be avoided or doses adjusted
Use of PPIs with NSAIDs may increase risk of NSAID‐induced intestinal injury and ulceration [156]
E. PRACTICAL NOTES
Effective clinical benefit of PPIs likely requires daily administration for several days [74]
Per manufacturer, requires reconstitution with 0.9% NaCl to a 4 mg/mL solution and can be stored at room temperature for 24 h
PPIs are consistently superior to histamine type‐2 receptor antagonists (i.e., famotidine) at increasing gastric pH and preventing exercise‐induced gastritis in dogs and cats [78,79]; however, limited pharmacokinetic data on IV usage in the dog and cat is available. The data available suggests it takes up to 36 h to see the effectiveness of PPIs [74]; in a patient who is not currently on a PPI, famotidine remains the more effective choice at increasing gastric pH immediately prior to anesthesia
Thrombophlebitis is associated with IV administration in people, according to FDA data
Short‐acting barbiturate that, due to its longer residence time and low therapeutic index, has been replaced as a general anesthetic by other agents
Used in the treatment and control of seizures
Euthanasia solution
C. PHARMACOLOGY
CNS depression caused by activation of GABA receptors
Highly protein bound
Redistributes quickly (effect terminates shortly after administration), but hepatic metabolism and renal clearance are necessary for elimination
D. CONTRAINDICATIONS/PRECAUTIONS
As with most induction agents, crosses the placental barrier. Not recommended for C‐sections with viable fetuses
Cardiovascular and respiratory depression are common
If used as an anesthetic, excitement may occur during recovery
Patients with hypoalbuminemia or liver insufficiencies will have profound and prolonged effects
Use with caution in patients with renal insufficiencies
Do not use to treat seizures secondary to lidocaine toxicity
E. PRACTICAL NOTE
Controlled drug, Schedule II
The very alkalotic pH of pentobarbital will cause sloughing if extravasation of the drug occurs
Sometimes used to control seizures following myelograms
LXIX. Phenoxybenzamine alpha receptor blocker
A. DOSE AND DURATION
0.5–0.6 mg/kg PO q 12 h for ideally 14–20 days before surgery
B. CLINICAL APPLICATIONS
Administer prior to surgical removal of pheochromocytomas, to establish effective circulating volume, secondary to α reduction in chronic vasoconstriction because of catecholamine release from the pheochromocytoma
Inhibition of neuronal and extraneuronal uptake of catecholamines
Long‐acting
Metabolized in the liver
Excreted in the urine and bile
D. CONTRAINDICATIONS/PRECAUTIONS
Arrhythmias are still possible during excision of the pheochromocytoma; it is advisable to consider beta blockade if α receptor blockade is successful, and arrhythmias are still evident
Sedation may result from a reduction in sympathetic outflow at the level of the CNS
E. PRACTICAL NOTES
Reduction in mortality associated with pheochromocytomas, with preoperative administration [157]
Some owners report overt sedation in their pets while on this drug, so counseling owners as to this side‐effect is advisable to ensure the drug is consistently administered
Used intranasally (1% nasal solution is available) to reduce bleeding after a rhinoscopy, via local vasoconstriction
Topical 10% eye drops are occasionally used as part of a phacoemulsification procedure
C. PHARMACOLOGY
Potent, direct‐acting alpha‐1 agonist with no beta activity that results in smooth muscle contraction, causing vasoconstriction
Increases blood pressure by an increase in systemic vascular resistance
D. CONTRAINDICATIONS/PRECAUTIONS
Constriction of veins is greater than that of arteries
Likely to result in hypertension with a reflex bradycardia
Avoid in patients with preexisting hypertension and valvular cardiovascular disease (e.g., MR)
Extravasation may result in sloughing or necrosis of surrounding skin
E. PRACTICAL NOTES
Expect hypertension under anesthesia in patients topically administered this drug prior to phacoemulsification
Useful to manage hypotension in patients where increasing HR or workload is undesirable (i.e., patients with HCM or valvular stenosis)
Because profound vasoconstriction results in decreased perfusion, some prefer to monitor lactate levels. Increasing lactate levels may indicate that this drug is worsening perfusion in spite of improved BP
Treatment of hypotension due to ineffective circulating volume during anesthesia
C. PHARMACOLOGY
Crystalloid fluid
Balanced electrolyte solution
Replacement solution
Acetate buffer
D. CONTRAINDICATIONS/PRECAUTIONS
Caution if using high volumes or boluses in patients with congestive heart failure, as excessive volumes may result in pulmonary edema; consider reduced rates and avoid bolus
Relatively short‐lived if not administered as a part of a CRI
B. CLINICAL APPLICATIONS
Treatment of patients with hypokalemia
C. PHARMACOLOGY
As the primary intracellular cation, K+ is vital to many physiologic processes (nerve transmission, muscular contraction, renal function, and normal intracellular tonicity, to name a few)
The gradient between intracellular and extracellular K+ is maintained by an active ion transport system
In normal homeostasis, the K+ absorbed from the gastrointestinal tract exceeds what is lost through the kidneys. When this balance is not maintained, patients will become hypokalemic and require K+ supplementation
D. CONTRAINDICATIONS/PRECAUTIONS
Potassium is necessary to prevent muscle weakness, but extreme caution is used when providing supplementation by any route other than oral
Hyperkalemia is fatal in a high enough dosage
Caution in patients with renal insufficiencies
Never use bolus fluids supplemented with potassium
E. PRACTICAL NOTES
Place ECG on patient and monitor for changes if using potassium supplementation
ECG changes associated with hyperkalemia include bradyarrhythmia, spiked T waves, prolonged P–R interval, absent P waves, widened QRS complexes, and asystole; ventricular tachycardia can also be seen
Monitor serum potassium levels every 30 min during supplementation during anesthesia
Injectable sedative‐hypnotic anesthetic used as an induction agent in dogs and cats because of its smooth inductions and recoveries
Noncumulative; useful for TIVA as repeat bolus or CRI. Including midazolam may reduce the propofol TIVA dose necessary, without prolonging recovery [142]
Often used as the maintenance agent of choice for patients with intracranial disease undergoing imaging such as an MRI, with demonstrably improved arterial pressures, decreased requirements for dopamine, and improved recovery scores in addition to the cerebral perfusion advantages when compared to isoflurane [160]
Used as an anticonvulsant in patients where other efforts have failed [161]
C. PHARMACOLOGY
Lipid‐based emulsion formulation
Acts via GABAA receptors
Rapidly redistributes; metabolized both hepatically and extrahepatically (e.g., in the muscle, lung, and kidney)
Like many multidose drugs, veterinary approved preserved formulation contains benzyl alcohol. Use with caution as a CRI in species such as cats
D. CONTRAINDICATIONS/PRECAUTIONS
Decreases ICP, cerebral metabolic rate of oxygen (CMRO2) consumption, and cerebral blood flow (CBF). There is no change in cerebral autoregulation. Systemic reviews in the human medical field find that propofol has lower mean ICP values and higher cerebral perfusion pressure compared to inhaled agents, making this the agent of choice in cases of intracranial disease [162]
May suppress the sympathetic nervous system to a greater extent than the parasympathetic nervous system. Bradycardia or even asystole may result if given rapidly to patients with high vagal tone
Systemic vasodilation after administration may result
Apnea occurs when administered rapidly
Muscle twitching and paddling (myoclonus) have been observed
May result in Heinz body formation and toxic changes in RBCs in cats with repeated administration [163,164]
No analgesia
Avoid in patients with allergies to eggs
Avoid in patients with increased triglycerides or cholesterol
Ventilation status must be carefully maintained and monitored in patients with neurologic disease
Use only unpreserved formulations of propofol for cat CRIs; CRIs in cats may result in prolonged recoveries
E. PRACTICAL NOTES
Ideal for patients with diminished liver function, as it is metabolized extrahepatically
Best administration technique is slowly, to effect
Preoxygenation for at least 3 min up to the point of intubation may prolong the period from apnea to desaturation at induction [165]
Ideal alternative to inhalant anesthetic for neurologic patients as TIVA. It is imperative to maintain an airway and administer oxygen
Animals have demonstrated pain on injection, particularly with the lipid emulsification formulation of propofol [16]
LXXVI. Propranolol nonselective beta‐blocker
A. DOSE AND DURATION
Dogs and cats: 0.02–0.1 mg/kg IV slowly to effect
Duration of 2–6 h
B. CLINICAL APPLICATIONS
Treatment of tachycardia and supraventricular arrhythmias
C. PHARMACOLOGY
Beta‐1 and beta‐2 blocker
Class II antiarrhythmic
Extensively protein bound
Dependent on liver metabolism; undergoes extensive first‐pass metabolism
D. CONTRAINDICATIONS/PRECAUTIONS
Patients with bradycardia or escape beats
Resulting bradycardia may cause a reduction in CO
Asthmatic patients
Use with caution in patients with liver insufficiencies or hypoproteinemia; drug may have profound effect and delayed clearance
E. PRACTICAL NOTES
Bronchoconstriction may result from beta‐2 blockade
In humans, a decrease in local anesthetic and opioid clearance has been reported with administration of propranolol. It is unknown whether this occurs in animals
Used for intraoperative analgesia and to significantly reduce inhalant requirement when used as a CRI [166]
Commonly used for patients with liver failure [167], hepatic shunts, or extremely critical patients
C. PHARMACOLOGY
Full mu agonist
Highly lipid soluble
Metabolized by plasma esterase
D. CONTRAINDICATIONS/PRECAUTIONS
May cause bradycardia and hypoventilation at high doses or following boluses
Caution in patients with head trauma or increased ICP if ventilation is not supported
E. PRACTICAL NOTES
Postoperatively, an alternative opioid is likely more suitable for analgesia due to remifentanil’s short duration
Acute opioid tolerance and hyperalgesia are reported for people exposed to remifentanil. These findings could not be confirmed in canine patients exposed to remifentanil [168]
Used to manage postoperative pain associated with OHE/castration or orthopedic surgeries in cats
Used to manage postoperative pain and inflammation in dogs associated with soft tissue surgeries
C. PHARMACOLOGY
Inhibits one or more steps in the metabolism of arachidonic acid (AA) and possesses both analgesic and antiinflammatory properties
Acts primarily to reduce the biosynthesis of prostaglandins by inhibiting cyclooxygenase (COX‐1 and COX‐2). In particular, robenacoxib is selective for the COX‐2 prostaglandin
NSAIDs are biotransformed in the liver to inactive metabolites that are excreted either by the kidney via glomerular filtration and tubular secretion or by the bile
D. CONTRAINDICATIONS/PRECAUTIONS
Although use as part of the premedication prior to the inflammatory event, as opposed to postoperative administration, provides preemptive and better analgesia, caution is advised if using this drug preoperatively, especially in dehydrated patients or those with preexisting renal, cardiovascular or hepatic dysfunction
COX‐2 inhibition by NSAIDs is thought to be responsible for the antipyretic, analgesic, and antiinflammatory actions of NSAIDs. However, concurrent inhibition of COX‐1 may result in many of the unwanted effects of NSAIDs, including gastric ulceration and renal toxicity. Robenacoxib is selective for COX‐2 inhibition
Inhibition of prostaglandins that regulate blood flow to the gastric mucosa and stimulate bicarbonate and mucus production may result in loss of GI protective mechanisms; there is evidence to suggest that COX‐2 may actually play an important role in GI healing [169]. Therefore, robenacoxib is contraindicated in cases of GI surgery
GI ulceration is the most common life‐threatening effect while vomiting is the most common adverse effect
May compromise renal blood flow
E. PRACTICAL NOTES
Injectable and oral formulations are available. Note in cats, the tablet dose is different from the injectable dose. Cats should only receive the manufactured 6 mg tablets for accurate dosing
Tablets are not scored and should not be halved. When administering prior to anesthesia, diligent monitoring of blood pressure, treatment of hypotension and administration of fluid therapy are recommended
Subsequent doses can be interchanged with tablet or injectable, paying close attention to dosing
It is recommended to assess serum biochemical baselines before administration of NSAIDs
All local anesthetics share a common chemical structure that includes a lipophilic, benzene ring and a hydrophilic amine group. This compound is then linked to either an ester or an amide. In the case of ropivacaine, there is an amide linkage
pKa 16. pKa determines the amount of ionized and unionized fraction of drug present in the plasma. At high pKa, greater will be the proportion of local anesthetic in the ionized, charged hydrophilic form at physiologic pH (7.4), and the onset of action will be slower. In contrast, at low pKa, a greater proportion of the nonionized lipid‐soluble form will be present at physiologic pH and the onset of action will be more rapid
% Ionized at physiological pH: 83
Lipid solubility (the main determinant of potency and onset of action) is 14
% Protein binding: 94; protein binding influences the duration of action. Only the unbound fraction of drug is pharmacologically active. The higher the protein binding, the longer the duration of action
D. CONTRAINDICATIONS/PRECAUTIONS
Do not administer IV; medication has high cardiotoxicity potential
E. PRACTICAL NOTES
Possible loss of motor function when used in epidural or nerve blocks, although ropivacaine is associated with less ataxia than other local anesthetics
If multiple blocks are performed, ensure total dosage for patient does not exceed the toxic dose
In an epidural, preservative‐free formulations are recommended
Do not dilute concentration to less than 2.5 mg/mL or block may not be effective
The addition of dexmedetomidine at 0.5 mg/mL of the volume for the local block volume may extend the duration of the block
NaHCO3 can be added to local anesthetic solutions to increase the pH, resulting in less sting upon injection when administering to conscious patients. Increasing the pH may also increase the lipid‐soluble fraction, providing a more rapid onset of action and prolonged duration of sensory blockage
At concentrations above 0.5%, ropivacaine produces sensory blockade similar to that obtained with bupivacaine, but there is less chance of inducing motor blockade. For this reason, it is considered very suitable for neuraxial analgesia
Anesthesia induction via facemask or induction chamber. Because the odor is not pungent, sevoflurane is the inhalant of choice for this method. However, the authors discourage the use of induction by any inhalant
C. PHARMACOLOGY
It is clear, colorless and the odor is reported to be pleasant and not irritating to the airways
Nonflammable and nonexplosive liquid
The exact mechanism of action by which inhalant anesthetic agents cause general anesthesia is not precisely known, but it is likely their influence on the electrical activity of the CNS, mediated at the level of the spinal cord, through actions at the lipid bilayer of the cell membrane
Most important effects include CNS depression, prevention of movement likely mediated at the level of the spinal cord, dose‐dependent cardiovascular and respiratory depression, decreased systemic vascular resistance (vasodilation) and hypotension, increased cerebral blood flow and intracranial pressure, depression of body temperature regulating centers, and muscular relaxation
Less soluble than isoflurane, sevoflurane acts rapidly, with faster induction and emergence than isoflurane, but not as fast as desflurane. Difference between isoflurane and sevoflurane is unlikely to have clinical significance
D. CONTRAINDICATIONS/PRECAUTION
Patients with preexisting extreme hypotension, cardiovascular derangements or reason for inability to handle vasodilation
Causes a dose‐dependent decrease in cardiovascular and respiratory depression
CNS depressant
In susceptible individuals, inhalant anesthesia may trigger a clinical syndrome known as malignant hyperthermia (MH). MH is a cellular hypermetabolic state that, if not treated quickly, causes death. Although it is mostly reported in human patients and pigs, other species have also been reported to be affected
The National Institute for Occupational Safety and Health Administration (NIOSH) recommends that no worker should be exposed to ceiling concentrations greater than 2 ppm of any halogenated anesthetic agent over a sampling period not to exceed 1 h
Results in by‐products when used with soda lime, including fluoride ions and compound “A” that may be toxic to the kidney. However, nephrotoxicity has not been demonstrated in clinical patients
To correct metabolic acidosis: perform base deficit calculation (see Equation 1). Give half of the dose slowly over 20 min IV. Reevaluate blood gas; if the patient still exhibits metabolic acidosis, give the other half of the dose slowly in the same fashion. Target pH correction is no more than 7.20
For hyperkalemia: 0.5–1.0 mEq/kg slow over 20 min IV
Duration variable by patient
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