Anesthetic drugs: A review and what's new (Proceedings)

• There is no single best way to anesthetize dogs and cats, making it imperative to be familiar with a variety of different anesthetic drugs and techniques. As a general rule when putting together an anesthetic plan, it is best to use relatively low doses of several different drugs (termed balanced anesthesia) rather than a large dose of a single drug to decrease unwanted side effects.

Drug selection should depend on

• Patient's physical status, temperament, type of procedure being performed (including length), present or anticipated pain, familiarity of anesthetic drugs, availability of equipment and personnel, cost of drugs

Sedative and tranquilizers

• Used for sedation, restraint, to reduce the amount of inhalant needed, to decrease vomiting, to increase muscle relaxation and to smooth out recovery

• Benzodiazepines

o General characteristics

• Sedation and neuroleptanalgesia (when given with an opioid), paradoxical excitement when given alone, decreases inhibition (licking, sniffing, biting, jumping off of table), anticonvulsant, minimal cardiovascular and respiratory depressant, reversible with flumazanil at 0.08 mg/kg IM, NO ANALGESIA

o Diazepam (0.1-0.2 mg/kg; IV only)

• Not compatible with other drugs because it is based in propylene glycol (can mix with ketamine only), not a reliable sedative when given alone, may cause dysphoria and/or aggression in cats

o Midazolam (0.1-0.2 mg/kg; SQ, IM, IV; duration of action 1-2 hours)

• Water soluble, not a reliable sedative in young dogs and cats, great sedation seen in rabbits, ferrets and some birds (doses vary)

• Phenothiazines

o Acepromazine (0.01-0.1 mg/kg- start low, you can always add more if needed)

• Profound sedation (dose dependent)

• Long onset of action (can take 15 minutes) and long duration of action

• Neuroleptic (when combined with an opioid)

• NO ANALGESIA

• Anti-emetic

• Negative cardiovascular side effects (dose dependent)

• Vasodilation, hypotension, direct cardiac depression

• Use with care (or not at all) in sick or debilitated animals

• Alpha-2 agonists (1 mcg/kg up to 10 mcg/kg SQ, IM, IV; duration of action ~ 90 min dose dependent)

o Dexmedetomidine

• Dose dependent sedation with some analgesia

• Reversible

• Peripheral vasoconstriction (pale mucous membranes, cold extremities)

• Bradycardia

• Treatment with anticholenergics not always recommended (causes increase in myocardial work)

• Increase urine production

• Vomiting

• Some animals refractory to drug

• Pre-existing stress, fear, anxiety, pain

• Co-administer with opioid and put in quiet area

• Can take up to 30 min to take effect!

• Effects tend to be more variable than with domitor

• Go low IV especially when coupling with opioid- you can always add more!

• 2-3 mcg/kg IV, 5-7 mcg/kg IM (opioids smooth sedation and decrease necessary dose)

• Low end for an anxiolytic, Middle for sedation and immobilization, High end for minor surgery (with analgesic of course)

• Alpha-2 antagonists

o Atipamezole

• Reverses effects of dexmedetomidine and other alpha-2 agonists, IV administration is not recommended but can be used in an emergency (use caution and give slowly), give equal volume of atipamazole as the volume of dexmedetomidine that was given

NSAIDS (Non-steroidal anti-inflammatory drugs)

• Block production of prostaglandins by binding and inhibiting the cyclooxygenase (COX) enzyme

• COX enzymes (COX-1 and COX-2) have important homeostatic functions

o COX-1 mediates prostaglandins (PGs) responsible for renal and GI blood flow and protection as well as platelet integrity

o COX-2 mediates PGs responsible for inflammation, pain, edema, fever as well as some other homeostatic functions

• COX-2 enzyme also mediates the PG E2 which helps maintain renal perfusion in the face of hypovolemia through vasodilation

• COX-2 selective NSAIDS are preferred

o By sparing the COX-1 enzyme GI effects are 50% less likely

o These drugs are not without potentially harmful side effects

• Avoid the use of NSAIDS in animals with...

o Renal or hepatic dysfunction, coagulopathies, GI disorders,shock, hypotension/hypovolemia

• By blocking the production of PG E2, renal perfusion is compromised

• Do not use in combination with corticosteroids

• Increases the likelihood of GI ulceration

Opioids

• Used to provide analgesia by binding to specific opioid receptors (delta, kappa, mu).

• General characteristics and side effects of opioids (pure mu agonists mainly)

o Minimal cardiovascular depression, dose dependent respiratory depression by increasing resting PaCO2, bradycardia from vagal stimulation, stimulates defecation followed by ileus, vomiting (direct stimulation of CTZ), urine retention from decrease sensation and urge, reversible, effects the body's ability to thermoregulate (panting (dogs) followed by hypothermia; hyperthermia has been seen in cats (CNS excitation?))

• Morphine (0.5-1.0 mg/kg SQ, IM, duration of action ~ 4-6 hours)

o Pure mu agonist

o Great analgesia with good sedation (CNS depressant in dogs, primates... Can cause excitation in other species)

o Inexpensive

o Antitussive

o Histamine release IV

o Absorbed well SQ, IM, IV, oral availability is poor do to the first pass effect

o High lipid solubility makes it a great choice for epidural use (0.1 mg/kg preservative free for 12-24 hours of analgesia!)

• Hydromorphone (0.1-0.2 mg/kg; SQ, IM, or IV; duration of action ~ 2-3 hours)

o Pure mu agonist

o Very similar to morphine but...

• Less vomiting, no histamine release IV, may cause hyperthermia in cats

• Oxymorphone (0.05-0.1 mg/kg SQ, IM, IV; duration of action ~2-3 hours)

o Pure mu agonist

o Very similar to hydromorphone but...

• Expensive and can be difficult to get, less panting

• Fentanyl injectable (2-25 mcg/kg/hr)

o Pure mu opioid, similar to morphine but...

• More potent, rapid onset and short duration of action

• 3-8 minutes after IV injection, last 20-30 minutes, given as a CRI

• Fentanyl Transdermal Patch

o 12-18 hours to achieve adequate blood levels, lasts up to three days from application, dose accordingly!

• Doesn't always provide adequate analgesia when used alone

• Must be properly adhered to work (designed for human skin)

• Methadone (0.3-0.6 mg/kg; SQ, IM, IV; duration of action ~ 3-4 hours)

o Mu agonist and NMDA antagonist

o Similar to morphine but...

• Analgesia not as good as morphine but still great, great for chronic pain (NMDA antagonism decreases wind-up), excellent oral absorption (per human studies)

• Butophanol (0.2-0.4 mg/kg; SQ, IM, IV; duration of action ~ 1-2 hours)

o Agonist/antagonist (agonizes kappa, antagonizes mu)

o Ceiling effect; high doses don't produce additional side effects or additional analgesia

o Less respiratory depression compared to morphine

o Only a mild analgesic in dogs and cats, great analgesic in birds (pain in birds is mediated by the kappa receptor)

o May be a good visceral analgesic in small animals (kappa receptors in the gut) but its short duration of action and high cost make it difficult to justify its use.

o Can be used as a mu reversal agent (leaves kappa analgesia)

• Buprenorphine (20-40 mcg/kg; IM, IV, Transmucosally in cats; duration of action ~ 8-10 hours)

o Partial mu agonist (binds avidly to mu receptor but doesn't elicit full effects and can be difficult to reverse)

o Good to great analgesia

o Slow onset of action (at least 30 minutes all routes)

o Can be given IM, IV or transmucosally in cats- not well absorbed SQ

• Liposome encapsulated hydromorphone

o Slow release injectable opioid

o Currently undergoing clinical trials

• Antagonists

o Naloxone (0.04 mg/kg; IM preferred; duration of action 30-60 min)

• Rapidly reverses all opioid induced clinical effects including analgesia!

• Should only use when absolutely necessary (overdose, respiratory depression)

• Can administer IV to effect

• Shorter duration of action than most opioids (around 1 hour) so renarcotization is possible

Others

• Gabapentin (2-10 mg/kg BID to QID PO in dogs, 2-5 mg/kg BID PO in cats)

o Effective at reducing hyperalgesia and allodynia associated with neuropathic pain and central sensitization as well as chronic and malignant pain

o Common side effects include mild sedation and ataxia

• Tramadol (3-6 and up to 10 mg/kg in severe cases BID to QID in dogs, 1-2 mg/kg BID to QID in cats)

o Weak mu agonist with monoamine reuptake inhibition and some potential NMDA antagonism

o Great analgesia for both acute and chronic pain

Anticholinergics

• Vagal inhibition

• Decreases oral and respiratory secretions and decreases GI motility

• Should be used only when there is a clear indication to do so (sinus bradycardia, incomplete A-V block), can cause tachycardia (increase myocardial work)

• Co-administration with ketamine has been shown to increase mortality in some young cats undergoing elective surgery

• May increase chance of esophageal reflux in dogs by reducing lower esophageal sphincter tone

• Should never be a substitute for diligent monitoring

• Two common drugs

o Atropine

• Great in an emergency to treat life-threatening bradycardia, fast onset, short duration, can cause serious tachycardia

o Glycopyrrolate (0.005-0.01 mg/kg IV)

• Slower onset and longer duration of action, better choice for non-emergency use

Injectable anesthetic agents

• Injectable agents provide a safer, less stressful alternative to "gassing down" an animal, it also less expensive, faster, there is less waste/pollution, and the anesthetist is given more control. All injectable anesthetics also depress some vital organ function- premedications are essential to decrease the necessary dose of induction drug.

• Much variability in available drugs

o Ketamine (5 mg/kg mixed with equal volume of benzodiazepine for induction)

• Short acting dissociative, cardiovascular stimulant, does not depress ventilation, somatic analgesic at sub-anesthetic doses (2-10 µg/kg/hr CRI)

• Not an adequate visceral analgesic or single analgesic (ever), increases intra-cranial and intra-ocular pressure, muscle rigidity

• Good induction agent for sick or debilitated animals (use caution in animals with heart issues)

o Propofol (2-6 mg/kg IV; titrate to effect)

• Ultra-short acting non-barbiturate with rapid metabolic clearance

• 90 seconds to peak effect then about 5 minutes to redistribute (non-cumulative)

• Rapid induction (administer slow and steady to avoid profound apnea)

• Cardiovascular depressant- titrate to effect and know your dose range!

• Pre-oxygenate to buy time!

• Can be re-dosed intra-op if patient gets light but you only need a fraction of the induction dose.

• Can be painful IV, may cause twitching, repeated dosing not recommended in cats

• Can be used as a CRI (ventilator patients in ICU, MH...)

o Thiopental (10-12 mg/kg IV; titrate to effect)

• Ultra-short acting barbiturate with rapid redistribution to muscle and fat

• IV only (can be irritating perivascularly)

• Cumulative

• Arrhythmogenic (bigeminy)

• Thin animals (sight hounds) may see prolonged effects

o Etomidate (1-2 mg/kg IV)

• Induction agent with minimal CV and respiratory depression

• May have brain protective properties after global ischemia

• Inhibits steroid production by adrenals up to 3 hours

• Vomiting/retching if under dosed

• Painful on IV injection (based in propylene glycol)

• Expensive

Inhalants

• Very potent vasodilators, dose dependent hypotension, respiratory depressants

• MAC-50; minimal alveolar concentration required to keep 50% or patients anesthetized during surgery.

• MAC-95; minimal alveolar concentration required to keep 95% of patients anesthetized during surgery. 1.5 X MAC-50

• Respiratory arrest typically occurs at 2-3 MAC

• Pre-meds and adjuncts are necessary to decrease MAC and increase anesthetic safety

o Isoflurane

• MAC 1.3% in dogs, 1.6% in cats

• Low blood solubility (rapid induction and recovery)

• Only 0.2% metabolized

o Sevoflurane

• Less potent than Iso

• MAC 2.3% in dogs, 2.6% in cats

• Lower blood solubility than iso (faster induction and recovery)

• 3% metabolized

References

Branson, KR. Injectable and alternative anesthetic techniques; Lamont, LA, Matthews, KA. Opioids, non-steroidsal anti-inflammatories, and analgesic adjuvants; Lemke, K. Anticholinergics and sedatives; Lin, H Dissociative Anesthetics; Steffey, EP, and Mama, KR. Inhalation Anesthetics; All In: Tranquilli WJ, Thurmon JC, Grimm KA, eds. Lumb & Jones Veterinary Anesthesia and Analgesia. Iowa: Blackwell, 2007

Plumb, DC. Veterinary Drug Handbook. Fourth Ed. Iowa State Press.