In most domestic species1 and in humans,2 propofol can be used as a sole agent to induce a state of anesthesia characterized by a rapid onset of unconsciousness and muscle relaxation devoid of excitement, paddling, or rigidity. In contrast, anesthetic induction with propofol alone in horses can cause excitement, myotonus, and brief but severe paddling or galloping movement during recumbency.3–5 Because of these effects, propofol alone is unsuitable for anesthetic induction for most horses.
Nonetheless, propofol offers other theoretical advantages as an anesthetic induction agent.1,2 It decreases intracranial pressure in patients with intracranial hypertension and may have neuroprotective properties. Furthermore, propofol reduces intraocular pressure, provided skeletal muscle tone is not increased. Propofol is rapidly metabolized to inactive glucuronide or sulfide conjugates by the liver and multiple extrahepatic tissues, which makes this drug a reasonable option for anesthesia in patients with hepatic or renal failure. In horses, propofol pharmacokinetics is described by a noncompartmental model with a short mean residence time of 14 minutes and a high clearance of 46 mL/kg/min.6 Because of this rapid elimination, the contribution of propofol administered for anesthetic induction to cardiovascular, respiratory, and CNS depression during anesthetic maintenance should similarly be temporally limited. Finally, horses recover from propofol without the emergence delirium that typifies many other anesthetic techniques,5,7–11 and propofol is included in postanesthetic sedation protocols specifically to improve the quality of recovery from anesthesia with other agents.12,13
Other muscle relaxants or sedatives have been administered in an effort to improve anesthetic induction quality for propofol in horses. Premedication with the α2-adrenoreceptor agonist detomidine,8,14 xylazine,4,6,8,10,11 or a combination of xylazine plus the opioid butorphanol9 reduces the incidence and severity of paddling and muscle rigidity but does not prevent it. Coadministration of the benzodiazepine midazolam with propofol to xylazine-premedicated horses does not appear to further improve anesthetic induction quality.15,16 However, administration of guaifenesin prior to anesthetic induction with propofol in horses sedated with xylazine7 or butorphanol17 results in excellent muscle relaxation and prevents the stereotypical galloping movement associated with other propofol induction techniques. To our knowledge, whether guaifenesin alone can allow for a satisfactory anesthetic induction with propofol has not been evaluated.
Guaifenesin (glyceryl guaiacolate) is a centrally acting muscle relaxant with an undetermined mechanism of action. When guaifenesin is administered IV, pharmacokinetics in horses has been described by a 1-compartment model18 or a 2-compartment model with a short (3.45-minute) distribution half-life.19 Guaifenesin has reasonably rapid elimination kinetics, with calculated drug clearance ranging from 6 to 10 mL/kg/min and a half-life ranging from 60 to 108 minutes.18–20 Moreover, in contrast to α2-adrenoreceptor agonists and opioids, guaifenesin causes only mild cardiovascular and respiratory depression, even at doses sufficient to cause recumbency.21,22
The purpose of the study reported here was to determine whether guaifenesin administered at a dose sufficient to induce profound muscle relaxation would allow for a rapid anesthetic induction with propofol without muscle rigidity and limb paddling in healthy adult horses. We hypothesized that the contribution of guaifenesin and propofol to cardiovascular depression during anesthetic maintenance with isoflurane or sevoflurane, as measured by the dose of the positive inotrope dobutamine required to maintain normotension, would be limited in duration and would correspond to rapid elimination of these anesthetic induction drugs.
Minimum alveolar concentration
Mean arterial blood pressure
UCSF Drug Product Services Laboratory, San Francisco, Calif.
Diprivan, AstraZeneca, Wilmington, Del.
Fraser Sweatman Inc, Lancaster, NY.
Mark 9, Bird Corp, Palm Springs, Calif.
Attane, Minrad, Orchard Park, NY.
SevoFlo, Abbott, Abbott Park, Ill.
LB2, Sensormedics, Anaheim, Calif.
DT-XX, BD, Franklin Lakes, NJ.
Ponemah, Data Sciences International, Saint Paul, Minn.
YSI, Yellow Springs, Ohio.
ABL700, Radiometer America, Westlake, Ohio.
Dobutrex, Lilly, Indianapolis, Ind.
Burdick and Jackson, Morristown, NJ.
Alfa Aesar, Ward Hill, Mass.
Spectrum, Gardena, Calif.
7890A, Agilent Technologies, Santa Clara, Calif.
7000A, Agilent Technologies, Santa Clara, Calif.
Sigma-Aldrich, St Louis, Mo.
HP 5-MS, Agilent Technologies, Santa Clara, Calif.
SPSS, version 11, SPSS Inc, Chicago, Ill.
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