Safety of Anticholinergics with Alpha-2 Agonists

In the Literature

Kramer BM, Hector RC, Rezende ML, Hess AM, Mama KR. Sedative and cardiopulmonary effects of intramuscular combinations of hydromorphone, acepromazine, dexmedetomidine, and glycopyrrolate followed by intravenous propofol and inhalant isoflurane anesthesia in healthy dogs. Am J Vet Res. 2022;83(10):ajvr.22.06.0098. doi:10.2460/ajvr.22.06.0098

The Research …

Use of alpha-2–adrenergic agonists (eg, dexmedetomidine) as preanesthetic agents provides advantages, including sedation and analgesia that can be reversed. Alpha-2 agonists are primarily used in patients without cardiac disease because vasoconstriction—with strong potential for subsequent increase in cardiac work, hypertension, and bradycardia—is expected to occur. Decreased heart rate can cause concern but is largely due to a normal physiologic response to hypertension in the early phase of sedation. Alpha-2 agonists are commonly administered in combination with opioids to enhance analgesia and sedation.

This crossover study evaluated the sedative and cardiovascular effects of hydromorphone given in conjunction with dexmedetomidine (HD); acepromazine (HA); acepromazine and dexmedetomidine (HAD); or acepromazine, dexmedetomidine, and glycopyrrolate (HADG) in 6 dogs receiving propofol and isoflurane after sedation. Physiologic and cardiopulmonary variables were measured at set time points after sedation. Although cardiopulmonary parameters (eg, heart rate, oxygen consumption) differed among groups, changes in postsedation parameters were mild and dissipated within 15 to 30 minutes after sedative administration.

Glycopyrrolate administration in the HADG group significantly increased heart rate, cardiac index, and indexes of oxygenation (eg, tissue oxygen delivery) compared with other groups, especially the HD group; however, blood pressure and rate pressure product (an indicator of myocardial workload) also increased. Indexes of oxygenation were lower in the HD group than in other groups but stayed within physiologic levels; anaerobic metabolism did not occur.

The HAD combination is of interest because acepromazine alleviated the decrease in cardiac index and indexes of oxygenation compared with the HD group and dexmedetomidine lessened the drop in packed cell volume (presumably caused by vasodilation from acepromazine administration) compared with the HA group. The HAD combination is used anecdotally for sedation and could also be used for its hemodynamic effects, although research using higher alpha-2–agonist dosages is necessary. Acepromazine may have protected against more profound cardiovascular changes in the HADG group.

The authors noted that a consideration of the study design was the low dose of dexmedetomidine (0.0025 mg/kg IM). Sedation was not significantly different among the study groups of calm dogs in a quiet setting. In the clinic, a higher dose is often needed, which may be problematic because adverse cardiovascular effects have been reported with higher doses of alpha-2 agonists administered in conjunction with glycopyrrolate.^1,2 Follow-up studies with higher dexmedetomidine doses and later glycopyrrolate administration (when bradycardia is mediated by dexmedetomidine’s central, rather than peripheral, effects) would be useful.

… The Takeaways

Key pearls to put into practice:

• Glycopyrrolate increases heart rate and indexes of oxygenation in dogs sedated with low-dose dexmedetomidine but also causes hypertension and may increase cardiac work.

• Tissue oxygenation as measured by indexes of oxygenation in dogs given dexmedetomidine at 0.0025 mg/kg IM alone was adequate and slightly improved by concurrent administration of acepromazine. This combination could be considered for enhanced sedation and hemodynamic effects, although further research is needed.

• Low-dose dexmedetomidine (0.0025 mg/kg IM) should be used and acepromazine strongly considered if glycopyrrolate is administered in conjunction with dexmedetomidine.