High-Dose Glucagon Has Hemodynamic Effects Regardless of Cardiac Beta-Adrenoceptor Blockade: A Randomized Clinical Trial
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
High-Dose Glucagon Has Hemodynamic Effects Regardless of Cardiac Beta-Adrenoceptor Blockade : A Randomized Clinical Trial. / Petersen, Kasper M.; Bøgevig, Søren; Riis, Troels; Andersson, Niklas W.; Dalhoff, Kim P.; Holst, Jens J.; Knop, Filip K.; Faber, Jens; Petersen, Tonny S.; Christensen, Mikkel B.
I: Journal of the American Heart Association, Bind 9, Nr. 21, e016828, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - High-Dose Glucagon Has Hemodynamic Effects Regardless of Cardiac Beta-Adrenoceptor Blockade
T2 - A Randomized Clinical Trial
AU - Petersen, Kasper M.
AU - Bøgevig, Søren
AU - Riis, Troels
AU - Andersson, Niklas W.
AU - Dalhoff, Kim P.
AU - Holst, Jens J.
AU - Knop, Filip K.
AU - Faber, Jens
AU - Petersen, Tonny S.
AU - Christensen, Mikkel B.
PY - 2020
Y1 - 2020
N2 - Background Intravenous high-dose glucagon is a recommended antidote against beta-blocker poisonings, but clinical effects are unclear. We therefore investigated hemodynamic effects and safety of high-dose glucagon with and without concomitant beta-blockade. Methods and Results In a randomized crossover study, 10 healthy men received combinations of esmolol (1.25 mg/kg bolus+0.75 mg/kg/min infusion), glucagon (50 µg/kg), and identical volumes of saline placebo on 5 separate days in random order (saline+saline; esmolol+saline; esmolol+glucagon bolus; saline+glucagon infusion; saline+glucagon bolus). On individual days, esmolol/saline was infused from -15 to 30 minutes. Glucagon/saline was administered from 0 minutes as a 2-minute intravenous bolus or as a 30-minute infusion (same total glucagon dose). End points were hemodynamic and adverse effects of glucagon compared with saline. Compared with saline, glucagon bolus increased mean heart rate by 13.0 beats per minute (95% CI, 8.0-18.0; P<0.001), systolic blood pressure by 15.6 mm Hg (95% CI, 8.0-23.2; P=0.002), diastolic blood pressure by 9.4 mm Hg (95% CI, 6.3-12.6; P<0.001), and cardiac output by 18.0 % (95% CI, 9.7-26.9; P=0.003) at the 5-minute time point on days without beta-blockade. Similar effects of glucagon bolus occurred on days with beta-blockade and between 15 and 30 minutes during infusion. Hemodynamic effects of glucagon thus reflected pharmacologic glucagon plasma concentrations. Glucagon-induced nausea occurred in 80% of participants despite ondansetron pretreatment. Conclusions High-dose glucagon boluses had significant hemodynamic effects regardless of beta-blockade. A glucagon infusion had comparable and apparently longer-lasting effects compared with bolus, indicating that infusion may be preferable to bolus injections. Registration Information URL: https://www.clinicaltrials.gov; Unique identifier: NCT03533179.
AB - Background Intravenous high-dose glucagon is a recommended antidote against beta-blocker poisonings, but clinical effects are unclear. We therefore investigated hemodynamic effects and safety of high-dose glucagon with and without concomitant beta-blockade. Methods and Results In a randomized crossover study, 10 healthy men received combinations of esmolol (1.25 mg/kg bolus+0.75 mg/kg/min infusion), glucagon (50 µg/kg), and identical volumes of saline placebo on 5 separate days in random order (saline+saline; esmolol+saline; esmolol+glucagon bolus; saline+glucagon infusion; saline+glucagon bolus). On individual days, esmolol/saline was infused from -15 to 30 minutes. Glucagon/saline was administered from 0 minutes as a 2-minute intravenous bolus or as a 30-minute infusion (same total glucagon dose). End points were hemodynamic and adverse effects of glucagon compared with saline. Compared with saline, glucagon bolus increased mean heart rate by 13.0 beats per minute (95% CI, 8.0-18.0; P<0.001), systolic blood pressure by 15.6 mm Hg (95% CI, 8.0-23.2; P=0.002), diastolic blood pressure by 9.4 mm Hg (95% CI, 6.3-12.6; P<0.001), and cardiac output by 18.0 % (95% CI, 9.7-26.9; P=0.003) at the 5-minute time point on days without beta-blockade. Similar effects of glucagon bolus occurred on days with beta-blockade and between 15 and 30 minutes during infusion. Hemodynamic effects of glucagon thus reflected pharmacologic glucagon plasma concentrations. Glucagon-induced nausea occurred in 80% of participants despite ondansetron pretreatment. Conclusions High-dose glucagon boluses had significant hemodynamic effects regardless of beta-blockade. A glucagon infusion had comparable and apparently longer-lasting effects compared with bolus, indicating that infusion may be preferable to bolus injections. Registration Information URL: https://www.clinicaltrials.gov; Unique identifier: NCT03533179.
KW - beta blocker
KW - glucagon
KW - hemodynamics
KW - toxicology
U2 - 10.1161/JAHA.120.016828
DO - 10.1161/JAHA.120.016828
M3 - Journal article
C2 - 33103603
AN - SCOPUS:85095666358
VL - 9
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
SN - 2047-9980
IS - 21
M1 - e016828
ER -
ID: 251639986