Lars W Andersen1,2,3, Dan Isbye4, Jesper Kjærgaard5, Camilla M Kristensen4, Søren Darling6, Stine T Zwisler6, Stine Fisker6, Jens Christian Schmidt6, Hans Kirkegaard1,3, Anders M Grejs2, Jørgen R G Rossau2, Jacob M Larsen7,8, Bodil S Rasmussen8,9, Signe Riddersholm7,8,10, Kasper Iversen11,12, Martin Schultz13, Jakob L Nielsen14, Bo Løfgren1,10, Kasper G Lauridsen1,10,15, Christoffer Sølling16, Kim Pælestik16, Anders G Kjærgaard17, Dorte Due-Rasmussen17, Fredrik Folke12,18,19, Mette G Charlot18, Rikke Malene H G Jepsen20, Sebastian Wiberg20, Michael Donnino21,22, Tobias Kurth23, Maria Høybye1, Birthe Sindberg1, Mathias J Holmberg1,24, Asger Granfeldt2. 1. Research Center for Emergency Medicine, Department of Clinical Medicine and Emergency Department, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. 2. Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark. 3. Prehospital Emergency Medical Services, Central Denmark Region, Aarhus, Denmark. 4. Department of Anesthesia, Centre of Head and Orthopedics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 5. Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 6. Department of Anesthesiology and Intensive Care, Odense University Hospital, Odense, Denmark. 7. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. 8. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. 9. Department of Anesthesia and Intensive Care, Aalborg University Hospital, Aalborg, Denmark. 10. Department of Medicine, Randers Regional Hospital, Randers, Denmark. 11. Department of Emergency Medicine, Herlev and Gentofte University Hospital, Copenhagen, Denmark. 12. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 13. Department of Internal Medicine, Herlev and Gentofte University Hospital, Copenhagen, Denmark. 14. Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Pennsylvania. 15. Unit of Clinical Simulation and Education, Herlev and Gentofte University Hospital, Copenhagen, Denmark. 16. Department of Anesthesiology and Intensive Care, Viborg Regional Hospital, Viborg, Denmark. 17. Department of Anesthesiology and Intensive Care, Horsens Regional Hospital, Horsens, Denmark. 18. Department of Cardiology, Herlev and Gentofte University Hospital, Copenhagen, Denmark. 19. Copenhagen Emergency Medical Services, University of Copenhagen, Copenhagen, Denmark. 20. Department of Anesthesiology, Zealand University Hospital, Køge, Denmark. 21. Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 22. Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 23. Institute of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany. 24. Department of Cardiology, Viborg Regional Hospital, Viborg, Denmark.
Abstract
Importance: Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes. Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021. Intervention: Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses. Main Outcomes and Measures: The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2). Results: Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively. Conclusions and Relevance: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03640949.
Importance: Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes. Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021. Intervention: Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses. Main Outcomes and Measures: The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2). Results: Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively. Conclusions and Relevance: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03640949.
Authors: Weibo Wan; Jingjing Zhou; Rong Lu; Chaoyang Wang; Shuli Hu; Mei Liu; Rong Xiong; Jing Kuang; Xuepeng Fan Journal: Evid Based Complement Alternat Med Date: 2022-07-06 Impact factor: 2.650
Authors: Changsheng Wang; Evelyne Bischof; Jing Xu; Qinyue Guo; Guanghui Zheng; Weiwei Ge; Juntao Hu; Elena Laura Georgescu Margarint; Jennifer L Bradley; Mary Ann Peberdy; Joseph P Ornato; Changqing Zhu; Wanchun Tang Journal: Front Cardiovasc Med Date: 2022-07-07