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Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial

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Harvard

Andersen, LW, Isbye, D, Kjærgaard, J, Kristensen, CM, Darling, S, Zwisler, ST, Fisker, S, Schmidt, JC, Kirkegaard, H, Grejs, AM, Rossau, JRG, Larsen, JM, Rasmussen, BS, Riddersholm, S, Iversen, K, Schultz, M, Nielsen, JL, Løfgren, B, Lauridsen, KG, Sølling, C, Pælestik, K, Kjærgaard, AG, Due-Rasmussen, D, Folke, F, Charlot, MG, Jepsen, RMHG, Wiberg, S, Donnino, M, Kurth, T, Høybye, M, Sindberg, B, Holmberg, MJ & Granfeldt, A 2021, 'Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial', JAMA - Journal of the American Medical Association, vol. 326, no. 16, pp. 1586-1594. https://doi.org/10.1001/jama.2021.16628

APA

Andersen, L. W., Isbye, D., Kjærgaard, J., Kristensen, C. M., Darling, S., Zwisler, S. T., Fisker, S., Schmidt, J. C., Kirkegaard, H., Grejs, A. M., Rossau, J. R. G., Larsen, J. M., Rasmussen, B. S., Riddersholm, S., Iversen, K., Schultz, M., Nielsen, J. L., Løfgren, B., Lauridsen, K. G., ... Granfeldt, A. (2021). Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA - Journal of the American Medical Association, 326(16), 1586-1594. https://doi.org/10.1001/jama.2021.16628

CBE

Andersen LW, Isbye D, Kjærgaard J, Kristensen CM, Darling S, Zwisler ST, Fisker S, Schmidt JC, Kirkegaard H, Grejs AM, Rossau JRG, Larsen JM, Rasmussen BS, Riddersholm S, Iversen K, Schultz M, Nielsen JL, Løfgren B, Lauridsen KG, Sølling C, Pælestik K, Kjærgaard AG, Due-Rasmussen D, Folke F, Charlot MG, Jepsen RMHG, Wiberg S, Donnino M, Kurth T, Høybye M, Sindberg B, Holmberg MJ, Granfeldt A. 2021. Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA - Journal of the American Medical Association. 326(16):1586-1594. https://doi.org/10.1001/jama.2021.16628

MLA

Vancouver

Author

Andersen, Lars W ; Isbye, Dan ; Kjærgaard, Jesper ; Kristensen, Camilla M ; Darling, Søren ; Zwisler, Stine T ; Fisker, Stine ; Schmidt, Jens Christian ; Kirkegaard, Hans ; Grejs, Anders M ; Rossau, Jørgen R G ; Larsen, Jacob M ; Rasmussen, Bodil S ; Riddersholm, Signe ; Iversen, Kasper ; Schultz, Martin ; Nielsen, Jakob L ; Løfgren, Bo ; Lauridsen, Kasper G ; Sølling, Christoffer ; Pælestik, Kim ; Kjærgaard, Anders G ; Due-Rasmussen, Dorte ; Folke, Fredrik ; Charlot, Mette G ; Jepsen, Rikke Malene H G ; Wiberg, Sebastian ; Donnino, Michael ; Kurth, Tobias ; Høybye, Maria ; Sindberg, Birthe ; Holmberg, Mathias J ; Granfeldt, Asger. / Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest : A Randomized Clinical Trial. In: JAMA - Journal of the American Medical Association. 2021 ; Vol. 326, No. 16. pp. 1586-1594.

Bibtex

@article{b0657c980e984c249eab16f358efb77e,
title = "Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial",
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.",
keywords = "Aged, Cardiovascular Agents/adverse effects, Confidence Intervals, Denmark, Double-Blind Method, Epinephrine/administration & dosage, Female, Glucocorticoids/administration & dosage, Heart Arrest, Humans, Hyperglycemia/epidemiology, Hyponatremia/epidemiology, Male, Methylprednisolone/administration & dosage, Neurologic Examination, Placebos/pharmacology, Return of Spontaneous Circulation/drug effects, Treatment Outcome, Uncertainty, Vasoconstrictor Agents/administration & dosage, Vasopressins/administration & dosage",
author = "Andersen, {Lars W} and Dan Isbye and Jesper Kj{\ae}rgaard and Kristensen, {Camilla M} and S{\o}ren Darling and Zwisler, {Stine T} and Stine Fisker and Schmidt, {Jens Christian} and Hans Kirkegaard and Grejs, {Anders M} and Rossau, {J{\o}rgen R G} and Larsen, {Jacob M} and Rasmussen, {Bodil S} and Signe Riddersholm and Kasper Iversen and Martin Schultz and Nielsen, {Jakob L} and Bo L{\o}fgren and Lauridsen, {Kasper G} and Christoffer S{\o}lling and Kim P{\ae}lestik and Kj{\ae}rgaard, {Anders G} and Dorte Due-Rasmussen and Fredrik Folke and Charlot, {Mette G} and Jepsen, {Rikke Malene H G} and Sebastian Wiberg and Michael Donnino and Tobias Kurth and Maria H{\o}ybye and Birthe Sindberg and Holmberg, {Mathias J} and Asger Granfeldt",
year = "2021",
month = oct,
day = "26",
doi = "10.1001/jama.2021.16628",
language = "English",
volume = "326",
pages = "1586--1594",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "16",

}

RIS

TY - JOUR

T1 - Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest

T2 - A Randomized Clinical Trial

AU - Andersen, Lars W

AU - Isbye, Dan

AU - Kjærgaard, Jesper

AU - Kristensen, Camilla M

AU - Darling, Søren

AU - Zwisler, Stine T

AU - Fisker, Stine

AU - Schmidt, Jens Christian

AU - Kirkegaard, Hans

AU - Grejs, Anders M

AU - Rossau, Jørgen R G

AU - Larsen, Jacob M

AU - Rasmussen, Bodil S

AU - Riddersholm, Signe

AU - Iversen, Kasper

AU - Schultz, Martin

AU - Nielsen, Jakob L

AU - Løfgren, Bo

AU - Lauridsen, Kasper G

AU - Sølling, Christoffer

AU - Pælestik, Kim

AU - Kjærgaard, Anders G

AU - Due-Rasmussen, Dorte

AU - Folke, Fredrik

AU - Charlot, Mette G

AU - Jepsen, Rikke Malene H G

AU - Wiberg, Sebastian

AU - Donnino, Michael

AU - Kurth, Tobias

AU - Høybye, Maria

AU - Sindberg, Birthe

AU - Holmberg, Mathias J

AU - Granfeldt, Asger

PY - 2021/10/26

Y1 - 2021/10/26

N2 - 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.

AB - 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.

KW - Aged

KW - Cardiovascular Agents/adverse effects

KW - Confidence Intervals

KW - Denmark

KW - Double-Blind Method

KW - Epinephrine/administration & dosage

KW - Female

KW - Glucocorticoids/administration & dosage

KW - Heart Arrest

KW - Humans

KW - Hyperglycemia/epidemiology

KW - Hyponatremia/epidemiology

KW - Male

KW - Methylprednisolone/administration & dosage

KW - Neurologic Examination

KW - Placebos/pharmacology

KW - Return of Spontaneous Circulation/drug effects

KW - Treatment Outcome

KW - Uncertainty

KW - Vasoconstrictor Agents/administration & dosage

KW - Vasopressins/administration & dosage

UR - http://www.scopus.com/inward/record.url?scp=85116316690&partnerID=8YFLogxK

U2 - 10.1001/jama.2021.16628

DO - 10.1001/jama.2021.16628

M3 - Journal article

C2 - 34587236

VL - 326

SP - 1586

EP - 1594

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 16

ER -

ID: 67902972