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Although there is consensus in the literature on hemodynamic management of septic shock in the resuscitation phase, the best way to conduct the weaning of vasopressor drugs in the stabilization phase remains open. The present study aims to study the incidence of hypotension in the weaning phase of vasopressor drugs- norepinephrine and vasopressin.
A randomized, open-case clinical trial with 2 arms will be conducted: initial suspension of norepinephrine (norepinephrine group) versus initial vasopressin (vasopressin group).
The selection of patients who will participate in the study will be for convenience. The randomization of the patients will be done by opaque envelopes 1:1, grouped into blocks, generated by random numbers.
The study will be carried out in the intensive care unit of a tertiary hospital in Southern Brazil, taking into account the clinical and surgical patients. In the intensive care unit, after randomization, patients will be identified by posters, attached to the bed. The titration of vasoactive drugs will be criterion of the assistant team.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| norepinephrine group | Experimental | Initial suspension of norepinephrine. |
|
| vasopressin group | Experimental | Initial suspension of vasopressin. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Norepinephrine | Other | The patients will be randomized for the initial suspension of norepinephrine (norepinephrine group). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of hypotension | Evaluation of the incidence of hypotension in the first 24 hours after discontinuation of one of the vasoactive drugs: norepinephrine or vasopressin. It is defined as hypotension the drop in mean blood pressure below 65 mmHg, triggering one or more of the following measures: a) administration of crystalloid or colloid aliquot, b) dose increase of the remaining vasoactive drug or c) re-establishment of the drug vasoactive paused. | The first 24 hours after the start of reduction of one of the vasopressors. |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality | Evaluation of the mortality in first 28 days after discontinuation of one of the vasoactive drugs. | Mortality in a 28-day follow-up, from the beginning of the reduction of one of the vasopressors. |
| Length of stay in intensive care unit |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Cassio Mallmann, MD | casmallmann@yahoo.com.br | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Nossa Senhora da Conceicao | Porto Alegre | Rio Grande do Sul | 91350-200 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11529214 | Result | Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001 Aug 23;345(8):588-95. doi: 10.1056/NEJMra002709. No abstract available. | |
| 34605781 | Result | Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Moller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337. No abstract available. |
| Label | URL |
|---|---|
| Borges RB, et al. Power and Sample Size for Health Researchers: uma ferramenta para cálculo de tamanho amostral e poder do teste voltado a pesquisadores da área da saúde. | View source |
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| D018805 | Sepsis |
| D003919 | Diabetes Insipidus |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D009638 | Norepinephrine |
| D014667 | Vasopressins |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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A randomized, parallel, open-case clinical trial.
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| Vasopressin | Other | The patients will be randomized for the initial suspension of vasopressin (vasopressin group). |
|
Evaluation of the length of stay in intensive care unit.
| In a 28-day follow-up, from the beginning of reduction of one of the vasopressors. |
| Time of use of the vasoactive drugs | Quantify the time spent using vasoactive drugs after the removal of the first drug (norepinephrine or vasopressin) in days. | Follow-up of up to 7 days, from the beginning of reduction of one of the vasopressors. |
| Incidence of arrhythmias | Quantify the incidence of arrhythmias with hemodynamic repercussions in 24 hours after withdrawal of the first drug (norepinephrine or vasopressin). This group includes events in which hemodynamic worsening required electrical or chemical cardioversion. | The first 24 hours after the start of reduction of one of the vasopressors. |
| Incidence of hemodialysis | Quantify the incidence of hemodialysis, independent of dialysis modality, excluding patients on dialysis chronic. | The first 72 hours after the start of reduction of one of the vasopressors. |
| 18305265 | Result | Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D; VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008 Feb 28;358(9):877-87. doi: 10.1056/NEJMoa067373. |
| 31958982 | Result | Der-Nigoghossian C, Hammond DA, Ammar MA. Narrative Review of Controversies Involving Vasopressin Use in Septic Shock and Practical Considerations. Ann Pharmacother. 2020 Jul;54(7):706-714. doi: 10.1177/1060028020901521. Epub 2020 Jan 20. |
| 23796235 | Result | Russell JA, Fjell C, Hsu JL, Lee T, Boyd J, Thair S, Singer J, Patterson AJ, Walley KR. Vasopressin compared with norepinephrine augments the decline of plasma cytokine levels in septic shock. Am J Respir Crit Care Med. 2013 Aug 1;188(3):356-64. doi: 10.1164/rccm.201302-0355OC. |
| 22518026 | Result | Gordon AC, Wang N, Walley KR, Ashby D, Russell JA. The cardiopulmonary effects of vasopressin compared with norepinephrine in septic shock. Chest. 2012 Sep;142(3):593-605. doi: 10.1378/chest.11-2604. |
| 29319721 | Result | Nascente APM, Freitas FGR, Bakker J, Bafi AT, Ladeira RT, Azevedo LCP, Lima A, Machado FR. Microcirculation improvement after short-term infusion of vasopressin in septic shock is dependent on noradrenaline. Clinics (Sao Paulo). 2017 Dec;72(12):750-757. doi: 10.6061/clinics/2017(12)06. |
| 29859008 | Result | Yin A, Yamada A, Stam WB, van Hasselt JGC, van der Graaf PH. Quantitative systems pharmacology analysis of drug combination and scaling to humans: the interaction between noradrenaline and vasopressin in vasoconstriction. Br J Pharmacol. 2018 Aug;175(16):3394-3406. doi: 10.1111/bph.14385. Epub 2018 Jul 10. |
| 27398737 | Result | Stolk RF, van der Poll T, Angus DC, van der Hoeven JG, Pickkers P, Kox M. Potentially Inadvertent Immunomodulation: Norepinephrine Use in Sepsis. Am J Respir Crit Care Med. 2016 Sep 1;194(5):550-8. doi: 10.1164/rccm.201604-0862CP. |
| 12519925 | Result | Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003 Jan 9;348(2):138-50. doi: 10.1056/NEJMra021333. No abstract available. |
| 27483065 | Result | Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJ; VANISH Investigators. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016 Aug 2;316(5):509-18. doi: 10.1001/jama.2016.10485. |
| 34752520 | Result | Smith SE, Newsome AS, Tackett RL. Prescribing of Pressor Agents in Septic Shock: A Survey of Critical Care Pharmacists. J Pharm Technol. 2019 Oct;35(5):187-193. doi: 10.1177/8755122519846164. Epub 2019 May 8. |
| 26903338 | Result | Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. |
| 19926252 | Result | Bauer SR, Aloi JJ, Ahrens CL, Yeh JY, Culver DA, Reddy AJ. Discontinuation of vasopressin before norepinephrine increases the incidence of hypotension in patients recovering from septic shock: a retrospective cohort study. J Crit Care. 2010 Jun;25(2):362.e7-362.e11. doi: 10.1016/j.jcrc.2009.10.005. |
| 28618919 | Result | Hammond DA, McCain K, Painter JT, Clem OA, Cullen J, Brotherton AL, Chopra D, Meena N. Discontinuation of Vasopressin Before Norepinephrine in the Recovery Phase of Septic Shock. J Intensive Care Med. 2019 Oct;34(10):805-810. doi: 10.1177/0885066617714209. Epub 2017 Jun 15. |
| 28750598 | Result | Bissell BD, Magee C, Moran P, Bastin MLT, Flannery AH. Hemodynamic Instability Secondary to Vasopressin Withdrawal in Septic Shock. J Intensive Care Med. 2019 Sep;34(9):761-765. doi: 10.1177/0885066617716396. Epub 2017 Jul 28. |
| 29328496 | Result | Sacha GL, Lam SW, Duggal A, Torbic H, Reddy AJ, Bauer SR. Hypotension Risk Based on Vasoactive Agent Discontinuation Order in Patients in the Recovery Phase of Septic Shock. Pharmacotherapy. 2018 Mar;38(3):319-326. doi: 10.1002/phar.2082. Epub 2018 Feb 8. |
| 29784057 | Result | Jeon K, Song JU, Chung CR, Yang JH, Suh GY. Incidence of hypotension according to the discontinuation order of vasopressors in the management of septic shock: a prospective randomized trial (DOVSS). Crit Care. 2018 May 21;22(1):131. doi: 10.1186/s13054-018-2034-9. |
| 31983763 | Result | Bredhold BE, Winters SD, Callison JC Jr, Heidel RE, Allen LM, Hamilton LA. Impact of the Sequence of Norepinephrine and Vasopressin Discontinuation in Patients Recovering From Septic Shock. Hosp Pharm. 2020 Feb;55(1):26-31. doi: 10.1177/0018578718817469. Epub 2018 Dec 5. |
| 33977793 | Result | Taylor A, Jones T, Forehand CC, Smith SE, Dykes H, Newsome AS. Vasopressor Discontinuation Order in Septic Shock With Reduced Left Ventricular Function. J Pharm Pract. 2022 Dec;35(6):879-885. doi: 10.1177/08971900211015080. Epub 2021 May 12. |
| 34404892 | Result | Song X, Liu X, Evans KD, Frank RD, Barreto EF, Dong Y, Liu C, Gao X, Wang C, Kashani KB. The order of vasopressor discontinuation and incidence of hypotension: a retrospective cohort analysis. Sci Rep. 2021 Aug 17;11(1):16680. doi: 10.1038/s41598-021-96322-7. |
| 39890531 | Derived | Mallmann C, Galiotto TMB, de Oliveira MS, Moraes RB. Reduction of norepinephrine versus vasopressin in the stabilization phase of septic shock: RENOVA clinical trial. Med Intensiva (Engl Ed). 2025 Oct;49(10):502147. doi: 10.1016/j.medine.2025.502147. Epub 2025 Jan 30. |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D010900 | Pituitary Diseases |
| D004700 | Endocrine System Diseases |
| D000588 |
| Amines |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |