Septic Shock
Conditions
Keywords
vasopressin, septic shock, vasopressor weaning
Brief summary
In this study, we aim to evaluate the incidence of hypotension during vasopressin weaning by comparing two methods - titrated reduction versus abrupt withdrawal - through the conduct of a randomized clinical trial.
Detailed description
Catecholamine infusions are usually tapered gradually in a titrated manner. However, little is known about how to manage adjunctive therapies such as vasopressin. While catecholamines have a short half-life (2-3 minutes), vasopressin's half-life ranges from 10 to 20 minutes. Although endogenous vasopressin levels are depleted in the early phase of shock, they are restored during recovery. Given its pharmacokinetic profile and the endogenous dynamics across different phases of shock, the optimal approach to vasopressin withdrawal - whether titrated or abrupt - remains unclear. In 2021, a study was published comparing abrupt versus gradual vasopressin discontinuation. This was a retrospective observational study including 1,318 patients. Using ICU length of stay as the primary outcome, no significant difference was observed between groups (abrupt discontinuation: 7.9 days; gradual discontinuation: 7.3 days; p = 0.6). Similarly, there was no difference in the incidence of clinically significant hypotension (abrupt: 39.7%; gradual: 41.7%; p = 0.53). However, when stratifying patients based on whether catecholamine infusions were still ongoing at the time of vasopressin discontinuation, the results reversed in terms of ICU stay (abrupt: 9.2 days; gradual: 7.6 days), although this difference was not statistically significant (p = 0.24). In 2023, another retrospective observational study was published comparing abrupt versus gradual vasopressin withdrawal, including 74 patients. No difference was found in the incidence of clinically significant hypotension (abrupt: 57.1%; gradual: 52.3%; p = 0.68), nor in ICU length of stay. It is important to note, however, that in this cohort only patients who had already discontinued catecholamines prior to vasopressin withdrawal were included.
Interventions
OTHERTitrated weaning of vasopressin.
The titrated group will follow the vasopressin weaning protocol used in the DOVSS study (reduction of 0.01 U/min per hour).
OTHERAbrupt weaning of vasopressin.
The abrupt group will discontinue the vasopressin infusion at the time of randomization, without dose titration.
Sponsors
Hospital Nossa Senhora da Conceicao
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age over 18 years * Admitted to the Intensive Care Unit * Patients with vasopressor dependent sepsis * Receiving combined norepinephrine and vasopressin therapy
Exclusion criteria
* Withdrawal/reduction of vasopressin related to a plan of treatment limitation or palliative care * Withdrawal/reduction of vasopressin associated with the initiation of adrenaline or any other vasopressor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hypotension within the first 24 hours | 24 hours | Incidence of hypotension with clinical repercussions within the first 24 hours after titrated reduction or abrupt withdrawal of vasopressin. Definition of hypotension with clinical repercussions: mean arterial pressure \< 60 mmHg, leading to: * administration of crystalloid/colloid bolus and/or * increase in norepinephrine dose and/or * reinitiation or increase in vasopressin dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hypotension within the first hour | First hour | Incidence of hypotension with clinical repercussions within the first hour after titrated reduction or abrupt withdrawal of vasopressin. Definition of hypotension with clinical repercussions: mean arterial pressure \< 60 mmHg, leading to: * administration of crystalloid/colloid bolus and/or * increase in norepinephrine dose and/or * reinitiation or increase in vasopressin dose. |
| Vasopressor-free days | 7 days | Number of days a patient is alive and free of vasopressor between randomization and day 7. Non-survivors will be considered to have zero vasopressor-free days. |
| Vasopressin-free days | 7 days | Number of days a patient is alive and free of vasopressin between randomization and day 7. Non-survivors will be considered to have zero vasopressin-free days. |
| Renal replacement therapy | 7 days | Initiation of hemodialysis between randomization and day 7, excluding chronic dialysis patients. |
| Hypotension stratified according to vasopressin duration | 24 hours | Incidence of hypotension with clinical repercussions within the first 24 hours after titrated reduction or abrupt withdrawal of vasopressin, stratified according to vasopressin duration: \< 48 hours ≥ 48 hours Definition of hypotension with clinical repercussions: mean arterial pressure \< 60 mmHg, leading to: * administration of crystalloid/colloid bolus and/or * increase in norepinephrine dose and/or * reinitiation or increase in vasopressin dose. |
| ICU-free days | 28 days | Number of days a patient is alive and outside the ICU between randomization and day 28. Non-survivors will be considered to have zero ICU-free days. |
| Ischemic events | 28 days | Occurrence of mesenteric ischemia, ischemic stroke, digital ischemia and acute coronary syndrome between randomization and day 28. |
| All-cause mortality | 28 days | All-cause mortality within 28 days after randomization. |
| Cardiac arrhythmias | 7 days | Incidence of arrhythmias with hemodynamic consequences between randomization and day 7, defined as hemodynamic deterioration requiring electrical or chemical cardioversion. |
Countries
Brazil
Contacts
Primary ContactWagner Luis Nedel, Critical Care Physician, PhD
Backup ContactRafael Barberena Moraes, Critical Care Physician, PhD
Outcome results
None listed