Early Multimodal Vasopressors—Are We Ready for It?*

Wieruszewski, Patrick M.; Khanna, Ashish K.

doi:10.1097/ccm.0000000000005344

Cited by 6 publications

(5 citation statements)

References 16 publications

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“…Norepinephrine is the first-choice [2], but high doses increase the risk of adverse effects such as tachyarrhythmia, myocardial dysfunction, peripheral ischemia, and even immunosuppression [5,6]. Therefore, a combination of agents targeting different systems involved in blood pressure regulation and endothelial function has been recently proposed [7][8][9]. This "multimodal strategy" could help to restore tissue perfusion while decreasing the potential toxicity of single agents [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Based on large datasets, it is increasingly recognized that a higher exposure to catecholamine vasopressors is associated with an increased risk of multiple organ failure and death in septic shock [8,16,17]; thus, the time of norepinephrine requirement is a justified intermediate patient-centered outcome [18] in order to pave the way for adding catecholamine-sparing agents to a multimodal strategy [7,19]. We designed this RCT to assess if early adjunctive MB administration could reduce the time to vasopressor discontinuation in patients with septic shock, as compared to placebo.…”

Section: Introductionmentioning

confidence: 99%

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Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial

et al. 2023

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Purpose Methylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its’ optimal timing, dosing and safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock. Methods In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days. Results Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59–83] vs 94 h [IQR 74–141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration. Conclusion In patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials. Trial registration ClinicalTrials.gov registration number NCT04446871, June 25, 2020, retrospectively registered.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial

et al. 2023

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“…Several models have been proposed to describe the interaction between argipressin and anti-inflammatory cytokine expression (13)(14)(15)(16)(17)(18)(19), which is suggestive of the immunomodulatory properties of argipressin (13). Patients with septic shock have reduced argipressin activity, and exogenous administration of argipressin can restore vascular tone and blood pressure, reducing the need for catecholamines (20)(21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Argipressin-norepinephrine association in the treatment of septic shock: the use of the polydistrectual resistance index as an assessment of vascular compliance

Barile,

Mazzotta,

Izzi

et al. 2023

Front. Anesthesiol.

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IntroductionThe hemodynamic management of septic patients involves initial fluid therapy, followed by the use of vasoconstrictors in case of treatment failure. The latest Surviving Sepsis Campaign guidelines suggest the synergistic use of argipressin in addition to norepinephrine when hemodynamic optimization is not achieved with norepinephrine alone.MethodsIn our single-center retrospective observational study, the primary endpoint is the safety of initial norepinephrine-argipressin association treatment, assessed through a reduction in Resistance Index. Our secondary endpoint includes the efficacy of this combination, measured by an increase in Mean Arterial Pressure and a reduction in Resistance Index as an indicator of organ perfusion. The Resistance Index (RI) is evaluated through Power Doppler ultrasound. RI is crucial for assessing multi-district vascular tone and multiorgan perfusion. Patients were categorized into three groups based on their treatment. In Group 1, we analyzed patients treated with norepinephrine alone in incremental doses; in Group 2, we analyzed patients receiving the initial norepinephrine-argipressin association treatment (norepinephrine 0.05 mcg/kg/min-argipressin 0.03 IU/min); in the third group (Group 3), we analyzed patients given argipressin (0.03 IU/min) after norepinephrine (<0.10–0.25≥ mcg/kg/min) to stabilize their hemodynamics (MAP > 65 mmHg). RI measurements were taken in the Renal Artery (ARE), Radial Artery (AR), Central Retinal Artery (CRA), and Superior Mesenteric Artery (AMS) at four different time points: T0 before vasopressor therapy, T1 at 1 h, T2 at 24 h, and T3 at 48 h after vasopressor infusion.ResultsA total of 48 patients were divided into three groups: 17 patients in Group 1, 16 in Group 2, and 15 in Group 3. In Group 1, an increase in Mean Arterial Pressure (MAP) was observed, but there was an increase in RIs in the right CRI and left ARE. In Group 2, there was an improvement in MAP and a reduction in RIs in the right/left CRI, left ARE, AMS, and right AR. In Group 3, there was an increase in MAP and a reduction in RIs in the right/left CRI, left ARE, AMS, and right AR.ConclusionEarly norepinephrine-argipressin association treatment appears to be a valid strategy for hemodynamic optimization in this patient population.

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“…[16][17][18][19] Until further elucidated, clinicians may consider an early, multimodal approach to vasopressor selection in septic shock. 20 Our study serves to add to the literature regarding vasopressor optimization, specifically that early vasopressin therapy may be beneficial in reducing the need for RRT, ICU LOS, NOA, and mortality. We hope our article further calls attention to the fact that there is much to be learned regarding the optimal approach to vasopressor therapy and how that approach impacts clinical outcomes.…”

mentioning

confidence: 96%

“…16-19 Until further elucidated, clinicians may consider an early, multimodal approach to vasopressor selection in septic shock. 20…”

mentioning

confidence: 99%

Comment: Does Early Vasopressin in Septic Shock Improve Outcomes? An Important Piece to This Emerging Puzzle Has Arrived

McCloskey¹,

Gibson²,

Pope³

et al. 2023

Ann Pharmacother

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Early Multimodal Vasopressors—Are We Ready for It?*

Abstract: Institute: Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders.

Cited by 6 publications

References 16 publications

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial

Argipressin-norepinephrine association in the treatment of septic shock: the use of the polydistrectual resistance index as an assessment of vascular compliance

Comment: Does Early Vasopressin in Septic Shock Improve Outcomes? An Important Piece to This Emerging Puzzle Has Arrived

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