ArticleCritical care (London, England)2021
Norepinephrine potentiates the efficacy of volume expansion on mean systemic pressure in septic shock.
Article in Critical care (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07481097 (Hemodynamic Resuscitation Guided by Non-Invasive Mean Systemic Filling Pressure to Prevent Acute Kidney Injury in Septic Shock), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Hemodynamic Resuscitation Guided by Non-Invasive Mean Systemic Filling Pressure to Prevent Acute Kidney Injury in Septic Shock: A Randomized Controlled Trial Integrating Renal Doppler Indices
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Early norepinephrine for patients with septic shock: an updated systematic review and meta-analysis with trial sequential analysis.Critical care (London, England) · 2025Pooled it
- Morphological changes in the arterial pressure waveform following hemodynamic therapies in critical care: A clinical proof-of-concept study in older adults.Physiological reports · 2026Observational
- The usual suspects: a pragmatic framework to identify and address reversible contributors in apparent refractory septic shock.Critical care (London, England) · 2026Review
- Current and future strategies aiming at reducing catecholamine exposure in septic shock.Critical care (London, England) · 2026Review
- Mechanism of paraventricular nucleus HPhysiological reports · 2026Article
- Pulse Waveform Changes During Vasopressor Therapy Assessed Using Remote Photoplethysmography: A Case Series.Journal of clinical medicine · 2026Article
- ESICM 2025 haemodynamic recommendations: a remarkable achievement and raising questions.Intensive care medicine · 2026Article
- The time course of fluid responsiveness.Annals of intensive care · 2026Review
- Unnecessary fluid therapy in patients with shock: Five classic fluid pitfalls and five ways to do it better.Annals of intensive care · 2026Review
- Review
- Vasopressin and its analogues in patients with septic shock: holy Grail or unfulfilled promise?Critical care (London, England) · 2025Review
- Real-time changes in pulse pressure during a 10-second end-expiratory occlusion test reliably detect preload responsiveness.Critical care (London, England) · 2025Article
- Right ventricle and venous system: bridging physiology and clinical practice. A narrative review.Critical care science · 2025Review
- Pediatric fluid resuscitation: an oxymoron?Frontiers in pediatrics · 2025Article
- Fluid accumulation syndrome in sepsis and septic shock: pathophysiology, relevance and treatment-a comprehensive review.Annals of intensive care · 2024Review
- Candent issues in pneumonia. Reflections from the Fifth Annual Meeting of Spanish Experts 2023.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2024Review
- Evidence for a personalized early start of norepinephrine in septic shock.Critical care (London, England) · 2023Article
- The Eight Unanswered and Answered Questions about the Use of Vasopressors in Septic Shock.Journal of clinical medicine · 2023Review
- Fluids and Early Vasopressors in the Management of Septic Shock: Do We Have the Right Answers Yet?Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures) · 2023Review
- How I personalize fluid therapy in septic shock?Critical care (London, England) · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThrough venous contraction, norepinephrine (NE) increases stressed blood volume and mean systemic pressure (Pms) and exerts a "fluid-like" effect. When both fluid and NE are administered, Pms may not only result from the sum of the effects of both drugs. Indeed, norepinephrine may enhance the effects of volume expansion: because fluid dilutes into a more constricted, smaller, venous network, fluid may increase Pms to a larger extent at a higher than at a lower dose of NE. We tested this hypothesis, by mimicking the effects of fluid by passive leg raising (PLR).
methodsIn 30 septic shock patients, norepinephrine was decreased to reach a predefined target of mean arterial pressure (65-70 mmHg by default, 80-85 mmHg in previously hypertensive patients). We measured the PLR-induced increase in Pms (heart-lung interactions method) under high and low doses of norepinephrine. Preload responsiveness was defined by a PLR-induced increase in cardiac index ≥ 10%.
resultsNorepinephrine was decreased from 0.32 [0.18-0.62] to 0.26 [0.13-0.50] µg/kg/min (p < 0.0001). This significantly decreased the mean arterial pressure by 10 [7-20]% and Pms by 9 [4-19]%. The increase in Pms (∆Pms) induced by PLR was 13 [9-19]% at the higher dose of norepinephrine and 11 [6-16]% at the lower dose (p < 0.0001). Pms reached during PLR at the high dose of NE was higher than expected by the sum of Pms at baseline at low dose, ∆Pms induced by changing the norepinephrine dose and ∆Pms induced by PLR at low dose of NE (35.6 [11.2] mmHg vs. 33.6 [10.9] mmHg, respectively, p < 0.01). The number of preload responders was 8 (27%) at the high dose of NE and 15 (50%) at the low dose.
conclusionsNorepinephrine enhances the Pms increase induced by PLR. These results suggest that a bolus of fluid of the same volume has a greater haemodynamic effect at a high dose than at a low dose of norepinephrine during septic shock.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.