Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial

Permpikul, Chairat; Tongyoo, Surat; Viarasilpa, Tanuwong; Trainarongsakul, Thavinee; Chakorn, Tipa; Udompanturak, Suthipol

doi:10.1164/rccm.201806-1034oc

Cited by 231 publications

(204 citation statements)

References 21 publications

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“…Notwithstanding, the optimal starting point for vasopressor administration remains controversial. The persistence of arterial hypotension has detrimental effects on outcomes and some studies suggest the advantages of early administration of vasopressors [38,39], while others found an association between early administration and mortality [40,41].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of resuscitation, and association between use of dynamic tests of fluid responsiveness and outcomes in septic patients: results of a multicenter prospective cohort study in Argentina

Dubin

Loudet

Edul

et al. 2020

Ann. Intensive Care

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Background: Resuscitation of septic patients regarding goals, monitoring aspects and therapy is highly variable. Our aim was to characterize cardiovascular and fluid management of sepsis in Argentina, a low and middle-income country (LMIC). Furthermore, we sought to test whether the utilization of dynamic tests of fluid responsiveness, as a guide for fluid therapy after initial resuscitation in patients with persistent or recurrent hypoperfusion, was associated with decreased mortality.Methods: Secondary analysis of a national, multicenter prospective cohort study (n = 787) fulfilling Sepsis-3 definitions. Epidemiological characteristics, hemodynamic management data, type of fluids and vasopressors administered, physiological variables denoting hypoperfusion, use of tests of fluid responsiveness, and outcomes, were registered. Independent predictors of mortality were identified with logistic regression analysis.Results: Initially, 584 of 787 patients (74%) had mean arterial pressure (MAP) < 65 mm Hg and/or signs of hypoperfusion and received 30 mL/kg of fluids, mostly normal saline (53%) and Ringer lactate (35%). Vasopressors and/ or inotropes were administered in 514 (65%) patients, mainly norepinephrine (100%) and dobutamine (9%); in 22%, vasopressors were administered before ending the fluid load. After this, 413 patients (53%) presented persisting or recurrent hypotension and/or hypoperfusion, which prompted administration of additional fluid, based on: lactate levels (66%), urine output (62%), heart rate (54%), central venous O 2 saturation (39%), central venous-arterial PCO 2 difference (38%), MAP (31%), dynamic tests of fluid responsiveness (30%), capillary-refill time (28%), mottling (26%), central venous pressure (24%), cardiac index (13%) and/or pulmonary wedge pressure (3%). Independent predictors of mortality were SOFA and Charlson scores, lactate, requirement of mechanical ventilation, and utilization of dynamic tests of fluid responsiveness. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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Section: Discussionmentioning

confidence: 99%

Characteristics of resuscitation, and association between use of dynamic tests of fluid responsiveness and outcomes in septic patients: results of a multicenter prospective cohort study in Argentina

Dubin

Loudet

Edul

et al. 2020

Ann. Intensive Care

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“…Very early-VPs (n = 93) Delayed-VPs (n = 93) p APACHE II acute physiology and chronic health evaluation, SOFA sequential organ failure assessment, CHF cardiac heart failure, ESRF end-stage renal failure, COPD chronic obstructive pulmonary disease, VP vasopressor, VPs vasopressor start, FRLoad first fluid load with resuscitative intention, SAP systolic arterial pressure, DAP diastolic arterial pressure, MAP mean arterial pressure, HR heart rate, PP pulse pressure, DSI diastolic shock index (HR to DAP ratio), BE base excess, SvO 2 oxygen venous saturation, Pv-aCO 2 venous-to-arterial carbon dioxide difference, PvaCO 2 /Da-vO 2 ratio venous-arterial carbon dioxide to arterial-venous oxygen differences ratio, CVP central venous pressure, LOS-ICU intensive care unit -length of stay, LOS-Hospital hospital -length of stay, RRT renal replacement therapy *Including only patients receiving renal replacement therapy at least for one session intervals, which prevents establishing precisely the number of minutes spent in hypotension in each group. A recent randomized trial addressed the issue about the early introduction of norepinephrine in patients with septic shock [36]. Nevertheless, very low and non-titrated doses of norepinephrine were used while the idea of administering a fixed dose of fluids before to start of the "non-blinded" vasopressor support was maintained.…”

Section: Allmentioning

confidence: 99%

“…Finally, delays in correcting hypotension are associated with increased risk of death in septic patients [33][34][35], whereby prompt correction of hypotension might influence clinical outcomes. Indeed, a recent phase II randomized controlled trial suggested that early use of norepinephrine might improve the possibility to achieve more sustained mean arterial pressure levels and adequate tissue perfusion parameters [36]. However, this trial was limited by a specificity of the protocol requesting administration of a fixed dose of vasopressors in the early group, which is not the usual way of administering vasopressors.…”

Section: Introductionmentioning

confidence: 99%

Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis

et al. 2020

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Background: Optimal timing for the start of vasopressors (VP) in septic shock has not been widely studied since it is assumed that fluids must be administered in advance. We sought to evaluate whether a very early start of VP, even without completing the initial fluid loading, might impact clinical outcomes in septic shock.Methods: A total of 337 patients with sepsis requiring VP support for at least 6 h were initially selected from a prospectively collected database in a 90-bed mixed-ICU during a 24-month period. They were classified into veryearly (VE-VPs) or delayed vasopressor start (D-VPs) categories according to whether norepinephrine was initiated or not within/before the next hour of the first resuscitative fluid load. Then, VE-VPs (n = 93) patients were 1:1 propensity matched to D-VPs (n = 93) based on age; source of admission (emergency room, general wards, intensive care unit); chronic and acute comorbidities; and lactate, heart rate, systolic, and diastolic pressure at vasopressor start. A riskadjusted Cox proportional hazard model was fitted to assess the association between VE-VPs and day 28 mortality. Finally, a sensitivity analysis was performed also including those patients requiring VP support for less than 6 h. Results: Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (0[0-510] vs. 1500[650-2300] mL, p < 0.001) and during the first 8 h of resuscitation (1100[500-1900] vs. 2600[1600-3800] mL, p < 0.001), with no significant increase in acute renal failure and/or renal replacement therapy requirements. VE-VPs was related with significant lower net fluid balances 8 and 24 h after VPs. VE-VPs was also associated with a significant reduction in the risk of death compared to D-VPs (HR 0.31, CI95% 0.17-0.57, p < 0.001) at day 28. Such association was maintained after including patients receiving vasopressors for < 6 h. Conclusion: A very early start of vasopressor support seems to be safe, might limit the amount of fluids to resuscitate septic shock, and could lead to better clinical outcomes.

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“…Very early continuous infusion of norepinephrine seems to be bene cial in septic shock and leads to shortened ICU stay and earlier restoration of circulation [12][13][14]. If continuous norepinephrine infusion is restricted to ICU settings, delays in shock therapy are probably inevitable.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Outcome and Characteristics of Critical Care for Non-Trauma Patients in the Emergency Department

Kreß

Rüppel

Haake

et al. 2020

Preprint

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Background: Emergency medical care for critically ill patients varies between different emergency departments (ED) and health care systems, while resuscitation of trauma patients is always performed within the ED. In many ED critically ill patients are treated and stabilized while in many German ED they are transferred to intensive care units (ICU) without performing of critical care measures in the ED. Against this background we conducted this retrospective analysis of prospectively collected critically ill patients treated with an ED critical care concept in a 754-bed teaching hospital. Methods: The collective of prospectively collected critically ill patients (October 1st 2018 to March 31st 2019) was analysed after ethical approval. Patient characteristics, performed critical care measures, short-term outcomes and the comparison of admission characteristics between survivors and non-survivors were evaluated. Additionally the accordance of ED diagnoses and discharge diagnoses were analysed.Results: Overall 243/19,854 patients (1.22%) were treated within the resuscitation room. After exclusion of trauma patients, 193 critically ill patients were included. Overall mortality was 29% (n=56), 24-hour mortality was 13% (n=25). Patient characteristics (vital signs, blood gas analysis) differed significantly between survivors and non-survivors except for respiratory rate and pain scale. Conducted critical care measures (number ± standard deviation; e.g. endotracheal intubation, arterial-line): 4.06±1.73 (survivors) and 4.70±2.0 (non-survivors) p=0.0453. The length of ED stay was 148.2±202.7 min. Admission diagnoses matched with hospital discharge diagnoses in 73.7%.Conclusions: Critical care stabilisation of non-trauma patients was feasible in routine care. The observed mortality was high and non-survivors showed significantly more impaired vital parameters and blood gas analysis parameters. Vital parameters together with blood gas analysis enable ED risk stratification of CIP. Although a first diagnostic workup was performed within the ED, admission and discharge diagnoses matched only in 73.7%. However, stabilisation and diagnostic workup of CIP enables optimal allocation to specialized ICUs. Future (randomised) trials have to evaluate of resuscitation room stabilisation for non-trauma patients is beneficial in contrast to direct ICU admission. Trial registration: The study was registered retrospectively in the Clinical Trials Centre of the RWTH Aachen University (Germany), registration number CTC-A 20-131.

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Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial

Cited by 231 publications

References 21 publications

Characteristics of resuscitation, and association between use of dynamic tests of fluid responsiveness and outcomes in septic patients: results of a multicenter prospective cohort study in Argentina

Characteristics of resuscitation, and association between use of dynamic tests of fluid responsiveness and outcomes in septic patients: results of a multicenter prospective cohort study in Argentina

Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis

Short-Term Outcome and Characteristics of Critical Care for Non-Trauma Patients in the Emergency Department

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