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Principles of vasopressor treatment. MAP-mean arterial pressure; ScVO 2 -central venous oxygen saturation; pCO 2 Gap-difference between partial pressure of CO 2 in venous blood and arterial blood; SVV-stroke volume variation; PPV-pulse pressure variation.
Source publication
Despite the abundant literature on vasopressor therapy, few studies have focused on vasopressor-sparing strategies in patients with shock. We performed a scoping-review of the published studies evaluating vasopressor-sparing strategies by analyzing the results from randomized controlled trials conducted in patients with shock, with a focus on vasop...
Contexts in source publication
Context 1
... administration is part of the continuum from initial resuscitation to shock reversal. As for fluid therapy, the management of vasopressors can be divided into several phases: an initial resuscitation phase with the objective of obtaining the target blood pressure to restore tissue perfusion as quickly as possible, a stabilization phase, and a weaning phase (Figure 2). When the patient is stabilized, active management, including pharmacological therapies and hemodynamic strategies, may be introduced to decrease the time to vasopressor discontinuation. ...
Context 2
... stability can be defined as a blood pressure variation of less than 10% without changing the vasopressor dose, and with an improvement in tissue perfusion (capillary refill time, hyperlactatemia, diuresis, and venous oxygen saturation) [7]. When blood pressure is controlled, the cardiac and vascular properties are gradually restored and the withdrawal of vasopressor drugs can be initiated (Figure 2). As the pathological process may not be symmetrical during acute circulatory failure and recovery, and as catecholamine administration leads to the down-regulation of adrenergic receptors [30], it is unlikely that vasopressor withdrawal is a parallel process to the initial resuscitation phase. ...
Context 3
... administration is part of the continuum from initial resuscitation to shock reversal. As for fluid therapy, the management of vasopressors can be divided into several phases: an initial resuscitation phase with the objective of obtaining the target blood pressure to restore tissue perfusion as quickly as possible, a stabilization phase, and a weaning phase (Figure 2). When the patient is stabilized, active management, including pharmacological therapies and hemodynamic strategies, may be introduced to decrease the time to vasopressor discontinuation. ...
Context 4
... stability can be defined as a blood pressure variation of less than 10% without changing the vasopressor dose, and with an improvement in tissue perfusion (capillary refill time, hyperlactatemia, diuresis, and venous oxygen saturation) [7]. When blood pressure is controlled, the cardiac and vascular properties are gradually restored and the withdrawal of vasopressor drugs can be initiated (Figure 2). As the pathological process may not be symmetrical during acute circulatory failure and recovery, and as catecholamine administration leads to the down-regulation of adrenergic receptors [30], it is unlikely that vasopressor withdrawal is a parallel process to the initial resuscitation phase. ...
Context 5
... the pathological process may not be symmetrical during acute circulatory failure and recovery, and as catecholamine administration leads to the down-regulation of adrenergic receptors [30], it is unlikely that vasopressor withdrawal is a parallel process to the initial resuscitation phase. Optimization and weaning should be part of a protocolized process (Figure 2). Firstly, a blood pressure target aiming to optimize organ perfusion should be defined by taking into account that a lower blood pressure objective may be possible. ...
Context 6
... recent study published in the JAMA showed that the use of this index with a therapeutic management decision algorithm reduces hypotension time [146]. Figure 2. Principles of vasopressor treatment. ...
Context 7
... and weaning should be part of a protocolized process (Figure 2 Firstly, a blood pressure target aiming to optimize organ perfusion should be defined b taking into account that a lower blood pressure objective may be possible. Secondly, phy sicians should consider the early use of intravenous hydrocortisone, non-catecholamine gic vasopressors (vasopressin and blue methylene), and maintaining normothermia. ...
Citations
... The usual procedure for weaning from vasopressor agents is based on hemodynamic, clinical (skin perfusion, mottling, hourly diuresis), and biological (SVO 2 , pCO 2 gap, arterial lactates) parameters (18). Weaning criteria are stability of MAP for more than one hour defined by a variation of less than 10%, without worsening of tissue hypoperfusion markers (19). If there is open-label norepinephrine treatment, this treatment is weaned first. ...
for the NOVACC study group, Prospective randomized double-blind study to evaluate the superiority of Vasopressin versus Norepinephrine in the management of the patient at renal risk undergoing cardiac surgery with cardiopulmonary bypass (NOVACC trial), Abstract Background: Cardiac surgery-associated acute kidney injury (CS-AKI) affects up to 30% of patients, increasing morbidity and healthcare costs. This
... En l'absence d'étude randomisée évaluant la noradrénaline par rapport à un placebo ou dans le contexte de l'optimisation de la pression artérielle, nous ne pouvons pas conclure à un effet causal entre l'exposition à la noradrénaline et les résultats postopératoires. Nos résultats fournissent des données qui peuvent aider les médecins à concevoir d'autres études axées sur le type de vasopresseur, les objectifs hémodynamique, la gestion de l'exposition à la noradrénaline [29], les stratégies d'économie de vasopresseurs [30], et leur impact sur les résultats [31]. Parce que nous avons identifié plusieurs facteurs de risque d'utilisation de la noradrénaline, les médecins sont en mesure de sélectionner une population à haut risque de complications postopératoires pour laquelle un ensemble stratégies périopératoires peut être cliniquement pertinent pour améliorer le pronostic [32,33]. ...
pidémiologie, facteurs et complications associée à l'utilisation de noradrénaline en chirurgie cardiaque avec circulation extracorporelle : une étude observationnelle française multicentrique et prospective § ANREA-801 § En raison de son intérêt pour les lecteurs de la revue nous republions ici en français cet article paru dans ACCPM sous la référence : Guinot PG, Durand B, Besnier E, Mertes PM, Bernard C, Nguyen M, et al. Epidemiology, risk factors and outcomes of norepinephrine use in cardiac surgery with cardiopulmonary bypass: a multicentric prospective study. Anaesth Crit Care
... Nevertheless, not all the patients show the same cardiovascular response to NE infusion: the blood pressure constantly increases, whereas cardiac output (CO) might not increase in some patients [2]. Because of this reason, restoring blood pressure with NE infusion may not always be associated with an improvement of tissue perfusion [3]. ...
Background
Norepinephrine is a commonly used drug for treating vasoplegic acute circulatory failure in ICU. The prediction of norepinephrine macro- and micro-circulatory response is complicated by its uneven receptors’ distribution between the arterial and the venous structures, and by the presence of a physiological vascular waterfall (VW) that disconnects the arterial and the venous circulation in two pressure systems. The objectives of this study were to describe the VW in patients with arterial hypotension due to vasodilatory circulatory shock, and its behavior according to its response to norepinephrine infusion.
Methods
A prospective, observational, bi-centric study has included adult patients, for whom the physician decided to initiate norepinephrine during the six first hours following admission to the ICU after cardiac surgery, and unresponsive to a fluid challenge. The mean systemic pressure (MSP) and the critical closing pressure (CCP) were measured at inclusion and after norepinephrine infusion.
Results
Thirty patients were included. Norepinephrine increased arterial pressure and total peripheral resistances in all cohort. The cohort was dichotomized as VW responders (patients with a change of VW over the least significant change (≥ 93% increase in VW)), and as VW non-responders. In 19 (63%) of the 30 patients, VW increased from 3.47 [− 14.43;7.71] mmHg to 43.6 [25.8;48.1] mmHg, p < 0.001) with norepinephrine infusion, being classified as VW responders. The VW responders improved cardiac index (from 1.8 (0.6) L min ⁻¹ m ⁻² to 2.2 (0.5) L min ⁻¹ m ⁻² , p = 0.002), capillary refill time (from to 4.2 (1.1) s to 3.1 (1) s, p = 0.006), and pCO 2 gap (from 9 [7;10] mmHg to 6 [4;8] mmHg, p = 0.04). No baseline parameters were able to predict the VW response to norepinephrine. In comparison, VW non-responders did not significantly change the VW (from 5 [-5;16] mmHg to -2 [-12;15] mmHg, p = 0.17), cardiac index (from 1.6 (0.3) L min ⁻¹ m ⁻² to 1.8 (0.4) L min ⁻¹ m ⁻² , p = 0.09) and capillary refill time (from 4.1 (1) s to 3.7 (1.4), p = 0.44).
Conclusions
In post-cardiac surgery patients with vasoplegic arterial hypotension, the vascular waterfall is low. Norepinephrine did not systematically restore the vascular waterfall. Increase of the vascular waterfall was associated with an improvement of laboratory and clinical parameters of tissue perfusion.
... Thus, during recovery from peripheral hypoperfusion, an increase in fluid requirement may occur because of blood redistribution. Indeed, fluid loading has been suggested as one of the basic managements for hypotension that occurs when decreasing the noradrenaline dose 45 . Second, when abnormal PP with prolonged CRT and mottled skin is present, hypoperfusion of the gastrointestinal tract occurs simultaneously 46,47 , which may contribute to increased fluid requirements because of concurrent gastrointestinal ischemia and secondary sepsis. ...
Abnormal peripheral perfusion (PP) worsens the prognosis of patients with septic shock. Polymyxin B-direct hemoperfusion (PMX-DHP) increases blood pressure and reduces vasopressor doses. However, the modification of PP following administration of PMX-DHP in patients with vasopressor-dependent septic shock have not yet been elucidated. A retrospective exploratory observational study was conducted in patients with septic shock treated with PMX-DHP. Pulse-amplitude index (PAI), vasoactive inotropic score (VIS), and cumulative fluid balance data were extracted at PMX-DHP initiation (T0) and after 24 (T24) and 48 (T48) h. Changes in these data were analyzed in all patients and two subgroups (abnormal PP [PAI < 1] and normal PP [PAI ≥ 1]) based on the PAI at PMX-DHP initiation. Overall, 122 patients (abnormal PP group, n = 67; normal PP group, n = 55) were evaluated. Overall and in the abnormal PP group, PAI increased significantly at T24 and T48 compared with that at T0, with a significant decrease in VIS. Cumulative 24-h fluid balance after PMX-DHP initiation was significantly higher in the abnormal PP group. PMX-DHP may be an effective intervention to improve PP in patients with abnormal PP; however, caution should be exercised as fluid requirements may differ from that of patients with normal PP.
... In this way, a recent study in septic shock was unable to demonstrated an association between preload and arterial hypotension following norepinephrine decrease [30]. Because volume depletion can improve ventriculo-arterial coupling, it may improve catecholamines weaning in congestive patients [31]. Our findings might suggest that ventriculo-arterial coupling might be also useful in this setting as monitoring tool of adequate decongestion, contributing to the already known applications in ICU patients [19]. ...
Purpose:
Congestion was shown to hamper organ perfusion, but the exact timing of diuretic initiation during hemodynamic de-escalation in shock is unclear. The aim of this study was to describe the hemodynamic effects of diuretic initiation in the stabilized shock.
Methods:
We performed a monocentric, retrospective analysis, in a cardiovascular medico-surgical ICU. We included consecutive resuscitated adult patients, for whom the clinician decided to introduce loop diuretic treatment for clinical signs of fluid overload. The patients were hemodynamically evaluated at the moment of diuretic introduction and 24 h later.
Results:
Seventy ICU patients were included in this study, with a median duration of ICU stay before diuretic initiation of 2 [1-3] days. 51(73%) patients were classified as congestive (central venous pressure > 12 mmHg). After treatment, the cardiac index increased towards normal values in the congestive group (2.7 ± 0.8 L min- 1 m- 2 from 2.5 ± 0.8 L min- 1 m- 2, p = 0.042), but not in the non-congestive group (2.7 ± 0.7 L min- 1 m- 2 from baseline 2.7 ± 0.8 L min- 1 m- 2, p = 0.968). A decrease in arterial lactate concentrations was observed in the congestive group (2.1 ± 2 mmol L- 1 vs. 1.3 ± 0.6 mmol L- 1, p < 0.001). The diuretic therapy was associated with an improvement of ventriculo-arterial coupling comparing with baseline values in the congestive group (1.69 ± 1 vs. 1.92 ± 1.5, p = 0.03). The norepinephrine use decreased in congestive patients (p = 0.021), but not in the non-congestive group (p = 0.467).
Conclusion:
The initiation of diuretics in ICU congestive patients with stabilized shock was associated with improvement of cardiac index, ventriculo-arterial coupling, and tissue perfusion parameter. These effects were not observed in non-congestive patients.
... The heterogeneity of I 2 is not considered statistically significant if it is not exceeded 50%. The heterogeneity has three degrees of low (25%), medium (50%) and high (75%) classified by Guinot et al. [20]. Substantial heterogeneity was identified as p < 0.05 or I 2 > 50%. ...
Background
To update a meta-analysis of randomized controlled trials (RCTs) and further explore the outcome of IV vitamin C (IVVC) administration in sepsis or septic shock patients.
Methods
This study is a meta-analysis of RCTs. The RCTs of vitamin C therapy in sepsis or septic shock were searched in PubMed, EMBASE and Clinical Trials.gov from inception to January 16, 2023. We registered the protocol with PROSPERO (CRD42022354875). The primary outcome was delta Sequential Organ Failure Assessment (SOFA) score at 72–96 h. Two reviewers independently assessed RCTs according to eligibility criteria: (1) study type: RCT; (2) patient population: patients ≥ 18 years with sepsis or septic shock; (3) intervention: IVVC at any doses as monotherapy or combined with thiamine or and hydrocortisone compared with standard of care, no intervention or placebo (defined as control group); (4) the RCT described short-term mortality or SOFA score. Then, two authors independently extracted related information from RCTs.
Results
Eighteen RCTs ( n = 3364 patients) were identified in this meta-analysis. There were significant effects in the delta SOFA score from baseline to 72–96 h (MD, − 0.62; 95% CI, − 1.00 to − 0.25; p = 0.001) and the duration of vasopressor use (MD, − 15.07; 95% CI, − 21.59 to − 8.55; p < 0.00001) with IVVC therapy. Treatment with IVVC was not shown to improve short-term mortality (OR, 0.89; 95% CI, 0.77 to 1.04; p = 0.14); nevertheless, dose at 25–100 mg/kg/d subgroup associated with a significant reduction in short-term mortality (OR, 0.80; 95% CI, 0.65 to 0.97; p = 0.03). An increase adverse event was observed in IVVC therapy (OR, 1.98; 95% CI, 1.06 to 3.68; p = 0.03).
Conclusion
In this meta-analysis, IVVC in sepsis or septic shock patients significantly improved delta SOFA score and reduced the duration of vasopressor use, whereas it was not associated with reduction in short-term mortality and had higher adverse events.
... 7 Using a sparing effect on a vasopressor patient will reduce the patient's morbidity and length of stay (LOS). 43 Our study showed that administration of Ang-2 could be a sparing effect, thus reducing the dose of vasopressors which could minimize the adverse effect of using them. ...
Background:
Patients with severe vasodilation accompanied by refractory hypotension despite high doses of vasopressors were associated with a high mortality rate. The Ang-2 for the Treatment of High-Output Shock (ATHOS) 3 trial demonstrated that angiotensin 2 (Ang-2) could effectively increase MAP and blood pressure in vasodilatory shock patients. This systematic review aims to summarize the impact of Ang-2 for the treatment of vasodilatory shock on clinical outcomes, including length of stay, MAP level (before and after), and mortality also Ang-2 dose needed.
Methods:
A systematic search in PubMed, Sage, ScienceDirect, Scopus and Gray literature was conducted to obtain studies about the use of Ang-2 in vasodilatory shock patients.
Results:
In all of the studies that we obtained, there were different results regarding mortality in patients with vasodilatory shock with Ang-2. Mortality was significantly lower when Ang-2 was administered to patients with elevated renin. The initial dose of Ang-2 can be started at 10-20 ng/kg/min, but there is no agreement on the maximum dose. Ang-2 may be considered a third-line vasopressor if the targeted MAP has not been achieved after administration of norepinephrine >200 ng/kg/min for more than 6 hours. Although not statistically significant, the use of Ang-2 can reduce the length of stay in the ICU and in the hospital when compared to patients without Ang-2 therapy, in addition to reducing the dose of vasopressor.
Conclusion:
Overall, the use of Ang-2 has potential to be a regimen for patients with vasodilatory shock. Further study is needed to obtain more data.
... The heterogeneity of I 2 is not considered statistically signi cant if it is not exceed 50%. The heterogeneity has three degrees of low (25%), medium (50%), and high (75%) classi ed by Guinot et al [20]. Substantial heterogeneity was identi ed as p < 0.05 or I 2 > 50%. ...
Background: To update a meta-analysis of randomized controlled trials (RCTs) and further explore the outcome of IV vitamin C (IVVC) administration in sepsis or septic shock patients.
Methods: This study is a meta-analysis of RCTs. The RCTs of vitamin C therapy in sepsis were searched in PubMed, EMBASE and Clinical Trials.gov since August 16, 2022. We registered the protocol with PROSPERO (CRD42022354875). The primary outcome was mortality included 28-day, 30-day, or in hospital mortality. Two reviewers independently assessed RCTs according to eligibility criteria: 1) Study type: RCT; 2) patient population: patients ≥18 years with sepsis or septic shock; 3) intervention: IVVC at any doses as monotherapy or combined with thiamine or and hydrocortisone compared with standard of care, no intervention, or placebo (defined as control group) ; 4) the RCT described primary outcome. Then, two authors independently extracted related information from RCTs.
Results: Eighteen RCTs (n=2980 patients) were identified in this meta-analysis. Treatment with IVVC was not shown to improve mortality (odds ratio,0.87; 95% CI, 0.75–1.02; p=0.09; I²=44%) regardless of different dose or type of therapy, whereas there was significant effects in duration of vasopressor use (MD, –15.31; 95% CI, –21.92 to –8.69; p<0.00001; I² =59%) and change in the Sequential Organ Failure Assessment (SOFA) score from baseline to 72–96 hours (MD, –0.64; 95% CI, –1.15 to –0.13; p=0.01; I²=65%), and was relatively safe in sepsis or septic shock patients (OR, 1.22; 95% CI, 0.98–1.51; p=0.08; I²=40%).
Conclusion: In this meta-analysis, IVVC in sepsis or septic shock patients was relatively safe and significantly shorten the duration of vasopressor use and improved the change of SOFA score, whereas it was not associated with reduction in mortality.
... MAP: mean arterial pressure; SAP: systolic arterial pressure; SV: stroke volume; HR: heart rate; CO: cardiac output; Â designates multiplication Continuous monitoring of ventriculo-arterial coupling: A place for dynamic arterial elastance Dynamic arterial elastance (Ea dyn ) is the ratio of respiratory variation of pulse pressure to respiratory variation of SV. 23 Ea dyn can be measured with several haemodynamic monitors (MOSTCARE, PICCO) TM or with cardiac echography. Given that its measure is based on the relationship between SV and pulse pressure, Ea dyn may be an indicator of ventriculo-arterial coupling. ...
As an extension of the traditional heart-centred pressure-flow model, the ventriculo-arterial coupling concept is based on the pressure–volume relationship of the left ventricle and the vascular system. Even though ventriculo-arterial coupling has been studied in cardiology for more than 30 years, its value in clinical practice in anaesthesia and ICU remains poorly known and used.
The clinical interest in ventriculo-arterial coupling is derived from its strong connection with cardiac energetics and efficiency. An alteration of ventriculo-arterial coupling is a marker of disease severity and is associated with outcome. The main categories of cardio-circulatory failures observed in ICU patients commonly exhibit alterations in ventriculo-arterial coupling with typical patterns. Furthermore, the effectiveness of usual haemodynamic treatments and interventions correlates with ventriculo-arterial coupling improvements in ICU patients. Consequently, treatment and management bundles may be proposed to specifically target the correction of ventriculo-arterial uncoupling to optimise the patients’ haemodynamic status and outcome. Restoring ventriculo-arterial coupling with treatments improves outcomes in subgroups of ICU patients.
Even though ventriculo-arterial coupling evaluation cannot be considered as a part of the basic core curriculum of anaesthesiologists and ICU residents, anaesthesia and ICU practitioners must be familiarised with the clinical significance of ventriculo-arterial (un)coupling and availability of its bedside noninvasive evaluation. The understanding of ventriculo-arterial coupling may be particularly important in complex haemodynamic clinical situations.
... Although vasoactive agents have been used and studied for more than six decades, the optimal choice of vasopressor remains uncertain [4][5][6]. Over the years, there have been significant changes in trends in vasoactive medication use [7]. High quality research led to a significant decline in the use of epinephrine, dopamine, and dobutamine as the first-line infusions and a shift towards norepinephrine and vasopressin as the firstand second-line vasoactive agents, respectively [8][9][10][11][12]. ...
Background
Major international guidelines state that norepinephrine should be used as the first-line vasopressor to achieve adequate blood pressure in patients with hypotension or shock. However, recent observational studies report that in the United Kingdom and Australia, metaraminol is often used as second line medication for cardiovascular support.
Aim of the study
The aim of this study was to carry out a systematic review of metaraminol use for management of shock in critically unwell patients and carry out a survey evaluating whether UK critical care units use metaraminol and under which circumstances.
Methods
A systematic review literature search was conducted. A short telephone survey consisting of 6 questions regarding metaraminol use was conducted across 30 UK critical care units which included a mix of tertiary and district general intensive care units.
Results
Twenty-six of thirty contacted centres responded to our survey. Metaraminol was used in 88% of them in various settings and circumstances (emergency department, theatres, medical emergencies on medical wards), with 67% reporting use of metaraminol infusions in the critical care setting. The systematic literature review revealed several case reports and only two studies conducted in the last 20 years investigating the effect of metaraminol as a stand-alone vasopressor. Both studies focused on different aspects of metaraminol use and the data was incomparable, hence we decided not to perform a meta-analysis.
Conclusions
Metaraminol is widely used as a vasopressor inside and outside of the critical care setting in the UK despite limited evidence supporting its safety and efficacy for treating shock. Further service evaluation, observational studies and prospective randomised controlled trials are warranted to validate the role and safety profile of metaraminol in the treatment of the critically unwell patient.
