Although guidelines provide excellent expert guidance for managing patients with septic shock, they leave room for personalization according to patients' condition. Hemodynamic monitoring depends on ...the evolution phase: salvage, optimization, stabilization, and de-escalation. Initially during the salvage phase, monitoring to identify shock etiology and severity should include arterial pressure and lactate measurements together with clinical examination, particularly skin mottling and capillary refill time. Low diastolic blood pressure may trigger vasopressor initiation. At this stage, echocardiography may be useful to identify significant cardiac dysfunction. During the optimization phase, echocardiographic monitoring should be pursued and completed by the assessment of tissue perfusion through central or mixed-venous oxygen saturation, lactate, and carbon dioxide veno-arterial gradient. Transpulmonary thermodilution and the pulmonary artery catheter should be considered in the most severe patients. Fluid therapy also depends on shock phases. While administered liberally during the resuscitation phase, fluid responsiveness should be assessed during the optimization phase. During stabilization, fluid infusion should be minimized. In the de-escalation phase, safe fluid withdrawal could be achieved by ensuring tissue perfusion is preserved. Norepinephrine is recommended as first-line vasopressor therapy, while vasopressin may be preferred in some patients. Essential questions remain regarding optimal vasopressor selection, combination therapy, and the most effective and safest escalation. Serum renin and the angiotensin I/II ratio may identify patients who benefit most from angiotensin II. The optimal therapeutic strategy for shock requiring high-dose vasopressors is scant. In all cases, vasopressor therapy should be individualized, based on clinical evaluation and blood flow measurements to avoid excessive vasoconstriction. Inotropes should be considered in patients with decreased cardiac contractility associated with impaired tissue perfusion. Based on pharmacologic properties, we suggest as the first test a limited dose of dobutamine, to add enoximone or milrinone in the second line and substitute or add levosimendan if inefficient. Regarding adjunctive therapies, while hydrocortisone is nowadays advised in patients receiving high doses of vasopressors, patients responding to corticosteroids may be identified in the future by the analysis of selected cytokines or specific transcriptomic endotypes. To conclude, although some general rules apply for shock management, a personalized approach should be considered for hemodynamic monitoring and support.
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.
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 very-early (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 risk-adjusted 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.
Patients subjected to VE-VPs received significantly less resuscitation fluids at vasopressor starting (00-510 vs. 1500650-2300 mL, p < 0.001) and during the first 8 h of resuscitation (1100500-1900 vs. 26001600-3800 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.
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.
Septic shock: a microcirculation disease De Backer, Daniel; Ricottilli, Francesco; Ospina-Tascón, Gustavo A
Current opinion in anaesthesiology,
04/2021, Letnik:
34, Številka:
2
Journal Article
The aim of this study was to discuss the implication of microvascular dysfunction in septic shock.
Resuscitation of sepsis has focused on systemic haemodynamics and, more recently, on peripheral ...perfusion indices. However, central microvascular perfusion is altered in sepsis and these alterations often persist despite normalization of various macro haemodynamic resuscitative goals. Endothelial dysfunction is a key element in sepsis pathophysiology. It is responsible for the sepsis-induced hypotension. In addition, endothelial dysfunction is also implicated involved in the activation of inflammation and coagulation processes leading to amplification of the septic response and development of organ dysfunction. It also promotes an increase in permeability, mostly at venular side, and impairs microvascular perfusion and hence tissue oxygenation.Microvascular alterations are characterized by heterogeneity in blood flow distribution, with adequately perfused areas in close vicinity to not perfused areas, thus characterizing the distributive nature of septic shock. Such microvascular alterations have profound implications, as these are associated with organ dysfunction and unfavourable outcomes. Also, the response to therapy is highly variable and cannot be predicted by systemic hemodynamic assessment and hence cannot be detected by classical haemodynamic tools.
Microcirculation is a key element in the pathophysiology of sepsis. Even if microcirculation-targeted therapy is not yet ready for the prime time, understanding the processes implicated in microvascular dysfunction is important to prevent chasing systemic hemodynamic variables when this does not contribute to improve tissue perfusion.
Clinical and pathophysiological understanding of septic shock has progressed exponentially in the previous decades, translating into a steady decrease in septic shock-related morbidity and mortality. ...Even though large randomized, controlled trials have addressed fundamental aspects of septic shock resuscitation, many questions still exist. In this review, we will describe the current standards of septic shock resuscitation, but the emphasis will be placed on evolving concepts in different domains such as clinical resuscitation targets, adequate use of fluids and vasoactive drugs, refractory shock, and the use of extracorporeal therapies. Multiple research opportunities remain open, and collaborative endeavors should be performed to fill in these gaps.
Fluid boluses are administered to septic shock patients with the purpose of increasing cardiac output as a means to restore tissue perfusion. Unfortunately, fluid therapy has a narrow therapeutic ...index, and therefore, several approaches to increase safety have been proposed. Fluid responsiveness (FR) assessment might predict which patients will effectively increase cardiac output after a fluid bolus (FR+), thus preventing potentially harmful fluid administration in non-fluid responsive (FR-) patients. However, there are scarce data on the impact of assessing FR on major outcomes. The recent ANDROMEDA-SHOCK trial included systematic per-protocol assessment of FR. We performed a post hoc analysis of the study dataset with the aim of exploring the relationship between FR status at baseline, attainment of specific targets, and clinically relevant outcomes.
ANDROMEDA-SHOCK compared the effect of peripheral perfusion- vs. lactate-targeted resuscitation on 28-day mortality. FR was assessed before each fluid bolus and periodically thereafter. FR+ and FR- subgroups, independent of the original randomization, were compared for fluid administration, achievement of resuscitation targets, vasoactive agents use, and major outcomes such as organ dysfunction and support, length of stay, and 28-day mortality.
FR could be determined in 348 patients at baseline. Two hundred and forty-two patients (70%) were categorized as fluid responders. Both groups achieved comparable successful resuscitation targets, although non-fluid responders received less resuscitation fluids (0 0-500 vs. 1500 1000-2500 mL; p 0.0001), exhibited less positive fluid balances, but received more vasopressor testing. No difference in clinically relevant outcomes between FR+ and FR- patients was found, including 24-h SOFA score (9 5-12 vs. 8 5-11, p = 0.4), need for MV (78% vs. 72%, p = 0.16), need for RRT (18% vs. 21%, p = 0.7), ICU-LOS (6 3-11 vs. 6 3-16 days, p = 0.2), and 28-day mortality (40% vs. 36%, p = 0.5). Only thirteen patients remained fluid responsive along the intervention period.
Systematic assessment allowed determination of fluid responsiveness status in more than 80% of patients with early septic shock. Fluid boluses could be stopped in non-fluid responsive patients without any negative impact on clinical relevant outcomes. Our results suggest that fluid resuscitation might be safely guided by FR assessment in septic shock patients.
ClinicalTrials.gov identifier, NCT03078712. Registered retrospectively on March 13, 2017.
THE ENDOTHELIUM IN SEPSIS Ince, Can; Mayeux, Philip R; Nguyen, Trung ...
Shock
45, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis ...include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up-regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014.
A recent randomized controlled trial showed that a peripheral perfusion-guided resuscitation strategy was associated with lower mortality and less organ dysfunction when compared with lactate-guided ...resuscitation strategy in patients with septic shock, but the difference in the primary outcome, 28-day mortality, did not reach the proposed statistical significance threshold (
= 0.06). We tested different analytic methods to aid in the interpretation of these results.
To reassess the results of the ANDROMEDA-SHOCK trial using both Bayesian and frequentist frameworks.
All patients recruited in ANDROMEDA-SHOCK were included. Both a
Bayesian analysis and a mixed logistic regression analysis were performed. The Bayesian analysis included four different priors (optimistic, neutral, null, and pessimistic) for mortality endpoints. The probability of having a Sequential Organ Failure Assessment in the lowest quartile at 72 hours was assessed using Bayesian networks.
In the Bayesian analysis, the posterior probability that a peripheral perfusion-targeted resuscitation strategy is superior to lactate-targeted resuscitation at 28 days was above 90% for all priors; the probability of benefit at 90 days was above 90% for all but the pessimistic prior. Using an optimistic prior, posterior median odds ratios were 0.61 (95% credible interval, 0.41-0.90) and 0.68 (95% credible interval, 0.47-1.01) for 28-day and 90-day mortality, respectively. The comparable frequentist odds ratios for 28-day and 90-day mortality were 0.61 (95% confidence interval CI, 0.38-0.92) and 0.70 (95% CI, 0.45-1.08), respectively. The odds that that patients in the peripheral perfusion-targeted resuscitation arm had Sequential Organ Failure Assessment scores in the lower quartile at 72 hours was 1.55 (95% CI, 1.02-2.37).
Peripheral perfusion-targeted resuscitation may result in lower mortality and faster resolution of organ dysfunction when compared with a lactate-targeted resuscitation strategy.
Background
Reported risk of bleeding complications after central catheter access in patients with thrombocytopenia is highly variable. Current guidelines recommend routine prophylactic platelet (PLT) ...transfusion before central venous catheter placement in patients with severe thrombocytopenia. Nevertheless, the strength of such recommendations is weak and supported by observational studies including few patients with very low PLT counts (<20 × 109/L). This study aims to assess the risk of bleeding complications related to using or not using prophylactic PLT transfusion before ultrasound‐guided central venous access in patients with very low PLT counts.
Methods
This was a retrospective cohort study of patients with very low PLT counts (<20 × 109/L) subjected to ultrasound‐guided central venous catheterization between January 2011 and November 2019 in a university hospital. Bleeding complications were graded according to the Common Terminology Criteria for Adverse Events. A multivariate logistic regression was conducted to assess the risk of major and minor bleeding complications comparing patients who did or did not receive prophylactic PLT transfusion for the procedure. Multiple imputation by chained equations was used to handle missing data. A two‐tailed p < 0.05 was considered statistically significant.
Results
Among 221 patients with very low PLT counts, 72 received prophylactic PLT transfusions while 149 did not. Baseline characteristics were similar between transfused and nontransfused patients. No major bleeding events were identified, while minor bleeding events were recognized in 35.7% of patients. Multivariate logistic regression analysis showed no significant differences in bleeding complications between patients who received prophylactic PLT transfusions and those who did not (odds ratio 0.83, 95% confidence interval 0.45–1.55, p = 0.567). Additional complete case and sensitivity analyses yielded results similar to those of the main analysis.
Conclusions
In this single‐center retrospective cohort study of ultrasound‐guided central venous access in patients with very low PLT counts, no major bleeding was identified, and prophylactic PLT transfusions did not significantly decrease minor bleeding events.
How to assess tissue oxygenation? De Backer, Daniel; Ospina-Tascón, Gustavo A
Current opinion in critical care,
06/2023, Letnik:
29, Številka:
3
Journal Article
To discuss the different techniques used to assess tissue oxygenation in critically ill patients.
While historically the analysis of oxygen consumption (VO2)/oxygen delivery (DO2) relationships has ...provided important information, methodological limitations prevent its use at bedside. PO2 measurements, while attractive, are unfortunately of limited value in the presence of microvascular blood flow heterogeneity which is observed in many critically ill conditions including sepsis. Surrogates of tissue oxygenation are hence used. Elevated lactate levels may suggest inadequate tissue oxygenation, but other sources than tissue hypoxia can also contribute to hyperlactatemia so that lactate measurements should be used in combination with other measurements of tissue oxygenation. Venous O2 saturation can be used to evaluate the adequacy of DO2 in respect to VO2, but it can be misleading normal or even high in sepsis. Measurements of Pv-aCO2 and computation of Pv-aCO2/CavO2 are very promising as physiologically sound, easy to measure, rapidly respond to therapy, and are associated with outcome. An elevated Pv-aCO2 reflects an impaired tissue perfusion while an increased Pv-aCO2/CavO2 ratio reflects tissue dysoxia.
Recent studies have highlighted the interest of surrogate measurements of tissue oxygenation and in particular PCO2 gradients.
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