Geo-economic Influence on the Effect of Fluid Volume for Sepsis Resuscitation: A Meta-Analysis.

Rationale: Sepsis management relies on fluid resuscitation avoiding fluid overload and its related organ congestion. Objectives: To explore the influence of country income group on risk-benefit balance of fluid management strategies in sepsis. Methods: We searched e-databases for all randomized controlled trials on fluid resuscitation in patients with sepsis or septic shock up to January 2023, excluding studies on hypertonic fluids, colloids, and depletion-based interventions. The effect of fluid strategies (higher versus lower volumes) on mortality was analyzed per income group (i.e., low- and middle-income countries [LMICs] or high-income countries [HICs]). Measurements and Main Results: Twenty-nine studies (11,798 patients) were included in the meta-analysis. There was a numerically higher mortality in studies of LMICs as compared with those of HICs: median, 37% (interquartile range [IQR]: 26-41) versus 29% (IQR: 17-38; P = 0.06). Income group significantly interacted with the effect of fluid volume on mortality: Higher fluid volume was associated with higher mortality in LMICs but not in HICs: odds ratio (OR), 1.47; 95% confidence interval (95% CI): 1.14-1.90 versus 1.00 (95% CI: 0.87-1.16), P = 0.01 for subgroup differences. Higher fluid volume was associated with increased need for mechanical ventilation in LMICs (OR, 1.24 [95% CI: 1.08-1.43]) but not in HICs (OR, 1.02 [95% CI: 0.80-1.29]). Self-reported access to mechanical ventilation also significantly influenced the effect of fluid volume on mortality, which increased with higher volumes only in settings with limited access to mechanical ventilation (OR: 1.45 [95% CI: 1.09-1.93] vs. 1.09 [95% CI: 0.93-1.28], P = 0.02 for subgroup differences). Conclusions: In sepsis trials, the effect of fluid resuscitation approach differed by setting, with higher volume of fluid resuscitation associated with increased mortality in LMICs and in settings with restricted access to mechanical ventilation. The precise reason for these differences is unclear and may be attributable in part to resource constraints, participant variation between trials, or other unmeasured factors.

Direct assessment of microcirculation in shock: a randomized-controlled multicenter study.

PURPOSE: Shock is a life-threatening condition characterized by substantial alterations in the microcirculation. This study tests the hypothesis that considering sublingual microcirculatory perfusion variables in the therapeutic management reduces 30-day mortality in patients admitted to the intensive care unit (ICU) with shock. METHODS: This randomized, prospective clinical multicenter trial-recruited patients with an arterial lactate value above two mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of the cause of shock. All patients received sequential sublingual measurements using a sidestream-dark field (SDF) video microscope at admission to the intensive care unit (± 4 h) and 24 (± 4) hours later that was performed blindly to the treatment team. Patients were randomized to usual routine or to integrating sublingual microcirculatory perfusion variables in the therapy plan. The primary endpoint was 30-day mortality, secondary endpoints were length of stay on the ICU and the hospital, and 6-months mortality. RESULTS: Overall, we included 141 patients with cardiogenic (n = 77), post cardiac surgery (n = 27), or septic shock (n = 22). 69 patients were randomized to the intervention and 72 to routine care. No serious adverse events (SAEs) occurred. In the interventional group, significantly more patients received an adjustment (increase or decrease) in vasoactive drugs or fluids (66.7% vs. 41.8%, p = 0.009) within the next hour. Microcirculatory values 24 h after admission and 30-day mortality did not differ [crude: 32 (47.1%) patients versus 25 (34.7%), relative risk (RR) 1.39 (0.91-1.97); Cox-regression: hazard ratio (HR) 1.54 (95% confidence interval (CI) 0.90-2.66, p = 0.118)]. CONCLUSION: Integrating sublingual microcirculatory perfusion variables in the therapy plan resulted in treatment changes that do not improve survival at all.

Perspectives on peripheral perfusion assessment.

PURPOSE OF REVIEW: The ANDROMEDA-SHOCK trial positioned capillary refill time (CRT) assessment as a novel resuscitation target for septic shock.The purpose of this article is to summarize pathophysiological determinants of CRT, review new technical developments on peripheral perfusion assessment, and explore recent evidence on the role of CRT monitoring in septic shock and other critical conditions. RECENT FINDINGS: A growing body of evidence supports the role of peripheral perfusion assessment as a warning and prognostic signal in a variety of clinical conditions among severely ill patients. Recent physiological studies demonstrated a rapid improvement of CRT after a single fluid bolus or a passive leg raising maneuver, a fact which may have diagnostic and therapeutic implications. Moreover, a couple of posthoc analyses of ANDROMEDA-SHOCK trial, reinforce that a normal CRT at the start of septic shock resuscitation, or its rapid normalization, thereafter may be associated with significant better outcomes. SUMMARY: Recent data confirm the relevance of peripheral perfusion assessment in septic shock and other conditions in critically ill patients. Future studies should confirm these findings, and test the potential contribution of technological devices to assess peripheral perfusion.

The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.

Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03078712. Registered retrospectively on March 13, 2017.

Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task force of the European Society of Intensive Care Medicine.

PURPOSE: Hand-held vital microscopes (HVMs) were introduced to observe sublingual microcirculatory alterations at the bedside in different shock states in critically ill patients. This consensus aims to provide clinicians with guidelines for practical use and interpretation of the sublingual microcirculation. Furthermore, it aims to promote the integration of routine application of HVM microcirculatory monitoring in conventional hemodynamic monitoring of systemic hemodynamic variables. METHODS: In accordance with the Delphi method we organized three international expert meetings to discuss the various aspects of the technology, physiology, measurements, and clinical utility of HVM sublingual microcirculatory monitoring to formulate this consensus document. A task force from the Cardiovascular Dynamics Section of the European Society of Intensive Care Medicine (with endorsement of its Executive Committee) created this consensus as an update of a previous consensus in 2007. We classified consensus statements as definitions, requirements, and/or recommendations, with a minimum requirement of 80% agreement of all participants. RESULTS: In this consensus the nature of microcirculatory alterations is described. The nature of variables, which can be extracted from analysis of microcirculatory images, is presented and the needed dataset of variables to identify microcirculatory alterations is defined. Practical aspects of sublingual HVM measurements and the nature of artifacts are described. Eleven statements were formulated that pertained to image acquisitions and quality statements. Fourteen statements addressed the analysis of the images, and 13 statements are related to future developments. CONCLUSION: This consensus describes 25 statements regarding the acquisition and interpretation of microcirculatory images needed to guide the assessment of the microcirculation in critically ill patients.

Evaluación de la microcirculación con sidestream dark field (SDF) Microscan® como método de monitorización en microcirugía en modelo porcino / Microcirculation assessment with sidestream dark field (SDF) Microscan® as flap monitoring method in microsurgery in a porcine model

Objetivo: Determinar la factibilidad de la monitorización en microcirugía por medio de la evaluación no invasiva de la microcirculación con sidestream dark field (SDF) y compararla con otros métodos. Materiales y métodos: Estudio experimental. En 8 cerdos se elevó colgajo pectoral y se disecó pedículo. Se llevó a cabo una instalación sucesiva de dispositivos cutáneos para la evaluación de la microcirculación: SDF para evaluar flujo, y near infrared spectroscopy (NIRS) para evaluar saturación de O2 (SatO2). Posteriormente se evaluó la oclusión venosa, arterial y total con pinzamiento durante 180 s. Resultados: SDF en oclusión venosa: disminución del flujo: 51 s (59-62); SDF en oclusión arterial: disminución del flujo: 3 s (1-5); SDF en oclusión vascular total: disminución del flujo: 3,5 s (2-5). NIRS en oclusión venosa: disminución de la SatO2:15,2 ± 5,3%; NIRS en oclusión arterial: disminución de la SatO2 23,9 ± 13,8%; NIRS en oclusión vascular total: disminución de la SatO2 23,85 ± 13,9%. Doppler en oclusión venosa: no desapareció; Doppler en oclusión arterial y oclusión vascular total: desapareció a los 2 s. En cada una de las mediciones, los cambios clínicos fueron más tardíos que los observados con SDF. Conclusión: Es factible la monitorización en microcirugía por medio de la evaluación de la microcirculación con Microscan®. Este método permite realizar el diagnóstico de oclusión vascular más tempranamente que con NIRS y evaluación clínica.

Aim: Determine the feasibility of using SDF Microscan® as a non-invasive method for monitoring free flap microcirculation, and compare it to other methods. Materials and methods: Experimental study. In 8 pigs a pectoral myocutaneous flap was raised. Microcirculation was evaluated using: SDF Microscan®, near infrared spectroscopy (NIRS), clinical examination and Doppler. Venous, arterial and total occlusion was performed by clamping the vascular pedicle. Mean time to blood flow impairment diagnosis was measured. Results: SDF in venous occlusion: reduced microcirculatory flow index at: 51 s (59-62). SDF in arterial occlusion: reduced microcirculatory flow index at: 3 s (1-5). SDF in total vascular occlusion: reduced microcirculatory flow index at: 3.5 s (2-5). NIRS in venous occlusion: SatO2 decrease was 15.2 ± 5.3%. NIRS in arterial occlusion: SatO2 decrease was 23.9 ± 13.8%. NIRS in total vascular occlusion: SatO2 decrease was 23.85 ± 13.9%. Doppler in venous occlusion: The signal did not disappear. Doppler arterial and total vascular occlusion disappears at 2 s. The clinical changes were later than SDF. Conclusion: Microcirculation monitoring is feasible using SDF Microscan® in a pig model. This method allows to detect blood flow disruption earlier than NIRS and clinical evaluation.