When to stop septic shock resuscitation: clues from a dynamic perfusion monitoring.

BACKGROUND: The decision of when to stop septic shock resuscitation is a critical but yet a relatively unexplored aspect of care. This is especially relevant since the risks of over-resuscitation with fluid overload or inotropes have been highlighted in recent years. A recent guideline has proposed normalization of central venous oxygen saturation and/or lactate as therapeutic end-points, assuming that these variables are equivalent or interchangeable. However, since the physiological determinants of both are totally different, it is legitimate to challenge the rationale of this proposal. We designed this study to gain more insights into the most appropriate resuscitation goal from a dynamic point of view. Our objective was to compare the normalization rates of these and other potential perfusion-related targets in a cohort of septic shock survivors. METHODS: We designed a prospective, observational clinical study. One hundred and four septic shock patients with hyperlactatemia were included and followed until hospital discharge. The 84 hospital-survivors were kept for final analysis. A multimodal perfusion assessment was performed at baseline, 2, 6, and 24 h of ICU treatment. RESULTS: Some variables such as central venous oxygen saturation, central venous-arterial pCO2 gradient, and capillary refill time were already normal in more than 70% of survivors at 6 h. Lactate presented a much slower normalization rate decreasing significantly at 6 h compared to that of baseline (4.0 [3.0 to 4.9] vs. 2.7 [2.2 to 3.9] mmol/L; p < 0.01) but with only 52% of patients achieving normality at 24 h. Sublingual microcirculatory variables exhibited the slowest recovery rate with persistent derangements still present in almost 80% of patients at 24 h. CONCLUSIONS: Perfusion-related variables exhibit very different normalization rates in septic shock survivors, most of them exhibiting a biphasic response with an initial rapid improvement, followed by a much slower trend thereafter. This fact should be taken into account to determine the most appropriate criteria to stop resuscitation opportunely and avoid the risk of over-resuscitation.

Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study.

PURPOSE: The role of dobutamine during septic shock resuscitation is still controversial since most clinical studies have been uncontrolled and no physiological study has unequivocally demonstrated a beneficial effect on tissue perfusion. Our objective was to determine the potential benefits of dobutamine on hemodynamic, metabolic, peripheral, hepatosplanchnic and microcirculatory perfusion parameters during early septic shock resuscitation. METHODS: We designed a randomized, controlled, double-blind, crossover study comparing the effects of 2.5-h infusion of dobutamine (5 mcg/kg/min fixed-dose) or placebo in 20 septic shock patients with cardiac index ≥2.5 l/min/m(2) and hyperlactatemia. Primary outcome was sublingual perfused microvascular density. RESULTS: Despite an increasing cardiac index, heart rate and left ventricular ejection fraction, dobutamine had no effect on sublingual perfused vessel density [9.0 (7.9-10.1) vs. 9.1 n/mm (7.9-9.9); p = 0.24] or microvascular flow index [2.1 (1.8-2.5) vs. 2.1 (1.9-2.5); p = 0.73] compared to placebo. No differences between dobutamine and placebo were found for the lactate levels, mixed venous-arterial pCO2 gradient, thenar muscle oxygen saturation, capillary refill time or gastric-to-arterial pCO2 gradient. The indocyanine green plasma disappearance rate [14.4 (9.5-25.6) vs. 18.8 %/min (11.7-24.6); p = 0.03] and the recovery slope of thenar muscle oxygen saturation after a vascular occlusion test [2.1 (1.1-3.1) vs. 2.5 %/s (1.2-3.4); p = 0.01] were worse with dobutamine compared to placebo. CONCLUSIONS: Dobutamine failed to improve sublingual microcirculatory, metabolic, hepatosplanchnic or peripheral perfusion parameters despite inducing a significant increase in systemic hemodynamic variables in septic shock patients without low cardiac output but with persistent hypoperfusion.

Severe abnormalities in microvascular perfused vessel density are associated to organ dysfunctions and mortality and can be predicted by hyperlactatemia and norepinephrine requirements in septic shock patients.

PURPOSE: The aims of this study are to determine the general relationship of perfused vessel density (PVD) to mortality and organ dysfunctions and to explore if patients in the lowest quartile of distribution for this parameter present a higher risk of bad outcome and to identify systemic hemodynamic and perfusion variables that enhances the probability of finding a severe underlying microvascular dysfunction. MATERIALS AND METHODS: This is a retrospective multicenter study including 122 septic shock patients participating in 7 prospective clinical trials on which at least 1 sublingual microcirculatory assessment was performed during early resuscitation. RESULTS: Perfused vessel density was significantly related to organ dysfunctions and mortality, but this effect was largely explained by patients in the lowest quartile of distribution for PVD (P = .037 [odds ratio {OR}, 8.7; 95% confidence interval {CI}, 1.14-66.78] for mortality). Hyperlactatemia (P < .026 [OR, 1.23; 95% CI, 1.03-1.47]) and high norepinephrine requirements (P < .019 [OR, 7.04; 95% CI, 1.38-35.89]) increased the odds of finding a severe microvascular dysfunction. CONCLUSIONS: Perfused vessel density is significantly related to organ dysfunctions and mortality in septic shock patients, particularly in patients exhibiting more severe abnormalities as represented by the lowest quartile of distribution for this parameter. The presence of hyperlactatemia and high norepinephrine requirements increases the odds of finding a severe underlying microvascular dysfunction during a sublingual microcirculatory assessment.

Persistent Sepsis-Induced Hypotension without Hyperlactatemia: A Distinct Clinical and Physiological Profile within the Spectrum of Septic Shock.

Introduction. A subgroup of septic shock patients will never develop hyperlactatemia despite being subjected to a massive circulatory stress. Maintenance of normal lactate levels during septic shock is of great clinical and physiological interest. Our aim was to describe the clinical, hemodynamic, perfusion, and microcirculatory profiles associated to the absence of hyperlactatemia during septic shock resuscitation. Methods. We conducted an observational study in septic shock patients undergoing resuscitation. Serial clinical, hemodynamic, and perfusion parameters were registered. A single sublingual microcirculatory assessment was performed in a subgroup. Patients evolving with versus without hyperlactatemia were compared. Results. 124 septic shock patients were included. Patients without hyperlactatemia exhibited lower severity scores and mortality. They also presented higher platelet counts and required less intensive treatment. Microcirculation was assessed in 45 patients. Patients without hyperlactatemia presented higher PPV and MFI values. Lactate was correlated to several microcirculatory parameters. No difference in systemic flow parameters was observed. Conclusion. Persistent sepsis-induced hypotension without hyperlactatemia is associated with less organ dysfunctions and a very low mortality risk. Patients without hyperlactatemia exhibit less coagulation and microcirculatory derangements despite comparable macrohemodynamics. Our study supports the notion that persistent sepsis-induced hypotension without hyperlactatemia exhibits a distinctive clinical and physiological profile.

Soporte vital extracorpóreo en adultos con insuficiencia respiratoria aguda refractaria / Extra-corporeal life support for adults with refractory severe respiratory failure / Suporte vital extracorpóreo em adultos com insuficiência respiratória aguda refratária

Resumen: Introducción: El soporte vital extracorpóreo (ECLS - por sus siglas en inglés extra-corporeal life support) se aplica exitosamente en neonatos con insuficiencia respiratoria aguda (IRA). Las dificultades técnicas, los costos y los resultados desalentadores confinaron a esta técnica como última estrategia en adultos. Nuestro objetivo es reportar nuestra experiencia con ECLS en adultos. Material y métodos: Se analizaron pacientes adultos tratados con ECLS entre febrero de 2002 y enero de 2012. Se recolectaron variables demográficas y cardiopulmonares. Los datos son expresados como mediana (rango). Se analizaron las diferencias entre los pacientes afectados con IRA aislada y con síndrome cardiopulmonar por Hantavirus (SCPH) con test U de Mann Whitney y se consideró estadísticamente significativo un valor de p < 0.05. Resultados: Se aplicó ECLS a15 pacientes. Cinco venoarteriales (VA), siete venovenoso (V-V) y tres asistencias pulmonares extracorpóreas sin bomba (P-ELA). Se describen variables demográficas, cardiopulmonares, diagnóstico, tiempo en ECLS y los desenlaces. Los días en ventilación mecánica (VM), la estadía en UCI y hospital fueron: 17 (4-49), 38 (4-93) y 46 (4-102) días respectivamente. Siete de los 15 pacientes fallecieron (47%). Dos pacientes murieron por shock séptico por bacilos Gram negativos después de un ECLS exitoso. La única diferencia estadísticamente significativa entre los pacientes con IRA aislada (ECLS-VV venovenosa o P-ELA) y los pacientes con SCPH (ECLS-VA venoarterial) fue el lactato al ingreso (p < 0.05). Conclusión: ECLS es una estrategia útil como rescate de adultos con IRA refractaria a estrategias de VM avanzada. El progreso en los equipos y el uso de algoritmos en la toma de decisiones han contribuido a reducir la morbimortalidad.

Abstract: Introduction: Extra-corporeal life support (ECLS) is an established technique for neonates with acute respiratory failure (ARF). Technical difficulties, expense and discouraging outcomes explains its confinement to a last resource tool for adults with ARF. Our objective is report the experience with adult ECLS in two hospitals. Material and methods: All consecutive adult patients treated with different ECLS techniques from 2002 to 2012 were analyzed. Demographic and cardiopulmonary variables were collected. Data are expressed as median (range). The differences between patients affected with ARF isolated and patients with hantavirus cardiopulmonary syndrome was obtained with Mann Whitney U test and a value of p < 0.05 was considered statistically significant. Results: Fifteen patients received ECLS. Five were veno-arterial (VA), 7 veno-venous (VV), and 3 pumpless extracorporeal lung assist (P-ELA). Demographic, cardiopulmonary variables, diagnosis, time on ECLS and outcome are described. Mechanical ventilation (MV), ICU and hospital stay were 17 (4-49), 38 (4-93) and 46 (4-102) days respectively. All patients who required VA-ECLS were affected for Hanta cardiopulmonary syndrome. Seven of fifteen patients died. Two out of five VA-ECLS suffered some degree of lower extremity (arterial cannulation) compartmental syndrome and a mild abnormal gait sequel affected them. Vascular accesses and bleeding were not a concern. Two patients died due to septic shock from gram negative bacilli after leaving ECLS. Conclusion: ECLS for catastrophic ARF in adults is useful therapeutic option to rescue patients who do not respond to conventional MV strategies. The progress in technical devices, use an algorithm to medical decision making contribute to reducing morbidity and mortality.

Resumo: Introdução: O suporte de vida extracorpórea (ECLS) é usado com sucesso em neonatos com insuficiência respiratória aguda (IRA). As dificuldades técnicas, custos e resultados decepcionantes confinaram a esta técnica como última estratégia em adultos. Nosso objetivo é relatar nossa experiência com ECLS em adultos. Métodos: Foram analisados pacientes adultos tratados com ECLS entre 2002 e 2012. Foram recolhidas as variáveis demográficas e cardiopulmonares. Os dados são expressos em mediana (desvio padrão). As diferenças entre os pacientes com IRA isolada e com síndrome cardiopulmonar por Hantavírus foi analisada com o teste U de Mann Whitney e foi considerou um valor estatisticamente significativo p < 0.05. Resultados: Quinze pacientes receberam ECLS. Cinco veno-arteriais (VA), 7 veno-venosas (V-V) e trêis asssistências pulmonares extracorpóreas sem bomba (P-ELA). Se descrevem variáveis demográficas, cardiopulmonar, diagnóstico, tempo no ECLS e os resultados. Os dias de ventilação mecânica (VM), tempo de UTI e hospitalar foram: 17 (4-49), 38 (4-93) e 46 (4-102) dias respectivamente. Sete dos quinze pacientes morreram (47%). Dois pacientes morreram com choque séptico por bacilos gram negativos depois de um ECLS exitoso. A única diferença estatisticamente significativa entre os pacientes com IRA isolada (ECLS-VV ou P-ELA) e pacientes com SCPH (ECLS-VA) foi o lactato na admissão (p < 0.05). Conclusão: O ECLS é uma estratégia útil como resgate de adultos com IRA refractária a estratégias de VM avançada. O progresso dos equipamentos e o uso de algoritmos na tomada de decisões têm ajudado a reduzir a morbimortalidade.

Relationship of systemic, hepatosplanchnic, and microcirculatory perfusion parameters with 6-hour lactate clearance in hyperdynamic septic shock patients: an acute, clinical-physiological, pilot study.

BACKGROUND: Recent clinical studies have confirmed the strong prognostic value of persistent hyperlactatemia and delayed lactate clearance in septic shock. Several potential hypoxic and nonhypoxic mechanisms have been associated with persistent hyperlactatemia, but the relative contribution of these factors has not been specifically addressed in comprehensive clinical physiological studies. Our goal was to determine potential hemodynamic and perfusion-related parameters associated with 6-hour lactate clearance in a cohort of hyperdynamic, hyperlactatemic, septic shock patients. METHODS: We conducted an acute clinical physiological pilot study that included 15 hyperdynamic, septic shock patients undergoing aggressive early resuscitation. Several hemodynamic and perfusion-related parameters were measured immediately after preload optimization and 6 hours thereafter, with 6-hour lactate clearance as the main outcome criterion. Evaluated parameters included cardiac index, mixed venous oxygen saturation, capillary refill time and central-to-peripheral temperature difference, thenar tissue oxygen saturation (StO2) and its recovery slope after a vascular occlusion test, sublingual microcirculatory assessment, gastric tonometry (pCO2 gap), and plasma disappearance rate of indocyanine green (ICG-PDR). Statistical analysis included Wilcoxon and Mann-Whitney tests. RESULTS: Five patients presented a 6-hour lactate clearance <10%. Compared with 10 patients with a 6-hour lactate clearance ≥10%, they presented a worse hepatosplanchnic perfusion as represented by significantly more severe derangements of ICG-PDR (9.7 (8-19) vs. 19.6 (9-32)%/min, p < 0.05) and pCO2 gap (33 (9.1-62) vs. 7.7 (3-58) mmHg, p < 0.05) at 6 hours. No other systemic, hemodynamic, metabolic, peripheral, or microcirculatory parameters differentiated these subgroups. We also found a significant correlation between ICG-PDR and pCO2 gap (p = 0.02). CONCLUSIONS: Impaired 6-hour lactate clearance could be associated with hepatosplanchnic hypoperfusion in some hyperdynamic septic shock patients. Improvement of systemic, metabolic, and peripheral perfusion parameters does not rule out the persistence of hepatosplanchnic hypoperfusion in this setting. Severe microcirculatory abnormalities can be detected in hyperdynamic septic shock patients, but their role on lactate clearance is unclear. ICG-PDR may be a useful tool to evaluate hepatosplanchnic perfusion in septic shock patients with persistent hyperlactatemia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01271153.