Clinical risk factors for early mortality in patients with community-acquired septic shock. The importance of adequate source control.

OBJECTIVE: To evaluate the incidence and risk factors for early mortality (EM) in the ICU in patients with community-acquired septic shock (CASS). DESIGN: A retrospective cohort study of patients with CASS admitted to the ICU (2003-2016). SETTING: ICU at a University Hospital in Spain. PATIENTS: All consecutive patients admitted to the ICU with CASS. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: CASS was defined according to the Sepsis-3 definitions. EM were defined as occurring within of 72h following ICU admission. A multinomial logistic regression analysis was performed to identify the risk factors associated with early deaths. RESULTS: During the study period, 625 patients met the Sepsis-3 criteria and admitted with CASS. 14.4% of all patients died within the first 72h. Of 161 patients who died in the ICU, 90 (55.9%) died within the first 72h. The percentage of early and late mortality did not vary significantly during the study period. The need and adequacy of source control were significantly lower in patients with EM. In the multivariate analysis, ARDS, non-respiratory infections, bacteremia and severity at admission were variables independently associated with EM. The only factor that decreased EM was adequate source control in patients with infections amenable to source control. CONCLUSIONS: The incidence of EM has remained stable over time, which means that more than half of the patients who die from CASS do so within the first 72h. Infections where adequate source control can be performed have lower EM.

Clinical risk factors for early mortality in patients with community-acquired septic shock. The importance of adequate source control.

OBJECTIVE: To evaluate the incidence and risk factors for early mortality (EM) in the ICU in patients with community-acquired septic shock (CASS). DESIGN: A retrospective cohort study of patients with CASS admitted to the ICU (2003-2016). SETTING: ICU at a University Hospital in Spain. PATIENTS: All consecutive patients admitted to the ICU with CASS. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: CASS was defined according to the Sepsis-3 definitions. EM were defined as occurring within of 72h following ICU admission. A multinomial logistic regression analysis was performed to identify the risk factors associated with early deaths. RESULTS: During the study period, 625 patients met the Sepsis-3 criteria and admitted with CASS. 14.4% of all patients died within the first 72h. Of 161 patients who died in the ICU, 90 (55.9%) died within the first 72h. The percentage of early and late mortality did not vary significantly during the study period. The need and adequacy of source control were significantly lower in patients with EM. In the multivariate analysis, ARDS, non-respiratory infections, bacteremia and severity at admission were variables independently associated with EM. The only factor that decreased EM was adequate source control in patients with infections amenable to source control. CONCLUSIONS: The incidence of EM has remained stable over time, which means that more than half of the patients who die from CASS do so within the first 72h. Infections where adequate source control can be performed have lower EM.

Central venous-to-arterial carbon dioxide difference combined with arterial-to-venous oxygen content difference (PcvaCO2/CavO2) reflects microcirculatory oxygenation alterations in early septic shock.

PURPOSE: To explore the relationship between central venous-to-arterial carbon dioxide difference (PcvaCO2), PcvaCO2/arterial-venous oxygen content difference ratio (PcvaCO2/CavO2) and the microcirculatory status, evaluated by using near-infrared spectroscopy, in septic shock patients. METHODS: Observational study in a 30-bed mixed ICU. Fifty septic shock patients within the first 24 h of ICU admission were studied. After restoration of mean arterial pressure, hemodynamic, metabolic and microcirculatory parameters were simultaneously evaluated. Local tissue oxygen saturation (StO2), and local hemoglobin index (THI) were measured on the thenar eminence by means of near-infrared spectroscopy. A transient vascular occlusion test was performed in order to obtain StO2 deoxygenation rate (DeO2), local oxygen consumption (nirVO2), and reoxgenation rate (ReO2). RESULTS: At inclusion, increased PcvaCO2 values were associated with lower StO2 and THI, whereas increased PcvaCO2/CavO2 values were associated with lower DeO2, nirVO2, and ReO2. Multiple regression models confirmed the association between PcvaCO2/CavO2 and nirVO2, while PcvaCO2 was only related to CI, and not to microcirculatory parameters. CONCLUSIONS: In a population of early septic shock patients, increases in PcvaCO2 and PcvaCO2/CavO2 reflected different alterations at the microcirculatory level. While PcvaCO2 was related to global flow, the PcvaCO2/CavO2 ratio was associated to impaired local oxygen utilization and diminished microvascular reactivity.

Respiratory quotient estimations as additional prognostic tools in early septic shock.

Central venous-to-arterial carbon dioxide difference (PcvaCO2), and its correction by the arterial-to-venous oxygen content difference (PcvaCO2/CavO2) have been proposed as additional tools to evaluate tissue hypoxia. Since the relationship between pressure and content of CO2 (CCO2) might be affected by several factors, some authors advocate for the use of CcvaCO2/CavO2. The aim of the present study was to explore the factors that might intervene in the difference between PcvaCO2/CavO2 and CcvaCO2/CavO2, and to analyze their association with mortality. Observational study in a 30-bed mixed ICU. Fifty-two septic shock patients within the first 24 h of ICU admission were studied. After restoration of mean arterial pressure, hemodynamic and metabolic parameters were evaluated. A total of 110 sets of measurements were performed. Simultaneous PcvaCO2/CavO2 and CcvaCO2/CavO2 values were correlated, but agreement analysis showed a significant proportional bias. The difference between PcvaCO2/CavO2 and CcvaCO2/CavO2 was independently associated with pH, ScvO2, baseline CcvaCO2/CavO2 and hemoglobin. A stepwise regression analysis showed that pH was the single best predictor for the magnitude of such difference, with very limited effect of other variables. At inclusion, variables associated with ICU-mortality were lactate, pH, PcvaCO2/CavO2, and the difference between PcvaCO2/CavO2 and CcvaCO2/CavO2. Initial ScvO2, PcvaCO2, CcvaCO2/CavO2, and cardiac index were not different in survivors and non-survivors. In a population of early septic shock patients, simultaneous values of PcvaCO2/CavO2 and CcvaCO2/CavO2 were not equivalent, and the main determinant of the magnitude of the difference between these two parameters was pH. The PcvaCO2/CavO2 ratio was associated with ICU mortality, whereas CcvaCO2/CavO2 was not.

Microcirculatory monitoring in septic patients: Where do we stand? / Monitorizando la microcirculación en el paciente séptico: ¿en qué punto estamos?

Microcirculatory alterations play a pivotal role in sepsis-related morbidity and mortality. However, since the microcirculation has been a ‘black box’, current hemodynamic management of septic patients is still guided by macrocirculatory parameters. In the last decades, the development of several technologies has shed some light on microcirculatory evaluation and monitoring, and the possibility of incorporating microcirculatory variables to clinical practice no longer seems to be beyond reach. The present review provides a brief summary of the current technologies for microcirculatory evaluation, and attempts to explore the potential role and benefits of their integration to the resuscitation process in critically ill septic patients

Las alteraciones microcirculatorias juegan un papel fundamental en la morbimortalidad asociada a la sepsis. Sin embargo, puesto que la microcirculación ha sido una «caja negra», el manejo hemodinámico actual del paciente séptico sigue basándose en la corrección de parámetros macrocirculatorios. Durante las últimas décadas, el desarrollo de diferentes tecnologías ha permitido arrojar algo de luz sobre la posibilidad de evaluar y monitorizar la microcirculación, y a día de hoy, la incorporación de variables microcirculatorias a la práctica clínica ya no parece una quimera. El presente trabajo de revisión presenta, de forma sucinta, las diferentes tecnologías que permiten evaluar la microcirculación, y pretende explorar el posible papel, así como los potenciales beneficios, de la integración de estas tecnologías en el proceso de reanimación del paciente crítico séptico

Microcirculatory monitoring in septic patients: Where do we stand?

Microcirculatory alterations play a pivotal role in sepsis-related morbidity and mortality. However, since the microcirculation has been a "black box", current hemodynamic management of septic patients is still guided by macrocirculatory parameters. In the last decades, the development of several technologies has shed some light on microcirculatory evaluation and monitoring, and the possibility of incorporating microcirculatory variables to clinical practice no longer seems to be beyond reach. The present review provides a brief summary of the current technologies for microcirculatory evaluation, and attempts to explore the potential role and benefits of their integration to the resuscitation process in critically ill septic patients.

Central venous-to-arterial carbon dioxide difference and the effect of venous hyperoxia: A limiting factor, or an additional marker of severity in shock?

Central venous-to-arterial carbon dioxide difference (PcvaCO2) has demonstrated its prognostic value in critically ill patients suffering from shock, and current expert recommendations advocate for further resuscitation interventions when PcvaCO2 is elevated. PcvaCO2 combination with arterial-venous oxygen content difference (PcvaCO2/CavO2) seems to enhance its performance when assessing anaerobic metabolism. However, the fact that PCO2 values might be altered by changes in blood O2 content (the Haldane effect), has been presented as a limitation of PCO2-derived variables. The present study aimed at exploring the impact of hyperoxia on PcvaCO2 and PcvaCO2/CavO2 during the early phase of shock. Prospective interventional study. Ventilated patients suffering from shock within the first 24 h of ICU admission. Patients requiring FiO2 ≥ 0.5 were excluded. At inclusion, simultaneous arterial and central venous blood samples were collected. Patients underwent a hyperoxygenation test (5 min of FiO2 100%), and arterial and central venous blood samples were repeated. Oxygenation and CO2 variables were calculated at both time points. Twenty patients were studied. The main cause of shock was septic shock (70%). The hyperoxygenation trial increased oxygenation parameters in arterial and venous blood, whereas PCO2 only changed at the venous site. Resulting PcvaCO2 and PcvaCO2/CavO2 significantly increased [6.8 (4.9, 8.1) vs. 7.6 (6.7, 8.5) mmHg, p 0.001; and 1.9 (1.4, 2.2) vs. 2.3 (1.8, 3), p < 0.001, respectively]. Baseline PcvaCO2, PcvaCO2/CavO2 and ScvO2 correlated with the magnitude of PO2 augmentation at the venous site within the trial (ρ -0.46, p 0.04; ρ 0.6, p < 0.01; and ρ 0.7, p < 0.001, respectively). Increased PcvaCO2/CavO2 values were associated with higher mortality in our sample [1.46 (1.21, 1.89) survivors vs. 2.23 (1.86, 2.8) non-survivors, p < 0.01]. PcvaCO2 and PcvaCO2/CavO2 are influenced by oxygenation changes not related to flow. Elevated PcvaCO2 and PcvaCO2/CavO2 values might not only derive from cardiac output inadequacy, but also from venous hyperoxia. Elevated PcvaCO2/CavO2 values were associated with higher PO2 transmission to the venous compartment, suggesting higher shunting phenomena.

Fluid therapy and the hypovolemic microcirculation.

PURPOSE OF REVIEW: In shock states, optimizing intravascular volume is crucial to promote an adequate oxygen delivery to the tissues. Our current practice in fluid management pivots on the Frank-Starling law of the heart, and the effects of fluids are measured according to the induced changes on stroke volume. The purpose of this review is to evaluate the boundaries of current macrohemodynamic approach to fluid administration, and to introduce the microcirculatory integration as a fundamental part of tissue perfusion monitoring. RECENT FINDINGS: Macrocirculatory changes induced by volume expansion are not always coupled to proportional changes in microcirculatory perfusion. Loss of hemodynamic coherence limits the value of guiding fluid therapy according to macrohemodynamics, and highlights the importance of evaluating the ultimate target of volume administration, the microcirculation. SUMMARY: Current approach to intravascular volume optimization is made from a macrohemodynamic perspective. However, several situations wherein macrocirculatory and microcirculatory coherence is lost have been described. Future clinical trials should explore the usefulness of integrating the microcirculatory evaluation in fluid optimization.

Saturación tisular de oxígeno en el paciente crítico / Tissue oxygen saturation in the critically ill patient

Los objetivos de la reanimación hemodinámica van dirigidos a la restauración de variables macrocirculatorias de presión y flujo de marcado carácter global. Sin embargo, a día de hoy, múltiples trabajos han evidenciado que, a pesar de la normalización de estas variables, pueden persistir alteraciones de la perfusión tanto a nivel regional como microcirculatorio, y que dichas alteraciones se han correlacionado de forma independiente con un pronóstico desfavorable del paciente. Esta evidencia ha propiciado un creciente interés por nuevas tecnologías dirigidas a la evaluación de la circulación regional y la microcirculación. La espectroscopia de luz cercana al infrarrojo nos permite monitorizar la saturación tisular de oxígeno, y ha sido propuesta como medida rápida, no invasiva y continua de la circulación regional. La presente revisión trata de exponer la evidencia actual sobre la espectroscopia de luz cercana al infrarrojo y su potencial uso clínico en la reanimación de los pacientes críticos en shock

Hemodynamic resuscitation seeks to correct global macrocirculatory parameters of pressure and flow. However, current evidence has shown that despite the normalization of these global parameters, microcirculatory and regional perfusion alterations can persist, and these alterations have been independently associated with a poorer patient prognosis. This in turn has lead to growing interest in new technologies for exploring regional circulation and microcirculation. Near infra-red spectroscopy allows us to monitor tissue oxygen saturation, and has been proposed as a noninvasive, continuous and easy-to-obtain measure of regional circulation. The present review aims to summarize the existing evidence on near infra-redspectroscopy and its potential clinical role in the resuscitation of critically ill patients in shock

[Tissue oxygen saturation in the critically ill patient]. / Saturación tisular de oxígeno en el paciente crítico.

Hemodynamic resuscitation seeks to correct global macrocirculatory parameters of pressure and flow. However, current evidence has shown that despite the normalization of these global parameters, microcirculatory and regional perfusion alterations can persist, and these alterations have been independently associated with a poorer patient prognosis. This in turn has lead to growing interest in new technologies for exploring regional circulation and microcirculation. Near infra-red spectroscopy allows us to monitor tissue oxygen saturation, and has been proposed as a noninvasive, continuous and easy-to-obtain measure of regional circulation. The present review aims to summarize the existing evidence on near infra-red spectroscopy and its potential clinical role in the resuscitation of critically ill patients in shock.

Skeletal muscle oxygen saturation (StO2) measured by near-infrared spectroscopy in the critically ill patients.

According to current critical care management guidelines, the overall hemodynamic optimization process seeks to restore macrocirculatory oxygenation, pressure, and flow variables. However, there is increasing evidence demonstrating that, despite normalization of these global parameters, microcirculatory and regional perfusion alterations might occur, and persistence of these alterations has been associated with worse prognosis. Such observations have led to great interest in testing new technologies capable of evaluating the microcirculation. Near-infrared spectroscopy (NIRS) measures tissue oxygen saturation (StO2) and has been proposed as a noninvasive system for monitoring regional circulation. The present review aims to summarize the existing evidence on NIRS and its potential clinical utility in different scenarios of critically ill patients.

Prognostic implications of tissue oxygen saturation in human septic shock.

PURPOSE: To analyze the prognostic value of tissue oxygen saturation (StO(2)) in septic shock patients with restored mean arterial pressure (MAP). METHODS: This was a prospective observational study of patients admitted to the ICU in the early phase of septic shock, after restoration of MAP. Demographic data, severity score, hemodynamics, blood lactate, acid-base status, and StO(2) were measured at inclusion followed by a transient vascular occlusion test (VOT) to obtain the StO(2)-deoxygenation (DeOx) and StO(2)-reoxygenation (ReOx) rates. Sequential organ failure assessment (SOFA) score was measured at inclusion and after 24 h. RESULTS: Thirty-three patients were studied. StO(2) was 76 ± 10%, DeOx -12.2 ± 4.2%/min, and ReOx 3.02 ± 1.70%/s. MAP showed a significant correlation with VOT-derived slopes (r = -0.4, p = 0.04 for DeOx; and r = 0.55, p < 0.01 for ReOx). After 24 h, 17 patients (52%) had improved SOFA scores. Patients who did not improve their SOFA showed less negative DeOx values at inclusion. The association between DeOx and SOFA evolution was not affected by MAP. Both DeOx and ReOx impairment correlated with longer ICU stay (r = 0.44, p = 0.05; and r = -0.43, p = 0.05, respectively). CONCLUSIONS: In a population of septic shock patients with restored MAP, impaired DeOx was associated with no improvement in organ failures after 24 h. Decrements in DeOx and ReOx were associated with longer ICU stay. DeOx and ReOx were linked to MAP, and thus, their interpretation needs to be made relative to MAP.