Early Resuscitation Of Septic Shock Research Articles

Subclinical cardiac dysfunction may impact on fluid and vasopressor administration during early resuscitation of septic shock

BackgroundAccording to the Surviving Sepsis Campaign (SSC) fluids and vasopressors are the mainstays of early resuscitation of septic shock while inotropes are indicated in case of tissue hypoperfusion refractory to fluids and vasopressors, suggesting severe cardiac dysfunction. However, septic cardiac disfunction encompasses a large spectrum of severities and may remain “subclinical” during early resuscitation. We hypothesized that “subclinical” cardiac dysfunction may nevertheless influence fluid and vasopressor administration during early resuscitation. We retrospectively reviewed prospectically collected data on fluids and vasoconstrictors administered outside the ICU in patients with septic shock resuscitated according to the SSC guidelines that had reached hemodynamic stability without the use of inotropes. All the patients were submitted to transpulmonary thermodilution (TPTD) hemodynamic monitoring at ICU entry. Subclinical cardiac dysfunction was defined as a TPTD-derived cardiac function index (CFI) ≤ 4.5 min−1.ResultsAt ICU admission, subclinical cardiac dysfunction was present in 17/40 patients (42%; CFI 3.6 ± 0.7 min−1 vs 6.6 ± 1.9 min−1; p < 0.01). Compared with patients with normal CFI, these patients had been resuscitate with more fluids (crystalloids 57 ± 10 vs 47 ± 9 ml/kg PBW; p < 0.01) and vasopressors (norepinephrine 0.65 ± 0.25 vs 0.43 ± 0.29 mcg/kg/min; p < 0.05). At ICU admission these patients had lower cardiac index (2.2 ± 0.6 vs 3.6 ± 0.9 L/min/m2, p < 0.01) and higher systemic vascular resistances (2721 ± 860 vs 1532 ± 480 dyn*s*cm−5/m2, p < 0.01).ConclusionsIn patients with septic shock resuscitated according to the SSC, we found that subclinical cardiac dysfunction may influence the approach to fluids and vasopressor administration during early resuscitation. Our data support the implementation of early, bedside assessment of cardiac function during early resuscitation of septic shock.

Using pCO2 Gap in the Differential Diagnosis of Hyperlactatemia Outside the Context of Sepsis: A Physiological Review and Case Series.

Introduction There is an inverse relationship between cardiac output and the central venous-arterial difference of partial pressures of carbon dioxide (pCO2 gap), and pCO2 gap has been used to guide early resuscitation of septic shock. It can be hypothesized that pCO2 gap can be used outside the context of sepsis to distinguish type A and type B lactic acidosis and thereby avoid unnecessary fluid resuscitation in patients with high lactate, but without organ hypoperfusion. Methods We performed a structured review of the literature enlightening the physiological background. Next, we retrospectively selected a series of case reports of nonseptic critically ill patients with elevated lactate, in whom both arterial and central venous blood gases were simultaneously measured and the diagnosis of either type A or type B hyperlactataemia was conclusively known. In these cases, we calculated venous-arterial CO2 and O2 content differences and pCO2 gap. Results Based on available physiological data, pCO2 can be considered as an acceptable surrogate of venous-arterial CO2 content difference, and it should better reflect cardiac output than central venous saturation or indices based on venous-arterial O2 content difference. In our case report of nonseptic patients, we observed that if global hypoperfusion was present (i.e., in type A lactic acidosis), pCO2 gap was elevated (>1 kPa), whilst in the absence of it (i.e., in type B lactic acidosis), pCO2 gap was low (<0.5 kPa). Conclusion Physiological rationale and a small case series are consistent with the hypothesis that low pCO2 gap in nonseptic critically ill is suggestive of the absence of tissue hypoperfusion, mandating the search for the cause of type B lactic acidosis rather than administration of fluids or other drugs aimed at increasing cardiac output.

Prognostic value of difference between peripheral venous and arterial partial pressure of carbon dioxide in patients with septic shock: a pilot study

To evaluate the prognostic value of the difference between peripheral venous and arterial partial pressure of carbon dioxide in patients with septic shock following early resuscitation. This prospective study was conducted among the patients with septic shock treated in our department during the period from May, 2017 to May, 2018. Peripheral venous, peripheral arterial and central venous blood samples were collected simultaneously and analyzed immediately at bedside after 6-h bundle treatment. Arterial blood lactate concentration (Lac) and the arterial (PaCO2), peripheral venous (PpvCO2) and central venous partial pressure of carbon dioxide (PcvCO2) were recorded. The differences between PpvCO2 and PaCO2 (Ppv-aCO2) and between PcvCO2 and PaCO2 (Pcv-aCO2) were calculated. Pearson correlation analysis was used to test the agreement between Pcv-aCO2 and Ppv-aCO2. Multivariable logistic regression analysis was performed to analyze the possible risk factors for 28-day mortality, and the receiver-operating characteristic curve (ROC) was plotted to assess the prognostic values of these factors for 28-day mortality. A total of 62 patients were enrolled in this study, among who 35 survived and 27 died during the 28-day period. Compared with the survivor group, the patients died within 28 days showed significantly higher Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score (24.2±6.0 vs 20.5±4.9, P=0.011), sequential organ failure assessment (SOFA) score (14.9±4.7 vs 12.2±4.5, P=0.027), PcvaCO2 (5.5±1.6 vs 7.1±1.7, P &lt; 0.001), PpvaCO2 (7.1±1.8 vs 10.0±2.7, P &lt; 0.001), and arterial lactate level (3.3±1.2 vs 4.2±1.3, P=0.003) after 6-h bundle treatment. Pearson correlation analysis showed that Ppv-aCO2 was significantly correlated with Pcv-aCO2 (r=0.897, R2= 0.805, P &lt; 0.001). Multiple logistic regression analysis identified Ppv-aCO2 (β=0.625, P=0.001, OR=1.869, 95% CI: 1.311-2.664) and lactate level (β=0.584, P=0.041, OR=1.794, 95%CI: 1.024-3.415) as the independent risk factors for 28-day mortality. The maximum area under the ROC (AUC) of Ppv-aCO2 was 0.814 (95%CI: 0.696- 0.931, P &lt; 0.001), and at the best cut- off value of 9.05 mmHg, Ppv-aCO2 had a sensitivity of 70.4% and a specificity of 88.6% for predicting 28-day mortality. The AUC of lactate level was 0.732 (95%CI: 0.607-0.858, P=0.002), and its sensitivity for predicting 28-day mortality was 70.4% and the specificity was 74.3% at the best cut-off value of 3.45 mmol/L; The AUC of Pcv-aCO2 was 0.766 (95%CI: 0.642-0.891, P &lt; 0.001), and its sensitivity was 66.7% and the specificity was 80.0% at the best cut-off value of 7.05 mmHg. A high Ppv-aCO2 after early resuscitation of septic shock is associated with poor outcomes. Ppv-aCO2 is well correlated with Pcv-aCO2 and can be used as an independent indicator for predicting 28-day mortality in patients with septic shock.

Persistent hyperlactatemia-high central venous-arterial carbon dioxide to arterial-venous oxygen content ratio is associated with poor outcomes in early resuscitation of septic shock

ObjectiveSeveral studies reported Pv-aCO2/Ca-vO2 ratio as a surrogate of VCO2/VO2 to detect global tissue hypoxia. The present study aimed to evaluate the prognostic value of Pv-aCO2/Ca-vO2 ratio combined with lactate levels during the early phases of resuscitation in septic shock. MethodsA retrospective study was conducted in 144 septic shock patients in a 30-bed mixed ICU. A Pv-aCO2/Ca-vO2 ratio>1.4 was considered abnormal. Patients were classified into four predefined groups according to lactate levels and Pv-aCO2/Ca-vO2 ratio after the first 6h of resuscitation. Sequential Organ Failure Assessment (SOFA) score at day 3 was assessed. A Kaplan-Meier curve showed the survival probabilities at day 28 using a log-rank test to evaluate the differences between groups. A receiver operating characteristics (ROC) curve evaluated the ability of lactate, Pv-aCO2/Ca-vO2 ratio and Pv-aCO2/Ca-vO2 ratio combined with lactate to predict mortality at day 28. ResultsCombination of hyperlactatemia and high Pv-aCO2/Ca-vO2 ratio was associated with poor SOFA scores and low survival rates at day 28 (P<0.001). The Cox multivariate survival analysis demonstrated that Pv-aCO2/Ca-vO2 ratio and lactate at T6 were independent predictors of mortality at day 28. The area under the ROC curve of the Pv-aCO2/Ca-vO2 ratio combined with lactate for predicting mortality at day 28 was highest and superior to that of lactate and Pv-aCO2/Ca-vO2 ratios. ConclusionCombination of Pv-aCO2/Ca-vO2 ratio and lactate at early stages of resuscitation of septic shock can better predict the prognosis of patients. The Pv-aCO2/Ca-vO2 ratio may become a useful parameter supplementary to lactate in the resuscitation of septic shock.

Central Venous Oxygen Saturation above 75% on Day Three of Septic Shock is Associated with Tripled Mortality

Background: Central venous oxygen saturation (ScvO2) is commonly used to identify global oxygen uptakedelivery mismatches. A level above 70% was the declared goal in early resuscitation of septic shock for over a decade. Recent evidence leads to doubts and levels higher than 80% may represent harmful conditions. This study ´s aim was to identify favourable ScvO2 levels in treatment of septic shock. Methods: Electronic data of patients suffering from septic shock who have been admitted to the surgical intensive care unit of a university hospital were analysed surveying a period of six years with focus on the association of ScvO2 levels with in-hospital mortality. Results: Data from 238 individuals were included. No difference was found comparing initially measured values of ScvO2 of survivors to non-survivors. Patients whose levels of ScvO2 never exceeded 70% (n=28) had a higher mortality rate (73.2% vs. 54.3%, p<0.05). On day three patients with values above 75% (n=32) had higher mortality rates (59.4% vs. 38.5%, p<0.05). A mortality rate of 100% was detected if ScvO2 levels exceeded 84% (n=6). Conclusions: ScvO2 develops from a therapy guiding parameter to a prognostic marker. Reaching levels of at least 70% within the first 72 h of disease is favourable in regard to prognosis. Exceeding 75% after day two is associated with higher mortality. These findings require further confirmation. At this point it can be assumed that a varying, time-dependent ScvO2 approach might be required for clinical decision-making.

Early administration of low dose norepinephrine for the prevention of organ dysfunctions in patients with sepsis

The importance of vasopressors in achieving the mean arterial pressure target in the early resuscitation of septic shock has been demonstrated and sepsis has been recently defined as a systemic response to infection with the presence of some degree of organ dysfunction [1, 2]. However, timing of norepinephrine (NE) for the prevention of organ dysfunctions in sepsis has not been investigated.

Venous congestion: are we adding insult to kidney injury in sepsis?

In critical illness, septic shock is a contributing factor in nearly half of all cases of acute kidney injury (AKI). Traditional approaches to prevention of organ dysfunction in early sepsis have focused on prevention of hypoperfusion by optimisation of systemic haemodynamics, primarily by fluid resuscitation. Fluid administration to a target central venous pressure (CVP) of 8 to 12 mmHg (12 to 15 mmHg in mechanically ventilated patients) is currently recommended for the early resuscitation of septic shock. However, in the previous issue of Critical Care, Legrand and colleagues report that higher CVP in the first 24 hours of ICU admission with septic shock was associated with increased risk for development or persistence of AKI over the next 5 days. This study highlights a potential association between venous congestion and the development of septic AKI, suggesting that CVP-targeted fluid resuscitation in septic shock might not be beneficial for renal function.

Persistently high venous-to-arterial carbon dioxide differences during early resuscitation are associated with poor outcomes in septic shock

IntroductionVenous-to-arterial carbon dioxide difference (Pv-aCO2) may reflect the adequacy of blood flow during shock states. We sought to test whether the development of Pv-aCO2 during the very early phases of resuscitation is related to multi-organ dysfunction and outcomes in a population of septic shock patients resuscitated targeting the usual oxygen-derived and hemodynamic parameters.MethodsWe conducted a prospective observational study in a 60-bed mixed ICU in a University affiliated Hospital. 85 patients with a new septic shock episode were included. A Pv-aCO2 value ≥ 6 mmHg was considered to be high. Patients were classified in four predefined groups according to the Pv-aCO2 evolution during the first 6 hours of resuscitation: (1) persistently high Pv-aCO2 (high at T0 and T6); (2) increasing Pv-aCO2 (normal at T0, high at T6); (3) decreasing Pv-aCO2 (high at T0, normal at T6); and (4) persistently normal Pv-aCO2 (normal at T0 and T6). Multiorgan dysfunction at day-3 was compared for predefined groups and a Kaplan Meier curve was constructed to show the survival probabilities at day-28 using a log-rank test to evaluate differences between groups. A Spearman-Rho was used to test the agreement between cardiac output and Pv-aCO2. Finally, we calculated the mortality risk ratios at day-28 among patients attaining normal oxygen parameters but with a concomitantly increased Pv-aCO2.ResultsPatients with persistently high and increasing Pv-aCO2 at T6 had significant higher SOFA scores at day-3 (p < 0.001) and higher mortality rates at day-28 (log rank test: 19.21, p < 0.001) compared with patients who evolved with normal Pv-aCO2 at T6. Interestingly, a poor agreement between cardiac output and Pv-aCO2 was observed (r2 = 0.025, p < 0.01) at different points of resuscitation. Patients who reached a central venous saturation (ScvO)2 ≥ 70% or mixed venous oxygen saturation (SvO2) ≥ 65% but with concomitantly high Pv-aCO2 at different developmental points (i.e., T0, T6 and T12) had a significant mortality risk ratio at day-28.ConclusionThe persistence of high Pv-aCO2 during the early resuscitation of septic shock was associated with more severe multi-organ dysfunction and worse outcomes at day-28. Although mechanisms conducting to increase Pv-aCO2 during septic shock are insufficiently understood, Pv-aCO2 could identify a high risk of death in apparently resuscitated patients.

Oxygen Tissue Saturation Is Lower in Nonsurvivors than in Survivors after Early Resuscitation of Septic Shock

Growing evidence suggests that the microvascular dysfunction is the key element of the pathogenesis of septic shock. This study's purpose was to explore whether the outcome of septic shock patients after early resuscitation using early goal-directed therapy is related to their muscle tissue oxygenation. Tissue oxygen saturation (Sto2) was monitored in septic shock patients using a tissue spectrometer (InSpectra Model 325; Hutchinson Technology, Hutchinson, MN). For the purpose of this retrospective study, the Sto2 values were collected at the first measurement done after the macrohemodynamic variables (mean arterial pressure, urine output, central venous saturation in oxygen) were optimized. After the hemodynamic variables were corrected, no difference was observed between the nonsurvivors and survivors, with the exception of pulse oximetry saturation (94% [92-97%] vs. 97% [94-99%], P = 0.04). The Sto2 values were significantly lower in the nonsurvivors than in the survivors (73% [68-82%] vs. 84% [81-90%], P = 0.02). No correlations were found between the Sto2 and Spo2 (P = 0.7). In septic shock patients, tissue oxygen saturation below 78% is associated with increased mortality at day 28. Further investigations are required to determine whether the correction of an impaired level of tissue oxygen saturation may improve the outcome of these patients.

Heart rate variability in the early resuscitation of septic shock

The assessment of heart rate variability (HRV) has provided valuable insight in sepsis. Impaired HRV has been shown to be diagnostic of sepsis, heralding its onset, and prognostic of its impact, correlating with the development of sepsis-induced organ failure and death.