Tissue oxygen saturation is predictive of lactate clearance in patients with circulatory shock.

BACKGROUND: Tissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2 and lactate clearance was unknown. METHODS: This was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2 on 6-hour lactate clearance > 10% since StO2 initially monitored was assessed. RESULTS: A total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac < 10% group (11 ± 3 vs. 15 ± 4, p = 0.007). Other baseline characteristics were comparable between groups. Compared to non-clearance group, StO2 in deltoid, thenar and knee were significantly higher in clearance group. The area under the receiver operating curves (AUROC) of BSA-weighted StO2 for prediction of lactate clearance (0.92, 95% CI [Confidence Interval] 0.82-1.00) was significantly higher than StO2 of masseter (0.65, 95% CI 0.45-0.84; p < 0.01), deltoid (0.77, 95% CI 0.60-0.94; p = 0.04), thenar (0.72, 95% CI 0.55-0.90; p = 0.01), and similar to knee (0.87, 0.73-1.00; p = 0.40), mean StO2 (0.85, 0.73-0.98; p = 0.09). Additionally, BSA-weighted StO2 model had continuous net reclassification improvement (NRI) over the knee StO2 and mean StO2 model (continuous NRI 48.1% and 90.2%, respectively). The AUROC of BSA-weighted StO2 was 0.91(95% CI 0.75-1.0) adjusted by mean arterial pressure and norepinephrine dose. CONCLUSIONS: Our results suggested that BSA-weighted StO2 was a strong predictor of 6-hour lactate clearance in patients with shock.

Accuracy of Mean Value of Central Venous Pressure from Monitor Digital Display: Influence of Amplitude of Central Venous Pressure during Respiration.

Background A simple measurement of central venous pressure (CVP)-mean by the digital monitor display has become increasingly popular. However, the agreement between CVP-mean and CVP-end (a standard method of CVP measurement by analyzing the waveform at end-expiration) is not well determined. This study was designed to identify the relationship between CVP-mean and CVP-end in critically ill patients and to introduce a new parameter of CVP amplitude (ΔCVP= CVPmax - CVPmin) during the respiratory period to identify the agreement/disagreement between CVP-mean and CVP-end.Methods In total, 291 patients were included in the study. CVP-mean and CVP-end were obtained simultaneously from each patient. CVP measurement difference (|CVP-mean - CVP-end|) was defined as the difference between CVP-mean and CVP-end. The ΔCVP was calculated as the difference between the peak (CVPmax) and the nadir value (CVPmin) during the respiratory cycle, which was automatically recorded on the monitor screen. Subjects with |CVP-mean - CVP-end|≥ 2 mmHg were divided into the inconsistent group, while subjects with |CVP-mean - CVP-end| < 2 mmHg were divided into the consistent group.Results ΔCVP was significantly higher in the inconsistent group [7.17(2.77) vs.5.24(2.18), P<0.001] than that in the consistent group. There was a significantly positive relationship between ΔCVP and |CVP-mean - CVP-end| (r=0.283, P <0.0001). Bland-Altman plot showed the bias was -0.61 mmHg with a wide 95% limit of agreement (-3.34, 2.10) of CVP-end and CVP-mean. The area under the receiver operating characteristic curves (AUC) of ΔCVP for predicting |CVP-mean - CVP-end| ≥ 2 mmHg was 0.709. With a high diagnostic specificity, using ΔCVP<3 to detect |CVP-mean - CVP-end| lower than 2mmHg (consistent measurement) resulted in a sensitivity of 22.37% and a specificity of 93.06%. Using ΔCVP>8 to detect |CVP-mean - CVP-end| >8 mmHg (inconsistent measurement) resulted in a sensitivity of 31.94% and a specificity of 91.32%.Conclusions CVP-end and CVP-mean have statistical discrepancies in specific clinical scenarios. ΔCVP during the respiratory period is related to the variation of the two CVP methods. A high ΔCVP indicates a poor agreement between these two methods, whereas a low ΔCVP indicates a good agreement between these two methods.

Ursodeoxycholic Acid (UDCA) Reduces Hepatocyte Apoptosis by Inhibiting Farnesoid X Receptor (FXR) in Hemorrhagic Shock (HS).

BACKGROUND: Hemorrhagic shock (HS) is the most common cause of potentially preventable death after traumatic injury. Acute liver injury is an important manifestation of HS. Apoptosis plays an important role in liver injury. Farnesoid X receptor (FXR) can alleviate liver injury. This study aimed to examine the effects of ursodeoxycholic acid (UDCA) on hepatocyte apoptosis in HS and its relationship with the FXR pathway. METHODS: Mice were randomly divided into 4 groups: sham group, HS group, HS + UDCA group, and FXR (-) + HS + UDCA group. There were 6 mice in each group. As to the model of HS, MAP of 40 ± 5 mmHg was maintained for 1 hour. As to UDCA intervention, UDCA (300mg/kg) was given nasally. Real-time RT-PCR and Western blotting were used to detect changes in the expression level of Caspase-3, Bax, LC3Ⅰ, LC3Ⅱ, Bcl-2, and Beclin-1 in the liver. TUNEL assay was used to detect changes in hepatocyte apoptosis. RESULTS: The expression level of Caspase-3 and Bax in the liver decreased significantly after treatment with UDCA under HS conditions. The expression level of LC3Ⅰ, LC3Ⅱ, Bcl-2, and Beclin-1 in the liver increased significantly after treatment with UDCA under HS conditions. TUNEL positive percentage of liver decreased significantly after treatment with UDCA under HS conditions. In the case of FXR (-), the influence of UDCA was inhibited. CONCLUSION: These results indicated that UDCA could reduce hepatocyte apoptosis during HS through the FXR pathway.

Changes of farnesoid X receptor and Takeda G-protein coupled receptor 5 following biliary tract external drainage in hemorrhagic shock.

Since biliary tract external drainage (BTED) is increasingly used to treat patients with shock, it is necessary to clarify pathophysiological changes following BTED in hemorrhagic shock (HS). The present study aimed to investigate the effect of BTED on farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR-5) expression in HS. A total of 24 Sprague-Dawley rats were randomly allocated to sham, BTED, HS and HS + BTED groups. Rat models of HS were induced by drawing blood from the femoral artery until a mean arterial pressure of 40±5 mmHg was achieved and maintained for 60 min. Rat models of BTED were induced by inserting a catheter into the bile duct. The distal end of the bile duct was ligated, and the catheter was passed through the rat flank to allow external collection of bile. Reverse transcription-quantitative PCR, western blotting and immunohistochemistry were performed to detect changes in expression levels of FXR and TGR-5 in the jejunum, ileum and liver. Expression levels of FXR and TGR-5 increased significantly in jejunum and liver following HS (P<0.05). BTED significantly decreased expression levels of FXR in the liver (P<0.05) and TGR-5 in the jejunum, ileum and liver (P<0.05). In conclusion, expression levels of FXR and TGR-5 increased in HS but BTED decreased expression levels of FXR and TGR-5 in HS.

Cross-sectional study for the clinical application of extracorporeal membrane oxygenation in Mainland China, 2018.

BACKGROUND: To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018. METHODS: Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database. RESULTS: The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31-63), and 1346 were male. The average hospital stay was 17 days (IQR 7-30), and the average costs per case was $36,334 (IQR 22,547-56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality. CONCLUSIONS: Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.

Progress of mechanical power in the intensive care unit.

Mechanical power of ventilation, currently defined as the energy delivered from the ventilator to the respiratory system over a period of time, has been recognized as a promising indicator to evaluate ventilator-induced lung injury and predict the prognosis of ventilated critically ill patients. Mechanical power can be accurately measured by the geometric method, while simplified equations allow an easy estimation of mechanical power at the bedside. There may exist a safety threshold of mechanical power above which lung injury is inevitable, and the assessment of mechanical power might be helpful to determine whether the extracorporeal respiratory support is needed in patients with acute respiratory distress syndrome. It should be noted that relatively low mechanical power does not exclude the possibility of lung injury. Lung size and inhomogeneity should also be taken into consideration. Problems regarding the safety limits of mechanical power and contribution of each component to lung injury have not been determined yet. Whether mechanical power-directed lung-protective ventilation strategy could improve clinical outcomes also needs further investigation. Therefore, this review discusses the algorithms, clinical relevance, optimization, and future directions of mechanical power in critically ill patients.

Effect of mean arterial pressure change by norepinephrine on peripheral perfusion index in septic shock patients after early resuscitation.

BACKGROUND: The peripheral perfusion index (PI), as a real-time bedside indicator of peripheral tissue perfusion, may be useful for determining mean arterial pressure (MAP) after early resuscitation of septic shock patients. The aim of this study was to explore the response of PI to norepinephrine (NE)-induced changes in MAP. METHODS: Twenty septic shock patients with pulse-induced contour cardiac output catheter, who had usual MAP under NE infusion after early resuscitation, were enrolled in this prospective, open-label study. Three MAP levels (usual MAP -10 mmHg, usual MAP, and usual MAP +10 mmHg) were obtained by NE titration, and the corresponding global hemodynamic parameters and PI were recorded. The general linear model with repeated measures was used for analysis of variance of related parameters at three MAP levels. RESULTS: With increasing NE infusion, significant changes were found in MAP (F = 502.46, P < 0.001) and central venous pressure (F = 27.45, P < 0.001) during NE titration. However, there was not a significant and consistent change in continuous cardiac output (CO) (F = 0.41, P = 0.720) and PI (F = 0.73, P = 0.482) at different MAP levels. Of the 20 patients enrolled, seven reached the maximum PI value at usual MAP -10 mmHg, three reached the maximum PI value at usual MAP, and ten reached the maximum PI value at usual MAP +10 mmHg. The change in PI was not significantly correlated with the change in CO (r = 0.260, P = 0.269) from usual MAP -10 mmHg to usual MAP. There was also no significant correlation between the change in PI and change in CO (r = 0.084, P = 0.726) from usual MAP to usual MAP +10 mmHg. CONCLUSIONS: Differing MAP levels by NE infusion induced diverse PI responses in septic shock patients, and these PI responses may be independent of the change in CO. PI may have potential applications for MAP optimization based on changes in peripheral tissue perfusion.

Ursodeoxycholic Acid (UDCA) Promotes Lactate Metabolism in Mouse Hepatocytes through Cholic Acid (CA) - Farnesoid X Receptor (FXR) Pathway.

BACKGROUND: Persistent hyperlactatemia is associated with greater mortality in shock. Liver is the main site of lactate metabolism. METHOD: In the first part, freshly isolated hepatocytes were incubated in 10% fetal bovine serum William's E medium supplemented with 10 mM lactate. Cells were then exposed to 100 µM ursodeoxycholic acid (UDCA), with no addition (control) for 2, 4, 6, 8 h. In the second part, hepatocytes were treated with Silencer select siRNA targeting FXR or scramble siRNA. The siRNA treatment was repeated twenty four hours later, and the cells were used in the experiments twenty-four hours after the second treatment. Then hepatocytes were incubated in 10% fetal bovine serum William's E medium supplemented with 10 mM lactate. Cells were then exposed to 100 µM UDCA for 2, 4, 6, 8 h. Lactate concentration was determined by ABL80 automatic blood gas analyzer. RESULTS: UDCA increased ability of hepatocytes to remove lactate. After the knockdown of FXR, effects caused by UDCA were weakened. CONCLUSION: These results demonstrate that UDCA promotes lactate metabolism in mouse hepatocytes through CA-FXR pathway.

Resuscitation incoherence and dynamic circulation-perfusion coupling in circulatory shock.

OBJECTIVE: Poor tissue perfusion/cellular hypoxia may persist despite restoration of the macrocirculation (Macro). This article reviewed the literatures of coherence between hemodynamics and tissue perfusion in circulatory shock. DATA SOURCES: We retrieved information from the PubMed database up to January 2018 using various search terms or/and their combinations, including resuscitation, circulatory shock, septic shock, tissue perfusion, hemodynamic coherence, and microcirculation (Micro). STUDY SELECTION: The data from peer-reviewed journals printed in English on the relationships of tissue perfusion, shock, and resuscitation were included. RESULTS: A binary (coherence/incoherence, coupled/uncoupled, or associated/disassociated) mode is used to describe resuscitation coherence. The phenomenon of resuscitation incoherence (RI) has gained great attention. However, the RI concept requires a more practical, systematic, and comprehensive framework for use in clinical practice. Moreover, we introduce a conceptual framework of RI to evaluate the interrelationship of the Macro, Micro, and cell. The RI is divided into four types (Type 1: Macro-Micro incoherence + impaired cell; Type 2: Macro-Micro incoherence + normal cell; Type 3: Micro-Cell incoherence + normal Micro; and Type 4: both Macro-Micro and Micro-cell incoherence). Furthermore, we propose the concept of dynamic circulation-perfusion coupling to evaluate the relationship of circulation and tissue perfusion during circulatory shock. CONCLUSIONS: The concept of RI and dynamic circulation-perfusion coupling should be considered in the management of circulatory shock. Moreover, these concepts require further studies in clinical practice.

Role of Combining Peripheral with Sublingual Perfusion on Evaluating Microcirculation and Predicting Prognosis in Patients with Septic Shock.

BACKGROUND: Measurement of general microcirculation remains difficult in septic shock patients. The peripheral perfusion index (PI) and sublingual microcirculation monitoring are thought to be possible methods. This study was performed to determine whether assessing microcirculation by PI and a new parameter, proportion of perfusion vessel change rate (△PPV) from sublingual microcirculation monitoring, can be associated with patients' outcome. METHODS: A prospective observational study was carried out, including 74 patients with septic shock in a mixed intensive care unit. Systemic hemodynamic variables were obtained at T0 and 6 h after (T6). PI and sublingual microcirculation indicators were obtained using a bedside monitor and a sidestream dark-field device, respectively. The t-test, analysis of variance, Mann-Whitney U-test, Kruskal-Wallis test, receiver operating characteristic curve analysis with the Hanley-McNeil test, survival curves using the Kaplan-Meier method, and the log-rank (Mantel-Cox) test were used to statistical analysis. RESULTS: Systemic hemodynamics and microcirculation data were obtained and analyzed. Patients were divided into two groups based on whether the first 6 h lactate clearance (LC) was ≥20%; PI and △PPV were lower at T6 in the LC <20% group compared with LC ≥20% (PI: 1.52 [0.89, 1.98] vs. 0.79 [0.44, 1,81], Z = -2.514, P = 0.012; △PPV: 5.9 ± 15.2 vs. 17.9 ± 20.0, t = -2.914, P = 0.005). The cutoff values of PI and △PPV were 1.41% and 12.1%, respectively. The cutoff value of the combined indicators was 1.379 according to logistic regression. Area under the curve demonstrated 0.709 (P < 0.05), and the sensitivity and specificity of using combined indicators were 0.622 and 0.757, respectively. Based on the PI and △PPV cutoff, all the participants were divided into the following groups: (1) high PI and high △PPV group, (2) high PI and low △PPV group, (3) low PI and high △PPV group, and (4) low PI and low △PPV group. The highest Sequential Organ Failure Assessment score (14.5 ± 2.9) was in the low PI and low △PPV group (F = 13.7, P < 0.001). Post hoc tests showed significant differences in 28-day survival rates among these four groups (log rank [Mantel-Cox], 20.931; P < 0.05). CONCLUSION: PI and △PPV in septic shock patients are related to 6 h LC, and combining these two parameters to assess microcirculation can predict organ dysfunction and 28-day mortality in patients with septic shock.

Assessment of Lung Recruitment by Electrical Impedance Tomography and Oxygenation in ARDS Patients.

We hypothesized that not all patients with appreciably recruited lung tissue during a recruitment maneuver (RM) show significant improvement of oxygenation. In the present study, we combined electrical impedance tomography (EIT) with oxygenation measurements to examine the discrepancies of lung ventilation and perfusion versus oxygenation after RM.A 2-minute RM (20 cm H2O positive end-expiratory pressure [PEEP] + 20 cm H2O pressure control) was prospectively conducted in 20 acute respiratory distress syndrome patients from January 2014 to December 2014. A decremental PEEP trial was performed to select the PEEP level after RM. A positive response to RM was identified as PaO2 + PaCO2 ≥400 mm Hg. Relative differences in the distribution of ventilation and perfusion in the most dependent region of interest (ROI4) were monitored with EIT and denoted as the ventilation-perfusion index.Ten patients were found to be responders and 10 patients to be nonresponders. No significant difference in baseline PaO2/FiO2 was observed between nonresponders and responders. A significantly higher PaO2/FiO2 ratio during RM and higher PEEP set after PEEP titration were recorded in responders. In both responders and nonresponders, the proportion of ventilation distributed in ROI4 compared with the global value was lower than the cardiac-related activity before RM, but this situation was reversed after RM (P < 0.01 in each group). Six out of 10 nonresponders exhibited a remarkable increase in ventilation in ROI4. A significant difference in the relative ventilation-perfusion index was found between the patients with remarkable and insufficient lung tissue reopening in the nonresponder group (P < 0.01).A discrepancy between lung tissue reopening and oxygenation improvement after RM was observed. EIT has the potential to evaluate the efficacy of RM by combining oxygenation measurements.

High central venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio is associated with poor lactate clearance in septic patients after resuscitation.

OBJECTIVE: Recently, the central venoarterial carbon dioxide difference/arterial-central venous oxygen difference (P(v-a)CO2/C(a-v)O2) ratio has been suggested as an additional indicator of anaerobic metabolism. We investigated the relationship between the P(v-a)CO2/C(a-v)O2 ratio and 8-hour lactate clearance (LC) in septic patients after resuscitation. METHODS AND RESULTS: We prospectively obtained 168 sets of measurements from 84 septic patients. The arterial and central venous blood gases were measured simultaneously at enrollment and 8 hours after resuscitation. The P(v-a)CO2/C(a-v)O2 (r = -0.24, P = .028) at T8 was negatively correlated with 8-hour LC after resuscitation in all patients. The patients with 8-hour LC ≥ 10% exhibited significantly lower P(v-a)CO2/C(a-v)O2 ratios and intensive care unit mortality after resuscitation than the patients with 8-hour LC < 10%. The area under the receiver operating characteristic curve of the P(v-a)CO2/C(a-v)O2 ratio for the detection of LC ≥ 10% was the greatest and was significantly better than that of the central venous oxygen saturation and similar to that of the P(v-a)CO2. Moreover, a P(v-a)CO2/C(a-v)O2 < 1.23 at T8 is related to poor 8-hour LC rate (LC ≥ 10%) in the patients with normalized central venous oxygen saturation values (≥70%) after resuscitation. CONCLUSIONS: The high P(v-a)CO2/C(a-v)O2 ratio is associated with poor LC after resuscitation. The P(v-a)CO2/C(a-v)O2 ratio may provide useful information for assessing the LC potential and optimizing the LC rate.

The effect of variable arterial transducer level on the accuracy of pulse contour waveform-derived measurements in critically ill patients.

We know that a 10 cm departure from the reference level of pressure transducer position is equal to a 7.5 mmHg change of invasive hemodynamic pressure monitoring in a fluid-filled system. However, the relationship between the site level of a variable arterial pressure transducer and the pulse contour-derived parameters has yet to be established in critically ill patients. Moreover, the related quantitative analysis has never been investigated. Forty-two critically ill patients requiring PiCCO-Plus cardiac output monitoring were prospectively studied. The phlebostatic axis was defined as the zero reference level; the arterial pressure transducer was then vertically adjusted to different positions (+5, +10, +15, +20, -20, -15, -10, -5 cm) of departure from the zero reference site. The pulse contour waveform-derived parameters were recorded at each position. Elevation of the pressure transducer caused significantly positive changes in the continuous cardiac index (+CCI), stroke volume index (+SVI), and stroke volume variation (+SVV), and negative changes in the rate of left ventricular pressure rise during systole (-dP/dtmax), the systemic vascular resistance index (-SVRI), and vice versa. At the 5 cm position, the SVRI changes reached statistical significance with error. At the 10 cm position, the changes in CCI and dP/dtmax reached statistical significance with error, while the change in SVV reached statistical significance at 15 cm. The change rate of CCI was more than 5 % at the 15 cm position and approximately 10 % at the 20 cm position. On average, for every centimeter change of the transducer, there was a corresponding 0.014 L/min/m(2) CCI change and 0.36 % change rate, a 1.41 mmHg/s dP/dtmax change and 0.13 % change rate, and a 25 dyne/s/cm(5) SVRI change and 1.2 % change rate. The variation of arterial transducer position can result in inaccurate measurement of pulse contour waveform-derived parameters, especially when the transducer's vertical distance is more than 10 cm from the phlebostatic axis. These findings have clinical implications for continuous hemodynamic monitoring.