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High central venous oxygen saturation is associated with mitochondrial dysfunction in septic shock: A prospective observational study.

ABSTRACT: To test the hypothesis that an impaired mitochondrial function is associated with altered central venous oxygen saturation (ScvO2 ), venous-to-arterial carbon dioxide tension difference (delta PCO2 ) or serum lactate in sepsis patients. This prospective cohort study was conducted in a single tertiary emergency department between April 2017 and March 2019. Patients with suspected sepsis were included in the study. Serum lactate was obtained in sepsis, ScvO2 and delta PCO2 were evaluated in septic shock patients. Mitochondrial function was determined from the peripheral blood mononuclear cells. Forty-six patients with suspected sepsis were included. Of these, twenty patients were septic shock. Mitochondrial oxidative stress levels were increased in the high ScvO2 group (ScvO2 > 80%, n = 6), compared with the normal (70%-80%, n = 9) and low ScvO2 (<70%, n = 5) groups. A strong linear relationship was observed between the mitochondrial oxidative stress and ScvO2 (r = .75; P = .01). However, mitochondrial respiration was increased in the low ScvO2 group. In addition, mitochondrial complex II protein levels were significantly decreased in the high ScvO2 group (P < .05). Additionally, there was no correlation between serum lactate, delta PCO2 , and mitochondria oxidative stress or mitochondria function. ScvO2 can be potentially useful for developing new therapeutics to reduce mitochondrial dysfunction in septic shock patient.

SUBMITTER: Wittayachamnankul B

PROVIDER: S-EPMC7294163 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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High central venous oxygen saturation is associated with mitochondrial dysfunction in septic shock: A prospective observational study.

Wittayachamnankul Borwon B Apaijai Nattayaporn N Sutham Krongkarn K Chenthanakij Boriboon B Liwsrisakun Chalerm C Jaiwongkam Thidarat T Chattipakorn Siriporn C SC Chattipakorn Nipon N

Journal of cellular and molecular medicine 20200430 11

To test the hypothesis that an impaired mitochondrial function is associated with altered central venous oxygen saturation (ScvO2 ), venous-to-arterial carbon dioxide tension difference (delta PCO2 ) or serum lactate in sepsis patients. This prospective cohort study was conducted in a single tertiary emergency department between April 2017 and March 2019. Patients with suspected sepsis were included in the study. Serum lactate was obtained in sepsis, ScvO2 and de ...[more]

PMID: 32352229

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Project description:BackgroundReduced cellular ATP synthesis due to impaired mitochondrial function of immune cells may be a factor influencing the immune response in septic shock. We investigate changes in mitochondrial function and bioenergetics of human monocytes and lymphocyte subsets.MethodsThirty patients with septic shock were studied at ICU admission, after 24 and 48 hours, and after resolution of shock. Enzymatic activities of citrate synthase and mitochondrial complexes I, IV, and ATP synthase and ATP content of monocytes, T-cells and B-cells and pro-inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokine plasma concentrations were compared to samples from 20 healthy volunteers.ResultsLarge variations in mitochondrial enzymatic activities of immune cells of septic patients were detected. In monocytes, maximum levels of citrate synthase activity in sepsis were significantly lower when compared to controls (p = 0.021). Maximum relative enzymatic activity (ratio relative to citrate synthase activity) of complex I (p<0.001), complex IV (p = 0.017) and ATP synthase (p<0.001) were significantly higher. In T-cells, maximum levels of citrate synthase (p = 0.583) and relative complex IV (p = 0.602) activity did not differ between patients and controls, whereas levels of relative complex I (p = 0.006) and ATP synthase (p = 0.032) were significantly higher in septic patients. In B-cells of patients, maximum levels of citrate synthase activity (p = 0.004) and relative complex I (p<0.001) were significantly higher, and mean levels of relative complex IV (p = 0.042) lower than the control values, whereas relative ATP synthase activity did not differ (p = 1.0). No significant difference in cellular ATP content was detected in any cell line (p = 0.142-0.519). No significant correlations between specific cytokines and parameters of mitochondrial enzymatic activities or ATP content were observed.ConclusionsSignificant changes of mitochondrial enzymatic activities occur in human peripheral blood immune cells in septic shock when compared to healthy controls. Assessed sub-types of immune cells showed differing patterns of regulation. Total ATP-content of human immune cells did not differ between patients in septic shock and healthy volunteers.

Project description:BackgroundContinuous monitoring of central venous oxygen saturation (ScvO2) has been proposed as a prognostic indicator in several pathological conditions, including cardiac diseases, sepsis, trauma. To our knowledge, no studies have evaluated ScvO2 in polytraumatized patients with brain injury so far. Thus, the aim of the present study was to assess the prognostic role of ScvO2 monitoring during first 24 hours after trauma in this patients' population.MethodsThis prospective, non-controlled study, carried out between April 2006 and March 2008, was performed in a higher level Trauma Center in Florence (Italy). In the study period, 121 patients affected by major brain injury after major trauma were recruited. Inclusion criteria were: 1. Glasgow Coma Scale (GCS) score <or= 13; 2. an Injury Severity Score (ISS) >or= 15. Exclusion criteria included: 1. pregnancy; 2. age < 14 years; 3. isolated head trauma; 4. death within the first 24 hours from the event; 5. the lack of ScvO2 monitoring within 2 hours from the trauma. Demographic and clinical data were collected, including Abbreviated Injury Scale (AIS), Injury Severity Score (ISS), Simplified Acute Physiologic Score II (SAPS II), Marshall score. The worst values of lactate and ScvO2 within the first 24 hours from trauma, ICU length of stay (LOS), and 28-day mortality were recorded.ResultsPatients who deceased within 28 days showed higher age (53 +/- 16.6 vs 43.8 +/- 19.6, P = 0.043), ISS core (39.3 +/- 14 vs 30.3 +/- 10.1, P < 0.001), AIS score for head/neck (4.5 +/- 0.7 vs 3.4 +/- 1.2, P = 0.001), SAPS II score (51.3 +/- 14.1 vs 42.5 +/- 15, P = 0.014), Marshall Score (3.5 +/- 0.7 vs 2.3 +/- 0.7, P < 0.001) and arterial lactate concentration (3.3 +/- 1.8 vs 6.7 +/- 4.2, P < 0.001), than survived patients, whereas ScvO2 resulted significantly lower (66.7% +/- 11.9 vs 70.1% +/- 8.9 vs, respectively; P = 0.046). Patients with ScvO2 values <or= 65% also showed higher 28-days mortality rate (31.3% vs 13.5%, P = 0.034), ICU LOS (28.5 +/- 15.2 vs 16.6 +/- 13.8, P < 0.001), and total hospital LOS (45.1 +/- 20.8 vs 33.2 +/- 24, P = 0.046) than patients with ScvO2 > 65%.ConclusionScvO2 value less than 65%, measured in the first 24 hours after admission in patients with major trauma and head injury, was associated with higher mortality and prolonged hospitalization.

Project description:BackgroundCentral venous oxygen saturation (ScvO2) is often used to help to guide resuscitation of critically ill patients. The standard gold technique for ScvO2 measurement is the co-oximetry (Co-oximetry_ScvO2), which is usually incorporated in most recent blood gas analyzers. However, in some hospitals, those machines are not available and only calculated ScvO2 (Calc_ScvO2) is provided. Therefore, we aimed to investigate the agreement between Co-oximetry_ScvO2 and Calc_ScvO2 in a general population of critically ill patients and septic shock patients.MethodsA total of 100 patients with a central venous catheter were included in the study. One hundred central venous blood samples were collected and analyzed using the same point-of-care blood gas analyzer, which provides both the calculated and measured ScvO2 values. Bland and Altman plot, intra-class correlation coefficient (ICC), and Cohen's Kappa coefficient were used to assess the agreement between Co-oximetry_ScvO2 and Calc_ScvO2. Multiple linear regression analysis was performed to investigate the independent explanatory variables of the difference between Co-oximetry_ScvO2 and Calc_ScvO2.ResultsIn all population, Bland and Altman's analysis showed poor agreement (+4.5 [-7.1, +16.1]%) between the two techniques. The ICC was 0.754 [(95% CI: 0.393-0.880), P< 0.001], and the Cohen's Kappa coefficient, after categorizing the two variables into two groups using a cutoff value of 70%, was 0.470 (P <0.001). In septic shock patients (49%), Bland and Altman's analysis also showed poor agreement (+5.6 [-6.7 to 17.8]%). The ICC was 0.720 [95% CI: 0.222-0.881], and the Cohen's Kappa coefficient was 0.501 (P <0.001). Four independent variables (PcvO2, Co-oximetry_ScvO2, venous pH, and Hb) were found to be associated with the difference between the measured and calculated ScvO2 (adjusted R2 = 0.8, P<0.001), with PcvO2 being the main independent explanatory variable because of its highest absolute standardized coefficient. The area under the receiver operator characteristic curves (AUC) of PcvO2 to predict Co-oximetry_ScvO2 ? 70% was 0.911 [95% CI: 0.837-0.959], in all patients, and 0.903 [95% CI: 0.784-0.969], in septic shock patients. The best cutoff value was ? 36 mmHg (sensitivity, 88%; specificity, 83%), in all patients, and ? 35 mmHg (sensitivity, 94%; specificity, 71%) in septic shock patients.ConclusionsThe discrepancy between the measured and calculated ScvO2 is clinically not acceptable. We do not recommend the use of calculated ScvO2 to guide resuscitation in critically ill patients. In situations where the Co-oximetry technique is not available, relying on PcvO2 to predict the measured ScvO2 value above or below 70% could be an option.

Dataset Information

High central venous oxygen saturation is associated with mitochondrial dysfunction in septic shock: A prospective observational study.

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High central venous oxygen saturation is associated with mitochondrial dysfunction in septic shock: A prospective observational study.

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