Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis

OBJECTIVE: During sepsis, after an initial stimulation immune cells down-regulate their functions, leading to a state of immunosuppression. Because the mechanisms of such down-regulation are unclear, we investigated the hypothesis of an energetic failure of immune cells to participate in immune dysfunction. DESIGN: Cohort of septic shock patients to study peripheral blood mononuclear cells (PBMCs) biological energy in comparison to healthy volunteer cells. SETTING: Critical care unit and laboratory, university hospital. SUBJECTS: Eighteen severe sepsis or septic shock patients and 32 healthy volunteers. INTERVENTIONS: Ex vivo measurement of oxygen consumption in PBMCs taken from patients. The PBMCs' mitochondrial oxidative phosphorylation was investigated using adenosine diphosphate stimulation. The plasma factors implication was tested, using healthy cells incubated in septic plasma, or septic cells incubated in healthy plasma, at different time points of sepsis. The relationship between monocyte human leukocyte antigen-DR expression and bioenergetic results was tested. MEASUREMENTS AND MAIN RESULTS: Baseline oxygen consumption was higher in septic PBMCs (p < .01), with an attenuated response to adenosine diphosphate stimulation (p < .01). Oxygen consumption of healthy PBMCs incubated in septic plasma mimicked the septic cell response, with amplitude depending on the duration of sepsis (days 0-28). Septic cells incubated in healthy plasma partially recovered normal patterns. Septic plasma incubation increased the fraction of decoupling oxygen consumption (p = .021). A relationship between oxygen consumption (baseline or adenosine diphosphate stimulated) and human leukocyte antigen-DR expression was observed for incubation with plasma sampled at different time points of septic shock. CONCLUSION: Energetic failure of PBMCs in sepsis may be a factor associated with the modulation of immune response and human leukocyte antigen-DR phenotype, partially driven by plasma factors.     

Clinical spectrum, frequency, and significance of myocardial dysfunction in severe sepsis and septic shock

ObjectiveTo determine the frequency and spectrum of myocardial dysfunction in patients with severe sepsis and septic shock using transthoracic echocardiography and to evaluate the impact of the myocardial dysfunction types on mortality.Patients and MethodsA prospective study of 106 patients with severe sepsis or septic shock was conducted from August 1, 2007, to January 31, 2009. All patients underwent transthoracic echocardiography within 24 hours of admission to the intensive care unit. Myocardial dysfunction was classified as left ventricular (LV) diastolic, LV systolic, and right ventricular (RV) dysfunction. Frequency of myocardial dysfunction was calculated, and demographic, hemodynamic, and physiologic variables and mortality were compared between the myocardial dysfunction types and patients without cardiac dysfunction.ResultsThe frequency of myocardial dysfunction in patients with severe sepsis or septic shock was 64% (n=68). Left ventricular diastolic dysfunction was present in 39 patients (37%), LV systolic dysfunction in 29 (27%), and RV dysfunction in 33 (31%). There was significant overlap. The 30-day and 1-year mortality rates were 36% and 57%, respectively. There was no difference in mortality between patients with normal myocardial function and those with left, right, or any ventricular dysfunction.ConclusionMyocardial dysfunction is frequent in patients with severe sepsis or septic shock and has a wide spectrum including LV diastolic, LV systolic, and RV dysfunction types. Although evaluation for the presence and type of myocardial dysfunction is important for tailoring specific therapy, its presence in patients with severe sepsis and septic shock was not associated with increased 30-day or 1-year mortality.     

Jejunal luminal nitric oxide during severe hypovolemia and sepsis in anesthetized pigs

OBJECTIVE: Lowered gut blood perfusion and the associated intestinal mucosal barrier dysfunction is considered important in the pathophysiology leading to critical illness. Intestinal mucosal nitric oxide formation has been attributed a key role in the regulation of epithelial permeability and other properties of the intestinal mucosal barrier. This study was performed to delineate intestinal mucosal NO formation during hypovolemia or sepsis, both of which are associated with intestinal hypoperfusion. MATERIALS AND METHODS: Seventeen pigs were subjected to 2 h of severe hypovolemia (bleeding induced) or sepsis (systemic infusion of live Escherichia coli) or no treatment (controls). Jejunal mucosal NO production was monitored by a tonometer. Mesenteric blood flow was measured as portal venous blood flow by an ultrasonic transit time flowmeter probe, and oxygen delivery and consumption were calculated from regional blood samples. RESULTS: Intestinal perfusion and oxygen delivery were reduced by the same order of magnitude in both groups. Jejunal mucosal NO production and oxygen consumption decreased markedly in the hypovolemia group but remained stable in the group subjected to septic shock. CONCLUSIONS: These data suggest that blood loss inhibits jejunal mucosal NO production as part of a general downregulation of nonvital organs. Sepsis represents a more complex stress condition with activation/maintenance of host defense mechanisms as reflected by maintained jejunal mucosal NO production despite reduced gut blood perfusion.     

A pilot-controlled study of a polymyxin B-immobilized hemoperfusion cartridge in patients with severe sepsis secondary to intra-abdominal infection

Endotoxin is an important pathogenic trigger for sepsis. The polymyxin B-immobilized endotoxin removal hemoperfusion cartridge, Toraymyxin (hereafter PMX), has been shown to remove endotoxin in preclinical and open-label clinical studies. In a multicenter, open-label, pilot, randomized, controlled study conducted in the intensive care unit in six academic medical centers in Europe, 36 postsurgical patients with severe sepsis or septic shock secondary to intra-abdominal infection were randomized to PMX treatment of 2 h (n = 17) or standard therapy (n = 19). PMX was well tolerated and showed no significant side effects. There were no statistically significant differences in the change in endotoxin levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. There was also no significant difference in the change in interleukin (IL)-6 levels from baseline to 6 to 8 h after treatment or to 24 h after treatment between the two groups. Patients treated with PMX demonstrated significant increases in cardiac index (CI; P = 0.012 and 0.032 at days 1 and 2, respectively), left ventricular stroke work index (LVSWI, P = 0.015 at day 2), and oxygen delivery index (DO2I, P = 0.007 at day 2) compared with the controls. The need for continuous renal replacement therapy (CRRT) after study entry was reduced in the PMX group (P = 0.043). There was no significant difference between the groups in organ dysfunction as assessed by the Sequential Organ Failure Assessment (SOFA) scores from day 0 (baseline) to day 6. Treatment using the PMX cartridge is safe and may improve cardiac and renal dysfunction due to sepsis or septic shock. Further studies are needed to prove this effectiveness.     

Effect of high dose norepinephrine versus epinephrine on cerebral and myocardial blood flow during CPR

Several animal studies have demonstrated an improvement in cerebral blood flow (CBF) and myocardial blood flow (MBF) after the administration of epinephrine (E) 0.20 mg/kg during closed chest CPR. The administration of norepinephrine (NE) in doses of 0.12 and 0.16 mg/kg demonstrated a trend toward improved CBF and MBF during CPR over that seen with E 0.20 mg/kg in the same animal model. The purpose of this study was to compare the effects of a higher dose of NE 0.20 mg/kg to E 0.20 mg/kg to determine if increasing doses of NE would demonstrate further improvement in CBF and MBF during CPR. Fourteen immature swine were anesthetized and instrumented for regional blood flow and hemodynamic measurements. After 10 min of ventricular fibrillation (VF), CPR was begun using a mechanical thumper. After 3 min of CPR, the animals received either E 0.20 mg/kg (n = 7) or NE 0.20 mg/kg (n = 7) through a right atrial catheter. CPR was continued for an additional 3.5 min and defibrillation was then attempted. CBF (ml/min/100 g), MBF (ml/min/100 g), myocardial oxygen delivery (MDo2; ml O2/min/100 g), myocardial oxygen consumption (MVo2; ml O2/min/100 g), and myocardial oxygen extraction ratios (ER, MVo2/MDo2) were measured during normal sinus rhythm (NSR), during CPR, and during CPR following drug administration. Following drug administration, CBF, MBF, MDo2 and MVo2 rose while ER fell in both E and NE groups. There were no significant differences between groups in CBF, ER, or intravascular pressures following drug administration (P greater than or equal to 0.07). The NE group demonstrated significantly higher MBF (118.9 +/- 73.1 vs. 62.2 +/- 45.3, P = 0.04), MVo2 (14.2 +/- 7.7 vs. 7.0 +/- 3.8, P = 0.05), and MDo2 (19.9 +/- 13.4 versus 9.4 +/- 6.3, P = 0.05) compared to the E group following drug administration While NE improved MBF and MDo2 over E during CPR, there was a trend toward lower resuscitation rates with NE (57.1% vs. 85.7% P = 0.56). Any benefit of higher MBF and MDo2 with NE 0.20 mg/kg appears to be offset by proportionately high MVo2 and a trend toward lower resuscitation rates in the NE 0.20 mg/kg animals.     

Optical spectroscopy demonstrates elevated intracellular oxygenation in an endotoxic model of sepsis in the perfused heart

Recent clinical studies of patients with sepsis have shown that the delivery of adequate oxygen alone does not necessarily result in improved organ function or survival. This study was undertaken to determine if optical spectroscopy could detect higher intracellular oxygenations in isolated, perfused guinea pig hearts that have been treated with endotoxin (lipopolysaccharide [LPS]) than in controls. Four hours after intraperitoneal injection with LPS, adult guinea pigs were anesthetized, and hearts were excised and perfused in the Langendorff manner. Six control and eight LPS-exposed guinea pigs were studied. Myoglobin oxygen saturation was determined from analysis of optical reflectance spectra acquired from the left ventricular free wall. Myoglobin saturation was significantly higher at baseline with LPS than in controls (96.0% +/- 0.8% vs. 89.4% +/- 1.7%, P < 0.001). At the end of 30 s of ischemia, myoglobin saturation decreased to 15% +/- 1% in controls, but to only 60% +/- 7% in the LPS group. Myocardial performance was determined by measured left ventricular developed pressure, which was significantly depressed in the LPS-exposed hearts relative to controls (30 +/- 4 mmHg vs. 67 +/- 9 mmHg, P < 0.001). Myocardial oxygen consumption, calculated from measurements of arterial and venous PO2 and coronary flow, was lower in LPS hearts relative to controls (0.199 +/- 0.021 mL oxygen x min(-1) x g(-1) vs. 0.157 +/- 0.006 mL oxygen x min(-1) x g(-1)). In this model of sepsis in the perfused guinea pig heart, intracellular oxygenation was higher and oxygen consumption was lower than in controls. Cellular dysfunction seen in sepsis may be caused by compromised oxygen use rather than insufficient oxygen delivery. Optical spectroscopy has the potential to noninvasively monitor patients and their responses to therapy.     

Cardiac troponins I and T are biological markers of left ventricular dysfunction in septic shock

BACKGROUND: Cardiac depression in severe sepsis and septic shock is characterized by left ventricular (LV) failure. To date, it is unclear whether clinically unrecognized myocardial cell injury accompanies, causes, or results from this decreased cardiac performance. We therefore studied the relationship between cardiac troponin I (cTnI) and T (cTnT) and LV dysfunction in early septic shock. METHODS: Forty-six patients were consecutively enrolled, fluid-resuscitated, and treated with catecholamines. Cardiac markers were measured at study entry and after 24 and 48 h. LV function was assessed by two-dimensional transesophageal echocardiography. RESULTS: Increased plasma concentrations of cTnI (>/=0.4 microgram/L) and cTnT (>/=0.1 microgram/L) were found in 50% and 36%, respectively, of the patients at one or more time points. cTnI and cTnT were significantly correlated (r = 0.847; P <0.0001). Compared with cTnI-negative patients, cTnI-positive subjects were older, presented higher Acute Physiology and Chronic Health Evaluation II scores at diagnosis, and tended to have a worse survival rate and a more frequent history of arterial hypertension or previous myocardial infarction. In contrast, the two groups did not differ in type of infection or pathogen, or in dose and type of catecholamine administered. Continuous electrocardiographic monitoring in all patients and autopsy in 12 nonsurvivors did not disclose the occurrence of acute ischemia during the first 48 h of observation. LV dysfunction was strongly associated with cTnI positivity (78% vs 9% in cTnI-negative patients; P <0.001). In multiple regression analysis, both cTnI and cTnT were exclusively associated with LV dysfunction (P <0.0001). CONCLUSIONS: These findings suggest that in septic shock, clinically unrecognized myocardial cell injury is a marker of LV dysfunction. The latter condition tends to occur more often in severely ill older patients with underlying cardiovascular disease. Further studies are needed to determine the extent to which myocardial damage is a cause or a consequence of LV dysfunction.     

Platelet-activating factor and arachidonic acid metabolites mediate tumor necrosis factor and eicosanoid kinetics and cardiopulmonary dysfunction during bacteremic shock

OBJECTIVE: Platelet-activating factor (PAF) and eicosanoids are putative mediators of septic shock that are associated with release of tumor necrosis factor (TNF). The purpose of this investigation was to a) examine temporal patterns of TNF and arachidonic acid metabolite release in a porcine model of bacteremic shock and b) selectively block PAF, thromboxane A2, prostacyclin, and leukotrienes to determine the relationships among these inflammatory response mediators and the alterations in cardiorespiratory dysfunction for which they are required. DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty-four female Yorkshire swine. INTERVENTIONS: Animals were divided into six experimental groups: five septic groups receiving an infusion of Aeromonas hydrophila at 0.2 mL/kg/hr, gradually increasing to 0.4 mL/kg/hr over 4 hrs. Each of four septic groups was pretreated with a specific mediator inhibitor (PAF receptor antagonist, n = 6; prostacyclin antibody, n = 5; leukotriene synthesis inhibitor, n = 5; and thromboxane receptor antagonist, n = 6). One septic group (n = 6) received no mediator inhibitor and served as a septic control, and one anesthesia control group (n = 6) received no intervention. MEASUREMENTS AND MAIN RESULTS: PAF receptor blockade significantly increased systemic hypotension and mixed venous oxygen saturation and decreased pulmonary artery pressure, oxygen extraction and consumption, hemoconcentration, and levels of TNF and eicosanoids. Leukotriene inhibition increased mean arterial pressure, pulmonary and systemic vascular resistance indices, and arterial and mixed venous oxygen saturation and reduced pulmonary hypertension, oxygen delivery, oxygen extraction, oxygen consumption, and all measured mediators. Thromboxane receptor blockade lowered TNF and leukotriene levels, ameliorated systemic and pulmonary vasoconstriction, and significantly increased arterial and tissue oxygenation compared with septic controls. Prostacyclin antagonism reduced prostacyclin plasma concentrations, arterial hypoxemia, and oxygen consumption during sepsis and increased circulating leukotriene B4. CONCLUSIONS: Elevations in plasma TNF predictably precede peak levels of eicosanoids in this model. PAF, leukotrienes, and thromboxane A2 are necessary for pulmonary hypertension during bacteremia. Systemic hypotension and increased vascular permeability are mediated by both leukotrienes and PAF. There are complex interactions among mediators during sepsis and further studies are required to define these relationships.     

Myocardial oxygen consumption during dobutamine infusion in endotoxemic pigs

PURPOSE: Dobutamine infusion is used to increase whole-body oxygen delivery in septic patients to satisfy unmet oxygen demand of hypoxic tissues. However, dobutamine infusion also increases myocardial work and myocardial oxygen consumption. Our goal was to determine the importance of this effect as a fraction of the increase in whole-body oxygen consumption, in a porcine model of septic shock. MATERIALS AND METHODS: Four hours after a 50 microg/kg infusion of Escherichia coli endotoxin (0111: B4, Sigma) in eight anesthetized pigs, whole-body oxygen delivery and myocardial oxygen delivery and consumption were calculated from blood flow and arterial and venous oxygen content measurements. We directly measured whole-body oxygen consumption by analysis of inhaled and exhaled gases using a metabolic cart. Then dobutamine 10 and 20 microg/kg/min was infused and measurements were repeated. RESULTS: Dobutamine infusion increased whole-body oxygen delivery but did not increase metabolic cart measured whole-body oxygen consumption. Dobutamine infusion of 10 and 20 microg/kg/min increased myocardial oxygen consumption by 7.0 +/- 0.6 (80 +/-10%) and 12.0 +/- 2.0 mL O2/min (142 +/- 30%), respectively (P < .01). CONCLUSIONS: In this porcine model of sepsis, dobutamine infusion significantly increases myocardial oxygen consumption. Because whole-body oxygen consumption does not change, dobutamine infusion may fail to increase and may decrease oxygen consumption by other organs.     

The cardiovascular hemodynamics and leukotriene kinetics during prostacyclin and anti-prostacyclin antibody infusions in septic shock

This study evaluated whether or not prostacyclin (PGI2) was necessary or sufficient by itself in a pathophysiologic concentration to mediate the cardiovascular dysfunction of septic shock. Anesthetized adult swine received anesthesia only (ANESTHESIA CONTROL, n = 6); graded Aeromonas hydrophila, 10(10)/mL, infusion at 0.2 mL/kg/h that increased to 4.0 mL/kg/h over 3 h (SEPTIC SHOCK CONTROL, n = 6); pathophysiologic prostacyclin infusion to match septic shock control plasma levels without bacteremia (PGI2 INFUSION, n = 6), or graded Aeromonas hydrophila plus anti-prostacyclin antibody infusion (ANTI-PGI2-Ab INFUSION, n = 5). This graded porcine bacteremia model was 100% lethal after 4 h. Cardiovascular hemodynamics, arterial blood gases, and plasma levels of arachidonate metabolites were measured at baseline and hourly over a 4-h period. The results showed that PGI2 was not a necessary mediator of impaired cardiovascular hemodynamics in graded bacteremia, as anti-PGI2 antibody infusion did not improve the cardiac index, systemic vascular resistance, or peripheral oxygen balance in septic animals. Also, PGI2 was not sufficient alone to cause the cardiovascular dysfunction of sepsis, as pathophysiologic infusion of PGI2 did not reproduce such changes in normal animals. PGI2 blockade during bacteremia significantly increased LTC4D4E4, and LTB4 whereas PGI2 infusion suppressed LTC4D4E4 concentration, suggesting that endogenous PGI2 may blunt leukotriene release during septic shock. These results indicate a complex dynamic equilibrium among prostacyclin and leukotrienes in septic shock.     

Left ventricular systolic and diastolic function in septic shock

Summary Objective: The identification of myocardial dysfunction in septic shock has not yet been fully elucidated. We therefore studied patients with persistently vasopressor-dependent septic shock, both with invasive haemodynamic monitoring and transoesophageal two-dimensional and Doppler echocardiography (TEE). Design: Prospective study. Setting: General ICU in University Hospital. Patients and methods: All patients were monitored with arterial and pulmonary artery catheters. Haemodynamics were obtained concomitantly with TEE measurements. TEE was performed at three levels: a) a midpapillary short axis view of the left ventricle (LV) in order to measure end-systolic and end-diastolic areas; b) at the level of both the mitral valve for early (E) and late (A) filling parameters and c) the level of the right upper pulmonary vein for systolic (S) and diastolic (D) filling characteristics. Each parameter was characterised by maximal flow velocity and time velocity integral. Results: Although the measurements of cardiac index demonstrated a wide range, three subsets of patients were identified post hoc after analysis on the basis of different Doppler patterns: first, patients with a LV without regional wall motion abnormalities and both E/A and S/D greater than 1 (group 1); second, patients with a comparable haemodynamic condition, apparently normal LV systolic function but with altered Doppler patterns: S/D less than 1 in conjunction with E/A more than 1 (group 2); finally, patients with compromised global LV systolic function, E/A less than 1 and S/D less than (group 3). Conclusions: Notwithstanding the known various interfering factors which limit the broad applicability of TEE to determine LV function in septic shock, our data suggest that cardiac dysfunction in septic shock shows a continuum from isolated diastolic dysfunction to both diastolic and systolic ventricular failure. These data strengthen the need of including the evaluation of pulmonary venous Doppler parameters in each investigation in order to obtain supplementary information to interpret diastolic function of the LV in septic shock patients. Received: 29 February 1996 Accepted: 10 February 1997     

Early course of microcirculatory perfusion in eye and digestive tract during hypodynamic sepsis

ABSTRACT: INTRODUCTION: The aim of the study was to evaluate and compare the microcirculatory perfusion during experimental sepsis in different potentially available parts of the body, such as sublingual mucosa, conjunctiva of the eye, and mucosa of jejunum and rectum. METHODS: Pigs were randomly assigned to sepsis (n = 9) and sham (n = 4) groups. The sepsis group received a fixed dose of live Escherichia coli infusion over a 1-hour period (1.8 × 109/kg colony-forming units). Animals were observed 5 hours after the start of E. coli infusion. In addition to systemic hemodynamic assessment, we performed conjunctival, sublingual, jejunal, and rectal evaluation of microcirculation by using Sidestream Dark Field (SDF) videomicroscopy at the same time points: at baseline, and at 3 and 5 hours after the start of live E. coli infusion. Assessment of microcirculatory parameters of convective oxygen transport (microvascular flow index (MFI) and proportion of perfused vessels (PPV)), and diffusion distance (perfused vessel density (PVD) and total vessel density (TVD)) was done by using a semiquantitative method. RESULTS: Infusion of E. coli resulted in a hypodynamic state of sepsis associated with low cardiac output and increased systemic vascular resistance despite fluid administration. Significant decreases in MFI and PPV of small vessels were observed in sublingual, conjunctival, jejunal, and rectal locations 3 and 5 hours after the start of E. coli infusion in comparison with baseline variables. Correlation between sublingual and conjunctival (r = 0.80; P = 0.036), sublingual and jejunal (r = 0.80; P = 0.044), and sublingual and rectal (r = 0.79; P = 0.03) MFI was observed 3 hours after onset of sepsis. However, this strong correlation between the sublingual and other regions disappeared 5 hours after the start of E. coli infusion. Overall, the sublingual mucosa exhibited the most-pronounced alterations of microcirculatory flow in comparison with conjunctival, jejunal, and rectal microvasculature (P < 0.05). CONCLUSIONS: In this pig model, a time-dependent correlation exists between sublingual and microvascular beds during the course of a hypodynamic state of sepsis.     

Biphasic and monophasic transthoracic defibrillation in pigs with acute left ventricular dysfunction.

OBJECTIVE: Our purpose was to compare biphasic versus monophasic shock success for VF termination in a porcine model of acute left ventricular (LV) dysfunction. BACKGROUND: For the termination of ventricular fibrillation (VF), transthoracic biphasic waveform shocks achieve higher success rates than monophasic shocks. However, the effectiveness of biphasic versus monophasic defibrillation in a setting of left ventricular dysfunction has not been reported. METHODS: In 23 open-chest adult swine (15-25 kg), LV dysfunction [> or =25% decline in cardiac output (CO)] was induced by continuous inhalation of halothane (1-1.75%). Each pig randomly received transthoracic biphasic and monophasic shocks at three energy levels (30, 50 and 100 J) in two conditions: baseline and LV dysfunction. Halothane effect on left ventricular size and contraction was measured by echocardiography in three additional swine. RESULTS: With halothane, pigs demonstrated a decline in CO (baseline 4.16+/-0.19, halothane 2.72+/-0.19 l/min, P<0.01), mean arterial pressure (baseline 107.2+/-3.5, halothane 80.1+/-3.4 mmHg, P<0.01) and increased left ventricular end-diastolic pressure (baseline 6.4+/-0.9, halothane 12.7+/-0.8 mmHg, P<0.01). LV diameters increased and fractional shortening fell. During baseline, biphasic shocks achieved significantly greater success (termination of VF) compared to monophasic waveforms (100 J: biphasic 83.3+/-9.5 versus monophasic 38.9+/-9.5%, P<0.01; 50 J: biphasic 67.1+/-8.8 versus monophasic 11.8+/-5.7%, P<0.01; 30 J: biphasic: 31.9+/-6.4 versus monophasic 0+/-0%, P<0.01). The superiority of the biphasic waveform to terminate VF was retained during LV dysfunction at all energy levels (100 J: biphasic 78.3+/-7.3 versus monophasic 37.5+/-8.1%, P<0.01; 50 J: biphasic 65.5+/-11.5 versus monophasic 11.7+/-5.9%, P<0.01; 30 J: biphasic: 40.6+/-8.0 versus monophasic 3.1+/-3.1%, P<0.01). Within both waveforms, there were no significant differences in percent shock success at any energy level comparing baseline with LV dysfunction. CONCLUSION: In this porcine model of acute LV dysfunction, biphasic waveform shocks were not only superior to monophasic waveform shocks for termination of VF during baseline, but retained superiority to monophasic waveform shocks when LV dysfunction was present.     

Systemic hemodynamics in constant hemofiltration in patients with septic shock

Hemodiafiltration (HDF) is a method of pathogenetic therapy for the systemic inflammatory response syndrome in patients with sepsis and shock irrespective of renal failure. Systemic hemodynamics was examined in 18 patients with septic shock treated by HDF (2 groups). HDF was associated with stabilization of systemic hemodynamics in 50% patients (cardiac index, total peripheral resistance, index of the left heart work increased and the number of heart beats, central venous pressure, mean pressure in the pulmonary artery, pulmonary capillary wedging pressure decreased, oxygen consumption index increased, etc.), which allowed a reduction of the initial dopamine and norepinephrine doses 3-fold and lower by the end of days 3-4 of HDF treatment. An opposite tendency was observed in group 2 (refractory shock). Despite high (72.2%) mortality which was mainly caused by the progress of multiple organ dysfunction or untimely surgical intervention, it is obvious that HDF created conditions for surviving the critical period of disease in patients with progressive sepsis.     

Possible role of TNF on procalcitonin release in a baboon model of sepsis.

Procalcitonin (PCT) has been described as an early and discriminating marker of bacteria-associated sepsis in patients. However, little is known of its source and actions, especially with regard to its relation to tumor necrosis factor (TNF). TNF is responsible for the release of several other mediators of sepsis e.g., chemokines. We tested the hypothesis that plasma PCT levels during sepsis differ with regard to the degree of TNF availability. Severe hyperdynamic sepsis was induced in baboons (n = 14) by i.v. infusion of live E. coli (approximately 2 x 10(9) colony-forming units/kg) over 2 h. Animals were pretreated 2 h before E. coli either with 1 mg/kg humanized anti-TNF antibody (CDP571) or placebo (Ringer solution). Plasma PCT levels at baseline was barely detectable, but increased to about 4000 pg/mL at 4 h after E. coli infusion. Levels were maximal between 8 and 24 h and had returned nearly to baseline at 72 h. Although no TNF could be measured in the treated group, PCT levels were not different between the placebo and the TNF antibody treatment group. We conclude that PCT levels are not dependent on the systemic presence of TNF in an E. coli sepsis model in baboons. Such sepsis induced PCT release is clearly different from the previously reported PCT release during infusion of rhTNF in volunteers or chimpanzees.     

Correlation of left ventricular systolic dysfunction determined by low ejection fraction and 30-day mortality in patients with severe sepsis and septic shock: A systematic review and meta-analysis

Introduction

The prognostic implications of myocardial dysfunction in patients with sepsis and its association with mortality are controversial. Several tools have been proposed to evaluate cardiac function in these patients, but their usefulness beyond guiding therapy is unclear. We review the value of echocardiographic estimate of left ventricular ejection fraction (LVEF) in the setting of severe sepsis and/or septic shock and its correlation with 30-day mortality.

Methods

We conducted a systematic review and meta-analysis to evaluate the prognostic functionality of newly diagnosed LV systolic dysfunction by transthoracic echocardiography on critical ill patients admitted to the intensive care unit with severe sepsis or septic shock.

Results

A search of EMBASE and PubMed, Ovide MEDLINE, and Cochrane CENTRAL medical databases yielded 7 studies meeting inclusion criteria reporting on a total of 585 patients. The pooled sensitivity of depressed LVEF for mortality was 52% (95% confidence interval [CI], 29%-73%), and pooled specificity was 63% (95% CI, 53%-71%). Summary receiver operating characteristic curve showed an area under the curve of 0.62 (95% CI, 0.58-0.67). The overall mortality diagnostic odd ratio for septic patients with LV systolic dysfunction was 1.92 (95% CI, 1.27-2.899). Statistical heterogeneity of studies was moderate.

Conclusion

The presence of new LV systolic dysfunction associated with sepsis and defined as low LVEF is neither a sensitive nor a specific predictor of mortality. These findings are limited because of the heterogeneity and underpower of the studies. Further research into this method is warranted.     

Impaired sarcoplasmic calcium release inhibits myocardial contraction in experimental sepsis

PURPOSE: In septic shock, myocardial dysfunction develops over the course of illness, but the mechanism of this depression is not clear. In this study, mechanisms of myocardial dysfunction were examined in a porcine model of Escherichia coli sepsis. MATERIALS AND METHODS: Animals were subjected to 4 hours of bacteria infusion (n = 5) (septic group) or saline infusion (n = 5) (nonseptic group), after which trabeculae were removed from the right ventricle and placed into a recirculating water bath. Measurements of steady-state contraction (SSC) were obtained at 0.5, 1, and 2 Hz. Indirect indices were used to assess abnormalities in myocardial calcium metabolism in sepsis. Extrasystoles (ES) were used to assess transsarcolemmal (TSL) calcium flux and were measured at 300 milliseconds, 400 milliseconds, and 500 milliseconds after the preceding stimulus. Postrest contraction (PRC) is an indicator of SR recirculation from the uptake to the release site and was obtained after interposing intervals of rest between steady-state beats at 0.5 Hz. Rapid-cooling contracture (RCC) is an indicator of sarcoplasmic reticulum (SR) content and was obtained at 0.5, 1, and 2 Hz and after interposing intervals of rest at 0.5 Hz. RESULTS: SSC was not different between groups at 0.5 Hz, but compared with the nonseptic group, SSC decreased at 1 and 2 Hz in the septic group (P < .05). PRC and TSL were not different between groups. During rest intervals, calcium leaks out of SR through the ryanodine channel (ie, SR calcium release channel). In the septic group, as assessed by RCC, SR calcium leak was less than that found in the nonseptic group. CONCLUSION: These results indicate that myocardial dysfunction in sepsis is frequency dependent, and that the mechanism is most likely caused by inhibition of SR calcium release owing to blockade of the ryanodine channel.     

脓毒症患者膈肌功能障碍的床旁超声评估的应用价值研究北大核心CSCD

目的探讨脓毒症及感染性休克患者膈肌功能障碍的危险因素及床旁超声评估的应用价值。方法前瞻性收集2020年1月至2021年5月入住宁夏医科大学总医院重症医学科(ICU)脓毒症及感染性休克患者作为研究对象,选择普通术后患者及健康志愿者作为术后对照组与正常对照组。收集一般临床资料,动态观察脓毒症及感染性休克患者超敏C反应蛋白(high sensitive c-reactive protein,hs-CRP)、白细胞介素-6(interleukin-6,IL-6)、血清白蛋白、转铁蛋白、前白蛋白水平、血乳酸、动静脉二氧化碳分压差、中心静脉血氧饱和度等指标。并用间接测热法测量静息能量水平计算能量缺失值,床旁超声评估膈肌移动度(diaphragm excursion,DE)、吸气末膈肌厚度及呼气末膈肌厚度,计算相关参数。DE<10 mm或膈肌增厚分数(diaphragmatic thickness fraction,DTF)<20%诊断为膈肌功能障碍。结果⑴感染性休克组、脓毒症组及术后对照组三组患者入ICU第1天,DE均低于正常对照组[10.3(9.0,13.6)mm、12.3(9.1,15.0)mm、12.9(10.5,15.7)mm vs.22.0(16.0,24.6)mm,均P<0.05];DTF<20%发生率均高于正常对照组(32.7%、41.9%、33.3%vs.0%,均P<0.05);且感染性休克组和脓毒症组DE<10 mm发生率均高于术后对照组和正常对照组(分别为36.7%、35.5%vs.10.0%、0%,均P<0.05)。入ICU第7天,感染性休克组DE较脓毒症组减低[10.5(6.8,13.5)mm vs.14.4(10.6,18.6)mm,P<0.05]。⑵各指标相关性分析:脓毒症和感染性休克患者入ICU第1、3、7天的DE均与当天的hs-CRP呈负相关(r值分别为-0.253、-0.436、-0.455,均P<0.05);入ICU第3天,DE还与IL-6呈负相关(r=-0.338,P=0.009),且DTF与hs-CRP呈负相关(r=-0.375,P=0.004)。入ICU第1天,脓毒症和感染性休克患者DTF与转铁蛋白呈正相关(r=0.221,P=0.049)。入ICU第3、7天,其DE与前白蛋白呈正相关(r值分别为0.318、0.408,均P<0.05)。结论脓毒症和感染性休克患者入住ICU首日已出现膈肌功能障碍,主要表现为膈肌移动度及膈肌增厚分数减低,且与炎症反应和蛋白质高分解代谢程度相关。     

严重脓毒症和脓毒性休克患者复苏治疗与血糖控制的非线性相关分析研究

目的 研究严重脓毒症和脓毒性休克患者复苏治疗与应用胰岛素强化治疗应激性高血糖之间的关系,探讨非线性观点在脓毒症患者治疗中的价值.方法 回顾性分析129例严重脓毒症和脓毒性休克患者的住院资料,根据充分复苏标准完成所需时间(每6 h一组)分为8组,采用非线性最小二乘法比较各复苏组充分复苏完成所需时问与单位时间胰岛素用量之间的关系.结果 各复苏组充分复苏完成所需时间与单位时间胰岛素用量之间存在指数回归关系,指数曲线方程(^y)=e0.7393-0.0152x(a=0.739 3,b=0.015 2),且拟合度甚佳(R2=0.976 943 6).结论 在严重脓毒症和脓毒性休克患者的治疗过程中,复苏治疗完成的时问与机体紊乱的内分泌系统恢复有密切的关系,符合非线性观点.因此治疗上重在帮助机体重建已紊乱的网络,恢复其正常的生理谐振;而不仅仅是给予受损器官充分的支持和修复.     

严重脓毒症和脓毒性休克患者复苏治疗与血糖控制的非线性相关分析研究

目的 研究严重脓毒症和脓毒性休克患者复苏治疗与应用胰岛素强化治疗应激性高血糖之间的关系,探讨非线性观点在脓毒症患者治疗中的价值.方法 回顾性分析129例严重脓毒症和脓毒性休克患者的住院资料,根据充分复苏标准完成所需时间(每6 h一组)分为8组,采用非线性最小二乘法比较各复苏组充分复苏完成所需时问与单位时间胰岛素用量之间的关系.结果 各复苏组充分复苏完成所需时间与单位时间胰岛素用量之间存在指数回归关系,指数曲线方程(^y)=e0.7393-0.0152x(a=0.739 3,b=0.015 2),且拟合度甚佳(R2=0.976 943 6).结论 在严重脓毒症和脓毒性休克患者的治疗过程中,复苏治疗完成的时问与机体紊乱的内分泌系统恢复有密切的关系,符合非线性观点.因此治疗上重在帮助机体重建已紊乱的网络,恢复其正常的生理谐振;而不仅仅是给予受损器官充分的支持和修复.