Changes in muscle tissue oxygenation during stagnant ischemia in septic patients

Objective To determine changes in the rate of thenar muscles tissue deoxygenation during stagnant ischemia in patients with severe sepsis and septic shock.Design and setting Prospective observational study in the medical ICU of a general hospital.Patients and participants Consecutive patients admitted to ICU with septic shock (n=6), severe sepsis (n=6), localized infection (n=3), and healthy volunteers (n=15).Interventions Upper limb ischemia was induced by rapid automatic pneumatic cuff inflation around upper arm.Measurements and results Thenar muscle tissue oxygen saturation (StO₂) was measured continuously by near-infrared spectroscopy before and during upper limb ischemia. StO₂ before intervention was comparable in patients with septic shock, severe sepsis, or localized infection and healthy volunteers (89 [65, 92]% vs. 82 [72, 91]% vs. 87 [85, 92]% vs. 83 [79, 93]%, respectively; p>0.1). The rate of StO₂ decrease during stagnant ischemia after initial hemodynamic stabilization was slower in septic shock patients than in those with severe sepsis or localized infection and in controls (–7.0 [–3.6, –11.0] %/min vs. –10.4 [–7.8, –13.3] %/min vs. –19.5 [–12.3, –23.3] vs. –37.4 [–27.3, –56.2] %/min, respectively; p=0.041). At ICU discharge the rate of StO₂ decrease did not differ between the septic shock, severe sepsis, and localized infection groups (–17.0 [–9.3, –28.9] %/min vs. –19.9 [–13.3, –23.6] %/min vs. –23.1 [–20.7, –26.2] %/min, respectively), but remained slower than in controls (p<0.01). The rate of StO₂ decrease was correlated with Sequential Organ Failure Assessment (SOFA) score (r=0.739, p<0.001).Conclusions After hemodynamic stabilization thenar muscle tissue oxygen saturation during stagnant ischemia decreases slower in septic shock patients than in patients with severe sepsis or localized infection and in healthy volunteers. During ICU stay and improvement of sepsis the muscle tissue deoxygenation rate increases in survivors of both septic shock and severe sepsis and was correlated with SOFA score.     

Increased lactate/pyruvate ratio with normal b-hydroxybutyrate/acetoacetate ratio and lack of oxygen supply dependency in a patient with fatal septic shock

We report a case of fatal septic shock, with hyperlactatemia and blood cultures positive for Streptococcus pneumoniae, in a 70-year-old patient. On two occasions (5 days, and 2 days before the patient‘s death), the relationship between oxygen delivery (D˙O₂) and consumption (V˙O₂) was examined in conjunction with two presumed markers of tissue oxygenation: the lactate/pyruvate ratio (L/P), and the β-hydroxybutyrate acetoacetate ratio (βOHB/AcAc). Increasing D˙O₂ by about 30% (“oxygen flux test”) failed to increase V˙O₂. The βOHB/AcAc ratio remained within normal limits, thus suggesting uncompromised tissue oxygenation at the hepatic level. The L/P ratio remained persistently above normal limits, thus suggesting actual organ or regional hypoxia. This case shows that during an overwhelming septic shock, the “oxygen flux test” can be negative, despite the presence of hyperlactatemia and of an increased L/P ratio suggestive of impaired tissue oxygenation. Received: 7 December 1995 Accepted: 2 September 1996     

Delivery dependent oxygen consumption in patients with septic shock: Daily variations,relationship with outcome and the sick-euthyroid syndrome

Delivery dependent oxygen consumption (DDOC) is observed in patients with sepsis and vital organ dysfunction, and has been related to outcome. Similarly the sick-euthyroid syndrome is associated with a high mortality. We examined the daily variations of DDOC and its relation to hormonal changes, particularly those of the thyroid. In 22 patients, 14 with septic shock and 8 post-operative controls, oxygen delivery was increased by increasing cardiac output with vasodilation by phentolamine, during a total of 207 days. DDOC varied markedly between consecutive days in individual patients with sepsis, in both survivors and non-survivors. DDOC was related to severity of illness, assessed by APACHE II score (r=0.50,p=0.017), and plasma levels of triiodothyronine (T₃),r=–0.49,p=0.011, and thyroxine (T₄),r=–0.53,p=0.012. No correlation was observed between DDOC and outcome, nor blood levels of lactate, epinephrine, norepinephrine, dopamine or cortisol. In conclusion, we observed a marked disturbance of systemic oxygen uptake autoregulation in patients with septic shock which varied during the clinical course and was related to the sick-euthyroid syndrome.With the technical assistance of J. Lopez     

Splanchnic blood flow is greater in septic shock treated with norepinephrine than in severe sepsis

Objective To assess global and splanchnic blood flow and oxygen transport in patients with sepsis with and without norepinephrine treatment.Design Prospective, clinical study.Setting University hospital intensive care unit.Patients A convenience sample of 15 septic shock patients treated with norepinephrine and 13 patients with severe sepsis who did not receive norepinephrine.Measurements and main results There were no differences between the two groups in global haemodynamics and oxygen transport. Splanchnic blood flow and oxygen delivery (splanchnic DO₂ 303±43 ml/min per m²) and consumption (splanchnic VO₂ 100±13 ml/min per m²) were much higher in the septic shock group compared with the severe sepsis group (splanchnic DO₂ 175±19 ml/min per m², splanchnic VO₂ 61±6 ml/min per m²). Gastric mucosal pH was subnormal in both groups (septic shock 7.29±0.02, severe sepsis 7.25±0.02) with no significant difference. No significant differences between groups were detected in lactate values.Conclusion These data confirm a redistribution of blood flow to the splanchnic region in sepsis that is even more pronounced in patients with septic shock requiring norepinephrine. However, subnormal gastric mucosal pH suggested inadequate oxygenation in part of the splanchnic region due to factors other than splanchnic hypoperfusion. Progress in this area will depend on techniques that address not only total splanchnic blood flow, but also inter-organ flow distribution, intra-organ distribution, and other microcirculatory or metabolic malfunctions.     

Dynamic near-infrared spectroscopy measurements in patients with severe sepsis

This study evaluated near-infrared spectroscopy (NIRS)-derived measurements in hemodynamically stable patients with severe sepsis, as compared with similar measurements in healthy age-matched volunteers. Prospective, preliminary, observational study in a surgical intensive care unit and clinical research center at a university health center. We enrolled 10 patients with severe sepsis and 9 healthy age-matched volunteers. For patients with severe sepsis, we obtained pulmonary artery catheter and laboratory values three times daily for 3 days and oxygen consumption values via metabolic cart once daily for 3 days. For healthy volunteers, we obtained all noninvasive measurements during a single session. We found lower values in patients with severe sepsis (versus healthy volunteers), in tissue oxygen saturation (StO2), in the StO2 recovery slope, in the tissue hemoglobin index, and in the total tissue hemoglobin increase on venous occlusion. Patients with severe sepsis had longer StO2 recovery times and lower NIRS-derived local oxygen consumption values versus healthy volunteers. In our preliminary study, NIRS provides a noninvasive continuous method to evaluate peripheral tissue oxygen metabolism in hemodynamically stable patients with severe sepsis. Further research is needed to demonstrate whether these values apply to broader populations of patients with systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock.     

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.     

Skeletal muscle oxygen saturation does not estimate mixed venous oxygen saturation in patients with severe left heart failure and additional severe sepsis or septic shock

Introduction  

Low cardiac output states such as left heart failure are characterized by preserved oxygen extraction ratio, which is in contrast to severe sepsis. Near infrared spectroscopy (NIRS) allows noninvasive estimation of skeletal muscle tissue oxygenation (StO₂). The aim of the study was to determine the relationship between StO₂ and mixed venous oxygen saturation (SvO₂) in patients with severe left heart failure with or without additional severe sepsis or septic shock.     

Kinetics of circulating immunoglobulin M in sepsis: relationship with final outcome

Introduction

The aim of this study was to investigate the kinetics of immunoglobulin M (IgM) during the different stages of sepsis.

Methods

In this prospective multicenter study, blood sampling for IgM measurement was done within the first 24 hours from diagnosis in 332 critically ill patients; in 83 patients this was repeated upon progression to more severe stages. Among these 83 patients, 30 patients with severe sepsis progressed into shock and IgM was monitored daily for seven consecutive days. Peripheral blood mononuclear cells (PBMCs) were isolated from 55 patients and stimulated for IgM production.

Results

Serum IgM was decreased in septic shock compared to patients with systemic inflammatory response syndrome (SIRS) and patients with severe sepsis. Paired comparisons at distinct time points of the sepsis course showed that IgM was decreased only when patients deteriorated from severe sepsis to septic shock. Serial measurements in these patients, beginning from the early start of vasopressors, showed that the distribution of IgM over time was significantly greater for survivors than for non-survivors. Production of IgM by PBMCs was significantly lower at all stages of sepsis compared with healthy controls.

Conclusions

Specific changes of circulating IgM occur when patients with severe sepsis progress into septic shock. The distribution of IgM is lower among non-survivors.     

Procollagen type III aminoterminal propeptide as biomarker of host response in severe sepsis

Purpose

The purpose of this study is to test the hypothesis that procollagen type III aminoterminal propeptide (PIIINP) is early elevated in septic episodes and can indicate the acute organ dysfunction/failure characterizing severe sepsis.

Materials and Methods

This prospective study included 107 consecutive septic patients (44 with sepsis, 13 with severe sepsis, and 50 with septic shock) and 45 controls. After blood sampling (within 48 hours after onset of septic episodes), serum was assayed. Patients were followed up, and their disease severity was daily evaluated.

Results

Procollagen type III aminoterminal propeptide (median [range]) increased in patients with sepsis (9.4 [2.2-42.4] ng/mL) compared with controls (3.6 [1.9-4.9] ng/mL; P < .001), exhibiting further significant increase in patients with severe sepsis and septic shock (19.5 [6.0-52.4] and 20.2 [1.8-89.2] ng/mL, respectively; P < .01-.001 vs sepsis). Among biomarkers of host response severity, PIIINP was the sole that was independently associated with severe sepsis/septic shock (P = .01). The area under the receiver operating characteristic curve for PIIINP to predict which patients with sepsis would eventually develop severe sepsis/septic shock was 0.87; the cutoff of 12 ng/mL had sensitivity 82% and specificity 89%.

Conclusions

Increased serum PIIINP can signify severe sepsis/septic shock and predict which patients with sepsis will eventually develop severe sepsis/septic shock, thus representing a biomarker of risk stratification of patients with sepsis.     

Neutrophil chemotaxis and receptor expression in clinical septic shock

Objective To examine the hypothesis that neutrophil chemotaxis to interleukin-8 (IL-8) is reduced in septic shock. Surface expression of neutrophil CXC chemokine receptors and the adhesion molecule CD11b were also examined and associations between disease severity, gas exchange and receptor expression were studied.Design Prospective cohort clinical study.Setting Intensive care unit in a tertiary referral teaching hospital.Patients Patients with septic shock (n=15) and healthy controls (n=8) were studied.Measurements and results Daily (for 5 consecutive days) flow cytometric measurements of chemokine and integrin surface expression. In vitro neutrophil chemotaxis to IL-8 was also compared between patients with sepsis and healthy controls. CXCR2 expression significantly fell, CD11b expression increased and CXCR1 expression was unchanged throughout the study in the septic group compared with healthy controls. CD11b positively correlated with increasing APACHE II scores (p<0.0001) and worsening PaO₂/FIO₂ ratios (p<0.0001). CXCR2 expression negatively correlated with both APACHE II scores (p=0.016) and PaO₂/FIO₂ ratios (p=0.01). There was no correlation between CXCR1 expression and either APACHE II score or PaO₂/FIO₂ ratios. Chemotaxis to IL-8 was reduced in patients with sepsis compared with healthy volunteers.Conclusions Surface expression of the chemokine receptor CXCR2 and the -integrin CD11b, but not CXCR1, were reduced on neutrophils isolated from patients with septic shock compared with healthy controls. Chemotaxis to IL-8 was also reduced in neutrophils from septic patients compared with healthy controls. The changes in receptor expression correlated with measures of disease severity.     

Sepsis severity is the major determinant of circulating thrombopoietin levels in septic patients

OBJECTIVE: To measure serum thrombopoietin levels and to investigate their relationship with platelet counts and other potential determinants in septic patients. DESIGN: Prospective study comparing septic patients and healthy volunteers. SETTING: General intensive care units in two tertiary university hospitals. PATIENTS: A total of 152 consecutive septic patients (69 with sepsis, 24 with severe sepsis, and 59 with septic shock). Twenty-two healthy volunteers served as control subjects. Sepsis severity was determined by grading septic patients in those having sepsis, severe sepsis, and septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After blood sampling, platelet counts, and serum thrombopoietin, interleukin-6 and C-reactive protein levels were measured. Platelets did not decrease in patients with sepsis, but they significantly decreased in patients with severe sepsis and septic shock (p <.01 vs. controls and sepsis). In contrast, thrombopoietin levels (median [range]) increased in patients with sepsis (159 [34-1272] pg/mL) compared with controls (57 [33-333] pg/mL, p <.001), exhibiting further significant increase in patients with severe sepsis and septic shock (461 [73-1550] and 522 [45-2313] pg/mL, respectively, p <.001 vs. sepsis). In multiple regression analysis, thrombopoietin levels were independently related only to sepsis severity (higher in patients with increased sepsis severity, p <.001) and platelet counts (higher in patients with lower platelet counts, p =.004). Sepsis severity accounted for most of the variance explained by the model. Thrombopoietin was significantly related to interleukin-6 (r =.26) and C-reactive protein (r =.37, p <.001 for both). In serial measurements, interleukin-6 peak values constantly preceded those of thrombopoietin, whereas peaks in thrombopoietin levels coincided with clinical episodes of septic shock. CONCLUSIONS: Sepsis severity is the major determinant of elevated thrombopoietin levels in septic patients, whereas platelet count is a secondary determinant. Thrombopoietin represents a potential marker of sepsis severity.     

Utilisation de la SvO2

Monitoring of O₂ venous saturation (SvO₂) is easily performed with fiberoptic pulmonary artery catheters and is used in circulatory shock to assess global balance between tissue O₂ supply and O₂ demand (VO₂). Simultaneous measurement of SvO₂ and continuous Cardiac Output (CO), as recently allowed by modified artery catheters, improve SvO₂ interpretation. Indeed, a decrease in SvO₂ may result from a decrease in arterial O₂ saturation, a decrease in hemoglobin or CO or from an increase in VO₂. SvO₂ is a surrogate marker of tissue O₂ extraction (EO₂) with SvO₂ = 1 – EO₂. When EO₂ is altered, as observed in septic shock, SvO₂ does not anymore guarantee correct interpretation of tissue oxygenation. Central venous O₂ saturation (ScvO₂) can be monitored with more easiness and a lower risk than mixed venous O₂ saturation with a good correlation between SvO₂ and ScvO₂. ScvO₂ has been recently used for early goal-directed therapy in patients with severe sepsis in order to improve hemodynamics at the emergency room; this was associated with a 16% reduction (p = 0.009) in in-hospital mortality.     

The prognostic value of muscle StO<Subscript>2</Subscript> in septic patients

Objective: To quantify sepsis-induced alterations in changes in muscle tissue oxygenation (StO₂) after an ischemic challenge using near-infrared spectroscopy (NIRS), and to test the hypothesis that these alterations are related to outcome. Design Prospective study. Setting Thirty-one-bed, university hospital Department of Intensive Care. Patients Seventy-two patients with severe sepsis or septic shock, 18 hemodynamically stable, acutely ill patients without infection, and 18 healthy volunteers. Interventions Three-minute occlusion of the brachial artery using a cuff inflated 50 mmHg above systolic arterial pressure. Measurements and main results Thenar eminence StO₂ was measured continuously by NIRS before (StO₂baseline), during, and after the 3-min occlusion. Changes in StO₂ were assessed by the slope of increase in StO₂ during the first 14 s following the ischemic period and by the difference between the maximum StO₂ and StO₂baseline (Δ). The slope was lower in septic patients than in controls and volunteers [2.3 (1.3–3.6), 4.8 (3.5–6.0), and 4.7 (3.2–6.3) %/s, p < 0.001]. Δ was also significantly lower in septic patients than in the other groups. Slopes were lower in septic patients with than without shock [2.0 (1.2–2.9) vs 3.2 (1.8–4.5) %/s, p < 0.05]. In 52 septic patients, in whom the slope was obtained every 24 h for 48 h, slopes were higher in survivors than in non-survivors and tended to increase in survivors but not in non-survivors. Conclusions Altered recovery in StO₂ after an ischemic challenge is frequent in septic patients and more pronounced in the presence of shock. The presence and persistence of these alterations in the first 24 h of sepsis are associated with worse outcome. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Dysfunction of vasomotor reactivity in severe sepsis and septic shock

Objective: Perfusion abnormalities are an overall phenomenon in severe sepsis and septic shock, leading to organ dysfunction. We investigated whether carbon dioxide (CO₂)-induced vasomotor reactivity (VMR) is impaired in septic patients, compared with values obtained outside sepsis. Design: Prospective, clinical study. Setting: Six-bed neurologic critical care unit of a university hospital. Patients and participants: Eight consecutive patients with severe sepsis and septic shock. Measurements and results: CO₂-reactivity was measured during and outside a period of severe sepsis or septic shock according to ACCP/SCCM criteria by means of transcranial Doppler sonography and near-infrared spectroscopy (NIRS). VMR was calculated as the percentage change of cerebral blood flow velocity (normalized CO₂-reactivity, NCR) and absolute changes in concentration of oxygenated hemoglobin, deoxygenated hemoglobin, total hemoglobin (HbO₂, Hb, HbT) and Hbdiff (difference between HbO₂ and Hb) in µmol/l per 1% increase in end-tidal CO₂ (CR-HbO₂, CR-Hb, CR-HbT, CR-Hbdiff). NCR and NIRS-reactivities were significantly reduced during severe sepsis and septic shock compared with values outside sepsis (mean, SD, Wilcoxon): NCR 11.0 (7.1) versus 30.7 (13.0), p<0.02; CR-HbO₂ 0.70 (0.61) versus 2.33 (1.11), p<0.02; CR-Hb -0.17 (0.74) versus -1.42 (1.28), p<0.04; CR-HbT 0.53 (0.48) versus 1.05 (0.40), p<0.03; CR-Hbdiff 0.91 (1.33) versus 3.75 (2.33), p<0.02. This indicates a severely disturbed VMR. Conclusions: In the advent of a disturbed cerebral autoregulation, critical drops in blood pressure during sepsis are transferred directly into the vascular bed, leading to cerebral hypoperfusion. This mechanism might contribute to the pathogenesis of septic encephalopathy.     

Continuous monitoring of mixed venous oxygen saturation in septic shock

Fiberoptic pulmonary artery catheters provide a practical method for continuously measuring the amount of oxygen in mixed venous blood. To characterize the usefulness of mixed venous oxygen saturation in managing patients with sepsis, we performed serial hemodynamic measurements on 20 patients with documented septic shock. There was a highly significant positive correlation between increases or decreases of 5% or more in mixed venous oxygen saturation and corresponding changes in oxygen delivery (r = 0.95) and oxygen consumption (r = 0.96). Mixed venous oxygen saturation less than 65% was clinically unacceptable in patients with sepsis and was associated with a poor prognosis. In this study, measurement of mixed venous oxygen saturation was a valuable predictor of survival in patients with septic shock and provided a means of continuously monitoring the status of tissue oxygenation.     

Bench-to-bedside review: Sepsis is a disease of the microcirculation

Microcirculatory perfusion is disturbed in sepsis. Recent research has shown that maintaining systemic blood pressure is associated with inadequate perfusion of the microcirculation in sepsis. Microcirculatory perfusion is regulated by an intricate interplay of many neuroendocrine and paracrine pathways, which makes blood flow though this microvascular network a heterogeneous process. Owing to an increased microcirculatory resistance, a maldistribution of blood flow occurs with a decreased systemic vascular resistance due to shunting phenomena. Therapy in shock is aimed at the optimization of cardiac function, arterial hemoglobin saturation and tissue perfusion. This will mean the correction of hypovolemia and the restoration of an evenly distributed microcirculatory flow and adequate oxygen transport. A practical clinical score for the definition of shock is proposed and a novel technique for bedside visualization of the capillary network is discussed, including its possible implications for the treatment of septic shock patients with vasodilators to open the microcirculation.     

Cerebral blood flow is proportional to cardiac index in patients with septic shock

In patients with septic shock, the cardiac index is often increased. Maldistribution of blood flow and regional hypoperfusion has been implicated as a key factor in the pathogenesis of organ dysfunction in these patients. We have investigated the relationship between cerebral blood flow and cardiac index in patients with septic shock. We used Doppler ultrasound techniques to investigate limb and carotid blood flow in 15 patients with septic shock and 9 nonseptic controls. In the nonseptic control patients, common femoral and brachial blood flow were proportional to cardiac index (r = 0.73 and 0.76; P = .038 and .017, respectively) reflecting a protective redistribution of flow to more vital organs. However, this relationship was absent in patients with septic shock (r = 0.23 and 0.21). Furthermore, in the septic patients but not the nonseptic controls, cerebral blood flow was correlated with the cardiac index (r = 0.66, P < .05 vs R = −0.36, NS in nonseptic controls). Carotid flow was independent of mean arterial pressure, Paco₂ and Pao₂ in patients with septic shock. These data are consistent with a loss of autoregulation of cerebral blood flow and a change in the control of limb blood flow in humans with septic shock.     

Renal haemodynamic, microcirculatory, metabolic and histopathological responses to peritonitis-induced septic shock in pigs

Introduction

Our understanding of septic acute kidney injury (AKI) remains incomplete. A fundamental step is the use of animal models designed to meet the criteria of human sepsis. Therefore, we dynamically assessed renal haemodynamic, microvascular and metabolic responses to, and ultrastructural sequelae of, sepsis in a porcine model of faecal peritonitis-induced progressive hyperdynamic sepsis.

Methods

In eight anaesthetised and mechanically ventilated pigs, faecal peritonitis was induced by inoculating autologous faeces. Six sham-operated animals served as time-matched controls. Noradrenaline was administered to maintain mean arterial pressure (MAP) greater than or equal to 65 mmHg. Before and at 12, 18 and 22 hours of peritonitis systemic haemodynamics, total renal (ultrasound Doppler) and cortex microvascular (laser Doppler) blood flow, oxygen transport and renal venous pressure, acid base balance and lactate/pyruvate ratios were measured. Postmortem histological analysis of kidney tissue was performed.

Results

All septic pigs developed hyperdynamic shock with AKI as evidenced by a 30% increase in plasma creatinine levels. Kidney blood flow remained well-preserved and renal vascular resistance did not change either. Renal perfusion pressure significantly decreased in the AKI group as a result of gradually increased renal venous pressure. In parallel with a significant decrease in renal cortex microvascular perfusion, progressive renal venous acidosis and an increase in lactate/pyruvate ratio developed, while renal oxygen consumption remained unchanged. Renal histology revealed only subtle changes without signs of acute tubular necrosis.

Conclusion

The results of this experimental study argue against the concept of renal vasoconstriction and tubular necrosis as physiological and morphological substrates of early septic AKI. Renal venous congestion might be a hidden and clinically unrecognised contributor to the development of kidney dysfunction.     

Toe temperature versus transcutaneous oxygen tension monitoring during acute circulatory failure

Measurements of toe temperature and transcutaneous PO₂ (P_tcO₂) have been both suggested for non-invasive assessment of peripheral blood flow in acute circulatory failure. The underlying principle of the two methods is that cutaneous vasoconstriction occurs early when tissue perfusion is altered. In 15 patients, we compared the two measurements during cardiogenic shock (27 measurements) or septic shock (29 measurements). Toe-ambiant temperature gradient and P_tcO₂ correlated well together (r=0.66, p(0.001) especially in hyperkinetic septic shock (r=0.79, p(0.001). In cardiogenic shock, toe-ambiant temperature correlated well with cardiac index (r=0.63), stroke index (r=0.64) and oxygen transport (r=0.65), and these correlations were stronger than for P_tcO₂. In septic shock, both techniques were poor indicators of blood flow indexes but P_tcO₂ rather correlated with arterial pressure (r=0.66) and left ventricular work (r=0.66). Trend evaluation of data revealed in cardiogenic shock that the increase in toe temperature usually preceded the increase in P_tcO₂. Since measurement of P_tcO₂ is technically more complicated, correlates less well with standard hemodynamic parameters and later reflects cardiovascular improvement, it has no advantage over measurement of toe temperature in circulatory shock. In cardiogenic shock, measurements of toe temperature can reliably track cardiac output changes. In septic states, however, non-invasive assessment of skin perfusion is of limited interest.     

ADAMTS-13, von Willebrand factor and related parameters in severe sepsis and septic shock

BACKGROUND: Insufficient control of von Willebrand factor (VWF) multimer size as a result of severely deficient ADAMTS-13 activity results in thrombotic thrombocytopenic purpura associated with microvascluar thrombosis and platelet consumption, features not seldom seen in severe sepsis and septic shock. METHODS: ADAMTS-13 activity and VWF parameters of 40 patients with severe sepsis or septic shock were compared with those of 40 healthy controls of the same age and gender and correlated with clinical findings and sepsis outcome. RESULTS: ADAMTS-13 activity was significantly lower in patients than in healthy controls [median 60% (range 27-160%) vs. 110% (range 63-200%); P < 0.001]. VWF parameters behaved reciprocally and both VWF ristocetin cofactor activity (RCo) and VWF antigen (VWF:Ag) were significantly (P < 0.001) higher in patients compared with controls. Neither ADAMTS-13 activity nor VWF parameters correlated with disease severity, organ dysfunction or outcome. However, a contribution of acute endothelial dysfunction to renal impairment in sepsis is suggested by the significantly higher VWF propeptide and soluble thrombomodulin levels in patients with increased creatinine values as well as by their strong positive correlations (creatinine and VWF propeptide r(s) = 0.484, P < 0.001; creatinine and soluble thrombomodulin r(s) = 0.596, P < 0.001). CONCLUSIONS: VWF parameters are reciprocally correlated with ADAMTS-13 activity in severe sepsis and septic shock but have no prognostic value regarding outcome.