Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Microdialysis (MD) provides the opportunity to monitor tissue metabolic changes. This study aimed to describe the kinetics of MD-derived metabolites during the course of critical sepsis, to assess whether these metabolites are useful in grading sepsis severity, and to investigate their prognostic use. To this end, 54 mechanically ventilated septic patients were prospectively studied, out of which 39 had shock. ⋯ In conclusion, critical sepsis is characterized by high tissue lactate and pyruvate levels and a preserved lactate-pyruvate ratio, suggesting a nonischemic mechanism for raised blood lactate levels. Septic shock is associated with higher tissue lactate and glycerol levels compared with sepsis without shock. Elevated tissue lactate, pyruvate, and glycerol levels are related to poor clinical outcome, with the latter constituting an independent predictor.
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We studied whether low hemoglobin concentrations during normovolemia change the myocardial electrical current (electrocardiogram) in a pig model. Normovolemic anemia was achieved by stepwise replacing blood with colloids (hydroxyethyl starch 6%). We measured the length of the PQ-, QT-, QTc, and the ST interval as well as the amplitude of the Q wave and T wave at hemoglobin concentrations of 9.5, 8.0, 5.5, 3.8, and 3.3 g·dL. ⋯ Results were verified performing a time-frequency analysis on single heartbeats. During severe anemia and normovolemia, electrocardiographic changes can be detected. Further investigations are warranted to elucidate whether these changes indicate myocardial hypoxia.
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Renal injury is one of the severe and common complications that occurs early in neonates with asphyxia, and reactive oxygen species have been implicated to play an important role on its pathogenesis. Improved renal recovery has been shown previously with N-acetyl-l-cysteine (NAC) in various acute kidney injuries. Using a subacute swine model of neonatal hypoxia-reoxygenation (H/R), we examined whether NAC can sustain its beneficial effect on renal recovery for 48 h. ⋯ N-acetyl-l-cysteine treatment also improved the renal function with the attenuation of elevated urinary N-acetyl-β-d-glucosaminidase activity and plasma creatinine concentration observed in H/R controls (both P < 0.05). The tissue levels of lipid hydroperoxides and caspase 3 in the kidney of NAC-treated animals were significantly lower than those of H/R controls. Conclusively, postresuscitation administration of NAC elicits a prolonged beneficial effect in improving renal functional recovery and reducing oxidative stress in newborn piglets with H/R insults for 48 h.
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There is a need for insight into factors that contribute to late mortality of sepsis patients. Immunomodulatory effects have been ascribed to blood transfusion. This retrospective cohort study investigates the association between the development of nosocomial bacterial infection and transfusion of leukodepleted red blood cells (RBCs) or platelets (PLTs) in survivors of the initial phase of sepsis. ⋯ In conclusion, transfusion of RBCs and PLTs is associated with the onset of secondary bacterial infection in sepsis patients. Storage time of RBCs influences this increased risk. These findings suggest that immunomodulatory effects of blood transfusion contribute to adverse outcome in the convalescent phase of sepsis.
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Randomized Controlled Trial
Thrombomodulin alfa in the treatment of infectious patients complicated by disseminated intravascular coagulation: subanalysis from the phase 3 trial.
To investigate treatment effects of thrombomodulin alfa (TM-α) in patients with disseminated intravascular coagulation (DIC) having infection as the underlying disease, retrospective subanalysis of a double-blind, randomized controlled phase 3 trial was conducted. In the phase 3 trial, 227 DIC patients (full-analysis set) having infection and/or hematologic malignancy as the underlying disease received either TM-α (0.06 mg·kg for 30 min once daily) or heparin (8 U·kg·h for 24 h) for 6 days using the double-dummy method. Among these patients, 147 patients with noninfectious comorbidity leading to severe thrombocytopenia (e.g., hematologic malignancy, or aplastic anemia) were excluded from the present analysis, and 80 patients with infectious disease and DIC were extracted and subjected to the present retrospective subanalysis. ⋯ In the TM-α and heparin groups, DIC resolution rates were 67.5% (27/40) and 55.6% (20/36), and 28-day mortality rates were 21.4% (9/42) and 31.6% (12/38), respectively. Mortality rates of patients who recovered from DIC were 3.7% (1/27) in the TM-α group and 15% (3/20) in the heparin group. These results suggest TM-α may be valuable in the treatment of DIC associated with infection.