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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Decompensation is a major prehospital threat to survival from trauma/hemorrhage shock (T/HS) after controlling bleeding. We recently showed higher than expected mortality from a combat-relevant rat model of T/HS (27 mL/kg hemorrhage) with tourniquet (TQ) and permissive hypotensive resuscitation (PHR) with Plasmalyte. Mortality and fluid requirements were reduced by resuscitation with 25% albumin presaturated with oleic acid (OA-sat) compared with fatty-acid -free albumin or Plasmalyte. ⋯ Decompensation was due to vascular decompensation rather than loss of cardiac performance. Albumin concentration was lower in decompensating groups, suggesting decreased stressed volume, which may explain the association of low albumin on admission with poor outcomes after trauma. Our findings suggest that acute decompensation may be common after trauma and severe hemorrhage treated with TQ and PHR and OA-sat albumin may benefit early survival and reduce transfusion volume by improving venous constriction and preventing decompensation.
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Sepsis-induced immunosuppression involves both innate and adaptive immunity and is associated with the increased expression of checkpoint inhibitors, such as programmed cell-death protein 1 (PD-1). The expression of PD-1 is associated with poor outcomes in septic patients, and in models of sepsis, blocking PD-1 or its ligands with antibodies increased survival and alleviated immune suppression. While inhibitory antibodies are effective, they can lead to immune-related adverse events (irAEs), in part due to continual blockade of the PD-1 pathway, resulting in hyperactivation of the immune response. ⋯ Altered survival was associated with improved macrophage phagocytic activity and T-cell production of interferon-γ. Further, myeloperoxidase levels and esterase-positive cells were significantly reduced in LD01-treated mice. Taken together, these data establish that LD01 modulates host immunity and is a viable therapeutic candidate for alleviating immunosuppression that characterizes sepsis and other infectious diseases.
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Persistent Inflammation, Immune Suppression, and Catabolism Syndrome (PICS) is a disease state affecting patients who have a prolonged recovery after the acute phase of a large inflammatory insult. Trauma and sepsis are two pathologies after which such an insult evolves. In this review, we will focus on the key clinical determinants of PICS: Immunosuppression and cellular dysfunction. ⋯ In this review, we will discuss how regulatory T cells (Tregs), innate lymphoid cells, natural killer T cells (NKT cells), TCR-a CD4- CD8- double-negative T cells (DN T cells), and B cells can contribute to the development of post-traumatic and septic immunosuppression. Altogether, we seek to fill a gap in the understanding of the contribution of lymphocyte immunosuppression and dysfunction to the development of chronic immune disbalance. Further, we will provide an overview of promising diagnostic and therapeutic interventions, whose potential to overcome the detrimental immunosuppression after trauma and sepsis is currently being tested.
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Observational Study
Association Between the Oxygen Consumption: Lactate Ratio and Survival in Critically Ill Patients With Sepsis.
Mitochondrial dysfunction leading to impairment of oxygen extraction, referred to as cytopathic hypoxia, contributes to morbidity in sepsis. Oxygen consumption (VO2) may be a useful measure of the severity of cytopathic hypoxia. We monitored VO2 and carbon dioxide production (VCO2) in septic patients and investigated the association with hospital survival. ⋯ The VO2:lactate ratio was significantly higher in survivors, while there was no association between median VO2 alone and survival. There was a significant difference in change in VCO2 over time between survivors and non-survivors.
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Particularly for protracted bleeding situations, the realization of a relevant blood loss is necessary for early initiation of therapy to avoid hemodynamic instability and shock. The frequently used visual assessment of blood loss is known to be incorrect. An innovative option to address this problem is a mobile application using colorimetric image correction and analysis. ⋯ The blood loss measured in the sponges correlated strong with the reference blood loss, showing the smallest median overestimation and the smallest deviation in underestimation. The visual estimation shows serious errors, where the gravimetric method is prone to errors, especially in dilution. The colorimetric method offers an easily implementable possibility to monitor blood loss in real time and to initiate early diagnostic and therapeutic measures in case of persistent blood loss. The influence of real-time estimation of colorimetric blood loss on transfusion decisions should be the subject of future studies.