Persistent Sepsis-Induced Hypotension without Hyperlactatemia: A Distinct Clinical and Physiological Profile within the Spectrum of Septic Shock

Introduction. A subgroup of septic shock patients will never develop hyperlactatemia despite being subjected to a massive circulatory stress. Maintenance of normal lactate levels during septic shock is of great clinical and physiological interest. Our aim was to describe the clinical, hemodynamic, perfusion, and microcirculatory profiles associated to the absence of hyperlactatemia during septic shock resuscitation. Methods. We conducted an observational study in septic shock patients undergoing resuscitation. Serial clinical, hemodynamic, and perfusion parameters were registered. A single sublingual microcirculatory assessment was performed in a subgroup. Patients evolving with versus without hyperlactatemia were compared. Results. 124 septic shock patients were included. Patients without hyperlactatemia exhibited lower severity scores and mortality. They also presented higher platelet counts and required less intensive treatment. Microcirculation was assessed in 45 patients. Patients without hyperlactatemia presented higher PPV and MFI values. Lactate was correlated to several microcirculatory parameters. No difference in systemic flow parameters was observed. Conclusion. Persistent sepsis-induced hypotension without hyperlactatemia is associated with less organ dysfunctions and a very low mortality risk. Patients without hyperlactatemia exhibit less coagulation and microcirculatory derangements despite comparable macrohemodynamics. Our study supports the notion that persistent sepsis-induced hypotension without hyperlactatemia exhibits a distinctive clinical and physiological profile

Clinical Study Persistent Sepsis-Induced Hypotension without Hyperlactatemia: A Distinct Clinical and Physiological Profile within the Spectrum of Septic Shock

Introduction. A subgroup of septic shock patients will never develop hyperlactatemia despite being subjected to a massive circulatory stress. Maintenance of normal lactate levels during septic shock is of great clinical and physiological interest. Our aim was to describe the clinical, hemodynamic, perfusion, and microcirculatory profiles associated to the absence of hyperlactatemia during septic shock resuscitation. Methods. We conducted an observational study in septic shock patients undergoing resuscitation. Serial clinical, hemodynamic, and perfusion parameters were registered. A single sublingual microcirculatory assessment was performed in a subgroup. Patients evolving with versus without hyperlactatemia were compared. Results. 124 septic shock patients were included. Patients without hyperlactatemia exhibited lower severity scores and mortality. They also presented higher platelet counts and required less intensive treatment. Microcirculation was assessed in 45 patients. Patients without hyperlactatemia presented higher PPV and MFI values. Lactate was correlated to several microcirculatory parameters. No difference in systemic flow parameters was observed. Conclusion. Persistent sepsis-induced hypotension without hyperlactatemia is associated with less organ dysfunctions and a very low mortality risk. Patients without hyperlactatemia exhibit less coagulation and microcirculatory derangements despite comparable macrohemodynamics. Our study supports the notion that persistent sepsisinduced hypotension without hyperlactatemia exhibits a distinctive clinical and physiological profile

Current concepts in acute liver failure

Acute liver failure (ALF) is a severe condition secondary to a myriad of causes associated with poor outcomes. The prompt diagnosis and identification of the aetiology allow the administration of specific treatments plus supportive strategies and to define the overall prognosis, the probability of developing complications and the need for liver transplantation. Pivotal issues are adequate monitoring and the institution of prophylactic strategies to reduce the risk of complications, such as progressive liver failure, cerebral oedema, renal failure, coagulopathies or infections. In this article, we review the main aspects of ALF, including the definition, diagnosis and complications. Also, we describe the standard-of-care strategies and recent advances in the treatment of ALF. Finally, we include our experience of care patients with ALF

Terapia ocupacional y paciente crítico

This study was conducted in The Unit Critics adult patients, Clinical Hospital of the Catholic University of Chile (UPC- HCPUC), in2012, where the characteristics of critical patients were explored to obtain a profile of global health while in the UPC, in order todetermine whether it would be possible to make an intervention from occupational therapy to be a contribution to this unit.A prospective, observational study in medical UPC-surgery for 25 days. The results allowed to characterize critical patients of this unit,as a subject with high probability of impairment of consciousness, edema in hand, limitation of joint range of motion (ROM ) in the wristand fingers, and lack of stimuli that evoke your reality prior to hospitalization.Finally, from the analysis of the profile of critical patient - HCPUC UPC and the context to which it is exposed, it is concluded that earlyintervention occupational therapy could reduce and prevent the appearance of certain signs associated with critical patient, checkinghypothesized that given the characteristics of this patient, it would be an intervention from Occupational TherapyEl presente estudio fue realizado en la Unidad de Pacientes Críticos adultos, del Hospital Clínico de la Pontificia Universidad Católica de Chile (UPC-HCPUC), durante el año 2012, donde se exploraron las características del paciente crítico, para obtener un perfil de salud global durante su estadía en la UPC, con el fin de determinar si sería posible realizar una intervención desde la Terapia Ocupacional que fuese un aporte a esta unidad. Se realizó un estudio prospectivo, observacional en la UPC médico–quirúrgica durante 25 días. Los resultados obtenidos permitieron caracterizar al paciente crítico de esta unidad, como un sujeto con alta probabilidad de presentar compromiso de conciencia, edema en mano, limitación de rango de movimiento articular (ROM) en muñeca y dedos, y carencia de estímulos que evoquen su realidad previa a la hospitalización. Finalmente, a partir del análisis del perfil del paciente crítico de la UPC-HCPUC y del contexto al que se encuentra expuesto, se concluye que la intervención temprana de Terapia Ocupacional podría disminuir y prevenir la aparición de algunos signos asociados al paciente crítico, comprobándose la hipótesis, que dadas las características de este paciente, sería posible realizar una intervención desde la Terapia Ocupacional

SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19). An aspect of high uncertainty is whether the SARS-CoV-2 per se or the systemic inflammation induced by viral infection directly affects cellular function and survival in different tissues. It has been postulated that tissue dysfunction and damage observed in COVID-19 patients may rely on the direct effects of SARS-CoV-2 viral proteins. Previous evidence indicates that the human immunodeficiency virus and its envelope protein gp120 increase the activity of connexin 43 (Cx43) hemichannels with negative repercussions for cellular function and survival. Here, we evaluated whether the spike protein S1 of SARS-CoV-2 could impact the activity of Cx43 hemichannels. Results We found that spike S1 time and dose-dependently increased the activity of Cx43 hemichannels in HeLa-Cx43 cells, as measured by dye uptake experiments. These responses were potentiated when the angiotensin-converting enzyme 2 (ACE2) was expressed in HeLa-Cx43 cells. Patch clamp experiments revealed that spike S1 increased unitary current events with conductances compatible with Cx43 hemichannels. In addition, Cx43 hemichannel opening evoked by spike S1 triggered the release of ATP and increased the [Ca2+]i dynamics elicited by ATP. Conclusions We hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences

Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study

Purpose: Perfusion assessment during septic shock resuscitation is difficult and usually complex determinations. Capillary refill time (CRT) and central-to-toe temperature difference (Tc-toe) have been proposed as objective reproducible parameters to evaluate peripheral perfusion. The comparative evolution of peripheral vs metabolic perfusion parameters in septic shock resuscitation has not been studied. We conducted a prospective observational clinical-physiologic study to address this subject. Methods: Patients with sepsis-related circulatory dysfunction were resuscitated according to a standard local algorithm. Perfusion assessment included serial determinations of metabolic (central venous O-2 saturation [ScvO(2)] and central venous to arterial PCO2 gradient [P(cv-a)CO2]) and peripheral perfusion parameters (CRT and Tc-toe, among others). Successful resuscitation was defined as a normal plasma lactate at 24 hours. Results: Forty-one patients were included. The presence of normal values for both CRT and Tc-toe considered together at 6 hours was independently associated with a successful resuscitation (P = .02), as compared with the behavior of metabolic parameters. Capillary refill time was the first parameter to be significantly normalized. Conclusion: Early recovery of peripheral perfusion anticipates a successful resuscitation compared with traditional metabolic parameters in septic shock patients. Our findings support the inclusion of serial peripheral perfusion assessment in multimodal monitoring strategies for septic shock resuscitation. (C) 2012 Elsevier Inc. All rights reserve

Relationship of systemic, hepatosplanchnic, and microcirculatory perfusion parameters with 6-hour lactate clearance in hyperdynamic septic shock patients: an acute, clinical-physiological, pilot study

Background: Recent clinical studies have confirmed the strong prognostic value of persistent hyperlactatemia and delayed lactate clearance in septic shock. Several potential hypoxic and nonhypoxic mechanisms have been associated with persistent hyperlactatemia, but the relative contribution of these factors has not been specifically addressed in comprehensive clinical physiological studies. Our goal was to determine potential hemodynamic and perfusion-related parameters associated with 6-hour lactate clearance in a cohort of hyperdynamic, hyperlactatemic, septic shock patients. Methods: We conducted an acute clinical physiological pilot study that included 15 hyperdynamic, septic shock patients undergoing aggressive early resuscitation. Several hemodynamic and perfusion-related parameters were measured immediately after preload optimization and 6 hours thereafter, with 6-hour lactate clearance as the main outcome criterion. Evaluated parameters included cardiac index, mixed venous oxygen saturation, capillary refill time and central-to-peripheral temperature difference, thenar tissue oxygen saturation (StO(2)) and its recovery slope after a vascular occlusion test, sublingual microcirculatory assessment, gastric tonometry (pCO(2) gap), and plasma disappearance rate of indocyanine green (ICG-PDR). Statistical analysis included Wilcoxon and Mann-Whitney tests. Results: Five patients presented a 6-hour lactate clearance = 10%, they presented a worse hepatosplanchnic perfusion as represented by significantly more severe derangements of ICG-PDR (9.7 (8-19) vs. 19.6 (9-32)%/min, p <0.05) and pCO(2) gap (33 (9.1-62) vs. 7.7 (3-58) mmHg, p <0.05) at 6 hours. No other systemic, hemodynamic, metabolic, peripheral, or microcirculatory parameters differentiated these subgroups. We also found a significant correlation between ICG-PDR and pCO(2) gap (p = 0.02). Conclusions: Impaired 6-hour lactate clearance could be associated with hepatosplanchnic hypoperfusion in some hyperdynamic septic shock patients. Improvement of systemic, metabolic, and peripheral perfusion parameters does not rule out the persistence of hepatosplanchnic hypoperfusion in this setting. Severe microcirculatory abnormalities can be detected in hyperdynamic septic shock patients, but their role on lactate clearance is unclear. ICG-PDR may be a useful tool to evaluate hepatosplanchnic perfusion in septic shock patients with persistent hyperlactatemi