The Effects of Dobutamine in Septic Shock: An Updated Narrative Review of Clinical and Experimental Studies.

The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of fluids, vasopressors, and inotropes. Dobutamine is the inotrope most commonly recommended and used for this purpose. Despite the fact that dobutamine was introduced almost half a century ago in the treatment of septic shock, and there is widespread use of the drug, several aspects of its pharmacodynamics remain poorly understood. In normal subjects, dobutamine increases contractility and lacks a direct effect on vascular tone. This results in augmented cardiac output and blood pressure, with reflex reduction in systemic vascular resistance. In septic shock, some experimental and clinical research suggest beneficial effects on systemic and regional perfusion. Nevertheless, other studies found heterogeneous and unpredictable effects with frequent side effects. In this narrative review, we discuss the pharmacodynamic characteristics of dobutamine and its physiologic actions in different settings, with special reference to septic shock. We discuss studies showing that dobutamine frequently induces tachycardia and vasodilation, without positive actions on contractility. Since untoward effects are often found and therapeutic benefits are occasional, its profile of efficacy and safety seems low. Therefore, we recommend that the use of dobutamine in septic shock should be cautious. Before a final decision about its prescription, efficacy, and tolerance should be evaluated throughout a short period with narrow monitoring of its wanted and side effects.

Lack of change in the respiratory quotient during oxygen supply dependence in endotoxemic shock: a subanalysis of an experimental controlled study.

OBJECTIVE: To evaluate if the reductions in systemic and renal oxygen consumption are associated with the development of evidence of anaerobic metabolism. METHODS: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep, we measured the respiratory quotient by indirect calorimetry and its systemic, renal, and intestinal surrogates (the ratios of the venous-arterial carbon dioxide pressure and content difference to the arterial-venous oxygen content difference. The Endotoxemic Shock Group (n = 12) was measured at baseline, after 60 minutes of endotoxemic shock, and after 60 and 120 minutes of fluid and norepinephrine resuscitation, and the values were compared with those of a Control Group (n = 12) without interventions. RESULTS: Endotoxemic shock decreased systemic and renal oxygen consumption (6.3 [5.6 - 6.6] versus 7.4 [6.3 - 8.5] mL/minute/kg and 3.7 [3.3 - 4.5] versus 5.4 [4.6 - 9.4] mL/minute/100g; p < 0.05 for both). After 120 minutes of resuscitation, systemic oxygen consumption was normalized, but renal oxygen consumption remained decreased (6.3 [5.9 - 8.2] versus 7.1 [6.1 - 8.6] mL/minute/100g; p = not significance and 3.8 [1.9 - 4.8] versus 5.7 [4.5 - 7.1]; p < 0.05). The respiratory quotient and the systemic, renal and intestinal ratios of the venous-arterial carbon dioxide pressure and content difference to the arterial-venous oxygen content difference did not change throughout the experiments. CONCLUSION: In this experimental model of septic shock, oxygen supply dependence was not associated with increases in the respiratory quotient or its surrogates. Putative explanations for these findings are the absence of anaerobic metabolism or the poor sensitivity of these variables in detecting this condition.

Lack of change in the respiratory quotient during oxygen supply dependence in endotoxemic shock: a subanalysis of an experimental controlled study / Ausência de alteração no quociente respiratório durante a dependência do suprimento de oxigênio no choque endotoxêmico: subanálise de um estudo experimental controlado

ABSTRACT Objective: To evaluate if the reductions in systemic and renal oxygen consumption are associated with the development of evidence of anaerobic metabolism. Methods: This is a subanalysis of a previously published study. In anesthetized and mechanically ventilated sheep, we measured the respiratory quotient by indirect calorimetry and its systemic, renal, and intestinal surrogates (the ratios of the venous-arterial carbon dioxide pressure and content difference to the arterial-venous oxygen content difference. The Endotoxemic Shock Group (n = 12) was measured at baseline, after 60 minutes of endotoxemic shock, and after 60 and 120 minutes of fluid and norepinephrine resuscitation, and the values were compared with those of a Control Group (n = 12) without interventions. Results: Endotoxemic shock decreased systemic and renal oxygen consumption (6.3 [5.6 - 6.6] versus 7.4 [6.3 - 8.5] mL/minute/kg and 3.7 [3.3 - 4.5] versus 5.4 [4.6 - 9.4] mL/minute/100g; p < 0.05 for both). After 120 minutes of resuscitation, systemic oxygen consumption was normalized, but renal oxygen consumption remained decreased (6.3 [5.9 - 8.2] versus 7.1 [6.1 - 8.6] mL/minute/100g; p = not significance and 3.8 [1.9 - 4.8] versus 5.7 [4.5 - 7.1]; p < 0.05). The respiratory quotient and the systemic, renal and intestinal ratios of the venous-arterial carbon dioxide pressure and content difference to the arterial-venous oxygen content difference did not change throughout the experiments. Conclusion: In this experimental model of septic shock, oxygen supply dependence was not associated with increases in the respiratory quotient or its surrogates. Putative explanations for these findings are the absence of anaerobic metabolism or the poor sensitivity of these variables in detecting this condition.

RESUMO Objetivo: Avaliar se as reduções do consumo de oxigênio sistêmico e renal estão associadas ao desenvolvimento de evidências de metabolismo anaeróbico. Métodos: Esta é uma subanálise de estudo já publicado. Em ovinos anestesiados e ventilados mecanicamente, medimos o quociente respiratório por calorimetria indireta e seus substitutos sistêmicos, renais e intestinais (as razões entre a diferença de pressão venoarterial do teor de dióxido de carbono e a diferença arteriovenosa do teor de oxigênio). O Grupo Choque Endotoxêmico (n = 12) foi medido inicialmente, após 60 minutos do choque endotoxêmico e após 60 e 120 minutos da ressuscitação com fluidos e norepinefrina, e os valores foram comparados com os do Grupo Controle (n = 12) sem intervenções. Resultados: O choque endotoxêmico diminuiu o consumo de oxigênio sistêmico e renal (6,3 [5,6 - 6,6] versus 7,4 [6,3 - 8,5] mL/minuto/kg e 3,7 [3,3 - 4,5] versus 5,4 [4,6 - 9,4] mL/minuto/100g; p < 0,05 para ambos). Após 120 minutos de ressuscitação, o consumo sistêmico de oxigênio foi normalizado, mas o consumo renal de oxigênio permaneceu reduzido (6,3 [5,9 - 8,2] versus 7,1 [6,1 - 8,6] mL/minuto/100g; p = NS e 3,8 [1,9 - 4,8] versus 5,7 [4,5 - 7,1]; p < 0,05). O quociente respiratório e as razões sistêmica, renal e intestinal entre a diferença na pressão venoarterial do teor de dióxido de carbono e a diferença arteriovenosa do teor de oxigênio não se alteraram ao longo dos experimentos. Conclusão: Nesse modelo experimental de choque séptico, a dependência do suprimento de oxigênio não foi associada a aumentos no quociente respiratório ou em seus substitutos. As explicações possíveis para esses achados são a ausência de metabolismo anaeróbico ou a baixa sensibilidade dessas variáveis na detecção dessa condição.

Venous Minus Arterial Carbon Dioxide Gradients in the Monitoring of Tissue Perfusion and Oxygenation: A Narrative Review.

According to Fick's principle, the total uptake of (or release of) a substance by tissues is the product of blood flow and the difference between the arterial and the venous concentration of the substance. Therefore, the mixed or central venous minus arterial CO2 content difference depends on cardiac output (CO). Assuming a linear relationship between CO2 content and partial pressure, central or mixed venous minus arterial PCO2 differences (Pcv-aCO2 and Pmv-aCO2) are directly related to CO. Nevertheless, this relationship is affected by alterations in the CO2Hb dissociation curve induced by metabolic acidosis, hemodilution, the Haldane effect, and changes in CO2 production (VCO2). In addition, Pcv-aCO2 and Pmv-aCO2 are not interchangeable. Despite these confounders, CO is a main determinant of Pcv-aCO2. Since in a study performed in septic shock patients, Pmv-aCO2 was correlated with changes in sublingual microcirculation but not with those in CO, it has been proposed as a monitor for microcirculation. The respiratory quotient (RQ)-RQ = VCO2/O2 consumption-sharply increases in anaerobic situations induced by exercise or critical reductions in O2 transport. This results from anaerobic VCO2 secondary to bicarbonate buffering of anaerobically generated protons. The measurement of RQ requires expired gas analysis by a metabolic cart, which is not usually available. Thus, some studies have suggested that the ratio of Pcv-aCO2 to arterial minus central venous O2 content (Pcv-aCO2/Ca-cvO2) might be a surrogate for RQ and tissue oxygenation. In this review, we analyze the physiologic determinants of Pcv-aCO2 and Pcv-aCO2/Ca-cvO2 and their potential usefulness and limitations for the monitoring of critically ill patients. We discuss compelling evidence showing that they are misleading surrogates for tissue perfusion and oxygenation, mainly because they are systemic variables that fail to track regional changes. In addition, they are strongly dependent on changes in the CO2Hb dissociation curve, regardless of changes in systemic and microvascular perfusion and oxygenation.

Microcirculatory effects of rewarming in experimental hemorrhagic shock.

BACKGROUND: Rewarming is a recommended therapy during the resuscitation of hypothermic patients with hemorrhagic shock. In experimental models, however, it increases inflammatory response and mortality. Although microcirculation is potential target of inflammation, the microvascular effects of rewarming during the resuscitation of hemorrhagic shock have not been studied. Our goal was to assess the systemic and microcirculatory effects of an increase in core temperature (T°) during the retransfusion of hemorrhagic shock in sheep. Our hypothesis was that rewarming could hamper microcirculation. METHODS: In anesthetized and mechanically ventilated sheep, we measured systemic, intestinal, and renal hemodynamics and oxygen transport. O2 consumption (VO2) and respiratory quotient were measured by indirect calorimetry. Cortical renal, intestinal villi and sublingual microcirculation were assessed by IDF-videomicroscopy. After basal measurements, hemorrhagic shock was induced and T° was reduced to ~33 °C. After 1 h of shock and hypothermia, blood was retransfused and Ringer lactate solution was administered to prevent arterial hypotension. In the control group (n = 12), T° was not modified, while in the intervention (rewarming) group, it was elevated ~3 °C. Measurements were repeated after 1 h. RESULTS: During shock, both groups showed similar systemic and microvascular derangements. After retransfusion, VO2 remained decreased compared to baseline in both groups, but was lower in the control compared to the rewarming group. Perfused vascular density has a similar behavior in both groups. Compared to baseline, it remained reduced in peritubular (control vs. rewarming group, 13.8 [8.7-17.5] vs. 15.7 [10.1-17.9] mm/mm2, PNS) and villi capillaries (14.7 [13.6-16.8] vs. 16.3 [14.2-16.9] mm/mm2, PNS), and normalized in sublingual mucosa (19.1 [16.0-20.3] vs. 16.6 [14.7-17.2] mm/mm2, PNS). CONCLUSIONS: This is the first experimental study assessing the effect of rewarming on systemic, regional, and microcirculatory perfusion in hypothermic hemorrhagic shock. We found that a 3 °C increase in T° neither improved nor impaired the microvascular alterations that persisted after retransfusion. In addition, sublingual mucosa was less susceptible to reperfusion injury than villi and renal microcirculation.

Role of Pv-aCO2 gradient and Pv-aCO2/Ca-vO2 ratio during cardiac surgery: a retrospective observational study.

INTRODUCTION: Arterial lactate, mixed venous O2 saturation, venous minus arterial CO2 partial pressure (Pv-aCO2) and the ratio between this gradient and the arterial minus venous oxygen content (Pv-aCO2/Ca-vO2) were proposed as markers of tissue hypoperfusion and oxygenation. The main goals were to characterize the determinants of Pv-aCO2 and Pv-aCO2/Ca-vO2, and the interchangeability of the variables calculated from mixed and central venous samples. METHODS: 35 cardiac surgery patients were included. Variables were measured or calculated: after anesthesia induction (T1), end of surgery (T2), and at 6...8.ßhours intervals after ICU admission (T3 and T4). RESULTS: Macrohemodynamics was characterized by increased cardiac index and low systemic vascular resistances after surgery (p.ß<.ß0.05). Hemoglobin, arterial-pH, lactate, and systemic O2 metabolism showed significant changes during the study (p.ß<.ß0.05). Pv-aCO2 remained high and without changes, Pv-aCO2/Ca-vO2 was also high and decreased at T4 (p.ß<.ß0.05). A significant correlation was observed globally and at each time interval, between Pv-aCO2 or Pv-aCO2/Ca-vO2 with factors that may affect the CO2 hemoglobin dissociation. A multilevel linear regression model with Pv-aCO2 and Pv-aCO2/Ca-vO2 as outcome variables showed a significant association for Pv-aCO2 with SvO2, and BE (p.ß<.ß0.05), while Pv-aCO2/Ca-vO2 was significantly associated with Hb, SvO2, and BE (p.ß<.ß0.05) but not with cardiac output. Measurements and calculations from mixed and central venous blood were not interchangeable. CONCLUSIONS: Pv-aCO2 and Pv-aCO2/Ca-vO2 could be influenced by different factors that affect the CO2 dissociation curve, these variables should be considered with caution in cardiac surgery patients. Finally, central venous and mixed values were not interchangeable.

Role of Pv-aCO2 gradient and Pv-aCO2/Ca-vO2 ratio during cardiac surgery: a retrospective observational study

Abstract Introduction: Arterial lactate, mixed venous O2 saturation, venous minus arterial CO2 partial pressure (Pv-aCO2) and the ratio between this gradient and the arterial minus venous oxygen content (Pv-aCO2/Ca-vO2) were proposed as markers of tissue hypoperfusion and oxygenation. The main goals were to characterize the determinants of Pv-aCO2 and Pv-aCO2/Ca-vO2, and the interchangeability of the variables calculated from mixed and central venous samples. Methods: 35 cardiac surgery patients were included. Variables were measured or calculated: after anesthesia induction (T1), end of surgery (T2), and at 6-8 hours intervals after ICU admission (T3 and T4). Results: Macrohemodynamics was characterized by increased cardiac index and low systemic vascular resistances after surgery (p < 0.05). Hemoglobin, arterial-pH, lactate, and systemic O2 metabolism showed significant changes during the study (p < 0.05). Pv-aCO2 remained high and without changes, Pv-aCO2/Ca-vO2 was also high and decreased at T4 (p < 0.05). A significant correlation was observed globally and at each time interval, between Pv-aCO2 or Pv-aCO2/Ca-vO2 with factors that may affect the CO2 hemoglobin dissociation. A multilevel linear regression model with Pv-aCO2 and Pv-aCO2/Ca-vO2 as outcome variables showed a significant association for Pv-aCO2 with SvO2, and BE (p < 0.05), while Pv-aCO2/Ca-vO2 was significantly associated with Hb, SvO2, and BE (p < 0.05) but not with cardiac output. Measurements and calculations from mixed and central venous blood were not interchangeable. Conclusions: Pv-aCO2 and Pv-aCO2/Ca-vO2 could be influenced by different factors that affect the CO2 dissociation curve, these variables should be considered with caution in cardiac surgery patients. Finally, central venous and mixed values were not interchangeable.

Comparison of central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio and lactate levels as predictors of mortality in critically ill patients: a systematic review and meta-analysis. / Comparação da proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo de oxigênio arterial menos venoso central e níveis de lactato como preditores de mortalidade em pacientes críticos: uma revisão sistemática e metanálise.

OBJECTIVE: The central venousarterial carbon dioxide pressure to arterial-central venous oxygen content ratio (Pcv-aCO2/Ca-cvO2) is frequently used as a surrogate for tissue oxygenation. We aimed to identify and synthesize literature and quality of evidence supporting Pcv-aCO2/Ca-cvO2 as a predictor of mortality in critically ill patients compared with lactate. METHODS: We searched several databases for studies measuring Pcv-aCO2/Ca-cvO2 in critically ill patients. Independent investigators performed the article screening and data extraction. A random-effects metaanalysis was performed. Pooled standardized mean differences (SMD) were used to compare the prognostic ability of Pcv-aCO2/Ca-cvO2 and lactate. RESULTS: We initially retrieved 172 studies; 17 were included for qualitative description, and 10 were included for quantitative synthesis. The mean Pcv-aCO2/Ca-cvO2 was higher in nonsurvivors than in survivors (pooled SMD = 0.75; 95%CI 0.34 - 1.17; I2 = 83%), as was the case with lactate levels (pooled SMD = 0.94; 95%CI 0.34 - 1.54; I2 = 92%). Both tests were statistically significant predictors of mortality, albeit with overlapping 95%CIs between them. CONCLUSION: Moderate-quality evidence showed little or no difference in the ability of Pcv-aCO2/Ca-cvO2, compared with lactate, to predict mortality. Nevertheless, our conclusions are limited by the considerable heterogeneity among the studies.PROSPERO registration: CRD42019130387.

OBJETIVO: A proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo de oxigênio arterial menos venoso central (Pcv-aCO2/Ca-cvO2) é frequentemente usada como substituta para a oxigenação tecidual. O objetivo deste estudo foi identificar e sintetizar a literatura e a qualidade das evidências que suportam a Pcv-aCO2/Ca-cvO2 como um preditor de mortalidade em comparação com o lactato em pacientes críticos. MÉTODOS: Pesquisamos vários bancos de dados procurando estudos que tivessem medido a Pcv-aCO2/Ca-cvO2 em pacientes críticos. Pesquisadores independentes realizaram a triagem dos artigos e a extração de dados. Uma metanálise de efeitos aleatórios foi realizada. Diferenças médias padronizadas agrupadas foram usadas para comparar a capacidade prognóstica da Pcv-aCO2/Ca-cvO2 e do lactato. RESULTADOS: Inicialmente, obtivemos 172 estudos; 17 foram incluídos para descrição qualitativa, e dez foram incluídos para síntese quantitativa. A média de Pcv-aCO2/Ca-cvO2 foi maior nos não sobreviventes do que nos sobreviventes (diferença média padronizada agrupada de 0,75; IC95% 0,34 - 1,17; I2 = 83%), assim como os níveis de lactato (diferença média padronizada agrupada = 0,94; IC95% 0,34 - 1,54; I2 = 92%). Ambos os testes foram preditores estatisticamente significativos de mortalidade, embora com sobreposição de IC95% entre eles. CONCLUSÃO: Evidências de qualidade moderada mostraram pouca ou nenhuma diferença na capacidade da Pcv-aCO2/Ca-cvO2, em comparação com o lactato, em predizer mortalidade. No entanto, nossas conclusões são limitadas pela considerável heterogeneidade entre os estudos.Registro no PROSPERO: CRD42019130387.

Retrospective evaluation of jugular venous blood variables and mortality in critically ill hospitalized cats.

OBJECTIVE: To evaluate clinicopathological variables associated with hospital mortality in critically ill cats with compromised hemodynamics and tissue hypoperfusion. DESIGN: Retrospective observational study. SETTING: Private referral center. ANIMALS: Fifty-seven critically ill cats with compromised hemodynamics or tissue hypoperfusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The electronic medical records were searched for all cats admitted from June 2014 to November 2020. Cats were included in the study if the medical records clearly identified the presence of compromised hemodynamics and tissue hypoperfusion. Blood samples were obtained by percutaneous puncture of the external jugular vein, and blood gases, electrolytes, L-lactate concentration, and glucose were measured by a point-of-care analyzer. A predictive logistic regression model for mortality was performed. A total of 57 cats were ultimately included in the study. Thirty-five cats died. Eighteen of them were euthanized because of the severity of illness, and 17 died naturally. Twenty-two cats were discharged alive from the hospital. After adjusting for the Acute Patient Physiologic and Laboratory Evaluation (APPLE) fast score and disease category, jugular venous partial pressure of oxygen (Pvjo2 ) and HCT at admission were independent predictors of hospital mortality (HCT: odds ratio [OR], 0.763, 95% confidence interval [CI]: 0.625-0.930; P = 0.008; Pjvo2 : OR, 0.858; 95% CI: 0.749-0.984; P = 0.029). The association of these variables with mortality was maintained after conducting a sensitivity analysis and excluding cats that died by euthanasia. CONCLUSIONS: In cats with hemodynamic instability and tissue hypoperfusion, HCT and Pvjo2 behaved as independent predictors of mortality. Both variables seem to reflect the magnitude of oxygen debt and tissue hypoperfusion.

Comparação da proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo de oxigênio arterial menos venoso central e níveis de lactato como preditores de mortalidade em pacientes críticos: uma revisão sistemática e metanálise / Comparison of central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio and lactate levels as predictors of mortality in critically ill patients: a systematic review and meta-analysis

RESUMO Objetivo: A proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo de oxigênio arterial menos venoso central (Pcv-aCO2/Ca-cvO2) é frequentemente usada como substituta para a oxigenação tecidual. O objetivo deste estudo foi identificar e sintetizar a literatura e a qualidade das evidências que suportam a Pcv-aCO2/Ca-cvO2 como um preditor de mortalidade em comparação com o lactato em pacientes críticos. Métodos: Pesquisamos vários bancos de dados procurando estudos que tivessem medido a Pcv-aCO2/Ca-cvO2 em pacientes críticos. Pesquisadores independentes realizaram a triagem dos artigos e a extração de dados. Uma metanálise de efeitos aleatórios foi realizada. Diferenças médias padronizadas agrupadas foram usadas para comparar a capacidade prognóstica da Pcv-aCO2/Ca-cvO2 e do lactato. Resultados: Inicialmente, obtivemos 172 estudos; 17 foram incluídos para descrição qualitativa, e dez foram incluídos para síntese quantitativa. A média de Pcv-aCO2/Ca-cvO2 foi maior nos não sobreviventes do que nos sobreviventes (diferença média padronizada agrupada de 0,75; IC95% 0,34 - 1,17; I2 = 83%), assim como os níveis de lactato (diferença média padronizada agrupada = 0,94; IC95% 0,34 - 1,54; I2 = 92%). Ambos os testes foram preditores estatisticamente significativos de mortalidade, embora com sobreposição de IC95% entre eles. Conclusão: Evidências de qualidade moderada mostraram pouca ou nenhuma diferença na capacidade da Pcv-aCO2/Ca-cvO2, em comparação com o lactato, em predizer mortalidade. No entanto, nossas conclusões são limitadas pela considerável heterogeneidade entre os estudos. Registro no PROSPERO:CRD42019130387

ABSTRACT Objective: The central venousarterial carbon dioxide pressure to arterial-central venous oxygen content ratio (Pcv-aCO2/Ca-cvO2) is frequently used as a surrogate for tissue oxygenation. We aimed to identify and synthesize literature and quality of evidence supporting Pcv-aCO2/Ca-cvO2 as a predictor of mortality in critically ill patients compared with lactate. Methods: We searched several databases for studies measuring Pcv-aCO2/Ca-cvO2 in critically ill patients. Independent investigators performed the article screening and data extraction. A random-effects metaanalysis was performed. Pooled standardized mean differences (SMD) were used to compare the prognostic ability of Pcv-aCO2/Ca-cvO2 and lactate. Results: We initially retrieved 172 studies; 17 were included for qualitative description, and 10 were included for quantitative synthesis. The mean Pcv-aCO2/Ca-cvO2 was higher in nonsurvivors than in survivors (pooled SMD = 0.75; 95%CI 0.34 - 1.17; I2 = 83%), as was the case with lactate levels (pooled SMD = 0.94; 95%CI 0.34 - 1.54; I2 = 92%). Both tests were statistically significant predictors of mortality, albeit with overlapping 95%CIs between them. Conclusion: Moderate-quality evidence showed little or no difference in the ability of Pcv-aCO2/Ca-cvO2, compared with lactate, to predict mortality. Nevertheless, our conclusions are limited by the considerable heterogeneity among the studies. PROSPERO registration:CRD42019130387

Incidence and determinats of augmented renal clearance in traumatic brain injury: A prospective observational study.

PURPOSE: To characterize the incidence, timing, and predictors of augmented renal clearance (ARC) in patients with traumatic brain injury (TBI). MATERIALS AND METHODS: In 61 patients with TBI, creatinine clearance (CrCl) was prospectively measured from urine samples, over seven days. ARC was defined as a CrCl >130 mL/min/1.73 m2 in at least one day. We compared patients with and without ARC. RESULTS: We performed 295 determinations of CrCl. ARC was present in 82% of the patients and arose in the first 2 days in 86% of them. ARC was more frequent in patients with associated injuries (100 vs. 75%, P = 0.02). There was a trend to a more aggressive resuscitation in patients with ARC but young age was the only independent predictor. Hospital length of stay was higher in ARC (15 [8-25] vs. 6 [3-19] days, P < 0.05). CONCLUSIONS: ARC is very common and has an early appearance in patients with TBI. Young age is its main determinant.

Clinical characteristics, respiratory management, and determinants of oxygenation in COVID-19 ARDS: A prospective cohort study.

PURPOSE: To identify determinants of oxygenation over time in patients with COVID-19 acute respiratory distress syndrome (ARDS); and to analyze their characteristics according to Berlin definition categories. MATERIALS AND METHODS: Prospective cohort study including consecutive mechanically ventilated patients admitted between 3/20/2020-10/31/2020 with ARDS. Epidemiological and clinical data on admission; outcomes; ventilation, respiratory mechanics and oxygenation variables were registered on days 1, 3 and 7 for the entire population and for ARDS categories. RESULTS: 1525 patients aged 61 ± 13, 69% male, met ARDS criteria; most frequent comorbidities were obesity, hypertension, diabetes and respiratory disease. On admission, 331(21%), 849(56%) and 345(23%) patients had mild, moderate and severe ARDS; all received lung-protective ventilation (mean tidal volumes between 6.3 and 6.7 mL/kg PBW) and intermediate PEEP levels (10-11 cmH2O). PaO2/FiO2, plateau pressure, static compliance, driving pressure, ventilation ratio, pH and D-dimer >2 mg/L remained significantly different among the ARDS categories over time. In-hospital mortality was, respectively, 55%, 58% and 70% (p < 0.000). Independent predictors of changes of PaO2/FiO2 over time were BMI; preexistent respiratory disease; D-dimer >2 mg/L; day 1-PEEP, and day 1-ventilatory ratio. CONCLUSION: Hypoxemia in patients with COVID-19-related ARDS is associated with comorbidities, deadspace and activated coagulation markers, and disease severity-reflected by the PEEP level required.

Capacidad estructural, recursos humanos tecnológicos y requerimientos de ventilación mecánica en 58 unidades de cuidados intensivos en argentina durante la pandemia por SARS-CoV-2. Estudio SATICOVID-19 / Structural capacity, technological human resources and mechanical ventilation requirements in 58 intensive care units in Argentina during the SARS-CoV-2 pandemic. A SATICOVID-19 Study

Resumen Durante la pandemia por SARS-CoV-2 hubo un marcado requerimiento de camas de cuidados críticos, insumos y profesionales entrenados para asistir a pacientes con insuficiencia respiratoria grave. La Sociedad Argentina de Terapia Intensiva (SATI) diseñó un estudio para caracterizar estos aspectos en las Unidades de Cuidados Intensivos (UCIs). Estudio multicéntrico, de cohorte prospectiva; las UCIs participantes completaron un formulario al final del estudio (31/10/2020) sobre características hospitalarias, número de camas de áreas críticas pre- e intra-pandemia, incorporación de profesionales, insumos y recursos tecnológicos, y carga de trabajo. Participaron 58 UCIs; 28(48%) de Provincia de Buenos Aires, 22(38%) de Ciudad Autónoma de Bue nos Aires, 10(17%) de otras; 31(53%) UCIs pertenecían al sector público; 23(47%) al privado-seguridad social. En 35/58(60%) hospitales las camas de cuidados críticos aumentaron de 902 a 1575(75%); 37% en UCI y 63% principalmente en Unidad Coronaria y Emergencias-shock room. En 41/55(75%) UCIs se incorporó personal: 27(49%) médicos/as (70% intensivistas), 36(65%) enfermeros/as, 28(51%) kinesiólogos/as, 20(36%) personal de limpieza, y 1(2%) otros/as; 96% de las UCIS reportaron disponer de respiradores suficientes, y 95%, insumos y EPP suficientes. De todos los pacientes en ventilación mecánica invasiva, 55% [43-64] presentaron COVID-19. Se requirió oxigenoterapia como soporte no invasivo en 14% [8-24] de los ingresos por COVID-19. Se registró una importante expansión de las áreas críticas operativas, secundariamente al aumento de camas, personal, y adecuada disponibilidad de respiradores e insumos esenciales. La carga de la enfermedad crítica por COVID-19 fue intensa, constituyendo más de la mitad de los pacientes en ventilación mecánica.

Abstract During the SARS-CoV-2 pandemic, there was a marked requirement for critical care beds, supplies and trained professionals to assist patients with severe respiratory failure. The Argentine Society of Intensive Care (SATI) designed a study to characterize these aspects in intensive care units (ICUs). Multicenter, prospective cohort study; the participating ICUs completed a form at the end of the study (31/10/2020) on hospital characteristics, number of beds in pre- and intra-pandemic critical areas, incorporation of professionals, technological resources, and workload. Fifty-eight ICUs participated; 28(48%) were located in Buenos Aires Province, 22(38%) in Buenos Aires Autonomous City and 10 (17%) in other provinces; 31 (53%) of UCIs belonged to the public sector; 23 (47%) to the private-social security. In 35/58 (60%) of the hospitals critical care beds increased from 902 to 1575 (75%), 37% in ICU and 63% mainly in Coronary Care Unit and Emergency-shock room. In 41/55 (75%) UCIs, staff were incorporated: 27(49%) physicians (70% intensivists), 36 (65%) nurses, 28 (51%) respiratory therapists, 20(36%) cleaning staff, and 1(2%) others. A 96% of the ICUS reported having sufficient ventilators and 95% enough sup plies and PPE. Of all patients on invasive mechanical ventilation, 55% [43-64] had COVID-19. Oxygen therapy was required as noninvasive support in 14% [8-24] of COVID-19 admissions. There was a significant expansion of critical operational areas, secondary to the increase in beds, staff, and adequate availability of ventilators and essential supplies. The burden of critical illness from COVID-19 was intense, with more than half of patients on mechanical ventilation.

[Structural capacity, technological human resources and mechanical ventilation requirements in 58 intensive care units in Argentina during the SARS-CoV-2 pandemic. A SATICOVID-19 Study]. / Capacidad estructural, recursos humanos tecnológicos y requerimientos de ventilación mecánica en 58 unidades de cuidados intensivos en Argentina durante la pandemia por SARS-CoV-2. Estudio SATICOVID-19.

During the SARS-CoV-2 pandemic, there was a marked requirement for critical care beds, supplies and trained professionals to assist patients with severe respiratory failure. The Argentine Society of Intensive Care (SATI) designed a study to characterize these aspects in intensive care units (ICUs). Multicenter, prospective cohort study; the participating ICUs completed a form at the end of the study (31/10/2020) on hospital characteristics, number of beds in pre- and intra-pandemic critical areas, incorporation of professionals, technological resources, and workload. Fifty-eight ICUs participated; 28(48%) were located in Buenos Aires Province, 22(38%) in Buenos Aires Autonomous City and 10 (17%) in other provinces; 31 (53%) of UCIs belonged to the public sector; 23 (47%) to the private-social security. In 35/58 (60%) of the hospitals critical care beds increased from 902 to 1575 (75%), 37% in ICU and 63% mainly in Coronary Care Unit and Emergency-shock room. In 41/55 (75%) UCIs, staff were incorporated: 27(49%) physicians (70% intensivists), 36 (65%) nurses, 28 (51%) respiratory therapists, 20(36%) cleaning staff, and 1(2%) others. A 96% of the ICUS reported having sufficient ventilators and 95% enough supplies and PPE. Of all patients on invasive mechanical ventilation, 55% [43-64] had COVID-19. Oxygen therapy was required as noninvasive support in 14% [8-24] of COVID-19 admissions. There was a significant expansion of critical operational areas, secondary to the increase in beds, staff, and adequate availability of ventilators and essential supplies. The burden of critical illness from COVID-19 was intense, with more than half of patients on mechanical ventilation.

Durante la pandemia por SARS-CoV-2 hubo un marcado requerimiento de camas de cuidados críticos, insumos y profesionales entrenados para asistir a pacientes con insuficiencia respiratoria grave. La Sociedad Argentina de Terapia Intensiva (SATI) diseñó un estudio para caracterizar estos aspectos en las Unidades de Cuidados Intensivos (UCIs). Estudio multicéntrico, de cohorte prospectiva; las UCIs participantes completaron un formulario al final del estudio (31/10/2020) sobre características hospitalarias, número de camas de áreas críticas pre- e intra-pandemia, incorporación de profesionales, insumos y recursos tecnológicos, y carga de trabajo. Participaron 58 UCIs; 28(48%) de Provincia de Buenos Aires, 22(38%) de Ciudad Autónoma de Buenos Aires, 10(17%) de otras; 31(53%) UCIs pertenecían al sector público; 23(47%) al privado-seguridad social. En 35/58(60%) hospitales las camas de cuidados críticos aumentaron de 902 a 1575(75%); 37% en UCI y 63% principalmente en Unidad Coronaria y Emergencias-shock room. En 41/55(75%) UCIs se incorporó personal: 27(49%) médicos/as (70% intensivistas), 36(65%) enfermeros/as, 28(51%) kinesiólogos/as, 20(36%) personal de limpieza, y 1(2%) otros/as; 96% de las UCIS reportaron disponer de respiradores suficientes, y 95%, insumos y EPP suficientes. De todos los pacientes en ventilación mecánica invasiva, 55% [43-64] presentaron COVID-19. Se requirió oxigenoterapia como soporte no invasivo en 14% [8-24] de los ingresos por COVID-19. Se registró una importante expansión de las áreas críticas operativas, secundariamente al aumento de camas, personal, y adecuada disponibilidad de respiradores e insumos esenciales. La carga de la enfermedad crítica por COVID-19 fue intensa, constituyendo más de la mitad de los pacientes en ventilación mecánica.

Current practice and evolving concepts in septic shock resuscitation.

Clinical and pathophysiological understanding of septic shock has progressed exponentially in the previous decades, translating into a steady decrease in septic shock-related morbidity and mortality. Even though large randomized, controlled trials have addressed fundamental aspects of septic shock resuscitation, many questions still exist. In this review, we will describe the current standards of septic shock resuscitation, but the emphasis will be placed on evolving concepts in different domains such as clinical resuscitation targets, adequate use of fluids and vasoactive drugs, refractory shock, and the use of extracorporeal therapies. Multiple research opportunities remain open, and collaborative endeavors should be performed to fill in these gaps.

Clinical characteristics and outcomes of invasively ventilated patients with COVID-19 in Argentina (SATICOVID): a prospective, multicentre cohort study.

BACKGROUND: Although COVID-19 has greatly affected many low-income and middle-income countries, detailed information about patients admitted to the intensive care unit (ICU) is still scarce. Our aim was to examine ventilation characteristics and outcomes in invasively ventilated patients with COVID-19 in Argentina, an upper middle-income country. METHODS: In this prospective, multicentre cohort study (SATICOVID), we enrolled patients aged 18 years or older with RT-PCR-confirmed COVID-19 who were on invasive mechanical ventilation and admitted to one of 63 ICUs in Argentina. Patient demographics and clinical, laboratory, and general management variables were collected on day 1 (ICU admission); physiological respiratory and ventilation variables were collected on days 1, 3, and 7. The primary outcome was all-cause in-hospital mortality. All patients were followed until death in hospital or hospital discharge, whichever occurred first. Secondary outcomes were ICU mortality, identification of independent predictors of mortality, duration of invasive mechanical ventilation, and patterns of change in physiological respiratory and mechanical ventilation variables. The study is registered with ClinicalTrials.gov, NCT04611269, and is complete. FINDINGS: Between March 20, 2020, and Oct 31, 2020, we enrolled 1909 invasively ventilated patients with COVID-19, with a median age of 62 years [IQR 52-70]. 1294 (67·8%) were men, hypertension and obesity were the main comorbidities, and 939 (49·2%) patients required vasopressors. Lung-protective ventilation was widely used and median duration of ventilation was 13 days (IQR 7-22). Median tidal volume was 6·1 mL/kg predicted bodyweight (IQR 6·0-7·0) on day 1, and the value increased significantly up to day 7; positive end-expiratory pressure was 10 cm H2O (8-12) on day 1, with a slight but significant decrease to day 7. Ratio of partial pressure of arterial oxygen (PaO2) to fractional inspired oxygen (FiO2) was 160 (IQR 111-218), respiratory system compliance 36 mL/cm H2O (29-44), driving pressure 12 cm H2O (10-14), and FiO2 0·60 (0·45-0·80) on day 1. Acute respiratory distress syndrome developed in 1672 (87·6%) of patients; 1176 (61·6%) received prone positioning. In-hospital mortality was 57·7% (1101/1909 patients) and ICU mortality was 57·0% (1088/1909 patients); 462 (43·8%) patients died of refractory hypoxaemia, frequently overlapping with septic shock (n=174). Cox regression identified age (hazard ratio 1·02 [95% CI 1·01-1·03]), Charlson score (1·16 [1·11-1·23]), endotracheal intubation outside of the ICU (ie, before ICU admission; 1·37 [1·10-1·71]), vasopressor use on day 1 (1·29 [1·07-1·55]), D-dimer concentration (1·02 [1·01-1·03]), PaO2/FiO2 on day 1 (0·998 [0·997-0·999]), arterial pH on day 1 (1·01 [1·00-1·01]), driving pressure on day 1 (1·05 [1·03-1·08]), acute kidney injury (1·66 [1·36-2·03]), and month of admission (1·10 [1·03-1·18]) as independent predictors of mortality. INTERPRETATION: In patients with COVID-19 who required invasive mechanical ventilation, lung-protective ventilation was widely used but mortality was high. Predictors of mortality in our study broadly agreed with those identified in studies of invasively ventilated patients in high-income countries. The sustained burden of COVID-19 on scarce health-care personnel might have contributed to high mortality over the course of our study in Argentina. These data might help to identify points for improvement in the management of patients in middle-income countries and elsewhere. FUNDING: None. TRANSLATION: For the Spanish translation of the Summary see Supplementary Materials section.