The Levels of Inflammatory Regulatory Factors in Acute Leukemia Complicated by Infection and Its Clinical Significance / 中国实验血液学杂志

OBJECTIVE@#To explore the expression levels and clinical significance of helper T cell 1/helper T cell 2 (Th1/Th2) cytokine and interleukin-6 (IL-6) in patients with acute leukemia (AL) complicated by infection.@*METHODS@#68 patients with AL complicated by infection admitted to Wuhan Fifth Hospital from May 2017 to January 2020 were enrolled as study group, 50 AL patients without infection were enrolled as AL group, and 30 healthy volunteers checked in physical examination center were enrolled as healthy control group. The levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10), and peripheral blood Th1/Th2 cells subsets were measured and compared among the three groups. The serum IL-6, IL-10, TNF-α and Th1/Th2 were compared between the patients with mild to moderate infection (n=52) and septic shock (n=16). The relationship between IL-6, IL-10, TNF-α, Th1/Th2 and AL infection was analyzed.@*RESULTS@#The levels of IL-6, IL-10 , TNF-α, and the proportion of Th2 of the patients in study group and AL group were significantly higher than those in healthy control group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in healthy control group (P<0.001). The levels of IL-6, IL-10 and TNF-α, and the proportion of Th2 the patients in study group were significantly higher than those in AL group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in AL group (P<0.001). The serum IL-6, IL-10 and TNF-α level of the patients in septic shock group were significantly higher than those in mild-to-moderate infection group (P<0.001), while Th1/Th2 was lower than those in mild-to-moderate infection group (P<0.001). The results of ROC curve analysis showed that the area under the ROC curve (AUC) values of IL-6, IL-10, TNF-α and Th1/Th2 alone for the diagnosis of septic shock were 0.779, 0.761, 0.724 and 0.718, which were lower than that their combination (0.910) (P<0.05).@*CONCLUSION@#The levels of serum IL-6, IL-10 and TNF-α are high in patients with AL complicated infection and septic shock, while Th1/Th2 cell subsets is low. The combined detection of serum IL-6, IL-10, TNF-α and Th1/Th2 is a good diagnostic value for predicting the occurrence of severe septic shock.

Sobrecarga de fluidos em pacientes com choque séptico e depuração de lactato como alvo terapêutico: um estudo de coorte retrospectiva / Fluid overload in patients with septic shock and lactate clearance as a therapeutic goal: a retrospective cohort study

RESUMO Objetivo: Avaliar se a sobrecarga de fluidos na terapia hídrica é fator prognóstico para pacientes com choque séptico quando ajustada para os alvos de depuração de lactato. Métodos: Este estudo envolveu uma coorte retrospectiva e foi conduzido em um hospital de cuidados nível IV localizado em Bogotá, na Colômbia. Foi organizada uma coorte de pacientes com choque séptico, e suas características e balanço hídrico foram documentados. Os pacientes foram estratificados por níveis de exposição segundo a magnitude da sobrecarga de fluidos por peso corporal após 24 horas de terapia. A mortalidade foi determinada aos 30 dias, e foi desenvolvido um modelo de regressão logística incondicional com ajuste para fatores de confusão. A significância estatística foi estabelecida com nível de p ≤ 0,05. Resultados: Foram 213 pacientes com choque séptico e, após o tratamento, 60,8% deles tiveram depuração de lactato acima de 50%. Dentre os pacientes 97 (46%) desenvolveram sobrecarga de fluidos ≥ 5%, e apenas 30 (13%) desenvolveram sobrecarga ≥ 10%. Pacientes com sobrecarga de fluidos ≥ 5% receberam, em média, 6.227mL de soluções cristaloides (DP ± 5.838mL) em 24 horas, enquanto os não expostos receberam 3.978mL (DP ± 3.728mL), com p = 0.000. Os pacientes que desenvolveram sobrecarga de fluidos foram mais frequentemente tratados com ventilação mecânica (70,7% versus 50,8%; p = 0,003), albumina (74,7% versus 55,2%; p = 0,003) e corticosteroides (53,5% versus 35,0%; p = 0,006) do que os que não desenvolveram sobrecarga de fluidos. Em análise multivariada, o balanço acumulado de fluidos não se associou com mortalidade (RC 1,03; IC95% 0,89 - 1,20). Conclusão: Após ajuste para severidade da condição e depuração adequada de lactato, a ocorrência de balanço hídrico positivo não se associou com aumento da mortalidade nessa coorte latino-americana de pacientes sépticos.

ABSTRACT Objective: To assess whether fluid overload in fluid therapy is a prognostic factor for patients with septic shock when adjusted for lactate clearance goals. Methods: This was a retrospective cohort study conducted at a level IV care hospital in Bogotá, Colombia. A cohort of patients with septic shock was assembled. Their characteristics and fluid balance were documented. The patients were stratified by exposure levels according to the magnitude of fluid overload by body weight after 24 hours of therapy. Mortality was determined at 30 days, and an unconditional logistic regression model was created, adjusting for confounders. The statistical significance was established at p ≤ 0.05. Results: There were 213 patients with septic shock, and 60.8% had a lactate clearance ≥ 50% after treatment. Ninety-seven (46%) patients developed fluid overload ≥ 5%, and only 30 (13%) developed overload ≥ 10%. Patients exhibiting fluid overload ≥ 5% received an average of 6227mL of crystalloids (SD ± 5838mL) in 24 hours, compared to 3978mL (SD ± 3728mL) among unexposed patients (p = 0.000). The patients who developed fluid overload were treated with mechanical ventilation (70.7% versus 50.8%) (p = 0.003), albumin (74.7% versus 55.2%) (p = 0.003) and corticosteroids (53.5% versus 35.0%) (p = 0.006) more frequently than those who did not develop fluid overload. In the multivariable analysis, cumulative fluid balance was not associated with mortality (OR 1.03; 95%CI 0.89 - 1.20). Conclusions: Adjusting for the severity of the condition and adequate lactate clearance, cumulative fluid balance was not associated with increased mortality in this Latin American cohort of septic patients.

Asociación entre el sitio de infección y la mortalidad hospitalaria en pacientes con sepsis atendidos en urgencias de hospitales de tercer nivel en Medellín, Colombia / Association between site of infection and in-hospital mortality in patients with sepsis admitted to emergency departments of tertiary hospitals in Medellin, Colombia

RESUMEN Objetivo: Determinar en pacientes con sepsis admitidos en el servicio de urgencias la asociación entre el foco infeccioso principal y la mortalidad intrahospitalaria como desenlace principal o requerimiento de ingreso a unidad de cuidados intensivos como desenlace secundario. Métodos: Análisis secundario de cohorte prospectiva multicéntrica. Se incluyeron pacientes mayores de 18 años con diagnóstico de sepsis grave o choque séptico atendidos en las salas de urgencias de 3 hospitales de alta complejidad. De 5022 elegibles, se incluyeron 2510 participantes. Análisis de regresión logística múltiple para mortalidad. Resultados: El sitio de infección más frecuente fue tracto urinario, presente en el 27,8% de los casos, seguido de neumonía en el 27,5% y foco intraabdominal en el 10,8%. En el 5,4% de los casos no se identificó foco claro al ingreso. Mediante regresión logística se encontró asociación significativa entre los siguientes sitios de infección y mortalidad intrahospitalaria al tomar como referencia el grupo de infección urinaria: neumonía (OR 3,4; IC95%, 2,2 - 5,2; p < 0,001), piel y tejidos blandos (OR 2,6; IC95%, 1,4 - 5,0; p = 0,003), torrente sanguíneo (OR 2,0; IC95%, 1,1 - 3,6; p = 0,018), sin foco claro (OR 2,0; IC95%, 1,1 - 3,8; p = 0,028), e intraabdominal (OR 1,9; IC95%, 1,1 - 3,3; p = 0,024). Conclusiones: Existe una asociación significativa entre los diferentes sitios de infección y la mortalidad intrahospitalaria o requerimiento de unidad de cuidados intensivos en pacientes con sepsis o choque séptico, siendo la infección de vías urinarias la que confiere el menor riesgo, lo que se deberá tener en cuenta en los modelos pronósticos de estas condiciones.

ABSTRACT Objective: To determine the association between the primary site of infection and in-hospital mortality as the main outcome, or the need for admission to the intensive care unit as a secondary outcome, in patients with sepsis admitted to the emergency department. Methods: This was a secondary analysis of a multicenter prospective cohort. Patients included in the study were older than 18 years with a diagnosis of severe sepsis or septic shock who were admitted to the emergency departments of three tertiary care hospitals. Of the 5022 eligible participants, 2510 were included. Multiple logistic regression analysis was performed for mortality. Results: The most common site of infection was the urinary tract, present in 27.8% of the cases, followed by pneumonia (27.5%) and intra-abdominal focus (10.8%). In 5.4% of the cases, no definite site of infection was identified on admission. Logistic regression revealed a significant association between the following sites of infection and in-hospital mortality when using the urinary infection group as a reference: pneumonia (OR 3.4; 95%CI, 2.2 - 5.2; p < 0.001), skin and soft tissues (OR 2.6; 95%CI, 1.4 - 5.0; p = 0.003), bloodstream (OR 2.0; 95%CI, 1.1 - 3.6; p = 0.018), without specific focus (OR 2.0; 95%CI, 1.1 - 3.8; p = 0.028), and intra-abdominal focus (OR 1.9; 95%CI, 1.1 - 3.3; p = 0.024). Conclusions: There is a significant association between the different sites of infection and in-hospital mortality or the need for admission to an intensive care unit in patients with sepsis or septic shock. Urinary tract infection shows the lowest risk, which should be considered in prognostic models of these conditions.

Influence of perfusion status on central and mixed venous oxygen saturation in septic patients / Influência do status perfusional nas saturações venosas de oxigênio central e mista em pacientes sépticos

Abstract Background and objectives Although there is controversy regarding the role of venous oxygen saturation in the initial resuscitation of septic patients with hypoperfusion these markers are still widely used. This study aimed to evaluate the correlation and concordance between central (SvcO2) and mixed (SvO2) oxygen saturation in septic shock patients with or without hypoperfusion in addition to the impact of these differences in patient conduction. Methods Patients with septic shock were monitored with pulmonary artery catheter and the following subgroups of hypoperfusion were analyzed: 1) lactate > 28 mg.dL-1; 2) base excess ≤ -5 mmol.L-1; 3) venoarterial CO2 gradient > 6 mmHg; 4) SvO2 < 65%; 5) SvcO2 < 70%; 6) lactate > 28 mg.dL-1 and SvO2 < 70%; 7) lactate > 28 mg.dL-1 and SvcO2 < 75%. Results Seventy-seven samples from 24 patients were included. There was only a moderate correlation between SvO2 and SvcO2 (r = 0.72, p = 0.0001) and there was no good concordance between these variables (7.35% bias and 95% concordance limits of -3.0% to 17.7%). Subgroup analysis according to the presence of hypoperfusion showed no differences in concordance between variables. There was discordance regarding clinical management in 13.8% (n = 9) of the cases. Conclusions There is a moderate correlation between SvO2 and SvcO2; however, the concordance between them is inadequate. It was not possible to demonstrate that the presence of hypoperfusion alters the concordance between SvO2 and SvcO2. The use of SvO2 instead of SvcO2 may lead to changes in clinical management in a small but clinically relevant portion of patients.

Resumo Justificativa e objetivos Embora haja controvérsias sobre o papel das saturações venosas de oxigênio na ressuscitação inicial do paciente séptico com hipoperfusão, esses marcadores são ainda bastante usados. Este estudo procurou avaliar a correlação e a concordância entre as saturações venosas central (SvcO2) e mista (SvO2) de oxigênio em pacientes com choque séptico, na presença ou não de hipoperfusão, além do impacto dessas diferenças na condução clínica do paciente. Métodos Foram incluídos pacientes com choque séptico monitorados com cateter de artéria pulmonar e analisados os seguintes subgrupos de hipoperfusão: 1) Lactato > 28 mg.dL-1; 2) Excesso de bases ≤ -5 mmoL.L-1; 3) Gradiente venoarterial de CO2 > 6 mmHg; 4) SvO2 < 65%; 5) SvcO2 < 70%; 6) Lactato > 28 mg.dL-1 e SvO2 < 70%; 7) Lactato > 28 mg.dL-1 e SvcO2 < 75%. Resultados Foram incluídas 70 amostras de 24 pacientes. Houve apenas correlação moderada entre SvO2 e SvcO2 (r = 0,72; p = 0,0001) e não houve boa concordância entre essas variáveis (viés de 7,35% e limites de concordância de 95% de -3,0%-17,7%). A análise dos subgrupos de acordo com a presença de hipoperfusão não mostrou diferenças na concordância entre as variáveis. Houve discordância na conduta clínica em 13,8% dos casos (n = 9). Conclusões Existe correlação moderada entre SvO2 e SvcO2, entretanto a concordância entre elas é inadequada. Não foi possível demonstrar que a presença de hipoperfusão altera a concordância entre a entre SvO2 e SvcO2. O uso da SvO2 em vez da SvcO2 pode levar a alterações na conduta clínica numa parcela pequena, porém clinicamente relevante, dos pacientes.

Aldosterone secretion in patients with septic shock: a prospective study / Secreção de aldosterona em pacientes com choque séptico: estudo prospectivo

OBJECTIVE: To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS: In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS: Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS: Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

OBJETIVO: Avaliar os níveis séricos dos principais fatores que regulam a ativação da zona glomerulosa e a produção de aldosterona em pacientes com choque séptico, assim como sua resposta ao teste de cortrosina em alta dose (250 µg). SUJEITOS E MÉTODOS: Em 27 portadores de choque séptico, foram aferidos níveis basais de aldosterona, cortisol, ACTH, renina, sódio, potássio e lactato, bem como realizado teste de cortrosina. RESULTADOS: Renina se correlacionou com níveis basais de aldosterona e sua variação após teste de cortrosina. Cortisol basal e sua variação não se correlacionaram com ACTH. Apenas três pacientes apresentaram disfunção concomitante da secreção de aldosterona e cortisol. CONCLUSÕES: Ativação das zonas fasciculada e glomerulosa são independentes. Secreção de aldosterona é dependente da integridade do sistema renina-angiotensina-aldosterona, enquanto secreção de cortisol não parece predominantemente dependente do eixo hipotálamo-hipófise-adrenal. Esses resultados sugerem que a ativação da adrenal em pacientes críticos ocorre por múltiplos mecanismos.

Fisiopatología del shock: Nuevas perspectivas / Pathophysiology of shock: New perspectives

La actividad metabólica puede modificarse mediante la regulación de la población mitocondrial en distintas enfermedades críticas. A través de observaciones y ensayos clínicos examinamos esta adaptación metabólica en el shock cardiogénico, hemorrágico y séptico. La caída de la disponibilidad de O2 (DO2) llevaría a una reducción de la población mitocondrial y consecuentemente a una disminución del consumo de O2 (VO2). Esta secuencia permite atenuar y aun evitar la adquisición de una deuda de O2, considerada hasta hoy base fundamental de la fisiopatología del shock. El costo de esta adaptación mitocondrial es menor energía disponible y el déficit energético resultante ha sido relacionado con la falla orgánica múltiple (FOM), importante complicación de diversos procesos inflamatorios agudos y estados de shock. La FOM es mejor tolerada que el metabolismo anaeróbico y es potencialmente reversible si se revierten las causas desencadenantes y se reestablece el nivel energético por medio de la biogénesis mitocondrial.El desacople de la fosforilación oxidativa mitocondrial ocurre tanto en diversos modelos experimentales de shock como así también en el shock séptico en el hombre. Esta alteración mitocondrial puede ser detectada por un aumento desmesurado del VO2 en respuesta al incremento terapéutico de la DO2. Este aumento de la actividad metabólica puede ser equívocamente interpretado como la fase de repago de una deuda de O2.

Metabolic activity can be down-regulated throughout the reduction of mitochondrial population. Lowering O2 demand in cardiogenic, hemorrhagic and septic shock is here examined through clinical observations and trials. A decrease in the availability of O2 will be followed by reductions in mitochondrial population and, therefore, in a decrease in O2 demand. This response may lessen or prevent the acquisition of an O2 debt; until now, cornerstone in the pathophysiology of shock. The cost of this adaptation is less energy production, and the resulting energy deficit has been linked to multiple organ failure (MOF), a complication of acute inflammatory processes and shock. MOF is better tolerated than anaerobic metabolism and is potentially reversible if the triggering causes are reversed and the energy level is re-established through mitochondrial biogenesis.Decoupling of mitochondrial oxidative phosphorylation occurs in both experimental models and in clinical septic shock. In critical patients this phenomenon may be detected by an inordinate increase in VO2 in response to a therapeutically increased DO2. This hipermetabolic stage can be mistakenly interpreted as the repayment phase of an O2 debt.

Uso de bicarbonato de sódio na acidose metabólica do paciente gravemente enfermo / Sodium bicarbonate in the critically ill patient with metabolic acidosis

A acidose lática é um distúrbio do equilíbrio ácido-base muito frequente em pacientes internados em unidades de terapia intensiva e está associado a um mau prognóstico. Embora exista um acúmulo substancial de evidências de que níveis cítricos de acidemia provocam inúmeros efeitos adversos sobre o funcionamento celular, a utilização de bicarbonato de sódio para o tratamento da acidose lática em pacientes gravemente enfermos permanece alvo de controvérsias. Neste artigo, pretendemos:1) analisar as principais diferenças entre as acidoses hiperclorêmicas e as acidoses orgânicas, com ânion gap (AG) elevado, visando embasar a discussão sobre os fundamentos da terapia com bicarbonato de sódio nas acidoses metabólicas; 2) avaliar os riscos associados à persistência de níveis críticos de acidemia, contrastando-os com os riscos do uso de bicarbonato de sódio; 3) analisar criticamente as evidências da literatura sobre o uso de bicarbonato de sódio no tratamento da acidose lática do paciente crítico, com ênfase em ensaios clínicos randomizados em seres humanos; 4) fornecer um fundamento para a utilização judiciosa de bicarbonato de sódio nesta situação.

Lactic acidosis is a disorder of acid-base balance very common in patients hospitalized in intensive care units and is associated with a poor prognosis. Although there is a substantial accumulation of evidence that levels of citric acidemia leading to numerous adverse effects on cell function, the use of sodium bicarbonate to treat lactic acidosis in critically ill patients remains a subject of controversies. In this article we will: 1) analyze the main differences between the hyperchloremic acidosis and organic acidosis with anion gap (AG) high, in order to base the discussion on the fundamentals of therapy with sodium bicarbonate in metabolic acidosis, 2) assess the risks associated with the persistence of critical levels of acidemia, contrasting them with the risks of using sodium bicarbonate, 3) critically examine the evidence in the literature about the use of sodium bicarbonate in treating lactic acidosis in critically ill patients, with emphasis on tests clinical trials in humans, 4) provide a foundation for the judicious use of sodium bicarbonate in this situation.

Efeitos hemodinâmicos e metabólicos da infusão de vasopressina em crianças com choque: [revisão] / Hemodynamic and metabolic effects of vasopressin infusion in children with shock: [review]

OBJETIVO: A vasopressina é um hormônio neuropeptídico utilizado clinicamente há mais de 50 anos, com papel importante na homeostase circulatória e na regulação da osmolalidade sérica. Seu papel no tratamento do choque vem recebendo ênfase recentemente. Foram revisadas a fisiologia deste neuro-hormônio e as evidências disponíveis para sua utilização no contexto de choque com vasodilatação na criança. FONTES DOS DADOS: MEDLINE, usando os termos vasopressin, vasodilation, shock, septic shock, e sinônimos e termos relacionados, além de publicações clássicas referentes ao tema, sendo escolhidas as mais representativas. SÍNTESE DOS DADOS: A vasopressina é sintetizada na neuro-hipófise e liberada em resposta à diminuição da volemia ou ao aumento da osmolalidade plasmática. A ação da vasopressina dá-se pela ativação de vários receptores acoplados à proteína G, os quais são classificados, de acordo com sua localização e rotas de transmissão intracelular, em receptores V1 (ou V1b), V2 e V3 (ou V1b) e por receptores de ocitocina. A função central da vasopressina é causar vasoconstrição, embora, em determinados órgãos, possa promover vasodilatação seletiva. Diversos estudos clínicos em adultos e crianças apontam efeitos benéficos e seguros da vasopressina no tratamento do choque com vasodilatação por diversas causas. CONCLUSÃO: As evidências são restritas, os estudos na maioria são retrospectivos e com número reduzido de pacientes, mas já há uma experiência bastante significativa no que diz respeito a seu uso em pediatria. A vasopressina possui um efeito clinico benéfico na criança e pode ser indicada no tratamento do choque refratário com vasodilatação, depois de adequada reposição volêmica e quando altas doses de outros vasopressores não foram eficazes.

OBJECTIVE:Vasopressin is a neuropeptide hormone which has been used clinically for more than 50 years and plays a major role in circulatory homeostasis and in the regulation of serum osmolality. Recent work has emphasized its role in the treatment of septic shock. This paper reviews the physiology of this neurohormone and the available evidence in favor of its use as a vasodilator for children in shock. SOURCES: MEDLINE, using the terms vasopressin, vasodilation, shock and septic shock, plus synonyms and related terms. Classic publications on the topic were also reviewed and selected depending on their relevance to the study objectives. SUMMARY OF THE FINDINGS: Vasopressin is synthesized in the neurohypophysis and released in response to a decrease in plasma volume or an increase in serum osmolality. The action of vasopressin is mediated by the activation of oxytocin receptors and of several G protein-coupled receptors, which are classified according to their location and intracellular transmission routes as V1 receptors (or V1b), V2 and V3 receptors (or V1b). The main role of vasopressin is to induce vasoconstriction. However, in certain organs, it can also induce selective vasodilation. Several clinical studies in adults and children have reported that the effects of vasopressin for the treatment of vasodilatory septic shock, due to a variety of causes, are both beneficial and safe. CONCLUSIONS: The evidence is restricted. Most studies are retrospective and include a small number of patients. Nevertheless, there is significant experience concerning the use of vasopressin in Pediatrics. Vasopressin has a beneficial clinical effect in children and can be indicated in the treatment of refractory vasodilatory shock, after adequate volume resuscitation and when high doses of other vasopressors are not effective.

Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue

To investigate the role of nitric oxide in human sepsis, ten patients with severe septic shock requiring vasoactive drug therapy and mechanical ventilation were enrolled in a prospective, open, non-randomized clinical trial to study the acute effects of methylene blue, an inhibitor of guanylate cyclase. Hemodynamic and metabolic variables were measured before and 20, 40, 60, and 120 min after the start of a 1-h intravenous infusion of 4 mg/kg of methylene blue. Methylene blue administration caused a progressive increase in mean arterial pressure (60 [55-70] to 70 [65-100] mmHg, median [25-75th percentiles]; P<0.05), systemic vascular resistance index (649 [479-1084] to 1066 [585-1356] dyne s-1 cm-5 m-2; P<0.05) and the left ventricular stroke work index (35 [27-47] to 38 [32-56] g m-1 m-2; P<0.05) from baseline to 60 min. The pulmonary vascular resistance index increased from 150 [83-207] to 186 [121-367] dyne s-1 cm-5 m-2 after 20 min (P<0.05). Mixed venous saturation decreased from 65 [56-76] to 63 [55-69] per cent (P<0.05) after 60 min. The PaO2/FiO2 ratio decreased from 168 [131-215] to 132 [109-156] mmHg (P<0.05) after 40 min. Arterial lactate concentration decreased from 5.1 + or - 2.9 to 4.5 + or - 2.1 mmol/l, mean + or - SD (<0.05) after 60 min. Heart rate, cardiac filling pressures, cardiac output, oxygen delivery and consumption did not change. Methylene blue administration was safe and no adverse effect was observed. In severe human septic shock, a short infusion of methylene blue increases systemic vascular resistance and may improve myocardial function. Although there was a reduction in blood lactate concentration, this was not explained by an improvement in tissue oxygenation, since overall oxygen availability did not change. However, there was a significant increase in pulmonary vascular tone and a deterioration in gas exchange. Further studies are needed to demonstrate if nitric oxide blockade with methylene blue can be safe for patients with septic shock and, particularly, if it has an effect on pulmonary function.

Biochemistry of free radicals: from electrons to tissues

Free radicals are chemical species with an unpaired electron in the outer valence orbitals. The unpaired electron makes them paramagnetic (physics) and relatively reactive (chemistry). The free radiclas that are normal metabolites in aerobic biological systems have varied reactivities, ranging from the high reactivity of hydroxyl radical (t(1/2) = 10(-9) s)) to the low reactivity of melanins (t (1/2) = days)). The univalent reduction of oxygen that takes place in mammalian organs produces superoxide radicals at a rate of about 2 per cent of the total oxygen uptake. The primary production of superoxide radicals sustains a free radical chain reaction involving a series of reactive oxygen species (hydrogen peroxide, hydroxyl and peroxyl radical and singlet oxygen). Nitric oxide is almos tunreactive as free radical except for its termination reaction with superoxide radical to yield the strong oxidant peroxynitrite. Nitric oxide also reacts with ubiquinol in a redox reaction, with cytochrome oxidase competitively with oxygen, and oxymyoglobin and oxyhemoglobin displacing oxygen. Septic shock and endotoxemia produce muscle dysfunction and oxidative stress due to increased steady state concentrations of reative oxygen and nitrogen species.

Metabolismo de drogas en el higado de sepsis: conclusiones acerca de la farmacocinetica del cloramfenicol / Drug metabolism in the liver of sepsis: conclusiones about the pharmacokinetrics of cloramphenicol

En nueve pacientes en shock séptico por anaerobios, cinco de ellos con diverso grado de fallo hepático (hígado de sepsis), se determinó concentración hemática de cloramfenicol a 5 minutos, 1, 2, 3 y 6 horas de inyección IV de la primeira de 3 dosis diarias correspondientes a 50 mg/k/día; en el grupo con comp5romiso hepático se repitió el procedimiento con la siguiente dosis, previa infusión de dos horas con dopaminas 3- 10 mcg/k/minuto, como intento de compensación hemodinámica. A partir de los datos experimentales se realizó el ajuste por computación de la curva concentración-tiempo y la regresión lineal con un ajuste p=0.001, determinándose vida media (VM), volumen de distribución (Vd), constante de eliminación (K) y clearance (CI). En el grupo shock séptico sin compromiso hepático se observó comportamiento uniformes, con concentraciones alejadas de niveles tóxico-medulares, y parámetros farmacocinéticos sensiblemente cercanos a los normales, con moderada prolongación de Vm. Ante el fallo hepático, aunque con variabilidad individual, las concentraciones alcanzan niveles tóxico-medulares (25 mcg/ml), destacándose un descenso estadísticamente significativo del CI promedio (p=0.001), con moderado descenso del Vd respecto a normales. Ante el intento de compensación hemodinámica con dopamina, vuelven a incrementarse concentraciones de cloramfenicol en el grupo con hígado de sepsis sufriendo nuevos deterioros Vm, Vd y CI promedios, aunque también com comportamiento no-uniforme. Se enfatiza en la significación práctica de esta metodología en el manejo de drogas en la insuficiencia hepática severa, lo que permitirá valorar matemáticamente diversos componentes patogénicos. Se concluye, que si bien cada paciente debiera ser individualmente evaluado, la dosificación de cloramfenicol no debe sufrir modificaciones en shock séptico sin fallo hepático, mientras que ante esta eventualidad, la dosis debiera disminuirse a la mitad, prolongándose el intervalo al doble apróximadamente