Significado biológico y utilidad clínica del lactato en la sepsis / Biological significance and clinical utility of lactate in sepsis

La sepsis es un problema global de salud y la progresión hacia el shock séptico se asocia con un incremento marcado de la morbimortalidad. En este escenario, el aumento del lactato plasmático demostró ser un indicador de gravedad y un predictor de mortalidad, y suele interpretarse casi exclusivamente como marcador de baja perfusión tisular. Sin embargo, últimamente se produjo un cambio de paradigma en la exégesis del metabolismo y propiedades biológicas del lactato. En efecto, la adaptación metabólica al estrés, aun con adecuado aporte de oxígeno, puede justificar la elevación del lactato circulante. Asimismo, otras consecuencias fisiopatológicas de la sepsis, como la disfunción mitocondrial, se asocian con el desarrollo de hiperlactatemia sin que necesariamente se acompañen de baja perfusión tisular. Interpretar el origen y la función del lactato puede resultar de suma utilidad clínica en la sepsis, especialmente cuando sus niveles circulantes fundamentan las medidas de reanimación.

Sepsis is a global health problem; progression to septic shock is associated with a marked increase in morbidity and mortality. In this setting, increased plasma lactate levels demonstrated to be an indicator of severity and a predictor of mortality, and are usually interpreted almost exclusively as a marker of low tissue perfusion. However, a recent paradigm shift has occurred in the exegesis of lactate metabolism and its biological properties. Indeed, metabolic adaptation to stress, even with an adequate oxygen supply, may account for high circulating lactate levels. Likewise, other pathophysiological consequences of sepsis, such as mitochondrial dysfunction, are associated with the development of hyperlactatemia, which is not necessarily accompanied by low tissue perfusion. Interpreting the origin and function of lactate may be of great clinical utility in sepsis, especially when circulating lactate levels are the basis for resuscitative measures.

Relación entre el tiempo de circulación extracorpórea y el pinzamiento aórtico con diferentes variables de evolución postquirúrgicas / Relationship between cardiopulmonary bypass time and aortic cross clamping time with different variables of post-surgical evolution

Resumen Justificación: La mayor cantidad de cirugías cardiacas realizadas a nivel mundial se efectúa con circulación extracorpórea y pinzamiento de la aorta, lo que conlleva una serie de alteraciones fisiopatológicas que deben ser reconocidas por el personal de salud que participa en la atención de estos pacientes. Objetivo: Describir el perfil y los factores de riesgo presentes en los pacientes sometidos a cirugía cardiaca con circulación extracorpórea, y analizar la existencia de una potencial relación entre el tiempo de circulación extracorpórea y el pinzamiento aórtico, con la aplicación de desfibrilaciones tras al pinzado de la aorta, la necesidad de soporte cardiovascular farmacológico, el comportamiento del nivel de lactato plasmático y la mortalidad. Métodos: Se desarrolló un estudio observacional y descriptivo con una muestra de 104 pacientes electivos, sometidos a intervención quirúrgica y circulación extracorpórea, en el Hospital México, desde octubre de 2016 a noviembre de 2017. Se caracterizó la población en estudio, se analizaron los factores de riesgo incluido el EuroSCORE I y II, el tiempo de circulación extracorpórea, el tiempo de pinzamiento aórtico, las desfibrilaciones posteriores al pinzamiento aórtico, e lactato inmediatamente postcirculación extracorpórea, y a las 2, 6, 24 h postquirúrgicas, el uso de soporte cardiovascular farmacológico en infusión continua posterior a la circulación extracorpórea y mortalidad a los 30 días. Resultados: La edad media fue 56,4 años, predominó el sexo masculino (69 %) y la hipertensión arterial fue el factor de riesgo más frecuente (76,07 %). Se registró un tiempo de pinzado aórtico menor a 100 min en 61 pacientes (58,65 %) y superior a ese tiempo en 43 pacientes (41,35 %). El EuroSCORE I promedio fue del 4,21 % (DE: 4,80), mientras que el EuroSCORE II fue del 2,37 % (DE: 2,41). El tiempo promedio de circulación extracorpórea fue de 129 minutos (DE: 36,88) y el de pinzado aórtico, de 94 minutos (DE:32,04). Hubo un pico de lactato a las 6 horas postquirúrgicas (5,13 mmol/L, DE:2,89); un 8,65 % de los pacientes fueron desfibrilados después del retiro de la pinza en la aorta; se utilizó soporte cardiovascular en el 16,35 % y la mortalidad quirúrgica fue del 1,92 %. Conclusiones: En el estudio, el tiempo de circulación extracorpórea y el pinzado aórtico junto con el uso de inotrópicos, vasoconstrictores, hiperlactatemia y mortalidad quirúrgica, no alcanzó una relación significativa.

Abstract Justification: Currently, the largest number of cardiac surgeries performed worldwide are performed with cardiopulmonary bypass and aortic cross clamp, which leads to a series of pathophysiological alterations that are important for health personnel involved in the care of these patients. Objective: To describe the profile and risk factors present in patients undergoing cardiac surgery with cardiopulmonary bypass and the existence of a potential relationship between the cardiopulmonary bypass time and aortic cross clamping time, with the use of post clamp defibrillations, pharmacological cardiovascular support, plasma lactate behavior and mortality. Methods: An observational and descriptive study was carried out with a sample of 104 elective patients, undergoing surgical intervention and cardiopulmonary bypass at Hospital México, from October 2016 to November 2017. The study population was characterized, risk factors were analyzed including EuroSCORE I and II, CPB time, aortic cross clamping time, post-aortic clamping defibrillation, lactate immediately after extracorporeal circulation and at 2, 6, 24 hours postoperatively, use of pharmacological cardiovascular support in continuous infusion after extracorporeal circulation and mortality at 30 days. Results: The mean age was 56.4 years, the male sex predominated (69%) and arterial hypertension was the most frequent risk factor (76.07%). Aortic cross clamp time of less than 100 min was recorded in 61 patients (58.65%) and greater than that time in 43 patients (41.35%). The average EuroSCORE I was 4.21% (SD: 4.80), while the EuroSCORE II was 2.37% (SD: 2.41). The average cardiopulmonary bypass time was 129 minutes (SD: 36.88) and aortic cross clamp time was 94 minutes (SD: 32.04). There was a lactate peak at 6 postoperative hours (5.13 mmol/L, SD: 2.89); 8.65% of patients were defibrillated after removal the clamp in the aorta; pharmacological cardiovascular support was used in 16.35% and surgical mortality was 1.92%. Conclusions: In this study, cardiopulmonary bypass time and aortic cross clamp time together with the use of inotropics, vasoconstrictors, hyperlactatemia and surgical mortality did not reach a significant relationship.

Renal tubular acidosis associated with trimethoprim-sulfamethoxazole poisoning / Acidosis tubular renal asociada a intoxicación por trimetoprim-sulfametoxazol

Abstract The combination of trimethoprim-sulfamethoxazole (TMP-SMZ or cotrimoxazole) has a bactericidal effect on gram-positive cocci and gram-negative bacilli. It is used clinically for skin and soft tissue, respiratory and urinary tract infections, and is also relevant for prophylaxis and treatment of opportunistic infections in immunosuppressed patients. Its use at established doses in immunocompetent patients is safe, with a low rate of adverse events. However, in immunosuppressed individuals (human immunodeficiency virus [HIV], transplants, or steroid users), the adverse effects (AEs) of this medication reach 83%; and, when administered parenterally at high doses, lactic acidosis has been documented secondary to the polyethylene glycol vehicle. We present two cases of patients who ingested an overdose of TMP-SMZ and developed type 2 renal tubular acidosis (RTA), which has not been described with this medication, and whose hyperlactatemia is not explained by the polyethylene glycol excipient, as it was taken orally.

Resumen La combinación de trimetoprim-sulfametoxazol (TMP-SMZ o cotrimoxazol) tiene efecto bactericida sobre cocos gram positivos y bacilos gram negativos, con uso clínico en infecciones de piel y tejidos blandos, del tracto respiratorio y urinario, además con relevancia en la profilaxis y tratamiento de infecciones oportunistas en pacientes inmunosupresos. Su uso en pacientes inmunocompetentes a dosis establecidas es seguro, con una baja tasa de eventos adversos. Sin embargo, en población con inmunosupresión: virus de inmunodeficiencia humana (VIH), trasplante, o usuarios de esteroides; los efectos adversos (EA) por este medicamento alcanzan 83% y por administración parenteral en dosis elevadas se ha documentado acidosis láctica secundaria al vehículo polietilenglicol. Presentamos dos casos de pacientes que ingirieron TMP-SMZ en sobredosis, desarrollando acidosis tubular renal (ATR) tipo 2, la cual no se ha descrito en este medicamento y cuya hiperlactatemia no es explicable por el excipiente polietilenglicol debido a que el consumo fue oral.

Repercusión neurológica por cambios en el flujo sanguíneo cerebral en neonatos sometidos a cirugía cardiovascular / Neurological repercussions of changes in cerebral blood flow in neonates undergoing cardiovascular surgery

Resumen Introducción: La cirugía de cardiopatías congénitas puede generar alteraciones perfusorias cerebrales con repercusión neurológica. Objetivo: Analizar la relación del índice de resistencia (IR) vascular cerebral periquirúrgico con funciones neurológicas mediatas posteriores a cirugía de cardiopatía congénita. Método: Estudio de cohorte prospectivo de 34 neonatos en quienes se determinó IR de la arteria basilar, niveles séricos de oxígeno, dióxido de carbono y lactato, antes y después de procedimientos paliativos o correctivos. Relacionamos el IR prequirúrgico con la capacidad posquirúrgica para iniciar la vía enteral o restablecer la respiración espontánea no asistida. Resultados: Se integraron tres grupos: 17 neonatos con IR alto > 0.73, cinco con IR normal de 0.63 a 0.73 y seis con IR bajo < 0.63. En los primeros persistió IR alto en el posquirúrgico, con hiperlactatemia e hipoxia persistentes; en 86 % no se logró iniciar la vía enteral ni retirar la ventilación asistida. En los segundos, el IR se mantuvo en valores normales. En los terceros, si bien el IR, el lactato sérico y la presión arterial de oxígeno tendieron a normalizarse, 71 % presentó daño neurológico grave. Conclusiones: Los cambios en el IR fueron frecuentes, aunque el daño neurológico parece presentarse más cuando el IR se mantiene alto, posiblemente asociado a flujos cerebrales bajos.

Abstract Introduction: Surgery for congenital heart disease can generate cerebral perfusion-associated alterations with neurological repercussions. Objective: To analyze the relationship of peri-surgical cerebrovascular resistance index (RI) with mediate neurological functions after congenital heart disease surgery. Method: Prospective cohort study of 34 neonates in whom basilar artery RI, serum oxygen, carbon dioxide and lactate levels were determined before and after palliative or corrective procedures. We related pre-surgical RI with post-surgical ability to initiate the enteral route or to restore unassisted spontaneous breathing. Results: Three groups were formed: 17 neonates with high RI (> 0.73), five with normal RI (0.63-0.73) and six with low RI (< 0.63). In the former group, high RI persisted in the postoperative period, with persistent hyperlactatemia and hypoxia; in 86%, the enteral route could not be initiated, and neither could assisted ventilation be withdrawn. In the second group, IR remained within normal values. In the third group, although RI, serum lactate and arterial oxygen pressure tended to normalize, 71% had severe neurological damage. Conclusions: RI changes were common, although neurological damage appears to occur more commonly when RI remains high, possibly associated with low cerebral blood flow.

Hiperlactatemia en pacientes hospitalizados por asma: Frecuencia e implicaciones clínicas / Hyperlactatemia in hospitalized patients with asthma. Frequency and clinical implications

Se ha descrito un incremento del lactato sanguíneo en algunos pacientes tratados por agudización del asma. Sin embargo, se desconoce su frecuencia y el significado clínico en la práctica clínica habitual. El objetivo del estudio ha sido evaluar las características asociadas a la presencia de hiperlactatemia en la gasometría arterial de pacientes que requirieron ingreso en la sala de neumonología por agudización del asma. Se realizó un estudio retrospectivo de las altas hospitalarias de un servicio de neumonología durante 3 años (2015 a 2017) analizando los valores del ácido láctico en la gasometría arterial y su posible relación con datos de antecedentes clínicos, de laboratorio, tratamiento, espirometría, estancia hospitalaria o uso de unidades de cuidados críticos. Se incluyeron 112 pacientes con 182 ingresos. Presentaron en alguna ocasión hiperlactatemia (> 2.2 mmol/l) 32 pacientes (29%). En 42 de los 182 ingresos (23%) se observó aumento de lactato, en quienes tenían mayor estancia hospitalaria (mediana 6 vs. 5 días, p = 0.013). En 8 de los 10 ingresos en unidades de cuidados críticos se observó hiperlactatemia, en general tras recibir el tratamiento broncodilatador. En las gasometrías con hiperlactatemia existía una correlación significativa entre lactato y bicarbonato (r = -0.417, p=0.003) y el exceso de base (r = -0.484, p < 0.001). La hiperlactatemia es relativamente frecuente en las gasometrías realizadas a los pacientes hospitalizados por asma (23% de los ingresos). Los ingresos con hiperlactatemia se asociaron a una internación más prolongada.

Increased levels of lactic acid have been described in patients treated for asthma exacerbation. However, the frequency and clinical significance of hyperlactatemia in real-world practice is unknown. The objective of the study was to evaluate the characteristics associated with hyperlactatemia in blood gas analysis of patients with asthma exacerbation hospitalized in a pulmonary department. This is a retrospective 3-year study (2015 to 2017) of patients discharged from the pulmonary department. The level of lactic acid in the blood gas test and the possible relationship with clinical, laboratory, therapy, spirometric values, hospitalization length and use of critical care resources were analyzed. A total of 112 patients with 182 admissions were included in the study. Thirty-two (29%) patients had hyperlactatemia in at least one blood gas analysis. Elevated lactic acid was observed in 42 of 182 admissions (23%), which had larger length hospital stay (median, 6 vs. 5 days, p = 0.013). Hyperlactatemia was present in 8 of 10 admissions in the critical care units, mainly after receiving bronchodilator therapy. There was a significant correlation between lactate level and bicarbonate level (r = -0.417, p = 0.003) and between lactate level and base excess (r = -0.484, p < 0.001) in cases with hiperlactatemia. Hyperlactatemia is a relatively frequent finding in blood gas analysis of patients hospitalized because of asthma (23% of admissions). These admissions with hiperlactatemia are associated with larger hospital length of stay.

Blood lactate increases with the progression of mitral valve disease in dogs / Aumento de lactato sanguíneo com progressão de valvopatia mitral em cães

In dogs with congestive heart failure, the upregulated sympathetic tone causes vasoconstriction that impairs peripheral blood supply, therefore causing the accumulation of lactate. In this prospective cross-sectional study with a longitudinal component, blood lactate was quantified in 10 healthy and 34 myxomatous mitral valve disease (MMVD) dogs to investigate its potential use as a diagnostic and prognostic biomarker. While there were no differences in lactate concentration between control animals and stages B1 (3.31±0.62mmol/L) and B2 (3.32±0.46mmol/L) dogs, significant differences were found between healthy (2.50±0.69mmol/L) and both C (3.99±0.47mmol/L) and D (6.97±1.23mmol/L) animals. When a cut-off of 3.35mmol/L was used, lactate was able to distinguish dogs with normal and remodeled hearts with a sensitivity of 78.2% and specificity of 63.6%. Also, significant correlations existed between lactate and indicators of cardiac remodeling. Finally, animals with blood lactate <3.5mmol/L carried a better prognosis when compared with dogs in which lactate was >5.0mmol/L. Our results suggest that the progression of MMVD results in accumulation of lactate within the bloodstream, which is likely attributable to the impaired peripheral tissue perfusion. In MMVD dogs, blood lactate may be used as a surrogate for cardiac remodeling, and an increased concentration is associated with a worse prognosis regarding the time to evolve into congestive heart failure.(AU)

Em cães com insuficiência cardíaca congestiva, o tônus simpático hiperregulado causa vasoconstrição e interfere com o suprimento sanguíneo periférico, resultando no acúmulo de lactato. Neste estudo prospectivo transversal com um componente longitudinal, o lactato sanguíneo foi quantificado em 10 cães saudáveis e 34 cães com doença mixomatosa da valva mitral (DMVM) para investigar seu potencial como biomarcador diagnóstico e prognóstico. Embora não tenham sido identificadas diferenças na concentração de lactato entre animais controle e cães com DMVM nos estágios B1 (3,31±0,62mmol/L) e B2 (3,32±0,46mmol/L), diferenças significativas foram constatadas entre os cães saudáveis (2,50±0,69mmol/L) e cães com DMVM estágio C (3,99±0,47mmol/L) ou D (6,97±1,23mmol/L). Quando utilizado o valor de corte de 3,35mmol/L, o lactato foi capaz de diferenciar cães com corações normais daqueles com corações remodelados com sensibilidade de 78,2% e especificidade de 63,6%. Além disso, correlações significativas foram encontradas entre o lactato e os indicadores de remodelamento cardíaco. Por fim, os animais com lactato sanguíneo <3,5mmol/L tiveram prognóstico melhor comparativamente aos cães com concentrações >5,0mmol/L. Nossos resultados sugerem que a progressão da DMVM resulta no acúmulo de lactato na corrente sanguínea, fato que é provavelmente atribuído à perfusão periférica prejudicada. Em cães com DMVM, o lactato sanguíneo pode ser utilizado como indicador de remodelamento cardíaco, cuja concentração elevada está associada com pior prognóstico relativo ao tempo para evoluir para insuficiência cardíaca congestiva.(AU)

Anti-Diabetic Effect of Cotreatment with Quercetin and Resveratrol in Streptozotocin-Induced Diabetic Rats

Quercetin and resveratrol are known to have beneficial effects on the diabetes and diabetic complication, however, the effects of combined treatment of these compounds on diabetes are not fully revealed. Therefore, the present study was designed to investigate the combined antidiabetic action of quercetin (QE) and resveratrol (RS) in streptozotocin (STZ)-induced diabetic rats. To test the effects of co-treated with these compounds on diabetes, serum glucose, insulin, lipid profiles, oxidative stress biomarkers, and ions were determined. Additionally, the activities of hepatic glucose metabolic enzymes and histological analyses of pancreatic tissues were evaluated. 50 male Sprague-Dawley rats were divided into five groups; normal control, 50 mg/kg STZ-induced diabetic, and three (30 mg/kg QE, 10 mg/kg RS, and combined) compound-treated diabetic groups. The elevated serum blood glucose levels, insulin levels, and dyslipidemia in diabetic rats were significantly improved by QE, RS, and combined treatments. Oxidative stress and tissue injury biomarkers were dramatically inhibited by these compounds. They also shown to improve the hematological parameters which were shown to the hyperlactatemia and ketoacidosis as main causes of diabetic complications. The compounds treatment maintained the activities of hepatic glucose metabolic enzymes and structure of pancreatic β-cells from the diabetes, and it is noteworthy that cotreatment with QE and RS showed the most preventive effect on the diabetic rats. Therefore, our study suggests that cotreatment with QE and RS has beneficial effects against diabetes. We further suggest that cotreatment with QE and RS has the potential for use as an alternative therapeutic strategy for diabetes.

Clinical Application of the Quick Sepsis-Related Organ Failure Assessment Score at Intensive Care Unit Admission in Patients with Bacteremia: A Single-Center Experience of Korea / 대한구급학회지

BACKGROUND: We evaluated the clinical usefulness of the quick Sepsis-Related Organ Failure Assessment (qSOFA) score (based on the 2016 definition of sepsis) at intensive care unit admission in Korean patients with bacteremia. METHODS: We retrospectively analyzed clinical data from 236 patients between March 2011 and February 2016. In addition to the qSOFA, the Modified Early Warning score (MEWS) and systemic inflammatory response syndrome (SIRS) criteria were calculated. RESULTS: The patients' median age was 69 years, and 61.0% were male. Of the patients, 127 (53.8%) had a qSOFA score ≥2 points. They had significantly higher rates of septic shock, thrombocytopenia, and hyperlactatemia, and increased requirements for ventilator care, neuromuscular blocking agents, vasopressors, and hemodialysis within 72 hours after intensive care unit admission. They also had a significantly higher 28-day mortality rate. When analyzed using common thresholds (MEWS ≥5 and ≥2 SIRS criteria), patients with a MEWS ≥5 had the same results as those with a qSOFA score ≥2 (P < 0.05). However, patients with ≥2 SIRS criteria showed no significant differences. CONCLUSIONS: Our results show that a qSOFA score ≥2 at admission is a useful screening tool for predicting disease severity and medical resource usage within 72 hours after admission, and for predicting 28-day mortality rates in patients with bacteremia. In addition, qSOFA scores may be more useful than SIRS criteria in terms of prognostic utility.

Korean Shock Society septic shock registry: a preliminary report

OBJECTIVE: To evaluate the clinical characteristics, therapeutic interventions, and outcomes of patients with septic shock admitted to the emergency department (ED). METHODS: This study was a preliminary, descriptive analysis of a prospective, multi-center, observational registry of the EDs of 10 hospitals participating in the Korean Shock Society. Patients aged 19 years or older who had a suspected or confirmed infection and evidence of refractory hypotension or hypoperfusion were included. RESULTS: A total of 468 patients were enrolled (median age, 71.3 years; male, 55.1%; refractory hypotension, 82.9%; hyperlactatemia without hypotension, 17.1%). Respiratory infection was the most common source of infection (31.0%). The median Sepsis-related Organ Failure Assessment score was 7.5. The sepsis bundle compliance was 91.2% for lactate measurement, 70.3% for blood culture, 68.4% for antibiotic administration, 80.3% for fluid resuscitation, 97.8% for vasopressor application, 68.0% for central venous pressure measurement, 22.0% for central venous oxygen saturation measurement, and 59.2% for repeated lactate measurement. Among patients who underwent interventions for source control (n=117, 25.1%), 43 (36.8%) received interventions within 12 hours of ED arrival. The in-hospital, 28-day, and 90-day mortality rates were 22.9%, 21.8%, and 27.1%, respectively. The median ED and hospital lengths of stay were 6.8 hours and 12 days, respectively. CONCLUSION: This preliminary report revealed a mortality of over 20% in patients with septic shock, which suggests that there are areas for improvement in terms of the quality of initial resuscitation and outcomes of septic shock patients in the ED.

The First Korean case of combined oxidative phosphorylation deficiency-17 diagnosed by clinical and molecular investigation / 소아과

Combined oxidative phosphorylation deficiency-17 (COXPD-17) is very rare and is caused by homozygous or compound heterozygous mutations in the ELAC2 gene on chromosome 17p12. The ELAC2 gene functions as a mitochondrial tRNA processing gene, and only 4 different pathogenic mutations have been reported in ELAC2-associated mitochondrial dysfunction involving oxidative phosphorylation. Affected patients show various clinical symptoms and prognosis, depending on the genotype. We report a novel mutation in the ELAC2 gene (c.95C>G [p.Pro32Arg], het), in an infant with COXPD-17 who presented with encephalopathy including central apnea and intractable epilepsy, and growth and developmental retardation. During hospitalization, consistently elevated serum lactic acid levels were noted, indicative of mitochondrial dysfunction. The patient suddenly died of shock of unknown cause at 5 months of age. This is the first case report of COXPD-17 in Korea and was diagnosed based on clinical characteristics and genetic analysis.

Coupling killing to neutralization: combined therapy with ceftriaxone/Pep19-2.5 counteracts sepsis in rabbits

Sepsis, which is induced by severe bacterial infections, is a major cause of death worldwide, and therapies combating the disease are urgently needed. Because many drugs have failed in clinical trials despite their efficacy in mouse models, the development of reliable animal models of sepsis is in great demand. Several studies have suggested that rabbits reflect sepsis-related symptoms more accurately than mice. In this study, we evaluated a rabbit model of acute sepsis caused by the intravenous inoculation of Salmonella enterica. The model reproduces numerous symptoms characteristic of human sepsis including hyperlactatemia, hyperglycemia, leukopenia, hypothermia and the hyperproduction of several pro-inflammatory cytokines. Hence, it was chosen to investigate the proposed ability of Pep19-2.5—an anti-endotoxic peptide with high affinity to lipopolysaccharide and lipoprotein—to attenuate sepsis-associated pathologies in combination with an antibiotic (ceftriaxone). We demonstrate that a combination of Pep19-2.5 and ceftriaxone administered intravenously to the rabbits (1) kills bacteria and eliminates bacteremia 30 min post challenge; (2) inhibits Toll-like receptor 4 agonists in serum 90 min post challenge; (3) reduces serum levels of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor α); and (4) reverts to hypothermia and gives rise to temperature values indistinguishable from basal levels 330 min post challenge. The two components of the combination displayed synergism in some of these activities, and Pep19-2.5 notably counteracted the endotoxin-inducing potential of ceftriaxone. Thus, the combination therapy of Pep19-2.5 and ceftriaxone holds promise as a candidate for human sepsis therapy.

Clinical Application of the Quick Sepsis-Related Organ Failure Assessment Score at Intensive Care Unit Admission in Patients with Bacteremia: A Single-Center Experience of Korea / 대한중환자의학회지

BACKGROUND: We evaluated the clinical usefulness of the quick Sepsis-Related Organ Failure Assessment (qSOFA) score (based on the 2016 definition of sepsis) at intensive care unit admission in Korean patients with bacteremia. METHODS: We retrospectively analyzed clinical data from 236 patients between March 2011 and February 2016. In addition to the qSOFA, the Modified Early Warning score (MEWS) and systemic inflammatory response syndrome (SIRS) criteria were calculated. RESULTS: The patients' median age was 69 years, and 61.0% were male. Of the patients, 127 (53.8%) had a qSOFA score ≥2 points. They had significantly higher rates of septic shock, thrombocytopenia, and hyperlactatemia, and increased requirements for ventilator care, neuromuscular blocking agents, vasopressors, and hemodialysis within 72 hours after intensive care unit admission. They also had a significantly higher 28-day mortality rate. When analyzed using common thresholds (MEWS ≥5 and ≥2 SIRS criteria), patients with a MEWS ≥5 had the same results as those with a qSOFA score ≥2 (P < 0.05). However, patients with ≥2 SIRS criteria showed no significant differences. CONCLUSIONS: Our results show that a qSOFA score ≥2 at admission is a useful screening tool for predicting disease severity and medical resource usage within 72 hours after admission, and for predicting 28-day mortality rates in patients with bacteremia. In addition, qSOFA scores may be more useful than SIRS criteria in terms of prognostic utility.

Association between Metformin Use and Risk of Lactic Acidosis or Elevated Lactate Concentration in Type 2 Diabetes

PURPOSE: Metformin can reduce diabetes-related complications and mortality. However, its use is limited because of potential lactic acidosis-associated adverse effects, particularly in renal impairment patients. We aimed to investigate the association of metformin use with lactic acidosis and hyperlactatemia in patients with type 2 diabetes. MATERIALS AND METHODS: This was a cross-sectional study from a tertiary university-affiliated medical center. A total of 1954 type 2 diabetes patients were recruited in 2007–2011, and stratified according to the estimated glomerular filtration rate of 60 mL/min/1.73 m2. Lactic acidosis was defined as plasma lactate levels >5 mmol/L and arterial pH <7.35. RESULTS: Metformin was used in 61.4% of the patients with type 2 diabetes mellitus. Plasma lactate levels were not different in the patients with and without metformin use. There was no difference in prevalence of hyperlactatemia and lactic acidosis between the patients with and without metformin use (18.9% vs. 18.7%, p=0.905 for hyperlactatemia and 2.8% vs. 3.3%, p=0.544 for lactic acidosis). Similar results were observed in the patients with estimated glomerular filtration rate <60 mL/min/1.73 m². Most patients with lactic acidosis had at least one condition related to hypoxia or poor tissue perfusion. Multiple regression analysis indicated no association between metformin use and lactic acidosis, whereas tissue hypoxia was an independent risk factor for lactic acidosis [odds ratio 4.603 (95% confidence interval, 1.327–15.965)]. CONCLUSION: Metformin use was not associated with hyperlactatemia or lactic acidosis in patients with type 2 diabetes.

What is the Clinical Significance of Initial Lactate Measurement Compared to Carboxyhemoglobin Measurement in Carbon Monoxide Poisoning?

PURPOSE: This study was performed to compare clinical significance between lactate and carboxyhemoglobin (COHb) in a patient with carbon monoxide (CO) poisoning. METHODS: We conducted a 13-year retrospective study on CO poisoning patients who visited the emergency departments of the Medical Center between October 2004 and January 2016. The patients were divided into two groups according to initial lactate levels. Patients with serum lactate levels of ≤2 mmol/L were classified as the normolactatemia group (n=14), and patients with serum lactate levels of >2 mmol/L were classified as the hyperlactatemia group (n=34). General characteristics, clinical features, and laboratory findings of the two groups were compared. In addition, we compared initial lactate levels with COHb levels according to complications, neurological disorder, myocardial enzyme elevation, and abnormal Glasgow Coma Scale (GCS) score in patients with CO poisoning. We also analyzed the correlation between laboratory parameters and lactate levels. RESULTS: Forty-eight patients were enrolled in this study. The hyperlactatemia group had significantly more neurological disorders and consciousness disorders than the normolactatemia group (p<0.001), and COHb, creatine phosphokinase MB, and troponin I levels were also significantly higher in the hyperlactatemia group (p<0.001, p=0.017, and p=0.007). Lactate levels were significantly elevated in patients with elevated cardiac enzymes (p=0.001), neurological disorders (p<0.001), complications (p=0.001), and abnormal GCS score (p<0.001), whereas COHb levels were not significantly increased in all subjects. The correlation between COHb and lactate levels was weak (r=0.313, p=0.030), and a positive correlation was found between lactate and bicarbonate (HCO3), white blood cell, and troponin I (p<0.001). The diagnostic value of lactate for severe CO poisoning was analyzed using a receiver operating characteristic curve. The optimal cut-off value of lactate was 2.2 mmol/L with 83.3% sensitivity and 91.7% specificity (p<0.001). CONCLUSION: Lactate has significant diagnostic efficacy in patients with CO poisoning. It is recommended that lactate level be measured for appropriate treatment and prognostic evaluation of CO poisoning.

Valores de lactato sérico e sua correlação com parâmetros clínicos de cães saudáveis, mensurados durante atendimento ambulatorial veterinário / Serum lactate values and its correlation with clinical parameters evaluated at veterinary ambulatorial exam

A mensuração do lactato sérico é utilizada na rotina médica como marcador prognóstico de pacientes em estado de emergência. Sua interpretação não deve ser feita de forma isolada, mas conjunta aos demais parâmetros clínicos, pois seus valores podem sofrer interferência do estresse metabólico ou ambiental, contenção física e/ ou manipulação dos pacientes. Assim, buscou-se mensurar os valores do lactato sérico e parâmetros clínicos de cães saudáveis, bem como as suas correlações, durante o atendimento clínico ambulatorial veterinário. Para isso, foram avaliados 80 cães, machos ou fêmeas, com idade de um a oito anos, atendidos para revacinação anual polivalente. Foram considerados cães saudáveis os que não apresentaram intercorrências clínicas nos últimos 60 dias e alterações nos exames físicos e nos valores de hemograma e glicemia sérica. Foram mensurados inicialmente o peso corporal, a frequência cardíaca (FC) e respiratória (FR), tempo de preenchimento capilar (TPC), coloração de mucosas, temperatura retal (TR), periférica (TP) e a diferença entre TR e a TP, o Delta T°C. Por último, realizaram-se os exames de hemograma e glicemia sérica, juntamente com a mensuração do lactato sérico, utilizando para isso um lactímetro portátil, por meio da amostra sanguínea obtida da veia cefálica. Além disso, havendo a correlação dos valores do lactato séricos com o peso corporal os cães foram divididos conforme o cálculo do 33° e 66° percentil. Os cães avaliados evidenciaram valores médios de 18,3±12,1 kg de peso corporal e 3,0±1,9 anos de idade; FC de 126,6±29,1bpm, FR de 66±24mpm, TR de 38,9±0,4°C, TP de 31,5±1,0°C, Delta TºC de 7,3±1,0°C e lactato sérico de 3,2±0,4mmol/L; com este último, evidenciando intervalo de confiança a 95% de 3,1-3,3mmol/L e correlação significativa (p<0,05) dos seus valores com o peso corporal (r=0,6) e a frequência cardíaca (r=0,4). Os valores do lactato sérico obtidos foram comparados entre os grupos de cães conforme o peso corporal, evidenciando diferenças significativas (p<0,05) entre eles. Dessa forma, pode se concluir que os valores do lactato sérico em cães hígidos sob atendimento ambulatorial é de 3,2mmol/L, com o intervalo de confiança de 3,1-3,3mmol/L, ressaltando a influência que a FC e o peso corporal podem exercer nos seus valores.(AU)

The measurement of serum lactate is used in the medical routine as a prognosis marker of emergency patients. Its interpretation should not be done disconnectedly from the other clinical parameters once metabolical or environmental stress as well as restraint and/or manipulation of patients can interfere. Thus we tried to measure the levels of serum lactate and clinical parameters of healthy dogs, as their correlation during veterinarian outpatient clinical care. For that we evaluated 80 dogs, males and females, with age ranging from one to eight years, met for polyvalent annual revaccination. We considered to be healthy those dogs that had no clinical events in the last 60 days or alteration in physical exams, blood exam values and serum glycemia. We initially measured body weight, heart rate (HR) and respiratory (RR), capillary refill time, mucosa's coloring, rectal temperature (RT), peripheral temperature (PT) and the difference between RT and PT, Delta T°C. Finally we did the blood exam and the serum glycemia, as well as the serum lactate measurement. For that we used a portable lactimeter, using the blood sample taken from the cephalic vein. Furthermore, when there was correlation between the serum lactate values and the body weight, we divided the dogs according to the calculation of 33 and 66 percentile. Evaluated dogs showed average values of 18.3±12.1 kg of body weight and 3.0±1.9 of age; with HR of 126.6±29.1bpm, RR of 66±24mpm, RT of 38.9±0.4°C, PT of 31.5±1,0°C, Delta T°C of 7.3±1.0°C and serum lactate of 3.2±0.4mmol/L; with the latter showing range of 3.1-3.3mmol/L with 95% of reliability and significant correlation (p<0.05) between its values and the body weight (r=0.6) and the heart rate (r=0.4). The serum lactate values obtained were compared between the dogs' groups according to their body weight, showing distinguished differences between them. Thereby we concluded that the serum lactate values in dogs under outpatient care is 3.2mmol/L, with a trust gap of 3.1-3.3mmol/L, highlighting the influence that HR and body weight can have on its values.(AU)

Prognostic Value of Blood Lactate for Mortality of Acutely Poisoned Patients in Emergency Department

PURPOSE: Patients suffering from acute poisoning by different substances often visit the emergency department (ED) and receive various prognoses according to the toxic material and patients' condition. Hyperlactatemia, which is an increased blood lactate level that generally indicates tissue hypoperfusion, is commonly utilized as a prognostic marker in critically ill patients such as those with sepsis. This study was conducted to investigate the relationships between blood lactate and clinical prognosis in acute poisoned patients. METHODS: This retrospective study was conducted from January 2013 to June 2014 at a single and regional-tertiary ED. We enrolled study patients who were examined for blood test with lactate among acute intoxicated patients. The toxic materials, patient demographics, laboratory data, and mortalities were also reviewed. Additionally, we analyzed variables including blood lactate to verify the correlation with patient mortality. RESULTS: A total of 531 patients were enrolled, including 24 (4.5%) non-survivors. Patient age, Glasgow coma scale (GCS), serum creatinine (Cr), aspartate transaminase (AST), and serum lactate differed significantly between survivors and non-survivors in the binary logistic regression analysis. Among these variables, GCS, AST, and lactate differed significantly. The median serum lactate levels were 2.0 mmol/L among survivors and 6.9 mmol/L among non-survivors. The AUC with the ROC curve and odds ratio of the initial serum lactate were 0.881 and 3.06 (0.89-8.64), respectively. CONCLUSION: Serum lactate was correlated with fatalities of acute poisoning patients in the ED; therefore, it may be used as a clinical predictor to anticipate their prognoses.

The Use of the Ratio between the Veno-arterial Carbon Dioxide Difference and the Arterial-venous Oxygen Difference to Guide Resuscitation in Cardiac Surgery Patients with Hyperlactatemia and Normal Central Venous Oxygen Saturation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>After cardiac surgery, central venous oxygen saturation (ScvO 2 ) and serum lactate concentration are often used to guide resuscitation; however, neither are completely reliable indicators of global tissue hypoxia. This observational study aimed to establish whether the ratio between the veno-arterial carbon dioxide and the arterial-venous oxygen differences (P(v-a)CO 2 /C(a-v)O 2 ) could predict whether patients would respond to resuscitation by increasing oxygen delivery (DO 2 ).</p><p><b>METHODS</b>We selected 72 patients from a cohort of 290 who had undergone cardiac surgery in our institution between January 2012 and August 2014. The selected patients were managed postoperatively on the Intensive Care Unit, had a normal ScvO 2 , elevated serum lactate concentration, and responded to resuscitation by increasing DO 2 by >10%. As a consequence, 48 patients responded with an increase in oxygen consumption (VO 2 ) while VO 2 was static or fell in 24.</p><p><b>RESULTS</b>At baseline and before resuscitative intervention in postoperative cardiac surgery patients, a P(v-a)CO 2 /C(a-v)O 2 ratio ≥1.6 mmHg/ml predicted a positive VO 2 response to an increase in DO 2 of >10% with a sensitivity of 68.8% and a specificity of 87.5%.</p><p><b>CONCLUSIONS</b>P(v-a)CO 2 /C(a-v)O 2 ratio appears to be a reliable marker of global anaerobic metabolism and predicts response to DO 2 challenge. Thus, patients likely to benefit from resuscitation can be identified promptly, the P(v-a)CO 2 /C(a-v)O 2 ratio may, therefore, be a useful resuscitation target.</p>

Prognostic markers of canine pyometra / Marcadores prognósticos na piometra canina

The pyometra is a disease that affects middle age and elderly female dogs during diestrus. Hormonal, microbiological, biochemical and hematological aspects are well described. However, few studies have evaluated the role of each in the prognosis of canine pyometra. The aim of this study was to identify markers associated with clinical worsening of dogs with pyometra. We prospectively evaluated 80 dogs with pyometra treated surgically. Group 1 consisted of dogs that were discharged within 48 hours after surgery and Group 2 consisted of those who required prolonged hospitalization or died. The findings of hematological, biochemical and blood lactate levels were compared between groups and variables such as bacterial multidrug resistance, systemic inflammatory response syndrome (SIRS), hyperlactatemia and increased creatinine were analyzed through the dispersion of frequencies between groups. Among the variables studied, the presence of SIRS and elevated serum creatinine >2.5mg/mL were effective in predicting the worsening of the disease and can be used as prognostic markers of canine pyometra...

A piometra é doença que acomete as fêmeas da espécie canina de meia-idade a idosa durante o diestro. Aspectos hormonais, microbiológicos, hematológicos e bioquímicos são bem descritos. Entretanto, são poucos os estudos que avaliam o papel de cada um desses no prognóstico da piometra canina. O objetivo deste estudo foi identificar marcadores associados ao agravamento clínico de cadelas com piometra. Foram avaliadas prospectivamente 80 cadelas com piometra tratadas cirurgicamente. O grupo 1 foi composto por cadelas que receberam alta até 48 horas de pós-operatório, e o grupo 2 por aquelas que necessitaram de internamento prolongado ou morreram. Os achados hematológicos, bioquímicos e os níveis do lactato sanguíneo foram comparados entre os grupos, e variáveis como multirresistência bacteriana, síndrome da resposta inflamatória sistêmica (SIRS), hiperlactatemia e aumento da creatinina foram analisadas por meio da dispersão de frequências entre os grupos. Entre as variáveis estudadas, a presença de SIRS e a elevação da creatinina sérica >2,5mg/mL foram eficazes em predizer o agravamento da doença e podem ser utilizadas como marcadores prognósticos da piometra canina...

Reclassificando o espectro de pacientes septicos com o uso do lactato: sepse grave, choque criptico, choque vasoplegico e choque disoxico / Reclassifying the spectrum of septic patients using lactate: severe sepsis, cryptic shock, vasoplegic shock and dysoxic shock

Objetivo: A definição atual de sepse grave e choque séptico inclui um perfil heterogêneo de pacientes. Embora o valor prognóstico de hiperlactatemia seja bem estabelecido, ela está presente em pacientes com ou sem choque. Nosso objetivo foi comparar o prognóstico de pacientes sépticos estratificando-os segundo dois fatores: hiperlactatemia e hipotensão persistente. Métodos: Este estudo é uma análise secundária de um estudo observacional conduzido em dez hospitais no Brasil (Rede Amil - SP). Pacientes sépticos com valor inicial de lactato das primeiras 6 horas do diagnóstico foram incluídos e divididos em 4 grupos segundo hiperlactatemia (lactato >4mmol/L) e hipotensão persistente: (1) sepse grave (sem ambos os critérios); (2) choque críptico (hiperlactatemia sem hipotensão persistente); (3) choque vasoplégico (hipotensão persistente sem hiperlactatemia); e (4) choque disóxico (ambos os critérios). Resultados: Foram analisados 1.948 pacientes, e o grupo sepse grave constituiu 52% dos pacientes, seguido por 28% com choque vasoplégico, 12% choque disóxico e 8% com choque críptico. A sobrevida em 28 dias foi diferente entre os grupos (p<0,001), sendo maior para o grupo sepse grave (69%; p<0,001 versus outros), semelhante entre choque críptico e vasoplégico (53%; p=0,39) e menor para choque disóxico (38%; p<0,001 versus outros). Em análise ajustada, a sobrevida em 28 dias permaneceu diferente entre os grupos (p<0,001), sendo a maior razão de risco para o grupo choque disóxico (HR=2,99; IC95% 2,21-4,05). Conclusão: A definição de pacientes com sepse inclui quatro diferentes perfis, se considerarmos a presença de hiperlactatemia. Novos estudos são necessários para melhor caracterizar pacientes sépticos e gerar conhecimento ...

Objective: The current definition of severe sepsis and septic shock includes a heterogeneous profile of patients. Although the prognostic value of hyperlactatemia is well established, hyperlactatemia is observed in patients with and without shock. The present study aimed to compare the prognosis of septic patients by stratifying them according to two factors: hyperlactatemia and persistent hypotension. Methods: The present study is a secondary analysis of an observational study conducted in ten hospitals in Brazil (Rede Amil - SP). Septic patients with initial lactate measurements in the first 6 hours of diagnosis were included and divided into 4 groups according to hyperlactatemia (lactate >4mmol/L) and persistent hypotension: (1) severe sepsis (without both criteria); (2) cryptic shock (hyperlactatemia without persistent hypotension); (3) vasoplegic shock (persistent hypotension without hyperlactatemia); and (4) dysoxic shock (both criteria). Results: In total, 1,948 patients were analyzed, and the sepsis group represented 52% of the patients, followed by 28% with vasoplegic shock, 12% with dysoxic shock and 8% with cryptic shock. Survival at 28 days differed among the groups (p<0.001). Survival was highest among the severe sepsis group (69%, p<0.001 versus others), similar in the cryptic and vasoplegic shock groups (53%, p=0.39), and lowest in the dysoxic shock group (38%, p<0.001 versus others). In the adjusted analysis, the survival at 28 days remained different among the groups (p<0.001) and the dysoxic shock group exhibited the highest hazard ratio (HR=2.99, 95%CI 2.21-4.05). Conclusion: The definition of sepsis includes four different profiles if we consider the presence of hyperlactatemia. Further studies are needed to better characterize septic patients, to understand the etiology and to design adequate targeted treatments. .