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.

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.

Effects of Systemic Hypothermia on Microcirculation in Conditions of Hemodynamic Stability and in Hemorrhagic Shock.

INTRODUCTION: Although hypothermia is independently associated with an increased mortality in trauma patients, it might be an effective therapeutic approach for otherwise lethal hemorrhage. The effect of hypothermia on microcirculation, however, has been poorly studied in this setting. Our goal was to characterize the effects of hypothermia on microcirculation in normal conditions and in severe hemorrhagic shock. METHODS: In anesthetized and mechanically ventilated sheep, we measured cardiac output (CO), renal blood flow (RBF), and systemic and renal O2 consumption (VO2). Cortical renal, intestinal villi, and sublingual microcirculation was assessed by IDF-videomicroscopy. After basal measurements, sheep were assigned to hypothermia (n = 12) and normothermia (n = 12) groups. Central temperature was reduced to ∼34°C and maintained at baseline in each group, respectively. Measurements were repeated after 1 h of hemodynamic stable conditions and 1 h of severe hemorrhagic shock. RESULTS: In conditions of hemodynamic stability, the hypothermia group showed lower CO, RBF, and systemic and renal VO2 than the normothermia group. Red blood cell velocity was also lower in renal, villi, and sublingual microvascular beds (836 ±â€Š195 vs. 1,066 ±â€Š162, 916 ±â€Š105 vs. 1051 ±â€Š41, and 970 ±â€Š182 vs. 1,102 ±â€Š49 µm/s, respectively; P < 0.0001 for all). In hemorrhagic shock, most of the microvascular variables were similarly compromised in both the groups. In hypo- and normothermia groups, the percentage of reduction in perfused vascular density was higher in renal than in intestinal and sublingual microcirculation (66 ±â€Š31 vs. 31 ±â€Š23 and 15 ±â€Š15%, and 78 ±â€Š26 vs. 32 ±â€Š37 and 18 ±â€Š21%, P < 0.01 for both). CONCLUSIONS: This is the first experimental study assessing the effect of systemic hypothermia on microcirculation in severe hemorrhagic shock. The main finding was that hypothermia did not hamper additionally the microcirculatory derangements induced by hemorrhagic shock. In addition, renal microcirculation was more susceptible to hemorrhagic shock than villi and sublingual microcirculation.

Tamizaje de sífilis congénita en el binomio madre-hijo: validez de la sangre de cordón / Screening for congenital syphilis in mother-child binomial: validity of cord blood / Triagem da sífilis congênita no binomio mãe-filho: validade do sangue do cordão

La sangre de cordón es una alternativa no invasiva que ha sido empleada para el tamizaje de sífilis congénita. Los objetivos del trabajo fueron evaluar la validez del uso de sangre de cordón como muestra para tamizaje de casos presuntivos de sífilis congénita, determinar la prevalencia de sífilis materna, estudiar la tasa de casos presuntivos de sífilis congénita y establecer el porcentaje de madres no estudiadas para sífilis en el periparto. Se realizó un análisis retrospectivo y observacional entre junio de 2017 y mayo de 2018. Se relevaron datos de serología de sangre de cordón y sangre de la madre. Se utilizó Unheated Serum Reagin como prueba de tamizaje y FTA-Abs y/o quimioluminiscencia como confirmatorias. Se excluyeron los binomios madre-hijo sin estudio de sangre de cordón. Binomios madre-hijo estudiados: 2.487. Sensibilidad y especificidad: 82,29% IC 95% (73,17- 89,33) y 99,96% IC 95% (99,76-100,00), respectivamente. Prevalencia de sífilis materna: 4,04%. Tasa de caso presuntivo de sífilis congénita: 26/1.000 RNV. Madres sin registros de serología para sífilis en el periparto: 70 (2,86%). La sangre de cordón no sería una muestra válida para el tamizaje debido a la baja sensibilidad encontrada, aunque en muchos casos es la única oportunidad de evaluar el binomio madre-hijo.

Cord blood is a non-invasive alternative which has been used for screening of congenital syphilis. The aims of the present study were to evaluate the validity of the use of cord blood as a sample for the screening of a probable congenital syphilis case, to study the prevalence of maternal syphilis, to analyse the rate of probable congenital syphilis case and to determine the percentage of non-studied mothers for syphilis in the peripartum. A retrospective and observational analysis was conducted between June 2017 and May 2018. Cord blood and maternal blood serology results were taken from the Laboratory Information System. Unheated Serum Reagin was used as a screening test and FTA-Abs and/or quimioluminiscense as confirmatory studies. Infant-mother binomies without cord blood studies were excluded. Infant-mother binomies studied: 2487. Sensibility and specificity 82.29% [95% CI: 73.17 to 89.33] and 99.96% [95% CI: 99.76 to 100.00], respectively. MSP prevalence: 4.04%. Probable congenital syphilis case rate: 26/1000 NB. Non-studied mothers for syphilis in the peripartum: 70 (2.86%). Cord blood would not be a valid sample for screening due to the low sensibility found, although in many cases it is the only opportunity to evaluate the infant-mother binomies.

O sangue do cordão é uma alternativa não invasiva que tem sido usada para triagem da sífilis congênita. Os objetivos do trabalho foram avaliar a validade do uso do sangue do cordão como amostra para o rastreio de um caso presumível de sífilis congénita, determinar a prevalência da sífilis materna, estudar a taxa de caso presumível de sífilis congénita e estabelecer a percentagem de mães em que não se analisa a sífilis no periparto. Foi realizada entre junho de 2017 e maio de 2018 uma análise retrospectiva e observacional, onde foram colectados os dados do Sistema de Computação Laboratorial de sorologia sangue do cordão e sangue da mãe. Foi utilizado um Unheated Serum Reagin como teste de triagem e FTA-Abs e/ou quimiluminescência como confirmatórias. Os binomios mãe-filho foram excluídos sem o estudo do sangue do cordão. Binomios mãe-filho estudado: 2.487. Sensibilidade e especificidade: 82,29% IC 95% (73,17-89,33) y 99,96% IC 95% (99,76-100,00), respectivamente. Prevalência de SFM: 4,04%. Taxa CPSC: 26/1.000 RNV. Mães sem registros sorológicos para sífilis no periparto: 70 (2,86%). O sangue do cordão não seria uma amostra válida para triagem devido à baixa sensibilidade encontrada, no entanto em muitos casos é a única oportunidade do avaliar o binomios mãe-filho.

Effects of fluid and norepinephrine resuscitation in a sheep model of endotoxin shock and acute kidney injury.

The pathophysiology of renal failure in septic shock is complex. Although microvascular dysfunction has been proposed as a mechanism, there are controversial findings about the characteristics of microvascular redistribution and the effects of resuscitation. Our hypothesis was that the normalization of systemic hemodynamics with fluids and norepinephrine fails to improve acute kidney injury. To test this hypothesis, we assessed systemic and renal hemodynamics and oxygen metabolism in 24 anesthetized and mechanically ventilated sheep. Renal cortical microcirculation was evaluated by SDF-videomicroscopy. Shock (n = 12) was induced by intravenous administration of endotoxin. After 60 min of shock, 30 mL/kg of saline solution was infused and norepinephrine was titrated to reach a mean blood pressure of 70 mmHg for 2 h. These animals were compared with a sham group (n = 12). After endotoxin administration, mean blood pressure, cardiac index, and systemic O2 transport and consumption decreased (P < 0.05 for all). Resuscitation improved these variables. Endotoxin shock also reduced renal blood flow and O2 transport and consumption (205[157-293] vs. 131 [99-185], 28.4[19.0-38.2] vs. 15.8[13.5-23.2], and 5.4[4.0-8.8] vs. 3.7[3.3-4.5] mL·min-1·100 g-1, respectively); cortical perfused capillary density (23.8[23.5-25.9] vs. 17.5[15.1-19.0] mm/mm2); and creatinine clearance (62.4[39.2-99.4] vs. 10.7[4.4-23.5] mL/min). After 2 h of resuscitation, these variables did not improve (174[91-186], 20.5[10.8-22.7], and 3.8[1.9-4.8] mL·min-1·100 g-1, 19.9[18.6-22.1] mm/mm2, and 5.9[1.0-11.9] mL/min). In conclusion, endotoxin shock induced severe renal failure associated with decreased renal flow, O2 transport and consumption, and cortical microcirculation. Normalization of systemic hemodynamics with fluids and norepinephrine failed to improve renal perfusion, oxygenation, and function.NEW & NOTEWORTHY This experimental model of endotoxin shock induced severe renal failure, which was associated with abnormalities in renal regional blood flow, microcirculation, and oxygenation. Derangements included the compromise of peritubular microvascular perfusion. Improvements in systemic hemodynamics through fluids and norepinephrine were unable to correct these abnormalities.

Estudio de la interferencia por hemólisis en la determinación de bilirrubina total / Hemolysis interference study in determination of total bilirubin / Estudo da interferência por hemólise na determinação de bilirrubina total

La hemólisis es una causa frecuente de rechazo de muestras que genera un sesgo negativo en la determinación de bilirrubina total (BT). Los objetivos de este trabajo fueron determinar el grado de hemólisis (GH) para reemplazar la inspección visual subjetiva, establecer la magnitud de su interferencia y conocer la concentración inicial de hemoglobina a partir de la cual se produce interferencia clínicamente relevante (ICR). Se recolectaron sueros con diferentes concentraciones de BT. Se preparó un hemolizado para generar distintas concentraciones de interferente. Se cuantificó la BT mediante el método de diclorofenildiazonio en los sueros con las diferentes concentraciones de hemoglobina y se determinó GH midiendo absorbancia a 578 nm. Se consideró ICR cuando se superó la máxima inexactitud deseable. Para cada nivel de BT se determinó la concentración de hemoglobina máxima aceptable (CHbmáx aceptable) por sobre la cual se considera ICR. La Abs578 permitió definir cuatro GH (GH1, GH2, GH3 y GH4). A partir de los interferogramas se determinó la CHbmáx aceptable para cada nivel de BT; ésta mostró un aumento lineal con la BT. A partir de 14,8 mg/dL de BT no se encontró ICR en los rangos estudiados. El GH permite tomar conductas objetivas ante muestras hemolizadas según el algoritmo propuesto.

Hemolysis is a common cause for rejection of samples that generates a negative bias in total bilirubin (TB) determination. The objectives of this study were to determine the hemolysis degree (HD) to replace the subjective visual inspection, to establish the extent of their interference and to meet the initial hemoglobin concentration from which clinically relevant interference (CRI) occurs. Sera was collected at different TB concentrations.Hemolysate was prepared to generate different concentrations of interfering. TB was quantified by dichlorophenyldiazonium method in sera with several hemoglobin concentrations, and DH was determined by measuring absorbance at 578 nm (Abs578). CRI was considered when it exceeded the maximum desirable inaccuracy. For each TB level, the maximum acceptable concentration of hemoglobin (CHbmáx acceptable) above which ICR is considered was determined.The Abs578 made it possible to define four DH (DH1, DH2, DH3 and DH4). The CHbmax acceptable was determined for each level of TB from the interferograms; it showed a linear increase with TB. From 14,8 mg/dL BT, CRI was not found in the ranges studied. The DH makes it possible to have objective behaviours in hemolyzed samples according to the proposed algorithm.

A hemólise é uma causa frequente de rejeição de amostras que gera um viés negativo na determinação da bilirrubina total (BT). Os objetivos deste estudo foram: determinar o grau de hemólise (GH) para substituir a inspeção visual subjetiva, estabelecer a extensão da sua interferência e conhecer a concentração inicial de hemoglobina a partir da qual ocorre a interferência clinicamente relevante (ICR). Foram coletados soros com diferentes concentrações de BT. Um hemolisado foi preparado para gerar diferentes concentrações de interferente. Foi quantificada a BT pelo método de diclorofenil diazônio nos soros com as diferentes concentrações de hemoglobina e foi determinado o GH medindo a absorvância a 578 nm (Abs578). ICR foi considerada quando se superou a máxima inexatidão desejável. Para cada nível de BT foi determinada a concentração de hemoglobina máxima aceitável (CHbMax aceitável) acima da qual é considerada ICR. A Abs578 permitiu definir quatro GH (GH1, GH2, GH3 e GH4). A partir dos interferogramas se determinou a CHbMax aceitável para cada nível de BT; ela apresentou um aumento linear com a BT. A partir de 14,8 mg/dL de BT, a ICR não foi encontrada nos intervalos estudados. O GH permite ter condutas objetivas diante de amostras hemolisadas de acordo com o algoritmo proposto.