Correlación de índice PO2/FiO2 con parámetros inflamatorios y de coagulación en pacientes críticos con covid-19. Lombardía, 2020 / PO2/FiO2 index correlation with inflammatory and coagulation parameters in critically-ill patients with COVID-19 in Lombardy, 2020

RESUMEN Introducción: el conocimiento de la fisiopatología de la enfermedad ha revolucionado el enfoque tradicional en el tratamiento de las enfermedades causadas por virus respiratorios. Actualmente, se utilizan marcadores de la respuesta inflamatoria para diagnosticar, estratificar y predecir en muchos casos el comportamiento futuro del enfermo de covid-19. Objetivo: caracterizar la naturaleza de la relación entre el índice PO2/FiO2 y los parámetros inflamatorios y de coagulación en pacientes graves por la covid-19, en la región de Lombardía, Italia. Materiales y métodos: se realizó un estudio analítico, longitudinal, retrospectivo con 191 pacientes graves y críticos, que ingresaron con diagnóstico de covid-19 del 1 de abril al 20 mayo de 2020, en el Hospital Mayor de Crema, en la región de Lombardía, Italia. Resultados: las correlaciones evidenciadas fueron las siguientes: proteína C reactiva (-0,417) p = 0; procalcitonina (-0,152) p = 0,018; dímero D (-0,112) p = 0,061; fibrinógeno (-0,272) p = 0,000; creatinina plasmática (-0,320) p = 0,000; conteo de linfocitos (0,028) p = 0,000; troponina (-0,028) p = 0,142, y lactato (-0,191) p = 0,288. Conclusiones: los marcadores inflamatorios en la patogenia de la enfermedad juegan un rol capital, y el enfoque hacia este renglón del tratamiento médico antiinflamatorio de cualquier tipo es mandatorio. Se debe realizar un correcto monitoreo de la coagulación, usar heparinas de bajo peso molecular, así como mantener un adecuado soporte hemodinámico capaz de evitar las disoxias celulares que progresen al fallo multiorgánico (AU).

ABSTRACT Introduction: the knowledge of disease physiopathology has revolutionized the traditional approach in the treatment of diseases caused by respiratory viruses. Currently, the markers of inflammatory answer are used to diagnose, stratify and predict in many cases the future behavior of COVID-19 patients. Objective: to characterize the nature of the relationship between PO2/FiO2 (PAFI, Spanish acronym of PA= presión arterial [arterial pressure], FI=fracción inspirada [inspired fraction]) and coagulation and inflammatory parameters in seriously-ill patients with COVID-19, in the region of Lombardy, Italy. Materials and methods: a retrospective, longitudinal, analytic study was carried out in 191 severe and critical patients who were admitted in Hospadale Maggiori di Crema, in the region of Lombardy, Italy, with the diagnosis of COVID-19, in the period April 1st-May 20, 2020. Results: the evidenced correlations were the following: reactive C protein (-0.417) p=0; procalcitonin (PCT) (-0.152) p=0.018. D dimer (-0.112) p=0.061; Fibrinogen (-0.272) p=0.000; Plasma creatinine (-0.320) p=0.000; lymphocytes count (0,028) p=0,000; troponin (-0.028) p=0.142; and lactate (-0.191) p=0.288. Conclusions: inflammatory markers play a capital role in the disease pathogenesis, and approaching this item of the medical anti-inflammatory treatment is mandatory. It is useful to keep a correct coagulation screening, using low molecular weight heparins, and also keeping an adequate hemodynamic support able to avoid cell dysoxia progressing to multiorgan failure (AU).

Modelo temporal del comportamiento de pacientes críticos con covid-19 durante su estadía en cuidados intensivos. Lombardía, Italia / Temporal model of the behavior of critically ill patients with COVID-19 during their staying in intensive care. Lombardy, Italy

RESUMEN Introducción: una serie temporal es el producto de la observación de una variable en el tiempo. Es una herramienta matemática que se aplica con frecuencia en la salud. No se han elaborado modelos temporales que predigan el comportamiento de los pacientes durante su ingreso en la Unidad de Cuidados Intensivos. Objetivos: crear una serie temporal que permita predecir el comportamiento, durante su ingreso en la Unidad de Cuidados Intensivos, de pacientes graves producto de la covid-19 en la región de Lombardía, Italia. Materiales y métodos: analítico, longitudinal prospectivo con un grupo de pacientes críticos que ingresaron del 1 de abril al 1 de mayo de 2020, con diagnóstico de covid-19, en el Hospital Mayor de Crema, en la región de Lombardía, Italia. El universo estuvo constituido por 28 pacientes y se trabajó con el total de ellos. Resultados: composición por sexo: 48 % masculino. Media de edad: 83 años. Serie temporal: Modelo 1 que ajusta (Hold) PO2/FiO2 p = 0,251; Modelo 2 (ARIMA) SatO2/FiO2 p = 0,674 (en los dos primeros modelos el resultado se incrementó con los días, siguiendo un comportamiento predecible); Modelo 3 (ARIMA) p = 0,406 (en este caso, el resultado esperado decreció a medida que transcurrió el tiempo). Las funciones obtenidas permiten calcular el valor esperado según el día desde el ingreso. Conclusiones: predecir la evolución del paciente en la Unidad de Cuidados Intensivos permitió detectar tempranamente aquellos con una curva inesperada y dirigir hacia a ellos las terapéuticas más agresivas (AU).

ABSTRACT Introduction: a time series is the product of the observation of a variable in time. It is a mathematical tool frequently applied in health. No temporal models have been developed to predict patients' behavior during their staying in the Intensive Care Unit. Objectives: to create a time series allowing to predict the behavior of seriously-ill patients due to COVID-19, during their staying in the Intensive Care Unit in the region of Lombardy, Italy. Materials and methods: analytic, longitudinal prospective study with a group of critical patients who were admitted from April 1st to May 1st, with COVID-19 diagnosis, to Ospedale Maggiore di Crema, in the Lombardy region, Italy. The universe was formed by 28 patients and all of them were worked on. Results: 48% of patients were male. Average age: 83 years; Time series: Model 1 holding PO2/FiO2 p = 0.251; Model 2 (ARIMA) SatO2/FiO2 p = 0.674 (in the two first models the result increased with the days, following a predictable behavior=; Model 3 (ARIMA) p = 0.406 (in this case the expected result decreased as time passed). The obtained functions allow to calculate the expected value according to the day from the admission. Conclusions: predicting patient's evolution in the Intensive Care Unit allowed early detecting those with unexpected curves and targeting more aggressive therapies toward them (AU).

Scheduling of chemotherapy based on direct monitoring ofpO2 in tumor microenvironment by EPR oximetry / 中国癌症杂志

Background and purpose:Tumor microenvironment plays an important role in the introduction of foreign factors that mediate tumor acquired resistance. The antitumor effects of many chemotherapeutic agents depend on the level of oxygen pressure (pO2) in tumor microenvironment. This study aimed to evaluate electron paramagnetic reso-nance (EPR)-based monitoring on an oxygen-enriched tumor microenvironment to increase chemotherapeutic sensitivity. Methods:MCF-7 cells were used to establish human breast cancer in nude mice. EPR was used to directly measure pO2 levelin vivo. Tumor tissues were collected, and mitochondrial activity was assayed on the basis of the kinetics of enzyme-catalyzed reactions. A laser Doppler monitor was used to detect regional blood flow. Tumor apoptotic rate was analyzed by flow cytometry.Results:The tumor volume decreased more evidently in the chemotherapy group with oxy-gen-enriched environment than that in the conventional chemotherapy group after the treatment was administered (P<0.01). After chemotherapy was completed, the apoptotic rate of tumor cells was significantly higher in the chemotherapy group with oxygen-enriched environment than that in the conventional chemotherapy group (P<0.001). This study examined the mechanism ofpO2 changes in tumor microenvironment: This was related to the change of the balance between the oxygen consumption and the regional blood flow in the tumor tissues after chemotherapy.Conclusion:Based on the characteristics ofpO2 changes in the tumor microenvironment after chemotherapy was completed, the selection of chemotherapy mode forthe treatment inpO2 peak time window improves the sensitivity of chemotherapy, which provides a new idea for individual-ized chemotherapy in clinical applications.

Validation protocol for multiple blood gas analyzers in accordance with laboratory accreditation programs / Protocolo de validação de múltiplos equipamentos para análise de gases sanguíneos em conformidade com os programas de acreditação laboratorial

ABSTRACTIntroduction:The results of blood gas analysis using different instrumentation can vary widely due to the methodological differences, the calibration procedures and the use of different configurations for each type of instrument.Objective:The objective of this study was to evaluate multiple analytical systems for measurement of blood gases, electrolytes and metabolites in accordance with the accreditation program (PALC) of Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML).Materials and methods:20 samples were evaluated in three ABL800 Flex (Radiometer Medical ApS, Denmark) blood gas analyzers, and the results were compared with those of the device in use, which was considered the reference. The analysis of variance (Anova) was applied for statistical purposes, as well as the calculation of mean, standard deviation and coefficient of variation.Results:The p values obtained in the statistical analysis were: pH = 0.983, pO2 = 0.991, pCO2 = 0.353, lactate = 0.584, glucose = 0.995, ionized calcium = 0.983, sodium = 0.991, potassium = 0.926, chlorine = 0.029.Conclusion:The evaluation of multiple analytical systems is an essential procedure in the clinical laboratory for quality assurance and accuracy of the results.

RESUMOIntrodução:Os resultados da análise dos gases sanguíneos utilizando diferentes equipamentos podem apresentar grandes variações decorrentes das diferenças metodológicas, dos procedimentos de calibração e da aplicação de configurações distintas para cada tipo de instrumento.Objetivo:O objetivo deste trabalho foi avaliar múltiplos sistemas analíticos para teste de gases sanguíneos, eletrólitos e metabólitos, em conformidade com o Programa de Acreditação de Laboratórios Clínicos (PALC) da Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML).Materiais e métodos:Foram avaliadas 20 amostras em três analisadores de gases sanguíneos ABL800 Flex (Radiometer Medical ApS, Dinamarca) em relação ao equipamento em uso, que foi considerado referência. A análise de variância (Anova) foi aplicada para fins de estudo estatístico dos resultados obtidos nos quatro equipamentos, bem como o cálculo da média, do desvio padrão e do coeficiente de variação.Resultados:Os valores de p obtidos na análise estatística foram: pH = 0,983, pO2 = 0,991, pCO2 = 0,353, lactato = 0,584, glicose = 0,995, cálcio ionizado = 0,983, sódio = 0,991, potássio = 0,926 e cloro = 0,029.Conclusão:A avaliação de múltiplos sistemas analíticos é procedimento essencial no laboratório clínico para garantia da qualidade e da exatidão dos resultados.

Valores de referencia de gases arteriales y de electrolitos en caninos de la sabana de Bogotá / Reference Values of Arterial Gases and Electrolytes in Canines from the Bogotá Savanna / Valores de referência de gases arteriais e de eletrólitos em caninos da savana de Bogotá

Debido a la ausencia de valores de gasometría arterial que se ajusten a nuestras condiciones ambientales y a la amplia variedad de datos no actualizados en la literatura y utilizados en la práctica diaria, obtenidos con alturas, razas y equipos diferentes a los disponibles en nuestro medio, es necesario generar conocimiento propio ajustado a nuestra realidad. Se realizó una medición sistemática al azar de sangre arterial y venosa en 100 caninos sanos a la altura de la sabana de Bogotá (Chía: 2652 msnm; Cajicá: 2558 msnm; Sopó: 2650 msnm; La Calera: 2718 msnm y Bogotá: 2630 msnm), utilizando el analizador I-STAT® con cartucho EG7+. Se encontraron valores de referencia de gasometría, electrolitos, bases efectivas y pH. Los valores fueron comparados entre cuatro grupos por peso. Para cada parámetro se realizó estadística descriptiva basada en promedio, desviación estándar, error estándar, y se hallaron los límites de confianza (95%) y los intervalos con desviación estándar (una y dos desviaciones). Se evidenció disminución de PCO2, PO2, SO2, bicarbonato, BE. El pH se encontró levemente aumentado, similar a lo reportado por autores a grandes alturas y diferentes (no corroborado estadísticamente) a reportes en literatura, en los que la altura no fue una variable. Aun así son usados frecuentemente como referencia en la práctica de pequeños animales; solo la presentó diferencias estadísticas por grupos de peso. Como conclusión, se evidenció una regulación del pH sanguíneo eficaz a 2600 msnm, con diferentes valores de bicarbonato, PCO2, PO2, BE, que indican la necesidad de obtener y utilizar valores de referencia acordes con condiciones locales.

Due to the lack of arterial gas values that meet our environmental conditions and the wide variety of out-of-date data in literature and used in everyday practice, obtained with different heights, breeds and equipment to the ones available in our context, it becomes necessary to generate our own knowledge adjusted to our reality. A random systematic measurement of arterial and venous blood was made on 100 healthy canines in the Bogotá Savanna (Chia: 2652 m.a.s.l.; Cajica: 2558 m.a.s.l.; Sopo: 2650 m.a.s.l.; La Calera: 2718 m.a.s.l.; and Bogotá: 2630 m.a.s.l.;), using the I-STAT® analyzer with EG7+ cartridge. Reference values were found for gasometry, electrolytes, effective basis and pH. The values were compared between four groups by weight. Descriptive statistics were made for each parameter based on average, standard deviation and standard error, and the trust limits (95%) and the intervals with standard deviation (one and two deviations) were found. A decrease on PCO2, PO2, SO2, bicarbonate and BE was evident. The pH was found to be slightly increased, similar to the one reported by authors at great heights and different (not statistically confirmed) from reports in literature, where height was not a variable. Even so, they are frequently used as reference in the practice of small animals; only PO2 presented statistical differences by groups of weight. As a conclusion, effective regulation of blood pH was evident at 2600 m.a.s.l., with different bicarbonate values, PCO2, PO2, BE, which suggest the need to obtain and use reference values consistent with local conditions.

Devido à ausência de valores de gasometria arterial que se ajuste a nossas condições ambientais e à ampla variedade de dados não atualizados na literatura e utilizados na prática diária, obtidos com alturas, raças e equipes diferentes aos disponíveis em nosso meio, é necessário gerar conhecimento próprio ajustado a nossa realidade. Realizou-se uma medição sistemática ao azar de sangue arterial e venoso em 100 caninos sãos à altura da savana de Bogotá (Chia: 2652 msnm; Cajicá: 2558 msnm; Sopó: 2650 msnm; a Calera: 2718 msnm e Bogotá: 2630 msnm), utilizando o analisador I-STAT® com cartucho EG7+. Encontraram-se valores de referência de gasometria, eletrólitos, bases efetivas e pH. Os valores foram comparados entre quatro grupos por peso. Para cada parâmetro se realizou estatística descritiva baseada na média, no padrão de desvio, erro padrão, e se encontrou os limites de confiança (95%) e os intervalos com desvio padrão (um e dois desvios). Evidenciou-se diminuição de PCO2, PO2, SO2, bicarbonato, BE. O pH se encontrou levemente aumentado, similar ao reportado por autores a grandes alturas e diferentes (não corroborado estatisticamente) a relatórios em literatura, onde que a altura não foi uma variável.. Ainda assim são usados frequentemente como referência na prática de pequenos animais; só a PO2 apresentou diferenças estatísticas por grupos de peso. Como conclusão, se evidenciou uma regulação do pH sanguíneo eficaz a 2600 msnm, com diferentes valores de bicarbonato, PCO2, PO2, BE, que indicam a necessidade de obter e utilizar valores de referência acordes com condições locais.

Electrolyte and Gas Analysis from Dorsal Vein of Hand during General Inhalational Anesthesia / 대한구급학회지

BACKGROUND: To assess the acid-base status and to measure PO2 and PCO2, arterial blood gases (ABG) has been checked usually. We compared the venous blood gases (VBG) from dorsal vein of hand to ABG from radial artery, and tried to determine whether venous blood gas analysis (VBGA) could be the alternative of ABGA. METHODS: Thirty patients who needed continuous arterial pressure monitoring were chosen. At the completion of stability of HR and BP after induction of general inhalational anesthesia, the ABG from radial artery and VBG from dorsal vein of hand were compared. RESULTS: Laboratory findings were as follows (mean+/-SD): arterial pH, 7.44+/-0.04; venous pH, 7.43+/-0.04; arterial HCO3-, 25.56+/-2.39 mmol/L; venous HCO3-, 25.51+/-2.09 mmol/L. The mean values of arterial and venous PO2 were significantly different (247.8+/-48.9 mmHg versus 187.8+/-41.6 mmHg), but the arterial and venous PO2 values were significantly correlated (r=0.706). The PCO2 (r= 0.883), pH (r=0.912), and HCO3- (r=0.901) values, and base excesses of arterial and venous blood (r=0.926) were highly correlated. Also, arterial and venous serum electrolyte (sodium, potassium, and calcium) were highly correlated. CONCLUSIONS: Venous blood gas analysis from dorsal vein of hand can be effectively used as the alternative method to evaluate the acid-base status, PO2, and PCO2, instead of ABGA during general inhalational anesthesia.

Acid-Base and Blood-Gas Status of Newborn Umbilical Blood according to Induction-Delivery and Uterine Incision-Delivery Intervals under General Anesthesia for Cesaeran Section / 대한마취과학회지

In cesarean section under general anesthesia, inhalation anesthetics may compound fetal acidosis brought by maternal hypoxia or uteroplacental insufficiency. The chance af fetal distress may be increased with prolonged induction-delivery (ID) and uterine incision-delivery (UD) intervals in such cases. These studies were undertaken to evaluate the changes of fetal acid-base and blood-gas status according to these intervals in 58 parturients given cesarean section under general anesthesia. 58 neonates were divided into three groups according to their ID interval [group 1 (N=26): less than 6 minutes, group 2 (N=25): 6 to 10 minutes, group 3 (N=7): 10 to 15 minutes] and four groups according to their UD interval[group A (N=25): less than 60 seconds, group B (N=22): 60 to 90 seconds, group C (N=9): 90 to 120 seconds, group D (N=2): 120 to 180 seconds]. The pH, PCO2, PO2 and HCO3 values of the umbilical vein blood at delivery in the groups 1, 2, 3 divided according to ID intervals were 7.37+/-0.03, 7.36+/-0.04, 7.36+/-0.03; 39.75+/-4.83, 41.76+/- 4.03, 38.81+/-2.31; 34.35+/-745, 32.65+/-9.63, 30.89+/-11.28 (in mmHg); and 23.21+/-0.33, 23.30+/-0.26, 22.15+/-0.52 (in mEq/L), respectively, and in groups A, B, C, D divided according to UD intervals, they were 7.37+/-0.02, 7.37+/-0.02, 7.37+/-0.03, 7.36+/-0.06; 40.30+/-5.20, 40,63+/-3.11, 39.96+/-4.42, 40.03 +/-5.09; 32.35+/-8.23, 31.82+/-0.17, 35.67+/-8.35, 33.53+/-10.53 (in mmHg); and 23.14+0.26, 23.60+/-0.36, 22.88+/-0.67, 23.35+/-0.35 (in mEq/L), respectively. No significant differences in these values were present between these ID- or UD- based groups.

Enhancement of in vivo Radiosensitization by Combination with Pentoxifylline and Nicotinamide / 대한치료방사선과학회지

Pentoxifylline (PENTO) has been known to improve RBC fluidity, and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO also decreases the O2 release from RBC. Nicotinamide (N4) has been reported to decrease the number of acutely hypoxic cells in tumors by temporarily increasing tumor blood flow. Therefore, the purpose of this study was to examine whether the combination of PENTO and NA (PENTO+NA) would reduce the radioresistance of the the FSaII murine fibrosarcoma by oxygenation the hypoxic cells. We observed a significantly enhanced radiation-induced growth delay of the FSaII tumors by PENTO-NA. Thus the enhancement ration was between 2.5 and 2.8 in growth delay assay. The TCD50 of control tumors was about 57 Gy, but that of PENTO-NA treated tumors was about 32 Gy. The TCD50 was modified by a factor of 1.8. We also observed that PENTO+NA, changes in tumor blood flow and intratumor pO2 were measured using laser Doppler flowmetry and O2 microelectrode methods. The tumor blood flow significantly increased at 10 min. after injection of PENTO+NA. Furthermore, we also found that PENTO+NA significantly increased intratumor pO2 from 8 to 19 mmHg. We concluded that PENTO+NA was far more effective than NA alone or PENTO alone. The increase in the response of tumor in vivo to X-irradiation appeared to be due mainly to an increase in the tumor oxygenation. Further studies using various concentrations of PENTO alone and in combination with NA to obtain better sequencing and maximal radiosensitization are warranted.

Improving Oxygenation in the Murine Tumors by a perfluorochemical Emulsion (Fluosl-DA 20%) / 대한치료방사선과학회지

In the present study, a perfluorochemical emulsion (Fluosol-DA 20%) did not alter Do and and Dq values on cell survival curve, indicating that the lack of a direct effect of Fluosol-DA 20% on cellular radiosensitivity in vitro. The effect of Fluosol-DA 20% injection in combination with carbogen breathing was determined on the hupoxic cell fraction in SCK tumors. The hypoxic cell fraction in control SCK tumors was 0.39. This value decreased to 0.05 when the mice were i.v. injected with 12 ml/kg of Fluosol-DA 20% in a carbogen atomosphere. The measured mean and median PO2 values with a microelectorde in the control tumors was 9 mmHg and 4 mmHg, respectively. The treatment of the SCK tumors in the host mice with injected Fluosol-DA 20% in combination with carbogen breathing increased the mean and median PO2 values to 67 mmHg and 62 mmHg, respectively. Using carbogen breathing alone caused a moderate increase of tumor PO2. But Fluosol-DA 20% injection alone caused little change PO2 in the tumor. It was concluded that the combination of Fluosol-DA injection and carbogen breathing is an effective means to improve oxygenation of tumors.

The Effect of CSF Changes on the Action of Local Anesthetics in Pregnant Woman / 대한마취과학회지

Spinal fluid(CSF) was analyzed in ten pregnant women at term undergoing C-section with spinal anesthesia and in ten non-pregnant women undergoing gynecological operation with spinal anesthesia. The acid-base status, protein and sugar levels in the CSF of the CSF are summarized in Table-2 and Table-3. The pH was slightly higher in the pregnant group compared to that of the non-pregnant controls. The bicarbonate level and the total CO2 content were significantly lower in the pregnant group compared to non-pregnant controls. The protein and sugar level were lower in the pregnant group compared to non-pregnant controls. Acid base changes can markedly affect dissociation of the local anesthetics. More free base will be available for transfer across lipid barriers in a relatively more alkalotic medium which was found in spinal fluid of pregnant women. In addition, lower bicarbonate levels may also affect dissociation of local anesthetic and activity by changing the buffering capacity. In conclusion, our results show that pregnancy induces significant changes in the acid base balance of the spinal fluid. These changes may contribute to the facilitated spread of local anesthetics in both the epidural and subarachnoid spaces.