Impacts of a fraction of inspired oxygen adjustment protocol in COVID-19 patients under mechanical ventilation: A prospective cohort study.

Objective: We examined weather a protocol for fraction of inspired oxygen (FiO2) adjustment can reduce hyperoxemia and excess oxygen use in COVID-19 patients mechanically ventilated. Design: Prospective cohort study. Setting: Two intensive care units (ICUs) dedicated to COVID-19 patients in Brazil. Patients: Consecutive patients with COVID-19 mechanically ventilated. Interventions: One ICU followed a FiO2 adjustment protocol based on SpO2 (conservative-oxygen ICU) and the other, which did not follow the protocol, constituted the control ICU. Main variables of interest: Prevalence of hyperoxemia (PaO2 >100 mmHg) on day 1, sustained hyperoxemia (present on days 1 and 2), and excess oxygen use (FiO2 > 0.6 in patients with hyperoxemia) were compared between the two ICUs. Results: Eighty two patients from the conservative-oxygen ICU and 145 from the control ICU were included. The conservative-oxygen ICU presented lower prevalence of hyperoxemia on day 1 (40.2% vs. 75.9%, p < 0.001) and of sustained hyperoxemia (12.2% vs. 49.6%, p < 0.001). Excess oxygen use was less frequent in the conservative-oxygen ICU on day 1 (18.3% vs. 52.4%, p < 0.001). Being admitted in the control ICU was independently associated with hyperoxemia and excess oxygen use. Multivariable analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FiO2 use and adverse clinical outcomes. Conclusions: Following FiO2 protocol was associated with lower hyperoxemia and less excess oxygen use. Although those results were not associated with better clinical outcomes, adopting FiO2 protocol may be useful in a scenario of depleted oxygen resources, as was seen during the COVID-19 pandemic.

Objetivo: Evaluar si un protocolo para el ajuste de la FiO2 reduce la hiperoxemia y el uso excesivo de oxígeno en pacientes con COVID-19 en ventilación mecánica. Diseño: Estudio de cohorte prospectivo. Ámbito: Unidades de cuidados intensivos (UCI) dedicadas a pacientes con COVID-19 en Brasil. Pacientes: Pacientes con COVID-19. Intervenciones: Una UCI siguió un protocolo de ajuste de FiO2 basado en SpO2 (UCI de oxigenoterapia conservadora, N = 82) y la otra no siguió el protocolo (UCI control, N = 145). Principales variables de interés: Prevalencia de hiperoxemia (PaO2 > 100 mmHg) en el día 1, hiperoxemia sostenida (presente en los días 1 y 2) y exceso de uso de oxígeno (FiO2 > 0,6 en pacientes con hiperoxemia) entre las 2 UCI. Resultados: La UCI de oxigenoterapia conservadora presentó menor prevalencia de hiperoxemia en el día 1 (40,2 vs. 75,9%; p < 0,001) y de hiperoxemia sostenida (12,2 vs. 49,6%; p < 0,001). El uso excesivo de oxígeno fue menos frecuente en la UCI de oxigenoterapia conservadora el día 1 (18,3 vs. 52,4%; p < 0,001). El ingreso en la UCI control se asoció de forma independiente con la hiperoxemia y el uso excesivo de oxígeno. Los análisis multivariables no encontraron una relación independiente entre hiperoxemia o uso excesivo de FiO2 y resultados clínicos adversos. Conclusiones: Seguir el protocolo de FiO2 se asoció con menor hiperoxemia y menor consumo de oxígeno en exceso. Aunque esos resultados no se asociaron con mejores resultados clínicos, la adopción del protocolo FiO2 puede ser útil en un escenario de recursos de oxígeno agotados, como se vio durante la pandemia de COVID-19.

Impacts of a fraction of inspired oxygen adjustment protocol in COVID-19 patients under mechanical ventilation: A prospective cohort study.

OBJECTIVE: We examined weather a protocol for fraction of inspired oxygen (FiO2) adjustment can reduce hyperoxemia and excess oxygen use in COVID-19 patients mechanically ventilated. DESIGN: Prospective cohort study. SETTING: Two intensive care units (ICUs) dedicated to COVID-19 patients in Brazil. PATIENTS: Consecutive patients with COVID-19 mechanically ventilated. INTERVENTIONS: One ICU followed a FiO2 adjustment protocol based on SpO2 (conservative-oxygen ICU) and the other, which did not follow the protocol, constituted the control ICU. MAIN VARIABLES OF INTEREST: Prevalence of hyperoxemia (PaO2>100mmHg) on day 1, sustained hyperoxemia (present on days 1 and 2), and excess oxygen use (FiO2>0.6 in patients with hyperoxemia) were compared between the two ICUs. RESULTS: Eighty two patients from the conservative-oxygen ICU and 145 from the control ICU were included. The conservative-oxygen ICU presented lower prevalence of hyperoxemia on day 1 (40.2% vs. 75.9%, p<0.001) and of sustained hyperoxemia (12.2% vs. 49.6%, p<0.001). Excess oxygen use was less frequent in the conservative-oxygen ICU on day 1 (18.3% vs. 52.4%, p<0.001). Being admitted in the control ICU was independently associated with hyperoxemia and excess oxygen use. Multivariable analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FiO2 use and adverse clinical outcomes. CONCLUSIONS: Following FiO2 protocol was associated with lower hyperoxemia and less excess oxygen use. Although those results were not associated with better clinical outcomes, adopting FiO2 protocol may be useful in a scenario of depleted oxygen resources, as was seen during the COVID-19 pandemic.

Adherence to protective mechanical ventilation in COVID-19 versus non-COVID-19-associated acute respiratory distress syndrome: Comparison between two prospective cohorts.

OBJECTIVE: To compare adherence to protective mechanical ventilation (MV) parameters in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 with patients with ARDS from other etiologies. DESIGN: Multiple prospective cohort study. SETTING: Two Brazilian cohorts of ARDS patients were evaluated. One with COVID-19 patients admitted to two Brazilian intensive care units (ICUs) in 2020 and 2021 (C-ARDS, n=282), the other with ARDS-patients from other etiologies admitted to 37 Brazilian ICUs in 2016 (NC-ARDS, n=120). PATIENTS: ARDS patients under MV. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Adherence to protective MV (tidal volume ≤8mL/kg PBW; plateau pressure ≤30cmH2O; and driving pressure ≤15cmH2O), adherence to each individual component of the protective MV, and the association between protective MV and mortality. RESULTS: Adherence to protective MV was higher in C-ARDS than in NC-ARDS patients (65.8% vs. 50.0%, p=0.005), mainly due to a higher adherence to driving pressure ≤15cmH2O (75.0% vs. 62.4%, p=0.02). Multivariable logistic regression showed that the C-ARDS cohort was independently associated with adherence to protective MV. Among the components of the protective MV, only limiting driving pressure was independently associated with lower ICU mortality. CONCLUSIONS: Higher adherence to protective MV in patients with C-ARDS was secondary to higher adherence to limiting driving pressure. Additionally, lower driving pressure was independently associated with lower ICU mortality, which suggests that limiting exposure to driving pressure may improve survival in these patients.

Immunosuppression with cyclophosphamide favors reinfection with recombinant Toxoplasma gondii strains.

The aim of this study was to verify the effect of immunosuppression by cyclophosphamide (Cy) on susceptibility of BALB/c mice subjected to challenge with recombinant strains of Toxoplasma gondii. Animals were prime infected with the D8 (recombinant I/III) or the ME49 (type II) non-virulent strains, weekly immunosuppressed with Cy and challenged with the CH3 or EGS virulent strains (I/III). Parasites recovered from surviving mice were submitted to PCR-RFLP analysis to confirm co-infection. Prime-infection with the D8 strain conferred more protection against challenge with the CH3 and EGS strains when compared with ME49 prime infection. Cy treatment caused significant leukopenia in the infected mice, what probably favors reinfection after challenge. Reinfection was associated with increased levels of IgA. Otherwise, Cy-treated mice presented significantly lower IgA levels after challenge, suggesting involvement of this immunoglobulin on protection against reinfection. In conclusion, BALB/c mice susceptibility to reinfection by T. gondii is related to genetic differences among the strains used for primary and challenge infections. Alteration of the host's immune integrity by Cy probably compromises the protection previously established by primary infection.

Effect of saline infusion for the maintenance of blood volume on pulmonary gas exchange during temporary abdominal aortic occlusion.

We analyzed the effects of saline infusion for the maintenance of blood volume on pulmonary gas exchange in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. We studied 20 adult mongrel dogs weighing 12 to 23 kg divided into two groups: ischemia-reperfusion group (IRG, N = 10) and IRG submitted to saline infusion for the maintenance of mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, N = 10). All animals were anesthetized and maintained on spontaneous ventilation. After obtaining baseline measurements, occlusion of the supraceliac aorta was performed by the inflation of a Fogarty catheter. After 60 min of ischemia, the balloon was deflated and the animals were observed for another 60 min of reperfusion. The measurements were made at 10 and 45 min of ischemia, and 5, 30, and 60 min of reperfusion. Pulmonary gas exchange was impaired in the IRG-SS group as demonstrated by the increase of the alveolar-arterial oxygen difference (21 +/- 14 in IRG-SS vs 11 +/- 8 in IRG after 60 min of reperfusion, P = 0.004 in IRG-SS in relation to baseline values) and the decrease of oxygen partial pressure in arterial blood (58 +/- 15 in IRG-SS vs 76 +/- 15 in IRG after 60 min of reperfusion, P = 0.001 in IRG-SS in relation to baseline values), which was correlated with the highest degree of pulmonary edema in morphometric analysis (0.16 +/- 0.06 in IRG-SS vs 0.09 +/- 0.04 in IRG, P = 0.03 between groups). There was also a smaller ventilatory compensation of metabolic acidosis after the reperfusion. We conclude that infusion of normal saline worsened the gas exchange induced by pulmonary reperfusion injury in this experimental model.

Pentoxifylline decreases tumor necrosis factor and interleukin-1 during high tidal volume.

Tumor necrosis factor-alpha (TNF-alpha) is one of the most important proinflammatory cytokines which plays a central role in host defense and in the acute inflammatory response related to tissue injury. The major source of TNF-alpha are immune cells such as neutrophils and macrophages. We tested the hypothesis that pentoxifylline, a methylxanthine derivative, down-regulates proinflammatory cytokine expression during acute lung injury in rats. Male Wistar rats weighing 250 to 450 g were anesthetized ip with 50 mg/kg sodium thiopental and randomly divided into three groups: group 1 (N = 7): tidal volume (V T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and pentoxifylline infusion. The animals were ventilated with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 3 cmH2O, and normal saline or pentoxifylline injected into the left femoral vein. The mRNA of TNF-alpha rapidly increased in the lung tissue within 180 min of ventilation with a higher V T with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher V T with pentoxifylline infusion (TNF-alpha: plasma, 102.2+/-90.9 and BAL, 118.2+/-82.1; IL-1 : plasma, 45.2+/-42.7 and BAL, 50.2+/-34.9, P < 0.05). We conclude that TNF-alpha produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators.

Ventilation with high tidal volume induces inflammatory lung injury.

Mechanical ventilation with high tidal volumes (V(T)) has been shown to induce lung injury. We examined the hypothesis that this procedure induces lung injury with inflammatory features. Anesthetized male Wistar rats were randomized into three groups: group 1 (N = 12): V(T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min; group 2 (N = 10): V(T) = 21 ml/kg, RR = 16 breaths/min; group 3 (N = 11): V(T) = 42 ml/kg, RR = 8 breaths/min. The animals were ventilated with fraction of inspired oxygen of 1 and positive end-expiratory pressure of 2 cmH2O. After 4 h of ventilation, group 3, compared to groups 1 and 2, had lower PaO2 [280 (range 73-458) vs 517 (range 307-596), and 547 mmHg (range 330-662), respectively, P<0.05], higher wet lung weight [3.62 +/- 0.91 vs 1.69 +/- 0.48 and 1.44 +/- 0.20 g, respectively, P<0.05], and higher wet lung weight/dry lung weight ratio [18.14 (range 11.55-26.31) vs 7.80 (range 4.79-12.18), and 6.34 (range 5.92-7.04), respectively, P<0.05]. Total cell and neutrophil counts were higher in group 3 compared to groups 1 and 2 (P<0.05), as were baseline TNF-alpha concentrations [134 (range <10-386) vs 16 (range <10-24), and 17 pg/ml (range <10-23), respectively, P<0.05]. Serum TNF-alpha concentrations reached a higher level in group 3, but without statistical significance. These results suggest that mechanical ventilation with high V T induces lung injury with inflammatory characteristics. This ventilatory strategy can affect the release of TNF-alpha in the lungs and can reach the systemic circulation, a finding that may have relevance for the development of a systemic inflammatory response.

Physical activity in daily life assessed by an accelerometer in kidney transplant recipients and hemodialysis patients.

BACKGROUND: Sedentary lifestyle is a problem among hemodialysis (HD) patients, potentially attenuated after kidney transplantation. However, the effect of kidney transplantation on physical activity has not been thoroughly investigated. OBJECTIVE: This study sought to evaluate the physical activity in daily life in kidney transplant recipients (KTRs) compared with HD patients and to explore its relationship with clinical variables. METHODS: A cross-sectional study enrolled KTRs who received transplants at least 6 months before the study (N = 23; 48.3 ± 10.3 years) and patients undergoing HD for at least 6 months (N = 20; 47.3 ± 12.6 years). Time spent in different activities (walking, standing, sitting, and lying down) and number of steps taken, measured by a multiaxial accelerometer used for 12 h/d on 2 consecutive days for KTRs and on 4 consecutive days for HD patients, were evaluated. RESULTS: KTRs engaged in more active time per day (sum of walking and standing time) than HD patients (311 ± 87 vs 196 ± 54 min/d; P = .001), with longer walking (106 ± 53 vs 70 ± 27 min/d; P = .008) and standing time (205 ± 55 vs 126 ± 42 min/d; P < .001). Sixty-five percent of KTRs were classified as active (>7500 steps/d) compared with only 20% of the HD group (P < .05). The multivariate analysis showed that time posttransplantation was significantly associated with walking time and active time. CONCLUSIONS: By using an accelerometer, a precise method, this study showed that KTRs are significantly more active in daily life than HD patients, and that daily physical activity increases with time since transplantation.

New gentotypes of Toxoplasma gondii obtained from farm animals in Northeast Brazil.

Genotyping of Toxoplasma gondii in different regions of Brazil has shown high diversity and high frequency of virulent genotypes among Brazilian animals. The aim of the study was to characterize samples of T. gondii isolates obtained from naturally infected sheep, goats, pigs and free-range chickens slaughtered for human consumption in Rio Grande do Norte, Northeast Brazil. Nineteen T. gondii samples (isolated from 1 goat, 5 pigs and 13 free-range chickens) were genotyped. Six different genotypes were identified, including two novel genotypes. The archetype genotypes, i.e., types I, II and III, were not found. In mice, seventeen isolates (89.5%) were classified as virulent, and only two (10.5%) were classified as avirulent. This study displays the genotypic variability of the parasite in Northeast Brazil.

Effect of saline infusion for the maintenance of blood volume on pulmonary gas exchange during temporary abdominal aortic occlusion

We analyzed the effects of saline infusion for the maintenance of blood volume on pulmonary gas exchange in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. We studied 20 adult mongrel dogs weighing 12 to 23 kg divided into two groups: ischemia-reperfusion group (IRG, N = 10) and IRG submitted to saline infusion for the maintenance of mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, N = 10). All animals were anesthetized and maintained on spontaneous ventilation. After obtaining baseline measurements, occlusion of the supraceliac aorta was performed by the inflation of a Fogarty catheter. After 60 min of ischemia, the balloon was deflated and the animals were observed for another 60 min of reperfusion. The measurements were made at 10 and 45 min of ischemia, and 5, 30, and 60 min of reperfusion. Pulmonary gas exchange was impaired in the IRG-SS group as demonstrated by the increase of the alveolar-arterial oxygen difference (21 ± 14 in IRG-SS vs 11 ± 8 in IRG after 60 min of reperfusion, P = 0.004 in IRG-SS in relation to baseline values) and the decrease of oxygen partial pressure in arterial blood (58 ± 15 in IRG-SS vs 76 ± 15 in IRG after 60 min of reperfusion, P = 0.001 in IRG-SS in relation to baseline values), which was correlated with the highest degree of pulmonary edema in morphometric analysis (0.16 ± 0.06 in IRG-SS vs 0.09 ± 0.04 in IRG, P = 0.03 between groups). There was also a smaller ventilatory compensation of metabolic acidosis after the reperfusion. We conclude that infusion of normal saline worsened the gas exchange induced by pulmonary reperfusion injury in this experimental model.

Ventilation with high tidal volume induces inflammatory lung injury

Mechanical ventilation with high tidal volumes (V T) has been shown to induce lung injury. We examined the hypothesis that this procedure induces lung injury with inflammatory features. Anesthetized male Wistar rats were randomized into three groups: group 1 (N = 12): V T = 7 ml/kg, respiratory rate (RR) = 50 breaths/min; group 2 (N = 10): V T = 21 ml/kg, RR = 16 breaths/min; group 3 (N = 11): V T = 42 ml/kg, RR = 8 breaths/min. The animals were ventilated with fraction of inspired oxygen of 1 and positive end-expiratory pressure of 2 cmH2O. After 4 h of ventilation, group 3, compared to groups 1 and 2, had lower PaO2 [280 (range 73-458) vs 517 (range 307-596), and 547 mmHg (range 330-662), respectively, P<0.05], higher wet lung weight [3.62 ± 0.91 vs 1.69 ± 0.48 and 1.44 ± 0.20 g, respectively, P<0.05], and higher wet lung weight/dry lung weight ratio [18.14 (range 11.55-26.31) vs 7.80 (range 4.79-12.18), and 6.34 (range 5.92-7.04), respectively, P<0.05]. Total cell and neutrophil counts were higher in group 3 compared to groups 1 and 2 (P<0.05), as were baseline TNF-alpha concentrations [134 (range <10-386) vs 16 (range <10-24), and 17 pg/ml (range <10-23), respectively, P<0.05]. Serum TNF-alpha concentrations reached a higher level in group 3, but without statistical significance. These results suggest that mechanical ventilation with high V T induces lung injury with inflammatory characteristics. This ventilatory strategy can affect the release of TNF-alpha in the lungs and can reach the systemic circulation, a finding that may have relevance for the development of a systemic inflammatory response

Pentoxifylline decreases tumor necrosis factor and interleukin-1 during high tidal volume

Tumor necrosis factor-alpha (TNF-alpha) is one of the most important proinflammatory cytokines which plays a central role in host defense and in the acute inflammatory response related to tissue injury. The major source of TNF-alpha are immune cells such as neutrophils and macrophages. We tested the hypothesis that pentoxifylline, a methylxanthine derivative, down-regulates proinflammatory cytokine expression during acute lung injury in rats. Male Wistar rats weighing 250 to 450 g were anesthetized ip with 50 mg/kg sodium thiopental and randomly divided into three groups: group 1 (N = 7): tidal volume (V T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and pentoxifylline infusion. The animals were ventilated with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 3 cmH2O, and normal saline or pentoxifylline injected into the left femoral vein. The mRNA of TNF-alpha rapidly increased in the lung tissue within 180 min of ventilation with a higher V T with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher V T with pentoxifylline infusion (TNF-alpha: plasma, 102.2 ± 90.9 and BAL, 118.2 ± 82.1; IL-1ß: plasma, 45.2 ± 42.7 and BAL, 50.2 ± 34.9, P < 0.05). We conclude that TNF-alpha produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators