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BACKGROUND AND OBJECTIVE: Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal. This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF). METHODS: Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cleff) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days. RESULTS: HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (ß = - 8.90 (95% CI - 12.9 to - 4.87), p < 0.001) and tazobactam (ß = - 8.29 (95% CI - 13.5 to - 3.08), p = 0.002) and Cleff for each antibiotic (meropenem ß = - 10,206 (95% CI - 14,787 to - 5787), p = 0.001); tazobactam (ß = - 4551 (95% CI - 7781 to - 1322), p = 0.012); piperacillin (ß = - 3913 (95% CI - 6388 to - 1437), p = 0.002), even if the carryover effect influenced the Cleff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (ß = - 38.1 (95% CI - 47.9 to - 28.3), p < 0.001) and tazobactam (ß = - 4.45 (95% CI - 6.17 to - 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type. CONCLUSION: MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM.

Asunto(s)

Antibacterianos , Terapia de Reemplazo Renal Continuo , Estudios Cruzados , Meropenem , Diálisis Renal , Choque Séptico , Humanos , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Antibacterianos/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Choque Séptico/terapia , Choque Séptico/tratamiento farmacológico , Choque Séptico/sangre , Proyectos Piloto , Terapia de Reemplazo Renal Continuo/métodos , Diálisis Renal/métodos , Meropenem/uso terapéutico , Meropenem/administración & dosificación , Meropenem/farmacocinética , Tazobactam/uso terapéutico , Tazobactam/farmacocinética , Piperacilina/farmacocinética , Piperacilina/uso terapéutico , Piperacilina/administración & dosificación , Hemodiafiltración/métodos

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Background: Lung transplantation (LUTX) is often complicated by primary graft dysfunction (PGD). Plasma biomarkers hold potential for PGD phenotyping and targeted therapy. This scoping review aims to collect the available literature in search of serum biomarkers for PGD phenotyping. Methods: Following JBI and PRISMA guidelines, we conducted a systematic review searching MEDLINE, Web of Science, EMBASE and The Cochrane Library for papers reporting the association between serum biomarkers measured within 72 h of reperfusion and PGD, following International Society for Heart and Lung Transplantation (ISHLT) guidelines. We extracted study details, patient demographics, PGD definition and timing, biomarker concentration, and their performance in identifying PGD cases. Results: Among the 1050 papers screened, 25 prospective observational studies were included, with only nine conducted in the last decade. These papers included 1793 unique adult patients (1195 double LUTX, median study size 100 (IQR 44-119)). Most (n=21) compared PGD grade 3 to less severe PGD, but only four adhered to 2016 PGD definitions. Enzyme-linked immunosorbent assays and the multiplex bead array technique were utilised in 23 and two papers, respectively. In total, 26 candidate biomarkers were identified, comprising 13 inflammatory, three endothelial activation, three epithelial injury, three cellular damage and two coagulation dysregulation markers. Only five biomarkers (sRAGE, ICAM-1, PAI-1, SP-D, FSTL-1) underwent area under the receiver operating characteristic curve analysis, yielding a median value of 0.58 (0.51-0.78) in 406 patients (276 double LUTX). Conclusions: Several biomarkers exhibit promise for future studies aimed at PGD phenotyping after LUTX. To uncover the significant existing knowledge gaps, further international prospective studies incorporating updated diagnostic criteria, modern platforms and advanced statistical approaches are essential.

RESUMEN

BACKGROUND: Inconsistent data exists regarding the risk factors for bronchoalveolar lavage (BAL) positivity in lung donors, the incidence of donor-derived infections (DDI), and the effect of BAL positivity on lung transplant (LuTx) recipients' outcome. METHODS: A retrospective analysis was conducted on consecutive LuTx at a single center from January 2016 to December 2022. Donors' data, including characteristics, graft function and BAL samples were collected pre-procurement. Recipients underwent BAL before LuTx and about the 3rd, 7th and 14th day after LuTx. A DDI was defined as BAL positivity (bacterial growth ≥104 colony forming units) for identical bacterial species between donor and recipient. Recipients' pre-operative characteristics, intra-operative management, and post-operative outcomes were assessed. Two recipient cohorts were identified based on lung colonization status before undergoing LuTx. RESULTS: Out of 188 LuTx procedures performed, 169 were analyzed. Thirty-six percent of donors' BAL tested positive. Donors' characteristics and graft function at procurement were not associated with BAL positivity. Fourteen DDI were detected accounting for 23% of recipients receiving a graft with a positive BAL. Only among uncolonized recipients, receiving a graft with positive BAL is associated with higher likelihood of requiring invasive ventilation at 72 hours after LuTx on higher positive end-expiratory pressure levels having lower PaO2/FiO2, prolonged duration of mechanical ventilation and longer ICU stay. No difference in hospital length of stay was observed. CONCLUSIONS: Receiving a graft with a positive BAL, which is poorly predicted by donors' characteristics, carries the risk of developing a DDI and is associated to a worse early graft function among uncolonized recipients.

Asunto(s)

Líquido del Lavado Bronquioalveolar , Trasplante de Pulmón , Donantes de Tejidos , Humanos , Masculino , Estudios Retrospectivos , Femenino , Factores de Riesgo , Incidencia , Adulto , Persona de Mediana Edad , Líquido del Lavado Bronquioalveolar/microbiología , Lavado Broncoalveolar/métodos , Receptores de Trasplantes

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OBJECTIVES: Although respiratory failure is the most common feature in coronavirus disease 2019 (COVID-19), abdominal organ involvement is likewise frequently observed. To investigate visceral and thoracic circulation and abdominal organ damage in COVID-19 patients. MATERIALS AND METHODS: A monocentric observational study was carried on. In COVID-19 patients affected by acute respiratory distress syndrome (ARDS) (n = 31) or mild pneumonia (n = 60) thoracoabdominal circulation was evaluated using Doppler-ultrasound and computed tomography. The study also included non-COVID-19 patients affected by ARDS (n = 10) or portal hypertension (n = 10) for comparison of the main circulatory changes. RESULTS: Patients affected by COVID-19 ARDS showed hyperdynamic visceral flow and increased portal velocity, hepatic artery resistance-index, and spleen diameter relative to those with mild-pneumonia (p = 0.001). Splanchnic circulatory parameters significantly correlated with the main respiratory indexes (p < 0.001) and pulmonary artery diameter (p = 0.02). The chest and abdominal vascular remodeling pattern of COVID-19 ARDS patients resembled the picture observed in the PH group, while differed from that of the non-COVID ARDS group. A more severe COVID-19 presentation was associated with worse liver dysfunction and enhanced inflammatory activation; these parameters both correlated with abdominal (p = 0.04) and chest imaging measures (p = 0.03). CONCLUSION: In COVID-19 ARDS patients there are abdominal and lung vascular modifications that depict a portal hypertension-like pattern. The correlation between visceral vascular remodeling, pulmonary artery enlargement, and organ damage in these critically ill patients is consistent with a portal hyperlfow-like syndrome that could contribute to the peculiar characteristics of respiratory failure in these patients. CLINICAL RELEVANCE STATEMENT: our data suggest that the severity of COVID-19 lung involvement is directly related to the development of a portal hyperflow-like syndrome. These observations should help in defining the need for a closer monitoring, but also to develop dedicated therapeutic strategies.

Asunto(s)

COVID-19 , Hipertensión Portal , Síndrome de Dificultad Respiratoria , Humanos , COVID-19/complicaciones , COVID-19/fisiopatología , Masculino , Femenino , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Persona de Mediana Edad , Hipertensión Portal/fisiopatología , Anciano , SARS-CoV-2 , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler

RESUMEN

Purpose: This study aimed to investigate the effects of inspired oxygen fraction (FiO2) and positive end-expiratory pressure (PEEP) on gas exchange in mechanically ventilated patients with COVID-19. Methods: Two FiO2 (100%, 40%) were tested at 3 decreasing levels of PEEP (15, 10, and 5 cmH2O). At each FiO2 and PEEP, gas exchange, respiratory mechanics, hemodynamics, and the distribution of ventilation and perfusion were assessed with electrical impedance tomography. The impact of FiO2 on the intrapulmonary shunt (delta shunt) was analyzed as the difference between the calculated shunt at FiO2 100% (shunt) and venous admixture at FiO2 40% (venous admixture). Results: Fourteen patients were studied. Decreasing PEEP from 15 to 10 cmH2O did not change shunt (24 [21-28] vs 27 [24-29]%) or venous admixture (18 [15-26] vs 23 [18-34]%) while partial pressure of arterial oxygen (FiO2 100%) was higher at PEEP 15 (262 [198-338] vs 256 [147-315] mmHg; P < .05). Instead when PEEP was decreased from 10 to 5 cmH2O, shunt increased to 36 [30-39]% (P < .05) and venous admixture increased to 33 [30-43]% (P < .05) and partial pressure of arterial oxygen (100%) decreased to 109 [76-177] mmHg (P < .05). At PEEP 15, administration of 100% FiO2 resulted in a shunt greater than venous admixture at 40% FiO2, ((24 [21-28] vs 18 [15-26]%, P = .005), delta shunt 5.5% (2.3-8.8)). Compared to PEEP 10, PEEP of 5 and 15 cmH2O resulted in decreased global and pixel-level compliance. Cardiac output at FiO2 100% resulted higher at PEEP 5 (5.4 [4.4-6.5]) compared to PEEP 10 (4.8 [4.1-5.5], P < .05) and PEEP 15 cmH2O (4.7 [4.5-5.4], P < .05). Conclusion: In this study, PEEP of 15 cmH2O, despite resulting in the highest oxygenation, was associated with overdistension. PEEP of 5 cmH2O was associated with increased shunt and alveolar collapse. Administration of 100% FiO2 was associated with an increase in intrapulmonary shunt in the setting of high PEEP. Trial registration: NCT05132933.

Asunto(s)

COVID-19 , Enfermedades Pulmonares , Síndrome de Dificultad Respiratoria , Humanos , Respiración Artificial , Síndrome de Dificultad Respiratoria/terapia , COVID-19/complicaciones , COVID-19/terapia , Pulmón/diagnóstico por imagen , Respiración con Presión Positiva/métodos , Mecánica Respiratoria , Oxígeno

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Single lung transplantation (LUTX) can be the last therapeutic option for a growing cohort of patients suffering from end-stage respiratory failure. Postoperative ventilatory management of single LUTX recipients is challenged by the coexistence of the diseased native lung and a healthy-but fragile-graft. In this case report, in a single LUTX recipient with idiopathic pulmonary fibrosis, regional ventilation ( ), perfusion ( ), and / matching and subsequent measurement of shunt fraction ( Qs / Qt ) and alveolar dead space ( Vd / Vt ) were obtained by integrating electrical impedance tomography (EIT) with volumetric capnography and pulmonary thermodilution technique. Although the preoperative pulmonary scintigraphy showed predominant right lung perfusion (79.8% vs. 20.2%), the EIT documented the postoperative re-establishment of between the lungs (demonstrating the adequate functioning of vascular anastomoses), the diversion of to the graft and similar global Qs / Qt (17%) and Vd / Vt (29%) between native and graft lung. Electrical impedance tomography mapping allowed regional Qs / Qt and Vd / Vt assessment: the native right lung had a completely deranged distribution of and ( Qs / Qt 25%, Vd / Vt 46%), whereas the graft showed normal coupling of and ( Qs / Qt 8%, Vd / Vt 12%). Electrical impedance tomography may allow noninvasive, repeatable, bedside assessments of the lung / coupling after single LUTX.

Asunto(s)

Trasplante de Pulmón , Pulmón , Humanos , Impedancia Eléctrica , Pulmón/diagnóstico por imagen , Perfusión , Tomografía/métodos

RESUMEN

INTRODUCTION: The postoperative hemodynamic management after lung transplant (LUTX) is guided by limited evidence. We aimed to describe and evaluate risk factors and outcomes of postoperative vasoactive support of LUTX recipients. METHODS: In a single-center retrospective analysis of consecutive adult LUTX, two cohorts were identified: (1) patients needing prolonged vasoactive support (>12 h from ICU admission) (VASO+); (2) or not (VASO-). Postoperative hemodynamic characteristics were thoroughly analyzed. Risk factors and outcomes of VASO+ versus VASO- cohorts were assessed by multivariate logistic regression and propensity score matching. RESULTS: One hundred and thirty-eight patients were included (86 (62%) VASO+ versus 52 (38%) VASO-). Vasopressors (epinephrine, norepinephrine, dopamine) were used in the first postoperative days (vasoactive inotropic score at 12 h: 6 [4-12]), while inodilators (dobutamine, levosimendan) later. Length of vasoactive support was 3 [2-4] days. Independent predictors of vasoactive use were: LUTX indication different from cystic fibrosis (p = .003), higher Oto score (p = .020), longer cold ischemia time (p = .031), but not preoperative cardiac catheterization. VASO+ patients showed concomitant hemodynamic and graft impairment, with longer mechanical ventilation (p = .010), higher primary graft dysfunction (PGD) grade at 72 h (PGD grade > 0 65% vs. 31%, p = .004, OR 4.2 [1.54-11.2]), longer ICU (p < .001) and hospital stay (p = .013). Levosimendan as a second-line inodilator appeared safe. CONCLUSIONS: Vasoactive support is frequently necessary after LUTX, especially in recipients of grafts of lesser quality. Postoperative hemodynamic dysfunction requiring vasopressor support and graft dysfunction may represent a clinical continuum with immediate and long-term consequences. Further studies may elucidate if this represents a possible treatable condition.

Asunto(s)

Trasplante de Pulmón , Disfunción Primaria del Injerto , Adulto , Humanos , Estudios Retrospectivos , Simendán/farmacología , Trasplante de Pulmón/efectos adversos , Norepinefrina , Vasoconstrictores/uso terapéutico , Hemodinámica , Disfunción Primaria del Injerto/etiología

RESUMEN

Hyperammonemia after lung transplantation is a rare but potentially fatal condition. A 59-year-old male patient affected by pulmonary fibrosis underwent an uncomplicated bilateral lung transplant. Fourteen days after the procedure, the patient developed severe encephalopathy caused by elevated serum ammonia levels. Ureaplasma parvum and Mycoplasma hominis were found on bronchial aspirate and urinary samples as well as on pharyngeal and rectal swabs. Despite the initiation of multimodal therapy, brain damage due to hyperosmolarity was so extensive to evolve into brain death. The autopsy revealed glutamine synthetase hypo-expression in the hepatic tissue. The pathophysiology of hyperammonemia syndrome in lung transplant recipients remains unclear. Previous studies have described the presence of disorders of glutamine synthetase, while others considered the infection with urea-splitting microorganisms as a cause of hyperammonemia syndrome. Our report describes the case of a patient who developed hyperammonemia after a lung transplant in which both the aforementioned etiologies were documented. A high level of clinical suspicion for hyperammonemia syndrome should be maintained in lung transplant recipients. Timely recognition and treatment are critical to prevent the potentially dreadful evolution of this severe complication.

Asunto(s)

COVID-19 , Neumonía Asociada al Ventilador , Humanos , Neumonía Asociada al Ventilador/epidemiología , Estudios de Cohortes , Respiración Artificial/efectos adversos , Incidencia , COVID-19/complicaciones , Tratamiento Farmacológico de COVID-19 , Unidades de Cuidados Intensivos/estadística & datos numéricos , Esteroides , Dexametasona

Asunto(s)

Respiración con Presión Positiva , Síndrome de Dificultad Respiratoria , Adulto , Humanos , Pulmón , Ventiladores Mecánicos , Respiración , Síndrome de Dificultad Respiratoria/terapia , Respiración Artificial

RESUMEN

BACKGROUND: Acid-base status in full-term pregnant women is characterised by hypocapnic alkalosis. Whether this respiratory alkalosis is primary or consequent to changes in CSF electrolytes is not clear. METHODS: We enrolled third-trimester pregnant women (pregnant group) and healthy, non-pregnant women of childbearing age (controls) undergoing spinal anaesthesia for Caesarean delivery and elective surgery, respectively. Electrolytes, strong ion difference (SID), partial pressure of carbon dioxide ( [Formula: see text] ), and pH were measured in simultaneously collected CSF and arterial blood samples. RESULTS: All pregnant women (20) were hypocapnic, whilst only four (30%) of the controls (13) had an arterial [Formula: see text] <4.7 kPa (P<0.001). The incidence of hypocapnic alkalosis was higher in the pregnant group (65% vs 8%; P=0.001). The CSF-to-plasma Pco2 difference was significantly higher in pregnant women (1.5 [0.3] vs 1.0 [0.4] kPa; P<0.001), mainly because of a decrease in arterial Pco2 (3.9 [0.3] vs 4.9 [0.5] kPa; P<0.001). Similarly, the CSF-to-plasma difference in SID was less negative in pregnant women (-7.8 [1.4] vs -11.4 [2.3] mM; P<0.001), mainly because of a decreased arterial SID (31.5 [1.2] vs 36.1 [1.9] mM; P<0.001). The major determinant of the reduced plasma SID of pregnant women was a relative increase in plasma chloride compared with sodium. CONCLUSIONS: Primary hypocapnic alkalosis characterises third-trimester pregnant women leading to chronic acid-base adaptations of CSF and plasma. The compensatory SID reduction, mainly sustained by an increase in chloride concentration, is more pronounced in plasma than in CSF, as the decrease in Pco2 is more marked in this compartment. CLINICAL TRIAL REGISTRATION: NCT03496311.

Asunto(s)

Alcalosis , Femenino , Humanos , Embarazo , Equilibrio Ácido-Base , Bicarbonatos , Dióxido de Carbono , Cloruros , Electrólitos , Concentración de Iones de Hidrógeno , Tercer Trimestre del Embarazo , Sodio

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INTRODUCTION: The clinical trajectory of post-operative acute kidney injury (AKI) following lung transplantation for cystic fibrosis is unknown. METHODS: Incidence and risk factors for post-operative AKI, acute kidney disease (AKD) and chronic kidney disease (CKD) were retrospectively analyzed in cystic fibrosis patients undergoing lung transplantation. Logistic regressions, Chi-square, Cuzick rank tests, and Cox-proportional hazard models were used. RESULTS: Eighty-three patients were included. Creatinine peaked 3[2-4] days after transplantation, with 15(18%), 15(18%), and 20(24%) patients having post-operative AKI stages 1, 2, and 3, while 15(18%), 19(23%) and 10(12%) developed AKD stage 1, stage 2 and 3, respectively. Higher AKI stage was associated with worsening AKD (p = 0.009) and CKD (p = 0.015) stages. Of the 50 patients with AKI, 32(66%) transitioned to AKD stage > 0, and then 27 (56%) to CKD stage > 1. Female sex, extracorporeal membrane oxygenation support as a bridge to lung transplant and at the end of the surgery, the use of intraoperative blood components, and cold-ischemia time were associated with increased risk of post-operative AKI and AKD. Higher AKI stage prolonged invasive mechanical ventilation (p = 0.0001), ICU stay (p = 0.0001), and hospital stay (p = 0.0001), and increased the incidence of primary graft dysfunction (p = 0.035). Both AKI and AKD stages > 2 worsened long-term survival with risk ratios of 3.71 (1.34-10.2), p = 0.0131 and 2.65(1.02-6.87), p = 0.0443, respectively. DISCUSSION: AKI is frequent in cystic fibrosis patients undergoing lung transplantation, it often evolves to AKD and to chronic kidney disease, thereby worsening short- and long-term outcomes.

Asunto(s)

Lesión Renal Aguda , Fibrosis Quística , Fallo Renal Crónico , Trasplante de Pulmón , Insuficiencia Renal Crónica , Enfermedad Aguda , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Fibrosis Quística/complicaciones , Fibrosis Quística/cirugía , Femenino , Humanos , Riñón/fisiología , Fallo Renal Crónico/complicaciones , Trasplante de Pulmón/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Factores de Riesgo

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The acceptable duration of donor warm ischemia time (DWIT) after cardiocirculatory death (DCD) is still debated. We analyzed the biomolecular profile and function during ex vivo lung perfusion (EVLP) of DCD lungs and their correlation with lung transplantation (LuTx) outcomes. Donor data, procurement times, recipient outcomes, and graft function up to 1 year after LuTx were collected. During EVLP, the parameters of graft function and metabolism, perfusate samples to quantify inflammation, glycocalyx breakdown products, coagulation, and endothelial activation markers were obtained. Data were compared to a cohort of extended-criteria donors after brain death (EC-DBD). Eight DBD and seven DCD grafts transplanted after EVLP were analyzed. DCD's DWIT was 201 [188;247] minutes. Donors differed only regarding the duration of mechanical ventilation that was longer in the EC-DBD group. No difference was observed in lung graft function during EVLP. At reperfusion, "wash-out" of inflammatory cells and microthrombi was predominant in DCD grafts. Perfusate biomolecular profile demonstrated marked endothelial activation, characterized by the presence of inflammatory mediators and glycocalyx breakdown products both in DCD and EC-DBD grafts. Early graft function after LuTx was similar between DCD and EC-DBD. DCD lungs exposed to prolonged DWIT represent a potential resource for donation if properly preserved and evaluated.

RESUMEN

OBJECTIVE: To assess the impact of treatment with steroids on the incidence and outcome of ventilator-associated pneumonia (VAP) in mechanically ventilated COVID-19 patients. DESIGN: Propensity-matched retrospective cohort study from February 24 to December 31, 2020, in 4 dedicated COVID-19 Intensive Care Units (ICU) in Lombardy (Italy). PATIENTS: Adult consecutive mechanically ventilated COVID-19 patients were subdivided into two groups: (1) treated with low-dose corticosteroids (dexamethasone 6 mg/day intravenous for 10 days) (DEXA+); (2) not treated with corticosteroids (DEXA-). A propensity score matching procedure (1:1 ratio) identified patients' cohorts based on: age, weight, PEEP Level, PaO2/FiO2 ratio, non-respiratory Sequential Organ Failure Assessment (SOFA) score, Charlson Comorbidity Index (CCI), C reactive protein plasma concentration at admission, sex and admission hospital (exact matching). INTERVENTION: Dexamethasone 6 mg/day intravenous for 10 days from hospital admission. MEASUREMENTS AND MAIN RESULTS: Seven hundred and thirty-nine patients were included, and the propensity-score matching identified two groups of 158 subjects each. Eighty-nine (56%) DEXA+ versus 55 (34%) DEXA- patients developed a VAP (RR 1.61 (1.26-2.098), p = 0.0001), after similar time from hospitalization, ICU admission and intubation. DEXA+ patients had higher crude VAP incidence rate (49.58 (49.26-49.91) vs. 31.65 (31.38-31.91)VAP*1000/pd), (IRR 1.57 (1.55-1.58), p < 0.0001) and risk for VAP (HR 1.81 (1.31-2.50), p = 0.0003), with longer ICU LOS and invasive mechanical ventilation but similar mortality (RR 1.17 (0.85-1.63), p = 0.3332). VAPs were similarly due to G+ bacteria (mostly Staphylococcus aureus) and G- bacteria (mostly Enterobacterales). Forty-one (28%) VAPs were due to multi-drug resistant bacteria. VAP was associated with almost doubled ICU and hospital LOS and invasive mechanical ventilation, and increased mortality (RR 1.64 [1.02-2.65], p = 0.040) with no differences among patients' groups. CONCLUSIONS: Critically ill COVID-19 patients are at high risk for VAP, frequently caused by multidrug-resistant bacteria, and the risk is increased by corticosteroid treatment. TRIAL REGISTRATION: NCT04388670, retrospectively registered May 14, 2020.

Asunto(s)

Tratamiento Farmacológico de COVID-19 , COVID-19 , Neumonía Asociada al Ventilador , Adulto , COVID-19/epidemiología , Estudios de Cohortes , Dexametasona/uso terapéutico , Humanos , Incidencia , Unidades de Cuidados Intensivos , Neumonía Asociada al Ventilador/tratamiento farmacológico , Neumonía Asociada al Ventilador/epidemiología , Neumonía Asociada al Ventilador/etiología , Respiración Artificial/efectos adversos , Estudios Retrospectivos

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BACKGROUND: Evaluation of donor lung function relies on the arterial oxygen partial pressure to inspired oxygen fraction ratio (PaO2 /FiO2 ) measurement. Hemodynamic, metabolic derangements, and therapeutic intervention occurring during brain dead observation may influence the evaluation of gas exchange. METHODS: We performed a mathematical analysis to explore the influence of the extrapulmonary determinants on the interpretation of PaO2 /FiO2 in the brain-dead donor and during Ex-Vivo Lung Perfusion (EVLP). RESULTS: High FiO2 and increased mixed venous oxygen saturation, caused by increased delivery and reduced consumption of oxygen, raise the PaO2 /FiO2 despite substantial intrapulmonary shunt. Anemia does not modify the PaO2 /FiO2 -intrapulmonary shunt relationship. During EVLP, the reduced artero-venous difference in oxygen content increases the PaO2 /FiO2 without this corresponding to an optimal graft function, while the reduced perfusate oxygen-carrying capacity linearizes the PaO2 /FiO2 -intrapulmonary shunt relationship. CONCLUSIONS: Adopting PaO2 /FiO2 to evaluate graft suitability for transplantation should account for extrapulmonary factors affecting its interpretation.

Asunto(s)

Oxígeno , Intercambio Gaseoso Pulmonar , Presión Parcial , Análisis de los Gases de la Sangre , Pulmón

RESUMEN

BACKGROUND: Few data exist on high flow nasal cannula (HFNC) use in patients with acute respiratory failure (ARF) admitted to general wards. RATIONALE AND OBJECTIVES: To retrospectively evaluate feasibility and safety of HFNC in general wards under the intensivist-supervision and after specific training. METHODS: Patients with ARF (dyspnea, respiratory rate-RR > 25/min, 150 < PaO2/FiO2 < 300 mmHg during oxygen therapy) admitted to nine wards of an academic hospital were included. Gas-exchange, RR, and comfort were assessed before HFNC and after 2 and 24 h of application. RESULTS: 150 patients (81 male, age 74 [60-80] years, SOFA 4 [2-4]), 123 with de-novo ARF underwent HFNC with flow 60 L/min [50-60], FiO2 50% [36-50] and temperature 34 °C [31-37]. HFNC was applied a total of 1399 days, with a median duration of 7 [3-11] days. No major adverse events or deaths were reported. HFNC did not affect gas exchange but reduced RR (25-22/min at 2-24 h, p < 0.001), and improved Dyspnea Borg Scale (3-1, p < 0.001) and comfort (3-4, p < 0.001) after 24 h. HFNC failed in 20 patients (19.2%): 3 (2.9%) for intolerance, 14 (13.4%) escalated to NIV/CPAP in the ward, 3 (2.9%) transferred to ICU. Among these, one continued HFNC, while the other 2 were intubated and they both died. Predictors of HFNC failure were higher Charlson's Comorbidity Index (OR 1.29 [1.07-1.55]; p = 0.004), higher APACHE II Score (OR 1.59 [1.09-4.17]; p = 0.003), and cardiac failure as cause of ARF (OR 5.26 [1.36-20.46]; p = 0.02). CONCLUSION: In patients with mild-moderate ARF admitted to general wards, the use of HFNC after an initial training and daily supervision by intensivists was feasible and seemed safe. HFNC was effective in improving comfort, dyspnea, and respiratory rate without effects on gas exchanges. Trial registration This is a single-centre, noninterventional, retrospective analysis of clinical data.

Asunto(s)

Ventilación no Invasiva , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Anciano , Cánula , Disnea/etiología , Humanos , Masculino , Oxígeno , Terapia por Inhalación de Oxígeno/efectos adversos , Habitaciones de Pacientes , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos

RESUMEN

BACKGROUND: Consumption of platelets and coagulation factors during extracorporeal carbon dioxide removal (ECCO2 R) increases bleeding complications and associated mortality. Regional infusion of lactic acid enhances ECCO2 R by shifting the chemical equilibrium from bicarbonate to carbon dioxide. Our goal was to test if regional blood acidification during ECCO2 R inhibits platelet function and coagulation. METHODS: An ECCO2 R system containing a hemofilter circulated blood at 0.25 L/min in eight healthy ewes (Ovis aries) for 36 h. Three of the sheep received ECCO2 R with no recirculation compared to five sheep that received ECCO2 R plus 12 h of regional blood acidification via the hemofilter, placed upstream from the oxygenator, into which 4.4 M lactic acid was infused. Blood gases, platelet count and function, thromboelastography, coagulation-factor activity, and von Willebrand factor activity (vWF:Ag) were measured at baseline, at start of lactic acid infusion, and after 36 h of extracorporeal circulation. RESULTS: Twelve hours of regional acid infusion significantly inhibited platelet aggregation response to adenosine diphosphate; vWF; and platelet expression of P-selectin compared to control. It also significantly reduced consumption of fibrinogen and of coagulation factors V, VII, IX, compared to control. CONCLUSIONS: Regional acidification reduces platelet activation and vitamin-K-dependent coagulation-factor consumption during ECCO2 R. This is the first report of a simple method that may enhance effective anticoagulation for ECCO2 R.

Asunto(s)

Dióxido de Carbono , Factor de von Willebrand , Animales , Plaquetas , Circulación Extracorporea , Femenino , Concentración de Iones de Hidrógeno , Ácido Láctico/farmacología , Ovinos

RESUMEN

OBJECTIVES: Extracorporeal carbon dioxide removal is used to treat patients suffering from acute respiratory failure. However, the procedure is hampered by the high blood flow required to achieve a significant CO2 clearance. We aimed to develop an ultralow blood flow device to effectively remove CO2 combined with continuous renal replacement therapy (CRRT). DESIGN: Preclinical, proof-of-concept study. SETTING: An extracorporeal circuit where 200 mL/min of blood flowed through a hemofilter connected to a closed-loop dialysate circuit. An ion-exchange resin acidified the dialysate upstream, a membrane lung to increase Pco2 and promote CO2 removal. PATIENTS: Six, 38.7 ± 2.0-kg female pigs. INTERVENTIONS: Different levels of acidification were tested (from 0 to 5 mEq/min). Two l/hr of postdilution CRRT were performed continuously. The respiratory rate was modified at each step to maintain arterial Pco2 at 50 mm Hg. MEASUREMENTS AND MAIN RESULTS: Increasing acidification enhanced CO2 removal efficiency of the membrane lung from 30 ± 5 (0 mEq/min) up to 145 ± 8 mL/min (5 mEq/min), with a 483% increase, representing the 73% ± 7% of the total body CO2 production. Minute ventilation decreased accordingly from 6.5 ± 0.7 to 1.7 ± 0.5 L/min. No major side effects occurred, except for transient tachycardia episodes. As expected from the alveolar gas equation, the natural lung Pao2 dropped at increasing acidification steps, given the high dissociation between the oxygenation and CO2 removal capability of the device, thus Pao2 decreased. CONCLUSIONS: This new extracorporeal ion-exchange resin-based multiple-organ support device proved extremely high efficiency in CO2 removal and continuous renal support in a preclinical setting. Further studies are required before clinical implementation.

Asunto(s)

Terapia de Reemplazo Renal Continuo , Animales , Dióxido de Carbono , Soluciones para Diálisis , Femenino , Humanos , Oxígeno , Respiración Artificial/métodos , Porcinos

RESUMEN

PURPOSE: Radiologic criteria for the diagnosis of primary graft dysfunction (PGD) after lung transplantation are nonspecific and can lead to misinterpretation. The primary aim of our study was to assess the interobserver agreement in the evaluation of chest X-rays (CXRs) for PGD diagnosis and to establish whether a specific training could have an impact on concordance rates. Secondary aim was to analyze causes of interobserver discordances. MATERIAL AND METHODS: We retrospectively enrolled 164 patients who received bilateral lung transplantation at our institution, between February 2013 and December 2019. Three radiologists independently reviewed postoperative CXRs and classified them as suggestive or not for PGD. Two of the Raters performed a specific training before the beginning of the study. A senior thoracic radiologist subsequently analyzed all discordant cases among the Raters with the best agreement. Statistical analysis to calculate interobserver variability was percent agreement, Cohen's kappa and intraclass correlation coefficient. RESULTS: A total of 473 CXRs were evaluated. A very high concordance among the two trained Raters, 1 and 2, was found (K = 0.90, ICC = 0.90), while a poorer agreement was found in the other two pairings (Raters 1 and 3: K = 0.34, ICC = 0.40; Raters 2 and 3: K = 0.35, ICC = 0.40). The main cause of disagreement (52.4% of discordant cases) between Raters 1 and 2 was the overestimation of peribronchial thickening in the absence of unequivocal bilateral lung opacities or the incorrect assessment of unilateral alterations. CONCLUSION: To properly identify PGD, it is recommended for radiologists to receive an adequate specific training.

Asunto(s)

Competencia Clínica/estadística & datos numéricos , Trasplante de Pulmón , Disfunción Primaria del Injerto/diagnóstico por imagen , Radiografía/métodos , Radiólogos/educación , Adolescente , Adulto , Anciano , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto Joven

RESUMEN

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A "training sample" (March-June 2020) and a "testing sample" (September 2020-January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). "Training" and "testing" samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.