Browsing by Author "Graf, Jerónimo"
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Publication A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus(International Medical Press, 2015) Vial, Pablo; Valdivieso, Francisca; Calvo, Mario; Rioseco, María; Riquelme, Raúl; Araneda, Andrés; Tomicic, Vinko; Graf, Jerónimo; Paredes, Laura; Fiorenzano, Matías; Bidart, Teresa; Cuiza, Analía; Marco, Claudia; Hjelle, Brian; Ye, Chunyan; Hanfelt-Goade, Daniel; Vial, Cecilia; Rivera, Juan; Mertz, Gregory; Hantavirus Study Group in Chile; Delgado, IrisBACKGROUND: In Chile, Andes virus (ANDV) is the sole aetiological agent of hantavirus cardiopulmonary syndrome (HCPS) with mean annual incidence of 55 cases, 32% case fatality rate (CFR) and no specific treatment. Neutralizing antibody (NAb) titres at hospital admission correlate inversely with HCPS severity. We designed an open trial to explore safety and efficacy and evaluate pharmacokinetics of immune plasma as a treatment strategy for this disease. METHODS: We performed plasmapheresis on donors at least 6 months after HCPS and measured NAb titres through a focus-reduction neutralization test. Subjects admitted to 10 study sites with suspected/confirmed HCPS were eligible for treatment with immune plasma by intravenous infusion at an ANDV NAb dose of 5,000 U/kg. HCPS was confirmed through immunoglobulin M serology or reverse transcriptase-PCR. The main outcome was mortality within 30 days. RESULTS: From 2008-2012, we enrolled and treated 32 cases and confirmed HCPS in 29. CFR of hantavirus plasma-treated cases was 4/29 (14%); CFR of non-treated cases in the same period in Chile was 63/199 (32%; P=0.049, OR=0.35, CI=0.12, 0.99); CFR of non-treated cases at the same study sites between 2005-2012 was 18/66 (27%; (P=0.15, OR=0.43, CI=0.14, 1.34) and CFR in a previous methylprednisolone treatment study was 20/60 (33%; P=0.052, OR=0.32, CI=0.10, 1.00). We detected no serious adverse events associated to plasma infusion. Plasma NAb titres reached in recipients were variable and viral load remained stable. CONCLUSIONS: Human ANDV immune plasma infusion appears safe for HCPS. We observed a decrease in CFR in treated cases with borderline significance that will require further studies for confirmation.Publication Continuous prolonged prone positioning in COVID‑19‑related ARDS: a multicenter cohort study from Chile(2022) Cornejo, Rodrigo; Montoya, Jorge; Gajardo, Abraham; Graf, Jerónimo; Alegría, Leyla; Baghetti, Romyna; Irarrázaval, Anita; Santis, César; Pavez, Nicolás; Leighton, Sofía; Tomicic, Vinko; Morales, Daniel; Ruiz, Carolina; Navarrete, Pablo; Vargas, Patricio; Gálvez, Roberto; Espinosa, Victoria; Lazo, Marioli; Pérez Araos, Rodrigo; Garay, Osvaldo; Sepúlveda, Patrick; Martínez, Edgardo; Bruhn, Alejandro; SOCHIMI Prone-COVID-19 GroupBackground: Prone positioning is currently applied in time-limited daily sessions up to 24 h which determines that most patients require several sessions. Although longer prone sessions have been reported, there is scarce evidence about the feasibility and safety of such approach. We analyzed feasibility and safety of a continuous prolonged prone positioning strategy implemented nationwide, in a large cohort of COVID-19 patients in Chile. Methods: Retrospective cohort study of mechanically ventilated COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS), conducted in 15 Intensive Care Units, which adhered to a national protocol of continuous prone sessions ≥ 48 h and until PaO2:FiO2 increased above 200 mm Hg. The number and extension of prone sessions were registered, along with relevant physiologic data and adverse events related to prone positioning. The cohort was stratified according to the first prone session duration: Group A, 2-3 days; Group B, 4-5 days; and Group C, > 5 days. Multivariable regression analyses were performed to assess whether the duration of prone sessions could impact safety. Results: We included 417 patients who required a first prone session of 4 (3-5) days, of whom 318 (76.3%) received only one session. During the first prone session the main adverse event was grade 1-2 pressure sores in 97 (23.9%) patients; severe adverse events were infrequent with 17 non-scheduled extubations (4.2%). 90-day mortality was 36.2%. Ninety-eight patients (24%) were classified as group C; they exhibited a more severe ARDS at baseline, as reflected by lower PaO2:FiO2 ratio and higher ventilatory ratio, and had a higher rate of pressure sores (44%) and higher 90-day mortality (48%). However, after adjustment for severity and several relevant confounders, prone session duration was not associated with mortality or pressure sores. Conclusions: Nationwide implementation of a continuous prolonged prone positioning strategy for COVID-19 ARDS patients was feasible. Minor pressure sores were frequent but within the ranges previously described, while severe adverse events were infrequent. The duration of prone session did not have an adverse effect on safety.Item Extracorporeal Membrane Oxygenation for COVID-19–associated Severe Acute Respiratory Distress Syndrome in Chile(2021) Díaz, Rodrigo A.; Graf, Jerónimo; Zambrano, José M.; Ruiz, Carolina; Espinoza, Juan A.; Bravo, Sebastián I.; Salazar, Pablo A.; Bahamondes, Juan C.; Castillo, Luis B.; Gajardo, Abraham I.J.; Kursbaum, Andrés; Ferreira, Leonila L.; Valenzuela, Josefa; Castillo, Roberto E.; Pérez-Araos, Rodrigo; Bravo, Marcela; Aquevedo, Andrés F.; González, Mauricio G.; Pereira, Rodrigo; Ortega, Leandro; Santis, Cesar; Fernández, Paula A.; Cortés, Vilma; Cornejo, Rodrigo A.Rationale: The role of and needs for extracorporeal membrane oxygenation (ECMO) at a population level during the coronavirus disease (COVID-19) pandemic have not been completely established. Objectives: To identify the cumulative incidence of ECMO use in the first pandemic wave and to describe the Nationwide Chilean cohort of ECMO-supported patients with COVID-19. Methods: We conducted a population-based study from March 3 to August 31, 2020, using linked data from national agencies. The cumulative incidence of ECMO use and mortality risk of ECMO-supported patients were calculated and age standardized. In addition, a retrospective cohort analysis was performed. Outcomes were 90-day mortality after ECMO initiation, ECMO-associated complications, and hospital length of stay. Cox regression models were used to explore risk factors for mortality in a time-to-event analysis. Measurements and Main Results: Ninety-four patients with COVID-19 were supported with ECMO (0.42 per population of 100,000, 14.89 per 100,000 positive cases, and 1.2% of intubated patients with COVID-19); 85 were included in the cohort analysis, and the median age was 48 (interquartile range [IQR], 41-55) years, 83.5% were men, and 42.4% had obesity. The median number of pre-ECMO intubation days was 4 (IQR, 2-7), the median PaO2/FiO2 ratio was 86.8 (IQR, 64-99) mm Hg, 91.8% of patients were prone positioned, and 14 patients had refractory respiratory acidosis. Main complications were infections (70.6%), bleeding (38.8%), and thromboembolism (22.4%); 52 patients were discharged home, and 33 died. The hospital length of stay was a median of 50 (IQR, 24-69) days. Lower respiratory system compliance and higher driving pressure before ECMO initiation were associated with increased mortality. A duration of pre-ECMO intubation ≥10 days was not associated with mortality. Conclusions: Documenting nationwide ECMO needs may help in planning ECMO provision for future COVID-19 pandemic waves. The 90-day mortality of the Chilean cohort of ECMO-supported patients with COVID-19 (38.8%) is comparable to that of previous reports.Publication Increased respiratory dead space could associate with coagulation activation and poor outcomes in COVID-19 ARDS(2022) Graf, Jerónimo; Pérez, Rodrigo; López, RenéPurpose: To determine whether VDPhys/VT is associated with coagulation activation and outcomes. Materials and methods: We enrolled patients with COVID-19 pneumonia who were supported by invasive mechanical ventilation and were monitored using volumetric capnography. Measurements were performed during the first 24 h of mechanical ventilation. The primary endpoint was the likelihood of being discharge alive on day 28. Results: Sixty patients were enrolled, of which 25 (42%) had high VDPhys/VT (>57%). Patients with high vs. low VDPhys/VT had higher APACHE II (10[8-13] vs. 8[6-9] points, p = 0.002), lower static compliance of the respiratory system (35[24-46] mL/cmH2O vs. 42[37-45] mL/cmH2O, p = 0.005), and higher D-dimer levels (1246[1050-1594] ng FEU/mL vs. 792[538-1159] ng FEU/mL, p = 0.001), without differences in P/F ratio (157[112-226] vs. 168[136-226], p = 0.719). Additionally, D-dimer levels correlated with VDPhys/VT (r = 0.530, p < 0.001), but not with the P/F ratio (r = -0.103, p = 0.433). Patients with high VDPhys/VT were less likely to be discharged alive on day 28 (32% vs. 71%, aHR = 3.393[1.161-9.915], p = 0.026). Conclusions: In critically ill COVID-19 patients, increased VDPhys/VT was associated with high D-dimer levels and a lower likelihood of being discharged alive. Dichotomic VDPhys/VT could help identify a high-risk subgroup of patients neglected by the P/F ratio.Item Outcomes of Sepsis and Septic Shock in Cancer Patients: Focus on Lactate(2021) López, René; Pérez-Araos, Rodrigo; Baus, Fernanda; Moscoso, Camila; Salazar, Álvaro; Graf, Jerónimo; Montes, José Miguel; Samtani, SurajThe number of oncological patients (OP) admitted to intensive care units (ICU) for sepsis/septic shock has dramatically increased in recent years. The definition of septic shock has been modified, adding hyperlactatemia as a severity biomarker for mortality. However, it remains poorly reported in septic OP. We performed a retrospective analysis from a prospective database of sepsis/septic shock patients admitted to our ICU between September 2017 and September 2019 and followed until day 90. We identified 251 patients and 31.9% had active oncological comorbidity, mainly solid tumor (81.3%). Septic shock criteria were met for 112 (44.6%). Hyperlactatemia was observed in 136 (54.2%) patients and this was associated with a lower survival rate. Overall 90-day mortality was 15.1%. In OP vs. non-OP, hyperlactatemia was more frequent (65% vs. 49.1%, p = 0.013) and associated with lower survival (65.4% vs. 85.7%, p = 0.046). In OP, poor performance status was also associated with lower survival (HR 7.029 [1.998–24.731], p = 0.002) In an adjusted analysis, cancer was associated with lower 90-day survival (HR 2.690 [1.402–5.160], p = 0.003). In conclusion, septic OP remains a high mortality risk group in whom lactate levels and performance status could help with better risk stratification.Item Platelet Count in Patients with Mild Disease at Admission is Associated with Progression to Severe Hantavirus Cardiopulmonary Syndrome(2019) López, René; Vial, Cecilia; Graf, Jerónimo; Calvo, Mario; Ferrés, Marcela; Mertz, Gregory; Cuiza, Analía; Agüero, Begonia; Aguilera, Dante; Araya, Diego; Pailamilla, Ignacia; Paratori, Flavia; Torres-Torres, Víctor; Vial, Pablo; HantavirusStudy Group in ChileBACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) has a mortality up to 35-40% and its treatment is mainly supportive. A variable to predict progression from mild to severe disease is unavailable. This study was performed in patients with documented infection by Andes orthohantavirus, and the aim was to find a simple variable to predict progression to moderate/severe HCPS in patients with mild disease at admission. METHODS: We performed a retrospective analysis of 175 patients between 2001 and 2018. Patients were categorized into mild, moderate, and severe disease according to organ failure and advanced support need at hospital admission (e.g., mechanical ventilation, vasopressors). Progression to moderate/severe disease was defined accordingly. Clinical and laboratory variables associated with progression were explored. RESULTS: Forty patients with mild disease were identified; 14 of them progressed to moderate/severe disease. Only platelet count was different between those who progressed versus those that did not (37 (34-58) vs. 83 (64-177) K/mm3, p < 0.001). A ROC curve analysis showed an AUC = 0.889 (0.78-1.0) p < 0.001, with a platelet count greater than 115K /mm3 ruling out progression to moderate/severe disease. CONCLUSIONS: In patients with mild disease at presentation, platelet count could help to define priority of evacuation to tertiary care centers.Item Proteinuria in Hantavirus Cardiopulmonary Syndrome: A Frequent Finding Linked To Mortality(2021) López, René; Espinoza, Mauricio; Graf, Jerónimo; Mertz, Gregory; Ferrés, Marcela; Calvo, Mario; Vial, Cecilia; Vial, Pablo; Hantavirus Study Group in ChileObjectives: To determine the relative frequency and prognosis value of proteinuria in hantavirus cardiopulmonary syndrome (HCPS) due to Andes virus. Methods: This observational analytical study prospectively obtained data from patients admitted to 12 health centers in nine Chilean cities between 2001 and 2018. Only patients with confirmed Andes virus HCPS and laboratory characterization that included qualitative proteinuria determination at admission were considered. Results: The database involved 175 patients, 95 of them had a measurement of urine protein at the time of hospital admission. They were mainly male (71%) and the median age was 35 [22-47] years. Median duration of the febrile prodromal time was 5 [4-7] days. Hospital length of stay and hospital mortality rate were 10 [7-14] days and 21.1%, respectively. Seventy-three patients (77%) were identified with proteinuria at admission, which was associated with increased mortality rate (26% versus 5%, p=0.036) and the relative risk was 1.3 [1.1-1.6], p=0.002. Conclusions: Proteinuria is a frequent finding in patients with HCPS, which is associated with a higher mortality rate.Item Respiratory Support Adjustments and Monitoring of Mechanically Ventilated Patients Performing Early Mobilization: A Scoping Review(2021) González, Felipe; Camus, Agustín; Jasmén, Anita; Molina, Jorge; Pérez-Araos, Rodrigo; Graf, JerónimoThis scoping review is aimed to summarize current knowledge on respiratory support adjustments and monitoring of metabolic and respiratory variables in mechanically ventilated adult patients performing early mobilization. Data sources: Eight electronic databases were searched from inception to February 2021, using a predefined search strategy. Study selection: Two blinded reviewers performed document selection by title, abstract, and full text according to the following criteria: mechanically ventilated adult patients performing any mobilization intervention, respiratory support adjustments, and/or monitoring of metabolic/respiratory real-time variables. Data extraction: Four physiotherapists extracted relevant information using a prespecified template.Item Settings and monitoring of mechanical ventilation during physical therapy in adult critically ill patients: protocol for a scoping review(2019) González-Seguel, Felipe; Camus-Molina, Agustín; Jasmén, Anita; Pérez-Araos, Rodrigo; Molina, Jorge; Graf, JerónimoIntroduction Early mobilisation has been extensively advocated to improve functional outcomes in critically ill patients, even though consistent evidence of its benefits has remained elusive. These conflicting results could be explained by a lack of knowledge on the optimal dosage of physical therapy and a mismatch between ventilatory support and exercise-induced patient ventilatory demand. Modern mechanical ventilators provide realtime monitoring of respiratory/metabolic variables and ventilatory setting that could be used for physical therapy dosage or ventilatory support titration, allowing individualised interventions in these patients. The aim of this review is to comprehensively map and summarise current knowledge on adjustments of respiratory support and respiratory or metabolic monitoring during physical therapy in adult critically ill mechanically ventilated patients. Methods and analysis This is a scoping review protocol based on the methodology of the Joanna-Briggs-Institute. The search strategy will be conducted from inception to 30 June 2019 as a cut-off date in PubMed, CINAHL, Rehabilitation & Sport Medicine, Scielo Citation Index, Epistemónikos, Clinical Trials, PEDro and Cochrane Library, performed by a biomedical librarian and two critical care physiotherapists. All types of articles will be selected, including conference abstracts, clinical practice guidelines and expert recommendations. Bibliometric variables, patient characteristics, physical therapy interventions, ventilator settings and respiratory or metabolic monitoring will be extracted. The identified literature will be analysed by four critical care physiotherapists and reviewed by a senior critical care physician. Ethics and dissemination Ethical approval is not required. The knowledge-translation of the results will be carried out based on the End-of-Grant strategies: diffusion, issemination and application. The results will be published in a peer-review journal, presentations will be disseminated in relevant congresses, and recommendations based on the results will be developed through training for mechanical ventilation and physical therapy takeholders.Item Targeted high volume hemofiltration could avoid extracorporeal membrane oxygenation in some patients with severe Hantavirus cardiopulmonary syndrome(2021) López, René; Pérez-Araos, Rodrigo; Salazar, Álvaro; Espinoza, Mauricio; Vial, Cecilia; Graf, Jerónimo; Cuiza, Analia; Vial, PabloBackground: Hantavirus cardiopulmonary syndrome (HCPS) has a high lethality. Severe cases may be rescued by venoarterial extracorporeal membrane oxygenation (VA ECMO), alongside substantial complications. High volume hemofiltration (HVHF) is a depurative technique that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients. Methods: We implemented HVHF before VA ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF-responders if VA ECMO was avoided and HVHF-nonresponders if VA ECMO support was needed despite HVHF. A targeted-HVHF strategy compounded by aggressive hyperoncotic albumin, sodium bicarbonate, and calcium supplementation plus ultrafiltration to avoid fluid overload was implemented on three patients. Results: Patients had maximum serum lactate of 8.8 (8.7-12.8) mmol/L and a lowest cardiac index of 1.8 (1.8-1.9) L/min/m2 . The first two required VA ECMO. They were connected later to HVHF, displayed progressive tachycardia and declining stroke volume. The opposite was true for HVHF-responders who received targeted-HVHF. All patients survived, but one of the VA ECMO patients suffered a vascular complication. Conclusion: HVHF may contribute to support severe HCPS patients avoiding the need for VA ECMO in some. Early connection and targeted-HVHF may increase the chance of success.Publication Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study(2024) Ferrés, Marcela; Martínez, Constanza; Henriquez, Carolina; Marco, Claudia; Barrera, Aldo; Palma, Carlos; Barriga, Gonzalo; Cuiza, Analia; Ferreira, Leonila; Rioseco, María; Calvo, Mario; Fritz, Ricardo; Bravo, Sebastián; Bruhn, Alejandro; Graf, Jerónimo; Llancaqueo, Alvaro; Rivera, Gonzalo; Cerda, Carolina; Tischler, Nicole; Valdivieso, Francisca; Vial, Pablo; Mertz, Gregory; Vial Cox, María Cecilia; Le Corre, NicoleBackground: Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. Methods: In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. Findings: ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23-29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re-culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 2·58 [95% CI 1·42-5·18]). Interpretation: ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person-to-person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. Funding: National Institutes of Health and Agencia de Investigación y Desarrollo.