Evaluation of the discrimination and calibration of predictive scores of mortality in ECMO for patients with COVID-19.

BACKGROUND: The criteria for the selection of COVID-19 patients that could benefit most from ECMO organ support are yet to be defined. In this study, we evaluated the predictive performance of ECMO mortality predictive models in patients with COVID-19. We also performed a cost-benefit analysis depending on the mortality predicted probability. We conducted a retrospective cohort study in COVID-19 patients who received ECMO at two tertiary care hospitals between March 2020 to July 2021. MATERIALS AND METHODS: We evaluated the discrimination (C-statistic), calibration (Cox calibration), and accuracy of the prediction of death due to severe ARDS in V-V ECMO score (PRESERVE), the Respiratory Extracorporeal Membrane Oxygenation Survival Score (RESP) score, and the PREdiction of Survival on ECMO Therapy-Score (PRESET) score. In addition, we compared the RESP score with Plateau pressure instead of Peak pressure. RESULTS: We included a total of 36 patients, 29 (80%) of them male and with a median (IQR) APACHE of 10 (8-15). The PRESET score had the highest discrimination (AUROCs 0.81 [95%CI 0.67-0.94]) and calibration (calibration-in-the-large 0.5 [95%CI -1.4 to 0.3]; calibration slope 2.2 [95%CI 0.7/3.7]). The RESP score with Plateau pressure had higher discrimination than the conventional RESP score. The cost per QALY in the USA, adjusted to life expectancy, was higher than USD 100 000 in patients older than 45 years with a PRESET > 10. CONCLUSION: The PRESET score had the highest predictive performance and could help in the selection of patients that benefit most from this resource-demanding and highly invasive organ support.

High- Versus Low-Dose Dexamethasone for the Treatment of COVID-19-Related Acute Respiratory Distress Syndrome: A Multicenter, Randomized Open-Label Clinical Trial.

OBJECTIVE: To determine whether high-dose dexamethasone increases the number of ventilator-free days (VFD) among patients with acute respiratory distress syndrome (ARDS) caused by COVID-19. DESIGN: Multicenter, randomized, open-label, clinical trial. PARTICIPANTS: Consecutive patients with confirmed COVID-19-related ARDS were enrolled from June 17, 2020, to March 27, 2021, in four intensive care units (ICUs) in Argentina. INTERVENTION: 16 mg of dexamethasone intravenously daily for five days followed by 8 mg of dexamethasone daily for five days or 6 mg of dexamethasone intravenously daily for 10 days. MAIN OUTCOME AND MEASURES: The primary outcome was ventilator-free days during the first 28 days. The secondary outcomes were all-cause mortality at 28 and 90 days, infection rate, muscle weakness, and glycemic control in the first 28 days. RESULTS: Data from 98 patients who received at least one dose of dexamethasone were analyzed. The trial was prematurely terminated due to low enrollment rate. At 28 days after randomization, there was no difference between high- and low-dose dexamethasone groups in VFD (median, 0 [interquartile range [IQR] 0-14] vs. 0 [IQR 0-1] days; P = .231), or in the mean duration of mechanical ventilation (19 ± 18 vs. 25 ± 22 days; P = .078). The cumulative hazard of successful discontinuation from mechanical ventilation was increased by the high-dose treatment (adjusted sub-distribution hazard ratio: 1.84; 95% CI: 1.31 to 2.5; P < .001). None of the prespecified secondary and safety outcomes showed a significant difference between treatment arms. CONCLUSIONS: Among patients with ARDS due to COVID-19, the use of higher doses of dexamethasone compared with the recommended low-dose treatment did not show an increase in VFD. However, the higher dose significantly improved the time required to liberate them from the ventilator.

Sensitivity and specificity of a quick sequential [Sepsis-Related] organ failure assessment sepsis screening tool.

AIM: There is limited evidence on the diagnostic accuracy of a quick Sequential [Sepsis-Related] Organ Failure Assessment (qSOFA) sepsis screening (SS) tool in developing nation health settings. The aim of this study was to test the diagnostic accuracy of a qSOFA-based SS tool, and the predictive validity of the qSOFA score in hospital ward patients from Argentina. METHODS: Prospective observational study. Patients (≥18 years, without sepsis) were recruited within 24-48 hours of admission to a 169-bed tertiary referral private hospital in Buenos Aires. The index test was the qSOFA-based SS tool, and the reference standard sepsis diagnosed at discharge blindly evaluated with reference to the Sepsis-3. RESULTS: In 1151 patients (median age 69.9 [IQR, 29.0]); 47 (4.1%) had sepsis, 413 (35.9%) had infection and 691 (60.0%) other diagnoses at discharge. The qSOFA-based SS tool (index test) had moderate sensitivity (60%), good specificity (89%), a very low positive (19%) and very high negative (98%) predictive value for sepsis diagnosed at discharge according to the Sepsis-3 criteria (reference standard). For the same outcome, the qSOFA score in isolation had a reasonable predictive validity area under receiver operating characteristics curve 0.77 (95% CI 0.70-0.83) P < 0.001. CONCLUSION: The qSOFA score could reasonably discriminate patients at risk of developing sepsis; qSOFA-based screening may be valuable where no screening criteria are in place.

Improving sepsis screening and care in a developing nation health setting: A description of implementation.

Evidence on sepsis screening and care in developing nations is insufficient to inform implementation practices in hospital wards. The aim of this multi-method study was to describe and evaluate the implementation of a three-step intervention (sepsis screening, alert activation, care) in five wards in Argentina in 2017. The implementation involved three stages: (1) context assessment, (2) development/participation in implementation strategies, and (3) evaluation of intervention adherence. Results were variable. The context assessment (Stage 1) demonstrated the value of education, proactivity towards care and team structures. Strategies developed (Stage 2) included sepsis screening and response guide, education, team rounding, posters, champions, audit/feedback and knowledge brokering. In Stage 3, staff screened 92% patients (506/547) for sepsis at ≥60% of set times; only 33% (21/64) patients had a sepsis alert activated when needed. A similar proportion of patients who had alerts activated (n = 16, 76%) or not (n = 32, 74%) received at least one element of care. The use of implementation strategies resulted in adherence to some aspects of the intervention. Future research is needed to improve sepsis screening and alert activation and care in this setting.

Implementing a quick Sequential (Sepsis-Related) Organ Failure Assessment sepsis screening tool: an interrupted times series study.

OBJECTIVE: The aim of this study was to evaluate the outcomes of implementing a sepsis screening (SS) tool based on the quick Sequential [Sepsis-Related] Organ Failure Assessment (qSOFA) and the presence of confirmed/suspected infection. The implementation of the 6-h bundle was also evaluated. DESIGN: Interrupted times series with prospective data collection. SETTING: Five hospital wards in a developing nation, Argentina. PARTICIPANTS: A total of 1151 patients (≥18 years) recruited within 24-48 h of hospital admission. INTERVENTION: The qSOFA-based SS tool and the 6-h bundle. MAIN OUTCOME MEASURES: The primary outcome was the timing of implementation of the first 6-h bundle element. Secondary outcomes were related to the adherence to the screening procedures. RESULTS: Of 1151 patients, 145 (12.6%) met the qSOFA-based SS tool criteria, among them intervention (39/64) patients received the first 6-h bundle element earlier (median 8 h; 95% confidence interval (CI): 0.1-16) than baseline (48/81) patients (median 22 h; 95% CI: 3-41); these times, however, did not differ significantly (P = 0.525). Overall, 47 (4.1%) patients had sepsis; intervention patients (18/25) received the first 6-h bundle element sooner (median 5 h; 95% CI: 4-6) than baseline patients (15/22) did (median 12 h; 95% CI: 0-33); however, times were not significantly different (P = 0.470). While intervention patients were screened regularly, only one-third of patients who required sepsis alerts had them activated. CONCLUSION: The implementation of the qSOFA-based SS tool resulted in early, but not significantly improved, provision of 6-h bundle care. Screening procedures were regularly conducted, but sepsis alerts rarely activated. Further research is needed to better understand the implementation of sepsis care in developing settings.

Health inequities in the diagnosis and outcome of sepsis in Argentina: a prospective cohort study.

BACKGROUND: Socioeconomic variables impact health outcomes but have rarely been evaluated in critical illness. Low- and middle-income countries bear the highest burden of sepsis and also have significant health inequities. In Argentina, public hospitals serve the poorest segment of the population, while private institutions serve patients with health coverage. Our objective was to analyze differences in mortality between public and private hospitals, using Sepsis-3 definitions. METHODS: This is a multicenter, prospective cohort study including patients with sepsis admitted to 49 Argentine ICUs lasting 3 months, beginning on July 1, 2016. Epidemiological, clinical, and socioeconomic status variables and hospital characteristics were compared between patients admitted to both types of institutions. RESULTS: Of the 809 patients included, 367 (45%) and 442 (55%) were admitted to public and private hospitals, respectively. Those in public institutions were younger (56 ± 18 vs. 64 ± 18; p < 0.01), with more comorbidities (Charlson score 2 [0-4] vs. 1 [0-3]; p < 0.01), fewer education years (7 [7-12] vs. 12 [10-16]; p < 0.01), more frequently unemployed/informally employed (30% vs. 7%; p < 0.01), had similar previous self-rated health status (70 [50-90] vs. 70 [50-90] points; p = 0.30), longer pre-admission symptoms (48 [24-96] vs. 24 [12-48] h; p < 0.01), had been previously evaluated more frequently in any healthcare venue (28 vs. 20%; p < 0.01), and had higher APACHE II, SOFA, lactate levels, and mechanical ventilation utilization. ICU admission as septic shock was more frequent in patients admitted to public hospitals (47 vs. 35%; p < 0.01), as were infections caused by multiresistant microorganisms. Sepsis management in the ICU showed no differences. Twenty-eight-day mortality was higher in public hospitals (42% vs. 24%; p < 0.01) as was hospital mortality (47% vs. 30%; p < 0.01). Admission to a public hospital was an independent predictor of mortality together with comorbidities, lactate, SOFA, and mechanical ventilation; in an alternative prediction model, it acted as a correlate of pre-hospital symptom duration and infections caused by multiresistant microorganisms. CONCLUSIONS: Patients in public hospitals belonged to a socially disadvantaged group and were sicker at admission, had septic shock more frequently, and had higher mortality. Unawareness of disease severity and delays in the health system might be associated with late admission. This marked difference in outcome between patients served by public and private institutions constitutes a state of health inequity.

Predictive Validity of Sepsis-3 Definitions and Sepsis Outcomes in Critically Ill Patients: A Cohort Study in 49 ICUs in Argentina.

OBJECTIVES: The new Sepsis-3 definitions have been scarcely assessed in low- and middle-income countries; besides, regional information of sepsis outcomes is sparse. Our objective was to evaluate Sepsis-3 definition performance in Argentina. DESIGN: Cohort study of 3-month duration beginning on July 1, 2016. SETTINGS: Forty-nine ICUs. PATIENTS: Consecutive patients admitted to the ICU with suspected infection that triggered blood cultures and antibiotic administration. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified as having infection, sepsis (infection + change in Sequential Organ Failure Assessment ≥ 2 points), and septic shock (vasopressors + lactate > 2 mmol/L). Patients on vasopressors and lactate less than or equal to 2 mmol/L (cardiovascular dysfunction) were analyzed separately, as those on vasopressors without serum lactate measurement. Systemic inflammatory response syndrome was also recorded. Main outcome was hospital mortality. Of 809 patients, 6% had infection, 29% sepsis, 20% cardiovascular dysfunction, 40% septic shock, and 3% received vasopressors with lactate unmeasured. Hospital mortality was 13%, 20%, 39%, 51%, and 41%, respectively (p = 0.000). Independent predictors of outcome were lactate, Sequential Organ Failure Assessment score, comorbidities, prior duration of symptoms (hr), mechanical ventilation requirement, and infection by highly resistant microorganisms. Area under the receiver operating characteristic curves for mortality for systemic inflammatory response syndrome and Sequential Organ Failure Assessment were 0.53 (0.48-0.55) and 0.74 (0.69-0.77), respectively (p = 0.000). CONCLUSIONS: Increasing severity of Sepsis-3 categories adequately tracks mortality; cardiovascular dysfunction subgroup, not included in Sepsis-3, has distinct characteristics. Sequential Organ Failure Assessment score shows adequate prognosis accuracy-contrary to systemic inflammatory response syndrome. This study supports the predictive validity of Sepsis-3 definitions.

[Building a private high-volume center for pancreatic resection]. / Creación de un centro privado de alto volumen en cirugía pancreática.

INTRODUCTION: There is considerable evidence on the direct relationship between higher volume and lower mortality in the pancreatoduodenectomy (DPC). However, there is little evidence of morbidity and mortality in the process of building a high-volume pancreatic surgery center. Objective. To evaluate the morbidity and mortality of the DPC in the process of building a high-volume center for pancreatic resection. METHODS: All consecutive patients undergoing DPC from July 2007 through July 2009 at a single center were included. High volume center was defined as that doing more than 19 DPC per year and high volume surgeon as that doing 16 or more DPC per year. The analysis of data was carried out in two periods according to the number of DPC per year: the first (1998 to 2005) as low volume center and the second (2006 to 2012) as high volume center. RESULTS: Three hundred and thirty five DPC were conducted consecutively. All surgeries were performed by a high volume surgeon. One hundred and seven patients were operated in the first period and 228 in the second period. There were no significant differences in morbidity and mortality between the both periods. In the second period there were significantly less operative time and minor length ofstay. CONCLUSIONS: High volume surgeons in pancreatic surgery can transfer their experience to the creation of a high volume pancreatic surgery center without sacrificing the morbidity and mortality.

[ROX index, high-flow oxygen therapy and COVID-19 pneumonia]. / índice ROX, oxigenoterapia de alto flujo y neumonía por COVID-19.

INTRODUCTION: The objective was to evaluate the predictive value of the ROX index and describe the evolution of a population of patients admitted to intensive care for COVID-19 pneumonia who required high-flow oxygen therapy. METHODS: Retrospective cohort study in patients older than 18 years with a positive nasopharyngeal swab for SARS-COV-2 who were admitted to intensive care unit with acute respiratory failure and required high-flow oxygen therapy for > 2 hours. RESULTS: Of a total of 97 patients, 42 (43.3%) responded satisfactorily to treatment with high-flow nasal cannula (HFNC) and 55 (56.7%) failed treatment, requiring orotracheal intubation and invasive ventilatory support. Of the 55 patients who failed, 11 (20%) survived and 44 (80%) died during intensive care admission (p < 0.001). No patient who responded satisfactorily to HFNC treatment died during hospitalization. The ROC analysis identified the 12-hour ROX index as the best predictor of failure with an area under the curve of 0.75 (0.64-0.85) and a cut-off point of 6.23 as the best predictor of intubation [Sensitivity 0.85 (95% CI 0.70-0.94), Specificity 0.55 (95% CI 0.39-0.70)]. DISCUSSION: In patients with acute respiratory failure secondary to COVID-19 pneumonia treated with highflow oxygen therapy, the ROX index was a good predictor of success.

Introducción: El objetivo fue evaluar el valor predictivo del índice ROX (Ratio of Oxygen Saturation) y describir la evolución de una población de pacientes ingresados en cuidados intensivos por neumonía por COVID-19 que requirieron oxigenoterapia a alto flujo. Métodos: Estudio de cohorte retrospectivo en pacientes mayores de 18 años con hisopado nasofaríngeo positivo para SARS-CoV-2 que ingresaron a cuidados intensivos con insuficiencia respiratoria aguda y requirieron oxigenoterapia con alto flujo por > 2 h. Resultados: De un total de 97 pacientes 42 (43.3%) respondieron satisfactoriamente al tratamiento con cánula nasal de alto flujo (CNAF) y 55 (56.7%) fracasaron al tratamiento requiriendo intubación orotraqueal y soporte ventilatorio invasivo. De los 55 pacientes que fracasaron, 11 (20%) sobrevivieron y 44 (80%) fallecieron durante su internación en cuidados intensivos (p < 0.001). Ningún paciente que respondió satisfactoriamente al tratamiento con CNAF falleció durante su internación. El análisis ROC identificó el índice de ROX de las 12 horas como el mejor predictor de fracaso con un área bajo la curva de 0.75 (0.64-0.85) y un punto de corte de 6.23 como mejor predictor de intubación [sensibilidad 0.85 (IC 95% 0.70-0.94), especificidad 0.55 (IC 95% 0.39-0.70)]. Discusión: En pacientes con insuficiencia respiratoria aguda secundaria a neumonía por COVID-19 tratados con oxigenoterapia a alto flujo, el índice de ROX resultó un buen predictor de éxito.

High dose dexamethasone treatment for Acute Respiratory Distress Syndrome secondary to COVID-19: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The aim of this study is to explore the effectiveness and safety of high dose dexamethasone treatment for Acute Respiratory Distress Syndrome secondary to SARS-Cov-2 pneumonia. TRIAL DESIGN: Multicentre, randomized clinical trial, controlled, open label, parallel group, to evaluate the effectiveness and safety of high dose dexamethasone in adult patients with confirmed COVID-19, with Acute Respiratory Distress Syndrome. PARTICIPANTS: We will include patients with SARS-Cov-2 pneumonia who develop acute respiratory distress syndrome, in several intensive care units (ICU) in Buenos Aires, Argentina (CEMIC, Clinica Bazterrica, Sanatorio Sagrado Corazon) Inclusion criteria: Men and women, age ≥ 18 years old. Confirmed diagnosis of SARS-CoV-2 infection, by RT-PCR. Diagnosis of Acute Respiratory Distress Syndrome (hypoxemic respiratory failure not explained by cardiac disease + PaO2/FiO2 ratio < 300 with a Positive End-Expiratory Pressure ≥ 5 cm H2O + bilateral pulmonary infiltrates) Length of mechanical ventilation of at least 72 hours Informed consent (next of kin / legal guardian) Exclusion criteria: Pregnant or breast-feeding women. Terminal disease (advanced cancer; under palliative care; cardiovascular, respiratory, or renal disease with a life expectancy less ≤ 1 year). Therapeutic limitation (advance directives or do not resuscitate order) Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents, active cancer). Patients under chronic treatment with glucocorticoids for other diseases (≥ 8 mg prednisone, or equivalent) Participation in another randomized clinical trial. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard ICU patient care (group 1) or standard ICU patient care plus high dose dexamethasone (group 2). Group 1: dexamethasone up to 6 mg/24 hours for up to 10 days + ventilatory, hemodynamic, nutritional, and antimicrobial support according to international guidelines. Group 2: dexamethasone 16 mg/24 hours for 5 days followed by dexamethasone 8 mg/24 hours for 5 days + ventilatory, hemodynamic, nutritional, and antimicrobial support according to international guidelines. MAIN OUTCOME: The main result is ventilator-free days at 28 days (Days without ventilator support in the first 28 days following randomization). Secondary outcomes are 28-days and 90-days mortality, frequency of nosocomial infections in the first 28 days after randomization, Sequential Organ Failure Assessment (SOFA) score variation and prone position in the first 10-days, viral shedding 28-days after randomization, and delirium and muscle weakness at ICU discharge. RANDOMISATION: Treatment will be assigned according to site stratified randomization by permuted random blocks sequence 1:1 generated with a table in R language concealed in a randomization tool in REDCap (Research Electronic Data CAPture) platform. BLINDING (MASKING): This is an open trial, so no masking of treatment assignment will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Assuming a 3 days difference in ventilator-free days between treatment groups, with a mean of 9 days, and a standard deviation of 9 days; the necessary sample size would be 284 subjects (142 per group), with a power of 80% and a two-tailed alpha error of 0.05. TRIAL STATUS: The protocol with code 1264, version 3.0 on date: May 13, 2020 is approved by the local Ethics Committee. The trial is in the recruitment phase. Recruitment began May 22, 2020 and is anticipated to be complete by the end of December 2021. TRIAL REGISTRATION: The trial was registered under the title "Dexamethasone for COVID-19 Related ARDS: a Multicenter, Randomized Clinical Trial" with ClinicalTrials number NCT04395105, https://clinicaltrials.gov/ct2/show/NCT04395105 , registered on 20 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

[Convalescent plasma as a therapy for severe COVID-19 pneumonia]. / Plasma de convalecientes como terapia para la neumonía por COVID-19 grave.

The COVID-19 pandemic presented high mortality from its beginning, without effective treatment for seriously ill patients. Build on the experience in Argentine hemorrhagic fever with convalescent plasma, we incorporated 90 patients with COVID-19, of which 87 were evaluable, into a multicenter study. We collected 397 plasma donations from 278 convalescent donors. Patients received plasma with an IgG concentration of 0.7-0.8 (measured by Abbott chemiluminescence) for every 10 kg of body weight. Survival during the first 28 days was the primary objective; 77% were male, age 54 ± 15.6 y/o (range 27-85), body mass index 29.7 ± 4.4; hypertension 39% and diabetes 20.7%; 19.5% had an immunosuppressive condition, 23% were health workers. Plasma was administered to 55 (63%) on spontaneous breathing with oxygen supplementation (mainly oxygen mask with reservoir bag in 80%), and to 32 patients (37%) on mechanical ventilation. The 28-day survival rate was 80%; 91% in patients infused on spontaneous breathing and 63% in those on mechanical ventilation (p = 0.0002). There was a significant improvement in the WHO pneumonia clinical scale at 7 and 14 days, and in PaO2 / FiO2, ferritin and LDH, in the week post-infusion. We observed an episode of circulatory volume overload and a febrile reaction, both mild. Convalescent plasma infusions are feasible, safe, and potentially effective, especially before requiring mechanical ventilation. They are an attractive clinical option for treating severe forms of COVID-19 until other effective therapies become available.

La pandemia de COVID-19, presentó desde su inicio elevada mortalidad, sin tratamiento efectivo para pacientes graves. Basados en experiencia previa con plasma de convaleciente en fiebre hemorrágica Argentina, incorporamos a un estudio multicéntrico 90 pacientes con COVID-19 de los que 87 fueron evaluables. Colectamos 397 donaciones de plasma de 278 convalecientes. El plasma fue suministrado con una concentración de IgG de 0.7-0.8 (medidos por quimioluminiscencia Abbott) por cada 10 kg/ peso. La supervivencia a 28 días fue la variable de resultado primario. El 77% fueron varones, edad 54 ± 15.6 años (rango: 27-85); índice de masa corporal de 29.7 ± 4.4; tenían hipertensión 39%, diabetes 20.7%; 19.5% tenían alguna condición de inmunosupresión, y el 23% era personal de salud. Se administró plasma a 55 (63%) en respiración espontánea con oxígeno (con máscara reservorio en 80%), y a 32 (37%) en ventilación mecánica. La supervivencia global a 28 días fue del 80%; 91% en quienes recibían oxígeno suplementario y 63% en los que permanecían en ventilación mecánica (p = 0.0002). Hubo mejora significativa en la escala clínica de neumonía de la OMS a los 7 y a los 14 días. La ferritina, LDH y PaO2/FiO2, mejoraron en la semana post-infusión. Observamos un episodio de sobrecarga de volumen circulatorio y una reacción febril, leves. Las infusiones de plasma de convaleciente son factibles, seguras y potencialmente efectivas, especialmente antes de requerir ventilación mecánica. Constituyen una opción clínica atractiva para tratar formas graves de COVID-19 hasta que estén disponibles otras terapias eficaces.

Characteristics of resuscitation, and association between use of dynamic tests of fluid responsiveness and outcomes in septic patients: results of a multicenter prospective cohort study in Argentina.

BACKGROUND: Resuscitation of septic patients regarding goals, monitoring aspects and therapy is highly variable. Our aim was to characterize cardiovascular and fluid management of sepsis in Argentina, a low and middle-income country (LMIC). Furthermore, we sought to test whether the utilization of dynamic tests of fluid responsiveness, as a guide for fluid therapy after initial resuscitation in patients with persistent or recurrent hypoperfusion, was associated with decreased mortality. METHODS: Secondary analysis of a national, multicenter prospective cohort study (n = 787) fulfilling Sepsis-3 definitions. Epidemiological characteristics, hemodynamic management data, type of fluids and vasopressors administered, physiological variables denoting hypoperfusion, use of tests of fluid responsiveness, and outcomes, were registered. Independent predictors of mortality were identified with logistic regression analysis. RESULTS: Initially, 584 of 787 patients (74%) had mean arterial pressure (MAP) < 65 mm Hg and/or signs of hypoperfusion and received 30 mL/kg of fluids, mostly normal saline (53%) and Ringer lactate (35%). Vasopressors and/or inotropes were administered in 514 (65%) patients, mainly norepinephrine (100%) and dobutamine (9%); in 22%, vasopressors were administered before ending the fluid load. After this, 413 patients (53%) presented persisting or recurrent hypotension and/or hypoperfusion, which prompted administration of additional fluid, based on: lactate levels (66%), urine output (62%), heart rate (54%), central venous O2 saturation (39%), central venous-arterial PCO2 difference (38%), MAP (31%), dynamic tests of fluid responsiveness (30%), capillary-refill time (28%), mottling (26%), central venous pressure (24%), cardiac index (13%) and/or pulmonary wedge pressure (3%). Independent predictors of mortality were SOFA and Charlson scores, lactate, requirement of mechanical ventilation, and utilization of dynamic tests of fluid responsiveness. CONCLUSIONS: In this prospective observational study assessing the characteristics of resuscitation of septic patients in Argentina, a LMIC, the prevalent use of initial fluid bolus with normal saline and Ringer lactate and the use of norepinephrine as the most frequent vasopressor, reflect current worldwide practices. After initial resuscitation with 30 mL/kg of fluids and vasopressors, 413 patients developed persistent or recurrent hypoperfusion, which required further volume expansion. In this setting, the assessment of fluid responsiveness with dynamic tests to guide fluid resuscitation was independently associated with decreased mortality.

Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study.

INTRODUCTION: Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. METHODS: Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (DeltaPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. RESULTS: Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and DeltaPCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 +/- 0.7, 2.2 +/- 0.7, 2.0 +/- 0.8) and the percent of perfused capillaries (72 +/- 26, 71 +/- 27, 67 +/- 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 +/- 10,17 +/- 10,14 +/- 2 vessels/mm2, respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R2 = 0.95, P < 0.0001). CONCLUSIONS: Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.

Gastric tonometry versus cardiac index as resuscitation goals in septic shock: a multicenter, randomized, controlled trial.

INTRODUCTION: Resuscitation goals for septic shock remain controversial. Despite the normalization of systemic hemodynamic variables, tissue hypoperfusion can still persist. Indeed, lactate or oxygen venous saturation may be difficult to interpret. Our hypothesis was that a gastric intramucosal pH-guided resuscitation protocol might improve the outcome of septic shock compared with a standard approach aimed at normalizing systemic parameters such as cardiac index (CI). METHODS: The 130 septic-shock patients were randomized to two different resuscitation goals: CI >or= 3.0 L/min/m2 (CI group: 66 patients) or intramucosal pH (pHi) >or= 7.32 (pHi group: 64 patients). After correcting basic physiologic parameters, additional resuscitation consisting of more fluids and dobutamine was started if specific goals for each group had not been reached. Several clinical data were registered at baseline and during evolution. Hemodynamic data and pHi values were registered every 6 hours during the protocol. Primary end point was 28 days' mortality. RESULTS: Both groups were comparable at baseline. The most frequent sources of infection were abdominal sepsis and pneumonia. Twenty-eight day mortality (30.3 vs. 28.1%), peak Therapeutic Intervention Scoring System scores (32.6 +/- 6.5 vs. 33.2 +/- 4.7) and ICU length of stay (12.6 +/- 8.2 vs. 16 +/- 12.4 days) were comparable. A higher proportion of patients exhibited values below the specific target at baseline in the pHi group compared with the CI group (50% vs. 10.9%; P < 0.001). Of 32 patients with a pHi < 7.32 at baseline, only 7 (22%) normalized this parameter after resuscitation. Areas under the receiver operator characteristic curves to predict mortality at baseline, and at 24 and 48 hours were 0.55, 0.61, and 0.47, and 0.70, 0.90, and 0.75, for CI and pHi, respectively. CONCLUSIONS: Our study failed to demonstrate any survival benefit of using pHi compared with CI as resuscitation goal in septic-shock patients. Nevertheless, a normalization of pHi within 24 hours of resuscitation is a strong signal of therapeutic success, and in contrast, a persistent low pHi despite treatment is associated with a very bad prognosis in septic-shock patients.

Índice ROX, oxigenoterapia a alto flujo y neumonía por COVID-19 / ROX index, high-flow oxygen therapy and COVID-19 pneumonia

Resumen Introducción: El objetivo fue evaluar el valor predic tivo del índice ROX (Ratio of Oxygen Saturation) y describir la evolución de una población de pacientes ingresados en cuidados intensivos por neumonía por COVID-19 que requirieron oxigenoterapia a alto flujo. Métodos: Estudio de cohorte retrospectivo en paci entes mayores de 18 años con hisopado nasofaríngeo positivo para SARS-CoV-2 que ingresaron a cuidados intensivos con insuficiencia respiratoria aguda y requi rieron oxigenoterapia con alto flujo por > 2 h. Resultados: De un total de 97 pacientes 42 (43.3%) respondieron satisfactoriamente al tratamiento con cánula nasal de alto flujo (CNAF) y 55 (56.7%) fracasa ron al tratamiento requiriendo intubación orotraqueal y soporte ventilatorio invasivo. De los 55 pacientes que fracasaron, 11 (20%) sobrevivieron y 44 (80%) fallecier on durante su internación en cuidados intensivos (p < 0.001). Ningún paciente que respondió satisfac toriamente al tratamiento con CNAF falleció durante su internación. El análisis ROC identificó el índice de ROX de las 12 horas como el mejor predictor de fracaso con un área bajo la curva de 0.75 (0.64-0.85) y un punto de corte de 6.23 como mejor predictor de intubación [sensibilidad 0.85 (IC 95% 0.70-0.94), especificidad 0.55 (IC 95% 0.39-0.70)]. Discusión: En pacientes con insuficiencia respiratoria aguda secundaria a neumonía por COVID-19 tratados con oxigenoterapia a alto flujo, el índice de ROX resultó un buen predictor de éxito.

Abstract Introduction: The objective was to evaluate the pre dictive value of the ROX index and describe the evolu tion of a population of patients admitted to intensive care for COVID-19 pneumonia who required high-flow oxygen therapy. Methods: Retrospective cohort study in patients older than 18 years with a positive nasopharyngeal swab for SARS-COV-2 who were admitted to intensive care unit with acute respiratory failure and required high-flow oxygen therapy for > 2 hours. Results: Of a total of 97 patients, 42 (43.3%) responded satisfactorily to treatment with high-flow nasal cannula (HFNC) and 55 (56.7%) failed treatment, requiring orotra cheal intubation and invasive ventilatory support. Of the 55 patients who failed, 11 (20%) survived and 44 (80%) died during intensive care admission (p < 0.001). No patient who responded satisfactorily to HFNC treatment died during hospitalization. The ROC analysis identified the 12-hour ROX index as the best predictor of failure with an area under the curve of 0.75 (0.64-0.85) and a cut-off point of 6.23 as the best predictor of intubation [Sensitivity 0.85 (95% CI 0.70-0.94), Specificity 0.55 (95% CI 0.39-0.70)]. Discussion: In patients with acute respiratory failure secondary to COVID-19 pneumonia treated with high-flow oxygen therapy, the ROX index was a good predictor of success.

Incidence, risk factors, and outcome of ventilator-associated pneumonia.

OBJECTIVE: The purpose of this study is to determine the incidence, risk factors, and outcome of ventilator-associated pneumonia (VAP). DESIGN: Prospective cohort. SETTING: Three hundred sixty-one intensive care units (ICUs) from 20 countries. PATIENTS AND PARTICIPANTS: Two thousand eight hundred ninety-seven patients mechanically ventilated for more than 12 hours. MEASUREMENTS AND RESULTS: Baseline demographic data, primary indication for mechanical ventilation, daily ventilator settings, multiple organ failure over the course of mechanical ventilation, and outcome were collected. Ventilator-associated pneumonia was present in 439 patients (15%). Patients with VAP were more likely to have chronic pulmonary obstructive disease, aspiration, sepsis, and acute respiratory distress syndrome. Mortality in patients with VAP was 38%. Factors associated with mortality were severity of illness, limited activity before the onset of mechanical ventilation and development of shock, acute renal failure, and worsening of hypoxemia during the period of mechanical ventilation. Case-control analysis showed no increased mortality in patients with VAP (38.1% vs 37.9%, P = .95) but prolonged duration of mechanical ventilation and ICU stay. CONCLUSION: In a large cohort of mechanically ventilated patients, VAP is more likely in patients with underlying lung disease (acute or chronic). Ventilator-associated pneumonia was associated with a significant increase in ICU length of stay but no increase in mortality.

Improving quality in the intensive care unit setting.

Summarizing the mission of the ICU, the institution directive board and the unit director must generate a structure, proceedings criteria, management, and analysis of results capable of providing satisfactory care. Furthermore, they must take into account each organizational aspect that is necessary to offer an appropriate service for the patient. Medicine in general and intensive care in particular require that precautions be taken to avoid the patient and family feeling uncertain and fearful about the quality of the attention and care they receive.

Use of a dual lumen cannula for venovenous extra corporeal membrane oxygenation in a patient with acute respiratory distress syndrome and a previously inserted inferior vena cava filter: a case report.

Extracorporeal membrane oxygenation is used in refractory hypoxemia in many clinical settings. Thoracic trauma patients usually develop acute respiratory distress syndrome. Due to high risk of bleeding, thrombotic complications present in this context are particularly difficult to manage and usually require insertion of an inferior vena cava filter to prevent embolism from the distal veins to the pulmonary circulation. Here, we present a case of a thoracic trauma patient with severe acute respiratory distress syndrome requiring venovenous extracorporeal membrane oxygenation via a right internal jugular double lumen cannula due to a previously inserted inferior vena cava filter caused by distal bilateral calf muscle vein deep vein thrombosis.

Effects of high-dose of intravenous immunoglobulin and antibiotics on survival for severe sepsis undergoing surgery.

The objective of this study was to assess the impact on outcome of adjuvant therapy (high-dose of immunoglobulin [Ig] M-enriched intravenous Ig, IVIG) in intensive care unit (ICU) patients who underwent surgery by abdominal sepsis. This was a prospective, randomized, double-blind, controlled study set in the medical/surgical ICUs of seven teaching hospitals. Patients with severe sepsis and septic shock of intra-abdominal origin admitted to the ICU within 24 h after the onset of symptoms were included in the study. Polyvalent IgM-enriched Ig (Pentaglobin; IVIG group) at a dosage of 7 mL/kg/day for 5 days or an equal amount of 5% human albumin (control group) was randomized. Fifty-six patients were enrolled. The overall mortality rate was 37.5.%. Twenty patients had shock and 36 had severe sepsis (the mortality rate was 55.0% and 25.0%, respectively). In the intent-to-treat analysis, the mortality rate was reduced from 48.1% in patients treated with antibiotic (ATB) plus albumin to 27.5% (P = 0.06) for patients with ATB plus IVIG. The organ failure score (1.0 +/- 0.6 vs. 1.2 +/- 0.9), organ dysfunction score (1.7 +/- 1.1 vs. 1.8 +/- 1.0), and reoperation rate (17.2% vs. 29.6%) were not different between IVIG and control groups, respectively. Eight patients (14.3%) received inappropriate ATB initial therapy (IAT), and seven died (87.5%). IAT was the only variable independently associated with death (odds ratio, 19.4) in a logistic regression model. We conclude that IVIG administration, when used in combination with adequate antibiotics, improved the survival of surgical ICU patients with intra-abdominal sepsis. The initial choice of antibiotic has a dramatic impact on outcome.

Prognosis factors and outcome of community-acquired pneumonia needing mechanical ventilation.

PURPOSE: To evaluate the variables associated with mortality of patients with community-acquired pneumonia who require mechanical ventilation and to determine the attributable morbidity and intensive care unit (ICU) mortality of community-acquired pneumonia. MATERIAL AND METHODS: Retrospective cohort study carried out in 361 ICUs from 20 countries including 124 patients who required mechanical ventilation on the first day of admission to the hospital due to acute respiratory failure secondary to severe community-acquired pneumonia. To assess the factors associated with outcome, a forward stepwise logistic regression analysis was performed, and to determine the attributable mortality of community-acquired pneumonia, a matched study design was used. RESULTS: We found 3 independent variables significantly associated with death in patients with community-acquired pneumonia requiring mechanical ventilation: simplified acute physiological score greater than 45 (odds ratio, 5.5 [95% confidence interval, 1.7-12.3]), shock (odds ratio, 5.7 [95% confidence interval, 1.7-10.1]), and acute renal failure (odds ratio, 3.0 [95% confidence interval, 1.1-4.0]). There was no statistically significant difference in ICU mortality among patients with or without community-acquired pneumonia (32% vs 35%; P=.59). CONCLUSIONS: Community-acquired pneumonia needing mechanical ventilation is not a disease associated with higher mortality. The main determinants of patient outcome were initial severity of illness and the development of shock and/or acute renal failure.