Infection with SARS-CoV-2 variant Gamma (P.1) in Chile increased ICU admission risk three to five-fold.

The 2021 wave of SARS-CoV-2 infection in Chile was characterized by an explosive increase in ICU admissions, which disproportionately affected individuals younger than 60 years. This second wave was also accompanied by an explosive increase in Gamma (P.1) variant detections and the massive vaccine rollout. We unveil the role the Gamma variant played in stressing the use of critical care, by developing and calibrating a queueing model that uses data on new onset cases and actual ICU occupancy, symptom's onset to ICU admission interval, ICU length-of-stay, genomic surveillance, and vaccine effectiveness. Our model shows that infection with the Gamma (P.1) variant led to a 3.5-4.7-fold increase in ICU admission for people younger than 60 years. This situation occurred on top of the already reported higher infection rate of the Gamma variant. Importantly, our results also strongly suggest that the vaccines used in Chile (inactivated mostly, but also an mRNA), were able to curb Gamma variant ICU admission over infections.

Clinical characteristics, systemic complications, and in-hospital outcomes for patients with COVID-19 in Latin America. LIVEN-Covid-19 study: A prospective, multicenter, multinational, cohort study.

PURPOSE: The COVID-19 pandemic has spread worldwide, and almost 396 million people have been infected around the globe. Latin American countries have been deeply affected, and there is a lack of data in this regard. This study aims to identify the clinical characteristics, in-hospital outcomes, and factors associated with ICU admission due to COVID-19. Furthermore, to describe the functional status of patients at hospital discharge after the acute episode of COVID-19. MATERIAL AND METHODS: This was a prospective, multicenter, multinational observational cohort study of subjects admitted to 22 hospitals within Latin America. Data were collected prospectively. Descriptive statistics were used to characterize patients, and multivariate regression was carried out to identify factors associated with severe COVID-19. RESULTS: A total of 3008 patients were included in the study. A total of 64.3% of patients had severe COVID-19 and were admitted to the ICU. Patients admitted to the ICU had a higher mean (SD) 4C score (10 [3] vs. 7 [3)], p<0.001). The risk factors independently associated with progression to ICU admission were age, shortness of breath, and obesity. In-hospital mortality was 24.1%, whereas the ICU mortality rate was 35.1%. Most patients had equal self-care ability at discharge 43.8%; however, ICU patients had worse self-care ability at hospital discharge (25.7% [497/1934] vs. 3.7% [40/1074], p<0.001). CONCLUSIONS: This study confirms that patients with SARS CoV-2 in the Latin American population had a lower mortality rate than previously reported. Systemic complications are frequent in patients admitted to the ICU due to COVID-19, as previously described in high-income countries.

How far are we from predicting multi-drug interactions during treatment for COVID-19 infection?

Seriously ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hospitalized in intensive care units (ICUs) are commonly given a combination of drugs, a process known as multi-drug treatment. After extracting data on drug-drug interactions with clinical relevance from available online platforms, we hypothesize that an overall interaction map can be generated for all drugs administered. Furthermore, by combining this approach with simulations of cellular biochemical pathways, we may be able to explain the general clinical outcome. Finally, we postulate that by applying this strategy retrospectively to a cohort of patients hospitalized in ICU, a prediction of the timing of developing acute kidney injury (AKI) could be made. Whether or not this approach can be extended to other diseases is uncertain. Still, we believe it represents a valuable pharmacological insight to help improve clinical outcomes for severely ill patients.

Dexamethasone as risk-factor for ICU-acquired respiratory tract infections in severe COVID-19.

PURPOSE: Dexamethasone is the only drug that has consistently reduced mortality in patients with COVID-19, especially in patients needing oxygen or invasive mechanical ventilation. However, there is a growing concern about the relation of dexamethasone with the unprecedented rates of ICU-acquired respiratory tract infections (ICU-RTI) observed in patients with severe COVID-19. METHODS: This was a multicenter, prospective cohort study; conducted in ten countries in Latin America and Europe. We included patients older than 18 with confirmed SARS-CoV-2 requiring ICU admission. A multivariate logistic regression and propensity score matching (PSM) analysis was conducted to determine the relation between dexamethasone treatment and ICU-RTI. RESULTS: A total of 3777 patients were included. 2065 (54.7%) were treated with dexamethasone within the first 24 h of admission. After performing the PSM, patients treated with dexamethasone showed significantly higher proportions of VAP (282/1652 [17.1%] Vs. 218/1652 [13.2%], p = 0.014). Also, dexamethasone treatment was identified as an adjusted risk factor of ICU-RTI in the multivariate logistic regression model (OR 1.64; 95%CI: 1.37-1.97; p < 0.001). CONCLUSION: Patients treated with dexamethasone for severe COVID-19 had a higher risk of developing ICU-acquired respiratory tract infections after adjusting for days of invasive mechanical ventilation and ICU length of stay, suggesting a cautious use of this treatment.

Effect of positive end-expiratory pressure on lung injury and haemodynamics during experimental acute respiratory distress syndrome treated with extracorporeal membrane oxygenation and near-apnoeic ventilation.

BACKGROUND: Lung rest has been recommended during extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). Whether positive end-expiratory pressure (PEEP) confers lung protection during ECMO for severe ARDS is unclear. We compared the effects of three different PEEP levels whilst applying near-apnoeic ventilation in a model of severe ARDS treated with ECMO. METHODS: Acute respiratory distress syndrome was induced in anaesthetised adult male pigs by repeated saline lavage and injurious ventilation for 1.5 h. After ECMO was commenced, the pigs received standardised near-apnoeic ventilation for 24 h to maintain similar driving pressures and were randomly assigned to PEEP of 0, 10, or 20 cm H2O (n=7 per group). Respiratory and haemodynamic data were collected throughout the study. Histological injury was assessed by a pathologist masked to PEEP allocation. Lung oedema was estimated by wet-to-dry-weight ratio. RESULTS: All pigs developed severe ARDS. Oxygenation on ECMO improved with PEEP of 10 or 20 cm H2O, but did not in pigs allocated to PEEP of 0 cm H2O. Haemodynamic collapse refractory to norepinephrine (n=4) and early death (n=3) occurred after PEEP 20 cm H2O. The severity of lung injury was lowest after PEEP of 10 cm H2O in both dependent and non-dependent lung regions, compared with PEEP of 0 or 20 cm H2O. A higher wet-to-dry-weight ratio, indicating worse lung injury, was observed with PEEP of 0 cm H2O. Histological assessment suggested that lung injury was minimised with PEEP of 10 cm H2O. CONCLUSIONS: During near-apnoeic ventilation and ECMO in experimental severe ARDS, 10 cm H2O PEEP minimised lung injury and improved gas exchange without compromising haemodynamic stability.

[Acute kidney injury caused by rhabdomyolysis as a SARS-CoV-2 infection manifestation. Report of one case]. / Insuficiencia renal aguda secundaria a rabdomiolisis como manifestación de infección por SARS-CoV-2.

SARS-CoV-2 infection has a wide spectrum of clinical manifestations secondary to the impairment of different organs, including kidney. Rhabdomyolysis is produced by disintegration of striated muscle and the liberation of its contents to the extracellular fluid and bloodstream. This may produce hydro electrolytic disorders and acute kidney injury. We report a 35-year-old female with a history of SARS-CoV-2 infection who was hospitalized because of respiratory failure and developed renal failure. The etiologic study showed elevated total creatine kinase levels and a magnetic resonance imaging confirmed rhabdomyolysis. The patient required supportive treatment with vasoactive drugs, mechanic ventilation and kidney replacement therapy. She had a favorable evolution with resolution of respiratory failure and improvement of kidney function.

Intubation timing as determinant of outcome in patients with acute respiratory distress syndrome by SARS-CoV-2 infection.

PURPOSE: To determine whether time-to-intubation was associated with higher ICU mortality in patients with COVID-19 on mechanical ventilation due to respiratory insufficiency. MATERIALS AND METHODS: We conducted an observational, prospective, single-center study of patients with confirmed SARS-CoV-2 infection hospitalized with moderate to severe ARDS, connected to mechanical ventilation in the ICU between March 17 and July 31, 2020. We examined their general and clinical characteristics. Time-to-intubation was the time from hospital admission to endotracheal intubation. RESULTS: We included 183 consecutive patients; 28% were female, and median age was 62 years old. Eighty-eight patients (48%) were intubated before 48 h (early) and ninety-five (52%) after 48 h (late). Patients intubated early had similar admission PaO2/FiO2 ratio (123 vs 99; p = 0.179) but were younger (59 vs 64; p = 0.013) and had higher body mass index (30 vs 28; p = 0.006) compared to patients intubated late. Mortality was higher in patients intubated late (18% versus 43%), with admission PaO2/FiO2 ratio < 100 mmHg (OR 5.2; p = 0.011), of older age (OR 1.1; p = 0.001), and with previous use of ACE inhibitors (OR 4.8; p = 0.026). CONCLUSIONS: In COVID-19 patients, late intubation, Pafi <100, older age, and previous ACE inhibitors use were associated with increased ICU mortality.

Implementation of Distance-Based Simulation Training Programs for Healthcare Professionals: Breaking Barriers During COVID-19 Pandemic.

SUMMARY STATEMENT: The sudden rise of critically ill patients secondary to the SARS-CoV-2 pandemic has triggered a surge in healthcare response. This project's goal was to provide essential cognitive and technical skills to healthcare professionals returning to the workforce or reassigned to critical care clinical duties during the COVID-19 pandemic. The plan included the implementation of 4 distance-based simulation training programs, with asynchronous personalized feedback. The courses allowed the acquisition of skills for the complete critical care patient management chain: use of personal protection equipment, use of a high-flow nasal cannula, endotracheal intubation, and prone positioning. Participants logged into the platform, reviewed material, practiced while recording the session, and uploaded the video through the training platform. The expert tutor remotely delivered asynchronous feedback. Participants trained remotely until achieving course approval. Remote-based simulation seems a feasible and attractive alternative to provide adequate educational solutions, especially for remote and rural areas.

Towards an ideotype for food-fuel dual-purpose wheat in Argentina with focus on biogas production.

BACKGROUND: Wheat straw, one of the most abundant agricultural residues worldwide, can be used to produce biogas, which is considered one of the most efficiently produced renewable energies. Wheat grown with the dual-purpose of producing food and biogas should display simultaneously high grain and straw yields, low lodging susceptibility and high conversion efficiency of straw into biogas. The aims of this study were to determine the best food-fuel dual-purpose wheat candidates among 36 wheat genotypes-including French, CIMMYT and local (Criollo) germplasm-used in breeding programs in Argentina and to gain some insights into the relationships between key traits relevant for dual-purpose wheat genotypes. RESULTS: High variability in individual key traits for dual-purpose wheat ideotype has been found. Genotypes of French origin displayed the highest grain yield, and those of CIMMYT origin, the lowest straw yield. Genotypes of Criollo origin showed the highest lodging susceptibility, and French ones, the lowest. Straw yield was positively correlated with grain yield in all genotypes, and negatively correlated with plant height in genotypes of Criollo origin. Straw conversion into biogas was measured in terms of the biogas potential production and kinetic parameters Bmax (maximum specific biogas production) and k (first-order kinetic constant) were analyzed. All key traits were analyzed together by a principal component analysis. Baguette 31 and SNR Nogal, two genotypes of French origin, showed high grain yield, high-to-very high straw yield, low lodging susceptibility, and moderate-to-high Bmax and k. Buck Guapo and Buck Baqueano, two genotypes of Criollo origin, displayed good values for grain yield, straw yield and Bmax and k. However, their high lodging susceptibility precludes their production in shallow soils or high-input systems. Lastly, some old genotypes (e.g. Klein Atlas) harbored a good combination of all key traits and could prove valuable to be included in future breeding programs for dual-purpose wheat. CONCLUSIONS: While none of the genotypes excelled in every key trait, a few candidates showed potential for dual-purpose ideotype, particularly Baguette 31 and SNR Nogal. The challenge lays in gathering all attributes for food and 2G fuel in the same genotype.

Insuficiencia renal aguda secundaria a rabdomiolisis como manifestación de infección por SARS-CoV-2 / Acute kidney injury caused by rhabdomyolysis as a SARS-CoV-2 infection manifestation: report of one case

SARS-CoV-2 infection has a wide spectrum of clinical manifestations secondary to the impairment of different organs, including kidney. Rhabdomyolysis is produced by disintegration of striated muscle and the liberation of its contents to the extracellular fluid and bloodstream. This may produce hydro electrolytic disorders and acute kidney injury. We report a 35-year-old female with a history of SARS-CoV-2 infection who was hospitalized because of respiratory failure and developed renal failure. The etiologic study showed elevated total creatine kinase levels and a magnetic resonance imaging confirmed rhabdomyolysis. The patient required supportive treatment with vasoactive drugs, mechanic ventilation and kidney replacement therapy. She had a favorable evolution with resolution of respiratory failure and improvement of kidney function.

Simulation-Based Mastery Learning of Bronchoscopy-Guided Percutaneous Dilatational Tracheostomy: Competency Acquisition and Skills Transfer to a Cadaveric Model.

INTRODUCTION: Although simulation-based training has demonstrated improvement of procedural skills and clinical outcomes in different procedures, there are no published training protocols for bronchoscopy-guided percutaneous dilatational tracheostomy (BG-PDT). The objective of this study was to assess the acquisition of BG-PDT procedural competency with a simulation-based mastery learning training program, and skills transfer into cadaveric models. METHODS: Using a prospective interventional design, 8 trainees naive to the procedure were trained in a simulation-based mastery learning BG-PDT program. Students were assessed using a multimodal approach, including blind global rating scale (GRS) scores of video-recorded executions, total procedural time, and hand-motion tracking-derived parameters. The BG-PDT mastery was defined as proficient tracheostomy (successful procedural performance, with less than 3 puncture attempts, and no complications) with GRS scores higher than 21 points (of 25). After mastery was achieved in the simulator, residents performed 1 BG-PDT execution in a cadaveric model. RESULTS: Compared with baseline, in the final training session, residents presented a higher procedural proficiency (0% vs. 100%, P < 0.001), with higher GRS scores [8 (6-8) vs. 25 (24-25), P = 0.01] performed in less time [563 (408-600) vs. 246 (214-267), P = 0.01] and with higher movement economy. Procedural skills were further transferred to the cadaveric model. CONCLUSIONS: Residents successfully acquired BG-PDT procedural skills with a simulation-based mastery learning training program, and skills were effectively transferred to a cadaveric model. This easily replicable program is the first simulation-based BG-PDT training experience reported in the literature, enhancing safe competency acquisition, to further improve patient care.

Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial.

BACKGROUND: Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomized controlled trial to address the impact of a CRT-targeted (CRT-T) vs. a lactate-targeted (LAC-T) fluid resuscitation strategy on fluid balances within 24 h of septic shock diagnosis. In addition, we compared the effects of both strategies on organ dysfunction, regional and microcirculatory flow, and tissue hypoxia surrogates. RESULTS: Forty-two fluid-responsive septic shock patients were randomized into CRT-T or LAC-T groups. Fluids were administered until target achievement during the 6 h intervention period, or until safety criteria were met. CRT-T was aimed at CRT normalization (≤ 3 s), whereas in LAC-T the goal was lactate normalization (≤ 2 mmol/L) or a 20% decrease every 2 h. Multimodal perfusion monitoring included sublingual microcirculatory assessment; plasma-disappearance rate of indocyanine green; muscle oxygen saturation; central venous-arterial pCO2 gradient/ arterial-venous O2 content difference ratio; and lactate/pyruvate ratio. There was no difference between CRT-T vs. LAC-T in 6 h-fluid boluses (875 [375-2625] vs. 1500 [1000-2000], p = 0.3), or balances (982[249-2833] vs. 15,800 [740-6587, p = 0.2]). CRT-T was associated with a higher achievement of the predefined perfusion target (62 vs. 24, p = 0.03). No significant differences in perfusion-related variables or hypoxia surrogates were observed. CONCLUSIONS: CRT-targeted fluid resuscitation was not superior to a lactate-targeted one on fluid administration or balances. However, it was associated with comparable effects on regional and microcirculatory flow parameters and hypoxia surrogates, and a faster achievement of the predefined resuscitation target. Our data suggest that stopping fluids in patients with CRT ≤ 3 s appears as safe in terms of tissue perfusion. Clinical Trials: ClinicalTrials.gov Identifier: NCT03762005 (Retrospectively registered on December 3rd 2018).

Hypoxia-related parameters during septic shock resuscitation: Pathophysiological determinants and potential clinical implications.

BACKGROUND: Assessment of tissue hypoxia at the bedside has yet to be translated into daily clinical practice in septic shock patients. Perfusion markers are surrogates of deeper physiological phenomena. Lactate-to-pyruvate ratio (LPR) and the ratio between veno-arterial PCO2 difference and Ca-vO2 (ΔPCO2/Ca-vO2) have been proposed as markers of tissue hypoxia, but they have not been compared in the clinical scenario. We studied acute septic shock patients under resuscitation. We wanted to evaluate the relationship of these hypoxia markers with clinical and biochemical markers of hypoperfusion during septic shock resuscitation. METHODS: Secondary analysis of a randomized controlled trial. Septic shock patients were randomized to fluid resuscitation directed to normalization of capillary refill time (CRT) versus normalization or significant lowering of lactate. Multimodal assessment of perfusion was performed at 0, 2, 6 and 24 hours, and included macrohemodynamic and metabolic perfusion variables, CRT, regional flow and hypoxia markers. Patients who attained their pre-specified endpoint at 2-hours were compared to those who did not. RESULTS: Forty-two patients were recruited, median APACHE-II score was 23 [15-31] and 28-day mortality 23%. LPR and ΔPCO2/Ca-vO2 ratio did not correlate during early resuscitation (0-2 h) and the whole study period (24-hours). ΔPCO2/Ca-vO2 ratio derangements were more prevalent than LPR ones, either in the whole cohort (52% vs. 23%), and in association with other perfusion abnormalities. In patients who reached their resuscitation endpoints, the proportion of patients with altered ΔPCO2/Ca-vO2 ratio decreased significantly (66% to 33%, P=0.045), while LPR did not (14% vs. 25%, P=0.34). CONCLUSIONS: Hypoxia markers did not exhibit correlation during resuscitation in septic shock patients. They probably interrogate different pathophysiological processes and mechanisms of dysoxia during early septic shock. Future studies should better elucidate the interaction and clinical role of hypoxia markers during septic shock resuscitation.

Optimal target in septic shock resuscitation.

Septic shock presents a high risk of morbidity and mortality. Through therapeutic strategies, such as fluid administration and vasoactive agents, clinicians intend to rapidly restore tissue perfusion. Nonetheless, these interventions have narrow therapeutic margins. Adequate perfusion monitoring is paramount to avoid progressive hypoperfusion or detrimental over-resuscitation. During early stages of septic shock, macrohemodynamic derangements, such as hypovolemia and decreased cardiac output (CO) tend to predominate. However, during late septic shock, endothelial and coagulation dysfunction induce severe alterations of the microcirculation, making it more difficult to achieve tissue reperfusion. Multiple perfusion variables have been described in the literature, from bedside clinical examination to complex laboratory tests. Moreover, all of them present inherent flaws and limitations. After the ANDROMEDA-SHOCK trial, there is evidence that capillary refill time (CRT) is an interesting resuscitation target, due to its rapid kinetics and correlation with deep hypoperfusion markers. New concepts such as hemodynamic coherence and flow responsiveness may be used at the bedside to select the best treatment strategies at any time-point. A multimodal perfusion monitoring and an integrated analysis with macrohemodynamic parameters is mandatory to optimize the resuscitation of septic shock patients.

La criticidad de las Unidades de Intensivo. Ampliando las Unidades en tiempos de pandemia / Expanding ICU facilities in a pandemic scenario

Our country is suffering the effects of the ongoing pandemic of coronavirus disease (COVID-19). Because the vulnerability of healthcare systems, especially the intensive care areas they can rapidly be overloaded. That challenge the ICUs simultaneously on multiple fronts making urgent to increase the number of beds, without lowering the standards of care. The purpose of this article is to discuss some aspects of the national situation and to provide recommendations on the organizational management of intensive care units such as isolation protocols, surge in ICU bed capacity, ensure adequate supplies, protect and train healthcare workers maintaining quality clinical management.

[Expanding ICU facilities in a pandemic scenario]. / La criticidad de las Unidades de Intensivo. Ampliando las Unidades en tiempos de pandemia.

Our country is suffering the effects of the ongoing pandemic of coronavirus disease (COVID-19). Because the vulnerability of healthcare systems, especially the intensive care areas they can rapidly be overloaded. That challenge the ICUs simultaneously on multiple fronts making urgent to increase the number of beds, without lowering the standards of care. The purpose of this article is to discuss some aspects of the national situation and to provide recommendations on the organizational management of intensive care units such as isolation protocols, surge in ICU bed capacity, ensure adequate supplies, protect and train healthcare workers maintaining quality clinical management.