Extracorporeal Membrane Oxygenation for COVID-19-associated Severe Acute Respiratory Distress Syndrome in Chile: A Nationwide Incidence and Cohort Study.

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.

Dyspnoea and respiratory muscle ultrasound to predict extubation failure.

BACKGROUND: This study investigated dyspnoea intensity and respiratory muscle ultrasound early after extubation to predict extubation failure. METHODS: The study was conducted prospectively in two intensive care units in France and Canada. Patients intubated for at least 48 h were studied within 2 h after an extubation following a successful spontaneous breathing trial. Dyspnoea was evaluated by a dyspnoea visual analogue scale (Dyspnoea-VAS) ranging from 0 to 10 and the Intensive Care Respiratory Distress Observational Scale (IC-RDOS). The ultrasound thickening fraction of the parasternal intercostal and the diaphragm was measured; limb muscle strength was evaluated using the Medical Research Council (MRC) score (range 0-60). RESULTS: Extubation failure occurred in 21 out of 122 enrolled patients (17%). The median (interquartile range (IQR)) Dyspnoea-VAS and IC-RDOS were higher in patients with extubation failure versus success: 7 (4-9) versus 3 (1-5) (p<0.001) and 3.7 (1.8-5.8) versus 1.7 (1.5-2.1) (p<0.001), respectively. The median (IQR) ratio of parasternal intercostal muscle to diaphragm thickening fraction was significantly higher and MRC was lower in patients with extubation failure compared with extubation success: 0.9 (0.4-2.1) versus 0.3 (0.2-0.5) (p<0.001) and 45 (36-50) versus 52 (44-60) (p=0.012), respectively. The thickening fraction of the parasternal intercostal and its ratio to diaphragm thickening showed the highest area under the receiver operating characteristic curve (AUC) for an early prediction of extubation failure (0.81). AUCs of Dyspnoea-VAS and IC-RDOS reached 0.78 and 0.74, respectively. CONCLUSIONS: Respiratory muscle ultrasound and dyspnoea measured within 2 h after extubation predict subsequent extubation failure.

Reverse Triggering Dyssynchrony 24 h after Initiation of Mechanical Ventilation.

BACKGROUND: Reverse triggering is a delayed asynchronous contraction of the diaphragm triggered by passive insufflation by the ventilator in sedated mechanically ventilated patients. The incidence of reverse triggering is unknown. This study aimed at determining the incidence of reverse triggering in critically ill patients under controlled ventilation. METHODS: In this ancillary study, patients were continuously monitored with a catheter measuring the electrical activity of the diaphragm. A method for automatic detection of reverse triggering using electrical activity of the diaphragm was developed in a derivation sample and validated in a subsequent sample. The authors assessed the predictive value of the software. In 39 recently intubated patients under assist-control ventilation, a 1-h recording obtained 24 h after intubation was used to determine the primary outcome of the study. The authors also compared patients' demographics, sedation depth, ventilation settings, and time to transition to assisted ventilation or extubation according to the median rate of reverse triggering. RESULTS: The positive and negative predictive value of the software for detecting reverse triggering were 0.74 (95% CI, 0.67 to 0.81) and 0.97 (95% CI, 0.96 to 0.98). Using a threshold of 1 µV of electrical activity to define diaphragm activation, median reverse triggering rate was 8% (range, 0.1 to 75), with 44% (17 of 39) of patients having greater than or equal to 10% of breaths with reverse triggering. Using a threshold of 3 µV, 26% (10 of 39) of patients had greater than or equal to 10% reverse triggering. Patients with more reverse triggering were more likely to progress to an assisted mode or extubation within the following 24 h (12 of 39 [68%]) vs. 7 of 20 [35%]; P = 0.039). CONCLUSIONS: Reverse triggering detection based on electrical activity of the diaphragm suggests that this asynchrony is highly prevalent at 24 h after intubation under assist-control ventilation. Reverse triggering seems to occur during the transition phase between deep sedation and the onset of patient triggering.

Continuous prolonged prone positioning in COVID-19-related ARDS: a multicenter cohort study from Chile.

BACKGROUND: 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.

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.

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).

Experiencia de manejo de pacientes críticos con COVID-19 en Hospital Barros Luco: análisis descriptivo en un hospital público de alta complejidad / Experience of managing critical patients with COVID-19 at Hospital Barros Luco: descriptive analysis in a high complexity public Hospital

RELEVANCIA: La pandemia por COVID-19 (Coronavirus Disease-2019) se origina en diciembre de 2019. En Chile, a la fecha se han reportado 13.037 fallecidos con un enorme costo y esfuerzo asistencial, siendo limitada aun la evidencia en Chile acerca de esta enfermedad. OBJETIVOS: Describir el perfil clínico y ventilatorio de los pacientes con COVID-19 que requirieron manejo en la Unidad de Cuidados Intensivos en un Hospital Terciario de la Región Metropolitana. MÉTODOS: Estudio descriptivo, observacional y retrospectivo. Se extrajeron los datos de 64 pacientes ingresados entre el 24 de Marzo y el 15 de Mayo de 2020 en la UCI del Hospital Ramón Barros Luco Trudeau en el Sector Sur de la Región Metropolitana. Los resultados primarios en el estudio fueron Mortalidad en UCI, Mortalidad Intrahospitalaria y Mortalidad a 28 días. RESULTADOS: La mortalidad en UCI fue del 20%, existiendo una asociación entre Hipertensión Arterial y Enfermedad más Grave. La obesidad se asoció con mayores días UCI. En cuanto al soporte ventilatorio, 75% de los pacientes requirió apoyo con VMI al ingreso. Existe un perfil de mejor Compliance pulmonar y bajo potencial de reclutamiento durante la primera semana. Sin embargo, entre el 7mo. y 14vo día de enfermedad existe una rápida progresión hacia menor compliance pulmonar en cierto grupo de pacientes. CONCLUSIONES: Los casos más graves de COVID-19 se dan en pacientes de avanzada edad, hipertensos y obesos, con un aumento significativo en mortalidad cuando asociaron enfermedad renal crónica sobre todo en hemodiálisis. La progresión hacia deterioros severos de la elastancia pulmonar probablemente constituyen el signo ominoso de la enfermedad.