Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic: a matched analysis.

BACKGROUND: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. METHODS: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. RESULTS: Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. CONCLUSIONS: In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannula.

Characteristics and influence on quality of life of new-onset pain in critical COVID-19 survivors.

BACKGROUND: Pain is a clinical feature of COVID-19, however, data about persistent pain after hospital discharge, especially among ICU survivors is scarce. The aim of this study was to explore the incidence and characteristics of new-onset pain and its impact on Health-Related Quality of Life (HRQoL), and to quantify the presence of mood disorders in critically ill COVID-19 survivors. METHODS: This is a preliminary report of PAIN-COVID trial (NCT04394169) presenting a descriptive analysis in critically ill COVID-19 survivors, following in person interview 1 month after hospital discharge. Pain was assessed using the Brief Pain Inventory, the Douleur Neuropathique 4 questionnaire and the Pain Catastrophizing Scale. HRQoL was evaluated with the EQ 5D/5L, and mood disorders with the Hospital Anxiety and Depression Scale (HADS). RESULTS: From 27 May to 19 July 2020, 203 patients were consecutively screened for eligibility, and 65 were included in this analysis. Of these, 50.8% patients reported new-onset pain; 38.5% clinically significant pain (numerical rating score ≥3 for average pain intensity); 16.9% neuropathic pain; 4.6% pain catastrophizing thoughts, 44.6% pain in ≥2 body sites and 7.7% widespread pain. Patients with new-onset pain had a worse EQ-VAS and EQ index value (p < 0.001). Pain intensity was negatively correlated to both the former (Spearman ρ: -0.546, p < 0.001) and the latter (Spearman ρ: -0.387, p = 0.001). HADS anxiety and depression values equal or above eight were obtained in 10.8% and 7.7% of patients, respectively. CONCLUSION: New-onset pain in critically ill COVID-19 survivors is frequent, and it is associated with a lower HRQoL. Trial registration No.: NCT04394169. Registered 19 May 2020. https://clinicaltrials.gov/ct2/show/NCT04394169. SIGNIFICANCE: A substantial proportion of severe COVID-19 survivors may develop clinically significant persistent pain, post-intensive care syndrome and chronic ICU-related pain. Given the number of infections worldwide and the unprecedented size of the population of critical illness survivors, providing information about the incidence of new-onset pain, its characteristics, and its influence on the patients' quality of life might help establish and improve pain management strategies.

Predictors of failure with high-flow nasal oxygen therapy in COVID-19 patients with acute respiratory failure: a multicenter observational study.

PURPOSE: We aimed to describe the use of high-flow nasal oxygen (HFNO) in patients with COVID-19 acute respiratory failure and factors associated with a shift to invasive mechanical ventilation. METHODS: This is a multicenter, observational study from a prospectively collected database of consecutive COVID-19 patients admitted to 36 Spanish and Andorran intensive care units (ICUs) who received HFNO on ICU admission during a 22-week period (March 12-August 13, 2020). Outcomes of interest were factors on the day of ICU admission associated with the need for endotracheal intubation. We used multivariable logistic regression and mixed effects models. A predictive model for endotracheal intubation in patients treated with HFNO was derived and internally validated. RESULTS: From a total of 259 patients initially treated with HFNO, 140 patients (54%) required invasive mechanical ventilation. Baseline non-respiratory Sequential Organ Failure Assessment (SOFA) score [odds ratio (OR) 1.78; 95% confidence interval (CI) 1.41-2.35], and the ROX index calculated as the ratio of partial pressure of arterial oxygen to inspired oxygen fraction divided by respiratory rate (OR 0.53; 95% CI: 0.37-0.72), and pH (OR 0.47; 95% CI: 0.24-0.86) were associated with intubation. Hospital site explained 1% of the variability in the likelihood of intubation after initial treatment with HFNO. A predictive model including non-respiratory SOFA score and the ROX index showed excellent performance (AUC 0.88, 95% CI 0.80-0.96). CONCLUSIONS: Among adult critically ill patients with COVID-19 initially treated with HFNO, the SOFA score and the ROX index may help to identify patients with higher likelihood of intubation.

High-flow nasal oxygen in patients with COVID-19-associated acute respiratory failure.

PURPOSE: Whether the use of high-flow nasal oxygen in adult patients with COVID-19 associated acute respiratory failure improves clinically relevant outcomes remains unclear. We thus sought to assess the effect of high-flow nasal oxygen on ventilator-free days, compared to early initiation of invasive mechanical ventilation, on adult patients with COVID-19. METHODS: We conducted a multicentre cohort study using a prospectively collected database of patients with COVID-19 associated acute respiratory failure admitted to 36 Spanish and Andorran intensive care units (ICUs). Main exposure was the use of high-flow nasal oxygen (conservative group), while early invasive mechanical ventilation (within the first day of ICU admission; early intubation group) served as the comparator. The primary outcome was ventilator-free days at 28 days. ICU length of stay and all-cause in-hospital mortality served as secondary outcomes. We used propensity score matching to adjust for measured confounding. RESULTS: Out of 468 eligible patients, a total of 122 matched patients were included in the present analysis (61 for each group). When compared to early intubation, the use of high-flow nasal oxygen was associated with an increase in ventilator-free days (mean difference: 8.0 days; 95% confidence interval (CI): 4.4 to 11.7 days) and a reduction in ICU length of stay (mean difference: - 8.2 days; 95% CI - 12.7 to - 3.6 days). No difference was observed in all-cause in-hospital mortality between groups (odds ratio: 0.64; 95% CI: 0.25 to 1.64). CONCLUSIONS: The use of high-flow nasal oxygen upon ICU admission in adult patients with COVID-19 related acute hypoxemic respiratory failure may lead to an increase in ventilator-free days and a reduction in ICU length of stay, when compared to early initiation of invasive mechanical ventilation. Future studies should confirm our findings.

Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study.

BACKGROUND: Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone. METHODS: Prospective, multicenter, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory Sequential Organ Failure Assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate, and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP. RESULTS: A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO + awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95% CI 0.53-1.43), p = 0.60]. Patients treated with HFNO + awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0-2.5) vs 2 IQR 1.0-3.0] days (p = 0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95% CI 0.40-2.72), p = 0.92]. CONCLUSION: In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality.

Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS.

PURPOSE: The main characteristics of mechanically ventilated ARDS patients affected with COVID-19, and the adherence to lung-protective ventilation strategies are not well known. We describe characteristics and outcomes of confirmed ARDS in COVID-19 patients managed with invasive mechanical ventilation (MV). METHODS: This is a multicenter, prospective, observational study in consecutive, mechanically ventilated patients with ARDS (as defined by the Berlin criteria) affected with with COVID-19 (confirmed SARS-CoV-2 infection in nasal or pharyngeal swab specimens), admitted to a network of 36 Spanish and Andorran intensive care units (ICUs) between March 12 and June 1, 2020. We examined the clinical features, ventilatory management, and clinical outcomes of COVID-19 ARDS patients, and compared some results with other relevant studies in non-COVID-19 ARDS patients. RESULTS: A total of 742 patients were analysed with complete 28-day outcome data: 128 (17.1%) with mild, 331 (44.6%) with moderate, and 283 (38.1%) with severe ARDS. At baseline, defined as the first day on invasive MV, median (IQR) values were: tidal volume 6.9 (6.3-7.8) ml/kg predicted body weight, positive end-expiratory pressure 12 (11-14) cmH2O. Values of respiratory system compliance 35 (27-45) ml/cmH2O, plateau pressure 25 (22-29) cmH2O, and driving pressure 12 (10-16) cmH2O were similar to values from non-COVID-19 ARDS patients observed in other studies. Recruitment maneuvers, prone position and neuromuscular blocking agents were used in 79%, 76% and 72% of patients, respectively. The risk of 28-day mortality was lower in mild ARDS [hazard ratio (RR) 0.56 (95% CI 0.33-0.93), p = 0.026] and moderate ARDS [hazard ratio (RR) 0.69 (95% CI 0.47-0.97), p = 0.035] when compared to severe ARDS. The 28-day mortality was similar to other observational studies in non-COVID-19 ARDS patients. CONCLUSIONS: In this large series, COVID-19 ARDS patients have features similar to other causes of ARDS, compliance with lung-protective ventilation was high, and the risk of 28-day mortality increased with the degree of ARDS severity.

Características, evolución clínica y factores asociados a la mortalidad en UCI de los pacientes críticos infectados por SARS-CoV-2 en España: estudio prospectivo, de cohorte y multi-céntrico

Resumen Antecedentes: No se ha reportado plenamente la evolución clínica de los pacientes críticos de COVID-19 durante su ingreso en la unidad de cuidados intensivos (UCI), incluyendo las complicaciones médicas e infecciosas y terapias de soporte, así como su asociación con la mortalidad en ICU. Objetivo: El objetivo de este estudio es describir las características clínicas y la evolución de los pacientes ingresados en UCI por COVID-19, y determinar los factores de riesgo de la mortalidad en UCI de dichos pacientes. Métodos: Estudio prospectivo, multi-céntrico y de cohorte, que incluyó a los pacientes críticos de COVID-19 ingresados en 30 UCIs de España y Andorra. Se incluyó a los pacientes consecutivos de 12 de Marzo a 26 de Mayo de 2020 si habían fallecido o habían recibido el alta de la UCI durante el periodo de estudio. Se reportaron los datos demográficos, síntomas, signos vitales, marcadores de laboratorio, terapias de soporte, terapias farmacológicas, y complicaciones médicas e infecciosas, realizándose una comparación entre los pacientes fallecidos y los pacientes dados de alta. Resultados: Se incluyó a un total de 663 pacientes. La mortalidad general en UCI fue del 31% (203 pacientes). Al ingreso en UCI los no supervivientes eran más hipoxémicos [SpO2 sin mascarilla de no reinhalación, de 90 (RIC 83 - 93) vs 91 (RIC 87 - 94);p<0,001] y con mayor puntuación en la escala SOFA - Evaluación de daño orgánico secuencial - [SOFA, 7 (RIC 5 - 9) vs 4 (RIC 3 - 7);p<0,001]. Las complicaciones fueron más frecuentes en los no supervivientes: síndrome de distrés respiratorio agudo (SDRA) (95% vs 89%;p=0,009), insuficiencia renal aguda (IRA) (58% vs 24%;p<10-16), shock (42% vs 14%;p<10-13), y arritmias (24% vs 11%;p<10-4). Las súper-infecciones respiratorias, infecciones del torrente sanguíneo y los shock sépticos fueron más frecuentes en los no supervivientes (33% vs 25%;p=0,03, 33% vs 23%;p=0,01 y 15% vs 3%, p=10-7), respectivamente. El modelo de regresión multivariable reflejó que la edad estaba asociada a la mortalidad, y que cada año incrementaba el riesgo de muerte en un 1% (95%IC: 1 - 10, p=0,014). Cada incremento de 5 puntos en la escala APACHE II predijo de manera independiente la mortalidad [OR: 1,508 (1,081, 2,104), p= 0,015]. Los pacientes con IRA [OR: 2,468 (1,628, 3,741), p<10-4)], paro cardiaco [OR: 11,099 (3,389, 36,353), p= 0,0001], y shock séptico [OR: 3,224 (1,486, 6,994), p= 0,002] tuvieron un riesgo de muerte incrementado. Conclusiones: Los pacientes mayores de COVID-19 con puntuaciones APACHE II más altas al ingreso, que desarrollaron IRA en grados II o III y/o shock séptico durante la estancia en UCI tuvieron un riesgo de muerte incrementado. La mortalidad en UCI fue del 31%. Background: The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as their association with in-ICU mortality has not been fully reported. Objective: This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients. Methods: Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12th to May 26th, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients. Results: A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic [SpO2 with non-rebreather mask, 90 (IQR 83 to 93) vs 91 (IQR 87 to 94);p<0.001] and with higher sequential organ failure assessment score [SOFA, 7 (IQR 5 to 9) s 4 (IQR 3 to 7);p<0.001]. Complicatio s were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs 89%;p=0.009), acute kidney injury (AKI) (58% vs 24%;p<10-16), shock (42% vs 14%;p<10-13), and arrhythmias (24% vs 11%;p<10-4). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs 25%;p=0.03, 33% vs 23%;p=0.01 and 15% vs 3%, p=10-7), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1 to 10, p=0.014). Each 5-point increase in APACHE II independently predicted mortality [OR: 1.508 (1.081, 2.104), p= 0.015]. Patients with AKI [OR: 2.468 (1.628, 3.741), p<10-4)], cardiac arrest [OR: 11.099 (3.389, 36.353), p= 0.0001], and septic shock [OR: 3.224 (1.486, 6.994), p= 0.002] had an increased risk-of-death. Conclusions: Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades II or III and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%.