18–25 July 2021
Jose Chacko, Gagan Brar
Death and disability after critical illness
Higgins AM, et al. Predictors of death and new disability after critical illness: a multicenter prospective cohort study. Intensive Care Med. 2021;47(7):772-781
The PREDICT study was carried out to evaluate the prevalence and predictors of death or new-onset disability after critical illness.1 This prospective cohort study was conducted in six metropolitan intensive care units in Victoria, Australia. Adult patients who underwent more than 24 hours of mechanical ventilation were enrolled. The primary outcome was death or new disability at 6 months of follow-up. New disability was defined as a 10% increase in the World Health Organization Disability Assessment Score (WHODAS 2.0). Among the 628 patients assessed for the primary outcome, 370 (58.9%) had died or developed a new disability at 6 months, leaving 258 (41.1%) alive and without a new disability. Mortality occurred in 35% of patients, while 24% had developed a new disability at 6 months. On multivariable analysis, the independent predictors of death or new disability included age, severity of illness by the APACHE III score, and the pre-admission diagnosis. Compared to surgical admissions, patients who were admitted for medical illnesses including cardiac arrest, sepsis, or trauma had a higher odds of death or new disability. Thus, less than half of all patients admitted to the intensive care unit and ventilated for more than 24 hours were alive and free of new disability at 6 months. A predictive model including age, severity of illness, and diagnosis at admission provided an acceptable level of discriminative ability for the prediction of death or new disability at 6 months. This study is one of the few that have addressed long-term survival and functional outcomes after critical illness.
Novavax: another effective vaccine for COVID-19
Heath PT, et al. Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. N Engl J Med. Published online June 30, 2021:NEJMoa2107659
Most parts world is still reeling under the devastation perpetrated by the SARS-CoV-2 virus. Extensive research on vaccines is underway, with NVX-CoV2373 (Novavax) being one of the newer vaccines that have been evaluated for efficacy. Novavax is a recombinant nanoparticle spike protein combined with 50 μg of Matrix-M as adjuvant. An earlier study had demonstrated that two doses administered 21 days apart were safe and generated a robust immune response among previously healthy adult subjects. In the present phase III placebo-controlled study, two doses of the vaccine were administered at 21 days apart to adults 18–84 years old.2 Among the 15,187 participants who were randomized, 14,039 were included in the efficacy analysis; 27.9% were 65 years or older, while 44.6% had comorbidities. The primary endpoint was COVID-19 infection of any degree of severity, confirmed by RT-PCR, with the onset of symptoms 7 days or more after the second dose of the vaccine. Virologically confirmed infection occurred in 10 participants who had the vaccine compared to 96 who received placebo, providing a vaccine efficacy of 89.7% (95% CI: 80.2–94.6). There were no hospitalizations or deaths among patients who received the vaccine. Severe COVID-19 with abnormal vital signs and the requirement for supplemental oxygen occurred in 5 patients in the placebo group; one required hospitalization, three were evaluated in the emergency department, while one patient received home care. On post hoc analysis, the vaccine demonstrated 86.3% efficacy against the B.1.1.7 (alpha) variant and 96.4% efficacy against other variants. Serious adverse events were few and similar between groups.
This study revealed a high level of efficacy in preventing SARS-CoV-2 infection, including the B.1.1.7 variant. India is likely to approve the Novavax vaccine in the near future; hopefully, we will have yet another effective vaccine that will help curtail the spread of COVID-19. It is currently unknown if the Novavax vaccine is efficacious against the delta variant that has been responsible for the outbreak in many parts of India during the second “wave” of COVID-19 transmission.
Azithromycin therapy put to rest among outpatients with COVID-19
Oldenburg CE, et al. Effect of Oral Azithromycin vs. Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection: A Randomized Clinical Trial. JAMA. Published online July 16, 2021. doi:10.1001/jama.2021.11517
Azithromycin has been postulated to have activity against SARS-CoV-2 through its anti-inflammatory and antiviral properties. Previous studies with azithromycin alone or in combination with hydroxychloroquine have failed to demonstrate efficacy among outpatients or hospitalized patients with COVID-19 infection. The present study was conducted to evaluate the efficacy of azithromycin without concurrent hydroxychloroquine in the prevention of progression COVID-19 among outpatients.3 Outpatients with COVID-19 infection were enrolled through an internet-based survey conducted across the US. Adult patients who had tested positive for SARS-CoV-2 infection by nucleic acid amplification or antigen testing were included within 7 days of a positive result. Among the 604 patients screened, 263 were enrolled. Patients were randomized in a 2:1 ratio to receive azithromycin 1.2 g as a single dose or a matching placebo. The trial was terminated for futility on interim analysis. On follow-up at day 14, there was no difference in the number of patients who were symptom-free between the two groups. By day 21, five patients required hospitalization in the azithromycin group, compared to none in the placebo group. The authors recommended against the routine use of azithromycin among outpatients with COVID-19. Among the limitations of the study were a significant number of patients (24%) who did not complete the study. Besides, the requirement for hospitalization was initially planned as the primary outcome; however, the incidence of hospitalization was very low, resulting in an underpowered study. Hence, the primary outcome was changed to the absence of symptoms on day 14. In spite of the limitations, this study adds to the body of knowledge regarding the lack of efficacy of azithromycin among outpatients with COVID-19 infection.
Emergency airway management in COVID-19
Wong DJN, et al. Emergency Airway Management in Patients with COVID-19: A Prospective International Multicenter Cohort Study. Anesthesiology. 2021;135(2):292-303. doi:10.1097/ALN.0000000000003791
Safe management of the airway, reducing the risk to healthcare personnel and patients has evinced interest since the outbreak of the COVID-19 pandemic. In a multinational prospective observational study, Wong et al. evaluated the methodology of intubation, success and complication rates, and variability in practice between countries.4 Data were collected from 607 hospitals across 32 countries. Emergency endotracheal intubation was performed on 4,476 occasions by 1,722 clinicians during a 7-month period. Intubation was successful on the first attempt in 89.7% of episodes; four or more attempts were required on 0.5% of episodes. Failed intubation, defined as the requirement for an emergency surgical airway, four or more attempts, or the placement of a supraglottic airway, occurred in 0.8% of episodes. Intubation was more likely to be successful on the first attempt with rapid sequence induction, the use of powered air purifier respirators compared with non-powered respirators, and with operators who had previous experience with intubating COVID-19 patients. First attempt intubations were more likely to be successful in high compared to middle or low-income countries. Video laryngoscopy, employed on 75.2% of intubation attempts, was not associated with first attempt success. Besides, the use of non-powered respirators and the use of protective intubation boxes were also not associated with successful first attempt at intubation. The authors concluded that a relatively high risk of airway-related complications should be considered while intubating the COVID-19 patient. Rapid-sequence induction, the use of powered air purifier respirators, and operator experience are more likely to result in successful intubation at the first attempt.
Extracorporeal Membrane Oxygenation for COVID-19
Diaz RA, et al. Extracorporeal Membrane Oxygenation for COVID-19–associated Severe Acute Respiratory Distress Syndrome in Chile: A Nationwide Incidence and Cohort Study. Am J Respir Crit Care Med. 2021;204(1):34-43. doi:10.1164/rccm.202011-4166OC
Patients with severe acute respiratory distress syndrome who remain hypoxic in spite of conventional measures including invasive mechanical ventilation, sedation and neuromuscular blockade, titrated application of PEEP, and prone positioning may require extracorporeal support. Although initial reports with extracorporeal membrane oxygenation (ECMO) were unpromising, no clear picture has emerged yet regarding the requirement for and outcomes from ECMO use in patients with severe COVID-19 pneumonia. Against this background, Diaz et al. carried out a study to assess the cumulative incidence, patient characteristics, and outcomes from ECMO use among patients with refractory hypoxia following COVID-19 infection in Chile.5 The study was conducted over a 6-month period from March 3, to August 31, 2020, and included 94 patients who received ECMO support. ECMO was carried out in 1.2% of patients who underwent invasive mechanical ventilation. Among the 85 patients included in the final analysis, the median age was 48 years (IQR: 41–55), 83.5% were male, and 42.4% were obese. Patients were intubated for a median of 4 days prior to ECMO (IQR: 2–7). The median PaO2/FiO2 ratio was 86.8 mm Hg (IQR: 64–99) at the time of institution of ECMO. Prone ventilation was performed in most (91.8%) patients prior to ECMO. Fifty-two patients (61.2%) recovered and were discharged home, while 33 (38.8%) died. The median duration of hospital stay was 50 (IQR: 24–69) days. Common complications encountered were infections (70.6%), hemorrhage (38.8%), and embolism (22.4%). Low respiratory system compliance and high driving pressures prior to commencement of ECMO were associated with mortality; however, a duration of invasive ventilation of more than 10 days pre-ECMO was not associated with increased mortality. This study suggests that among COVID-19 patients with refractory hypoxia who fail to improve with conventional modalities of respiratory support, ECMO may be a reasonable option.
1. Higgins AM, Neto AS, Bailey M, et al. Predictors of death and new disability after critical illness: a multicentre prospective cohort study. Intensive Care Med. 2021;47(7):772-781. doi:10.1007/s00134-021-06438-7
2. Heath PT, Galiza EP, Baxter DN, et al. Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine. N Engl J Med. Published online June 30, 2021:NEJMoa2107659. doi:10.1056/NEJMoa2107659
3. Oldenburg CE, Pinsky BA, Brogdon J, et al. Effect of Oral Azithromycin vs Placebo on COVID-19 Symptoms in Outpatients With SARS-CoV-2 Infection: A Randomized Clinical Trial. JAMA. Published online July 16, 2021. doi:10.1001/jama.2021.11517
4. Wong DJN, El-Boghdadly K, Owen R, et al. Emergency Airway Management in Patients with COVID-19: A Prospective International Multicenter Cohort Study. Anesthesiology. 2021;135(2):292-303. doi:10.1097/ALN.0000000000003791
5. Diaz RA, Graf J, Zambrano JM, et al. Extracorporeal Membrane Oxygenation for COVID-19–associated Severe Acute Respiratory Distress Syndrome in Chile: A Nationwide Incidence and Cohort Study. Am J Respir Crit Care Med. 2021;204(1):34-43. doi:10.1164/rccm.202011-4166OC0.1016/j.jcrc.2020.03.011