IMPORTANCE: Vasopressors are commonly administered to intensive care unit (ICU) patients to raise blood pressure. Balancing risks and benefits of vasopressors is a challenge, particularly in older ...patients. OBJECTIVE: To determine whether reducing exposure to vasopressors through permissive hypotension (mean arterial pressure MAP target, 60-65 mm Hg) reduces mortality at 90 days in ICU patients aged 65 years or older with vasodilatory hypotension. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, pragmatic, randomized clinical trial was conducted in 65 ICUs in the United Kingdom and included 2600 randomized patients aged 65 years or older with vasodilatory hypotension (assessed by treating clinician). The study was conducted from July 2017 to March 2019, and follow-up was completed in August 2019. INTERVENTIONS: Patients were randomized 1:1 to vasopressors guided either by MAP target (60-65 mm Hg, permissive hypotension) (n = 1291) or according to usual care (at the discretion of treating clinicians) (n = 1307). MAIN OUTCOME AND MEASURES: The primary clinical outcome was all-cause mortality at 90 days. RESULTS: Of 2600 randomized patients, after removal of those who declined or had withdrawn consent, 2463 (95%) were included in the analysis of the primary outcome (mean SD age 75 years 7 years; 1387 57% men). Patients randomized to the permissive hypotension group had lower exposure to vasopressors compared with those in the usual care group (median duration 33 hours vs 38 hours; difference in medians, –5.0; 95% CI, –7.8 to –2.2 hours; total dose in norepinephrine equivalents median, 17.7 mg vs 26.4 mg; difference in medians, –8.7 mg; 95% CI, –12.8 to −4.6 mg). At 90 days, 500 of 1221 (41.0%) in the permissive hypotension compared with 544 of 1242 (43.8%) in the usual care group had died (absolute risk difference, −2.85%; 95% CI, −6.75 to 1.05; P = .15) (unadjusted relative risk, 0.93; 95% CI, 0.85-1.03). When adjusted for prespecified baseline variables, the odds ratio for 90-day mortality was 0.82 (95% CI, 0.68 to 0.98). Serious adverse events were reported for 79 patients (6.2%) in the permissive care group and 75 patients (5.8%) in the usual care group. The most common serious adverse events were acute renal failure (41 3.2% vs 33 2.5%) and supraventricular cardiac arrhythmia (12 0.9% vs 13 1.0%). CONCLUSIONS AND RELEVANCE: Among patients 65 years or older receiving vasopressors for vasodilatory hypotension, permissive hypotension compared with usual care did not result in a statistically significant reduction in mortality at 90 days. However, the confidence interval around the point estimate for the primary outcome should be considered when interpreting the clinical importance of the study. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN10580502
Purpose
To describe critical care patients with COVID-19 across England, Wales and Northern Ireland and compare them with a historic cohort of patients with other viral pneumonias (non-COVID-19) and ...with international cohorts of COVID-19.
Methods
Extracted data on patient characteristics, acute illness severity, organ support and outcomes from the Case Mix Programme, the national clinical audit for adult critical care, for a prospective cohort of patients with COVID-19 (February to August 2020) are compared with a recent retrospective cohort of patients with other viral pneumonias (non-COVID-19) (2017–2019) and with other international cohorts of critical care patients with COVID-19, the latter identified from published reports.
Results
10,834 patients with COVID-19 (70.1% male, median age 60 years, 32.6% non-white ethnicity, 39.4% obese, 8.2% at least one serious comorbidity) were admitted across 289 critical care units. Of these, 36.9% had a PaO
2
/FiO
2
ratio of ≤ 13.3 kPa (≤ 100 mmHg) consistent with severe ARDS and 72% received invasive ventilation. Acute hospital mortality was 42%, higher than for 5782 critical care patients with other viral pneumonias (non-COVID-19) (24.7%), and most COVID-19 deaths (88.7%) occurred before 30 days. Meaningful international comparisons were limited due to lack of standardised reporting.
Conclusion
Critical care patients with COVID-19 were disproportionately non-white, from more deprived areas and more likely to be male and obese. Conventional severity scoring appeared not to adequately reflect their acute severity, with the distribution across PaO
2
/FiO
2
ratio categories indicating acutely severe respiratory disease. Critical care patients with COVID-19 experience high mortality and place a great burden on critical care services.
IMPORTANCE: The optimal first-line mode of noninvasive respiratory support following extubation of critically ill children is not known. OBJECTIVE: To evaluate the noninferiority of high-flow nasal ...cannula (HFNC) therapy as the first-line mode of noninvasive respiratory support following extubation, compared with continuous positive airway pressure (CPAP), on time to liberation from respiratory support. DESIGN, SETTING, AND PARTICIPANTS: This was a pragmatic, multicenter, randomized, noninferiority trial conducted at 22 pediatric intensive care units in the United Kingdom. Six hundred children aged 0 to 15 years clinically assessed to require noninvasive respiratory support within 72 hours of extubation were recruited between August 8, 2019, and May 18, 2020, with last follow-up completed on November 22, 2020. INTERVENTIONS: Patients were randomized 1:1 to start either HFNC at a flow rate based on patient weight (n = 299) or CPAP of 7 to 8 cm H2O (n = 301). MAIN OUTCOMES AND MEASURES: The primary outcome was time from randomization to liberation from respiratory support, defined as the start of a 48-hour period during which the child was free from all forms of respiratory support (invasive or noninvasive), assessed against a noninferiority margin of an adjusted hazard ratio (HR) of 0.75. There were 6 secondary outcomes, including mortality at day 180 and reintubation within 48 hours. RESULTS: Of the 600 children who were randomized, 553 children (HFNC, 281; CPAP, 272) were included in the primary analysis (median age, 3 months; 241 girls 44%). HFNC failed to meet noninferiority, with a median time to liberation of 50.5 hours (95% CI, 43.0-67.9) vs 42.9 hours (95% CI, 30.5-48.2) for CPAP (adjusted HR, 0.83; 1-sided 97.5% CI, 0.70-∞). Similar results were seen across prespecified subgroups. Of the 6 prespecified secondary outcomes, 5 showed no significant difference, including the rate of reintubation within 48 hours (13.3% for HFNC vs 11.5 % for CPAP). Mortality at day 180 was significantly higher for HFNC (5.6% vs 2.4% for CPAP; adjusted odds ratio, 3.07 95% CI, 1.1-8.8). The most common adverse events were abdominal distension (HFNC: 8/281 2.8% vs CPAP: 7/272 2.6%) and nasal/facial trauma (HFNC: 14/281 5.0% vs CPAP: 15/272 5.5%). CONCLUSIONS AND RELEVANCE: Among critically ill children requiring noninvasive respiratory support following extubation, HFNC compared with CPAP following extubation failed to meet the criterion for noninferiority for time to liberation from respiratory support. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN60048867
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