Changes over time in characteristics, resource use and outcomes among ICU patients with COVID-19-A nationwide, observational study in Denmark

BACKGROUND: Characteristics and care of intensive care unit (ICU) patients with COVID‐19 may have changed during the pandemic, but longitudinal data assessing this are limited. We compared patients with COVID‐19 admitted to Danish ICUs in the first wave with those admitted later. METHODS: Among all Danish ICU patients with COVID‐19, we compared demographics, chronic comorbidities, use of organ support, length of stay and vital status of those admitted 10 March to 19 May 2020 (first wave) versus 20 May 2020 to 30 June 2021. We analysed risk factors for death by adjusted logistic regression analysis. RESULTS: Among all hospitalised patients with COVID‐19, a lower proportion was admitted to ICU after the first wave (13% vs. 8%). Among all 1374 ICU patients with COVID‐19, 326 were admitted during the first wave. There were no major differences in patient's characteristics or mortality between the two periods, but use of invasive mechanical ventilation (81% vs. 58% of patients), renal replacement therapy (26% vs. 13%) and ECMO (8% vs. 3%) and median length of stay in ICU (13 vs. 10 days) and in hospital (20 vs. 17 days) were all significantly lower after the first wave. Risk factors for death were higher age, larger burden of comorbidities (heart failure, pulmonary disease and kidney disease) and active cancer, but not admission during or after the first wave. CONCLUSIONS: After the first wave of COVID‐19 in Denmark, a lower proportion of hospitalised patients with COVID‐19 were admitted to ICU. Among ICU patients, use of organ support was lower and length of stay was reduced, but mortality rates remained at a relatively high level

Sesquiterpenes from <i>Thapsia </i><i>nitida</i> var. <i>meridionalis</i> and <i>Thapsia </i><i>nitida</i> var. <i>nitida</i>

Nine new eudesmanolides (1−9), two new guaianolides (12 and 13), and a new germacrane (10), along with a previously reported guaianolide (11), have been isolated from the roots of Thapsia nitida var. meridionalis. Thapsia nitida var. nitida also afforded compound 13 along with a new guaianolide (14). The structure of 13 was confirmed by X-ray crystallographic analysis. Compounds 1, 2, and 11−14 have been tested as potential inhibitors of the sarco- and endoplasmic Ca2+-dependent ATPases (SERCA) pump. None of them showed significant activities

Hyperglycemia and insulin use in patients with COVID-19 and severe hypoxemia allocated to 12 mg vs. 6 mg of dexamethasone:a secondary analysis of the COVID STEROID 2 randomized trial

Background: While dexamethasone has been shown to improve survival in COVID-19, its dose–response relationship with plasma glucose (PG) levels and insulin requirements is poorly understood. This study investigated the impact of 12 mg (higher dose) versus 6 mg (standard dose) of dexamethasone on hyper- or hypoglycemic events and the use of insulin. Methods: A secondary analysis of a subpopulation of the COVID STEROID 2 trial. Glycemic outcomes were assessed by time-to-event analysis of a hyperglycemic (two PG measurements ≥ 11.1 mmol/L), severe hyperglycemic (PG &gt; 20 mmol/L), hypoglycemic (&lt; 3.8 mmol/L) event or use of insulin, adjusted for age, diabetes status, hospital site, and mechanical ventilation. PG levels were compared before and after treatment allocation with linear mixed models to estimate changes in average PG levels over time. Results: Of 321 participants, 170 were allocated to the higher dose and 151 to the standard dose of dexamethasone. Time to a hyperglycemic event did not differ between groups, whereas severe hyperglycemic events were more frequent in the higher dose group (36%) than in the standard dose group (31%) with an adjusted subdistributional hazard ratio of 1.76 (95% CI [1.22–2.54], p = 0.003). Insulin use and hypoglycemic events did not differ between groups. The higher vs. standard dose group had an average PG increase of 0.5 mmol/L (95% CI [− 0.2 to 1.4], p = 0.149). Conclusion: Higher vs. standard doses of dexamethasone were associated with a higher incidence of severe hyperglycemia in patients with COVID-19 and severe hypoxemia, but the average increase in PG was similar between groups.</p

Stimulants for disorders of consciousness in the intensive care unit:a randomized, placebo-controlled trial

In the intensive care unit (ICU), management of unresponsive patients with brain injury focuses on preventing secondary brain damage. Therapeutic strategies that directly promote the recovery of consciousness are urgently needed. In an investigator-initiated, randomized, placebo-controlled, double-blind, cross-over trial, we studied the effects of apomorphine and methylphenidate in ICU patients with acute disorders of consciousness (DoC). We hypothesized that these stimulants would improve consciousness biomarkers assessed by automated pupillometry (primary outcome) and clinical signs of consciousness (secondary outcome).We randomized 50 ICU patients with DoC (14 female; mean age 63 +/- 10 years; 48 with non-traumatic brain injuries) to strata consisting of three consecutive treatment sessions during which apomorphine, methylphenidate or placebo were administered. In total, we administered 112 study medications, including 36 doses of apomorphine, 39 doses of methylphenidate and 37 doses of placebo. Missing administrations were due to death, ICU discharge or spontaneous consciousness recovery. Plasma concentrations of stimulants confirmed drug exposure. We found no adverse events related to the trial drugs.Pupillometry recordings of sufficient quality (n = 590) were available from 48 (96%) patients. A pupillary response to a verbal arithmetic command (i.e. &gt;= 3 pupillary dilations on five verbal arithmetic tasks) was identified during 70 (12%) of these recordings. Seven (15%) patients without any other observable response to spoken commands also passed a stricter threshold of &gt;= 4 pupillary dilations, suggesting cognitive motor dissociation. Apomorphine [odds ratio (OR) 1.35, 95% confidence interval (CI): 0.93 to 1.96] and methylphenidate (OR 1.29, 95% CI: 0.89 to 1.86) did not significantly increase pupillary responses. However, after study drug administration, 10 (20%) patients showed improved clinical arousal at least once. Signs of arousal were noted after one dose of placebo, four doses of apomorphine (OR 5.04, 95% CI: 0.56 to 120.7) and seven doses of methylphenidate (OR 9.96, 95% CI: 1.36 to 235.8). Changes toward higher consciousness level categories were observed once after placebo, four times after apomorphine (OR 5.67, 95% CI 0.63 to 169.46) and three times after methylphenidate (OR 3.41, 95% CI 0.34 to 88.00). In a post hoc analysis, patients with greater pupillary responsiveness showed better arousal, suggesting that this condition may predict stimulant drug effects.In conclusion, while pupillometry revealed no direct drug effects on overall pupillary responses, stimulants may have triggered clinical arousal in some patients, particularly in those with greater pupillary responsiveness. These findings require replication but should guide future pharmacological trials aimed at improving consciousness recovery after brain injury.Othman et al. studied the impact of apomorphine and methylphenidate on consciousness biomarkers and clinical arousal in intensive care unit patients with brain injury. Treatment did not alter overall pupillary responses, but some patients had transiently improved arousal, particularly those with greater pupillary responsiveness

Characteristics, interventions, and longer term outcomes of COVID‐19 ICU patients in Denmark—A nationwide, observational study

Background: Most data on intensive care unit (ICU) patients with COVID-19 originate in selected populations from stressed healthcare systems with shorter term follow-up. We present characteristics, interventions and longer term outcomes of the entire, unselected cohort of all ICU patients with COVID-19 in Denmark where the ICU capacity was not exceeded. Methods: We identified all patients with SARS-CoV-2 admitted to any Danish ICU from 10 March to 19 May 2020 and registered demographics, chronic comorbidities, use of organ support, length of stay, and vital status from patient files. Risk factors for death were analyzed using adjusted Cox regression analysis. Results: There were 323 ICU patients with confirmed COVID-19. Median age was 68 years, 74% were men, 50% had hypertension, 21% diabetes, and 20% chronic pulmonary disease; 29% had no chronic comorbidity. Invasive mechanical ventilation was used in 82%, vasopressors in 83%, renal replacement therapy in 26%, and extra corporeal membrane oxygenation in 8%. ICU stay was median 13 days (IQR 6-22) and hospital stay 19 days (11-30). Median follow-up was 79 days. At end of follow-up, 118 had died (37%), 15 (4%) were still in hospital hereof 4 in ICU as of 16 June 2020. Risk factors for mortality included male gender, age, chronic pulmonary disease, active cancer, and number of co-morbidities. Conclusions: In this nationwide, population-based cohort of ICU patients with COVID-19, longer term survival was high despite high age and substantial use of organ support. Male gender, age, and chronic co-morbidities, in particular chronic pulmonary disease, were associated with increased risk of death.</p

Long-term outcomes in COVID-19 patients admitted to intensive care in Denmark:A nationwide observational study

Background: Among ICU patients with COVID-19, it is largely unknown how the overall outcome and resource use have changed with time, different genetic variants, and vaccination status. Methods: For all Danish ICU patients with COVID-19 from March 10, 2020 to March 31, 2022, we manually retrieved data on demographics, comorbidities, vaccination status, use of life support, length of stay, and vital status from medical records. We compared patients based on the period of admittance and vaccination status and described changes in epidemiology related to the Omicron variant. Results: Among all 2167 ICU patients with COVID-19, 327 were admitted during the first (March 10–19, 2020), 1053 during the second (May 20, 2020 to June 30, 2021) and 787 during the third wave (July 1, 2021 to March 31, 2022). We observed changes over the three waves in age (median 72 vs. 68 vs. 65 years), use of invasive mechanical ventilation (81% vs. 58% vs. 51%), renal replacement therapy (26% vs. 13% vs. 12%), extracorporeal membrane oxygenation (7% vs. 3% vs. 2%), duration of invasive mechanical ventilation (median 13 vs. 13 vs. 9 days) and ICU length of stay (median 13 vs. 10 vs. 7 days). Despite these changes, 90-day mortality remained constant (36% vs. 35% vs. 33%). Vaccination rates among ICU patients were 42% as compared to 80% in society. Unvaccinated versus vaccinated patients were younger (median 57 vs. 73 years), had less comorbidity (50% vs. 78%), and had lower 90-day mortality (29% vs. 51%). Patient characteristics changed significantly after the Omicron variant became dominant including a decrease in the use of COVID-specific pharmacological agents from 95% to 69%. Conclusions: In Danish ICUs, the use of life support declined, while mortality seemed unchanged throughout the three waves of COVID-19. Vaccination rates were lower among ICU patients than in society, but the selected group of vaccinated patients admitted to the ICU still had very severe disease courses. When the Omicron variant became dominant a lower fraction of SARS-CoV-2 positive patients received COVID treatment indicating other causes for ICU admission.</p