Characteristics and Outcomes by Ceiling of Care of Subjects Hospitalized with COVID-19 During Four Waves of the Pandemic in a Metropolitan Area: A Multicenter Cohort Study.

INTRODUCTION: The profiles of patients with COVID-19 have been widely studied, but little is known about differences in baseline characteristics and in outcomes between subjects with a ceiling of care assigned at hospital admission and subjects without a ceiling of care. The aim of this study is to compare, by ceiling of care, clinical features and outcomes of hospitalized subjects during four waves of COVID-19 in a metropolitan area in Catalonia. METHODS: Observational study conducted during the first (March-April 2020), second (October-November 2020), third (January-February 2021), and fourth wave (July-August 2021) of COVID-19 in five centers of Catalonia. All subjects were adults (> 18 years old) hospitalized with a proven SARS-CoV-2 infection and with therapeutic ceiling of care assessed by the attending physician at hospital admission. RESULTS: A total of 5813 subjects were analyzed. Subjects with a ceiling of care were mainly older (difference in median age of 20 years), with more comorbidities (Charlson index 3 points higher) and with fewer clinical signs at baseline than patients without a ceiling of care. Some features of their clinical profiles changed among waves. There were differences in treatments received during hospital admission across waves, but not between subjects with and without a ceiling of care. Subjects with a ceiling of care had a death incidence more than four times the death incidence of subjects a without a ceiling of care (risk ratio (RR) ranging from 3.5 in the first wave to almost 6 in the third and fourth). Incidence of severe pneumonia and complications for subjects with a ceiling of care was around 1.5 times the incidence in subjects without a ceiling of care. DISCUSSION: Analysis of hospitalized subjects with SARS-CoV-2 infection should be stratified according to therapeutic ceiling of care to avoid bias and outcome misestimation.

Remifentanil pharmacodynamics during conscious sedation using algometry: a more clinically relevant pharmacodynamical model.

BACKGROUND: The Minto remifentanil pharmacokinetic/pharmacodynamic (PK/PD) model is used in target-controlled infusion (TCI) devices. The endpoint used to calculate the PD parameters, including the ke0, was the electroencephalogram (EEG), which only changes at high remifentanil concentrations. As the ke0 should adequately predict the time course of drug effects at clinically relevant concentrations, we evaluated the temporal agreement between effect-site concentrations estimated with the Minto model and pressure pain thresholds during conscious sedation. METHODS: We enrolled 100 patients scheduled for gynaecological surgery. The first group (35 subjects) received an effect site targeted remifentanil infusion (target 1.5 ng ml-1); the second group (35 subjects) received the same infusion and a 1 mg bolus of midazolam to evaluate anxiolytic effects; the control group (30 subjects) received a saline infusion. Algometry and vital signs were measured at different time points. RESULTS: The Minto model predicted stable effect-site concentrations within 1.5 min of starting the infusion. Haemodynamic variables stabilised within 5 min, whereas there was a significant increase in pressure pain threshold for up to 15 min in both remifentanil groups. Midazolam had no effect on pressure pain threshold. A PD model based on algometry and Minto PK model was developed. CONCLUSIONS: Our results demonstrate the limitation of the Minto PD model at low target remifentanil concentrations, with a discrepancy in the time course between EEG and pressure pain threshold changes. Clinicians should be aware that the time course of onset of analgesic effects is slower than the estimates of the Minto model. Investigators should consider using algometry data in future opioid PD modelling studies.

Immunomodulatory therapy, risk factors and outcomes of hospital-acquired bloodstream infection in patients with severe COVID-19 pneumonia: a Spanish case-control matched multicentre study (BACTCOVID).

OBJECTIVES: The effect of the use of immunomodulatory drugs on the risk of developing hospital-acquired bloodstream infection (BSI) in patients with COVID-19 has not been specifically assessed. We aim to identify risk factors for, and outcomes of, BSI among hospitalized patients with severe COVID-19 pneumonia. METHODS: We performed a severity matched case-control study (1:1 ratio) nested in a large multicentre prospective cohort of hospitalized adults with COVID-19. Cases with BSI were identified from the cohort database. Controls were matched for age, sex and acute respiratory distress syndrome. A Cox proportional hazard ratio model was performed. RESULTS: Of 2005 patients, 100 (4.98%) presented 142 episodes of BSI, mainly caused by coagulase-negative staphylococci, Enterococcus faecalis and Pseudomonas aeruginosa. Polymicrobial infection accounted for 23 episodes. The median time from admission to the first episode of BSI was 15 days (IQR 9-20), and the most frequent source was catheter-related infection. The characteristics of patients with and without BSI were similar, including the use of tocilizumab, corticosteroids, and combinations. In the multivariate analysis, the use of these immunomodulatory drugs was not associated with an increased risk of BSI. A Cox proportional hazard ratio (HR) model showed that after adjusting for the time factor, BSI was associated with a higher in-hospital mortality risk (HR 2.59; 1.65-4.07; p < 0.001). DISCUSSION: Hospital-acquired BSI in patients with severe COVID-19 pneumonia was uncommon and the use of immunomodulatory drugs was not associated with its development. When adjusting for the time factor, BSI was associated with a higher mortality risk.

Is the pharmacokinetics of bupivacaine equivalent after lumbar epidural administration through a needle or a catheter in male and female adults?

We assessed possible pharmacokinetic modifications due to different epidural injection techniques using either a needle or a catheter. Adult patients (n=23) undergoing lower abdominal or lower extremity surgery were randomly assigned a single bupivacaine epidural injection anesthesia (0.5%, 15 mL, 0.3 mL/s) through needle or catheter device. Plasma bupivacaine concentration was quantified using a validated HPLC method and non-compartmental pharmacokinetic parameters estimated. CMAX and TMAX were similar in both groups: 952 ± 346 ng/mL, 0.65 ± 0.5 1h in the needle group; 810 ± 307 ng/mL, 0.43 ± 0.29 h in the catheter group respectively. Plasma AUC0→∞ was also similar in both groups: 3868 ± 1687 ngh/mL for needle versus 4096 ± 1748 ngh/mL using catheter. The catheter group showed slower disposition than the needle group: t1/2=3.9 ± 2.3 h, MRT=6.0 ± 3.1 h versus 2.7 ± 1.03 h and 4.5 ± 1.2 h with needle administration respectively though it did not reach statistical significance, Cl/F and V/F were also similar. Lastly, female patients showed significant longer t1/2 after administration through catheter (5.7 ± 2.0 h) than needle (2.7 ± 0.6 h) group (P=0.0279). The device type does not affect the pharmacokinetics which is similar in both groups although sex-based differences might exist.