Risk factors associated with mortality among elderly patients with COVID-19: Data from 55 intensive care units in Spain.

INTRODUCTION AND OBJECTIVES: Critically-ill elderly ICU patients with COVID-19 have poor outcomes. We aimed to compare the rates of in-hospital mortality between non-elderly and elderly critically-ill COVID-19 ventilated patients, as well as to analyze the characteristics, secondary outcomes and independent risk factors associated with in-hospital mortality of elderly ventilated patients. PATIENTS AND METHODS: We conducted a multicentre, observational cohort study including consecutive critically-ill patients admitted to 55 Spanish ICUs due to severe COVID-19 requiring mechanical ventilation (non-invasive respiratory support [NIRS; include non-invasive mechanical ventilation and high-flow nasal cannula] and invasive mechanical ventilation [IMV]) between February 2020 and October 2021. RESULTS: Out of 5,090 critically-ill ventilated patients, 1,525 (27%) were aged ≥70 years (554 [36%] received NIRS and 971 [64%] received IMV. In the elderly group, median age was 74 years (interquartile range 72-77) and 68% were male. Overall in-hospital mortality was 31% (23% in patients <70 years and 50% in those ≥70 years; p<0.001). In-hospital mortality in the group ≥70 years significantly varied according to the modality of ventilation (40% in NIRS vs. 55% in IMV group; p<0.001). Factors independently associated with in-hospital mortality in elderly ventilated patients were age (sHR 1.07 [95%CI 1.05-1.10], p<0.001); previous admission within the last 30 days (sHR 1.40 [95%CI 1.04-1.89], p = 0.027); chronic heart disease (sHR 1.21 [95%CI 1.01-1.44], p = 0.041); chronic renal failure (sHR 1.43 [95%CI 1.12- 1.82], p = 0.005); platelet count (sHR 0.98 [95% CI 0.98-0.99], p<0.001); IMV at ICU admission (sHR 1.41 [95% CI 1.16- 1.73], p<0.001); and systemic steroids (sHR 0.61 [95%CI 0.48- 0.77], p<0.001). CONCLUSIONS: Amongst critically-ill COVID-19 ventilated patients, those aged ≥70 years presented significantly higher rates of in-hospital mortality than younger patients. Increasing age, previous admission within the last 30 days, chronic heart disease, chronic renal failure, platelet count, IMV at ICU admission and systemic steroids (protective) all comprised independent factors for in-hospital mortality in elderly patients.

Characterization of [3H]nisoxetine binding in rat vas deferens membranes: modulation by sigma and PCP ligands.

Sigma (sigma) and phencyclidine (PCP) receptor ligands, apart from their main effects on sigma receptors and NMDA receptor-mediated neurotransmission, have been found to interact with catecholamine systems in several central and peripheral tissues. In the present study the binding profile of [3H]nisoxetine ([3H]NIS), a selective marker of the noradrenaline transporter, has been characterized in rat vas deferens membranes to further study its modulation by a number of characteristic sigma and PCP ligands. The binding of [3H]NIS was found to be of high affinity (Kd = 1.63 +/- 0.36 nM), saturable, sodium-dependent and to a single population of binding sites (nH = 1.003 +/- 0.017). The maximal binding capacity was 1,625 +/- 500 fmol/mg of protein. Kinetic experiments gave a k(+1) of 3.9 x 10(7) min(-1)M(-1) and a k(-1) of 0.005 min(-1). The [3H]NIS binding was totally inhibited, with IC50 values in the micromolar range, by all the sigma and PCP ligands tested, with the following order of potency: haloperidol > dextromethorphan > dizocilpine > dextrorphan > (+)-3-PPP > PCP > tenocyclidine. This order correlates well with that described in other tissues using [3H]desmethylimipramine. The inhibition by all these compounds, except that of (+)-3-PPP, was competitive. These results suggest that sigma and PCP ligands bind, at low micromolar concentrations, to a site in the noradrenaline transporter that is labelled by [3H]NIS.

MK-801 enhances noradrenergic neurotransmission in rat vas deferens.

The effect of MK-801 (dizocilpine) on the noradrenergic neurotransmission of the epididymal portion of rat vas deferens has been investigated. This drug potentiated the electrically induced responses (46.6% +/- 5.09 at a concentration of 3.7 microM) and the contractile effect of exogenous noradrenaline with a concentration-dependent reduction of EC50 (from 0.99 +/- 0.11 microM to 0.06 +/- 0.01 microM). Moreover, MK-801 alone induced spontaneous contractile responses that were abolished by prazosin, not reversed by N-methyl-D-aspartate (NMDA) + glycine and that did not appear in organs obtained from reserpinized rats. In addition, MK-801 inhibited the [3H]noradrenaline uptake in slices from rat vas deferens (IC50 = 1.79 +/- 0.06 microM). Since these effects took place in the presence of magnesium and were sodium-dependent, a direct participation of the NMDA receptor complex can be ruled out, pointing to the inhibition of the cathecolamine uptake systems in the postganglionic sympathetic nerve endings as the most feasible mechanism.