BackgroundHaloperidol, a tranquilizing agent, is administered both to treat symptoms of psychotic disorders and to sedate agitated and delirious patients. Notably, haloperidol has been suggested to inhibit the immune response through unknown mechanisms. We hypothesized that the sedative modulates the immune response via NF-κB.Material/MethodsUsing flow cytometry, we analyzed the effects of haloperidol on expression CD80 and CD86 in RAW 264 cells and in primary macrophages derived from bone marrow. Secretion of interleukin (IL)-1β, IL-6, and IL-12 p40 was measured by enzyme-linked immunosorbent assay. In addition, NF-κB activation was evaluated using a reporter assay based on secretory embryonic alkaline phosphatase. Finally, synthetic antagonists were used to identify the dopamine receptor that mediates the effects of haloperidol.ResultsHaloperidol inhibited NF-κB activation, and thereby suppressed expression of CD80, as well as secretion of IL-1β, IL-6, and IL-12 p40. CD80 and IL-6 levels were similarly attenuated by a D2-like receptor antagonist, but not by a D1-like receptor antagonist.ConclusionsThe data strongly suggest that haloperidol inhibits the immune response by suppressing NF-κB signaling via the dopamine D2 receptor.
Background
Heterogeneity is an inherent nature of ARDS. Recruitment-to-inflation ratio has been developed to identify the patients who has lung recruitablity. This technique might be useful to identify the patients that match specific interventions, such as higher positive end-expiratory pressure (PEEP) or prone position or both. We aimed to evaluate the physiological effects of PEEP and body position on lung mechanics and regional lung inflation in COVID-19-associated ARDS and to propose the optimal ventilatory strategy based on recruitment-to-inflation ratio.
Methods
Patients with COVID-19-associated ARDS were consecutively enrolled. Lung recruitablity (recruitment-to-inflation ratio) and regional lung inflation (electrical impedance tomography [EIT]) were measured with a combination of body position (supine or prone) and PEEP (low 5 cmH2O or high 15 cmH2O). The utility of recruitment-to-inflation ratio to predict responses to PEEP were examined with EIT.
Results
Forty-three patients were included. Recruitment-to-inflation ratio was 0.68 (IQR 0.52–0.84), separating high recruiter versus low recruiter. Oxygenation was the same between two groups. In high recruiter, a combination of high PEEP with prone position achieved the highest oxygenation and less dependent silent spaces in EIT (vs. low PEEP in both positions) without increasing non-dependent silent spaces in EIT. In low recruiter, low PEEP in prone position resulted in better oxygenation (vs. both PEEPs in supine position), less dependent silent spaces (vs. low PEEP in supine position) and less non-dependent silent spaces (vs. high PEEP in both positions). Recruitment-to-inflation ratio was positively correlated with the improvement in oxygenation and respiratory system compliance, the decrease in dependent silent spaces, and was inversely correlated with the increase in non-dependent silent spaces, when applying high PEEP.
Conclusions
Recruitment-to-inflation ratio may be useful to personalize PEEP in COVID-19-associated ARDS. Higher PEEP in prone position and lower PEEP in prone position decreased the amount of dependent silent spaces (suggesting lung collapse) without increasing the amount of non-dependent silent spaces (suggesting overinflation) in high recruiter and in low recruiter, respectively.
The cuff leak test (CLT) has been widely accepted as a simple and noninvasive method for predicting post-extubation stridor (PES). However, its accuracy and clinical impact remain uncertain. We aimed to evaluate the reliability of CLT and to assess the impact of pre-extubation variables on the incidence of PES. A prospective observational study was performed on adult critically ill patients who required mechanical ventilation for more than 24 h. Patients were extubated after the successful spontaneous breathing trial, and CLT was conducted before extubation. Of the 191 patients studied, 26 (13.6%) were deemed positive through CLT. PES developed in 19 patients (9.9%) and resulted in a higher reintubation rate (8.1% vs. 52.6%, p < 0.001) and longer intensive care unit stay (8 [4.5–14] vs. 12 [8–30.5] days, p = 0.01) than patients without PES. The incidence of PES and post-extubation outcomes were similar in patients with both positive and negative CLT results. Compared with patients without PES, patients with PES had longer durations of endotracheal intubation and required endotracheal suctioning more frequently during the 24-h period prior to extubation. After adjusting for confounding factors, frequent endotracheal suctioning more than 15 times per day was associated with an adjusted odds ratio of 2.97 (95% confidence interval, 1.01–8.77) for PES. In conclusion, frequent endotracheal suctioning before extubation was a significant PES predictor in critically ill patients. Further investigations of its impact on the incidence of PES and patient outcomes are warranted.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.