ABSTRACT
Anxiety contributes to postsurgical pain, and midazolam is frequently prescribed preoperatively. Conflicting results have been described concerning the impact of midazolam on pain. This study aims to evaluate the effect of systemic midazolam on pain after open inguinal hernia repair, clarifying its relationship with preoperative anxiety. A prospective observational cohort study was conducted in three Portuguese ambulatory units between September 2018 and March 2020. Variable doses of midazolam were administered. Postsurgical pain was evaluated up to three months after surgery. We enrolled 306 patients and analyzed 281 patients. The mean preoperative anxiety Numeric Rating Scale score was 4 (3) and the mean Surgical Fear Questionnaire score was 22 (16); the mean midazolam dose was 1.7 (1.1) mg with no correlation to preoperative anxiety scores. Pain ≥4 was present in 67% of patients 24 h after surgery and in 54% at seven days; at three months, 27% were classified as having chronic postsurgical pain. Preoperative anxiety correlated to pain severity at all time points. In multivariable regression, higher midazolam doses were associated with less pain during the first week, with no apparent effect on chronic pain. However, subgroup analyses uncovered an effect modification according to preoperative anxiety: the decrease in acute pain occurred in the low-anxiety patients with no effect on the high-anxiety group. Inversely, there was an increase in chronic postsurgical pain in the very anxious patients, without any effect on the low-anxiety group. Midazolam, generally used as an anxiolytic, might impact distinctively on pain depending on anxiety.
ABSTRACT
The risk factors for coronavirus disease 2019 (COVID-19) severity are still poorly understood. Considering the pivotal role of the gut microbiota on host immune and inflammatory functions, we investigated the association between changes in the gut microbiota composition and the clinical severity of COVID-19. We conducted a multicenter cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: (1) the WHO Clinical Progression Scale-mild, 19 (16.5%); moderate, 37 (32.2%); or severe, 59 (51.3%), and (2) the location of recovery from COVID-19-ambulatory, 14 (household isolation, 12.2%); hospitalized in ward, 40 (34.8%); or hospitalized in the intensive care unit, 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing, and the data obtained were further related to the clinical parameters of COVID-19 patients. The risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison to mild COVID-19 patients, the gut microbiota of moderate and severe patients have: (a) lower Firmicutes/Bacteroidetes ratio; (b) higher abundance of Proteobacteria; and (c) lower abundance of beneficial butyrate-producing bacteria such as the genera Roseburia and Lachnospira. Multivariable regression analysis showed that the Shannon diversity index [odds ratio (OR) = 2.85, 95% CI = 1.09-7.41, p = 0.032) and C-reactive protein (OR = 3.45, 95% CI = 1.33-8.91, p = 0.011) are risk factors for severe COVID-19 (a score of 6 or higher in the WHO Clinical Progression Scale). In conclusion, our results demonstrated that hospitalized patients with moderate and severe COVID-19 have microbial signatures of gut dysbiosis; for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker of COVID-19 severity.