The effect of age on outpatient pediatric procedural sedation with intranasal dexmedetomidine and oral midazolam.

Procedural sedation for diagnostic examination is a common practice in children. The study aims to analyze the sedative effect and safety of intranasal dexmedetomidine combined with oral midazolam in outpatient pediatric procedural sedation across different age groups and to assess the incidence of sedation failure. From February 2021 to September 2021, children who underwent procedural sedation were retrospectively enrolled. The children were divided into 4 groups based on age: the infant group (0 to 1 year old), toddler group (1 to 3 years old), preschool group (3 to 6 years old), and school-age group (6 to 12 years old). Two-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam were used for sedation. The sedation success rate after rescue, sedation success rate, onset time of sedation, and the sedation time were recorded. The incidence of adverse events and the risk factors for sedation failure were also analyzed. A total of 4758 patients were identified. After exclusion, 3149 patients were ultimately enrolled. The combination of 2-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam resulted in a total success rate of 99.7% and a sedation success rate of 91.4%. The sedation success rate varied among the four groups: 90.2% in the infant group, 93.1% in the toddler group, 92.7% in the preschool group, and 78.4% in the school-age group. The sedation success rate was significantly lower in the school-age group compared to the other three groups (P < 0.001). The onset time of sedation was shorter in infant (22 min, IQR: 18-28 min, P < 0.001) and longer in the school-age group (30 min, IQR: 25-35 min, P < 0.05). Additionally, the infants had a longer sedation time (110 min, IQR: 90-135 min, P < 0.001) and a higher rate of delayed recovery (27.5%, all P < 0.001). The incidence of adverse events was low (4.70%), which bradycardia (2.03%) being the most common. Age (0-1 year and > 6 years), weight, ASA class II, and history of failed sedation were identified as risk factors of sedation failure.   Conclusion: Intranasal administration of 2-mcg/kg dexmedetomidine combined with oral administration of 0.5-mg/kg midazolam was found to be efficient and safety for pediatric procedural sedation. Different age groups of children exhibited distinct sedation characteristics, and age was identified as a risk factor affecting the efficacy of sedation. What is Known: • Procedural sedation for diagnostic examination is a common practice in children. • The combination of dexmedetomidine with midazolam can improve sedative effects. What is New: • The success rate of sedation using a combination of 2-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam was significantly lower in school-age children as compared to infants, toddlers, and preschoolers. • The onset time of sedation increased with age, and the sedation time was found to be longer in infant patients.

Endothelial cell dysfunction and targeted therapeutic drugs in sepsis.

Sepsis is a life-threatening organ dysfunction caused by an abnormal host response to microbial infections. During its pathogenesis, vascular endothelial cells (ECs) play a pivotal role as essential components in maintaining microcirculatory homeostasis. This article aims to comprehensively review the multifaceted physiological functions of vascular ECs, elucidate the alterations in their functionality throughout the course of sepsis, and explore recent advancements in research concerning sepsis-related therapeutic drugs targeting ECs.

A New Nomogram for Predicting 30-Day In-Hospital Mortality Rate of Acute Cholangitis Patients in the Intensive Care Unit.

Purpose: Acute cholangitis (AC) is a widespread acute inflammatory disease and the main cause of septic shock, which has a high death rate in hospitals. At present, the prediction models for short-term mortality of AC patients are still not ideal. We aimed at developing a new model that could forecast the short-term mortality rate of AC patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0). There were a total of 506 cases of AC patients that were included. Patients were given a 7 : 3 split between the training set and the validation set after being randomly assigned to one of the groups. Multivariate logistic regression was used to create an AC patient predictive nomogram for 30-day mortality. The overall efficacy of the model is evaluated using the area under the receiver operating characteristic curve (AUC), the calibration curve, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and a decision curve analysis (DCA). Results: Out of 506 patients, 14.0% (71 patients) died. The training cohort had 354 patients, and the validation cohort had 152 patients. GCS, SPO2, albumin, AST/ALT, glucose, potassium, PTT, and peripheral vascular disease were the independent risk factors according to the multivariate analysis results. The newly established nomogram had better prediction performance than other common scoring systems (such as SOFA, OASIS, and SAPS II). For two cohorts, the calibration curve demonstrated coherence between the nomogram and the ideal observation (P > 0.05). The clinical utility of the nomogram in both sets was revealed by decision curve analysis. Conclusion: The novel prognostic model was effective in forecasting the 30-day mortality rate for acute cholangitis patients.

Development of a Novel Nomogram Incorporating Red Blood Cell Distribution Width-Albumin Ratio for the Prediction of 30-day Mortality in Acute Pancreatitis Patients.

Purpose: The available nomograms used to predict acute pancreatitis (AP) are not comprehensive. We sought to investigate the effect of red blood cell distribution width (RDW)-albumin ratio (RA) on prognosis of patients with AP and develop a new nomogram to identify AP patients at high risk for mortality. Methods: We used data from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0). A total of 487 patients with acute pancreatitis were included. Patients enrolled in the study were randomly assigned to the training set and validation set at a 7 : 3 ratio. According to the 30-day mortality rate, the data were divided into a survival group and a death group. Multivariate logistic regression was used to establish a prognostic nomogram for predicting the 30-day mortality in AP patients. The area under the receiver operating characteristic curve (AUC), calibration curve, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and a decision curve analysis (DCA) are used to verify the overall performance of the model. Results: Among 487 patients, 54 patients died (11.1%). 338 patients were assigned to the training cohort and 149 were assigned to the validation cohort. The multivariate analysis results showed that RA, age, heart rate, temperature, AST/ALT, BUN, hemoglobin, potassium, and bilirubin were independent risk factors. The prediction performance of the newly established nomogram was better than those of other common scoring systems (including SOFA, OASIS, and APSIII). The nomogram suggests that RA (OR = 1.706, 95% CI: 1.367-2.185) is the most significant laboratory test indicator influencing prognosis. Conclusion: The new nomogram incorporating RA performed well in predicting AP short-term mortality. A prospective study with a larger sample is needed to validate our findings.

Antagonism of Cerebral High Mobility Group Box 1 Ameliorates Dendritic Cell Dysfunction in Sepsis.

Sepsis has emerged as a global health issue, and accounts for millions of deaths in intensive care units. Dysregulation of the immune response reportedly contributes to the pathogenesis and progression of this lethal condition, which involves both the dysfunction of immune cells and incompetent immunomodulatory mechanisms. High mobility group box 1 (HMGB1) is known as a later inflammatory mediator and is critically involved in the severity and prognosis of sepsis by inducing intractable inflammation and dysfunction of various immune cells. In the present study, we found that intracerebroventricular (ICV) injection of Box A, a specific antagonist of HMGB1, restored the dysregulated response of splenic dendritic cells (DCs) in septic mice by enhancing the expression of surface molecules, including CD80, CD86, and MHC-II, as well as improving DC priming of T lymphocytes. Cerebral HMGB1 was also confirmed to have potent inhibitory effects on DC functions when administrated by ICV injection in normal mice. The brain cholinergic system was found to mediate the immunomodulatory effects of central HMGB1, as it exhibited enhanced activity with persistent HMGB1 exposure. Furthermore, the inhibitory effects of cerebral HMGB1 on the response of peripheral DCs were also blocked by α7nAchR gene knockout. These findings provide novel insight into the relationship between cerebral HMGB1 and splenic DC dysfunction during sepsis, which is, at least in part, dependent on cholinergic system activity.