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Automated phenotyping of postoperative delirium-like behaviour in mice reveals the therapeutic efficacy of dexmedetomidine.

ABSTRACT: Postoperative delirium (POD) is a complicated and harmful clinical syndrome. Traditional behaviour analysis mostly focuses on static parameters. However, animal behaviour is a bottom-up and hierarchical organizational structure composed of time-varying posture dynamics. Spontaneous and task-driven behaviours are used to conduct comprehensive profiling of behavioural data of various aspects of model animals. A machine-learning based method is used to assess the effect of dexmedetomidine. Fourteen statistically different spontaneous behaviours are used to distinguish the non-POD group from the POD group. In the task-driven behaviour, the non-POD group has greater deep versus shallow investigation preference, with no significant preference in the POD group. Hyperactive and hypoactive subtypes can be distinguished through pose evaluation. Dexmedetomidine at a dose of 25 μg kg^-1 reduces the severity and incidence of POD. Here we propose a multi-scaled clustering analysis framework that includes pose, behaviour and action sequence evaluation. This may represent the hierarchical dynamics of delirium-like behaviours.

SUBMITTER: Cao S

PROVIDER: S-EPMC10397202 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Automated phenotyping of postoperative delirium-like behaviour in mice reveals the therapeutic efficacy of dexmedetomidine.

Cao Silu S Wu Yiling Y Gao Zilong Z Tang Jinxuan J Xiong Lize L Hu Ji J Li Cheng C

Communications biology 20230802 1

Postoperative delirium (POD) is a complicated and harmful clinical syndrome. Traditional behaviour analysis mostly focuses on static parameters. However, animal behaviour is a bottom-up and hierarchical organizational structure composed of time-varying posture dynamics. Spontaneous and task-driven behaviours are used to conduct comprehensive profiling of behavioural data of various aspects of model animals. A machine-learning based method is used to assess the effect of dexmedetomidine. Fourteen ...[more]

PMID: 37532767

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Project description:BackgroundClinical trials have shown that dexmedetomidine might decrease the occurrence of postoperative delirium after major surgery, but neurosurgical patients were excluded from these studies. We aimed to determine the feasibility of conducting a full-scale randomized controlled trial of the effect of prophylactic low-dose dexmedetomidine on postoperative delirium in patients after elective intracranial operation for brain tumors.MethodsIn this single-center, parallel-arm pilot randomized controlled trial, adult patients who underwent an elective intracranial operation for brain tumors were recruited. Dexmedetomidine (0.1 μg/kg/hour) or placebo was continuously infused from intensive care unit (ICU) admission on the day of surgery until 08:00 AM on postoperative day one. Adverse events during the study-drug administration were recorded. The primary feasibility endpoint was the occurrence of study-drug interruption. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU during the first five postoperative days. The assessable rate of delirium evaluation was documented.ResultsSixty participants were randomly assigned to receive either dexmedetomidine (n = 30) or placebo (n = 30). The study-drug was stopped in two patients (6.7%) in the placebo group due to desaturation after new-onset unconsciousness and an unplanned reoperation for hematoma evacuation and in one patient (3.3%) in the dexmedetomidine group due to unplanned discharge from the ICU. The absolute difference (95% confidence interval) of study-drug interruption between the two groups was 3.3% (- 18.6 to 12.0%), with a noninferiority P value of 0.009. During the study-drug infusion, no bradycardia occurred, and hypotension occurred in one patient (3.3%) in the dexmedetomidine group. Dexmedetomidine tended to decrease the incidence of tachycardia (10.0% vs. 23.3%) and hypertension (3.3% vs. 23.3%). Respiratory depression, desaturation, and unconsciousness occurred in the same patient with study-drug interruption in the placebo group (3.3%). Delirium was evaluated 600 times, of which 590 (98.3%) attempts were assessable except in one patient in the placebo group who remained in a coma after an unplanned reoperation.ConclusionsThe low rate of study-drug interruption and high assessable rate of delirium evaluation supported a fully powered trial to determine the effectiveness of low-dose dexmedetomidine on postoperative delirium in patients after intracranial operation for brain tumors.Trial registrationThe trial was registered at ClinicalTrials.gov (NCT04494828) on 31/07/2020.

Project description:BackgroundPostoperative delirium (POD) is a common neurocognitive complication after type A aortic dissection (TAAD), which seriously affects the recovery of patients, and the current intervention timing and treatment methods are still uncertain. This prospective observational cohort study aimed to discuss the effect of dexmedetomidine on POD in patients undergoing TAAD surgery.MethodsBetween February 2022 and March 2023, 167 eligible patients aged 18 to 85 years who underwent TAAD surgery participated in this study. The patients were assigned to either the dexmedetomidine or the control group, which did not receive dexmedetomidine treatment. The primary outcome of interest was the incidence of delirium within five days following surgery. Secondary outcomes included intubation duration, length of stay in the intensive care unit (ICU), total postoperative hospital stay, incidence of non-delirium complications, and all-cause mortality within seven days. To account for differences in baseline characteristics between the groups, propensity score matching (PSM) was utilized.ResultsBefore PSM, the dexmedetomidine group was made up of 120 patients, whereas the control group comprised 47. The occurrence rate of POD increased from 35.0% in the dexmedetomidine group to 42.6% in the control group, but there was no significant difference [odds ratio (OR) 0.73; 95% confidence interval (CI): 0.37-1.45; P=0.36]. After 1:1 PSM, there were 42 patients in each of the dexmedetomidine and control groups. The occurrence of POD was 28.6% and 45.2% in the dexmedetomidine and control groups, respectively, with no statistically significant difference observed (OR 0.48; 95% CI: 0.20-1.20; P=0.12). The dexmedetomidine group showed a shorter ICU hospitalization time and postoperative hospital stay than the control group, but the differences were not statistically significant. Furthermore, the two groups had no statistical differences in other secondary outcomes.ConclusionsIntraoperative dexmedetomidine did not decrease the occurrence rate of POD in TAAD patients. Additionally, no significant differences were observed between the dexmedetomidine and control groups regarding the occurrence of non-delirium complications, intubation time, ICU hospitalization time, and postoperative hospital stay.

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Automated phenotyping of postoperative delirium-like behaviour in mice reveals the therapeutic efficacy of dexmedetomidine.

Publications

Automated phenotyping of postoperative delirium-like behaviour in mice reveals the therapeutic efficacy of dexmedetomidine.

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