Daily Anesthesiology Research Analysis

Severely brain-injured patients may enter a spectrum of conditions collectively known as disorders of consciousness. This spectrum includes clinical conditions such as unresponsive wakefulness syndrome or minimally conscious state, where the behavioural assessment of consciousness can often be deceptive. To bridge this dissociation, neuroimaging techniques are employed to identify the residual brain functions. Each neuroimaging modality imperfectly captures distinct aspects of brain preservation-functional, anatomical, or both. In this study, we adopt a comprehensive approach by integrating the neurophysiology and neuroimaging modalities available from the standard and advanced clinical assessments through interpretable machine learning. The electrophysiological modalities included high-density EEG (resting state and task), whereas neuroimaging modalities included anatomical and resting-state functional MRI, diffusion MRI and 18F-fluorodeoxyglucose PET. Our investigation reveals that specific modalities, such as functional assessments, provide comprehensive insights into the currently evaluated state of consciousness, the diagnosis of the patients. Conversely, structural modalities offer valuable information about the patient's evolution within the consciousness spectrum. We validate the proposed analysis with data coming from other centres with different acquisition parameters. Importantly, we demonstrate that model performance improves with an increase in the number of modalities. We observe a higher inter-modality disagreement for minimally conscious state patients and those patients who improve. Lastly, we observe a difference in feature importances between diagnosis and prognosis, with an interaction between modality and anatomical structures: some subcortical markers tend to contribute more to prognosis, while other cortical markers are more informative for diagnosis. This integrative multimodal and machine learning methodology presents a promising avenue for a more nuanced understanding of disorders of consciousness, contributing to enhanced diagnostic precision, prognostic capabilities and the personalization of rehabilitative strategies in clinical practice.

BACKGROUND: Cardiac arrest (CA) is a major cause of mortality and morbidity. Accurate prediction of neurological outcome and survival remains challenging. In this context, our study aimed to explore novel molecular biomarkers that could provide additional insights into the pathophysiology of brain injury after CA and potentially distinguish patients with no brain injury (CPC 1) from those with any degree of neurological damage from moderate injury up to death (CPC 2-5), and complement existing prognostic tools. METHODS: Whole blood samples collected 48 h after return of spontaneous circulation were analyzed by RNA sequencing in a subgroup of 50 CA patients from the monocenter North Pole cohort, and by quantitative PCR in 233 patients from the same cohort as well as in 511 patients from the multicenter TTM trial. The association of gene expression changes with 6-month neurological outcome (assessed by the Cerebral Performance Category (CPC) score) and survival was studied. RESULTS: In a discovery phase with a subset of 50 patients from the North Pole cohort (25 CPC 1 and 25 CPC 5), direct RNA sequencing identified the solute carrier family 2 member 1 (SLC2A1), a gene encoding a major glucose transporter at the blood-brain barrier (GLUT1), as significantly upregulated in CPC 5 patients (dead with severe neurological impairment) compared to survivors without neurological sequelae (CPC 1). This upregulation was confirmed by quantitative PCR and extended to the entire North Pole cohort (p < 0.001). SLC2A1 was an independent predictor of neurological sequelae or death in this cohort. In the TTM trial, SLC2A1 was also upregulated in patients with neurological sequelae or death (p < 0.001) and was an independent predictor of neurological sequelae or death, providing an incremental predictive value to a baseline clinical model (odds ratio = 2.06, 95% confidence interval 1.31-3.4, p = 2.82E-03, and likelihood ratio test p < 0.001). CONCLUSION: Blood level of SLC2A1 is a tentative blood biomarker that may aid in neurological outcome prediction after CA and also provide new insights into post-CA injury mechanisms.

BACKGROUND: Postoperative pain and opioid-related adverse effects remain significant concerns in pediatric surgical patients. Esketamine, an NMDA receptor antagonist, may enhance analgesia and reduce opioid consumption at low doses. This study aimed to evaluate the effects of low-dose esketamine combined with hydromorphone for PCIA on postoperative pain control, bowel recovery, and safety in children undergoing abdominal surgery. METHODS: This randomized controlled clinical trial enrolled children aged from 3 to 12 years, who were scheduled to undergo abdominal surgery under general anesthesia and consented to the use of a PCIA pump. The study compared two groups. In the EH group (n = 49), esketamine (10 μg/kg/h) and hydromorphone (1 μg/kg/h), with bolus doses of hydromorphone 2 μg/kg and esketamine 20 μg/kg. In the H group (n = 49), analgesia was provided solely with hydromorphone (2 μg/kg/h), with bolus doses of 4 μg/kg. An identical lockout interval of 20 min was used. The primary outcome measured was the time-weighted average (TWA) pain score in the first 24 h postoperatively. Key secondary outcomes included the cumulative hydromorphone consumption within 48 h, the incidence of adverse events within 48 h, the time to first defecation, and the length of postoperative hospital stay. RESULTS: In comparison to the H group, the EH group demonstrated a significantly lower movement TWA pain score in the first 24 h postoperatively (1.90 vs 3.67; mean difference (MD), 1.23; 95% confidence interval (CI) (0.50-1.94), P < 0.001). Additionally, the EH group showed a marked reduction in cumulative hydromorphone consumption within 48 h postoperatively (0.05 mg/kg vs 0.11 mg/kg; MD, 0.06 (95% CI 0.05-0.07); P < 0.001), a decreased requirement rate for glycerin enema (8.2% vs 32.7%; relative risk (RR), 0.73 (95% CI 0.59-0.91); P = 0.003), and a shorter length of postoperative hospital stay (8 days vs 10 days; MD, 1.00 (95% CI 0.00-3.00); P = 0.025). CONCLUSIONS: Low-dose esketamine combined with hydromorphone for PCIA significantly reduces the movement TWA pain score in the first 24 h post-surgery and decreases hydromorphone consumption within the first 48 h. Additionally, it reduces the need for glycerin enemas and shortens the length of hospital stay in children who have undergone abdominal surgery. The observed reduction in movement TWA pain score in the first 24 h and opioid consumption may facilitate improved continuous support for the early recovery of these children. TRIAL REGISTRATION: The trial was registered before patient enrollment at the Chinese Clinical Trial Registry (www. chictr.org.cn) (ChiCTR2200064762, date of registration: October 17, 2022).