Postoperative pain-related outcomes and perioperative pain management in China: a population-based study.

Background: Postoperative pain poses a significant challenge to the healthcare system and patient satisfaction and is associated with chronic pain and long-term narcotic use. However, systemic assessment of the quality of postoperative pain management in China remains unavailable. Methods: In this cross-sectional study, we analyzed data collected from a nationwide registry, China Acute Postoperative Pain Study (CAPOPS), between September 2019 and August 2021. Patients aged 18 years or above were required to complete a self-reported pain outcome questionnaire on the first postoperative day (POD1). Perioperative pain management and pain-related outcomes, including the severity of pain, adverse events caused by pain or pain management, and perception of care and satisfaction with pain management were analyzed. Findings: A total of 26,193 adult patients were enrolled. There were 48.7% of patients who had moderate-to-severe pain on the first day after surgery, and pain severity was associated with poor recovery and patient satisfaction. The systemic opioid use was 68% on the first day after surgery, and 89% of them were used with intravenous patient-controlled analgesia, while the rate of postoperative nerve blocks was low. Interpretation: Currently, almost half of patients still suffer from moderate-to-severe pain after surgery in China. The relatively high rate of systemic opioid use and low rate of nerve blocks used after surgery suggests that more effort is needed to improve the management of acute postoperative pain in China. Funding: National Key Research and Development Program of China (No. 2018YFC2001905).

Intraoperative dexmedetomidine on postoperative pain in gastrointestinal surgery: an observational study.

BACKGROUND: Dexmedetomidine (DEX) is widely used for adjuvant sedation and analgesia in gastrointestinal surgeries. The authors aimed to reassess the effects of intraoperative DEX on acute pain by comprehensive analysis of the multiple dimensions of pain. MATERIALS AND METHODS: In this multicentre cohort study, patients undergoing gastrointestinal surgeries were prospectively enrolled in the China Acute Postoperative Pain Study. Patients were divided into DEX and non-DEX groups based on whether DEX was used during surgery. Patient satisfaction with pain treatment (rated on a numeric rating score, 0-10) and other pain-related outcomes were evaluated using the International Pain Outcome Questionnaire on the first postoperative day. The effects of intraoperative DEX were analyzed using logistic or linear regression for dichotomous or continuous variables, respectively. Propensity score matching and subgroup analyses were performed to appraise the correlation between intraoperative DEX and postoperative pain outcomes. RESULTS: Of the 1260 patients eligible for analysis, 711 (56.4%) received intraoperative DEX. Propensity score matching resulted in 415 patients in each group. Intraoperative DEX was associated with higher patient satisfaction (ß: 0.556; 95% CI: 0.366-0.745), and a decrease in the percentage of time spent in severe pain (ß: -0.081; 95% CI: -0.104- -0.058), anxiety (odds ratio: 0.394; 95% CI: 0.307-0.506), helplessness (odds ratio: 0.539; 95% CI: 0.411-0.707), and postoperative opioid consumption (ß: -16.342; 95% CI: -27.528- -5.155). CONCLUSIONS: Intraoperative DEX was associated with the prognosis of acute postoperative pain in multiple aspects in patients undergoing major gastrointestinal surgery, including increased patient satisfaction, and a reduction in the duration of severe pain, postoperative anxiety and helplessness, and postoperative opioid consumption. Future studies to determine the dose and timing of DEX administration on pain-related outcomes are warranted.

Assessing Hemorrhagic Shock Severity Using the Second Heart Sound Determined from Phonocardiogram: A Novel Approach.

Introduction: Hemorrhagic shock (HS) is a severe medical emergency. Early diagnosis of HS is important for clinical treatment. In this paper, we report a flexible material-based heart sound monitoring device which can evaluate the degree of HS through a phonocardiogram (PCG) change. Methods: Progressive hemorrhage treatments (H1, H2, and H3 stage) were used in swine to build animal models. The PCG sensor was mounted on the chest of the swine. Routine monitoring was used at the same time. Results: This study showed that arterial blood pressure decreased significantly from the H1 phase, while second heart sound amplitude (S2A) and energy (S2E) decreased significantly from the H2 phase. Both S2A and S2E correlated well with BP (p < 0.001). The heart rate, pulse pressure variation and serum hemoglobin level significantly changed in the H3 stage (p < 0.05). Discussion: The change of second heart sound (S2) was at the H2 stage and was earlier than routine monitoring methods. Therefore, PCG change may be a new indicator for the early detection of HS severity.

Association of Diabetes Mellitus With Postoperative Complications and Mortality After Non-Cardiac Surgery: A Meta-Analysis and Systematic Review.

Background: Although a variety of data showing that diabetes mellitus (DM) (Type 1 or Type 2) is associated with postoperative complication, there is still a lack of detailed studies that go through the specific diabetic subgroups. The goal of this meta-analysis is to assess the relationship between DM and various complications after non-cardiac surgery. Methods: We searched articles published in three mainstream electronic databases (PubMed, EMBASE, Web of science) before November, 2020. A random effects model was conducted since heterogeneity always exist when comparing results between different types of surgery. Results: This paper included 125 studies with a total sample size of 3,208,776 participants. DM was a risk factor for any postoperative complication (Odds ratio (OR)=1.653 [1.487, 1.839]). The risk of insulin-dependent DM (OR=1.895 [1.331, 2.698]) was higher than that of non-insulin-dependent DM (OR=1.554 [1.061, 2.277]) for any postoperative complication. DM had a higher risk of infections (OR=1.537 [1.322, 1.787]), wound healing disorders (OR=2.010 [1.326, 3.046]), hematoma (OR=1.369 [1.120, 1.673]), renal insufficiency (OR=1.987 [1.311, 3.013]), myocardial infarction (OR=1.372 [0.574, 3.278]). Meanwhile, DM was a risk factor for postoperative reoperation (OR=1.568 [1.124, 2.188]), readmission (OR=1.404 [1.274, 1.548]) and death (OR=1.606 [1.178, 2.191]). Conclusions: DM is a risk factor for any postoperative complications, hospitalization and death after non-cardiac surgery. These findings underscore the importance of preoperative risk factor assessment of DM for the safe outcome of surgical patients.

Dysfunction of EAAT3 Aggravates LPS-Induced Post-Operative Cognitive Dysfunction.

Numerous results have revealed an association between inhibited function of excitatory amino acid transporter 3 (EAAT3) and several neurodegenerative diseases. This was also corroborated by our previous studies which showed that the EAAT3 function was intimately linked to learning and memory. With this premise, we examined the role of EAAT3 in post-operative cognitive dysfunction (POCD) and explored the potential benefit of riluzole in countering POCD in the present study. We first established a recombinant adeno-associated-viral (rAAV)-mediated shRNA to knockdown SLC1A1/EAAT3 expression in the hippocampus of adult male mice. The mice then received an intracerebroventricular microinjection of 2 µg lipopolysaccharide (LPS) to construct the POCD model. In addition, for old male mice, 4 mg/kg of riluzole was intraperitoneally injected for three consecutive days, with the last injection administered 2 h before the LPS microinjection. Cognitive function was assessed using the Morris water maze 24 h following the LPS microinjection. Animal behavioral tests, as well as pathological and biochemical assays, were performed to clarify the role of EAAT3 function in POCD and evaluate the effect of activating the EAAT3 function by riluzole. In the present study, we established a mouse model with hippocampal SLC1A1/EAAT3 knockdown and found that hippocampal SLC1A1/EAAT3 knockdown aggravated LPS-induced learning and memory deficits in adult male mice. Meanwhile, LPS significantly inhibited the expression of EAAT3 membrane protein and the phosphorylation level of GluA1 protein in the hippocampus of adult male mice. Moreover, riluzole pretreatment significantly increased the expression of hippocampal EAAT3 membrane protein and also ameliorated LPS-induced cognitive impairment in elderly male mice. Taken together, our results demonstrated that the dysfunction of EAAT3 is an important risk factor for POCD susceptibility and therefore, it may become a promising target for POCD treatment.

Integrative Analysis of lncRNA and mRNA and Profiles in Postoperative Delirium Patients.

Delirium is a common serious complication that often occurs after major surgery. The goals of this study were to explore the expression profiles and functional networks of long non-coding RNAs (lncRNAs) and mRNAs in patients of postoperative delirium (POD). Microarray analysis was performed on the peripheral blood samples to identify differentially expressed (DE) lncRNAs and mRNAs in 4 POD patients and 4 non-POD volunteers. DE lncRNAs and mRNAs were validated by quantitative reverse transcription PCR (RT-qPCR). Bioinformatic analyses were performed to identify the critical biological functions and signaling pathways involved in POD. A total of 1195 DE lncRNAs and 735 DE mRNAs were identified between the POD and non-POD groups. Verified by the RT-qPCR, we identified 14 DE lncRNAs that may relate to the pathogenesis of POD. These 14 DE lncRNAs play important regulatory roles in "glutamate and 5-hydroxytryptamine," "synaptotagmin 7," "transient receptor potential channel," "interleukin-2 production." There was a regulatory relationship between lncRNA ENST00000530057 and synaptotagmin (Syt) 7 mRNA. The mRNA level of PCLO was up-regulated in POD group. This study showed abundant DE lncRNAs and mRNAs in POD that might help in deciphering the disease pathogenesis.

MiR-190a potentially ameliorates postoperative cognitive dysfunction by regulating Tiam1.

BACKGROUND: Postoperative cognitive dysfunction (POCD) affects a large number of post-surgery patients, especially for the elderly. However, the etiology of this neurocognitive disorder is largely unknown. Even if several studies have reported a small number of miRNAs as the essential modulatory factors in POCD, these findings are still rather limited. The aim of current study was to screen the POCD-related miRNAs in the hippocampus tissues and investigate the target genes of differentially expressed miRNAs and their biological functions underlying POCD pathophysiology. METHODS: The miRNA microarray was used to find the abnormal expression of miRNAs in the hippocampus tissues from the POCD model mice to normal mice (Discovery cohort, 3 vs 3). The nominal significant results were validated in an independent sample of hippocampus tissues of 10 mice based on same miRNA microarray (Replication cohort, 5 vs 5). Expression level of the most significantly abnormal miRNA was further validated by real-time quantitative polymerase chain reaction (PCR). To determine the expression pattern among miRNAs and genes and detect the interactions, we conducted a weighted gene co-expression network analysis (WGCNA) in the miRNAs and genes expression data from hippocampus tissue of wild type mice (n = 24). The target genes of miRNAs were predicted using the miRWalk3.0 software. Furthermore, we used the ClueGO software to decipher the pathways network and reveal the biological functions of target genes of miRNAs. RESULTS: We found that nine miRNAs showed significant associations with POCD in both datasets. Among these miRNAs, mmu-miR-190a-3p was the most significant one. By performing WGCNA analysis, we found 25 co-expression modules, of which mmu-miR-190a-3p was significantly anti-correlated with red module. Moreover, in the red module, 314 genes were significantly enriched in four pathways such as axon guidance and calcium signaling pathway, which are well-documented to be associated with psychiatric disorders and brain development. Also, 169 of the 314 genes were highly correlated with mmu-miR-190a-3p, and four genes (Sphkap, Arhgef25, Tiam1, and Ntrk3) had putative binding sites at 3'-UTR of mmu-miR-190a-3p. Based on protein-protein network analysis, we detected that Tiam1 was a central gene regulated by the mmu-miR-190a-3p. CONCLUSIONS: Taken together, we conclude that mmu-miR-190a-3p is involved in the etiology of POCD and may serve as a novel predictive indicator for POCD.