Background: The addition of the adjuvant dexmedetomidine to a nerve block improves the quality of the block and reduces perioperative opioid consumption. The aim of this study was to assess the effect of dexmedetomidine as an adjuvant for the thoracic paravertebral block (TPVB) in postoperative pain control after video-assisted thoracoscopic surgery (VATS). Methods: Sixty-six males, aged 15–40 years, with spontaneous pneumothorax scheduled for VATS wedge resection were enrolled. Following surgery, ultrasound-guided TPVB was performed on the T3 and T5 levels with 30 mL of 0.5% ropivacaine, plus adjuvant dexmedetomidine 50 μg or normal saline. The primary outcome was cumulative fentanyl consumption at 24 h. Pain severity, the requirement for additional rescue analgesics, hemodynamic variations, and side effects were also evaluated. Results: Median postoperative cumulative fentanyl consumption at 24 h was significantly lower in the dexmedetomidine group (122.6 (interquartile range (IQR) 94.5–268.0) μg vs. 348.1 (IQR, 192.8–459.2) μg, p-value = 0.001) with a Hodges–Lehman median difference between groups of 86.2 (95% confidence interval (CI), 4.2–156.4) mg. Coughing numeric rating scale (NRS) was lower in the dexmedetomidine group at postoperative 2, 4, 8, and 24 h. However, resting NRS differed significantly only after 4 h postoperative. Conclusions: Dexmedetomidine as an adjunct in TPVB provided effective pain relief and significantly reduced opioid requirement in VATS.
Nuclear factor of activated T cells (NFAT5) is a well-known transcription factor that regulates the expression of genes involved in osmotic stress. However, the role of NFAT5 in inflammatory pain remains unknown. Here, we studied the function of NFAT5 in inflammatory pain using NFAT5-heterozygous (Het) mice. To study inflammatory pain, we injected 10 µL of 2% formalin into the right hind paws of mice and monitored pain behaviors, such as licking, lifting, and flinching, for 60 min. After the first 15 min (phase I), there were no significant differences in pain behaviors between wild-type (WT) and NFAT5-Het mice. However, from 15–60 min (phase II), NFAT5-Het mice displayed significantly fewer pain behaviors compared to WT mice. Further, the expression levels of inflammatory-pain-related factors, including c-Fos, phosphorylated extracellular signal-regulated kinase (p-ERK), and phosphorylated n-methyl-D-aspartate receptor subunit 2B (p-NR2B), were significantly elevated in the spinal dorsal neurons of formalin-treated WT mice but was not elevated in NFAT5-Het mice. Similarly, c-Fos, p-ERK, and p-NR2B levels were significantly higher in glutamate-treated PC12 neuronal cells but were not affected by Nfat5 silencing in glutamate-treated PC12 cells. Altogether, our findings suggest that NFAT5 deficiency may mitigate formalin-induced inflammatory pain by upregulating mammalian target of rapamycin (mTOR) expression and downregulating its downstream factors in spinal dorsal neurons. Therefore, NFAT5 is a potential therapeutic target for the treatment of inflammatory pain.
Background: Although the loop electrosurgical excision procedure (LEEP) is a brief procedure, it can cause severe pain and discomfort to patients in the absence of adequate sedation. An admixture of ketamine with propofol (ketofol), may reduce patient movement due to insufficient sedation while providing hemodynamic and respiratory stability. This study evaluated the ability of two ratios of a propofol–ketamine combination, compared with propofol alone, to reduce patient movement during procedural sedation for LEEPs. Methods: One hundred and twenty women scheduled for a LEEP were randomly assigned to three groups. Anesthesia was induced with 1 mg/kg propofol (group P), 1 mg/kg propofol and 0.33 mg/kg ketamine (group K1), or 1 mg/kg propofol and 0.66 mg/kg ketamine (group K2). The primary outcome was the incidence of adduction motion in the lower extremities during the procedure. The requirements for respiratory interventions, changes in vital signs, sedation score, additional anesthetic usage, and surgeon and patient satisfaction were also evaluated. Results: The incidence of adduction motion was significantly lower in groups K1 and K2 than in group P (overall p-value <0.001) but did not differ significantly in groups K1 and K2. Group K2 needed more jaw thrust maneuvers than group K1. Additional propofol usage was lower and surgeon satisfaction scores higher in groups K1 and K2 than in group P. Conclusion: A propofol–ketamine combination is more effective than propofol alone in reducing procedural interference during LEEPs. However, increasing the dose of ketamine showed no additional benefit.
Background and objectives: There are several studies that sevoflurane could enhance proliferation of cancer cells, while others suggest no effect on clinical outcome. We conducted in vivo and in vitro experiments to investigate the effects of sevoflurane, a volatile anesthetic, on proliferation and outcomes of Lewis lung carcinoma (LLC) cells. Materials and Methods: A total of 37 mice were injected with LLC cells to compare the tumor size and survival of the sevoflurane exposed group (sevo group) and control group. The sevo group was exposed to 2% sevoflurane and 4 L/min of oxygen for 1 h per day 3 times per week, and the control group was exposed only to 4 L/min of oxygen. In vitro study, 12 plates incubated with LCC cells. 6 plates were exposed to 2% sevoflurane for 1 hr/day for 3 days and 6 plates were not exposed, and cell proliferation was compared after 3 days. Results: There were no significant differences in survival or tumor size between mice exposed to sevoflurane and control mice (survival: 29.06 ± 4.45 vs. 28.76 ± 3.75, p = 0.836; tumor size: 0.75 (0.41–1.02) vs. 0.49 (0.11–0.79), p = 0.153). However, in vitro study, the proliferation of LLC cells exposed to sevoflurane increased by 9.2% compared to the control group (p = 0.018). Conclusions: Sevoflurane (2 vol%) exposure could promote proliferation of LLC cells in vitro environment, but may not affect proliferation of LLC cells in vivo environment. These results suggest that in vitro studies on the effects of anesthetics on cancer may differ from those of in vivo or clinical studies.
Yeojung Kim, Chahyun Oh, Sookyoung Youn, Sangwon Yun, Hyunwoo Park, Wonhyung Lee, Yoon-Hee Kim, YoungKwon Ko, and Boohwi Hong. Anesth Pain Med 2019;14:222-9. https://doi.org/10.17085/apm.2019.14.2.222
Opioid-sparing effects of nefopam during patient-controlled analgesia (PCA) are well demonstrated. We hypothesized that postoperative pain control with an opioid-equivalent dose of nefopam as a single analgesic agent for PCA would not be inferior to fentanyl in laparoscopic gynecologic surgery. In total, 135 patients were randomly assigned to the N (nefopam 200 mg), NF (fentanyl 500 mcg + nefopam 100 mg), and F (fentanyl 1000 mcg) groups (n = 45 patients per group). The primary outcome was the numerical rating scale (NRS) score at rest at 6 h postoperatively, and the non-inferiority limit was set to 1. Secondary outcomes were pain severity and incidence of nausea and vomiting for 48 h postoperatively. Mean differences (MD) in primary outcome between the N and F groups were 0.4 (95% confidence interval (CI) −0.5 to 1.3). The upper limit of 95% CI exceeded the non-inferiority limit. The N group showed higher pain scores than the NF group (MD, 1.1; 95% CI, 0.3–1.9) in pairwise comparisons. No significant intergroup differences were observed in the cumulative dose of PCA usage and incidence of postoperative nausea and vomiting (PONV). In laparoscopic gynecological surgery, nefopam alone showed limited efficacy for postoperative pain control.