Effects of glycopyrrolate and atropine for oral secretions and perioperative hemodynamics in children undergoing tonsillectomy and adenoidectomy: a prospective, single-center, randomized, double-blind, controlled trial.

Introduction: Glycopyrrolate is commonly researched as a preoperative medication or in conjunction with cholinesterase inhibitors to counteract the lingering muscarinic effects of non-depolarizing muscarinic agents. However, studies have yielded inconsistent results regarding the superiority of glycopyrrolate over other anti-cholinergic drugs, such as atropine, particularly its effect on heart rate, blood pressure (BP), and glandular secretions. This study aimed to evaluate the differences in perioperative oral secretions, hemodynamics, and recovery quality with glycopyrrolate versus those with atropine before anesthesia induction in children undergoing tonsillectomy and adenoidectomy. Methods: In this prospective, single-center, randomized, double-blind, controlled trial, a total of 103 children were randomly assigned to group A (n = 51, glycopyrrolate 0.005 mg/kg) or B (n = 52, atropine 0.01 mg/kg). The follow-up anesthetic induction and maintenance protocols were the same in both groups. Vital signs, duration of surgery, extubation time, degree of wetness around the vocal cords during tracheal intubation, weight of oral secretions, and perioperative complications were recorded. Results: No significant differences were observed in the degree of wetness around the vocal cords during tracheal intubation, as well as in the weight of oral secretions, duration of surgery, or extubation time, between the two groups. The intraoperative and postoperative heart rates were lower in group A than in group B (110.18 ± 10.58 vs. 114.94 ± 11.14, p = 0.028; 96.96 ± 10.81 vs. 103.38 ± 10.09, p = 0.002). The differences observed in the intraoperative and preoperative heart rates were lower in group A than in group B (23.84 ± 9.62 vs. 29.65 ± 8.75, p = 0.002). The differences observed in the postoperative and preoperative heart rates were lower in group A than in group B (10.63 ± 9.97 vs. 18.09 ± 9.39, p = 0.000). Conclusion: Glycopyrrolate showed a smoother change in heart rate than atropine during and after tonsillectomy and adenoidectomy, with no effect on BP or recovery quality, and did not increase oral secretions. The findings indicate that glycopyrrolate can serve as an alternative to atropine to prevent secretions in anesthesia induction for tonsillectomy and adenoidectomy in children. Trial registration: This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2200063578; Date of Registration: 12/09/2022).

Effect of different head-high lateral extubation on adverse reactions in the peri-extubation period of pediatric OSAS surgery under general anesthesia.

BACKGROUND: Children with OSAS are prone to various airway complications during tracheal extubation after tonsillectomy and adenoidectomy due to oropharyngeal secretions and oozing blood. However, few studies have examined the effect of position on airway complications after tracheal extubation in children with OSAS. The aim of this study was to investigate the appropriate position for extubation in children with OASA. METHODS: A total of 459 children aged 3-14 years with OSAS who underwent tonsillectomy and adenoidectomy were recruited for this study. All children were treated with the same surgical approach and standard anesthesia methods of induction of anesthesia, tracheal intubation and maintenance of anesthesia. At the end of surgery, the children were delivered to the post anesthesia care unit and randomly divided into three groups: Group A: Head-high 0° in lateral position; Group B: Head-high 15° in lateral position; Group C: Head-high 30° in lateral position. The main outcomes of this study were the pulse oxygen saturation (SpO2) and the Sedation-Agitation Scale (SAS) scores of the children after extubation, the outflow of oral-nasal secretions and the respiratory complications. Secondary outcomes were blood pressure, heart rate, end-respiratory carbon dioxide, respiratory rate, and post-operative awakening time of the children in three groups. RESULTS: Data from a total of 423 children were statistically analyzed, 141 in Group A, 142 in Group B, and 140 in Group C. The main results showed a significant decrease in choking response after extubation in Group B (46.5%) and Group C (40.7%) compared to Group A (60.3%) (P < 0.05). The SAS score for postoperative agitation was higher in Group A (4.6 [Formula: see text] 0.9) than in Group B (4.4 [Formula: see text] 0.7) and Group C (4.3 [Formula: see text] 0.6) (P < 0.05). Also the SpO2 after extubation was higher in Group B (97.2%) and Group C (97.1%) than in Group A (95.8%) (P < 0.05). In contrast, there was no difference in the occurrence of respiratory complication and postoperative agitation in children between Group B and Group C (all P > 0.05). In addition, there was no difference in the amount of oral-nasal secretions among the children in the three groups (all P > 0.05). CONCLUSION: The head-high 15° lateral position and head-high 30° lateral position can reduce the incidence of airway complications and agitation and provide safe and comfortable extubation conditions for children during the peri-extubation period after tonsillectomy and adenoidectomy, which has certain clinical guidance value. TRIAL REGISTRATION: Registration Number: NO.ChiCTR2200055835(20,01,2022) https://www.chictr.org.cn.

Effect of Deliberate Hypotension on Regional Cerebral Oxygen Saturation During Functional Endoscopic Sinus Surgery: A Randomized Controlled Trial.

Background: Deliberate hypotension can reduce bleeding and improve visualization of the surgical field during functional endoscopic sinus surgery (FESS). However, hypotension may cause brain hypoperfusion and subsequent ischemic injuries, such as delayed awakening, stroke, postoperative delirium, and postoperative cognitive dysfunction. Near-infrared spectroscopy (NIRS) can be used to monitor real-time regional cerebral oxygen saturation (rSO2) levels to estimate brain perfusion. The present study aimed to evaluate the change in rSO2 induced by deliberate hypotension during FESS, and assess the impact of deliberate hypotension on the surgical process. Material and Methods: A randomized controlled trial was registered with the Chinese clinical trial registry (ChiCTR2000039846). A total of 40 patients were enrolled and randomly divided into the control and intervention groups, and finally, 39 patients were analyzed. Deliberate hypotension was induced in the intervention group using nicardipine and esmolol, whereas the control group received general anesthesia without deliberate hypotension. We recorded mean arterial pressure (MAP), saturation of pulse oximetry (SpO2), rSO2, and heart rate (HR) before induction of anesthesia (T0), immediately after induction of anesthesia (T1), at the beginning of the operation (corresponding with the establishment of deliberate hypotension) (T2), 10 min (T3) and 20 min (T4) after the operation began, at the end of the operation (corresponding with the end of deliberate hypotension) (T5), and 5 min (T6) and 15 min (T7) after the operation. The partial pressure of end-tidal carbon dioxide (PetCO2) was recorded at T1, T2, T3, T4, T5, and T6. The duration of surgery, intraoperative blood loss, tracheal extubation time, and the number of patients that experienced cerebral desaturation events (CDEs) were recorded. The surgical field was estimated postoperation based on the Fromme score. Results: A 30% decrease from the baseline MAP resulted in a decrease of intraoperative bleeding, improvement in the quality of the surgical field, and the shortening of the duration of surgery during FESS in the intervention group compared with the control group. In addition, rSO2 was reduced and no CDEs were experienced in the intervention group. Linear regression analysis demonstrated a correlation between the decline in rSO2 and that in MAP. Conclusions: A decrease in MAP to a certain level will cause a decrease of rSO2 in patients undergoing FESS under general anesthesia. Based on our findings, we recommend that the deliberate hypotensive target indicated by MAP be reduced by 30%, while PetCO2 is maintained at 35-40 mmHg and HR is maintained at about 60 beats per minute during FESS.

MMP-9 regulates CX3CL1/CX3CR1 in the early phase of neuropathic pain in chronic sciatic nerve constriction injury (CCI) rats.

BACKGROUND: To observe the effects of MMP-9 (matrix metalloproteases-9) on the mechanical allodynia and thermal hyperalgesia and the expression of CX3CL1 (CX3C chemokine ligand 1) protein in the spinal dorsal root ganglion (DRG) in rats with chronic sciatic nerve constriction injury (CCI). METHODS: A total of 84 male SD rats were randomly divided into seven groups, namely the normal group , the sham operation group , the model group , the CCI + MMP-9 group, the CCI + TIMP-1 group , the CCI + siRNA group, and the CCI + MM-siRNA group. The CCI model was prepared 5 days after implantation of intrathecal catheter. The rat paw mechanical withdrawal threshold (PWMT) and paw thermal withdrawal latency (PWTL) were measured 1 day before CCI surgery and 1, 2, 3 and 5 days after CCI respectively. Western blot (WB) was used to detect the expressions of the MMP-9 and the CX3CL1 protein in the L5 DRG of the spinal cord 1 day after CCI operation. RESULTS: (I) Behavioral assessment of hyperalgesia: compared with the Sham group, the PWMT and PWTL of the CCI group were significantly reduced at each time point after CCI surgery; compared with the CCI group, the PWMT and PWTL of the CCI + MMP-9 group decreased 1 day after CCI; for the PWMT and PWTL of the CCI + TIMP-1 group and CCI + siRNA group, PWMT and PWTL increased 1 day after CCI; (II) The expressions of MMP-9 and CX3CL1 protein in the DRG of the spinal cord: compared with Sham group, the expressions of MMP-9 and CX3CL1 protein in the DRG of the CCI group increased significantly 1 day after CCI surgery; compared with the CCI group, the expressions increased in the CCI + MMP-9 group 1 day after CCI . However, the expressions of MMP-9 and CX3CL1 in the CCI + TIMP-1 group and CCI + siRNA group were reduced on the first postoperative day. CONCLUSIONS: The mechanism of MMP-9 participating in the early phase of neuropathic pain (NP) in CCI rats is related to the upregulation of CX3CL1.

Acupuncture inhibits the activation of spinal microglia in the acute uterine cervical distension rats.

BACKGROUND: Although labor pain is treated clinically by the administration of local anesthetics alone or with opioids in the epidural or spinal spaces, however, the mechanisms of labor pain mechanisms have not been fully elucidated during to the lack of animal models, and the side effects of drugs still existed. Spinal microglia can be activated or mobilized under several pain states, and we want to explore the activation of spinal microglia is involved in the acute uterine cervical distension rats or not. METHODS: (I) The electromyographic (EMG) response to uterine cervical distension (UCD) was observed. Twenty-four Sprague-Dawley rats were randomly divided into three groups: standard group, sham group, and UCD group (n=8). EMG response to UCD was recorded at 30, 60 and 120 min after distension, respectively. The activation of microglia in the spinal cord at UCD 60 min was seen. Grouping following the first part (n=4), four rats were executed perfusion after distension of 60 min, the T12 to L2 spinal cord segments were removed for immunohistochemical analysis. (II) After successfully implantation of the intrathecal catheter, 36 Sprague-Dawley rats were randomly divided into the PBS group, minocycline group and UCD group (n=12). EMG response to UCD was recorded before distension and after 30, 60, and 120 min after distension (n=8). Four rats of each group were executed perfusion at 60 min after distension, the T12 to L2 spinal cord segments were removed for immunohistochemical analysis. (III) Thirty-six Sprague-Dawley rats were randomly divided into an electrical acupuncture group, non-acupuncture group, and UCD group (n=12). EMG response to UCD was recorded at 30, 60, and 120 min after distension. Four rats of each group were executed at 60 min after distension, and the T12 to L2 spinal cord segments were removed for immunohistochemical analysis to observe the effect of Hegu and Sanyinjiao acupuncture electric stimulation in the activation of spinal microglia. RESULTS: (I) EMG based value of sham group, standard group, and the UCD group were no statistical significance (P>0.05). After UCD, the EMG of the UCD group were increased at 30, 60, 120 min. Compared with fundamental values (P<0.05), which the most apparent EMG change at 60 min after UCD (P<0.05). Sixty min after UCD, compared with the sham group and the standard group, the EMG of the UCD group was higher (P<0.05), but no difference was observed between standard group and sham group (P>0.05). Compared with the sham group, the number of Iba1 (microglia markers)positive cells in thoracic, lumbar spinal cord (T12 to L2) was higher at 60 min after UCD (P<0.05), the most Iba1 labeled cells expressed in IV-V layer and X layer of lumbar spinal cord dorsal horn. (II) EMG based value of UCD group, PBS group, and minocycline group had no significant difference (P>0.05). Sixty min after UCD, compared with the PBS and UCD group, the EMG of the minocycline group was decreased significantly (P<0.05), but there was no difference between the PBS group and UCD group (P>0.05). At 30 and 120 min after UCD, the difference of EMG among the UCD group, PBS group, and minocycline group was no statistical significance (P>0.05). Compared with the PBS and UCD group, the number of Iba1 positive cells at the thoracic, lumbar spinal cord in the minocycline group decreased significantly (P<0.05). But no difference was observed between the PBS group and minocycline group (P>0.05). (III) In the fourth part of the study: EMG based value of electrical acupuncture group, non-acupuncture group, and UCD group were no different (P>0.05). Sixty min after UCD, compared with non-acupuncture and UCD group, the EMG of the acupuncture group was decreased significantly (P<0.05), but no difference was observed between the UCD group and non-acupuncture group (P>0.05). CONCLUSIONS: The activation of spinal microglia is involved in the formation of acute visceral pain induced by uterine cervical distension, Electrical acupuncturing Hegu, and Sanyinjiao alleviate pain, and the possible mechanism is inhibiting the activation of spinal microglia in the acute uterine cervical distension rats.

Intra-amygdala infusion of zeta inhibitory peptide attenuates neuropathic pain but not inflammatory pain in adult rats.

BACKGROUND: Protein kinase Mζ (PKMζ), a typical brain-specific PKC isoform, has been shown to be critical in the maintenance of long-term potentiation and memory storage. Zeta inhibitory peptide (ZIP), a peptide with selective inhibition of PKMζ, has been used in relieving experimental neuropathic pain and disrupting memory. The aim of this study was to investigate the effects of intra-amygdalar infusion of ZIP on neuropathic pain induced by chronic constriction injury (CCI), and inflammatory pain induced by complete Freund's adjuvant (CFA) in adult rats. METHODS: (I) ZIP was infused into the amygdala 30 minutes (min) before CCI was performed. Mechanical withdrawal threshold (MWT) was determined prior to the infusion of ZIP, and 30, 60, 90, 120, 150, 180 min after CCI (n=8 per group). (II) ZIP was infused into the amygdala 3, 7, 14 days after CCI (n=8 per group). MWT was measured 30 min before the infusion and 2, 12, 24 h after the infusion. (III) Three days after CCI, ZIP was infused into the amygdala repeatedly once a day for 2 days. MWT was measured before each infusion and 2 or 24 h after each infusion (n=8 per group). (IV) ZIP was infused into the amygdala 24 h after the establishment of inflammatory pain induced by complete Freund's adjuvant (CFA). MWT was determined 30 min before the infusion and 30, 60, 90, 120 and 150 min after the infusion (n=8 per group). RESULTS: As shown in figures, (I) amygdalar infusion of ZIP prior to the CCI produced no effect on CCI-induced hyperalgesia when compared to scr-ZIP or saline infusion [n=8, interaction effect, F (7.312, 76.776) =1.237, P>0.05; time as main factor, F (3.656, 76.776) =115.346, P<0.001; group as main factor, F (2, 21) =0.648, P>0.05]. (II) BLA infusion of ZIP significantly increased mechanical withdrawal threshold 7 days after CCI [n=8, interaction effect, F (5.476, 57.500) =15.279, P<0.001; time as main factor, F (2.738, 57.500) = 242.357, P<0.001; group as main factor, F (2,21) =4.786, P<0.05], just the same as 3 and 14 days after CCI (data not shown). (III) Bilateral injection of ZIP into the BLA significantly reduced mechanical hyperalgesia 2 h after the administration [n=8, paired t-test, t (0.05,7) =-5.561, P<0.05; n=8, paired t-test, t (0.05,7) =-4.745, P<0.05], and returned to baseline 24 h after the administration [n=8, paired t-test, t (0.05,7) =1.039, P>0.05; n=8, paired t-test, t (0.05,7) =-1.173, P>0.05]. (IV) ZIP produced no effect on mechanical withdrawal thresholds at all time points examined after the infusion, compared with scr-ZIP or saline control groups (n=8, interaction effect, F (6.135, 126) =1.724, P>0.05; group as main factor, F (2,21) =0.608, P>0.05). CONCLUSIONS: Intra-amygdala infusion of ZIP attenuates mechanical hyperalgesia induced by CCI but has no effect on inflammatory pain induced by CFA in rats, suggesting that amygdala PKMζ may be a therapeutic target in the treatment of neuropathic pain.

[Effects of intra-periaqueductal gray injection of zeta pseudosubstrate inhibitory peptide on sensory and affective components of pain].

OBJECTIVE: To explore the effects of intra-PAG injection of ZIP on sensory and affective components of pain. METHODS: For determining the role of ZIP on pain-induced aversion, the effects of intra-PAG injection of ZIP on formalin-induced conditioned place avoidance (F-CPA) was investigated. To determine the role of ZIP on pain perception, formalin-induced inflammatory pain model was established and the effects of intra-PAG injection of ZIP on formalin-induced nociceptive behaviors was investigated. RESULTS: In the NS-treated rats, the time in the pain-paired compartment during the test session was significantly shorter than that during the preconditioning session 2 and 24 hours after administration of the drug at both 1 and 7 day post-training (Group NS-1 d-2 h: (465.1 ± 40.6) vs (133.8 ± 29.4) s (P < 0.001); Group NS-7 d-2 h: (432.3 ± 43.7) vs (150.5 ± 26.6) s (P < 0.01); Group NS-1 d-24 h: (500.5 ± 20.6) vs (107.0 ± 15.7) s (P < 0.001); Group NS-7 d-24 h: (450.8 ± 27.4) vs (129.4 ± 21.1) s (P < 0.001)). On the contrary, in the ZIP-treated rats, no significant differences were observed in the time in the pain-paired compartment between the post-conditioning and pre-conditioning sessions at the same time-points. CPA scores also showed the attenuation of F-CPA by intra-PAG injection of ZIP in comparison to the saline-injected rats (P < 0.05). Compared with the intra-PAG saline-injected group, intra-PAG microinjection of ZIP did not affect the formalin-induced nociceptive behaviors (P > 0.05). CONCLUSION: The study suggests that PAG contributes to pain-related aversion in rats, and the mechanism of pain emotion encoding in PAG may attribute to the activation of targets of ZIP.

Intra-periaqueductal gray infusion of zeta inhibitory peptide attenuates pain-conditioned place avoidance in rats.

Pain is a complex experience that made up of sensory, emotional and cognitive dimensions, and the emotional factors have an important influence on intensity of pain perception. The role of periaqueductal gray (PAG) in sensory component of pain has been extensively studied, while data about pain affect are quite limited. Using formalin-induced conditioned place avoidance (F-CPA) test and inflammatory pain model, present study investigated the effect of intra-PAG infusion of zeta inhibitory peptide (ZIP) on noxious stimulation induced aversion, and the sensory component of pain. Intra-PAG injection of ZIP is sufficient to disrupt pain-induced aversion, but the ZIP infusion did not change inflammation induced pain hypersensitivity in rats. These findings suggest that PAG contributes to pain-related aversion in rats, and the mechanism of pain emotion encoding in PAG may attribute to the activation of targets of ZIP.

[Role of the CX3CR1/ERK5 pathway in spinal microglia for the development of neuropathic pain].

OBJECTIVE: To explore the role of spinal microglial CX3CR1/ERK5 pathway in the development of neuropathic pain. METHODS: The model of spinal nerve ligation (SNL) was established by ligating the L5 spinal nerve with 6-0 silk thread in male Sprague Dawley rats. The expression of activated ERK5 (p-ERK5) was examined by immunohistochemistry test. To detect the role of ERK5 in neuropathic pain, PWT and PWL were measured after an intrathecal knockdown of ERK5. For determining the regulating effect of CX3CL1/CX3CR1 on the activity of microglial ERK5, CX3CR1 was blocked by an intrathecal injection of anti-rat CX3CR1 antibody and the activity of spinal ERK5 tested. Then whether an intrathecal knockdown of ERK5 could reverse the effect of CX3CL1 on pain hypersensitivity and microglia activation was investigated. RESULTS: ERK5 was activated in spinal microglia after SNL compared to the sham group (61.75 ± 11.52 vs 2.2 ± 0.12; 58.01 ± 10.45 vs 1.1 ± 0.11) . The knockdown of ERK5 by an intrathecal injection of antisense oligonucleotides suppressed the mechanical (15.42 ± 3.46 vs 22.73 ± 3.21g; 13.63 ± 2.88 vs. 21.42 ± 4.12g) and thermal hyperalgesia (13.48 ± 2.01) vs (18.05 ± 3.71) s; (11.6 ± 2.33) vs (17.73 ± 1.42) s induced by nerve injury. The blockage of CX3CR1, a receptor of CX3CL1, significantly reduced the level of ERK5 activation following SNL (30.12 ± 8.60) vs (58.25 ± 11.5); (49.5 ± 12.12) vs (35.51 ± 3.74) (P < 0.05). In addition, the antisense knockdown of ERK5 reversed the CX3CL1-induced hyperalgesia and spinal microglia activation. CONCLUSIONS: CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through ERK5.