Different Anesthesia and Sedation Depths of BIS-guided Closed-loop Target-controlled Infusion on Perioperative Th1/Th2 Balance in Elderly Patients Undergoing Laparoscopic Radical Gastrectomy / 肿瘤防治研究

Objective To investigate the effect of BIS-guided closed-loop target-controlled infusion on perioperative Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy under different anesthesia and sedation depths. Methods We applied random number table method to divide 73 elderly patients undergoing elective laparoscopic radical gastrectomy into BIS closed-loop target-controlled infusion group with BIS value of 55(group H, n=36) and BIS value of 45(group L, n=37).Intravenous blood samples were collected immediately before surgery (T1), 2h after surgery (T2), 24h after surgery (T3) and 72h after surgery (T4).IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ were determined by flow cytometry microsphere array.We compared operation duration, postoperative PACU stay time and postoperative hospitalization time between two groups. Results Compared with T1, IL-6 and IL-10 concentration in group H at T2, T3 and T4 significantly increased (P < 0.05), IL-4 and TNF-α in group H at T4 were significantly increased (P < 0.05), IL-2 and IFN-γ in group H at T2 and T4 were significantly increased (P < 0.05), the concentration of IL-6 and IL-10 in group L at T2, T3 and T4 were increased (P < 0.05), IL-2 in group L at T4 was decreased (P < 0.05), and IFN-γ/IL-6 in two groups were decreased at T2, T3 and T4(P < 0.05).Compared with group L, IL-6 and IL-10 in group H were significantly increased at T2(P < 0.05), IFN-γ/IL-6 in group H was significantly decreased (P < 0.05), IL-2 and IL-10 in group H were significantly increased at T4(P < 0.05).Operation duration, postoperative PACU stay time and postoperative hospitalization time had no statistical significance between two groups (P > 0.05). Conclusion The anesthesia and sedation depth of BIS-guided closed-loop target-controlled infusion set at 45 is better than 55 in maintaining Th1/Th2 balance in elderly patients undergoing laparoscopic radical gastrectomy, but it has no obvious effect on long-term prognosis.

Clinical application and research progress of remimazolam / 中国临床药理学与治疗学

Remimazolam is a new ultra-short-acting sedative, with rapid onset and recovery, metabolism independent of liver and kidney function, light respiratory inhibition, stable hemodynamics, long time application without accumulation. Carboxylic acid metabolites have no pharmacological effects, and can be rapidly reversed by antagonist flumazenil, which is expected to become a new choice of clinical sedative. In this paper, pharmacological characteristics and recent research progress of remimazolam are reviewed, which can provide reference for clinical safe drug use.

Inflammatory cytokines in midbrain periaqueductal gray contribute to diabetic induced pain hypersensitivity through phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

Background@#Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG. @*Methods@#Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors. @*Results@#Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1β, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor [TNFR] subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling. @*Conclusions@#Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.

Inflammatory cytokines in midbrain periaqueductal gray contribute to diabetic induced pain hypersensitivity through phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

Background@#Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG. @*Methods@#Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors. @*Results@#Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1β, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor [TNFR] subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling. @*Conclusions@#Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.

Effects of different doses of dexmedetomidine on propofol-induced inhibition of responses to laryngeal mask airway insertion when combined with fentanyl in patients undergoing gynecological operation / 中华麻醉学杂志

Objective To evaluate the effects of different doses of dexmedetomidine on propofol-induced inhibition of responses to laryngeal mask airway (LMA) insertion when combined with fentanyl in patients undergoing gynecological operation.Methods One hundred and twenty-five ASA Ⅰ-Ⅱ female patients,aged 20-60 yr,scheduled for elective short-time surgery,were randomly divided into 5 groups (n =25 each):normal saline group (group NS) and different doses of dexmedetomidne groups (groups D1-4).Normal saline 40 ml and dexmedetomidne 0.4,0.6,0.8,1.0 μg/kg (in 40 ml of normal saline) were infused over 10 min in groups NS and D1-4,respectively.1％ propofol was then given by target-controlled infusion.The concentration of propofol was determined by using modified Dixon's up-and-down method.The initial plasma concentration of propofol was 3.0 μg/ml and the ratio between the 2 successive concentrations was 1.1.Fentanyl 1.5 μg/kg was injected intravenously when the effect-site concentration of propofol reached the preset plasma concentration.LMA was inserted 4 min later.When LMA insertion was successful,the concentration of propofol was decreased in the next patient and when LMA insertion failed,the concentration of propofol was increased in the next patient.Failure of LMA insertion was defined as difficulty in inserting LMA or body movement,corner of mouth movement,biting LMA,swallowing and/or lacrimation during insertion.The median effective target effect-site concentration and 95％ confidence interval of propofol blunting responses to LMA insertion when combined with fentanyl were calculated.Results The median effective target effect-site concentration (95％ confidence interval) of propofol blunting responses to LMA insertion when combined with fentanyl were 3.09 (2.83-3.36),2.48 (2.26-2.73),2.29 (2.18-2.41),2.04 (1.95-2.12) and 1.67 (1.55-1.81) μg/ml in groups NS and D1 4,respectively.Conclusion Dexmedetomidine can enhance propofol-induced inhibition of responses to LMA insertion when combined with fentanyl in dose-dependent manner in patients undergoing gynecological operation.

Effects of positive end-expiratory pressure after recruitment maneuvers on respiratory mechanics and gas exchange during laparoscopy in obese patients / 中华麻醉学杂志

Objective To investigate the effects of positive end-expiratory pressure (PEEP) after recruitment maneuvers (RM) on respiratory mechanics and gas exchange during laparoscopy in obese patients.Methods Sixty-three ASA physical status Ⅱ or Ⅲ patients,aged 42-64 yr,with body mass index 30-40kg/m2,were randomly allocated into 3 groups (n=21 each):PEEP0 group,PEEP5 group and PEEP10 group.PEEP was not given after RM in PEEP0 group.In PEEP5 and PEEP10 groups,a recruiting maneuver was followed by PEEP 5 and 10 cm H2 O,respectively,until the end of pneumoperitoneum.The intraabdominal pressure was set at 12mmHg in the three groups.Parameters of respiratory mechanics including peak airway pressure (Ppeak),airway plateau pressure (Peat),chest wall plateau pressure (PplatCW),airway resistance (Raw),elastance of respiratory system (ERS),elastanc of chest wall (ECW) and elastance of lung (EL) and parameters of gas exchange including oxygenation index (PaO2/FiO2),arterial to end-tidal difference in carbon dioxide (Da-ETCO2),alveolar-arterial oxygen tension difference (DA-aO2),and dead space/tidal volume ratio (VD/VT) were measured before pneumoperitoneum (T0),at 20 min of pneumoperitoneum (T1),at 10 min after the end of recruitment (T2),and at the end of pneumoperitoneum (T3).Results Da-ETCO2,ERS and Raw were decreased at T2,ECW and EL were decreased at T3 in PEEP5 group,and Da-ETCO2,VD/VT,DA-aO2,Pplatcw Raw and EL were decreased at T2.3,and PaO2/FiO2 was increased at T2,ECW was decreased at T3 in group PEEP10 as compared with that in group PEEP0 (P ＜ 0.05).Da-ETCO2 and VD/VT were decreased and PaO2/FiO2 was increased at T2,3,Raw was increased and EL was decreased at T2 in group PEEP10 as compared with that in group PEEP5 (P ＜ 0.01).Conclusion PEEP after RM can improve respiratory mechanics and gas exchange during laparoscopy in obese patients and PEEP maintained at 10 cm H2O after RM provides better efficacy than PEEP at 5 cm H2 O.

Effect of epidural block on postoperative cognitive dysfunction in elderly patients undergoing laparoscopic radical operation for gastric cancer under general anesthesia / 中华麻醉学杂志

Objective To evaluate the effect of epidural block on postoperative cognitive dysfunction in elderly patients undergoing laparoscopic radical operation for gastric cancer under general anesthesia.Methods Sixty ASA physical status Ⅰ or Ⅱ patients,aged 65-75 yr,with preoperative Mini-Mental State Examination (MMSE) score ＞ 23,scheduled for elective laparoscopic radical operation for gastric cancer under general anesthesia,were randomized into epidural block group (group E,n =30) and control group (group C,n =30) using a random number table.Epidural block was performed at T8,9 interspace before induction of anesthesia.Anesthesia was induced with iv injection of midazolam 0.03 mg/kg,propofol 1.0-1.5 mg/kg,fentanyl 3-4 μg/kg and rocuronium 0.9 mg/kg.The patients were endotracheally intubated and mechanically ventilated.Anesthesia was maintained with iv infusion of remifentanil 0.15-0.25 μg· kg-1· min 1 and propofol target-controlled infusion (target plasma concentration 2.5-3.0μg/ml).In group E,10 ml of mixture of 0.25％ ropivacaine and 0.04 mg/ml butorphanol was injected via the epidural catheter at 30 min before skin incision.In the two groups,the mixture 10 ml mentioned above was administered via the epidural catheter at 10 min before the end of operation followed by patientcontrolled epidural analgesia.The development of postoperative cognitive dysfunction (MMSE score ＜ 21) was recorded within 72 h after operation.Blood samples were collected from the internal jugular vein to detect the concentration of serum protein S-100β.Results The concentration of serum protein S-100β was significantly lower at 6,12 and 24 h after operation,and the incidence of postoperative cognitive dysfunction within 72 h after operation was lower in group E than in group C (P ＜ 0.05).Conclusion Epidural block can decrease the development of postoperative cognitive dysfunction in elderly patients undergoing laparoscopic radical operation for gastric cancer under general anesthesia.

Effect of preemptive analgesia with parecoxib sodium on postoperative cognitive function in the elderly patients / 中华麻醉学杂志

Objective To investigate the effect of preemptive analgesia with parecoxib sodium on postoperative cognitive junction in the elderly patients.Methods Sixty ASA ⅠorⅡ patients aged 69-83 yr weighing 47-73 kg undergoing elective operation on the femoral head or hip joint were randomly divided into 2 groups (n=30 each):control group (group C) and parecoxib group (group P).Their preoperative mini-mental state examination scores were more than 23.Parecoxib sodium 40 mg in 5 ml normal saline was injected iv before induction of anesthesia in group P. Patient-controlled intravenous analgesia with fentanyl and tramadol was used in all patients. VAS score was maintained ≤3. If VAS score was more than 3, a bolus of fentanyl 0.2 μg/kg was given iv.Venous blood samples were taken at 1 day before and 1, 4, 24 and 72 h after operation for determination of plasma concentrations of cortisol.Cognitive function was assessed by mini-mental state examination. The total amount of fentanyl and tramadol consumed was recorded. Results Plasma cortisol concentrations and incidence of postoperative cognitive dysfunction were significantly lower and the total amount of fentanyl and tramadol consumed was smaller in group P than in group C.Conclusion Preemptive analgesia with parecoxib sodium 40 mg can reduce the incidence of postoperative cognitive dysfunction in the elderly patients.

Incidence of postanesthetic shivering in patients undergoing radical operation for lung cancer under dexmedetomidine- assisted anesthesia / 中华麻醉学杂志

Objective To evaluate the incidence of postanesthetic shivering in patients undergoing radical operation for lung cancer under dexmedetomidine-assisted anesthesia.Methods Eighty ASA Ⅰ or Ⅱ patients,aged 50-75 yr,height 158-180 cm,weighing 48-79 kg,scheduled for radical operation for lung cancer under general anesthesia combined with epidural anesthesia,were randomly divided into 2 groups ( n =40 each): normal saline control group (group C) and dexmedetomidine group(group D).Anesthesia was induced with midazolam,fentanyl,propofol and rocuronium.The patients were tracheal intubated and mechanically ventilated.Anesthesia was maintained with sevoflurane inhalation and intermittent epidural ropivacaine.BIS was maintained at 40-55.Group D received dexmedetomidine intravenous infusion at 0.5 μg · kg- 1· h- 1 from immediately after tracheal intubation until 1 h before the end of operation,and group C received the equal volume of normal saline.The shivering within 1 h after operation was scored and recorded.Results The incidence rate of postanesthetic shivering was 50％ in group C and 10％ in group D.Compared with group C,the incidence rate and degree of shivering were decreased in group D( P ＜ 0.05).Conclusion Dexmedetomidine-assisted anesthesia can reduce the incidence of postanesthetic shivering in patients undergoing radical operation for lung cancer.

Effects of β_2 agonist salbutamol aerosol on the uptake of sevoflurane in elderly patients with chronic obstructive pulmonary disease / 复旦学报（医学版）

Objective To investigate the effects of β_2 agonist salbutamol aerosol on the uptake of sevoflurane in elderly patients with chronic obstructive pulmonary disease (COPD). Methods A randomized, placebo-controlled and double-blinded trial was designed. Twenty-six patients were recruited and randomly allocated to salbutamol group (group E, n=13) and placebo group (group C, n=13). Eligible patients were elderly patients with ASA physical status Ⅱ-Ⅲ, a body mass index (BMI) between 18 and 30 kg/m~2, well-defined clinical diagnosis of COPD. Routine monitoring (consists of a three-lead ECG, pulse oximetry, noninvasive blood pressure and expired gas analysis) was instituted and 500 mL Ringer's lactate solution was administered. Bispectral index (BIS) monitoring was initiated prior to induction. All subjects were received inhaled aerosol 200 μg according to manufacturers' recommendations 30 minutes before induction of anesthesia. Controlled ventilation was applied after the trachea was intubated. When stable hemodynamics was maintained for 5 minutes, fresh gas flow was set to 2 L/min with 2% sevoflurane in admixture, then HR, invasive arterial blood pressure (IABP), SpO_2, P_(ET)CO_2, bispectral index (BIS), minimum alveolar concentration (MAC), concentrations of inhaled sevoflurane (F_I) and end-tidal (F_E) were recorded at 1, 2, 3, 4, 5, 7,10, and 15 minutes after inhalation of sevoflurne. The P_(peak) and P_(plat) were also measured in 1, 5, and 10 minutes after the successful endotracheal intubation. Results Compared to the placebo group, the F_E was significantly higher at 2, 3, 4, and 5 minutes in experiment group. Peak airway pressure and plateau pressure in experiment group were strikingly lower than control group (P<0.05). There was no statistical significance about BIS variations between these groups in respective time in spite of increased MAC (P>0.05). Conclusions The increasing rate of alveolar concentration of sevoflurane was accelerated after the administration of inhaled salbutamol aerosol (200 μg) 30 minutes before induction of anesthesia, it might increase the uptake of sevoflurane.