Effect of Different Administration Routes of Dexmedetomidine on Postoperative Delirium in Elderly Patients Undergoing Elective Spinal Surgery: A Prospective Randomized Double-Blinded Controlled Trial.

BACKGROUND: Intravenous dexmedetomidine has been reported to decrease the occurrence of postoperative delirium (POD) in elderly patients. Nevertheless, some previous studies have indicated that intratracheal dexmedetomidine and intranasal dexmedetomidine are also effective and convenient. The current study aimed to compare the effect of different administration routes of dexmedetomidine on POD in elderly patients. METHODS: We randomly allocated 150 patients (aged 60 years or more) scheduled for spinal surgery to receive intravenous dexmedetomidine (0.6 µg/kg), intranasal dexmedetomidine (1 µg/kg) before anesthesia induction, or intratracheal dexmedetomidine (0.6 µg/kg) after anesthesia induction. The primary outcome was the frequency of delirium during the first 3 postoperative days. The secondary outcomes were the incidence of postoperative sore throat (POST) and sleep quality. Adverse events were recorded, and routine treatment was performed. RESULTS: Compared with the intranasal group, the intravenous group had a significantly lower occurrence of POD within 3 days (3 of 49 [6.1%] vs 14 of 50 [28.0%]; odds ratio [OR], 0.17; 95% confidence intervals [CIs], 0.05-0.63; P < .017). Meanwhile, patients in the intratracheal group had a lower incidence of POD than those in the intranasal group (5 of 49 [10.2%] vs 14 of 50 [28.0%]; OR, 0.29; 95% CI, 0.10-0.89; P < .017). Whereas, there was no difference between the intratracheal and intravenous groups (5 of 49 [10.2%] vs 3 of 49 [6.1%]; OR, 1.74; 95% CI, 0.40-7.73; P > .017). The rate of POST was lower in the intratracheal group than that in the other 2 groups at 2 hours after surgery (7 of 49 [14.3%] vs 12 of 49 [24.5%] vs 18 of 50 [36.0%], P < .017, respectively). Intravenous dexmedetomidine had the lowest Pittsburgh Sleep Quality Index score on the second morning after surgery (median [interquartile range {IQR}]: 4 [3-5] vs 6 [4-7] vs 6 [4-7], P < .017, respectively). Compared with the intranasal group, the intravenous group had a higher rate of bradycardia and a lower incidence of postoperative nausea and vomiting ( P < .017). The intranasal group was associated with the highest incidence of hypertension ( P < .017). CONCLUSIONS: For patients aged ≥60 years undergoing spinal surgery, compared with the intranasal route of dexmedetomidine, intravenous and intratracheal dexmedetomidine reduced the incidence of early POD. Meanwhile, intravenous dexmedetomidine was associated with better sleep quality after surgery, and intratracheal dexmedetomidine resulted in a lower incidence of POST. Adverse events were mild in all 3 administration routes of dexmedetomidine.

Effect of Dexmedetomidine combined with sufentanil for post- thoracotomy intravenous analgesia:a randomized, controlled clinical study.

BACKGROUND: Few studies have investigated the use of dexmedetomidine in patient-controlled intravenous analgesia (PCIA) after thoracic surgery. This study to evaluate the effect of dexmedetomidine combined with sufentanil for PCIA after thoracotomy under general anaesthesia. METHODS: Ninety-seven adults patients scheduled for thoracotomy surgery. All two groups received PCIA with either sufentanil alone (control group) or combining dexmedetomidine with sufentanil (dexmedetomidine group). Hemodynamic measurements, visual analog scale (VAS) scores at rest and at coughing, Ramsay sedation score (RSS), analgesic consumption, and postoperative nausea and vomiting (PONV) as well as drug-related adverse effects were compared at 2, 6, 12, 24, 36 and 48 h postoperatively. RESULTS: In the patients of the dexmedetomidine group, compared to the control group, the pain scores at rest or at coughing during 48 h postoperatively were lower (P < 0.001), the sedation scores were lower, the consumption of sufentanil and rescue meperidine were lower, and the number of episode of moderate PONV was three times lower. No signs of toxicity or local complications were observed. There was a non-significant trend for a lower HR and BP in the dexmedetomidine group vs. CONCLUSION: The combining dexmedetomidine with sufentanil for post-thoracotomy PCIA can improve pain control together with the decrease in sufentanil requirements, and improve postoperative patient's satisfaction compared with sufentanil alone in PCIA. TRIAL REGISTRATION: This trial was retrospectively registered on 27 April 2016 at the Chinese Clinical Trial Register (number: ChiCTR-ONC-16008376 ).

Opioid-Free Anesthesia for Pain Relief After Laparoscopic Cholecystectomy: A Prospective Randomized Controlled Trial.

Purpose: To compare the efficacies of opioid-free anesthesia (OFA) and opioid-based anesthesia (OBA) in laparoscopic cholecystectomy (LC). Patients and Methods: A total of 150 patients who underwent 3-port LC procedures were randomly divided into an OFA group with esketamine, dexmedetomidine and lidocaine intravenous combined with local anesthetic incision infiltration or an OBA group with remifentanil combined with local anesthetic incision infiltration. The primary outcome was the consumption of rescue analgesics within 24 hrs after surgery. Secondary outcomes included time to LMA removal, time to orientation recovery, time to unassisted walking, sleep quality on the night of surgery, time to first flatus, hemodynamics during induction of general anesthesia, postoperative pain level on the visual analog scale (VAS), incidence of postoperative nausea and vomiting (PONV) and global satisfaction score (GSS) within 24 hrs after surgery. Results: Both the consumption of rescue analgesics and the time to first flatus in the OFA group were significantly lower than those in the OBA group (P < 0.001 and P = 0.029, respectively). However, the time to LMA removal and the time to orientation recovery were significantly longer in the OFA group than in the OBA group (P < 0.001). In addition, the VAS scores at 2 hrs and 8 hrs after surgery and HR at laryngeal mask airway insertion in the OFA group were significantly lower than those in the OBA group (P = 0.002 and P = 0.001, and P =0.016, respectively). Conclusion: OFA may be beneficial for patients undergoing LC in that it could decrease the dosage of postoperative analgesics and pain intensity and even shorten the time to first flatus after surgery.

Up-regulation of HCN2 channels in a thalamocortical circuit mediates allodynia in mice.

Chronic pain is a significant problem that afflicts individuals and society, and for which the current clinical treatment is inadequate. In addition, the neural circuit and molecular mechanisms subserving chronic pain remain largely uncharacterized. Herein we identified enhanced activity of a glutamatergic neuronal circuit that encompasses projections from the ventral posterolateral nucleus (VPLGlu) to the glutamatergic neurons of the hindlimb primary somatosensory cortex (S1HLGlu), driving allodynia in mouse models of chronic pain. Optogenetic inhibition of this VPLGlu→S1HLGlu circuit reversed allodynia, whereas the enhancement of its activity provoked hyperalgesia in control mice. In addition, we found that the expression and function of the HCN2 (hyperpolarization-activated cyclic nucleotide-gated channel 2) were increased in VPLGlu neurons under conditions of chronic pain. Using in vivo calcium imaging, we demonstrated that downregulation of HCN2 channels in the VPLGlu neurons abrogated the rise in S1HLGlu neuronal activity while alleviating allodynia in mice with chronic pain. With these data, we propose that dysfunction in HCN2 channels in the VPLGlu→S1HLGlu thalamocortical circuit and their upregulation occupy essential roles in the development of chronic pain.

Effect of a Local Anesthetic Injection Kit on Pain Relief and Postoperative Recovery After Transumbilical Single-Incision Laparoscopic Cholecystectomy.

Purpose: This study was conducted to explore whether incisional infiltration using a local anesthetic injection kit could better relieve postoperative pain and enhance the quality of recovery compared with ultrasound-guided rectus sheath block (RSB) or conventional local anesthetic infiltration in patients undergoing transumbilical single-incision laparoscopic cholecystectomy (SILC). Patients and Methods: A total of 60 patients undergoing SILC with American Society of Anesthesiology functional status scores of I-II were randomized into the rectus sheath block group (RSB group), conventional local wound infiltration group (LAI-I group) and incisional infiltration using a local anesthetic injection kit group (LAI-II group). The primary outcomes were the patient-controlled intravenous analgesia (PCIA) demand frequency within 48 hours after the operation and postoperative pain measured by a visual analog scale (VAS) at 2 h, 4 h, 8 h, 24 h, and 48 h after surgery. Secondary outcomes were the total procedure times, cumulative consumption of anesthetic drugs, duration of surgery, duration and awaking time of anesthesia, early recovery indicator and side effects. Results: The PCIA demand frequency in LAI-II group was significantly lower compared with patients in the RSB and LAI-I group (both P < 0.001). Moreover, the total procedure times in LAI-I and LAI-II group was significantly shorter than that in the RSB group (P < 0.001, respectively), but it was comparable between LAI-I and LAI-II group (P = 0.471). Though lower at 2h and 4h postoperative in LAI-II group, pain scores at each time point had no statistical differences among three groups. There were no significant differences among three groups for other outcomes as well. Conclusion: The effect of ultrasound-guided RSB and conventional local anesthetic infiltration in SILC patients were found to be similar in terms of relieving postoperative pain and promoting recovery. Incisional infiltration using a local anesthetic injection kit can significantly reduce the demand frequency of PCIA, which serves as a rescue analgesic.

Morphine reduces the threshold of remote ischemic preconditioning against myocardial ischemia and reperfusion injury in rats: the role of opioid receptors.

OBJECTIVES: Opioid receptors mediate the cardioprotection of remote ischemic preconditioning (RIPC). The authors tested the hypothesis that morphine reduces the threshold of cardioprotection produced by RIPC. METHODS: A randomized, prospective study. SETTING: A university research laboratory. PARTICIPANTS: Forty-five male Sprague-Dawley rats. INTERVENTIONS: Anesthetized, open-chest, male Sprague-Dawley rats were assigned randomly to 1 of 7 treatment groups. RIPC1 and RIPC3 were, respectively, induced by 1 or 3 cycles of 5 minutes of femoral artery ischemia interspersed with 5 minutes of reperfusion. Morphine (MOR, 0.1 mg/kg) and the opioid receptor antagonist naloxone (NAL, 6 mg/kg) were administered 30 minutes before sustaining ischemia. MOR + RIPC1 and NAL + MOR + RIPC1 groups received the combination of MOR and RIPC1 in the absence or presence of NAL before coronary artery occlusion. Ischemia and reperfusion injury then were induced by 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion. MEASUREMENTS AND MAIN RESULTS: Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining. RIPC3 and the combination of MOR and RIPC1 groups significantly reduced the infarct size compared with the control group. RIPC1, MOR, and NAL did not affect infarct size. NAL pretreatment reversed cardioprotection of the combination of MOR and RIPC1 treatments. CONCLUSIONS: MOR reduces the threshold of RIPC, and opioid receptors mediate this augmentative effect.

A neural circuit for the suppression of feeding under persistent pain.

In humans, persistent pain often leads to decreased appetite. However, the neural circuits underlying this behaviour remain unclear. Here, we show that a circuit arising from glutamatergic neurons in the anterior cingulate cortex (GluACC) projects to glutamatergic neurons in the lateral hypothalamic area (GluLHA) to blunt food intake in a mouse model of persistent pain. In turn, these GluLHA neurons project to pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus (POMCArc), a well-known neuronal population involved in decreasing food intake. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that the GluACC → GluLHA → Arc circuit is activated in mouse models of persistent pain and is accompanied by decreased feeding behaviour in both males and females. Inhibition of this circuit using chemogenetics can alleviate the feeding suppression symptoms. Our study indicates that the GluACC → GluLHA → Arc circuit is involved in driving the suppression of feeding under persistent pain through POMC neuronal activity. This previously unrecognized pathway could be explored as a potential target for pain-associated diseases.

Morphine and myocardial ischaemia-reperfusion.

Coronary heart disease (CHD) is a cardiovascular disease with high mortality and disability worldwide. The main pathological manifestation of CHD is myocardial injury due to ischaemia-reperfusion, resulting in the death of cardiomyocytes (apoptosis and necrosis) and the occurrence of cardiac failure. Morphine is a nonselective opioid receptor agonist that has been commonly used for analgesia and to treat ischaemic heart disease. The present review focused on morphine-induced protection in an animal model of myocardial ischaemia-reperfusion and chronic heart failure and the effects of morphine on ST segment elevation myocardial infarction (STEMI) patients who underwent pre-primary percutaneous coronary intervention (pre-PPCI) or PPCI. The signalling pathways involved are also briefly described.

Comparison of a tube core and Magill forceps for nasotracheal intubation: a randomised controlled trial.

BACKGROUND: Magill forceps are frequently used to complete nasotracheal intubation (NTI). We aimed to identify a tube core that could conveniently facilitate the NTI process without using Magill forceps. METHODS: Sixty patients scheduled for oral and maxillofacial surgeries were enrolled in our study and divided into two groups (30 per group) with no differences with regard to demographic data. In the Magill forceps group (Group M), a wire-reinforced endotracheal catheter was inserted into the trachea using Magill forceps. However, in the tube core group (Group T), a tube core bent to the physiological curve of the nasal cavity and lubricated with aseptic paraffin oil was inserted into the endotracheal catheter and was then withdrawn after the endotracheal catheter was advanced through the glottis under direct vision. RESULTS: All NTIs were completed successfully, and Magill forceps were not used on any patient in Group T. There was a significant difference in total NTI time between the two groups (Group M, 59.7 (5.1) s vs Group T, 52.4 (3.1) s). Mild epistaxis was observed in 6 patients in Group M and 5 patients in Group T (6/30 vs 5/30, respectively). No damage to oral tissue or teeth was observed in either group. CONCLUSIONS: We conclude that using a tube core, consisting of a disposable sterilised stylet, is a convenient choice for NTI. TRIAL REGISTRATION: Patient enrolment was conducted after registration in the Chinese Clinical Trial Registry ( www.Chictr.org.cn , ChiCTR190002 7387). This trial was prospectively registered on 11 November 2019.

The dose response of sufentanil as an adjuvant to ropivacaine in cesarean section for relief from somato-visceral pain under epidural anesthesia in parturients with scarred uterus.

Visceral pain is common during epidural anesthesia with mini dose local anesthetics in parturients during cesarean section. To reduce or avoid this complication caused by traction on the abdominal viscera, this study aimed to determine the 50% effective dose (ED50) and 95% effective dose (ED95) of epidural sufentanil as an adjuvant combination with local anesthetics for relief visceral pain in parturients with scarred uterus undergoing elective cesarean section.One hundred parturients with scarred uterus undergoing elective cesarean section under epidural anesthesia were enrolled in this randomized, double-blinded, dose-ranging study. Parturients received 5, 10, 15, 20, and 25 µg epidural sufentanil as an adjuvant with 10 mL of 0.65% ropivacaine. Successful epidural anesthesia was defined as a sixth thoracic vertebra (T6) sensory level achieved within 20 minutes after epidural drugs administration and/or no visceral pain by traction on the abdominal viscera during the cesarean section. The ED50 and ED95 were calculated with a logistic regression model.ED50 and ED95 of epidural sufentanil for successful of the pain-free from visceral pain were 10.7 µg [95% confidence interval (CI): 2.4-14.4 µg) and 28.1 µg (95% CI: 19.4-44.0 µg), respectively. The onset time to sensory block, maximum Bromage scale and duration of motor block were significant different with dose of sufentanil >20 µg (P < .05, compared with the other dose groups). With the dose of epidural sufentanil >20 µg could result in an increase of incidence of maternals' adverse effects. Compared with a different dose of sufentanil, epidural administed sufentanil between 15 µg and 20 µg can maximize parturients' satisfaction.Our study showed that sufentanil could be used in combination with ropivacaine for relief from somato-visceral pain in patients with scarred uterus during elective cesarean section during epidural anesthesia, and that maximized parturients' satisfaction could be achieved when the use of sufentanil with the dose between 15 µg and 20 µg for epidural anesthesia.

The Analgesic Effect of Ropivacaine Combined With Dexmedetomidine for Incision Infiltration After Laparoscopic Cholecystectomy.

BACKGROUND: Local anesthetics infiltration is one consensus efficient strategy for pain relief after laparoscopic cholecystectomy (LC). The aim of this study was to investigate analgesia efficacy of incisional infiltration with ropivacaine plus dexmedetomidine. METHODS: Patients scheduled for LC were assigned to 4 groups by different medications for trocar wound infiltration. The incidence of adverse events and the analgesic effect of ropivacaine combined with dexmedetomidine for incision infiltration were recorded. RESULTS: Incisional infiltration of ropivacaine combining with dexmedetomidine could significantly reduce postoperative pain and the amount of pethidine requirement. Furthermore, it could also reduce time to walk without assistance, improve the efficacy of analgesia and sleep quality during the first night after LC, but did not increase the incidence of surgical adverse events. CONCLUSIONS: The use of ropivacaine and dexmedetomidine may be considered as an alternative treatment for postoperative pain in patients undergoing LC.

The optimal dose of dexmedetomidine added to an sufentanil-based analgesic regimen for postoperative pain control in spine surgery: A probit analysis study.

Postoperative spinal patients remain a challenge for provision of postoperative analgesia. Patient-controlled intravenous analgesia (PCIA) is a major method in reducing the severe pain after the surgery in our institution, but some adverse effects prevent the use of adequate dosage opioids.This study was determined using the probit analysis to investigate the optimal dose of dexmedetomidine (DEX) infusion for postoperative analgesia combined with sufentanil (SUF) in spine surgery.The dose of DEX needed to produce satisfactory analgesia conditions following combination of 3.0 µg/kg SUF in PCIA pump, which was diluted to 250 mL with a 4 mL/h as background infusion. Patients were recruited with age 35 to 65 years. The satisfactory criteria of postoperative analgesia were determined with a average satisfaction level of pain control, sedation, self-satisfaction, and adverse effects, among others. The dose of DEX was determined using the modified Dixon's up-and-down method (0.5 µg/kg as a step size). The first patient was test at 3.0 µg/kg DEX. The patient was assessed at 6, 12, 36 hours, and termination of PCIA following the continuous infusion of DEX-SUF mixture in PCIA after surgery.Twenty-five patients were enrolled by predetermined criteria. The optimal dose of DEX required for satisfactory analgesic was 4.33 (SD, 0.38) µg/kg combined with 3.0 µg/kg SUF via a PCIA volume of 250 mL by background infusion of 4 mL/h. Using probit analysis, the ED50 of DEX was 4.12 µg/kg (95% confidence limits 3.74-4.52 µg/kg) for satisfactory postoperative analgesic in spine surgery, the ED95 of DEX was 4.85 µg/kg (95% confidence limits 4.48-7.13 µg/kg). There was no report of somnolence or respiratory depression, relevant bradycardia or hypotension, or over sedation in this study.The optimal dose of DEX was 4.33 (0.38) µg/kg combined with 3.0 µg/kg SUF diluted to 250 mL with a background infusion of 4 mL/h for satisfactory analgesic after spine surgery. From probit analysis, ED50 and ED95 of DEX were 4.12 µg/kg (95% confidence limits 3.74-4.52 µg/kg) and 4.85 µg.kg (95% confidence limits 4.48-7.13 µg/kg), respectively.

Preoperative dexmedetomidine prevents tourniquet-induced hypertension in orthopedic operation during general anesthesia.

This study was a double-blinded randomized control trial designed to investigate the hemodynamic effects of dexmedetomidine on prolonged tourniquet inflation. Thirty-seven patients scheduled for elective orthopedic surgery of the lower limb under general anesthesia were recruited. They were randomly assigned to receive intravenous dexmedetomidine (DEX, 0.5 µg/kg; n = 18) or normal saline (CON; n = 19) before tourniquet inflation. Arterial blood pressure and heart rate were recorded every 10 minutes until 60 minutes after the start of tourniquet inflation and again immediately after deflation. In the DEX group, arterial pressure was not significantly changed, but in the CON group arterial pressure was significantly increased at 40, 50, and 60 minutes after the start of tourniquet inflation. Development of more than 30% increase in arterial pressure during tourniquet inflation was more frequent in the CON group than in the DEX group. Preoperative intravenous dexmedetomidine could therefore prevent tourniquet-induced hypertension in patients undergoing general anesthesia.