N6-cyclohexyladenosine is better than meperidine and buspirone at suppressing metabolism during TTM32 but does not improve outcome after cardiac arrest.

N6-clyclohexyladenosine (CHA) is an adenosine A1 receptor agonist that inhibits thermogenesis. Cardiovascular side effects however, limit use of CHA as a therapeutic. We and others have shown that this can be reversed by administering 8-p-(sulfophenyl)theophylline (8-SPT), a nonspecific antagonist that does not cross the BBB. Other evidence shows that CNS actions of CHA may contribute to bradycardia through enhanced vagal tone and other mechanisms. Here we test the hypothesis that 8-SPT pretreatment alone is sufficient to prevent hypotension caused by CHA. To test this hypothesis, we pretreated rats with 8-SPT alone, and in combination with other antagonists to test the hypothesis that direct action of CHA on the heart is the primary mechanism by which CHA induces bradycardia and hypotension. Results show that pretreatment with 8-SPT alone is not sufficient to prevent CHA-induced hypotension. Pretreatment with 8-SPT or atropine alone did not prevent the fall in mean arterial pressure (MAP) and heart rate (HR), however, pretreatment with 8-SPT (25 mg/kg) and atropine (1 mg/kg) 15 min before CHA (1 mg/kg) preserves MAP and HR baseline values after CHA administration. We next asked if blood pressure was managed during the transition into a hypometabolic state, would prolong CHA-mediated inhibition of metabolism after cardiac arrest improve outcome better than anti-shivering medications meperidine and buspirone. We found that CHA-mediated hypotension can be mitigated by pretreatment with atropine and 8-SPT. This combination administered after cardiac arrest facilitated temperature management and metabolic suppression better than meperidine and buspirone, however, did not improve survival.

Comparing intravenous lidocaine and pethidine for pain management in emergency department patients with femoral bone fracture: a randomized controlled trial.

BACKGROUND: Intravenous lidocaine has shown promise as an effective analgesic in various clinical settings, but its utility for pain management in emergency departments, especially for bone fractures, remains relatively understudied. OBJECTIVE: This study compared intravenous lidocaine to pethidine for femoral bone fracture pain management. METHODS: This double-blind, randomized, controlled clinical trial was conducted in the emergency department of AJA University of Medical Sciences affiliated hospitals. Patients aged 18-70 years-old with femoral bone fracture and experiencing severe pain, defined as a numerical rating scale (NRS) of pain ≥ 7, were included in the study. One group received intravenous pethidine (25 mg), while the other group received intravenous lidocaine (3 mg/kg, not exceeding 200 mg), infused with 250 ml saline over 20 min. Pain levels were evaluated before treatment administration (0 min) and at 10, 20, 30, 40, 50, and 60 min after treatment administration using the NRS. RESULTS: Seventy-two patients were enrolled in the study. Demographic characteristics and pain scores were similar between the two groups. The mean pain scores upon arrival for the lidocaine and pethidine groups were 8.50 ± 1 and 8.0 ± 1, respectively; after one hour, they were 4.0 ± 1 and 4.0 ± 1, respectively. While there was a statistically significant reduction in pain in both groups after one hour, there were no clinically or statistically significant differences between the two groups (p = 0.262). Pethidine had a higher incidence of adverse events, though not statistically significant. Additionally, females required more rescue analgesics. CONCLUSION: The administration of intravenous lidocaine is beneficial for managing pain in femoral bone fractures, suggesting that lidocaine could be a potent alternative to opioids. TRIAL REGISTRATION: IRCT20231213060355N1 ( https://irct.behdasht.gov.ir/trial/74624 ) (30/12/2023).

The Effect of Granisetron, Ondansetron, and Meperidine in Preventing Postoperative Shivering: Controlled Clinical Trial.

BACKGROUND: Recently, use of HT35 receptor antagonists to prevent postoperative shivering has attracted a great deal of attention. This study was conducted with the aim of investigating the effectiveness of granisetron as an HT35 antagonist when compared with ondansetron and meperidine in preventing postoperative shivering. MATERIAL AND METHODS: In this triple blind random clinical trial study, 90 patients 18-50 years of age with ASA Class I and II undergoing general anesthesia were randomly assigned into one of the three drug groups: O (4-mg ondansetron), G (40 µg/kg of granisetron), and P (25 mg meperidine), immediately before induction of anesthesia. After anesthesia induction, at the end of the surgery, after the entrance and after leaving the recovery state, central temperature, peripheral temperature, heart rate, systolic blood pressure, diastolic blood pressure, and shivering were measured and documented. Two-tailed P < 0.05 was considered significant. RESULTS: In the meperidine, ondansetron, and granisetron groups, 4 (13.3%), 3 (10%), and 10 (33.3%) of patients experienced shivering during recovery, where the difference between the ondansetron and granisetron groups was significant (p-value=0.02). The variations in the mean arterial pressure during the investigation stages only in the ondansetron group were not significant (p>0.05). At the beginning of recovery, the reduction of peripheral temperature significantly was lower in the ondansetron group (p<0.05), while reduction of the central temperature was significantly (p<0.05) higher in the granisetron group. By the end of the recovery, the variations in the peripheral temperature across the three groups were consistent with the changes at the beginning of recovery, but variations of the central temperature across the three groups was not significantly diverse. CONCLUSION: Granisetron was not found to be much effective in preventing postoperative shivering. Ondansetron and meperidine were equally effective in preventing postoperative shivering. Ondansetron also causes less hemodynamic changes compared to other drugs, while granisetron is more effective in terms of preventing nausea and vomiting.

Examining the efficacy of intravenous ibuprofen and meperidine for preventing post-operative shivering after laparoscopic cholecystectomy with general anesthesia.

Postoperative shivering is a common complication that can lead to increased postoperative complications. This study aimed to compare the effectiveness of intravenous ibuprofen and meperidine in preventing shivering following laparoscopic cholecystectomy. A total of 120 patients, aged 20-70 and classified as ASA I-II, were enrolled in this triple-blind clinical trial. The participants were randomly assigned to one of three groups: ibuprofen (800mg IV), meperidine (30 mg), or placebo (normal saline 2 ml), administered 30 minutes before the end of surgery. The occurrence of postoperative shivering was assessed and recorded at regular intervals (0, 5, 10, 15, 30, and 60 minutes after surgery). Additionally, postoperative pain levels were measured using a visual analog scale (VAS), sedation levels were evaluated using the Ramsay Sedation Scale (RSS), and the incidence of postoperative nausea and vomiting was documented. The prevalence and severity of postoperative shivering were not statistically significant between groups. The VAS was significantly lower in the meperidine group than the ibuprofen group throughout the study (p <0.001). The VAS was significantly lower in the ibuprofen group than the placebo group at 0 and 15 minutes after surgery. Although the incidence of nausea was slightly higher in the meperidine group, the difference was not statistically significant (p=0.75). Sedation scores were consistently lower in the ibuprofen group and higher in the meperidine group compared to the other groups (p<0.0001) The meperidine group had a significantly higher sedation score indicative of deep sleepiness (score of 4) than the other groups. Intravenous ibuprofen demonstrated comparable efficacy to meperidine in controlling shivering. Additionally, the incidence of nausea, vomiting, and sleepiness was lower in the intravenous ibuprofen group, suggesting it is a potential alternative to meperidine.

The Role of Adrenaline, Noradrenaline, and Cortisol in the Pathogenesis of the Analgesic Potency, Duration, and Neurotoxic Effect of Meperidine.

Background and Objectives: The purpose of the study was to investigate the role of adrenaline (ADR), noradrenaline (NDR), and cortisol in the pathogenesis of the analgesic potency, duration, and epilepsy-like toxic effect of meperidine. Materials and Methods: The experimental animals were separated into 11 groups of six rats. In the meperidine (MPD) and metyrosine + meperidine (MMPD) groups, paw pain thresholds were measured before and after the treatment between the first and sixth hours (one hour apart). In addition, ADR and NDR analyses were performed before and after the treatment, between the first and fourth hours (one hour apart). For the epilepsy experiment, caffeine, caffeine + meperidine, and caffeine + meperidine + metyrapone groups were created, and the treatment was applied for 1 day or 7 days. Groups were created in which caffeine was used at both 150 mg/kg and 300 mg/kg. Epileptic seizures were observed in epilepsy groups, latent periods were determined, and serum cortisol levels were measured. Results: In the MPD group, pain thresholds increased only at the first and second hours compared to pre-treatment, while ADR increased at the third hour, leading to a decrease in pain thresholds. In the MMPD group, the increase in paw pain thresholds at 1 and 6 h was accompanied by a decrease in ADR and NDR. In the caffeine (150 mg/kg) + meperidine group, 1-day treatment did not cause epileptic seizures, while seizures were observed and cortisol levels increased in the group in which treatment continued for 7 days. When cortisol levels were compared between the group in which caffeine (300 mg/kg) + meperidine + metyrapone was used for 7 days and the animals receiving caffeine (300 mg/kg) + metyrapone for 7 days, it was found that cortisol levels decreased and the latent period decreased. Conclusions: The current study showed that if serum ADR and cortisol levels are kept at normal levels, a longer-lasting and stronger analgesic effect can be achieved with meperidine, and epileptic seizures can be prevented.

Evaluating Caudal Block Enhancements in Pediatric Circumcision: Do Additional Analgesics Make a Difference?

BACKGROUND Caudal block is widely regarded as the top choice for multimodal analgesia in children undergoing urological surgeries, particularly circumcision. This study investigates the efficacy of caudal block and the necessity of rescue analgesia in circumcision surgeries. MATERIAL AND METHODS A prospective, single-blind study was conducted at Ordu University Training and Research Hospital from December 1, 2022, to July 1, 2023. The study randomly divided ASA class I-II children aged 1-12 years into 3 groups for circumcision surgery. Group C received only caudal block. Group CP received caudal block with 10 mg/kg intravenous paracetamol. Group CM received caudal block with 1 mg/kg intravenous meperidine. In each case, a caudal block was administered using 0.5 ml/kg of 0.125% bupivacaine under ultrasound guidance. The primary outcome of the study was total analgesic consumption; the secondary outcomes were pain scores and time to first analgesic administration. Pain severity was evaluated using FLACC and Wong-Baker scores at 0, 1, 4, and 24 h. RESULTS A total of 120 patients, 40 patients in each group, were included in the study. A significant difference was detected among all 3 groups in the Wong-Baker pain score (24th hour) (P<0.001). The FLACC and Wong-Baker pain scores did not differ significantly in the other time frames. The time of the first rescue analgesia and the total amount of analgesic taken in the first 24 h were the same for both groups (P=0.408 and P=0.238). CONCLUSIONS The addition of paracetamol or meperidine to caudal block does not enhance the quality of analgesia.

Pharmacologic interventions for the therapy of postanesthetic shivering in adults: a systematic review and network meta-analysis.

INTRODUCTION: Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare but can occur due to increased oxygen consumption. Previous systematic reviews are outdated and have summarized the evidence on the topic using only pairwise comparisons. The objective of this manuscript was a quantitative synthesis of evidence on pharmacological interventions to treat postanesthetic shivering. EVIDENCE ACQUSITION: Systematic review and frequentist network meta-analysis using the R package netmeta. Endpoints were the risk ratio (RR) of persistent shivering at one, five and 10 minutes after treatment with saline/placebo as the comparator. Data were retrieved from Medline, Embase, Central and Web of Science up to January 2022. Eligibility criteria were: randomized, controlled, and blinded trials comparing pharmacological interventions to treat shivering after general anesthesia. Studies on shivering during or after any type of regional anesthesia were excluded as well as sedated patients after cardiac surgery. EVIDENCE SYNTHESIS: Thirty-two trials were eligible for data synthesis, including 28 pharmacological interventions. The largest network included 1431 patients. The network geometry was two-centered with most comparisons linked to saline/placebo or pethidine. The best interventions were after one minute: doxapram 2 mg/kg, tramadol 2 mg/kg and nefopam 10 mg, after 5 minutes: tramadol 2 mg/kg, nefopam 10 mg and clonidine 150 µg and after 10 minutes: nefopam 10 mg, methylphenidate 20 mg and tramadol 1 mg/kg, all reaching statistical significance. Pethidine 25 mg and clonidine 75 µg also performed well and with statistical significance in all networks. CONCLUSIONS: Nefopam, tramadol, pethidine and clonidine are the most effective treatments to stop postanesthetic shivering. The efficacy of doxapram is uncertain since different doses showed contradictory effects and the evidence for methylphenidate is based on a single comparison in only one network. Furthermore, both lack data on side effects. Further studies are needed to clarify the efficacy of dexmedetomidine to treat postanesthetic shivering.

Impact of adding pethidine on disinhibition during bronchoscopy with midazolam: a propensity score matching analysis.

BACKGROUND: We sometimes experience disinhibition during bronchoscopy with sedation. However, the impact of adding pethidine on disinhibition has not yet been investigated. This study aimed to examine the additive impact of pethidine on disinhibition during bronchoscopy with midazolam. METHODS: This retrospective study involved consecutive patients who underwent bronchoscopy between November 2019 and December 2020 (sedated with midazolam: Midazolam group) and between December 2020 and December 2021 (sedated with midazolam plus pethidine: Combination group). The severity of disinhibition was defined as follows: moderate, disinhibition that always needed restraints by assistants; and severe, disinhibition that needed antagonization of sedation by flumazenil to continue bronchoscopy. One-to-one propensity score matching was used to match baseline characteristics between both groups. RESULTS: After propensity score matching with depression, the type of bronchoscopic procedure, and the dose of midazolam, 142 patients matched in each group. The prevalence of moderate-to-severe disinhibition significantly decreased from 16.2% to 7.8% (P = 0.028) in the Combination group. The Combination group had significantly better scores for sensation after bronchoscopy and feelings toward bronchoscopy duration than did the Midazolam group. Although the minimum SpO2 during bronchoscopy was significantly lower (88.0 ± 6.2 mmHg vs. 86.7 ± 5.0 mmHg, P = 0.047) and the percentage of oxygen supplementation significantly increased (71.1% vs. 86.6%, P = 0.001) in the Combination group, no fatal complications were observed. CONCLUSIONS: Adding pethidine could reduce disinhibition occurrence in patients undergoing bronchoscopy with midazolam, with better subjective patient outcomes during and after bronchoscopy. However, whether more patients may need oxygen supplementation and whether hypoxia occurs during bronchoscopy should be considered. CLINICAL TRIAL REGISTRATION: UMIN000042635.

Intra-articular remifentanil on postoperative pain in knee arthroscopic surgery; a double blind randomized clinical trial.

BACKGROUND: We aimed to assess the efficacy of intra-articular remifentanil in relieving postoperative pain after knee arthroscopy. METHODS: We conducted a double-blind randomized clinical trial study on 60 patients. Patients were divided into two equal groups. The control group received 25 ml of intra-articular normal saline, and the intervention group received 200 µg of remifentanil dissolved in 25 ml of saline. We evaluated at rest postoperative pain at 1, 3, 6, 12, 18, and 24 h after the surgery using the Visual Analog Scale (VAS). Patients with VAS scores of 4 or more received meperidine (pethidine). The first time meperidine was requested and the total amount of meperidine consumed was recorded. RESULTS: Out of 60 patients, 49 were male (81.6%), and the mean age of participants was 32.71 (7.02) years. An hour after the surgery, the control group showed a mean VAS score of 8.66 (1.26), and decreased to 2.53 (1.67) at the end of 24 h. The intervention group started with a mean VAS score of 2.23 (1.81) and ended at 0.10 (0.305). All patients in the control group and 11 (36.7%) patients in the intervention group asked for analgesics during follow-up. The mean total meperidine dose in the control and intervention groups was 108.33 (23.97) mg and 13.33 (19.40) mg, respectively (P < 0.001; 95% confidence interval of the difference 83.72 to 106.27). CONCLUSIONS: Intra-articular remifentanil may decrease postoperative pain and analgesic requirements in patients undergoing knee arthroscopy.

Inter-semispinal plane (ISP) block for postoperative analgesia following cervical spine surgery: A prospective randomized controlled trial.

STUDY OBJECTIVE: We evaluated the perioperative analgesic effects of the inter-semispinal plane (ISP) block in patients undergoing posterior cervical spine surgery. DESIGN: Prospective, randomized, controlled, double-blinded trial. SETTING: Operating room and surgical ward. PATIENTS: 60 patients aged 18-60 years of either gender, ASA I-II, undergoing elective posterior cervical spine surgery. INTERVENTIONS: Patients were randomly assigned into a control group (general anesthesia only), ISP group received bilateral ultrasound guided ISP block at the level of C5 using 20 ml bupivacaine 0.25% on each side. MEASUREMENTS: Visual analog scale (VAS), intraoperative fentanyl and 24 h postoperative pethidine consumptions and time to first rescue analgesic request were documented. MAIN RESULTS: The median (quartiles) of 24 h postoperative rescue pethidine consumption was significantly lower in the ISP group [0 (0-46.25) mg] compared to that of the control group [143 (116.75-169.00) mg]; P < 0.001). VAS was significantly lower in the ISP group at 30 min, 1 h, 2 h,4 h, 6 h, 8 h and 12 h postoperative compared to control group (P < 0.05). At 18 and 24 h, VAS was not significantly different between groups. The median (quartiles) of intraoperative fentanyl consumption in the ISP group [0 (0-40.75) µg] was significantly lower compared to that of the control group [63.5 (39.5-90.25) µg]; P < 0.001]. The time to first rescue analgesic administration was significantly longer in the ISP group compared to the control group (P < 0.001). CONCLUSION: Bilateral ultrasound-guided ISP block can provide decreased 24 h postoperative analgesic consumption as well as lower pain scores in the first 12 postoperative hours in patients undergoing posterior cervical spine surgery.

Efficacy of a local anesthetic gel infusion kit for pain relief after minimally invasive colorectal surgery: an open-label, randomized clinical trial.

Continuous wound infusion with local anesthesia is an effective method for reducing postoperative pain after laparoscopic colorectal surgery. However, most subcutaneous local anesthesia is delivered through continuous injection, which can be inconvenient for patients. This study compared the effectiveness of postoperative pain relief from the application of a local poloxamer 407-based ropivacaine hydrogel (Gel) to the incision site with continuous infusion-type ropivacaine administration (On-Q) in patients undergoing laparoscopic colorectal surgery. This prospective, randomized, non-inferiority study included 61 patients who underwent laparoscopic colorectal surgery with an incision length of 3-6 cm. All 61 patients were randomly assigned to the Gel group (poloxamer 407-based 0.75% ropivacaine, 22.5 mg) or the On-Q group (0.2% ropivacaine, 4 mg/hour for two days). Postoperative analgesia was induced in all patients with intravenous patient-controlled analgesia (IV-PCA). The outcome measures, which were assessed for 72 h after surgery, included the total amount of fentanyl consumed via IV-PCA (primary endpoint), and the amount of rescue analgesia (pethidine) and postoperative pain intensity assessed using a numeric rating scale (NRS) [secondary endpoints]. The Gel was administered to 31 patients and On-Q was used for 30 patients. There was no significant difference in the total usage of fentanyl between the two groups (Gel group, 1623.98 mcg; On-Q group, 1595.12 mcg; P = 0.806). There was also no significant difference in the frequency of analgesic rescue medication use (P = 0.213) or NRS scores (postoperative 6 h, P = 0.860; 24 h, P = 0.333; 48 h, P = 0.168; and 72 h, P = 0.655) between the two groups. The Gel, which continuously delivers a local anesthetic to operative sites, can thus be considered an effective device for analgesia and pain relief for midline incisions in laparoscopic colorectal surgery.

Comparison of analgesic consumption of hemophilic and non-hemophilic patients in knee arthroplasty.

BACKGROUND: Hemophilia is a rare hereditary bleeding disorder that develops as a result of factor VIII or IX deficiency. Long-term complications of hemophilia such as arthropathy, synovitis, and arthritis can lead to the development of recurrent chronic pain. Pain is therefore a critical aspect of hemophilia. The gold standard treatment for end-stage hemophilic knee arthropathy is total knee arthroplasty (TKA). The hypothesis of this study was that after knee replacement surgeries that cause severe post-operative pain, hemophilia patients with chronic analgesic consumption may experience higher levels of pain than non-hemophilic patients, and use more opioid and non-opioid drugs. METHODS: This retrospective study included 82 patients who were hemophilic and non-hemophilic TKA patients operated under general anesthesia. Seventy-three patients were evaluated and divided into two groups according to the diagnosis of hemophilia: 36 patients were investigated in the hemophilic group and 37 patients in the non-hemophilic group. RESULTS: Post-operative tramadol consumption (p=0.002) and pethidine consumption (p=0.003) were significantly higher in the group hemophilia. The length of stay in the hospital was also significantly longer in the hemophilic group (p=0.0001). CONCLUSION: In the light of these informations, we think that acute post-operative pain management of hemophilia patients should be planned as personalized, multimodal preventive, and pre-emptive analgesia.

Evaluation of ultrasound guided erector spinae plane block efficacy on post operative pain in lumbar spine surgery: a randomized clinical trial.

OBJECTIVES: Patients suffer notable levels of pain after lumbar spine surgery. The primary objective of this randomized clinical trial is to investigate the efficacy of erector spinae plane block (ESPB) on 24-h post-operative pain score of patients undergoing lumbar spine surgery. Cumulative opioid consumption and intraoperative bleeding were assessed as well. METHODS: Adult patient candidates for elective lumbar spine surgery were randomly assigned to case (ESPB) and control (no ESPB) groups. The block was performed under ultrasound guidance in prone position after induction of general anesthesia. Both groups received the same anesthesia medication and technique. Post-operative pain score, number of patients requiring rescue analgesia (meperidine), total amount of post-operative rescue analgesic demand in the first 24 h, and intraoperative bleeding were recorded. To compare pain score variable in time span, the ANOVA repeated measure test was used. All the statistical tests were two tailed and p<0.05 considered as statistically significant. RESULTS: In all time intervals, pain score in case group was significantly lower than control group. In case group, eight patients demanded rescue analgesic (40%) which was significantly lower than that in control group (15 patients [75%]) (p=0.025). Total amount of meperidine consumption was 57.50±45.95 in control group and 22.50±32.34 in case group (p=0.01) which was higher in control group and statistically significant. CONCLUSION: ESPB reduces post-operative pain score and opioid consumption, while it does not affect intraoperative bleeding in lumbar spine surgery.

Sedation quality of alfaxalone associated with butorphanol, methadone or pethidine in cats injected into the supraspinatus or the quadriceps muscle.

OBJECTIVES: The aim of this study was to compare the quality of sedation with three different anaesthetic protocols (alfaxalone combined with butorphanol, methadone or pethidine) administered intramuscularly in cats, and to evaluate the influence of the injection site (between supraspinatus and quadriceps muscles) on the onset and quality of sedation. METHODS: A total of 151 cats were selected for this study. Cats were sedated with alfaxalone (3 mg/kg) combined with either butorphanol (0.3 mg/kg; n = 50), methadone (0.3 mg/kg; n = 53) or pethidine (5 mg/kg; n = 48). The combination was injected intramuscularly into the supraspinatus (n = 79) or quadriceps muscle (n = 72). The data included a scoring system for the quality of sedation and physiological parameters, such as heart rate (HR), respiratory rate, body temperature and occurrence of mydriasis, monitored during the first 30 mins of anaesthesia. RESULTS: The opioid associated with alfaxalone influenced the overall sedation score, the degree of myorelaxation, the occurrence of mydriasis and HR. The overall sedation score was poorer with butorphanol than with methadone (P = 0.008), and butorphanol induced a lower degree of myorelaxation than methadone (P = 0.013). The injection into the supraspinatus showed better qualitative results for sedation and a faster onset time (in about 3 mins) than that into the quadriceps (P <0.001). HR decreased from baseline (P <0.001) and over time (P <0.001), mainly in cats of the butorphanol-supraspinatus and pethidine-quadriceps groups (P = 0.004). The occurrence of mydriasis was lower after butorphanol than after methadone and pethidine (P = 0.025), while the incidence of side effects did not differ among groups. CONCLUSIONS AND RELEVANCE: All three protocols provided a good quality of sedation and allowed performing the scheduled procedure. Moreover, the injection into the supraspinatus muscle showed superior results in all the qualitative scores of sedation and quicker onset time than that into the quadriceps muscle.

Femoral 3-in-1 Nerve Block for Total Knee Replacement, an Analgesic Approach Not to Be Neglected. Single Center Experience and Literature Review.

OBJECTIVES: Total Knee Replacement Surgery (TKR) is one of the most common elective orthopedic operations. Postoperative pain after total knee replacement, remains a challenge. In this retrospective observational study, we evaluated the effectiveness of 3-in-1 nerve block in patients after total knee arthroplasty compared to standard opioid treatment, and we state the reasons why this approach should still be considered. METHODS: To evaluate the effectiveness of the 3-in-1 nerve block, we assessed the acute pain service archive and compared the values of the visual analog scale, by separating patients into two groups according to the analgesic regimen they received as per local protocols. In group A, patients received 0.25% bupivacaine through a 3 in 1 block catheter and additional meperidine IM if needed, while in group B they received meperidine every six hours. RESULTS: Our analysis showed the statistically significant better effectiveness of 3-in-1 nerve block with bupivacaine administration in postoperative TKR pain control compared to repeated administration of meperidine. CONCLUSION: The results of our study suggest that 3-in-1 nerve block with bupivacaine is an option that must always be considered in order to alleviate post-operative pain after TKR.

Randomized single-blind comparative study of the midazolam/pethidine combination and midazolam alone during bronchoscopy.

BACKGROUND: Bronchoscopy can be a distress for the patient. There have been few studies on the combination of sedatives and opioids. The aim of this study was to demonstrate the usefulness and safety of administration of the combination of midazolam and pethidine during bronchoscopy. METHODS: In this prospective randomized single (patient)-blind study, we randomly assigned 100 patients who were scheduled to undergo bronchoscopy biopsy to receive treatment with either the midazolam/pethidine combination (combination group) or midazolam alone (midazolam group) during examinations. After the end of bronchoscopy, patients completed a questionnaire and the visual analogue scale was measured. The primary outcome was the patients' acceptance of re-examination assessed by visual analogue scale. We also assessed pain levels, vital signs, midazolam use, xylocaine use, and adverse events. Univariate analyses were performed using Fisher's exact test for categorical data, and the t-test or Mann-Whitney test was carried out for analysis of numeric data. All P-values were two-sided, and values < 0.05 were considered statistically significant. RESULTS: We analyzed 47 patients in the combination group and 49 patients in the midazolam group. The primary outcome was a good trend in the combination group, but not significantly different (3.82 ± 2.3 in combination group versus 4.17 ± 2.75 in midazolam alone, P = 0.400). In the combination group, the visual analog scale score for pain during bronchoscopy was significantly lower (1.10 ± 1.88 versus 2.13 ± 2.42, P = 0.022), and the sedation level score per the modified observer's assessment of alertness/sedation scale was significantly deeper (3.49 ± 0.98 versus 3.94 ± 1.03, P = 0.031). Maximal systolic blood pressure during testing was significantly lower (162.39 ± 23.45 mmHg versus 178.24 ± 30.24 mmHg, P = 0.005), and the number of additional administrations of midazolam was significantly lower (2.06 ± 1.45 versus 2.63 ± 1.35, P = 0.049). There were also significantly fewer adverse events (30 versus 41, P = 0.036). CONCLUSIONS: The combination uses of midazolam and pethidine for sedation resulted in significant improvements in the pain, blood pressure, additional use of midazolam, and safety during bronchoscopy among patients. TRIAL REGISTRATION: This study was registered in the University Medical Hospital Information Network in Japan (UMINCTR Registration number: UMIN000032230 , Registered: 13/April/2018).

Imrecoxib versus celecoxib as postoperative analgesia for patients receiving arthroscopic knee surgery: a randomized, controlled, non-inferiority study.

OBJECTIVE: Imrecoxib is a novel cyclooxygenase-2 inhibitor independently developed in China, which exhibits a good efficacy and tolerance in orthopedic disorders. The current study aimed to further compare its efficacy and safety with celecoxib as postoperative analgesia in arthroscopic knee surgery (AKS). METHODS: Patients receiving AKS were enrolled and randomly assigned to imrecoxib (n = 64) and celecoxib (n = 62) group to receive analgesia for 72 h after surgery. Pain at rest and movement, pethidine consumption, patient's satisfaction, Lysholm score, and adverse events were assessed after AKS. Meanwhile the upper limit of 95% CI of pain-score mean difference (MD) between imrecoxib and celecoxib was calculated, then, the non-inferiority was defined if the all-time-point upper limits of 95% CI less than 1. RESULTS: Imrecoxib was non-inferior to celecoxib for alleviating pain at rest (upper limit of 95% CI of MD ranging from 0.443 to 0.782, all time-point values less than 1); as well as for attenuating pain at movement (upper limit of 95% CI of MD ranging from 0.398 to 0.582, all time-point values less than 1). Moreover, rescue analgesia rate (P = 0.583), pethidine consumption (P = 0.454), patient's satisfaction at 72 h (P = 0.408), and Lysholm score at M3 (P = 0.776) were of no difference between imrecoxib group and celecoxib group. Additionally, the main adverse events in two groups were nausea (P = 0.425), constipation (P = 1.000), vomiting (P = 0.715), headache (P = 1.000), and dizziness (P = 0.667), which were mild and manageable. CONCLUSION: Imrecoxib is non-inferior to celecoxib in postoperative analgesia and exhibits an acceptable tolerance in patients undergoing AKS.

A hypothetical proposal to employ meperidine and tamoxifen in treatment of glioblastoma. Role of P-glycoprotein, ceramide and metabolic pathways.

Meperidine (pethidine) is a µ-opioid receptor (MOR) agonist widely used in the treatment of cancer pain. While MOR agonists in experimental models have demonstrated both pro- and antitumorigenic properties, meperidine has unique features which may be predominantly anticancer in nature. Meperidine both inhibits NMDA (N-methyl-D-Aspartate) receptors, which are involved in the progression of glioblastoma, and blocks NADH:Ubiquinone Oxidoreductase, which may hinder mitochondrial respiration. In the developing embryonic neural tissue, meperidine reduces cell proliferation around the neural tube and lowers the expression of the B RE (brain and reproductive organ-expressed). This is notable given that the B RE gene is implicated in cancer chemoresistance and gliomagenesis. Further, meperidine inhibits P-glycoprotein, which is involved in cancer multidrug resistance and the degradation of the sphingolipid backbone, ceramide. By enhancing the pro-autophagic and pro-apoptotic ceramide levels in cancer cells, meperidine stimulates cell death and reverses multidrug resistance. Tamoxifen, a safe medication employed in the treatment of breast cancer, directly blocks P-glycoprotein and boosts levels of ceramide both via inhibition of glycosylceramide synthase and ceramidase. Further, tamoxifen blocks NMDA-neurotoxicity and therefore it may act synergistically with meperidine in reducing glioblastoma progression associated with NMDA-activation. Finally, tamoxifen blocks glycolysis which may enhance the mitochondrial-blocking activity of meperidine to shut down energy metabolism of glioblastoma cells. Because of these properties, we believe that the combination of meperidine and tamoxifen merits study in cell culture and animal models to investigate a potential synergistic relationship in the treatment of glioblastoma.

The effect of continuous intercostal nerve block vs. single shot on analgesic outcomes and hospital stays in minimally invasive direct coronary artery bypass surgery: a retrospective cohort study.

BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) grafting surgery is accompanied by severe pain. Although continuous intercostal nerve block (CINB) has become one of the multimodal analgesic techniques in single port thoracoscopic surgery, its effects on MIDCAB are unclear. The purpose of this study was to compare the effects of CINB and single shot on analgesic outcomes and hospital stays in patients undergoing MIDCAB in a real-world setting. METHODS: A retrospective cohort study was carried out at Peking University Third Hospital, China. Two hundred and sixteen patients undergoing MIDCAB were divided into two groups: a CINB group and a single block (SI) group. The primary outcome was postoperative maximal visual analog scale (VAS); secondary outcomes included the number of patients with maximal VAS ≤ 3, the demand for and consumed doses of pethidine and tramadol, and the length of intensive care unit (ICU) and hospital stays. The above data and the area under the VAS curve in the 70 h after extubation for the two subgroups (No. of grafts = 1) were also compared. RESULTS: The maximum VAS was lower in the CINB group, and there were more cases with maximum VAS ≤ 3 in the CINB group: CINB 52 (40%) vs. SI 17 (20%), P = 0.002. The percentage of cases requiring tramadol and pethidine was less in CINB, P = 0.001. Among all patients, drug doses were significantly lower in the CINB group [tramadol: CINB 0 (0-100) mg vs. SI 100 (0-225) mg, P = 0.0001; pethidine: CINB 0 (0-25) mg vs. SI 25 (0-50) mg, P = 0.0004]. Further subgroup analysis showed that the area under the VAS curve in CINB was smaller: 28.05 in CINB vs. 30.41 in SI, P = 0.002. Finally, the length of ICU stay was shorter in CINB than in SI: 20.5 (11.3-26.0) h vs. 22.0 (19.0-45.0) h, P = 0.011. CONCLUSIONS: CINB is associated with decreased demand for rescue analgesics and shorter length of ICU stay when compared to single shot intercostal nerve block. Additional randomized controlled trial (RCT) is needed to support these findings.

Prevalence of opioid prescriptions in Taiwan (2008-2018).

BACKGROUND: Opioids are effective for severe pain; however, the safety issue is also a primary concern. To better understand the opioid use in Taiwan, we conducted this study. METHODS: Data on patients with opioid prescriptions, including morphine, fentanyl, pethidine, codeine, oxycodone, hydromorphone, and buprenorphine were collected using the Taiwan National Health Insurance Database (NHID). RESULTS: Our analysis of opioid prescriptions from 2008 to 2018 in Taiwan indicated that (1) A slow increase in prevalence of opioid prescription was found during the study period. Among the drugs studied, morphine accounted for the majority of the prescriptions written, with a gradual increase annually. Pethidine prescriptions showed a significant and rapid decline over the years; (2) medical centers prescribed the largest number of opioids, followed by regional hospitals, local hospitals, and clinics; (3) the number of prescriptions per year per capita in cancer group was much higher than that in noncancer group. In noncancer group, most of the prescriptions were used in acute pain service (98.7%); and (4) use of opioids increased with age in both cancer and noncancer patients. CONCLUSION: The total number of opioid prescriptions in Taiwan gradually increased annually, among which morphine was the most commonly used opioid. Cancer patients consumed more opioid prescriptions than noncancer patients and most of the prescriptions in noncancer patients were used in acute pain service. The number of prescriptions increased with the age of the patients in both cancer and noncancer patients. The low prescription rate of opioids in chronic pain in Taiwan is not similar as those in high opioid-consuming countries, such as United States.