Superior Analgesic Efficacy Research Articles

Comparative Analysis of Epidural Dexamethasone and Epidural Morphine (EM) for Postoperative Pain Control After Total Abdominal Hysterectomy: A Randomized Clinical Trial

Background: Epidural anesthesia is commonly utilized for pain management following lower abdominal surgeries; however, the search for an optimal analgesic additive continues. Objectives: This study aimed to compare the efficacy of epidural dexamethasone versus epidural morphine (EM) in managing postoperative pain after total abdominal hysterectomy. Methods: This randomized controlled trial enrolled patients undergoing total abdominal hysterectomy (TBAH) and assigned them to two groups: Group D (Dexamethasone), which received epidural dexamethasone (8 mg) with bupivacaine, and Group M (Morphine), which received epidural morphine (10 mg) with bupivacaine. Marcaine (bupivacaine) 0.25% was used in both groups. Baseline characteristics, surgical outcomes, physiological parameters, pain management, adverse effects, and blood sugar levels were analyzed and compared between the groups. Results: The groups exhibited similar initial characteristics and surgical outcomes. Vital signs, including heart rate (HR), mean arterial pressure, respiratory rate, and oxygen saturation, remained consistent before and after surgery. The Dexamethasone group (Group D) demonstrated superior pain control compared to the Morphine group (Group M). Patients in Group D required pain medication for a significantly shorter duration (24 hours vs. 36 hours, P < 0.05), representing a 50% reduction in medication duration. Additionally, Group D patients required fewer rescue analgesics (1.2 doses vs. 2.1 doses, P < 0.05), indicating a 43% decrease in the need for additional medication. The time to a visual analog scale (VAS) score exceeding 4 was significantly longer in Group D, indicating less intense pain for an extended period. Although no significant differences were observed in common postoperative side effects, Group D exhibited a lower incidence of these effects, albeit not statistically significant. Furthermore, Group D showed a significantly lower incidence of hyperglycemia at the 8th hour post-surgery compared to Group M (P < 0.05), suggesting a potential benefit of epidural dexamethasone in mitigating hyperglycemia risk. Conclusions: Epidural dexamethasone appears to offer superior analgesic efficacy compared to epidural morphine in postoperative pain management after total abdominal hysterectomy. The findings suggest that Group D (Dexamethasone) experienced improved pain management, reduced medication requirements, and a lower incidence of hyperglycemia. Further research with larger cohorts and extended follow-up is warranted to validate these findings and guide clinical practice.

Comparison of erector spinae plane and transversus abdominis plane block for postoperative analgesia after caesarean delivery under spinal anaesthesia: A randomised controlled trial

BackgroundTruncal blocks contribute to multimodal analgesia that enhances early recovery after caesarean delivery. The transversus abdominis plane (TAP) block is an established technique that offers somatic abdominal wall analgesia. The erector spinae plane (ESP) block is a fascial plane technique that may offer additional visceral analgesic effects. This study hypothesized that ESP block would offer superior analgesic efficacy to TAP block in women undergoing caesarean delivery under spinal anaesthesia. MethodsSixty-six ASA physical status grade 1–3 (≥18 years) patients undergoing elective caesarean delivery under spinal anaesthesia were randomly allocated to receive either bilateral ultrasound-guided TAP (N = 33) or ESP blocks at the T9 vertebral level (N = 35). The primary outcome measure was 24-hour cumulative morphine consumption. The secondary outcomes included time to first analgesic request, duration of block placement, numeric rating scale (NRS) pain scores at rest and movement, effect of pain on activities of daily living (ADLs) and care for the infant, patient analgesic satisfaction, frequency and severity of opioid-related side effects. ResultsThere was no statistically significant difference in mean (95% CI) 24-hour cumulative morphine consumption between groups: 32.0 (27.0 to 37.0) mg with TAP versus 27.0 (19.9 to 34.0) mg with ESP (p = 0.16). The mean (SD) duration of block placement was longer for ESP than for TAP blocks (10.7 (2.2) minutes versus 9.0 (2.5) minutes; p = 0.004). There were no significant differences in the other secondary outcomes. ConclusionThis study found similar postoperative opioid use and analgesic efficacy between ESP and TAP block after caesarean delivery performed under spinal anaesthesia.Trial Registration: South African National Clinical Trial Registry (DOH-27-102022-5278): https://sanctr.samrc.ac.za/TrialDisplay.aspx?TrialID=8100, Pan African Clinical Trials Registry (PACTR202301645957324): https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=24267.

The Comparative Efficacy of Intravenous Ibuprofen 400 mg and 800 mg in Acute Mechanical Low Back Pain: A Prospective, Randomized, Double-Blind Clinical Study

Objective: This study aimed to compare the analgesic efficacy of intravenous (IV) ibuprofen at doses of 400 mg and 800 mg for acute mechanical low back pain. Methods: A Prospective, randomized, double-blind controlled clinical trial design was employed. Patients with moderate to severe acute low back pain were recruited from emergency departments. Ethical approval was obtained, and patients provided written consent. The study adhered to ethical guidelines and Good Clinical Practice principles. Results: Of the 144 patients, demographic characteristics were similar between groups. The 800 mg IV ibuprofen group demonstrated superior analgesic efficacy compared to the 400 mg group, with no significant adverse effects reported. Conclusion: The study concludes that the 800 mg IV dose of ibuprofen was more effective in providing analgesia control for patients with acute mechanical low back pain at all time intervals except for the 30th minute.

Comparison of analgesic efficacy of ibuprofen and dexketoprofen in pain management of long bone fractures: a prospective, randomized, double-blind study.

Long bone fractures (LBF) often cause severe pain, impacting patients' quality of life. This prospective, randomized, double-blind study aimed to compare the analgesic efficacy of dexketoprofen (Dex) and ibuprofen (Ibu) in LBF patients in the emergency department. Conducted between August 10, 2023, and January 17, 2024, the study included 100 eligible patients randomized into Dex and Ibu groups. Visual analog scale (VAS) scores were measured at baseline and at 30, 60, and 120 min. DeltaVAS (ΔVAS) values and ΔVAS percentages (ΔVAS%) were calculated. Primary endpoints were ΔVAS scores (ΔVAS 30-60-120) and ΔVAS% for comparative analysis. Statistical analysis showed no significant difference in ΔVAS30 (p = 0.359). However, ΔVAS60 exhibited a significant difference (p = 0.027), as did ΔVAS120 (p = < 0.001). ΔVAS%30 showed no significance (p = 0.224), but ΔVAS%60 and ΔVAS%120 were clinically and statistically significant (p = 0.017 and p = < 0.001, respectively). Ibuprofen 800 mg demonstrated superior analgesic efficacy at 60 and 120 min compared to Dex in long bone fractures. These findings suggest ibuprofen's potential as an effective pain management option in emergency departments.

Comparison of Effectiveness and Safety of Oxycodone Hydrochloride and Fentanyl for Post-operative Pain Following Total Hip Arthroplasty: A Randomized Triple-Blind Trial.

Total hip replacement (THR) is frequently associated with intense post-surgical pain. Effective pain management is of crucial importance to improving patient's condition and increasing his/her satisfaction in the post-operative time. This study aimed to compare the analgesic effect and safety of oxycodone and fentanyl after THR. Seventy-two cases scheduled for elective THR were included in this randomized, triple-blind trial. The patients were equally randomized into 2 groups: Fentanyl group (50 ug of fentanyl) and oxycodone group (oxycodone 4 mg). Drugs were received 20 min prior to the end of the operation. Post-operative visual analog scale (VAS) measurements at rest and movement at the post-anesthesia care unit (PACU) and in the ward, 2 h, 4 h, and 8 h post-operatively exhibited a significantly reduced value in the oxycodone group compared to the fentanyl group (P-value < 0.05). Time to first rescue for analgesia was delayed significantly in the oxycodone compared to the fentanyl group (P-value < 0.001). Fentanyl consumption (ug) in the 1st post-operative 12 h, 24 h, and 48 h decreased significantly in the oxycodone group compared to the fentanyl group (P-value < 0.001). Post-operative nausea, vomiting, headache, and pruritus were matched between the 2 groups (P > 0.05). A bolus dose of 4 mg of oxycodone provided superior analgesic efficacy than 50 ug fentanyl as evidenced by significantly lower pain score, delayed onset to first request for analgesia, and the smaller amount of fentanyl consumption at 12, 24, and 48 h post-total hip arthroplasty compared to fentanyl. The incidence of adverse events was comparable between the 2 groups.

Superior analgesic efficacy of preemptive low-dose ketorolac compared with parecoxib after total knee arthroplasty: A retrospective propensity score matching study.

Total knee arthroplasty (TKA) is a routine orthopedic procedure often associated with significant postoperative pain. Efficient pain management is paramount for patient recovery, with nonsteroidal anti-inflammatory drugs (NSAIDs) being a common choice. Nevertheless, the specific NSAID and its dosing regimen can have varying impacts on outcomes. In this retrospective cohort study spanning from January 2016 to December 2020, we analyzed patients who underwent TKA. These patients were divided into two groups: one receiving preemptive low-dose ketorolac (15mg) followed by 15mg every 6h for 48h, and the other receiving parecoxib (40mg) every 12h for the same duration. We assessed pain scores, opioid consumption, and monitored adverse events. Our findings reveal that ketorolac yielded superior results compared to parecoxib. Specifically, patients receiving ketorolac reported significantly lower Visual Numeric Rating Scale (VNRS) scores at 8- and 20-h post-surgery. This trend was further confirmed by linear mixed models (p = .0084). Additionally, ketorolac was associated with reduced opioid consumption during the initial 24h. Importantly, the rates of adverse events were comparable between the two groups. The utilization of preemptive low-dose ketorolac demonstrates promising potential in bolstering pain control within the initial 24h post-TKA, potentially reducing the need for opioids. However, further exploration is required to thoroughly assess its prolonged analgesic effects and safety across various surgical contexts. These investigations could provide invaluable insights for optimizing pain management protocols.

Comparison of continuous pericapsular nerve group (PENG) block versus continuous fascia iliaca compartment block on pain management and quadriceps muscle strength after total hip arthroplasty: a prospective, randomized controlled study

BackgroundThis investigation aimed to evaluate the impact of continuous pericapsular nerve group (PENG) block and continuous fascia iliac compartment block (FICB) on postoperative pain following total hip arthroplasty (THA).MethodsThis prospective, randomized, and controlled trial recruited a cohort of fifty-seven patients with unilateral femoral neck fractures from Xi’an Aerospace General Hospital in northwest China between July 2020 and November 2021. These patients were randomly assigned to two groups: the continuous PENG block group (PENG group, n = 29) and the continuous FICB group (FICB group, n = 28). Under ultrasound guidance, PENG block and FICB procedures were performed prior to spinal anesthesia, utilizing 20 ml of 0.25% ropivacaine for PENG block and 30 ml of 0.25% ropivacaine for FICB. Subsequently, a catheter was inserted. All study participants received a standardized postoperative multimodal analgesic regimen, including intravenous administration of 30 mg Ketorolac tromethamine every eight hours and patient-controlled neural analgesia (PCNA) after surgery. Numerical rating scale (NRS) scores at rest and during exercise were recorded at various time points: prior to block (T0), 30 min post-blockade (T1), and 6 h (T2), 12 h (T3), 24 h (T4), and 48 h (T5) postoperatively. Additional data collected encompassed postoperative quadriceps muscle strength, the time of initial ambulation after surgery, the number of effective PCNA activations, rescue analgesia requirements, and occurrences of adverse events (such as nausea and vomiting, hematoma, infection, catheter detachment, or displacement) within 48 h following surgery.ResultsIn the PENG group, the resting NRS pain scores exhibited lower values at T1, T4, and T5 than those at T0. Furthermore, exercise NRS pain scores at T1-T5 were lower in the PENG group than in the FICB group. Similarly, during the same postoperative period, the PENG group demonstrated enhanced quadriceps strength on the affected side compared to the FICB group. Additionally, the PENG group displayed earlier postoperative ambulation and reduced occurrences of effective PCNA activations and rescue analgesia requirements compared to the FICB group.ConclusionContinuous PENG block exhibited superior analgesic efficacy after THA compared to continuous FICB, promoting recovery of quadriceps strength on the affected side and facilitating early postoperative ambulation.Trial RegistrationThis clinical trial was registered in the China Clinical Trials Center (http://www.chictr.org.cn) on 20/07/2020, with the registration number ChiCTR2000034821.

A Gel/Fiber composite formulation achieves sequential delivery based on multimodal analgesia reducing chronic pain

Pain management plays an essential role in medical care. Previous studies showed that pain is a dynamic process involving multiple mechanisms, which inspired the concept of multimodal analgesia. Therefore, a drug delivery system loaded with a single analgesic may be insufficient for pain control. In this study, an implantable thermogel/electrospun fiber (Gel/Fiber) system loaded with bupivacaine hydrochloride (BUP-HCl) and acetaminophen (APAP) was synthesized. In the composite, BUP-HCl was preferentially released from the hydrophilic thermogel to relieve nociceptive pain, followed by the release of APAP in a more sustained manner from hydrophobic fibers to reduce the inflammatory reaction. Pain behavioral study and activation assay of spinal glial cells in the chronic constriction injury (CCI) model demonstrated the superior analgesic efficacy and chronic pain prevention property of the Gel/Fiber system. Furthermore, the composite exhibited satisfactory biocompatibility, as shown by histological and pharmacokinetic analysis. These results indicate that the successful sequential BUP-HCl/APAP release by a Gel/Fiber system alleviates chronic pain with good biocompatibility.Our study may pave the way for the future application of extended-delivery systems.

Association of labor epidural analgesia exposure with long-term risk of autism spectrum disorder in offspring: A meta-analysis of observational studies.

A previous meta-analysis has demonstrated a superior analgesic efficacy of epidural analgesia (e.g. labor epidural analgesia) in comparison with non-epidural approaches. The widely accepted safety of labor epidural analgesia also endorses its current popularity in obstetric practice. However, the results of a recent large-scale longitudinal study that demonstrated a significant increase in risk of autism spectrum disorder in offspring from mothers with labor epidural analgesia exposure have raised some concerns over the safety of its use. The current meta-analysis aimed at examining the strength of evidence regarding this issue based on updated clinical data. Through systematically reviewing seven eligible observational studies involving 4,021,406 children from electronic databases, our results showed a slight but statistically significant increase in risk of autism spectrum disorder in children with exposure to labor epidural analgesia compared with those without. The finding was consistent in subgroup analysis focusing on siblings and children delivered vaginally. Nevertheless, despite the tendency of an increased risk of autism spectrum disorder in children exposed to labor epidural analgesia <4 h, this effect was not observed in those exposed to labor epidural analgesia >8 h (data from two studies). In conclusion, the level of evidence linking labor epidural analgesia to autism spectrum disorder development in offspring was very low based on the latest data because of the small effect size and the finding of a lack of cumulative dose-response effect in the current analysis. Further studies are warranted to provide an insight into this issue.

Comparison of suprainguinal approach with infrainguinal approach of fascia iliaca compartment block for postoperative analgesia.

Fascia iliaca compartment block (FICB) is increasingly being used for anaesthesia and analgesia of the hip, knee and thigh. It can be administered via two ultrasound-guided approaches, suprainguinal and infrainguinal. This study aimed to compare the analgesic efficacy of the suprainguinal approach of FICB with infrainguinal approach of FICB in patients undergoing above knee orthopaedic surgeries. In this single-centre, double-blinded randomised trial, 32 patients undergoing above knee lower limb orthopaedic surgery under spinal anaesthesia were randomised into group I (infrainguinal FICB) and S (suprainguinal FICB). They were given ultrasound-guided FICB with 30 mL 0.2% ropivacaine for postoperative analgesia using the respective approaches. Injection tramadol was administered as a rescue analgesic when Numeric Rating Scale (NRS) ≥4. A blinded observer recorded pain score (NRS) from the initiation of the block every 2 h for 24 h. Time to first rescue analgesia, total duration of analgesia and analgesic consumption, and patient satisfaction score were noted. The mean pain scores were comparable between the two groups at all time intervals till 24 h except at 12 h and 20 h, when pain intensity was significantly less in group S than in group I. Total tramadol consumption was also significantly less in group S. There was no significant difference in time to first rescue analgesia and total duration of analgesia between the two groups. At 24 h, the patient satisfaction score was significantly better in group S. Suprainguinal FICB has superior analgesic efficacy over infrainguinal FICB in terms of reduced pain intensity, reduced 24-h tramadol consumption and better patient satisfaction.

A prospective randomised trial comparing the analgesic efficacy of postoperative infusion of epidural bupivacaine and ropivacaine in orthopaedic surgeries

Background: Epidural administration of local anaesthetic provides effective pain relief. Commonly used epidural local anaesthetics are bupivacaine and ropivacaine. Most studies compared these drugs along with an opioid or any other adjuvants like clonidine, dexmedetomidine etc. Our aim was to compare the analgesic efficacy and safety of continuous infusion of epidural ropivacaine and bupivacaine without any adjuvants in postoperative patients. Materials and methods: A prospective randomized clinical study was conducted in a tertiary care hospital in 60 patients between the age groups of 20-years and 60-years undergoing elective lower limb orthopaedic procedures. Total patients were divided into two groups (A and B) of 30 each. Continuous epidural infusion was started with 6ml per hour of 0.125% bupivacaine in Group A and 6ml per hour of 0.2% ropivacaine in Group B postoperatively. After the commencement of epidural infusions, heart rate, blood pressure, Visual Analogue Score (VAS) and supplementary analgesic requirement were monitored postoperatively for 48 hrs. Results: Our observations showed no significant difference in haemodynamic parameters like heart rate and blood pressure. VAS showed a statistically significant difference with higher mean VAS score in Group B patients at one hour (p value = 0.0126), 12 hrs (p value = 0.031) and 24 hrs (p value = 0.0421) as compared to Group A. Add on analgesic requirement was also higher for Group B patients. Conclusions: Both bupivacaine and ropivacaine can be used effectively for postoperative analgesia but bupivacaine has a superior analgesic efficacy than ropivacaine with similar safety profile.

Comparative Supra-Inguinal Fascia Iliaca Compartment Block and Continuous Lumbar Epidural Analgesia for Total Hip Replacement: A Retrospective Study

Background: Optimal pain control is one of the major concerns in total hip arthroplasty (THA). Lumbar epidural analgesia (LEA) is considered a common modality for pain relief following THA. However, the benefits must be weighed against the possibility of adverse effects and complications. Supra-inguinal fascia iliaca compartment block (S-FICB) is an alternative to neuraxial analgesia and provides adequate analgesia with fewer adverse effects. Objective: To compare the efficacy of postoperative analgesia between S-FICB and LEA in THA patients. Material and Methods: The present study was a retrospective cohort study that included 58 patients who underwent THA. Thirty-nine patients received LEA and 19 patients received S-FICB. Numeric rating score (NRS) at rest and movement, morphine (MO) consumption, complications/side-effects, and satisfaction score were collected at 24 and 48 hours postoperative. Results: Twenty-four hours NRS at rest was lower in LEA group (median resting NRS: 0 (0, 1) versus 4 (2, 4), p=0.0003). Twenty-four hours MO equivalent consumption was also lower in LEA group (MO equivalent consumption (mg): 0 (0, 5) versus 3 (0, 6), p=0.027). However, intraoperative blood loss was higher in LEA group compared with S-FICB group (median BL: 600 mL (500, 1,000) versus 400 mL (250, 700), p=0.02). The incidence of itching was higher in LEA group. However, the satisfaction score, the incidence of hypotension, nausea/vomiting, and dizziness were not statistically different. Conclusion: LEA provided superior analgesic efficacy than S-FICB. However, LEA is associated with higher incidence of blood loss and itching. The length of hospital stays and level of patient satisfaction with the analgesic treatment were comparable between the two groups. Keywords: Total hip arthroplasty; Epidural; Fascia iliaca; Postoperative analgesia

Intercostal Cryo Nerve Block in Minimally Invasive Cardiac Surgery: The Prospective Randomized FROST Trial.

IntroductionIntercostal cryo nerve block has been shown to enhance pulmonary function recovery and pain management in post-thoracotomy procedures. However, its benefit have never been demonstrated in minimal invasive thoracotomy heart valve surgery (Mini-HVS). The purpose of the study was to determine whether intraoperative intercostal cryo nerve block in conjunction with standard of care (collectively referred to hereafter as CryoNB) provided superior analgesic efficacy in patients undergoing Mini-HVS compared to standard-of-care (SOC).MethodsFROST was a prospective, 3:1 randomized (CryoNB vs. SOC), multicenter trial in patients undergoing Mini-HVS. The primary endpoint was the 48-h postoperative forced expiratory volume in 1 s (FEV1) result. Secondary endpoints were visual analog scale (VAS) scores for pain at the surgical site and general pain, intensive care unit and hospital length-of-stay, total opioid consumption, and allodynia at 6 months postoperatively.ResultsA total of 84 patients were randomized to the two arms of the trial CryoNB (n = 65) and SOC (n = 19). Baseline Society of Thoracic Surgeons Predictive Risk of Mortality (STS PROM) score, ejection fraction, and FEV1 were similar between cohorts. A higher 48-h postoperative FEV1 result was demonstrated in the CryoNB cohort versus the SOC cohort (1.20 ± 0.46 vs. 0.93 ± 0.43 L; P = 0.02, one-sided two-sample t test). Surgical site VAS scores were similar between the CryoNB and SOC cohorts at all postoperative timepoints evaluated, but VAS scores not related to the surgical site were lower in the SOC group at 72, 94, and 120 h postoperatively. The SOC cohort had a 13% higher opioid consumption than the CryoNB cohort. One of 64 CryoNB patients reported allodynia that did not require pain medication at 10 months.ConclusionsThe results of FROST demonstrated that intercostal CryoNB provided enhanced FEV1 score at 48 h postoperatively with optimized analgesic effectiveness versus SOC. Future larger prospective randomized trials are warranted to determine whether intercostal CryoNB has an opioid-sparing effect in patients undergoing Mini-HVS.Trial RegistrationClinicaltrials.gov identifier: NCT02922153.

Postoperative Pain Management Using Supplemental Bupivacaine After Mandibular Orthognathic Surgery: A Triple-Blind Randomized Controlled Clinical Trial

The objective of this triple-blind, randomized, placebo-controlled trial was to assess the clinical analgesic efficacy of 0.5% bupivacaine in acute postoperative pain management after bilateral sagittal split ramus osteotomy (BSSO). Patients were randomly allocated into the experimental (0.5% bupivacaine with 1:200000 epinephrine) or control group (normal saline - placebo) using block randomization. The interventions were administered at the inferior alveolar nerve block and buccal nerve block sites bilaterally after the BSSO surgery. Analgesic efficacy was assessed in terms of the patient's pain perception measured by a numerical rating scale (0 to 10), rescue drug requirement, and duration of analgesia for 24 hours after the surgery. The statistical analysis was blinded to the allocation groups, and P-value of <.05 was considered as a significant difference for all tests. In total, 28 patients underwent BSSO (ie, 14 in each group). There was no significant difference in pain perception of patients injected with 0.5% bupivacaine and those administered with placebo during the 24 hours after the surgery (P > .05). Three patients in the bupivacaine group took the rescue drug after the surgery (mean duration - 268 minutes) and 1 patient in the placebo group took the rescue drug after 27 minutes. Postoperative use of bupivacaine did not show a superior analgesic efficacy when compared with normal saline in controlling acute postoperative pain after BSSO.

Does Inhaled Methoxyflurane Implement Fast and Efficient Pain Management in Trauma Patients? A Systematic Review and Meta-Analysis.

IntroductionEvidence on the use of inhaled methoxyflurane in the management of trauma pain is conflicting and obfuscated. This study aimed to determine the efficacy and safety of inhaled methoxyflurane for trauma pain on the basis of published randomized controlled trials (RCTs).MethodsRCTs assessing the efficacy of methoxyflurane in adults or adolescents with acute trauma pain published in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar were searched. The control groups were those that received placebo or standard analgesic treatment (SAT). The primary outcome was the change from baseline in pain scores during the first 30 min of treatment. Secondary outcomes included time to first pain relief, the proportion of patients experiencing pain relief, rescue analgesia rate, the treatment satisfaction of patients and investigators, and the methoxyflurane-related treatment-emergent adverse events (TEAEs).ResultsA total of nine RCTs (1806 patients) were identified. Results revealed that methoxyflurane provided a clinically unimportant benefit by improving the mean difference of change from baseline in pain intensity (from − 0.44 to − 1.23 cm, p < 0.001) at various time points within the first 20 min compared to control treatment. Besides, methoxyflurane decreased the time of onset of pain relief (mean difference − 5.29 min; 95% CI − 6.97 to − 3.62) and the proportion of patients who needed rescue analgesic medication (risk ratio 1.41; 95% CI 1.17–1.70) despite it increasing the risk of non-severe TEAEs (risk ratio 3.09; 95% CI 1.72–5.57). Notably, the benefit of almost all secondary pain-related outcomes was rendered clinically nonsignificant between methoxyflurane and SAT strata besides the time of onset of pain relief. The quality of evidence was low or very low in all outcomes.ConclusionsIn emergency situations without effective therapy, this systematic review and meta-analysis provides low-quality evidence that methoxyflurane can be used as a rapid-acting and effective treatment for acute trauma pain, although its utilization is associated a risk of non-severe TEAEs. However, the current evidence does not support the notion that inhaled methoxyflurane offered superior analgesic efficacy to SAT.Clinical Trial NumberPROSPERO registration number CRD42020223000.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00258-9.

Efficacy and Safety of Single and Multiple Doses of a Fixed-dose Combination of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: Results From 2 Phase 3, Randomized, Parallel-group, Double-blind, Placebo-controlled Studies.

A previous pilot study demonstrated that various fixed-dose combinations (FDCs) of ibuprofen (IBU) and acetaminophen (APAP) provided analgesic efficacy comparable to a higher dose of IBU, with the same safety profile. These studies further evaluated the chosen FDC IBU/APAP 250/500 mg formulation. Two phase 3 dental pain studies enrolled healthy young patients with ≥moderate pain after ≥3 third molar extractions who received single-dose FDC IBU/APAP 250/500 mg, IBU 250 mg, APAP 650 mg, or placebo evaluated over 12 hours (study 1) or multiple-dose FDC or placebo every 8 hours, evaluated over 48 hours (study 2). Time-weighted sum of pain intensity differences over 8 (SPID[11]0-8) and 24 (SPID[11]0-24) hours were primary outcomes, respectively. Time to meaningful pain relief and duration of pain relief were assessed; tolerability was evaluated by adverse events. Five hundred sixty-eight patients were randomized in study 1; 123 in study 2. Study 1: SPID[11]0-8 favored FDC significantly over placebo, IBU, and APAP (P<0.001, P=0.008, and P<0.001, respectively); study 2: SPID[11]0-24 significantly favored FDC over placebo (P<0.001), with sustained efficacy during multiple dosing. Time to meaningful pain relief occurred within 1 hour; pain relief duration was >8 hours in both studies. Adverse event rates were lowest with the FDC. FDC IBU/APAP 250/500 mg provides superior analgesic efficacy to individual monocomponents (IBU 250 mg and APAP 650 mg), a rapid onset of action, >8-hour duration of pain relief, is generally well tolerated, and may provide an additional nonopioid treatment option for acute pain.

Double-blind, randomized, placebo-controlled study of Xenon in cancer pain therapy

Objectives. To evaluate safety and efficacy of administering a 50/50 mixture of xenon and oxygen gases to patients with moderate-to-severe cancer pain. Materials and methods. The study included 131 patients with moderate-to-severe cancer pain, who had been randomized into two groups: patients to receive inhalation of a mixture of xenon and oxygen in a volume ratio of 50/50, and those to receive inhalation of a mixture of oxygen and air. Efficacy was evaluated based on the following measurements: intensity of pain by NRS 30 minutes after each procedure; at the end of treatment; 2 weeks after treatment. Safety was assessed by dynamics of hemodynamic and laboratory parameters; incidence of adverse events in each group. Results. The study results showed that the median decrease in pain intensity measured by NRS 30 minutes after inhalation of xenon-oxygen mixture was –19.00 (–24.50 to 13.25) against –4.00 (–6.00 to 2.00) in the placebo group: the results attested to statistically significant differences (p &lt; 0.001) and a superior analgesic efficacy of xenon-oxygen mixture over placebo. Following the course of treatment, a significant NRS-measured decrease from 50.00 (40.00–60.00) to 30.00 (20.00–41.25) mm was registered in the active treatment group compared to an unverifiable decrease in NRS from 60.00 (35,00–70.00) to 55.0 (35.00–60.00) mm in the placebo group. The course of xenon inhalations made it possible to significantly reduce average daily doses of tramadol from 210.9 ± 31.3 mg to 150.1 ± 28.3, and also significantly reduce NSAID intake. AEs (n = 8) were observed only in 7 patients in the group receiving xenon therapy. Аll AEs were mild. Conclusions. Xenon-oxygen mixture was safe and performed better than placebo for analgesia in cancer pain treatment.

Toxicity of metamizole on differentiating HL60 cells and human neutrophil granulocytes

Metamizole is an analgesic and antipyretic with a superior analgesic efficacy than paracetamol. Since metamizole can cause neutropenia and agranulocytosis, it is currently used in only few countries. In a previous study, we have shown that N-methyl-4-aminoantipyrine (MAA), the active metamizole metabolite, reacts with hemin and forms an electrophilic metabolite that is toxic for HL60 cells, but not for mature neutrophil granulocytes. In the current study, we investigated the toxicity of hemin (12.5 μM) and MAA (100 μM) on differentiating HL60 cells. In undifferentiated HL60 cells, hemin decreased the viability and this effect was significantly increased by MAA. Similarly, hemin/MAA was more toxic than hemin alone on human cord blood cells. At 3 days (metamyelocyte stage) and 5 days of differentiation (mature neutrophils), hemin/MAA was not toxic on HL60 cells, whereas hemin alone was still toxic. No toxicity was observed on freshly isolated human neutrophils. The protein expression of enzymes responsible for hemin metabolism increased with HL60 cell differentiation. Inhibition of heme oxygenase-1 or cytochrome P450 reductase increased the toxicity of hemin and hemin/MAA in undifferentiated, but only for hemin in differentiated HL60 cells. Similar to the enzymes involved in hemin metabolism, the protein expression of enzymes involved in antioxidative defense and the cellular glutathione pool increased with HL60 cell differentiation. In conclusion, HL60 cells become resistant to the toxicity of hemin/MAA and partly also of hemin during their differentiation. This resistance is associated with the development of heme metabolism and of the antioxidative defense system including the cellular glutathione pool.

Evaluation of Intravenous Parecoxib Infusion Pump of Patient-Controlled Analgesia Compared to Fentanyl for Postoperative Pain Management in Laparoscopic Liver Resection.

BackgroundAs laparoscopic liver resection is becoming a commonly used method for hepatic surgery, postoperative pain management is emerging as one of the trickiest problems after surgery. The ideal method of pain management is controversial and the optimal strategy for postoperative pain management after surgery remains unclear. The present study evaluated the postoperative analgesic efficacy of parecoxib and fentanyl, and the benefit of a new intravenous parecoxib infusion pump with patient-controlled analgesia after laparoscopic liver resection.Material/MethodsThis controlled, prospective, randomized, double-blind trial compared VAS scores among 3 groups of patients: a fentanyl group (FEN group) using a fentanyl citrate pump, an intravenous parecoxib group (IVPA group) receiving intravenous parecoxib, and a parecoxib pump group (PUPA group) receiving parecoxib sodium by analgesia pump. We enrolled 124 patients planned for laparoscopic liver resection. The primary outcome was VAS score at rest and with movement. Secondary outcomes were adverse effects (including nausea), sedation, pruritus, and quality of life.ResultFor all time intervals, the VAS scores were significantly lower in the PUPA group. VAS scores at rest and with movement in the PUPA group were the lowest among the 3 groups, while the scores in the FEN group were the highest. More adverse effects were detected in the FEN group, and no significant differences in adverse effects were found between the intravenous group and the parecoxib pump group.ConclusionsUse of the intravenous infusion parecoxib pump for patient-controlled analgesia provides superior analgesic efficacy and fewer adverse effects for patients after laparoscopic liver resection.

The Efficacy of Transversus Abdominis Plane Block for Abdominal Hysterectomy Post-operative Analgesia.

Introduction/backgroundAbdominal hysterectomy is an open surgical procedure associated with considerable post-operative pain. Narcotics are often required during patient recovery but can result in adverse side effects. Transversus abdominis plane block (TAP block) is a regional anesthetic technique that is found to be an effective post-operative analgesia for many types of abdominal surgeries, including abdominal hysterectomies. However recent literature shows contradicting results regarding TAP block’s analgesic effect on recovery from abdominal hysterectomies. This study investigated the efficacy of TAP block to reduce narcotic consumption and improve pain scores in abdominal hysterectomy patients.MethodsA single-center retrospective cohort study was performed. The inclusion criteria was patients who underwent abdominal hysterectomy at Winnie Palmer Hospital for Women & Babies (WPH) between January 12, 2015 and December 31, 2015. Exclusion criteria were patients who received a second surgery within the same hospitalization, experienced an in-hospital mortality event, received hysterectomy for known malignancy, stayed in the hospital less than 24 hours, and whose charts contained missing data points.Data collected were: age, weight, height, body mass index (BMI), length of hospital stay, total narcotic consumption (intra-operation, in the post-anesthesia care unit (PACU), first 24 hours after admittance, during entire hospital stay, total patient-controlled analgesia (PCA) quantity, and total oral narcotics quantity. All narcotics were converted into parental morphine units for analysis. Numeric pain rating scale (NPRS) scores at two, four, eight, 12, 16, 20, and 24 hours after leaving the PACU were collected. Two-tailed paired T-test was performed to compare the narcotic consumption and pain scores between the TAP block group and the non-TAP block group.ResultsWPH used ultrasound-guided bilateral TAP block for patients undergoing abdominal hysterectomies. 63 patient charts were evaluated with 32 in the TAP block group and 31 in the non-TAP block group. Narcotic consumption was significantly different in the PACU with TAP block group consuming less narcotics than non-TAP block group (5.05 vs 8.65 IV morphine equivalents, p=0.012). TAP block group’s mean narcotic consumption was not significantly lower than Non-TAP block group’s mean consumption during intra-operation, first 24 hours after admittance, and total hospital stay (p=0.419, p=0.533, p=0.754 respectively). Mean NPRS scores at all hours (2, 4, 8, 12, 16, 20, and 24) displayed no statistical difference between the two groups. Total patient-controlled analgesia (PCA) and total overall oral narcotic usage showed no statistically significant differences between TAP block group and Non-TAP block group (p=0.252, 0.669 respectively).ConclusionThe results of this study demonstrated that TAP block did reduce narcotic requirement in the PACU but did not exhibit superior analgesic efficacy after discharge from the PACU, nor reduce the total length of hospital stay.