Safety and efficacy of dexmedetomidine in combination with local anesthetics for orthopedic nerve blocks: a systematic review and meta-analysis.

INTRODUCTION: Peripheral nerve block, a common technique for managing postoperative pain and providing intraoperative analgesia, often includes adjuncts like dexmedetomidine (DEX) to enhance the effectiveness of local anesthetics. DEX, known for its α2-adrenoceptor agonist properties, extends sensory blockade and improves postoperative analgesia while offering sedative benefits. The objective of this study is to rigorously assess the effectiveness and safety of perineural DEX injection in orthopedic nerve block procedures, focusing on orthopedic surgeries to minimize heterogeneity and provide clearer insights for clinical practice. EVIDENCE ACQUISITION: This meta-analysis, registered on PROSPERO, involved a comprehensive literature search across multiple databases, focusing on RCTs comparing DEX with local anesthetics for peripheral nerve blocks in orthopedic surgery patients. The eligibility criteria included adult participants and various nerve block methods in orthopedic surgeries. Studies were rigorously appraised for methodological quality using Cochrane Handbook guidelines. GRADE profiler 3.6 was used for evidence grading. EVIDENCE SYNTHESIS: Among 1391 documents, 21 studies were included, focusing on DEX with local anesthetics in orthopedic nerve blocks. Findings showed significant improvements in analgesia duration, sensory and motor block duration, and reduced postoperative opioid consumption, with an increased risk of bradycardia. Quality assessments indicated moderate bias risk. CONCLUSIONS: DEX with local anesthetics significantly enhances nerve block effectiveness, extending analgesia and block durations while reducing opioid need. However, it requires careful monitoring due to increased bradycardia risk. These findings highlight the need for cautious use in clinical practice, considering both potential benefits and adverse effects.

Dexmedetomidine for analgesia and sedation in newborn infants receiving mechanical ventilation.

BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group. OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety. AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.

Tramadol-paracetamol for postoperative pain after spine surgery - A randomized, double-blind, placebo-controlled study.

OBJECTIVES: Multimodal pain management is one component in enhanced recovery after surgery protocol. Here we evaluate the efficacy of tramadol-paracetamol in acute postoperative pain and pain outcome at 12 months after spine surgery in randomized, double-blind, placebo-controlled trial. METHODS: We randomized 120 patients undergoing spine surgery to receive, for add-on pain management, two tramadol-paracetamol 37.5 mg/325 mg (n = 61) or placebo tablets (n = 59) twice a day for 5 postoperative days. In the hospital, multimodal pain management consisted of dexketoprofen and oxycodone. After discharge, patients were prescribed ibuprofen 200 mg, maximum 1,200 mg/day. Pain, analgesic use, and satisfaction with pain medication were followed up with the Brief Pain Inventory questionnaire before surgery and at 1 and 52 weeks after surgery. The primary outcome was patients' satisfaction with pain medication 1 week after surgery. RESULTS: At 1 week after surgery, patients' satisfaction with pain medication was similarly high in the two groups, 75% [interquartile range, 30%] in the placebo group and 70% [40%] in the tramadol-paracetamol group (p = 0.949) on a scale: 0% = not satisfied, 100% = totally satisfied. At 1 week, ibuprofen dose was lower in the placebo group 200 mg [1,000] compared to the tramadol-paracetamol group, 800 mg [1,600] (p = 0.016). There was no difference in the need for rescue oxycodone. Patients in the tramadol-paracetamol group had more adverse events associated with analgesics during the first postoperative week (relative risk = 1.8, 95% confidence interval, 1.2-2.6). CONCLUSION: Add-on pain treatment with tramadol-paracetamol did not enhance patients' satisfaction with early pain management after back surgery.

A comparison of port-site infiltration with bupivacaine alone vs. bupivacaine plus dexemedetomidine after diagnostic staging laparoscopy.

Objectives: To compare the effects of bupivacaine alone and in combination with dexmedetomidine following staging laparoscopies. METHODS: This triple-blinded, prospective study was conducted from June to September 2021 at a tertiary care cancer hospital in Lahore, Pakistan, and comprised adult patients having American Society of Anaesthesiologists grade I-III, weighing >30kg and undergoing diagnostic staging laparoscopy. The subjects were randomised into two equal groups. Group A received 6ml of 2mg/kg bupivacaine at each of the four laparoscopic port sites before skin closure, while group B additionally received 2µg/kg dexmedetomidine. The presence and severity of pain were recorded and assessed at 15 min, 1, 2 and 4 hours as well as at the time of discharge from the post-anaesthesia care unit. The time to first request for rescue analgesia, total morphine consumption, and the occurrence of any side effects during their stay were also recorded. Data was analysed using SPSS 23. RESULTS: Of the 30 patients, 15(50%) were in group A; 10(66.6%) males and 5(33.3%) females with mean age 43.27±7.59 years. There were 15(50%) patients in group B; 12(80%) males and 3(20%) females with mean age 41.36±12.42 years (p>0.05). Of the total, 29(96.66%) patients were classified as American Society of Anaesthesiologists grade II, and 1(3.33%) patient in group A was grade III. There was no significant difference between the groups in any of the outcome measures assessed (p>0.05), and none of the patients experienced any side effect throughout the post-operative stay. CONCLUSIONS: The combination of dexmedetomidine and bupivacaine had no significant improvement in pain relief compared to bupivacaine alone.

Effectiveness and safety of prehospital analgesia with nalbuphine and paracetamol versus morphine by paramedics - an observational study.

BACKGROUND: Despite the development of various analgesic concepts, prehospital oligoanalgesia remains very common. The present work examines prehospital analgesia by paramedics using morphine vs. nalbuphine + paracetamol. METHODS: Patients with out-of-hospital-analgesia performed by paramedics from the emergency medical services of the districts of Fulda (morphine) and Gütersloh (nalbuphine + paracetamol) were evaluated with regards to pain intensity at the beginning and the end of prehospital treatment using the Numeric-Rating-Scale for pain (NRS), sex, age, and complications. The primary endpoint was achievement of adequate analgesia, defined as NRS < 4 at hospital handover, depending on the analgesics administered (nalbuphine + paracetamol vs. morphine). Pain intensity before and after receiving analgesia using the NRS, sex, age and complications were also monitored. RESULTS: A total of 1,808 patients who received out-of-hospital-analgesia were evaluated (nalbuphine + paracetamol: 1,635 (90.4%), NRS-initial: 8.0 ± 1.4, NRS-at-handover: 3.7 ± 2.0; morphine: 173(9.6%), NRS-initial: 8.5 ± 1.1, NRS-at-handover: 5.1 ± 2.0). Factors influencing the difference in NRS were: initial pain intensity on the NRS (regression coefficient (RK): 0.7276, 95%CI: 0.6602-0.7950, p < 0.001), therapy with morphine vs. nalbuphine + paracetamol (RK: -1.2594, 95%CI: -1.5770 - -0.9418, p < 0.001) and traumatic vs. non-traumatic causes of pain (RK: -0.2952, 95%CI: -0.4879 - -0.1024, p = 0.002). Therapy with morphine (n = 34 (19.6%)) compared to nalbuphine + paracetamol (n = 796 (48.7%)) (odds ratio (OR): 0.274, 95%CI: 0.185-0.405, p < 0.001) and the initial NRS score (OR:0.827, 95%CI: 0.771-0.887, p < 0.001) reduced the odds of having an NRS < 4 at hospital handover. Complications occurred with morphine in n = 10 (5.8%) and with nalbuphine + paracetamol in n = 35 (2.1%) cases. Risk factors for complications were analgesia with morphine (OR: 2.690, 95%CI: 1.287-5.621, p = 0.008), female sex (OR: 2.024, 95%CI: 1.040-3.937, p = 0.0379), as well as age (OR: 1.018, 95%CI: 1.003-1.034, p = 0.02). CONCLUSIONS: Compared to morphine, prehospital analgesia with nalbuphine + paracetamol yields favourable effects in terms of analgesic effectiveness and a lower rate of complications and should therefore be considered in future recommendations for prehospital analgesia.

Efficacy of Postoperative Opioid-Sparing Regimens for Hand Surgery: A Systematic Review of Randomized Controlled Trials.

PURPOSE: Multiple interventions have been implemented to reduce opioid prescribing in upper extremity surgery. However, few studies have evaluated pain relief and patient satisfaction as related to failure of these protocols. We sought to evaluate the efficacy of limited and nonopioid ("opioid-sparing") regimens for upper extremity surgery as it pertains to patient satisfaction, pain experienced, and need for additional refills/rescue analgesia. METHODS: We aimed to systematically review randomized controlled trials of opioid-sparing approaches in upper extremity surgery. An initial search of studies evaluating opioid-sparing regimens after upper extremity surgery from the elbow distal yielded 1,320 studies, with nine meeting inclusion criteria. Patient demographics, surgery type, postoperative pain regimen, satisfaction measurements, and number of patients inadequately treated within each study were recorded. Outcomes were assessed using descriptive statistics. RESULTS: Nine randomized controlled trials with 1,480 patients were included. Six of nine studies (67%) reported superiority or equivalence of pain relief with nonopioid or limited opioid regimens. However, across all studies, 4.2% to 25% of patients were not adequately treated by the opioid-sparing protocols. This includes four of seven studies (57%) assessing number of medication refills or rescue analgesia reporting increased pill consumption, refills, or rescue dosing with limited/nonopioid regimens. Five of six studies (83%) reporting satisfaction outcomes found no difference in satisfaction with pain control, medication strength, and overall surgical experience using opioid-sparing regimens. CONCLUSIONS: Opioid-sparing regimens provide adequate pain relief for most upper extremity surgery patients. However, a meaningful number of patients on opioid-sparing regimens required greater medication refills and increased use of rescue analgesia. These patients also reported no difference in satisfaction compared with limited/nonopioid regimens. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Robotic-assisted hysterectomy for benign gynecologic disease in the United States: in-hospital use of opioid and non-opioid analgesics.

To compare the in-hospital opioid and non-opioid analgesic use among women who underwent robotic-assisted hysterectomy (RH) vs. open (OH), vaginal (VH), or laparoscopic hysterectomy (LH). Records of women in the United States who underwent hysterectomy for benign gynecologic disease were extracted from the Premier Healthcare Database (2013-2019). Propensity score methods were used to create three 1:1 matched cohorts stratified in inpatients [RH vs. OH (N = 16,821 pairs), RH vs. VH (N = 6149), RH vs. LH (N = 11,250)] and outpatients [RH vs. OH (N = 3139), RH vs. VH (N = 29,954), RH vs. LH (N = 85,040)]. Opioid doses were converted to morphine milligram equivalents (MME). Within matched cohorts, opioid and non-opioid analgesic use was compared. On the day of surgery, the percentage of patients who received opioids differed only for outpatients who underwent RH vs. LH or VH (maximum difference = 1%; p < 0.001). RH was associated with lower total doses of opioids in all matched cohorts (each p < 0.001), with the largest difference observed between RH and OH: median (IQR) of 47.5 (25.0-90.0) vs. 82.5 (36.0-137.0) MME among inpatients and 39.3 (19.5-66.0) vs. 60.0 (35.0-113.3) among outpatients. After the day of surgery, fewer inpatients who underwent RH received opioids vs. OH (78.7 vs. 87.5%; p < 0.001) or LH (78.6 vs. 80.6%; p < 0.001). The median MME was lower for RH (15.0; 7.5-33.5) versus OH (22.5; 15.0-55.0; p < 0.001). Minor differences were observed for non-opioid analgesics. RH was associated with lower in-hospital opioid use than OH, whereas the same magnitude of difference was not observed for RH vs. LH or VH.

Effect of an intravenous acetaminophen/ibuprofen fixed-dose combination on postoperative opioid consumption and pain after video-assisted thoracic surgery: a double-blind randomized controlled trial.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) often induces significant postoperative pain, potentially leading to chronic pain and decreased quality of life. This study aimed to evaluate the acetaminophen/ibuprofen combination effectiveness in reducing analgesic requirements and pain intensity in patients undergoing VATS. STUDY DESIGN: This is a double-blinded randomized controlled trial. METHODS: Adult patients scheduled for elective VATS for lung resection were randomized to receive either intravenous acetaminophen and ibuprofen (intervention group) or 100 mL normal saline (control group). Treatments were administered post-anesthesia induction and every 6 h for three cycles. The primary outcome was total analgesic consumption at 24 h postoperatively. Secondary outcomes were cumulative analgesic consumption at 2 and 48 h; analgesic-related side effects at 2, 24, and 48 h; quality of recovery at 24 h and 48 h postoperatively; pain intensity at rest and during coughing; and rescue analgesics use. Chronic postsurgical pain (CPSP) was assessed through telephone interviews 3 months postoperatively. RESULTS: The study included 96 participants. The intervention group showed significantly lower analgesic consumption at 24 h and 48 h postoperatively (24 h: median difference: - 100 µg equivalent intravenous fentanyl [95% confidence interval (CI) - 200 to - 5 µg], P = 0.037; 48 h: median difference: - 140 µg [95% CI - 320 to - 20 µg], P = 0.035). Compared to the controls, the intervention group exhibited a significantly lower quality of recovery 24 h post-surgery, with no significant difference at 48 h. All pain scores except for coughing at 48 h post-surgery were significantly lower in the intervention group compared to the controls. No significant differences were observed between the groups in postoperative nausea and vomiting occurrence, hospital stay length, and CPSP. CONCLUSION: Perioperative administration of acetaminophen/ibuprofen significantly decreased analgesic needs in patients undergoing VATS, providing an effective postoperative pain management strategy, and potentially minimizing the need for stronger analgesics.

Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial.

BACKGROUND: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass. METHODS: Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%. RESULTS: In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion - 3.1% (95% CI - 16.6-10.3%). CONCLUSIONS: In children aged 0-3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.

Clinical Efficacy of Percutaneous Balloon Compression Combined with Carbamazepine in the Treatment of Trigeminal Neuralgia: A Retrospective Study.

OBJECTIVE: To investigate the effect of percutaneous balloon compression combined with carbamazepine on patients with Trigeminal Neuralgia (TN). METHODS: The clinical data of 126 patients with TN admitted to our hospital from January, 2021 to January, 2022 were retrospectively analyzed. All patients underwent percutaneous balloon compression in our hospital. The patients were divided into a control group and an observation group, according to whether they continued to take carbamazepine after surgery. The general demographic data of patients, such as gender, age, family income, education level, pain site, diseased nerve, course of disease, and duration of pain were collected. Propensity score matching was used to balance the baseline data of the two groups, and the quality of life, treatment effect, and complications of the two groups were compared after matching. RESULTS: After treatment, the total effective rate of the observation group (95.00%) was higher than that of the control group (70.00%) (p < 0.05). Before treatment, there were no significant differences in the scores for quality of life dimensions between the two groups (p > 0.05). After treatment, the scores for each quality of life dimension in the observation group were higher than those in the control group. After treatment, the incidence of complications in the observation group (7.50%) was lower than that in the control group (30.00%) (p < 0.05). CONCLUSIONS: Percutaneous balloon compression combined with carbamazepine can effectively enhance the treatment of patients by improving their quality of life and reducing the occurrence of complications. These results can improve the clinical management of TN.

Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial.

BACKGROUND: Multimodal postoperative analgesia following total hip arthroplasty is recommended, but the optimal combination of drugs remains uncertain. The aim of the RECIPE trial was to investigate the relative benefit and harm of the different combinations of paracetamol, ibuprofen, and the analgesic adjuvant dexamethasone for treatment of postoperative pain following total hip arthroplasty. METHODS: The RECIPE trial was a randomised, blinded, placebo-controlled trial conducted at nine Danish hospitals. Adults scheduled for total hip arthroplasty were randomly assigned (1:1:1:1) using a computer-generated list with stratification by site to receive combinations of oral paracetamol 1000 mg every 6 h, oral ibuprofen 400 mg every 6 h, or a single-dose of intravenous dexamethasone 24 mg in the following groups: paracetamol plus ibuprofen, ibuprofen plus dexamethasone, paracetamol plus dexamethasone, and paracetamol plus ibuprofen plus dexamethasone. The primary outcome was 24 h intravenous morphine consumption, analysed in a modified intention-to-treat population, defined as all randomly assigned participants who underwent total hip arthroplasty. The predefined minimal important difference was 8 mg. Safety outcomes included serious and non-serious adverse events within 90 days and 24 h. The trial was registered with ClinicalTrials.gov, NCT04123873. FINDINGS: Between March 5, 2020, and Nov 15, 2022, we randomly assigned 1060 participants, of whom 1043 (589 [56%] women and 454 [44%] men) were included in the modified intention-to-treat population. 261 were assigned to paracetamol plus ibuprofen, 262 to ibuprofen plus dexamethasone, 262 to paracetamol plus dexamethasone, and 258 to paracetamol plus ibuprofen plus dexamethasone. Median 24 h morphine consumption was 24 mg (IQR 12-38) in the paracetamol plus ibuprofen group, 20 mg (12-32) in the paracetamol plus dexamethasone group, 16 mg (10-30) in the ibuprofen plus dexamethasone group, and 15 mg (8-26) in the paracetamol plus ibuprofen plus dexamethasone group. The paracetamol plus ibuprofen plus dexamethasone group had a significantly reduced 24 h morphine consumption compared with paracetamol plus ibuprofen (Hodges-Lehmann median difference -6 mg [99% CI -10 to -3]; p<0·0001) and paracetamol plus dexamethasone (-4 mg [-8 to -1]; p=0·0013), however, none of the comparisons showed differences reaching the minimal important threshold of 8 mg. 91 (35%) of 258 participants in the paracetamol plus ibuprofen plus dexamethasone group had one or more adverse events, compared with 99 (38%) of 262 in the ibuprofen plus dexamethasone group, 103 (39%) of 262 in the paracetamol plus dexamethasone group, and 165 (63%) of 261 in the paracetamol plus ibuprofen group. INTERPRETATION: In adults undergoing total hip arthroplasty, a combination of paracetamol, ibuprofen, and dexamethasone had the lowest morphine consumption within 24 h following surgery and the most favourable adverse event profile, with a lower incidence of serious and non-serious adverse events (primarily driven by differences in nausea, vomiting, and dizziness) compared with paracetamol plus ibuprofen. FUNDING: The Novo Nordisk Foundation and Næstved-Slagelse-Ringsted Hospitals' Research Fund.

Clinical validation of a fast-acting acetaminophen: a randomized, active and placebo controlled dental pain study.

OBJECTIVES: To address the need for faster pain relief of over-the-counter (OTC) analgesic users, a novel drug delivery technology was developed to achieve faster absorption of orally administered acetaminophen with the goal of delivering earlier onset of pain relief. Previous development studies suggested that a 1000 mg dose of this fast-acting acetaminophen (FA-acetaminophen) formulation provided faster absorption and onset of action versus, commercially available OTC fast-acting analgesics, 1000 mg of extra-strength acetaminophen (ES-acetaminophen) or 400 mg of liquid-filled ibuprofen capsules (LG-ibuprofen). This study was designed as the definitive trial evaluating the onset of pain relief of FA-acetaminophen versus these same OTC comparators. METHODS: This single-dose, randomized, double-blind, placebo- and active-controlled clinical trial compared analgesic onset, overall efficacy, and safety of FA-acetaminophen 1000 mg, ES-acetaminophen 1000 mg, LG-ibuprofen 400 mg, and placebo over 4 h in a postsurgical dental pain model. Following removal of 3 to 4 impacted third molars, 664 subjects with moderate-to-severe pain were randomized in a 4:4:2:1 ratio to FA-acetaminophen (249), ES-acetaminophen (232), LG-ibuprofen (124), or placebo (59). Mean age was 18.9 years; 45.5% were male; 57.5% had severe baseline pain intensity. Subjects stopped a first stopwatch if/when they had perceptible pain relief and a second stopwatch if/when their pain relief became meaningful to them. Pain intensity difference (PID) and pain relief (PAR) were obtained using an 11-point numerical rating scale. FINDINGS: FA-acetaminophen 1000 mg had faster median time to onset of pain relief (15.7 min) compared to ES-acetaminophen 1000 mg (20.2 min, p = 0.035), LG-ibuprofen 400 mg (23.2 min, p < 0.001), and placebo (non-estimable), statistically greater mean PAR and PID scores than other treatment groups at 15 and 30 min, and a statistically greater percentage of subjects with confirmed perceptible pain relief at 15 and 20 min. At 25 min, FA-acetaminophen 1000 mg had a statistically significantly greater percentage of subjects with confirmed perceptible pain relief than LG-ibuprofen 400 mg and placebo. No clinically significant adverse events were reported. CONCLUSIONS: This study supports previous studies, demonstrating faster onset of analgesia with FA-acetaminophen 1000 mg compared to OTC ES-acetaminophen 1000 mg and OTC LG-ibuprofen 400 mg. CLINICALTRIALS.GOV IDENTIFIER: NCT03224403 https://clinicaltrials.gov/ct2/show/NCT03224403.

The presence of abdominal pain associated with acetaminophen overdose does not predict severity of liver injury.

AIM: Whilst it is known that abdominal pain is a common symptom in patients with acetaminophen overdose, its association with severity of liver injury has not been clearly defined. This study investigates the association between the symptom of abdominal pain on presentation to hospital and the degree of liver injury post-acetaminophen overdose. METHODS: Admissions with acetaminophen poisoning, requiring treatment with acetylcysteine were identified and reviewed from a search of a large Australian tertiary hospital network from February 20th, 2014, to August 30th, 2018. Parameters such as presence of abdominal pain, time post-ingestion and peak ALT were collected. Single acute ingestions, staggered and repeated supratherapeutic ingestions were analysed. RESULTS: 539 cases were identified in the study period, 79% female, with mean age 25 (17-43) years. Patients presenting to the emergency department with abdominal pain post-acetaminophen overdose had a similar risk of developing hepatotoxicity or acute liver injury compared to patients without abdominal pain regardless of time to presentation. Patients presenting <8-h post-overdose with abdominal pain were as likely to develop hepatotoxicity (1/46, 2.2%) compared to those without abdominal pain (1/54 [1.9%]; OR = 1.18 [0.07 to 19.4]). Those presenting >8-h post-overdose with abdominal pain were as likely to develop hepatotoxicity (13/92, 14.1%) compared to those without abdominal pain (4/35 [11.4%]; OR = 1.28 [0.39 to 4.21]). CONCLUSIONS: The presence of abdominal pain after acetaminophen overdose was not predictive of the development of liver injury in patients receiving acetylcysteine treatment. Further prospective studies are required to confirm this finding. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Pain-related hospitalization and emergency room visit following initial analgesic prescription after outpatient surgery.

PURPOSE: Our study examined the association between outpatient postsurgical analgesic prescription and risk of insufficiently managed pain characterized by pain-associated hospital admission and emergency room (ER) visit. METHODS: Eligible individuals were children 1-17 years of age who filled an incident analgesic following an outpatient surgery during 2013-2018. Pain-associated hospital admission or ER visit were measured within 30 days following the outpatient surgical procedure. A hierarchical multivariable logistic regression model with patients nested under prescribers was fitted to test the association between incident analgesic prescription and risk of having pain-associated hospital admission or ER visit. RESULTS: Of 14 277 children meeting the inclusion criteria, 6224 (43.6%) received an incident opioid and 8053 (56.4%) received an incident non-opioid analgesic prescription respectively. There were a total of 523 (3.7%) children undergoing surgical procedures that had pain-related hospital admissions or ER visits with 5.1% initiated on non-opioid analgesics and 1.8% on opioid analgesics. The multilevel model indicated that initial opioid analgesic recipients were 32% less likely of having a pain-associated hospital admission or ER visit [aOR: 0.68 (95% CI: 0.3-0.8)]. CONCLUSION: Majority of postsurgical patients do not require additional pain management strategies. In the 3.7% of patients requiring additional pain management strategies, those initiated on non-opioid analgesics are more likely to have a pain-associated hospital admission or ER visit compared with their opioid recipient counterparts.

Pain management after total hip arthroplasty: comparative study of analgesic efficacy and tolerability between oral tramadol/dexketoprofen and injectable paracetamol + tramadol.

BACKGROUND: Multimodal analgesia for total hip arthroplasty (THA) is increasingly employed to reduce early postoperative pain and promote fast patient discharge. The aim of this study was to compare the efficacy and tolerability of tramadol/dexketoprofen (TRAM/DKP, Group A) versus paracetamol + tramadol (PARA+TRAM, Group B) in patients undergoing THA using minimally invasive direct anterior approach (DAA). METHODS: A single-centre, randomised, single-blind, parallel, interventional study conducted in 323 patients undergoing primary THA with DAA was performed. Group A consisted of 188 patients and Group B of 135. The primary endpoints were the change from baseline (measured 2 hours postoperatively) in pain intensity (PI) during the treatment period (48 hours), assessed by visual analogue scale (VAS) at pre-specified postoperative time-points (2, 8, 24, 48 hours) and the total rescue medication (RM) use during the first 24 hours postoperatively. RESULTS: As early as 2 hours after baseline, Group A showed a greater PI reduction from baseline compared to Group B (-26.24% vs. -6.87%; p < 0.001). A lower mean PI (VAS) score was consistently found over the entire observation period following treatment with TRAM/DKP than with PARA+TRAM as well as more than 2-fold higher proportion of responders at the end of treatment period. More patients in Group B required RM in comparison to those in Group A (15.6% vs. 3.7%, p < 0.001). Both treatments were well tolerated. CONCLUSIONS: After THA, oral TRAM/DKP provides faster and greater pain relief when compared to intravenous PARA+TRAM with limited consumption of RM and favourable tolerability profile. Our study expands the use of TRAM/DKP in the setting of major orthopaedic surgeries. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov (NCT04178109).

Comparison of intravenous ibuprofen and paracetamol for peri-operative analgesia in paediatric day care tonsillectomy.

OBJECTIVE: To determine the effectiveness of intravenous ibuprofen and acetaminophen as perioperative analgesics in paediatric patients undergoing day- care tonsillectomy with general anaesthesia. METHODS: The quasi-experimental stud y was conduc ted at the Ana esthe sia D epartment of Pa k Emirates M ilitary Hospital, Rawalpindi , Pak ist an, from July 20 21 to June 2022, and comp rised paediatric pa t ients aged 5-12 yea r s undergoing day- care tonsil lec tomy with gen era l anaesthesia. The sub jec ts were divid ed into two equa l groups. Patients in Group I received intravenous ibuprofen 7mg/kg and patients in Group P received intravenous paracetamol 10mg/kg im media t ely after induction of anaesthesi a. All patients recei ved standard general anaesthesia with endotracheal intubation. The primary outcome measured was revised faces pain score immediately after recovery and at the time of discharge 6 hours later. Adverse events were also noted. Data was analysed using SPSS 26. RESULTS: Of the 100 patients, there were 50(50%) in Group I; 21(42%) boys and 29(58%) girls with mean age 7.82±1.903 years. The remaining 50(50%) subjects were in Group P; 25(50%) boys and 25(50%) girls with mean age 7.68±1.812 years. At baseline, 44(88%) patients in Group I and 42(84%) in Group P reported no pain, while 6(12%) and 8(16%) patients in the two groups, respectively, reported pain (p=0.56). At discharge, 35(70%) patients in Group I and 18(36%) in Group P reported no pain (p<0.001). Adverse events were not significantly different between the groups (p>0.05). CONCLUSIONS: I ntravenous ibuprofen was found to b e a superior pain-killer than intravenous paracetamol for perioperative care of paediatric patients in day- care tonsillectomy.