Paracetamol overdose in Danish children and adolescents during the Covid-19 restrictions.

INTRODUCTION: To assess the effect of long-term isolation on the mental state of Danish youth. This study aimed to investigate trends in paracetamol overdoses among people under 18 years of age in Denmark during Covid-19 restrictions as an indicator of mental health. METHODS: All patients under the age of 18 years presenting with paracetamol overdose at one of the 18 paediatric departments in Denmark from 2016 to 2021 were included. They were identified in all Danish hospital databases using specific diagnostic codes. RESULTS: From 2016 to 2021, a total of 3,217 people under 18 years of age were admitted for paracetamol overdose. Among these, 86% (n = 2,755) were girls and 14% (n = 462) were boys. During 2020, a slight (7%) decrease in admissions was observed among both boys and girls compared with the preceding four-year mean value. In 2021, the number of overdoses among girls exceeded by 35% the former all-time high from 2016. Furthermore, the number of overdoses among girls exceeded the pre-four-year period mean value by 43%. Among boys, an 8% increase was seen from the highest ever previous value recorded in 2019 and a 23% increase compared with the previous four-year mean value. CONCLUSIONS: During the first year of restrictions, a slight decrease in paracetamol overdoses was observed, possibly associated with limited accessibility. The second year showed a considerable increase in paracetamol overdoses, which may imply an affected mental state among youth during the prolonged lockdown restrictions as seen in previous epidemics. Therefore, further studies are warranted to develop a pandemic preparedness plan to protect general mental health. FUNDING: None. TRIAL REGISTRATION: Not relevant.

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.

Acetaminophen induces mitochondrial apoptosis through proteasome dysfunctions.

Acetaminophen is a known antipyretic and non-opioid analgesic for mild pain and fever. Numerous studies uncover their hidden chemotherapeutics applications, including chronic cancer pain management. Acetaminophen also represents an anti-proliferative effect in some cancer cells. Few studies also suggest that the use of Acetaminophen can trigger apoptosis and impede cellular growth. However, Acetaminophen's molecular potential and precise mechanism against improper cellular proliferation and use as an effective anti-proliferative agent still need to be better understood. Here, our current findings show that Acetaminophen induces proteasomal dysfunctions, resulting in aberrant protein accumulation and mitochondrial abnormalities, and consequently induces cell apoptosis. We observed that the Acetaminophen treatment leads to improper aggregation of ubiquitylated expanded polyglutamine proteins, which may be due to the dysfunctions of proteasome activities. Our in-silico analysis suggests the interaction of Acetaminophen and proteasome. Furthermore, we demonstrated the accumulation of proteasome substrates and the depletion of proteasome activities after treating Acetaminophen in cells. Acetaminophen induces proteasome dysfunctions and mitochondrial abnormalities, leading to pro-apoptotic morphological changes and apoptosis successively. These results suggest that Acetaminophen can induce cell death and may retain a promising anti-proliferative effect. These observations can open new possible molecular strategies in the near future for developing and designing specific and effective proteasome inhibitors, which can be helpful in conjugation with other anti-tumor drugs for their better efficiency.

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.

Low doses of acetaminophen produce antidepressive-like effects through the opioid system in mice.

Acetaminophen (paracetamol) is one of the most popular analgesics for the management of fever and pain but few reports have investigated its antidepressant-like effect. Moreover, the role of the opioidergic pathway has been indicated in depression pathophysiology. This study aimed to examine the involvement of the opioid receptors in the antidepressant-like effect of acetaminophen after acute and sub-chronic administration using mice forced swimming test (FST). Our finding showed that administration of acetaminophen (50 and 100 mg/kg, i.p.) 30 min before the FST produced an antidepressant effect which was reduced by naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist). Moreover, we observed that acetaminophen in higher doses (200 and 400 mg/kg) was ineffective. Also, the response of the non-effective dose of acetaminophen (25 mg/kg) was potentiated by the non-effective dose of morphine (0.1 mg/kg) in the FST that was antagonized by naloxone. Also, in contrast to morphine (10 mg/kg), acetaminophen (100 mg/kg, i.p.) induced neither tolerance to the anti-immobility behavior nor withdrawal syndrome after repeated administration. In addition, RT-PCR showed that hippocampal mu- and kappa-opioid receptor mRNA expression increased in mice after repeated administration of acetaminophen; however, morphine therapy for 6 days did not affect kappa-opioid receptor expression. Our findings demonstrated that acetaminophen in lower doses but not high doses revealed an antidepressant-like activity without inducing tolerance and withdrawal syndromes. Moreover, the observed effect of acetaminophen may be via altering the opioid system, particularly hippocampal mu- and kappa-receptors.

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.

Use of metamizole and other non-opioid analgesics in Switzerland between 2014 and 2019: an observational study using a large health insurance claims database.

OBJECTIVE: To investigate claims patterns for metamizole and other non-opioid analgesics in Switzerland. To characterise users of these non-opioid analgesics regarding sex, age, comedications and canton of residence. METHODS: We conducted a retrospective descriptive study using administrative claims data of outpatient prescribed non-opioid analgesics of the Swiss health insurance company Helsana between January 2014 and December 2019. First, we evaluated the number of claims and defined daily doses  per year of metamizole, ibuprofen, diclofenac and paracetamol in adults aged 18 years or over. Second, we characterised new users of these non-opioid analgesics in terms of sex, age, claimed comedications and canton of residence. RESULTS: From 2014 to 2019, among the investigated non-opioid analgesics, metamizole showed the highest increase in claims (+9545 claims, +50%) and defined daily doses (+86,869 defined daily doses, +84%) per 100,000 adults. Metamizole users had the highest median age (62 years [IQR: 44-77]) compared to ibuprofen (47 years [IQR: 33-62]), diclofenac (57 years [IQR: 43-71]) and paracetamol (58 years [IQR: 39-75]) users. Metamizole users also more frequently claimed proton pump inhibitors, anticoagulants, platelet aggregation inhibitors and antihypertensive drugs than users of other non-opioid analgesics. While metamizole was most frequently claimed in German-speaking regions of Switzerland, ibuprofen and paracetamol were most frequently claimed in the French-speaking regions and diclofenac in German- and Italian-speaking regions. CONCLUSION: In Switzerland, metamizole was increasingly claimed between 2014 and 2019. Metamizole was most frequently claimed by older adults and patients with comedications suggestive of underlying conditions, which can be worsened or caused by use of nonsteroidal anti-inflammatory drugs. The lack of studies regarding the effectiveness and safety of metamizole in this population warrants further investigation.

Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field.

Acetaminophen (APAP), the most frequently used mild analgesic and antipyretic drug worldwide, is implicated in causing 46% of all acute liver failures in the USA and between 40% and 70% in Europe. The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine (NAC); however, its efficacy is limited in cases of advanced liver injury or when administered at a late stage. In the current study, we discovered that treatment with a moderate intensity static magnetic field (SMF) notably reduced the mortality rate in mice subjected to high-dose APAP from 40% to 0%, proving effective at both the initial liver injury stage and the subsequent recovery stage. During the early phase of liver injury, SMF markedly reduced APAP-induced oxidative stress, free radicals, and liver damage, resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione (GSH). During the later stage of liver recovery, application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery, even 24 h post overdose, when the effectiveness of NAC alone substantially declines. Overall, this study provides a non-invasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose. Of note, this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP, and potentially other toxic overdoses.

Evaluation of capillary miR-122 as a prognostic biomarker of paracetamol-induced liver toxicity.

INTRODUCTION: Paracetamol (acetaminophen) overdose is a leading cause of acute liver failure in many Western countries. Diagnostic tools for this poisoning may be suboptimal in some cases and new biomarkers have been investigated. We investigated the role of capillary microRNA-122 (miR-122) as a prognostic biomarker of liver injury in the clinical management of patients with paracetamol overdose. METHODS: In a paracetamol overdose patient cohort, miR-122 was measured by quantitative polymerase chain reaction in a blood drop obtained by a finger prick at the end of an antidote cycle treatment with N-acetylcysteine treatment (12 h). Liver injury was defined as serum alanine aminotransferase (ALT) activity > 100 IU/L collected at 10 or 20 h after the start of treatment. Pearson's correlation analyses were performed. RESULTS: In patients with paracetamol overdose, capillary miR-122 was positively correlated with ALT measured at 10 h and at 20 h (r = 0.83, P < 0.0001; r = 0.96, P < 0.0001, respectively). CONCLUSION: This work supports the potential use of capillary miR-122 as a prognostic biomarker of liver injury throughout clinical management of patients with paracetamol overdose. Capillary miR-122 can be measured in a blood drop collected by a finger prick, a minimally invasive diagnostic test for patient stratification.

Fixed-time interval vs on-demand oral analgesia after vaginal delivery: a randomized controlled trial.

BACKGROUND: Scheduled administration of analgesics was proven superior to on-demand dosing following cesarean deliveries. However, this protocol was not compared after vaginal delivery. OBJECTIVE: To compare the efficacy of a fixed- vs on-demand analgesic protocol for the management of pain in the first 24 hours after a vaginal delivery. STUDY DESIGN: This randomized, prospective, controlled trial was conducted at a single tertiary medical center between June 1, 2020 and June 30, 2022. Vaginally delivered patients were randomly assigned to receive oral analgesics (paracetamol 1 g + ibuprofen 400 mg) either every 6 hours for the first 24 hours postpartum (scheduled analgesia group) or as needed (on-demand group). Pain level during the first 24 hours postdelivery was measured using a 10-point visual analog scale. RESULTS: A total of 200 patients were randomized 1:1 to the 2 cohorts. Baseline and delivery characteristics, including oxytocin augmentation, epidural anesthesia, episiotomy rate, and neonatal birthweight, were comparable between groups. Patients in the scheduled group received more paracetamol and ibuprofen doses in the first 24 hours (2.9±1.3 and 2.9±1.2 doses vs 0.8±1.1 and 0.7±1.1 doses, respectively; P<.001). Pain score was comparable between study groups (5.31±1.92 vs 5.29±1.67; P=.626) even after subanalysis for primiparity, episiotomy, and vacuum-assisted delivery (P>.05). However, patients on a fixed treatment schedule were more likely to breastfeed their baby (98% vs 88%; P=.006) as than those receiving treatment on demand. In addition, they were more satisfied with their labor and delivery experience, as evaluated by Birth Satisfaction Scale questionnaires quality control (37.9±4.7 vs 31.1±5.2; P=.0324), patient attributes (35.0±5.1 vs 30.3±6.3; P=.0453), and stress experienced (58.1±8.5 vs 50.1±8.3; P=.0398). No side effects or adverse outcomes were reported in either group. CONCLUSION: A scheduled analgesic protocol for postpartum pain management following vaginal delivery revealed similar pain scores compared with an on-demand protocol, although it was associated with higher breastfeeding rates and higher maternal satisfaction.

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.