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.

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.

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.

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.

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.

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.

Assessing the impact of a new medical toxicology service on the treatment of paracetamol overdose at a large tertiary care hospital.

BACKGROUND: Paracetamol overdose is the most common cause of acute liver failure in the United States. Administration of acetylcysteine is the standard of care for this intoxication. Laboratory values and clinical criteria are used to guide treatment duration, but decision-making is nuanced and often complex and difficult. The purpose of this study was to evaluate the effect of the introduction of a medical toxicology service on the rate of errors in the management of paracetamol overdose. METHODS: This was a single center, retrospective, cohort evaluation. Patients with suspected paracetamol overdose were divided into two groups: those attending in the 1 year period before and those in the 1 year after the introduction of the medical toxicology service. The primary outcome was the frequency of deviations from the established management of paracetamol intoxication, using international guidelines as a reference. RESULTS: Fifty-four patients were eligible for the study (20 pre-toxicology-service, 34 post-toxicology-service). The frequency of incorrect therapeutic decisions was significantly lower in the post-toxicology service implementation versus the pre-implementation group (P = 0.005). DISCUSSION: Our study suggests that a medical toxicology service reduces the incidence of management errors, including the number of missed acetylcysteine doses in patients with paracetamol overdose. The limitations include the retrospective study design and that the study was conducted at a single center, which may limit generalizability. CONCLUSIONS: The implementation of a medical toxicology service was associated with a decrease in the number of errors in the management of paracetamol overdose.

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.

Sex Differences in Opioid Administration After Cardiac Surgery.

OBJECTIVES: To assess whether there are sex-based differences in the administration of opioid analgesic drugs among inpatients after cardiac surgery. DESIGN: A retrospective cohort study. SETTING: At a tertiary academic referral center. PARTICIPANTS: Adult patients who underwent cardiac surgery from 2014 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the cumulative oral morphine equivalent dose (OMED) for the postoperative admission. Secondary outcomes were the daily difference in OMED and the administration of nonopioid analgesics. The authors developed multivariate regression models controlling for known confounders, including weight and length of stay. A total of 3,822 patients (1,032 women and 2,790 men) were included. The mean cumulative OMED was 139 mg for women and 180 mg for men, and this difference remained significant after adjustment for confounders (adjusted mean difference [aMD], -33.21 mg; 95% CI, -47.05 to -19.36 mg; p < 0.001). The cumulative OMED was significantly lower in female patients on postoperative days 1 to 5, with the greatest disparity observed on day 5 (aMD, -89.83 mg; 95% CI, -155.9 to -23.80 mg; p = 0.009). By contrast, women were more likely to receive a gabapentinoid (odds ratio, 1.91; 95% CI, 1.42-2.58; p < 0.001). The authors found no association between patient sex and the administration of other nonopioid analgesics or specific types of opioid analgesics. The authors found no association between patient sex and pain scores recorded within the first 48 hours after extubation, or the number of opioids administered in close proximity to pain assessments. CONCLUSIONS: Female sex was associated with significantly lower amounts of opioids administered after cardiac surgery.

The Opioid Analgesic Reduction Study (OARS) Pilot: A Double-Blind Randomized Multicenter Trial.

BACKGROUND: With addiction rates and opioid deaths increasing, health care providers are obligated to help stem the opioid crisis. As limited studies examine the comparative effectiveness of fixed-dose combination nonopioid analgesia to opioid-containing analgesia, a comparative effectiveness study was planned and refined by conducting a pilot study. METHODS: The Opioid Analgesic Reduction Study (OARS) pilot, a stratified, randomized, multisite, double-blind clinical trial, was designed to test technology and procedures to be used in the full OARS trial. Participants engaged in the full protocol, enabling the collection of OARS outcome data. Eligible participants reporting to 1 of 5 sites for partial or full bony impacted mandibular third molar extraction were stratified by biologic sex and randomized to 1 of 2 treatment groups, OPIOID or NONOPIOID. OPIOID participants were provided 20 doses of hydrocodone 5 mg/acetaminophen 300 mg. NONOPIOID participants were provided 20 doses of ibuprofen 400 mg/acetaminophen 500 mg. OARS outcomes data, including pain experience, adverse effects, sleep quality, pain interference, overall satisfaction, and remaining opioid tablets available for diversion, were collected via surveys, electronic medication bottles, eDiary, and activity/sleep monitor. RESULTS: Fifty-three participants were randomized with 50 completing the OARS pilot protocol. Across all outcome pain domains, in all but 1 time period, NONOPIOID was better in managing pain than OPIOID (P < 0.05 level). Other outcomes suggest less pain interference, less adverse events, better sleep quality, better overall satisfaction, and fewer opioid-containing tablets available for diversion. DISCUSSION: Results suggest patients requiring impacted mandibular third molar extraction would benefit from fixed-dose combination nonopioid analgesia. KNOWLEDGE TRANSFER STATEMENT: Study results suggest fixed-dose nonopioid combination ibuprofen 400 mg/acetaminophen 500 mg is superior to opioid-containing analgesic (hydrocodone 5 mg/acetaminophen 500 mg). This knowledge should inform surgeons and patients in the selection of postsurgical analgesia.

Dexmedetomidine Prevents Chronic Incisional Pain After Brain Tumor Resection: A Secondary Analysis of the Randomized Control Trial.

BACKGROUND: Dexmedetomidine was reported to reduce postoperative acute pain after neurosurgery. However, the efficacy of dexmedetomidine for preventing chronic incisional pain is uncertain. METHODS: This article is a secondary analysis of a randomized, double-blind, placebo-controlled trial. Eligible patients were randomly allocated to either the dexmedetomidine group or the placebo group. Patients assigned to the dexmedetomidine group were given a 0.6 µg kg -1 dexmedetomidine bolus followed by a 0.4 µg kg -1 h -1 maintenance dose until dural closure; placebo patients were given comparable amounts of normal saline. The primary end point was the incidence of incisional pain at 3 months after craniotomy evaluated by numerical rating scale scores and defined as any score >0. The secondary end points were postoperative acute pain scores, sleep quality, and Short-Form McGill Pain Questionnaire (SF-MPQ-2) at 3 months after craniotomy. RESULTS: From January 2021 to December 2021, a total of 252 patients were included in the final analysis: the dexmedetomidine group (n = 128) and the placebo group (n = 124). The incidence of chronic incisional pain was 23.4% (30 of 128) in the dexmedetomidine group versus 42.7% (53 of 124) in the placebo group (risk ratio, 0.55; 95% confidence interval, 0.38-0.80; P = .001). The overall severity of chronic incisional pain was mild in both groups. Patients in the dexmedetomidine group had lower acute pain severity on movement than those in the placebo group for the first 3 days after surgery (all adjusted P < .01). Sleep quality did not differ between groups. However, the SF-MPQ-2 total sensory ( P = .01) and neuropathic pain descriptor ( P = .023) scores in the dexmedetomidine group were lower than those in the placebo group. CONCLUSIONS: Prophylactic intraoperative dexmedetomidine infusion reduces the incidence of chronic incisional pain as well as acute pain score after elective brain tumor resections.

Paracetamol (acetaminophen) poisoning: The early years.

Paracetamol (acetaminophen) was marketed in the 1950s as a nonprescription analgesic/antipyretic without any preclinical toxicity studies. It became used increasingly for self-poisoning, particularly in the UK and was belatedly found to cause acute liver damage, which could be fatal. Management of poisoned patients was difficult as maximum abnormalities of liver function were delayed for 3 days or more after an overdose. There was no treatment and the mechanism of hepatotoxicity was not known. The paracetamol half-life was prolonged with liver damage occurring when it exceeded 4 h and the Rumack-Matthew nomogram was an important advance that allowed stratification of patients into separate zones of risk. It is used to guide prognosis and treatment and its predictive value could be increased by combining it with the paracetamol half-life. The problems of a sheep farmer in Australia in the early 1970s led to the discovery of the mechanism of paracetamol hepatotoxicity, and the first effective treatment of overdosage with intravenous (IV) cysteamine. This had unpleasant side effects and administration was difficult. N-acetylcysteine soon became the treatment of choice for paracetamol overdose and given early it was very effective when administered either IV or orally. N-acetylcysteine could cause anaphylactoid reactions, particularly early during IV administration when the concentrations were highest. Simpler and shorter regimes with slower initial rates of infusion have now been introduced with a reduced incidence of these adverse effects. In addition, there has been a move to use larger doses of N-acetylcysteine given over longer periods for patients who are more severely poisoned and those with risk factors. There has been much interest recently in the search for novel biomarkers such as microRNAs, procalcitonin and cyclophilin that promise to have greater specificity and sensitivity than transaminases. Paracetamol-protein adducts predict hepatotoxicity and are specific biomarkers of toxic paracetamol metabolite exposure. Another approach would be measurement of the plasma levels of cysteine and inorganic sulfate. It is 50 years since the first effective treatment for paracetamol poisoning and, apart from liver transplantation, there is still no effective treatment for patients who present late.

Nonopioid Versus Opioid Analgesics After Thyroid and Parathyroid Surgery: A Systematic Review.

OBJECTIVE: To determine whether nonopioid analgesic regimens, taken after discharge for thyroid and parathyroid surgery have noninferior pain outcomes in comparison to opioid analgesic regimens. Secondarily, we sought to determine if nonopioid analgesic regimens decrease the number of opioid medications taken after thyroid and parathyroid surgery, and to assess adverse events associated with opioid versus nonopioid regimens. DATA SOURCES: PubMed, Embase, Cochrane. REVIEW METHODS: A comprehensive search of the literature was performed according to the PRISMA guidelines, and identified 1299 nonduplicate articles for initial review of which 2 randomized controlled trials (RCTs) were identified as meeting all eligibility criteria. Meta-analysis was not conducted due to heterogeneity in the data and statistical analyses. RESULTS: Both RCTs included in this systematic review found no significant differences in postoperative pain scores between individuals discharged with a nonopioid only analgesic regimen compared to analgesic regimen that included oral opioid medications. One study reported significantly increased number of postoperative calls related specifically to pain in the nonopioid arm compared to the opioid arm (15.6% vs. 3.2%, P = .045). CONCLUSION: This systematic review of RCTs revealed a limited number of studies examining nonopioid versus opioid postoperative pain medications among adults who undergo thyroid and parathyroid surgery. Among the 2 RCTs on this topic, there is a shared finding that nonopioid analgesic regimens are noninferior to opioid analgesic regimens in managing postoperative pain after thyroid and parathyroid surgery, supporting the use of nonopioid pain regimens given the risk of opioid dependence associated with prescription opioid medications.

Comparing Postoperative Pain With Laparoscopic Versus Robotic Sacrocolpopexy.

STUDY OBJECTIVE: To compare postoperative pain and pain-related outcomes after laparoscopic (LS-MISC) vs robotic minimally invasive sacrocolpopexy (R-MISC). DESIGN: A secondary analysis of an original placebo-controlled randomized controlled trial (RCT) examining preoperative intravenous (IV) acetaminophen on postoperative pain after MISC. SETTING: Planned secondary analysis of multicenter RCT. PATIENTS: Women undergoing MISC. INTERVENTIONS: Coprimary outcomes at 24 hours were total opioid use in morphine milligram equivalents (MMEs) and visual analog scale (VAS) pain scores comparing LS-MISC and R-MISC. The secondary outcome was pain scores using a pain diary through 7 days after the procedure. MEASUREMENTS AND MAIN RESULTS: The original study was a double-blind, multicenter, RCT comparing IV acetaminophen with placebo that took place between 2014 and 2017. Given that the original trial was unable to show an impact from the use of IV acetaminophen, our analysis focused on the impact of surgical modality. We included 90 subjects undergoing MISC: 65 LS-MISC and 25 R-MISC. Most were Caucasian (97.8%) and postmenopausal (88.9%) with mean age of 61.2 ± 7.2 years and body mass index of 27.6 ± 4.4 kg/m2. IV acetaminophen did not affect pain in the original study and was not different between LS-MISC and R-MISC. Concomitant hysterectomy was performed in 67% (LS-MISC) vs 60% (R-MISC, p = .49). LS-MISC underwent more perineorrhaphies (15.4% vs 0%, p = .04) and posterior repairs (18.5% vs 0%, p = .02). Operative time was longer with LS-MISC (208.5 ± 57.3 vs 143.6 ± 21.0 minutes, p <.01). Length of stay was longer with LS-MISC (0.9 ± 0.4 vs 0.7 ± 0.4 days, p = .02). Women undergoing LS-MISC consumed more opioid MMEs through 24 hours when including intraoperative opioids (48.5 ± 25.5 vs 35.1 ± 14.6 MME, p <.01). Using linear regression correcting for operative time and concomitant vaginal repairs, this difference disappeared. Likewise, when intraoperative opioids were excluded, there was no difference. There were no differences in 24-hour postoperative VAS scores, opioid use in the first week, or quality of life (Patient-Reported Outcomes Measurement Information System - Pain Interference Short Form, all p <.05). CONCLUSION: When comparing VAS pain scores, MME opioid usage, and quality of life between LS-MISC and R-MISC, either there was no difference or differences disappeared after adjusting for confounders. Overall, opioid use, pain scores, and opioid side effects were low.

Outcomes of hip fracture treatment with intravenous morphine and with other analgesics: postoperative analgesic medical expense, severity of pain and hospitalisation-a retrospective study.

AIMS: This study compares the postoperative medical costs and outcomes of hip fracture patients treated with intravenous (IV) versus other analgesics (weak opioids, NSAIDs or acetaminophen). METHODS: We performed a retrospective study at a tertiary hospital in Thailand, examining 1,531 patients who underwent hip fracture surgery between 2009 and 2020. We analyzed data on analgesic usage, costs, pain scores, and adverse effects. RESULTS: In the study of 1531 patients, 63% of patients received as-needed analgesics, and 37% received preemptive prescriptions. In both groups, IV morphine was the predominant choice. The mean cost for the IV group was marginally higher than the other analgesics group ($2277 vs $2174). The other analgesics group had a significantly higher consumption of acetaminophen and selective NSAIDs (p = 0.004). Pain scores were similar across both groups, but the IV group had a significantly higher incidence of gastrointestinal side effects (24% vs 10.5%, p < 0.01). CONCLUSION: The choice of IV or other analgesics in treating hip fractures affects analgesic usage, side effects, medical costs, and patient outcomes. Further studies across different regions are recommended.

An international survey of the treatment of massive paracetamol overdose in 2023.

INTRODUCTION: Changes in the commercialization of nonprescription drugs have made large quantities of paracetamol available to individuals, resulting in larger overdoses than previously observed. Although most patients with paracetamol overdose can be managed with acetylcysteine, patients with a massive overdose may become critically ill earlier and fail standard antidotal therapy. Several strategies are proposed for the management of these patients, including using increased doses of acetylcysteine, extracorporeal removal, and fomepizole. However, the benefits of these strategies remain largely theoretical, with sparse evidence for efficacy in humans. METHODS: This cross-sectional study surveys international practice patterns of medical toxicology providers regarding the management of a hypothetical patient with a massive paracetamol overdose. RESULTS: A total of 342 responses from 31 different nations were obtained during the study period. Sixty-one percent of providers would have increased their acetylcysteine dosing when treating the hypothetical massive overdose. Thirty percent of respondents recommended an indefinite infusion of acetylcysteine at 12.5 mg/kg/hour after the bolus dose, whereas 20 percent recommended following the "Hendrickson" protocol, which advocates for a stepwise increase in acetylcysteine dosing to match high paracetamol concentrations at the 300 mg/L, 400 mg/L, and 600 mg/L lines on the Rumack-Matthew nomogram. Ten percent of respondents stated they would have given "double dose acetylcysteine" but did not specify what that entailed. Forty-seven percent of respondents indicated that they would have given fomepizole, and 28 percent of respondents recommended extracorporeal removal. DISCUSSION: Our survey study assessed the approach to a hypothetical patient with a massive paracetamol overdose and demonstrated that, at minimum, most respondents would increase the dose of acetylcysteine. Additionally, almost half would also include fomepizole, and nearly one-third would include extracorporeal removal. CONCLUSIONS: There is considerable international variation for the treatment of both non-massive and massive paracetamol overdoses. Future research is needed to identify and standardize the most effective treatment for both non-massive and massive paracetamol overdoses.