Dose Of Acetaminophen Research Articles

Early Postoperative Acetaminophen Administration and Severe Acute Kidney Injury After Cardiac Surgery

Oxidative stress may contribute to the development of acute kidney injury (AKI) after cardiac surgery. Acetaminophen can be considered an antioxidant because it inhibits hemoprotein-catalyzed lipid peroxidation. We hypothesized that perioperative acetaminophen administration is associated with reduced AKI after cardiac surgery. Retrospective observational cohort study. Patients aged≥18 years who had cardiac surgery were identified from 2 publicly available clinical registries: the Medical Information Mart for Intensive Care III (MIMIC-III) and the eICU Collaborative Research Database (eICU). Administration of acetaminophen in the first 48 hours after surgery. Severe AKI in the first 7 days after surgery, defined as stage 2 or stage 3 AKI according to KDIGO criteria. Multivariable cause-specific hazards regression analysis. We identified 5,791 patients from the MIMIC-III and 3,840 patients from the eICU registries. The overall incidence of severe AKI was 58% (3,390 patients) in the MIMIC-III cohort and 37% (1,431 patients) in the eICU cohort. Acetaminophen was administered in the early postoperative period to 4,185 patients (72%) and 2,737 patients (71%) in these 2 cohorts, respectively. In multivariable regression models, early postoperative use of acetaminophen was associated with a lower risk of severe AKI in both the MIMIC-III (adjusted hazard ratio [AHR], 0.86 [95% CI, 0.79-0.94]) and eICU (AHR, 0.84 [95% CI, 0.72-0.97]) cohorts. The benefit was consistent across sensitivity and subgroup analyses. No data on acetaminophen dose. Early postoperative acetaminophen administration was independently associated with a lower risk of severe AKI in adults recovering from cardiac surgery. Prospective trials are warranted to assess the extent to which the observed association is causal and estimate the extent to which acetaminophen administration might prevent or reduce the severity of AKI.

Pharmacokinetics of single dose administration of three increasing doses of acetaminophen per os in 1-3-month-old foals.

Acetaminophen is a common analgesic and antipyretic drug used in human medicine and might be an alternative to nonsteroidal anti-inflammatory drugs for treating pain and pyrexia in foals. The pharmacokinetics and safety of differing doses of acetaminophen have not been investigated in foals. To determine the plasma pharmacokinetics and any changes in haematology and biochemistry profiles following oral administration of single doses of acetaminophen at 10, 20, and 40 mg/kg to foals. Randomised cross-over pharmacokinetic study. Six Quarter Horse (two colts and four fillies) foals received 10, 20, and 40 mg/kg acetaminophen orally once. Haematology and biochemistry profiles were performed before and 7 days after each drug administration. Blood samples were collected over 64 h after drug administration and were used to quantify plasma acetaminophen concentrations by liquid chromatography. Pharmacokinetic parameters were determined using compartmental analysis. Median (range) acetaminophen plasma concentrations were 4.4 (1.8-5.1), 6.3 (2.6-12.6), and 14 (7.3-18)μg/ml for the 10, 20, and 40 mg/kg doses, respectively. Median acetaminophen area under the concentration versus time curve (AUC)0-∞ ranged from 25 (11-32), 41 (22-74), and 105 (82-142)h × μg/ml for the 10, 20, and 40 mg/kg doses, respectively. Dose-normalised maximal concentrations and AUC0-∞ values were similar across dose concentrations (p > 0.05). Median terminal half-life for all doses was 2.7-2.8h. Haematology and biochemistry profiles were normal except for blood urea nitrogen and alkaline phosphatase concentrations. Foals were growing throughout the study, starting at 1month and ending at 3months. Deposition of drugs changes with age. The sample size was small and only single doses were evaluated. No liver biopsies were performed. Plasma disposition of acetaminophen after a single oral dose of 10, 20, and 40 mg/kg to 1-3-month-old foals varies greatly with the dose. The analgesic and antipyretic effect in foals is unknown.

Ocular penetration of oral acetaminophen in horses.

Acetaminophen (paracetamol) is increasingly used to treat painful conditions in horses but its ocular penetration has not been studied. To determine whether orally administered acetaminophen penetrates the aqueous humour of the normal equine eye and report an aqueous humour:serum acetaminophen concentration ratio in horses. In vivo experiment. Six privately owned horses with normal ophthalmic examinations weighing 568 ± 65 kg (mean ± standard deviation) and aged 11 ± 4 years were given 20 mg/kg acetaminophen orally every 12 h for a total of six doses. Physical exam parameters were recorded prior to, during, and after the dosing period. One hour after the final dose, horses were sedated and simultaneous aqueous humour and serum samples were collected and analysed for acetaminophen concentrations and selected eicosanoids. An aqueous humour:serum acetaminophen concentration ratio was calculated. A second aqueous humour sample was taken and analysed for eicosanoid concentrations 3 months after acetaminophen dosing. Physical exam data were compared between time points using a mixed model analysis (significance p < 0.05). Acetaminophen was detected in both serum and aqueous humour of all horses and mean ± standard deviation aqueous humour:serum acetaminophen concentration ratio was 44.9 ± 15.9%. No significant changes in physical exam parameters occurred during or after dosing. Eicosanoids were not detected in aqueous humour at any sampling point. Presence of acetaminophen in the aqueous humour may not relate to clinical effect. A therapeutic level of acetaminophen has not been determined in horses, and the absence of ocular inflammation does not reflect conditions in which acetaminophen may be used. Acetaminophen readily penetrates the aqueous humour of the normal equine eye after consecutive oral dosing. Further study is required to determine whether acetaminophen is useful in the treatment of ocular pain and inflammation.

Scheduled, Simultaneous Dosing of Pregabalin, Celecoxib, and Acetaminophen Markedly Reduces or Eliminates Opioid Use After ACL Reconstruction Using Allograft or Hamstring Tendon Autograft: A Randomized Clinical Trial

Opioid analgesics continue to be prescribed after ambulatory surgery despite untoward adverse effects, risk of overdose, and association with substance use disorder. The purpose was to investigate the use of a novel system to provide scheduled and simultaneous dosing of acetaminophen, celecoxib, and pregabalin after anterior cruciate ligament reconstruction (ACLR). It was hypothesized that this system would markedly reduce pain and opioid use compared with existing best practice. Randomized controlled trial; Level of evidence, 1. Included were 100 patients scheduled for elective, primary ACLR using allograft or hamstring tendon autograft. Selection criteria included age between 18 and 65 years and weight between 65 and 120 kg. Exclusion criteria were a known allergy to any drug used in the study or the use of opioid analgesics before surgery. Patients in the intervention group received a blister pack with scheduled, simultaneous doses of acetaminophen, celecoxib, and pregabalin; patients were also given oxycodone 5 mg as needed for breakthrough pain. Patients in the control group were prescribed ibuprofen and oxycodone 5 mg/acetaminophen 325 mg as needed for pain. The primary outcome measure was pain. Secondary outcomes were nausea, itching, and daily oxycodone use. Patients were asked to quantify their average pain at rest, nausea, and itching on an 11-point verbal scale (from 0 to 10). These data were recorded for 6 days during daily telephone contacts with patients after hospital discharge. Cumulative results for 6 days showed significantly lower values in the intervention group compared with the control group for pain (median [interquartile range], 28 [14-35] vs 35 [28-41], respectively; P = .009) and oxycodone use (median [interquartile range] number of tablets, 0 [0-2] vs 8 [1.25-16], respectively; P < .001). Based on these data, the upper tolerance limits for the number of oxycodone tablets required by 90% of patients in the intervention and control groups were 8 tablets and 30 tablets, respectively. Cumulative results for nausea and itching were also significantly lower for the intervention group. Most patients in the intervention group used no opioids during recovery. Simultaneous dosing of 3 nonopioid analgesics resulted in reduced postoperative pain and markedly lower opioid use. NCT04015908 (ClinicalTrials.gov identifier).

Comparing the effect of body wash with marshmallow plant and lukewarm water on reducing the temperature of febrile children: a randomized clinical trial

BackgroundFever is the most common reason for children’s visits to medical centers. Its management is an essential duty of a pediatric nurse. The aim of this study was to determine the effect of body wash with Marshmallow plant on children’s fever.MethodsThis parallel clinical trial was performed on 92 children aged 6 months to 10 years with a tympanic temperature above 38.3 °C. Participants were randomly assigned to groups. Simultaneously with receiving acetaminophen, body wash was performed in the control group with lukewarm water and in the intervention group with white Marshmallow extract. The children’s temperature; from the beginning of the study was checked and recorded every 15 min in the first hour and in the 4th and 6th hours. The time duration to resolve fever, the frequency of afebrile children at different times of the study, and the value of temperature reduction were primary outcomes. Heart rate, the need to administer the next dose of acetaminophen, and the time of fever recurrence were recorded as secondary outcomes.ResultsThe mean time duration to resolve fever in the intervention group was shorter than in the control group (B = 8.181, 95% CI 3.778–12.584, p < 0.001). The frequency of the children without fever was higher in the intervention group during different times of the study (p < 0.001). The mean value of temperature reduction in the intervention group was higher than the control group (B = -0.27 °C, 95% CI: -0.347 to -0.193, P < 0.001), although, after adjusting the effect of confounding variables it was not significant (P = 0.127). The mean of adjusted heart rate change (p = 0.771), the time of fever recurrence (P = 0.397), and the frequency of children requiring the next dose of acetaminophen (p = 0.397) did not show a significant difference between the groups.ConclusionBody wash with Marshmallow extract reduced children’s fever in a shorter period of time and to some extent a greater extent than the control group without side effects. Therefore, it can be used as an effective and safe complementary method to help reduce fever. However, more studies are necessary for this field.Trial registrationRegistration in Iranian Clinical Trials (RCTs) on 31.08.2020 with registration code: IRCT20200809048345N1.

Acetaminophen pharmacokinetics in infants and children with congenital heart disease.

Acetaminophen is routinely used for perioperative analgesia in children undergoing major surgical procedures. There are few estimates of acetaminophen pharmacokinetic parameters in children with congenital heart disease, especially those with cyanotic heart disease. The current study prospectively investigated differences in acetaminophen pharmacokinetics following surgery using cardiopulmonary bypass in children with cyanotic and acyanotic congenital heart disease. Children (2-6 years, 9-23 kg) presenting for median sternotomy for Fontan palliation (cyanotic patients) or two ventricle surgical repair (acyanotic patients) were eligible for inclusion. A single intravenous dose of acetaminophen (15 mg/kg) was administered at the start of sternal closure after separation from cardiopulmonary bypass. The time-course of acetaminophen concentrations were described using non-linear mixed effects models. One and two-compartment disposition models with first-order elimination were tested. Pharmacokinetic parameter estimates were scaled using allometry and standardized to a 70 kg person. There were 208 acetaminophen concentrations assayed from 30 children, 15 with cyanotic, and 15 with acyanotic heart disease. A 2-compartment model best described acetaminophen PK. Parameter estimates (population parameter variability, PPV%; 95% confidence interval, CI) were clearance CL 15.3L.h-1.70 kg-1 (22.2%; 13.8-16.7), intercompartment clearance Q 45.4L.h-1.70 kg-1 (22.4%; 25.2-61.9), central volume of distribution V1 33.5L.70 kg-1 (23.2%; 25.9-38.8), peripheral volume of distribution V2 32.1L.70 kg-1 (21.7%; 25.9-38.8). Neither clearance nor volume parameters differed between cyanotic and acyanotic patients. Acetaminophen pharmacokinetics were characterized using a 2-compartment model with first-order elimination following cardiac bypass surgery in children. Population pharmacokinetic parameter estimates were similar to other studies in children. No differences were detected between patients with cyanotic and acyanotic heart disease.

Orgafig® daily intake minimizes oxidative stress and tissue damage in the liver in the face of challenges with aflatoxin in the diet and consecutive doses of acetaminophen

Orgafig® daily intake minimizes oxidative stress and tissue damage in the liver in the face of challenges with aflatoxin in the diet and consecutive doses of acetaminophen

Liposomal bupivacaine reduces opioid requirements following Ravitch repair for pectus excavatum.

The management of post-operative pain after surgical repair of pectus excavatum with the Ravitch procedure is challenging. Although previous studies have compared various methods of pain control in these patients, few have compared different local anesthetics. This retrospective analysis compares the use of bupivacaine to its longer-acting form, liposomal bupivacaine, in patients who had undergone pectus excavatum repair with the Ravitch method. Eleven patients who received local infiltration with liposomal bupivacaine were matched to 11 patients who received local infiltration utilizing bupivacaine with epinephrine. The primary outcome was total morphine milligram equivalents per kilogram body weight (MME/kg) over the complete length of hospital stay. Secondary outcomes included total cumulative diazepam, acetaminophen, ondansetron, and NSAID dose per kilogram body weight (mg/kg) over the course of the hospital stay, chest tube drainage (ml/kg body weight), number of post-operative hours until the first bowel movement, Haller Index, patient request for magnesium hydroxide, average pain scores from post-operative day 1 to post-operative day 5, and length of hospital stay. Continuous variables were reported as medians with inter-quartile ranges, and categorical values were reported as percentages and frequencies. The total MME/kg [1.7 (1.2-2.4) vs 2.9 (2.0-3.9), P = 0.007] and hydromorphone (mg/kg) [0.1 (0.0-0.2) vs 0.3 (0.1-0.4), P = 0.006] use in the liposomal bupivacaine group versus bupivacaine with epinephrine was significantly reduced over total length of hospital stay. Similarly, there was a reduction in diazepam use in the liposomal bupivacaine group versus the bupivacaine group [0.4 (0.1-0.8) vs 0.6 (0.4-0.7), P = 0.249], but this did not reach statistical significance. The total dose of ondansetron (mg/kg) was not statistically different when comparing the liposomal bupivacaine group to the bupivacaine group [0.3 (0.0-0.5) vs 0.3 (0.2-0.6), P = 0.332]. Interestingly, the total dose of acetaminophen (mg/kg) was statistically increased in the liposomal bupivacaine group compared to the bupivacaine with epinephrine group [172 (138-183) vs 74 (55-111), P = 0.007]. Additionally, the total chest tube drainage (ml/kg) was significantly reduced in the liposomal bupivacaine group [9.3 (7.5-10.6) vs 12.8 (11.3-18.5), P = 0.027]. Finally, the percentage of patients without requests for magnesium hydroxide to promote laxation was significantly higher in the liposomal bupivacaine group than in the bupivacaine group (63.6% vs 18.2%, P = 0.027). The use of liposomal bupivacaine for local infiltration in patients who undergo the Ravitch procedure for pectus repair offers advantages over plain bupivacaine, including reduced opioid consumption and opioid-related side effects. However, more data are needed to understand the significance of these findings.

Model of Acute Liver Failure in an Isolated Perfused Porcine Liver—Challenges and Lessons Learned

Acute liver failure (ALF) is a rare but devastating disease associated with substantial morbidity and a mortality rate of almost 45%. Medical treatments, apart from supportive care, are limited and liver transplantation may be the only rescue option. Large animal models, which most closely represent human disease, can be logistically and technically cumbersome, expensive and pose ethical challenges. The development of isolated organ perfusion technologies, originally intended for preservation before transplantation, offers a new platform for experimental models of liver disease, such as ALF. In this study, female domestic swine underwent hepatectomy, followed by perfusion of the isolated liver on a normothermic machine perfusion device. Five control livers were perfused for 24 h at 37 °C, while receiving supplemental oxygen and nutrition. Six livers received toxic doses of acetaminophen given over 12 h, titrated to methemoglobin levels. Perfusate was sampled every 4 h for measurement of biochemical markers of injury (e.g., aspartate aminotransferase [AST], alanine aminotransferase [ALT]). Liver biopsies were taken at the beginning, middle, and end of perfusion for histological assessment. Acetaminophen-treated livers received a median dose of 8.93 g (8.21–9.75 g) of acetaminophen, achieving a peak acetaminophen level of 3780 µmol/L (3189–3913 µmol/L). Peak values of ALT (76 vs. 105 U/L; p = 0.429) and AST (3576 vs. 4712 U/L; p = 0.429) were not significantly different between groups. However, by the end of perfusion, histology scores were significantly worse in the acetaminophen treated group (p = 0.016). All acetaminophen treated livers developed significant methemoglobinemia, with a peak methemoglobin level of 19.3%, compared to 2.0% for control livers (p = 0.004). The development of a model of ALF in the ex vivo setting was confounded by the development of toxic methemoglobinemia. Further attempts using alternative agents or dosing strategies may be warranted to explore this setting as a model of liver disease.

S3300 Acetaminophen Toxicity Amplified: Drug-Induced Liver Injury in a Malnourished Patient

Introduction: Acetaminophen toxicity is a leading cause of acute liver injury and failure in the U.S. Excess acetaminophen results in formation of N-acetyl-p-benzoquinoneimine (NAPQI) which causes irreversible oxidative hepatocyte injury and cell necrosis. Treatment with N-acetylcysteine (NAC) replenishes glutathione stores which inactivate NAPQI. In a healthy adult, acetaminophen doses less than 4 g per 24 hours are considered safe. Toxicity from therapeutic doses of acetaminophen, in the setting of malnourishment, has been rarely reported and is presented here. Case Description/Methods: A 37-year-old female with a history of gastroparesis and chronic malnutrition was admitted for elevated liver enzymes on routine blood work. She reported symptoms of fatigue, nausea, and poor oral intake from suspected gastroparesis. She also admitted to taking 1300 mg of acetaminophen intermittently during the past week for myalgias. Exam revealed normal mentation without evidence of hepatic encephalopathy (HE), cachexia with a BMI of 15.2, and mild epigastric and left upper quadrant tenderness. Laboratory data (36 hours after last ingestion of acetaminophen) revealed an ALT of 1180 u/L, AST of 1950 u/L, ALP of 121 u/L, total bilirubin of 2.7 mg/dL, direct bilirubin of 2.5 mg/dL and INR of 1.6. Her acetaminophen level was 15.8 mcg/mL. A liver ultrasound was unremarkable. NAC was subsequently administered as per protocol 21 hour infusion. She was ruled out for other etiologies of acute liver injury. She never developed HE and her liver enzymes, along with INR, normalized at discharge. Discussion: This case highlights the lower threshold for toxicity of acetaminophen in a malnourished patient. In previous case reports, acetaminophen doses less than 2 g per 24 hours are listed as being safe in a nutritionally deficient patient. Our case questions this assertion given our patient ingested 65% of this amount. Evidence in the relatively limited pool of literature suggests that malnourished patients generally have low stores of glutathione, thereby limiting the metabolic clearance of acetaminophen ingested even at normal dosages, amplifying total acetaminophen levels, and leading to increased NAPQI. Prospective study is limited to rat models and single case reports. Fortunately, our patient was promptly treated with NAC and did not progress to liver failure. This case highlights the narrow therapeutic window of acetaminophen in malnourished patients, one that warrants close observation by clinicians.

Efficacy and safety of oral Nigella sativa oil for symptomatic treatment of knee osteoarthritis: A double-blind, randomized, placebo-controlled clinical trial

Background and purposeThe oil of Nigella sativa (NS) seeds has analgesic and anti-inflammatory effects. Therefore, the efficacy and safety of NS oil in the treatment of knee osteoarthritis were evaluated. Materials and methodsOne hundred and sixteen patients aged 50–70 years were randomly assigned to take 2.5 mL NS oil (N = 58) or placebo (N = 58) orally every 8 h for 1 month. WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) was the primary outcome measure and Visual Analog Scale (VAS) for pain, number of 500 mg acetaminophen tablets taken per day during the trial, patients’ satisfaction with the interventions, complete blood count and the blood levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine and blood urea nitrogen were the secondary outcome measures. ResultsFifty two and 54 patients respectively in the NS oil and placebo groups completed the study. The VAS scores were decreased by 33.96 ± 17.04% (NS oil group) and 9.21 ± 0.32% (placebo group) (p < 0.001), and WOMAC total scores were decreased by 27.72 ± 18.61% (NS oil group) and 1.34 ± 2.31% (placebo group) (p < 0.001) compared to baseline. The NS oil reduced the dose of acetaminophen significantly compared with the placebo (p = 0.001). The patients were significantly more satisfied with the NS oil than the placebo (p < 0.001). The NS oil had no significant effect on the other variables. There was no side effect. ConclusionOral NS oil safely reduces the osteoarthritis symptoms and analgesic dose in the knee osteoarthritis patients.

Population pharmacokinetic analysis of acetaminophen overdose with immediate release, extended release and modified release formulations

Objectives The introduction of delayed release formulations of acetaminophen (APAP) has created concern about the role of formulation in overdose. We examined the APAP overdose pharmacokinetic (PK) profiles to assess the role of dose, coingestants and formulation: immediate release (IR), extended release (ER), and modified release (MR) on APAP pharmacokinetic measures. Methods We collected by-subject APAP PK data: subject description, timed blood APAP concentrations, dose, and coingestants. We sought both overdose and randomized controlled trials (RCTs) for supratherapeutic doses involving ER or MR formulations. Data analysis and simulation used the non-linear mixed-effects modeling program NONMEM-version 7.4. Results The final dataset comprised 3,033 [APAP] from 356 subjects and 15 sources including 3 RCTs (179 subjects receiving IR, 122 ER, 65 MR). The final population PK (PopPK) model was a linear 2-compartment model with first-order (oral) absorption. Covariate relationships included: APAP absorption rate and bioavailability decreased with increased oral dose (p < 0.00005) for all 3 formulations (MR > ER > IR). Post hoc analyses showed opioid coingestant increased exposure (area under the curve, AUC) by factor of 1.6. Simulations of 100 g vs 10 g doses for IR, ER and MR showed overdose of the ER formulation exhibits slower absorption and lower C max, overall exposure (AUC) is less than 80% of an equivalent dose of IR acetaminophen. The overall exposure for the MR formulation is less than 70% of an equivalent dose of IR. Conclusions Acetaminophen ER and MR formulations have slower absorption and decreased bioavailability leading to a lower C max and later T max than the IR formulation. These results have potential clinical implications because delayed absorption could confound use of the Rumack-Matthew nomogram by underestimating the severity of ingestion early in the course of treatment.

Efficacy of single-shot adductor canal block before Versus after primary total knee arthroplasty - Does timing make a difference? A randomized controlled trial.

Total knee arthroplasty (TKA) is associated with severe postoperative pain. Multimodal analgesia, including peripheral nerve block, is recommended for post-operative pain relief. Administration of some pain medications prior to surgery has shown to be more effective than after the operation. This is a prospective, randomized controlled trial designed to compare the analgesic efficacy of the adductor canal block (ACB) performed immediately before or immediately after primary total knee arthroplasty (TKA). We hypothesized that ACB before the surgery will reduce postoperative pain and improve knee function. A total of 50 patients were enrolled and randomized into 2 groups, with 26 patients receiving a preoperative ACB and 24 receiving a postoperative ACB. Treatment groups were similar in terms of gender (p = .83), age (p = 0.61) weight (p = .39) and ASA score. Average visual analogue scale (VAS) on arrival to the post-anesthesia care unit (PACU) were 4.9 ± 3.2 in the preoperative ACB versus 3.4 ± 2.8 for the postoperative ACB (p = .075). VAS scores at different time points as well as the mean, minimal and maximal reported VAS scores were not significantly different between the two groups. The cumulative quantities of Fentanyl administered by the anesthesia team was comparable between the groups. Similarly, the dosage of Morphine, Tramadol, Acetaminophen and Dipyrone showed only small variations. The Quality of Recovery Score, Knee Society Scores and knee range of motion did not differ between the groups. Our findings demonstrate no significant differences in patient total narcotics consumption, pain scores and functional scores, between preoperative and postoperative ACB in patients undergoing TKA. The trial was registered at www.clinicaltrials.gov and was assigned the registration number NCT02908711. level I randomized controlled trial.

Analgesic Efficacy of Adjuvant Medications in the Pediatric Caudal Block for Infraumbilical Surgery: A Network Meta-Analysis of Randomized Controlled Trials.

Various adjuvants are added to local anesthetics in caudal block to improve analgesia. The comparative analgesic effectiveness and relative rankings of these adjuvants are unknown.This network meta-analysis (NMA) sought to evaluate the comparative analgesic efficacy and relative ranking of caudal adjuvants added to local anesthetics (versus local anesthetics alone) in pediatric infra-umbilical surgery. We searched the United States National Library of Medicine database (MEDLINE), PubMed, and Excerpta Medica database (Embase) for randomized controlled trials (RCTs) comparing caudal adjuvants (clonidine, dexmedetomidine, ketamine, magnesium, morphine, fentanyl, tramadol, dexamethasone, and neostigmine) among themselves, or to no adjuvant (control). We performed a frequentist NMA and employed Cochrane’s ‘Risk of Bias’ tool to evaluate study quality. We chose the duration of analgesia (defined as 'the time from caudal injection to the time of rescue analgesia') as our primary outcome. We also assessed the number of analgesic dose administrations and total dose of acetaminophen within 24 h.The duration of analgesia [87 randomized control trials (RCTs), 5285 patients] was most prolonged by neostigmine [mean difference: 513 min, (95% confidence interval, CI: 402, 625)]. Dexmedetomidine reduced the frequency of analgesic dose administrations within 24 h [29 RCTs, 1765 patients; -1.2 dose (95% CI: -1.6, -0.9)] and the total dose of acetaminophen within 24 h [18 RCTs, 1156 patients; -350 mg (95% CI: -467, -232)] the most. Among caudal adjuvants, neostigmine (moderate certainty), tramadol (low certainty), and dexmedetomidine (low certainty) prolonged the duration of analgesia the most. Dexmedetomidine also reduced the analgesic frequency and consumption more than other caudal adjuvants (moderate certainty).

P142. Single center, randomized controlled trial of intravenous vs oral acetaminophen administration in perioperative care of 1 and 2 level LLIFs with instrumented posterior lumbar fusion: a comparative effectiveness study

P142. Single center, randomized controlled trial of intravenous vs oral acetaminophen administration in perioperative care of 1 and 2 level LLIFs with instrumented posterior lumbar fusion: a comparative effectiveness study

Galangin Nanoparticles Protect Acetaminophen-Induced Liver Injury: A Biochemical and Histopathological Approach.

One of the main causes of acute liver failure is overdose with acetaminophen. Excessive consumption of acetaminophen leads to the production of NAPQI (N-acetyl-p-benzoquinone imine) through the activity of the enzyme cytochrome c oxidase. For this purpose, the effect of galangin nanoparticles with antioxidant activities will be evaluated for the treatment of acetaminophen-induced hepatotoxicity. In this study, after the synthesis of galangin nanoparticles and particle size determination, mice were divided into six groups. Before treatment, a single dose (350 mg/kg) of acetaminophen was administered by gavage in all groups. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), as well as biochemical factors FRAP and MDA in serum were measured and a histopathological study was performed. The prepared nanoparticles produced in this research were characterized by the SEM, DLS, and ZETA potential, and the average particle size was obtained in the range of 150 nm. Serum levels of liver enzymes (AST and ALT) in the nanoparticle group decreased significantly compared with the control group (P < 0.05). In the group without treatment, the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes increased significantly compared with the treatment groups. Also, galangin nanoparticles, at a dose of 20 mg/kg, improve cell damage in hepatocytes and preserve the tissue structure of the liver. Galangin nanoparticles reduce the acetaminophen-induced hepatotoxicity by reducing the number of liver function indices. According to our findings, the liver-protective effects of the nanoparticle may be due to its antioxidant properties.

A CASE REPORT ON N-ACETYLCYSTEINE (MUCINAC) INDUCED CHEST TIGHTNESS

N-Acetylcysteine is anapproved drug by the Food and Drug Administration (FDA) and recognized by the World Health Organization (WHO) as an essential drug[1]. It isa synthetic N-acetyl derivative and prodrug of the endogenous amino acid L-cysteine, a precursor of the antioxidant glutathione (GSH), with mucolytic, antioxidant, and anti-inflammatory activities[4]. Primarily approved for the treatment of potentially hepatotoxic doses of acetaminophen. It is also used in the treatment of respiratory disorders, especially in COPD and cystic fibrosis[6]. An unusual case of chest tightness due to mucinac (N-Acetylcysteine) was reported in a female patientwith a history of cancer in the left upper alveoluswas admitted to the hospital for radiotherapy + chemotherapy. She was prescribed tablet mucinac for excessive mucus and to improve respiratory symptoms. The patient developed chest tightness after ingestion of mucinactablets.According to the Naranjo scale the observed reaction was a probable ADR.Later tablet was stopped, replaced nebulization with budecort respule. Keywords: N-acetylcysteine, glutathione, antioxidant, anti-inflammatory, mucolytic, COPD, Cystic fibrosis, Chest tightness

Acetaminophen Disrupts the Development of Pharyngeal Arch-Derived Cartilage and Muscle in Zebrafish.

Acetaminophen is a common analgesic, but its potential effects on early embryonic development are not well understood. Previous studies using zebrafish (Danio rerio) have described the effects of acetaminophen on liver development and physiology, and a few have described gross physiological and morphological defects. Using a high but non-embryonic lethal dose of acetaminophen, we probed for defects in zebrafish craniofacial cartilage development. Strikingly, acetaminophen treatment caused severe craniofacial cartilage defects, primarily affecting both the presence and morphology of pharyngeal arch-derived cartilages of the viscerocranium. Delaying acetaminophen treatment restored developing cartilages in an order correlated with their corresponding pharyngeal arches, suggesting that acetaminophen may target pharyngeal arch development. Craniofacial cartilages are derived from cranial neural crest cells; however, many neural crest cells were still seen along their expected migration paths, and most remaining cartilage precursors expressed the neural crest markers sox9a and sox10, then eventually col2a1 (type II collagen). Therefore, the defects are not primarily due to an early breakdown of neural crest or cartilage differentiation. Instead, apoptosis is increased around the developing pharyngeal arches prior to chondrogenesis, further suggesting that acetaminophen may target pharyngeal arch development. Many craniofacial muscles, which develop in close proximity to the affected cartilages, were also absent in treated larvae. Taken together, these results suggest that high amounts of acetaminophen can disrupt multiple aspects of craniofacial development in zebrafish.

Determination the levels of total bilirubin, total protein and liver histopathological changes in hepatotoxic rats and the role of Beta vulgaris roots ethanolic extract

The present study was done to investigate the therapeutic efficiency of Beta vulgaris roots ethanolic extract versus N-acetylcysteine (NAC) in overcoming experimentally induced hapatotoxicity in rats by given double maximum therapeutic oral dose of Acetaminophen (N-acetyl-para-aminophenol (APAP). The experiment was performed by two parts: First part was involved the extraction of Beta vulgaris roots by using 90% ethanolic solvent and identification the main phytochemical constituents of Beta vulgaris roots ethanolic extract by GC-MS spectrometry analysis , while the second part of experiment was involved the determination and understand the therapeutic effect of Beta vulgaris roots ethanolic extract on hepatotoxicity induced by Acetaminophen which administered more than the recommended dose in rats. Three treated groups of male albino rats (12 rats each) and the dosing regimen was performed as follows: Each group was dosed (APAP) twice daily of (100 mg/kg) for 14 days as follows dosing regimen: Positive control group: Rats were daily administered Acetaminophen at dose (100 mg/kg) orally twice a day as (50 mg/kg) in the morning and (50 mg/kg) at the evening for 14 days followed by two weeks recovery.

Repeated acetaminophen administration damaged hippocampal tissue but did not affect prefrontal cortex or anxiety behaviors.

Acetaminophen is one of the most widely used over‑the‑counter drugs worldwide for the treatment of pain and fever. Although acetaminophen use is known to impair hippocampus‑related learning and memory, its effect on anxiety is not clear. Insulin‑like growth factor‑1 (IGF‑1) and matrix metalloproteinase‑2 (MMP2) are important for cellular survival, maintenance and tissue integrity. The aim of this study was to investigate the dose‑dependent effects of acetaminophen on anxiety levels as well as on hippocampus, prefrontal cortex and liver tissue. Doses of 100, 200 and 400 mg/kg acetaminophen were administered to male Sprague Dawley rats for 11 days and anxiety tests were conducted on the last day. Twenty‑four hours after the last acetaminophen administration, all animals were sacrificed and hippocampus, prefrontal cortex and liver tissues were removed for analyses. Hippocampal IGF‑1 and MMP2 levels were shown to decrease only at the highest dose of acetaminophen, which was accompanied by pathological changes in histology. The prefrontal cortex was not affected. Behavioral analyses also did not indicate changes in anxiety levels in the rats. Liver IGF‑1 and MMP2 levels decreased in all experimental groups. Serum alanine aminotransferase and aspartate aminotransferase levels increased in the 200 mg/kg and 400 mg/kg acetaminophen groups. Our findings showed that varying doses of acetaminophen did not affect the prefrontal cortex or anxiety levels. Further research is needed to elucidate the hippocampal and hepatic protective roles of IGF‑1 and MMP2 in acetaminophen toxicity and their potential use in therapeutic approaches.