Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training.

Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross-sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three-point bending and microcomputer tomography were measured in the femur. Follow-up experiments in human primary muscle cells were used to explore supra-physiological effects of ACE. Data were analyzed using a two-way ANOVA for treatment (ACE or placebo) and condition (exercise or non-exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey's adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p > .05). There was a treatment-by-condition effect for Young's Modulus where placebo exercise was significantly lower than placebo control (p < .05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated-AMPK was significantly increased with exercise (p < .05) and this was attenuated with ACE treatment. Furthermore, phospho-4EBP1 was depressed in the exercise group compared to the control (p < .05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p < .05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post-exercise.

Evolution of an Opioid Sparse Pain Management Program for Total Knee Arthroplasty With the Addition of Intravenous Acetaminophen.

BACKGROUND: Perioperative pain management for patients undergoing total knee arthroplasty (TKA) improves patient outcomes and facilitates recovery. In this study, we compared the effects of preoperative oral acetaminophen vs intravenous (IV) acetaminophen administered once intraoperatively and once postoperatively. METHODS: Two standardized, multimodal analgesia protocols were compared in patients undergoing primary, unilateral TKA. The oral acetaminophen cohort (OA) received doses of oral acetaminophen preoperatively and an as-needed basis postoperatively (n = 698). The IV acetaminophen cohort (IA) received 2 doses of IV acetaminophen, one intraoperative and one 6 hours postoperatively, with no oral acetaminophen given (n = 318). No other variables were significantly changed during the study period. RESULTS: The IV acetaminophen group demonstrated less narcotic usage on postoperative day 0 (OA: 13.3 mme [morphine mg equivalents], IA: 6.2 mme, P < .001) and overall usage (OA: 66.1 mme, IA: 48.5 mme, P < .001). Pain scores were statistically and clinically significantly decreased in the immediate postoperative (the first 8 hours) for the IA group (OA: patient-reported pain scores of 4.0; IA: patient-reported pain scores of 2.0, P < .001). Both groups progressed and completed their physical therapy similarly for each postoperative day. Length of stay and percent discharge home were slightly improved in the IA group as well, however did not reach statistical difference. CONCLUSION: An iterative approach to multimodal pain management after TKA led to improvements in narcotic usage, pain scores, and several quality measures. IV acetaminophen is an integral and effective part of our opioid-sparing multimodal pain regimen in TKA.

Acetaminophen-induced Acute Liver Failure Is More Common and More Severe in Women.

BACKGROUND & AIMS: Acetaminophen overdose is the leading cause of acute liver injury (ALI) and acute liver failure (ALF) in the developed world. Sex differences in acetaminophen-induced hepatotoxicity have not been described. METHODS: We collected data from the Acute Liver Failure Study Group cohort, a national registry of 32 academic medical centers in North America of adults with ALI or ALF, including 1162 patients with acetaminophen-induced ALI (n = 250) or acetaminophen-induced ALF (n = 912) from January 2000 through September 2016. We analyzed data on patient presentation, disease course, demographics, medical and psychiatric history, medication use, substance use, and details of acetaminophen ingestion. Sex differences in continuous and categorical variables were evaluated by Wilcoxon rank-sum and χ2 analysis or the Fisher exact test. Our primary aim was to evaluate sex differences in the presentation and clinical course of acetaminophen-induced acute liver injury or liver failure, and our secondary goal was to compare overall and transplant-free survival between sexes. RESULTS: Most patients with acetaminophen-induced ALI (68%) or ALF (76%) were women. Higher proportions of women than men had psychiatric disease (60% of women vs 48% of men, P < .01) and had co-ingestion with sedating agents (70% of women vs 52% of men, P < .01)-more than half of which were opioids. Higher proportions of women had severe hepatic encephalopathy (HE) (68% of women vs 58% of men), and required intubation (67% of women vs 59% of men, P values <.03). Higher proportions of women used vasopressors (26% of women vs 19% of men, P = .04) or mannitol (13% of women vs 6% of men, P < .01); proportions of male vs female patients with transplant-free survival were similar (68%). On adjusted analysis, women had higher risk of severe HE (adjusted odds ratio [AOR], 1.66; 95% CI, 1.17-2.35). We found a significant interaction between sex and co-ingestion of sedating agents (P < .01); co-ingestion increased odds of severe HE in women 2-fold (AOR, 1.86; 95% CI, 1.28-2.69; P < .01) but not in men (AOR; 0.62; 95% CI, 0.34-1.13; P = .12). CONCLUSIONS: In an analysis of the Acute Liver Failure Study Group cohort, we found acetaminophen-induced ALI and ALF to be more common among women. Women have greater critical care needs than men, and increased risk for severe HE, which could be due in part to increased use of sedatives. Future studies should investigate sex differences in acetaminophen metabolism and hepatotoxicity, particularly among users of opioids.

Decreased opioid consumption and enhance recovery with the addition of IV Acetaminophen in colorectal patients: a prospective, multi-institutional, randomized, double-blinded, placebo-controlled study (DOCIVA study).

BACKGROUND: We hypothesized that administration of IV acetaminophen alone would reduce the opioid consumption in post-operative colorectal surgery and reduce the side effects of narcotics. METHODS: Patients were randomized to receive either IV acetaminophen or placebo in addition to opioid PCA. Primary endpoints evaluated were opioid consumption and pain visual analogue scale score (PVASS) during first 48 h post-operatively. Secondary endpoints evaluated were time of return of GI function (ROGIF), time to diet ordered (TTDO), length of hospital stay (LOHS), and occurrence of ileus. RESULTS: 105 patients were enrolled and 97 remained in the study after exclusion (control group n = 50; study group n = 47). Mean ± SEs of opioid consumption in the study group was 21.5 ± 1.8 mg of morphine equivalent (ME) and 35.0 ± 3.3 mg ME at 24 and 48 h, respectively, versus 36.4 ± 4.1 mg ME and 59.7 ± 6.7 mg ME in the control group (p = 0.002 and 0.002). PVASS levels were lower in the study group at all intervals at 3, 8, 24, and 48 h (p = 0.02, 0.006, < 0.01, and 0.02). ROGIF, TTDO, and LOHS were also found to be lower in the study group (p ≤ 0.01, < 0.01, and 0.002). The rate of ileus was reduced by using IV acetaminophen (22% vs 2.1%; p = 0.004). CONCLUSIONS: IV acetaminophen helps to reduce opioid consumption for patients undergoing colorectal surgery. Additionally, there appears to be a shortened length of hospital stay, better pain control, reduced time to return of bowel function, and lower rate of post-operative ileus in patients receiving IV acetaminophen.

Randomized Prospective Trial Comparing the Use of Intravenous versus Oral Acetaminophen in Total Joint Arthroplasty.

BACKGROUND: Multimodal pain management has had a significant effect on improving total joint arthroplasty recovery and patient satisfaction. There is literature supporting that intravenous (IV) acetaminophen reduces postoperative pain and narcotic use in the total joint population. However, there are no studies comparing the effectiveness of IV vs oral (PO) acetaminophen as part of a standard multimodal perioperative pain regimen. METHODS: One hundred twenty patients undergoing hip and knee arthroplasty surgeries performed by one joint arthroplasty surgeon were prospectively randomized into 2 groups. Group 1 (63 patients) received IV and group 2 (57 patients) received PO acetaminophen in addition to a standard multimodal perioperative pain regimen. Each group received 1 gram of acetaminophen preoperatively and then every 6 hours for 24 hours. Total narcotic use and visual analog scale (VAS) scores were collected every 4 hours postoperatively. RESULTS: The 24-hour average hydromorphone equivalents given were not different between groups (3.71 vs 3.48) at 24 hours (P = .76), or at any of the individual 4-hour intervals. The 24-hour average visual analog scale scores in group 1 (IV) was 3.00 and in group 2 (PO) was 3.40 (P = .06). None of the 4-hour intervals were significantly different except the first interval (0-4 hour postoperatively), which favored the IV group (P = .03). CONCLUSION: The use of IV acetaminophen may have a role when given intraoperatively to reduce the immediate pain after surgery. Following that, it does not provide a significant benefit in reducing pain or narcotic use when compared with the much less expensive PO form.

Performance of the paracetamol-aminotransferase multiplication product in risk stratification after paracetamol (acetaminophen) poisoning: a systematic review and meta-analysis.

BACKGROUND: Risk stratification in paracetamol (acetaminophen) poisoning is crucial because hepatotoxicity is common and can be mitigated with treatment. However, current risk stratification tools have limitations. AIMS: We evaluated the diagnostic performance of the paracetamol concentration × aminotransferase multiplication product, for predicting hepatotoxicity after paracetamol overdose. METHODS: Medline, Cochrane Library and Embase were searched for eligible papers. We used random effects models to obtain pooled estimates of the likelihood ratios and diagnostic odds ratios, from which sensitivity and specificity were computed. We assessed two commonly used cut-off values of paracetamol × aminotransferase, 1500 mg/L × IU/L and 10,000 mg/L × IU/L. Using the confusion matrices of these two cut-offs, area under the summary receiver operator characteristic curve and optimal cut-off values in different clinical scenarios were established. RESULTS: Six studies comprising 5036 participants were included. In 4051 patients, using the cut-off of 1500 mg/L × IU/L, a diagnostic odds ratio of 31.90 (95%CI: 9.52-106.90), sensitivity of 0.98 (95%CI: 0.94-1.00) and specificity of 0.66 (95%CI: 0.49-0.89) were obtained. In 3983 patients, using the cut-off of 10,000 mg/L × IU/L, a diagnostic odds ratio of 99.34 (95%CI: 12.26-804.87), sensitivity of 0.65 (95%CI: 0.51-0.82) and specificity of 0.97 (95%CI: 0.95-1.00) were obtained. For staggered ingestions, the 1500 mg/L × IU/L cut-off yielded a diagnostic odds ratio of 69.53 (95%CI: 4.03-1199.75), sensitivity of 1.00 (95%CI: 0.87-1.00) and specificity of 0.74 (95%CI: 0.43-1.00). Next, using the 10,000 mg/L × IU/L cut-off in this scenario yielded a diagnostic odds ratio of 254.58 (95%CI: 11.12-5827.60), sensitivity of 0.79 (95%CI: 0.59-1.00) and specificity of 0.98 (95%CI: 0.94-1.00). The overall summary receiver operator characteristic curve was 0.91 (95%CI: 0.75-0.97), and the optimal cut-off value was 3840 mg/L × IU/L. The summary receiver operator characteristic curve in patients with staggered ingestions was 0.96 (95%CI: 0.85-0.99). The summary receiver operator characteristic curve in patients with staggered ingestions and whose paracetamol concentration was below the detectable limit of 10 mg/L at presentation was 0.97 (95%CI: 0.94-0.99). CONCLUSION: In this first meta-analysis, paracetamol × aminotransferase demonstrates its use in prognosticating hepatotoxicity in patients with paracetamol poisoning. It complements the Rumack-Matthew nomogram as it has shown promise in addressing two key limitations of the nomogram: it is usable after more than 24 h between overdose and acetylcysteine treatment, and it is applicable in staggered ingestions.

Neonatal withdrawal syndrome due to maternal codeine use.

Neonatal withdrawal from maternal drugs and medications is not uncommon. Codeine-containing analgesic preparations given to pregnant mothers for headache have been identified as a cause of neonatal withdrawal syndrome. The present case highlights the importance of obtaining a detailed maternal drug history including prescription and nonprescription drugs, and highlights the need for prenatal counselling for women who are taking narcotic-containing analgesics.

Il n'est pas rare de sevrer un nouveau-né des drogues et médicaments qu'a consommés la mère. Il est établi que les préparations analgésiques qui contiennent de la codéine et qui sont données aux femmes enceintes pour soulager les maux de tête représentent une cause de syndrome de sevrage néonatal. Le présent cas fait ressortir l'importance d'obtenir les antécédents détaillés de la mère quant à ses médicaments, qu'ils soient sur ordonnance ou en vente libre, ainsi que la nécessité de donner des conseils prénatals aux femmes qui prennent des analgésiques contenant des narcotiques.

Metabolomic Evaluation of N-Acetyl-p-Benzoquinone Imine Protein Adduct Formation with Therapeutic Acetaminophen Administration: Sex-based Physiologic Differences.

BACKGROUND: Acetaminophen (APAP)-associated transaminase elevation, induced by N-acetyl-p-benzoquinone imine (NAPQI) protein adduction, remains an area of research interest. Distinct from known genetic, physiologic, and dosage associations dictating severity of hepatic injury, no known factors predict an absence of protein adduct formation at therapeutic APAP dosing. HYPOTHESIS: Sex-based physiology is predictive of APAP-induced protein adduct formation and differential metabolite expression at therapeutic doses. METHODS: This retrospective study interrogated serum samples collected for a prior study investigating fluctuations of alanine aminotransferase (ALT) over time with 4G daily APAP dosing for ≥ 16 days in subjects from Denver, Colorado. Subjects were grouped by adduct formation (n = 184) vs no adducts (n = 20). Samples were run on ultra-high-performance liquid chromatography mass spectrometry from study days 0, 7, 16, and 31. Significant metabolite expressions were identified using t-tests with false discovery rate correction (FDR), partial least squares discriminant, and ANOVA simultaneous comparison analyses. Demographic and clinical data were explored using t-tests with FDR (age, weight, BMI, ALT) and Chi-square (sex, ethnicity, race) analyses. RESULTS: In pre-treatment samples, relative quantitation caprylic acid was expressed ninefold higher and 6-carboxyhexanoate was expressed threefold lower in subjects who did not develop adducts. Lactate had greater expression in the no adducts group (p = 0.001). Using absolute quantitation, glutathione was expressed 2.6-fold greater among no adduct subjects. Odds of males developing NAPQI protein adducts at therapeutic APAP dosing were 5.91 times lower than females (95% CI = 2.3-14.9; p = 0.0001). CONCLUSION: Multiple metabolites were differentially expressed based on adduct group and sex. Metabolites were identified unique to adduct development independent of sex. At therapeutic APAP dosing, males were less likely to develop APAP protein adducts. Further research into lipid biosynthesis and metabolism may provide further insight into physiology associated with adduct production.

A Systematic Review of the Link Between Autism Spectrum Disorder and Acetaminophen: A Mystery to Resolve.

The purpose of this study is to review the published papers investigating maternal acetaminophen (AP) use during pregnancy and its effect on the offspring's neurodevelopment, particularly autism spectrum disorders (ASD). Acetaminophen is an over-the-counter analgesic and antipyretic considered safe in pregnancy. Recent studies have found an association between acetaminophen and immune system alterations like asthma and adverse neurodevelopmental outcomes. We used online databases (PubMed/Medline/PubMed Central, Science Direct, and Google Scholar) to search the studies relevant to our topic. We screened the papers by titles, abstracts, and then full-text availability. The screened articles were checked for eligibility using relevant quality assessment tools for each study design, extracting and analyzing the data. We finalized 30 studies after the screening; 14 were ineligible. Our final selection included 16 high-quality papers - 13 prospective cohort studies, two review articles, and one meta-analysis. We found a wide range of neurodevelopmental outcomes in our data collection. So, we included autism spectrum disorders, intelligent quotient (IQ), attention-deficit/hyperactivity disorder (ADHD), isolated language, attention and executive function, communication, behavior, and psychomotor development. All studies showed an association between acetaminophen use and listed neurodevelopmental outcomes. Long-term use, increased dose, and frequency were associated with a stronger association. We extracted collective evidence from 16 studies suggesting acetaminophen's role in developing adverse neurodevelopmental outcomes. It is urgent to do more research on this association before pregnant women can be cautioned about the precise use of acetaminophen.

Opiate Use After Endoscopic Endonasal Transsphenoidal Surgery.

BACKGROUND: The literature on opiate use after endoscopic endonasal transsphenoidal surgery (EETS) is limited. OBJECTIVE: To determine the risk factors for higher opiate use following EETS and the quantity of opiates used after discharge. METHODS: A retrospective review of 144 patients undergoing EETS from July 2018 to July 2020 was conducted. Patient, tumor, and surgical factors were documented. Pain scores and medications used on postoperative days (POD) 0 and 1, and discharge prescriptions, were recorded. Opiate use was quantified using morphine milligram equivalents (MME) dose. Multiple linear regression determined risk factors independently associated with POD0 to 1 opiate use. RESULTS: On POD 0 to 1, mean pain score was 4.9/10 (standard deviation [SD] ± 2.0). Mean acetaminophen use was 3.4 tablets (SD ± 1.6; 650 mg per tablet). Mean opiate use was 35.6 MME (SD ± 36.3), equivalent to 4.7 tablets (SD ± 4.8) of oxycodone 5 mg. Multiple linear regression showed that current smokers required an additional 37.1 MME (P = .011), and patients with grade 3 intraoperative cerebrospinal fluid leaks required an additional 36.7 MME (P = .046) on POD0 to 1. On discharge, mean opiate prescription was 117.7 MME (SD ± 102.1), equivalent to 15.7 tablets (SD ± 13.6) of oxycodone 5 mg. Thirty-nine patients (27.1%) did not require prescriptions. Only 10 patients (6.9%) required opiate refill(s) within 30 days after surgery. CONCLUSION: Patients undergoing EETS have higher opiate needs compared to those undergoing endoscopic sinus surgery, although the overall requirements are still considered low. Independent risk factors associated with higher opiate use in the immediate postoperative period included current smokers and grade 3 intraoperative cerebrospinal fluid leaks.

Trends in emergency department visits for acetaminophen-related poisonings: 2011-2019. / Tendances des visites aux services des urgences pour des intoxications liées à l'acétaminophène, 2011 à 2019.

We examined trends in emergency department (ED) presentation rates for acetaminophenrelated poisonings across Canada. A total of 27123 cases of poisoning were seen in the electronic Canadian Hospitals Injury Reporting and Prevention Program (eCHIRPP) sentinel sites between April 2011 and February 2019; of these, 13.7% were related to acetaminophen use. A significant decreasing trend for both sexes was observed for unintentional poisonings (males: -10.3%; females: -8.0%). For intentional poisonings, there was a significant decrease among females only (-5.9%). Females have consistently displayed higher rates of ED presentations for both unintentional and intentional poisoning.

A total of 27123 cases of poisoning were captured in the eCHIRPP database, of which 3721 cases (13.7%) were acetaminophen related. About 50.3% of the poisonings were unintentional, 48.6% were intentional and 1.1% were of undetermined intent. There was a significant decreasing trend in acetaminophen poisonings, among all unintentional poisonings, for both males (−10.3%) and females (−8.0%). Among all intentional poisonings, there was a significant decrease for acetaminophen poisonings among females (−5.9%) but not among males. Compared to males, females had consistently higher rates of emergency department presentations for both unintentional and intentional acetaminophen-related poisonings.

Au total, nous avons relevé, sur les 27123 cas d'intoxication dans la base de données électronique du SCHIRPT, 3721 cas (13,7 %) liés à l'acétaminophène. Environ 50,3 % des intoxications étaient involontaires, 48,6 % intentionnelles et 1,1 % d'intention indéterminée. Nous avons observé une tendance décroissante significative des taux d'intoxication à l'acétaminophène au sein des intoxications involontaires chez les hommes (−10,3 %) comme chez les femmes (−8,0 %). Nous avons constaté une diminution significative des taux d'intoxication à l'acétaminophène au sein des intoxications intentionnelles chez les femmes (−5,9 %) mais pas chez les hommes. Comparativement aux hommes, les femmes présentaient des taux systématiquement plus élevés de consultation à un service des urgences pour des intoxications tant involontaires qu'intentionnelles liées à l'acétaminophène.

Idiosyncratic Drug Reaction: A Rare Mechanism of Acute Tylenol Toxicity.

Acetaminophen (APAP) is perhaps the most commonly used drug both inside and outside the hospital due to its relative safety and over-the-counter availability. Despite its safety, it can cause drug-related side effects, especially acute liver injury that can be unpredictable. Additionally, due to its variable, delayed and nonspecific symptomatology, it can pose a significant diagnostic challenge. Due to potential reversibility with an antidote and adverse outcome related to liver failure, timely recognition and treatment is key in suspected toxicity. Here we present a case of a young female who presented for the evaluation of seizure and found to have APAP-related liver failure with only 2 g of APAP taken over two days duration.

EDC IMPACT: Is exposure during pregnancy to acetaminophen/paracetamol disrupting female reproductive development?

Concern has been raised over chemical-induced disruption of ovary development during fetal life resulting in long-lasting consequences only manifesting themselves much later during adulthood. A growing body of evidence suggests that prenatal exposure to the mild analgesic acetaminophen/paracetamol can cause such a scenario. Therefore, in this review, we discuss three recent reports that collectively indicate that prenatal exposure in a period of 13.5 days post coitum in both rats and mouse can result in reduced female reproductive health. The combined data show that the exposure results in the reduction of primordial follicles, irregular menstrual cycle, premature absence of corpus luteum, as well as reduced fertility, resembling premature ovarian insufficiency syndrome in humans that is linked to premature menopause. This could especially affect the Western parts of the world, where the age for childbirth is continuously being increased and acetaminophen is recommended during pregnancy for pain and fever. We therefore highlight an urgent need for more studies to verify these data including both experimental and epidemiological approaches.

Corrigendum: Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans.

[This corrects the article on p. 54 in vol. 7, PMID: 27014068.].

Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans.

In non-febrile mouse models, high dose acetaminophen administration causes profound hypothermia. However, this potentially hazardous side-effect has not been confirmed in non-febrile humans. Thus, we sought to ascertain whether an acute therapeutic dose (20 mg⋅kg lean body mass) of acetaminophen would reduce non-febrile human core temperature in a sub-neutral environment. Ten apparently healthy (normal core temperature, no musculoskeletal injury, no evidence of acute illness) Caucasian males participated in a preliminary study (Study 1) to determine plasma acetaminophen concentration following oral ingestion of 20 mg⋅kg lean body mass acetaminophen. Plasma samples (every 20 min up to 2-hours post ingestion) were analyzed via enzyme linked immunosorbent assay. Thirteen (eight recruited from Study 1) apparently healthy Caucasian males participated in Study 2, and were passively exposed to 20°C, 40% r.h. for 120 min on two occasions in a randomized, repeated measures, crossover design. In a double blind manner, participants ingested acetaminophen (20 mg⋅kg lean body mass) or a placebo (dextrose) immediately prior to entering the environmental chamber. Rectal temperature, skin temperature, heart rate, and thermal sensation were monitored continuously and recorded every 10 min. In Study 1, the peak concentration of acetaminophen (14 ± 4 µg/ml) in plasma arose between 80 and 100 min following oral ingestion. In Study 2, acetaminophen ingestion reduced the core temperature of all participants, whereas there was no significant change in core temperature over time in the placebo trial. Mean core temperature was significantly lower in the acetaminophen trial compared with that of a placebo (p < 0.05). The peak reduction in core temperature in the acetaminophen trial was reached at 120 min in six of the thirteen participants, and ranged from 0.1 to 0.39°C (average peak reduction from baseline = 0.19 ± 0.09°C). There was no significant difference in skin temperature, heart rate, or thermal sensation between the acetaminophen and placebo trials (p > 0.05). The results indicate oral acetaminophen reduces core temperature of humans exposed to an environment beneath the thermal neutral zone. These results suggest that acetaminophen may inhibit the thermogenic mechanisms required to regulate core temperature during exposure to sub-neutral environments.

Multimodal analgesia reduces narcotic requirements and antiemetic rescue medication in laparoscopic Roux-en-Y gastric bypass surgery.

BACKGROUND: After bariatric surgery, patients are at risk for narcotic-related side effects. Multimodal pain management strategies should be used when possible to reduce the consumption of narcotic medication. The purpose of this study was to investigate whether multimodal analgesia reduces narcotic consumption and may have an influence on opioid-related side effects in patients undergoing laparoscopic Roux-en-Y gastric bypass surgery (LRYGB). METHODS: In this retrospective data analysis, we examined the data of a total of 181 consecutive patients undergoing LRYGB. In January 2011, i.v. acetaminophen became clinically available. Hydromorphone patient controlled analgesia (PCA) was replaced by i.v. acetaminophen and i.v. ketorolac (TNT-Tylenol and Toradol). The first 89 patients received postoperative hydromorphone PCA (PCA group). The next 92 patients received i.v. acetaminophen and i.v. ketorolac every 6 hours for the first 24 hours (TNT group). In the TNT group, 8 patients were excluded in the analysis. RESULTS: There were no differences in clinical characteristics between the groups except for smoking history. Patients treated with PCA required 4.2 mg hydromorphone in the postoperative period. Patients in the TNT group required 1.1 mg hydromorphone. This was a statistically significant reduction of opioids by 73.8%. After discharge from postanesthesia care unit, 34.8% of patients required antiemetic rescue medication (AERM) compared with 20.2% in the TNT group (P<.001). The relative risk (AERM/no AERM) in the postoperative period after postanesthesia care unit discharge is 1.75 (95% CI, 1.05-2.92). CONCLUSION: This study suggests that a multimodal analgesic regimen (TNT) can reduce postoperative narcotic consumption, which may lead to a reduction in the number of patients requiring AERM.