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This trial aimed to compare postoperative analgesia, opioid consumption, duration of ileus and hospital stay, and cytokine levels in patients undergoing laparoscopic cholecystectomies who received intravenous lidocaine in comparison with a control group. Prospective, longitudinal, double-blind, and randomized study. Operating room and postoperative recovery area. Forty-four American Society of Anesthesiologists I and II patients older than 17 years, undergoing laparoscopic cholecystectomy, under general anesthesia. The first group received intravenous lidocaine during the procedure until 1 hour postoperatively, whereas the second group received saline. Both groups received dipyrone and morphine patient-controlled analgesia. Pain was assessed by Visual Numeric Scale at rest and when coughing at different times after the end of the surgery. Blood samples were taken at the end of procedure and 24 hours later. The total morphine patient-controlled analgesia demand, the time for the first flatus, and the length of hospital stay were also recorded. Groups were similar in relation to sex (P= .2), age (P= .5), weight (P= .08), and length of surgery (P= .6). No differences were observed regarding the intensity of postoperative pain between the groups, either at rest (P= .76) or when coughing (P= .31), in morphine consumption (P= .9), and in the duration of ileus (P= .5) or length of hospital stay (P= .9). The inflammatory markers interleukin (IL)-1 (P= .02), IL-6 (P< .01), interferon-γ (P< .01), and tumor necrosis factor α (P< .01) showed significant reduction in the lidocaine group against the placebo group, except IL-10 (P= .01), that, because of its anti-inflammatory effects, increased its concentration. Intravenous lidocaine was not able to reduce postoperative pain, opioid consumption, and duration of ileus or length of hospital stay. However, its anti-inflammatory effect was noticeable. •IV lidocaine was used in the perioperative period of laparoscopic cholecystectomies.•No difference was observed regarding the intensity of pain between the groups.•Duration of ileus and opioid consumption were not reduced in the lidocaine group.•Lidocaine group showed reduction in inflammatory cytokine levels.

Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in human and veterinary medicine. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro-drug, which spontaneously breaks down after oral administration to structurally related pyrazolone compounds. Apart from its analgesic effect, the medication is an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic effect is a complex one, and most probably rests on the inhibition of a central cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system. Metamizole can block both PG-dependent and PG-independent pathways of fever induced by LPS, which suggests that this drug has a profile of antipyretic action distinctly different from that of NSAIDs. The mechanism responsible for the spasmolytic effect of metamizole is associated with the inhibited release of intracellular Ca2+ as a result of the reduced synthesis of inositol phosphate. Metamizole is predominantly applied in the therapy of pain of different etiology, of spastic conditions, especially affecting the digestive tract, and of fever refractory to other treatments. Co-administration of morphine and metamizole produces superadditive, antinociceptive effects. Metamizole is a relatively safe pharmaceutical preparation although it is not completely free from undesirable effects. Among these side-effects, the most serious one that raises most controversy is the myelotoxic effect. It seems that in the past the risk of metamizole-induced agranulocytosis was exaggerated. Despite the evidence showing no risk of teratogenic and embryotoxic effects, the drug must not be administered to pregnant women, although it is allowed to be given to pregnant and lactating animals. This paper seeks to describe the characteristics of metamizole in the light of current knowledge.

Chronic postoperative pain is the most common postoperative complication that impairs quality of life. Postoperative pain gradually develops into neuropathic pain. Multimodal analgesia targets multiple points in the pain pathway and influences the mechanisms of pain chronification. We investigated whether a lidocaine patch at the wound site or an infusion of metamizole and tramadol can reduce opioid consumption during laparoscopic colorectal surgery and whether the results are comparable to those of epidural analgesia. Patients were randomly divided into four groups according to the type of postoperative analgesia. Group 1 consisted of 20 patients who received an infusion of piritramide. Group 2 consisted of 21 patients who received an infusion of metamizole and tramadol. Group 3 consisted of 20 patients who received patient-controlled epidural analgesia. Group 4 consisted of 22 patients who received piritramide together with a 5% lidocaine patch on the wound site. The occurrence of neuropathic pain was also investigated. Piritramide consumption was significantly lowest in group 3 on the day of surgery and on the first and second day after surgery. Group 4 required significantly less piritramide than group 1 on the day of surgery and on the first and second day after surgery. The group with metamizole and tramadol required significantly less piritramide than groups 1 and 4 on the first and second day after surgery. On the day of surgery, this group required the highest amount of piritramide. Weak opioids such as tramadol in combination with non-opioids such as metamizole were as effective as epidural analgesia in terms of postoperative analgesia and opioid consumption. A lidocaine patch in combination with an infusion of piritramide have been able to reduce opioid consumption.

Purpose To determine the effects of high peri- and postoperative doses of vitamin C administration on severity of pain in postoperative period and functional outcome of the patients with trochanteric fracture treated with intramedullary nailing during a three-month follow-up. Methods A prospective, randomised, full-scale study included 74 patients who were randomly divided into vitamin C (intervention) and control groups. In the intervention group, patients received vitamin C perioperatively by intravenous route for 2 days, and oral vitamin C for 38 days postoperatively. Baseline characteristics, postoperative metamizole consumption, visual analogue scale (VAS) score, Harris hip score (HHS) value, and the prevalence of complications were evaluated in both groups. Results No significant differences were noted between the groups regarding age, gender, length of hospitalisation, and distribution in fracture type as well as in postoperative HHS values. Postoperative metamizole consumption was notably higher in the control group compared to the vitamin C group ( p  = 0.003). Postoperative VAS scores were higher in the control group than in the vitamin C group at all time follow-ups ( p  < 0.05). The group variable significantly contributed to VAS score, and age and gender variables significantly contributed to HHS value. Conclusion Significant reduction of subjective pain levels and lower analgesic consumption was found in patients who received vitamin C, suggesting that it should be considered as an adjuvant agent for analgesia in patients with hip fracture.

Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries have banned it due to the risk of agranulocytosis, skin necrosis, and other serious adverse effects. To assess the safety of metamizole compared to other commonly used non-opioid analgesics (paracetamol, ibuprofen, and acetylsalicylic acid). An overview of systematic reviews. The searches were performed in the PubMed, Cochrane Library, Embase, Scopus and LILACS databases. Systematic reviews of randomized and nonrandomized clinical trials with adult patients with mild to moderate pain that assessed the adverse effects of metamizole were included. A methodological quality assessment was performed through ROBIS. The protocol of this systematic review was submitted to the International Prospective Register of Systematic Reviews (Prospero, CRD42021295272). Of 387 identified studies, four were included, with a total of 20,643 participants, all submitted to a single dose by oral, intramuscular, or intravenous route. No study reported a serious adverse effect. However, 60 of 778 patients (7.7%) who used metamizole; 120/828 (14.5%) who used acetylsalicylic acid; 56/443 (12.6%) who used paracetamol; and 27/213 (12.7%) who used ibuprofen had mild adverse effects. A complementary statistical analysis showed that metamizole, at any dose, has a 38.8% lower chance of adverse effects compared to paracetamol and 46.8% compared to acetylsalicylic acid. The results shows that metamizole is a safe drug with evidence of a lower incidence of adverse effects compared to paracetamol and acetylsalicylic acid.

Purpose The prodrug metamizole is prescribed intravenously for postoperative pain in children, including off-label use in infants < 1 year. We aimed to assess the pharmacokinetics of the main metabolites of metamizole in children aged 3–72 months. Methods A single dose of 10 mg/kg metamizole was administered intravenously for postoperative analgesia. Pharmacokinetic samples were drawn at predefined time points. Pharmacokinetics of the main active metabolite 4-methylaminoantipyrine and three other metabolites was characterized by both non-compartmental and population pharmacokinetic analysis. AUC 0–inf of 4-methylaminoantipyrine was calculated by non-compartmental analysis for two age cohorts (3–23 months, 2–6 years) and compared with the 80–125% range of adult dose–adjusted reference exposure (AUC ref ). Population pharmacokinetic analysis investigated age and weight dependency of the pharmacokinetics and optimal dosing strategies to achieve equivalent adult exposure. Results A total of 25 children aged 5 months–5.8 years (7.8–24.8 kg) with at least one concentration sample were included; 19 children had ≥ 5 predefined samples up to 10 h after metamizole dose administration. AUC 0–inf of 4-methylaminoantipyrine in children 2–6 years was 29.9 mg/L/h (95% CI 23.4–38.2), significantly lower than AUC ref (80–125% range 39.2–61.2 mg/L/h). AUC 0–inf of 4-methylaminoantipyrine in infants < 2 years was 43.6 mg/L/h (95% CI 15.8–119.0), comparable with AUC ref , while infants < 12 months showed increased exposure. Observed variability could be partially explained by covariates weight and age. Conclusions Age-related changes in pharmacokinetics of 4-methylaminoantipyrine requires reduced weight–based IV dosing in infants < 1 year compared with infants and children up to 6 years (5 versus 10–20 mg/kg) to achieve equivalent adult exposure. Trial registration ClinicalTrials.gov identifier: NCT02660177 .

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of hypersensitivity reactions, with pyrazolones the most frequent drugs inducing selective reactions. Immediate selective hypersensitivity to pyrazolones is thought to be mediated by specific-IgE. Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved. Here we investigated whether main metabolites of metamizole (dipyrone) in human could be involved in the immune response using the basophil activation test (BAT). We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug. Our findings indicate that pyrazolone metabolites are useful for improving the in vitro diagnosis of allergic reactions to metamizole.

Dipyrone (metamizol) is regularly used in critical care for pain and fever treatment, especially in Germany and Spain. However, indication for antipyretic therapy in critically ill patients is currently unclear and data for both the risk and benefit of dipyrone treatment in the intensive care environment are scarce. We hypothesized that antipyretic efficiency of dipyrone would not exceed antipyretic efficiency of acetaminophen. We therefore aimed to compare temperature courses in critically ill patients receiving either intravenous dipyrone, acetaminophen or no antipyretic medication. We included 937 intensive care unit (ICU) patients with body temperature recordings of at least 37.5°C. We investigated temperature decrease associated with dipyrone or acetaminophen and additionally compared it to an untreated control group. Within the eight-hour study interval, maximum body temperature decrease in patients without antipyretic medication was -0.6°C (IQR: -1.0 to -0.4°C; n = 315). Maximal decrease in body temperature was higher both with dipyrone (-0.8°C (IQR: -1.2 to -0.4°C); p = 0.016; n = 341) and acetaminophen (-0.9°C (IQR: -1.6 to -0.6°C); p<0.001; n = 71), but did not differ between dipyrone and acetaminophen (p = 0.066). As compared to untreated patients, dipyrone only led to a marginal additional decrease in body temperature of only -0.1°C. Maximum of antipyretic effectiveness was reached four hours after administration. Antipyretic effectiveness of dipyrone in ICU patients may be overestimated. Given the lack of prospective data, clinical evidence for antipyretic dipyrone therapy in the ICU is insufficient and warrants further critical evaluation.

Background Dipyrone (Metamizole) is a potent pain reliever and fever reducer with muscle relaxant properties, most commonly used as an analgesic and antipyretic agent. Despite the fact that it has been banned in many high-income countries following confirmed studies of fatal agranulocytosis and adverse drug reactions, it is still widely used in various countries of the world. However, the antipyretic therapeutic indications of dipyrone in febrile children are currently unknown, and there is little information on the advantages and disadvantages of using dipyrone in febrile children. In febrile children, we expected that dipyrone’s antipyretic effectiveness wouldn’t be any more effective than ibuprofen. Therefore, the purpose of this research is to evaluate the effectiveness of oral dipyrone and oral ibuprofen as antipyretics in febrile children. Methods Several databases, including PubMed, Scopus, Web of Science, and Cochrane Library, were searched thoroughly using a pre-established search strategy for potential research. The studies included in this analysis comprised randomized controlled trials that compared the antipyretic effects of oral ibuprofen and oral dipyrone in febrile children. Data analysis was carried out using RevMan 5.4 software. Results Three studies were selected among the 27 publications we discovered to be applicable, and they underwent qualitative and quantitative analysis. The pooled analysis revealed no discernible difference between oral dipyrone and oral ibuprofen in terms of their antipyretic effects (Mean difference (MD) = 0.06; 95% confidence interval (CI): -0.08, 0.20). Conclusion Both oral dipyrone and ibuprofen are effective in reducing high-temperature levels in febrile children without any significant difference.

The cold pressor test (CPT) is widely implemented and offers a simple, experimental acute pain model utilizing cold pain. Previous trials have frequently paired the CPT with opioids in order to investigate the mechanisms underlying pharmacological analgesia, due to their known analgesic efficacy. However, opioid side effects may lead to unblinding and raise concerns about the safety of the experimental setting. Despite the established clinical efficacy of dipyrone (metamizole), its efficacy, tolerability, and safety in cold pressor pain has not been systematically addressed to date. This pooled analysis included data of 260 healthy volunteers from three randomized, placebo‐controlled, double‐blind substudies using the CPT following a pre‐test‐post‐test‐design. These substudies allow for comparing a single dose of 800 mg dipyrone with two different doses of the opioid tilidine/naloxone (50/4 mg and 100/8 mg, respectively). Outcomes included pain intensity ratings, pain tolerance, medication‐attributed side effects, as well as changes of blood pressure and heart rate. We demonstrate that both opioid doses and dipyrone had a comparable, significant analgesic effect on cold pressor pain. However, dipyrone was associated with significantly less self‐reported adverse effects and these were not significantly different from those under placebo. These results indicate that the combination of dipyrone and the CPT provides a safe, tolerable, and effective experimental model for the study of pharmacological analgesia. In combination with a CPT, dipyrone may be useful as a positive control, or baseline medication for the study of analgesic modulation.