Uterotrophic and in vitro screening for (anti)estrogenic activity of dipyrone.

Dipyrone is a commonly used analgesic in many countries and there is limited data on its possible endocrine disrupting effects. We performed a screening for in vivo and in vitro anti(estrogenic) activity of dipyrone. For the in vivo uterotrophic assay, immature female rats (22-days-old) were treated daily by oral gavage for three days with different doses of dipyrone alone (50, 100, 200 mg/kg/day) and associated with three ethynylestradiol (EE) doses (1, 3 and 10 µg/kg/day), which were based on a dose-response curve experiment. The uterine weight was used as a biomarker for estrogenicity. In a parallel in vitro approach, we used a yeast-based transcriptional activation reporter gene assay (Yeast Estrogen Screening - YES) for assessment of estrogenic agonistic and antagonistic effects of dipyrone and its main metabolites 4-methylaminoantipyrine (MAA) and 4-aminoantipyrine (AA). In the uterotrophic assay, animals that received EE at 1, 3 and 10 µg/kg/day showed an increase in relative uterine weight compared with vehicle-only rats (canola oil). Dipyrone did not increase uterine weight at any dose tested (50, 100 and 200 mg/kg/day) in relation to vehicle control, indicating absence of estrogenic activity. Furthermore, co-administration of dipyrone (50 and 200 mg/kg/day) and EE (1, 3 or 10 µg/kg/day) was unable to block EE estrogenic action in comparison to the groups treated with EE alone, indicating absence of antiestrogenic activity. In the YES assay dipyrone and its metabolites did not demonstrate estrogen agonistic or antagonistic properties in the yeast cells. These results suggest that dipyrone and its metabolites do not produce (anti)estrogenic effects in vivo or in vitro.

Tilidine and dipyrone (metamizole) in cold pressor pain: A pooled analysis of efficacy, tolerability, and safety in healthy volunteers.

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.

Drug dosing using estimated glomerular filtration rate: Misclassification due to metamizole interference in a creatinine assay.

BACKGROUND: The estimated glomerular filtration rate is a rather important measurement for patients under intensive care, since they often receive several drugs, and impaired renal function may result in misleading dosing. The estimated glomerular filtration is derived from mathematical models using serum creatinine, a measurement that suffers interference of some drugs, such as metamizole. This study intended to evaluate the impact on patient stratification for dose adjustment of two antimicrobials (meropenem and vancomycin) caused by metamizole interference in creatinine measurement by dry chemistry. METHODS: A cross-sectional study was conducted with a group of 108 hospitalized patients under metamizole prescriptions at fixed intervals. Serum creatinine concentrations were determined by enzymatic dry chemistry and Jaffé assays, and the estimated glomerular filtration rate was calculated through the CKD-EPI equation. Patients were stratified in groups according to their estimated glomerular filtration rate for drug dosing of vancomycin and meropenem. RESULTS: Creatinine values were significantly lower in measurements performed by the dry chemistry method in comparison to Jaffé assay (P < 0.0001) when patients are under metamizole treatment. A significant bias (-40.3%) was observed between those two methods, leading to a significant difference (P < 0.0001) in patient classification according to renal function using the CKD-EPI equation for dosing adjustment. CONCLUSIONS: During the validity of metamizole treatment, the stratification for drug dosing by the estimated glomerular filtration rate is not reliable if the creatinine measurement is done through dry chemistry. Clinical and laboratory staff must be aware of these limitations and cooperate to optimize pharmacotherapy.

¿Estamos sobredosificando el metamizol por vía parenteral? / Are we overdosing parenteral metamizole?

No disponible

Sacroiliac joint injections with the guidance of three-dimensional cone beam computed tomography (3D-CBCT) and fluoroscopy fusion.

BACKGROUND: We describe our diagnostic sacroiliac joint (SIJ) injection technique under the guidance of three-dimensional cone beam computed tomography (3D-CBCT) fused with real-time fluoroscopy. METHODS: A retrospective review of 17 patients (mean age 55.4 (range 40-74) years) who received a total of 23 diagnostic SIJ injections between March 2016 and November 2017 were performed. Pre- and post-procedure pain scores were reviewed from the medical records and then these findings were correlated with which patients were and were not diagnosed with SIJ pain by clinical management. The final diagnosis of SIJ-related pain was made in cases with at least 50% symptomatic improvement following SIJ-specific pain treatments. RESULTS: Some 87% (n=20/23) of injections achieved more than 50% pain relief after the diagnostic SIJ injection. The final diagnosis of the target SIJ-related pain after follow-up and management was found in 90% (n=18/20) of cases. There were two cases with positive tests diagnosed as non-SIJ pain including one with the diagnosis of femuroacetabular impingement and one with pain related to loosening of knee hardware. The sensitivity, specificity, positive predictive value, and negative predicative value of diagnostic SIJ injections were 100%, 60%, 89%, and 100%, respectively, with a 40% false-positive rate. There were no procedure-related complications. CONCLUSION: 3D-CBCT fused with real-time fluoroscopy for SIJ injection is accurate and safe.

4-Methylamino antipyrine determination in human plasma by high-performance liquid chromatography tandem mass spectrometry.

In the present study, a simple and rapid method for metamizole metabolite 4-methylamino antipyrine (MAA) determination in human plasma was developed, validated and successfully applied to a clinical trial. Chromatographic separation was achieved in HILIC mode on a YMC-Pack SIL column (100 × 2.0 mm; S-5 µm, 30 nm), with a mobile phase consisting of acetonitrile, water and formic acid. Protein precipitation of a small plasma volume using acetonitrile was selected for sample preparation. The multiple reaction monitoring transitions in the positive ionization mode were m/z 218.2 → 56.2 for MAA and m/z 221.2 → 56.2 for MAA-d3 (IS, internal standard). Concentration levels of MAA calibration standards were in the range of 0.100-20 µg/ml. Metamizole conversion into MAA in both water and organic media was investigated, and the level of the conversion in commercially available injection solutions was estimated.

Postoperative pain after tonsillectomy - the value of standardized analgesic treatment protocols.

OBJECTIVE: To alleviate pain after tonsillectomy (TE) with escalating gradual treatment protocols in a prospective trial. MATERIALS & METHODS: Following TE, 83 consecutive adult patients were treated with two different four-staged escalating analgesic protocols. Metamizole served as basic medication in protocol 1 (PT1; n = 44), whereas with protocol 2 (PT2; n = 39) ibuprofen was applied as baseline analgesic. Both protocols were escalated according to the patient´s needs to metamizole and ibuprofen vice versa and additional weak to strong opioids. The primary efficacy endpoint was defined as the minimum and maximum pain as well as pain on ambulation (NRS, 0-10). Secondary endpoints comprised analgesic score, patient satisfaction and treatment-related side-effects. RESULTS: Both patient groups exhibited similar demographic characteristics (PT1: Ø 28.8 years; 64% ♀ and PT2: Ø 26.6 years; 56% ♀). Maximum pain (6.7 ±â€¯1.9 vs. 7.6 ±â€¯1.6, t(81) = -2.254, p = 0.027) and pain on ambulation (5.0 ±â€¯1.8 vs. 5.8 ±â€¯1.8, t(81) = -2.114, p = 0.038) were significantly higher with PT2. 68.2% of patients with PT1 needed an escalation of analgesic treatment compared to 100% with PT2 (p < 0.001). The opioid consumption was also significantly higher with PT2 (43.2% vs. 71.8%, p < 0.001). There were no significant differences regarding functional impairments, side-effects and patient satisfaction (7.0 ±â€¯2.0 vs. 7.4 ±â€¯2.4, t(79) = -0.897, p = 0.373). CONCLUSION: Both treatment protocols yielded in a high degree of patient satisfaction but dissatisfactory pain relief following TE. Metamizole can be recommended as a basic medication allowing for improved pain relief. Reported pain intensities were independent of the amount of opioid intake. Further research is mandatory to standardize and improve analgesic treatment after TE.

Cerebellar syndrome after occipital nerve block: A case report.

BACKGROUND: Occipital nerve blocks are commonly used in the treatment of different types of refractory headaches. The procedure is considered safe, and serious complications have rarely been described. CASE PRESENTATION: We report a serious complication of occipital nerve blockade secondary to the penetration of local anesthetic and non-steroidal anti-inflammatory drugs into the posterior fossa in a patient affected by type I Arnold Chiari malformation. CONCLUSIONS: This case reminds that a proper injection technique is mandatory to avoid potentially severe complications when performing occipital nerve blocks.

Bloqueo del plano del erector espinal como manejo de dolor neuropático en paciente pediátrico postquemado / Erector spinalis plane block as a neuropathic pain management in post-burned pediatric patient

El manejo del dolor es una pieza crítica en el cuidado general del niño quemado. El dolor neuropático es una de sus consecuencias frecuentes, el cual puede aparecer al inicio o durante el proceso de cicatrización de heridas, acompañándose de sintomatología predominantemente por estimulación del sistema nervioso simpático, siendo su manejo un reto importante. El bloqueo del plano del erector espinal (ESP) es una técnica regional novedosa que se ha utilizado en diferentes tipos de cirugía, con resultados prometedores. Actualmente, el bloqueo ESP en la población pediátrica se viene realizando para cirugías de tórax, abdomen, cadera y genitales, con solo pocos informes. Hasta donde sabemos, el bloqueo ESP para dolor neuropático en niños aún no se ha reportado. El presente informe sugiere que el bloqueo ESP torácico realizado a nivel T4 podría proporcionar una analgesia amplia y efectiva en el dolor neuropático además de regular la sintomatología simpática, secundaria a los cambios fisiopatológicos relacionados con el grado de quemadura

Pain management is a critical piece in the general care of the burned child. Neuropathic pain is one of its frequent consequences, which may appear at the beginning or during the wound healing process, accompanied by symptoms predominantly due to stimulation of the sympathetic nervous system, its management being an important challenge. The spinal erector plane (ESP) block is a novel regional technique that has been used in different types of surgery, with promising results. Currently, the ESP block in the pediatric population has been performed for thorax, abdomen, hip and genital surgeries, with only a few reports. As far as we know, ESP block for neuropathic pain in children has not yet been reported. The present report suggests that the thoracic ESP blockade performed at the T4 level could provide a wide and effective analgesia in neuropathic pain in addition to regulating sympathetic symptomatology, secondary to the pathophysiological changes related to the degree of burn

Role of ß-Caryophyllene in the Antinociceptive and Anti-Inflammatory Effects of Tagetes lucida Cav. Essential Oil.

Tagetes lucida Cav. (Asteraceae) is an ancient medicinal plant commonly used to alleviate pain. Nevertheless, scientific studies validating this property are lacking in the literature. Animal models of pain were used to evaluate the antinociceptive and anti-inflammatory activities of T. lucida essential oil (TLEO) and a bioactive metabolite. The chemical constitution and possible toxicity of the extract and the mechanism of action of ß-caryophyllene were also explored. Temporal course curves and dose-response graphics were generated using TLEO (0.1-10 mg/kg or 3.16-31.62 mg/kg) and ß-caryophyllene (3.16-10 mg/kg). Metamizole (80 mg/kg) and indomethacin (20 mg/kg) were used as reference drugs in the formalin assay and writhing test in rats and mice, respectively. The ß-caryophyllene mechanism of action was explored in the presence of naloxone (1 mg/kg), flumazenil (10 mg/kg), WAY100635 (0.16 mg/kg), or nitro-l-arginine methyl ester (L-NAME) (20 mg/kg) in the formalin test in rats. GC/MS analysis demonstrated the presence of geranyl acetate (49.89%), geraniol (7.92%), and ß-caryophyllene (6.27%). Significant and dose-dependent antinociceptive response was produced by TLEO and ß-caryophyllene without the presence of gastric damage. In conclusion, ß-caryophyllene was confirmed as a bioactive compound in the T. lucida analgesic properties by involving the participation of receptors like opioids, benzodiazepines, and Serotonin 1A receptor (5-HT1A), as well as nitric oxide.

Intake of aspirin prior to metamizole does not completely prevent high on treatment platelet reactivity.

PURPOSE: Metamizole can sterically inhibit aspirin (ASA) from binding to cyclooxygenase 1 (COX1). It is recommended that ASA should be taken 30 min prior to metamizole to maintain the irreversible inhibition of arachidonic acid (AA)-induced platelet aggregation. We aimed to analyse the inhibitory effect of ASA and metamizole on AA-induced platelet aggregation over the course of the day. METHODS: We analysed hospitalized patients who ingested ASA at least 30 min prior to metamizole (recommended dosing group, n = 15), metamizole prior or simultaneously with ASA (not recommended dosing group, n = 16) and patients with unknown or mixed intake (mixed dosing group, n = 5). AA-induced light transmission (LTA) and impedance aggregometry (IA) were measured before, 1-2 and 5-6 h after the intake of ASA ± metamizole. RESULTS: Maximum AA-induced LTA prior to the intake of ASA was significantly lower and the rate of high on treatment platelet reactivity (HTPR) higher in the recommended compared with the not recommended dosing group (19.6% vs. 46.9%, p = 0.011 and 4/15 vs. 12/16 patients, p = 0.017). There was no difference when IA was used. Maximum AA-induced LTA after the intake of ASA ± metamizole was lower in patients in the not recommended but not in the recommended dosing group. All patients with HTPR in the recommended dosing group had regular inhibition of AA-induced LTA after discontinuation of metamizole. CONCLUSION: Co-medication of ASA and metamizole significantly influences platelet inhibition with variations during the day and can cause HTPR in patients taking ASA prior to metamizole or simultaneously.

Metamizole for Postoperative Pain in Pediatric Patients Undergoing Subarachnoid Anesthesia.

BACKGROUND: Efficient postoperative pain management, which is aimed at decreasing the risk of complications and drug-induced side effects, without affecting the quality of analgesia, is part of today's concept of enhanced recovery after surgery, that is, fast-track surgery. STUDY QUESTION: The objective of this study was to determine whether effective management of acute postoperative pain was possible without opioids, while avoiding complications, drug-induced side effects, and suboptimal treatment. Introduction of metamizole, which has regained popularity, into a multimodal analgesia regimen was used, as opioids are not routinely administered. STUDY DESIGN: The study was prospective, observational, unrandomized, and without the control group. MEASURES AND OUTCOMES: This study was performed in a pediatric hospital with 300 beds and an average of 1700 annual surgical interventions. The study group comprised 378 patients aged 1-17 years, undergoing lower abdominal or limb surgery between June 2016 and June 2017. Children underwent subarachnoid anesthesia combined with intravenous sedation and received not routinely but on demand postoperative opioid analgesia. The pain was self-assessed by the pediatric patient or was assessed by the nurse using pain scores. RESULTS: Metamizole proved to be safe, efficient, and very well tolerated by children. Multimodal analgesia using acetaminophen, nonsteroidal anti-inflammatory drug with metamizole for the treatment of moderate to severe pain in children undergoing surgery, required a single opioid dose in 292 patients (77.24%) of the 378 in this study. CONCLUSIONS: In pediatric patients undergoing surgery, subarachnoid anesthesia combined with intravenous sedation, multimodal analgesia that includes metamizole, and nonpharmacological complementary therapies in pain management enable avoidance or reduction of opioids to a single dose, without undertreatment. There is also a minimum of anesthesia, accelerated children's recovery and a rapid return to presurgical levels of function.

Evaluation of postoperative pain and toxicological aspects of the use of dipyrone and tramadol in cats.

OBJECTIVES: The aim of this study was to evaluate the effects of dipyrone and tramadol, used for 5 days, on postoperative pain, hematological and biochemical parameters, and oxidative markers on erythrocytes. METHODS: Twenty-eight healthy cats underwent ovariohysterectomy and were randomly allocated to four groups (each n = 7), according to the postoperative treatment administered intravenously: control (saline 1 ml q8h), DIP1 (dipyrone 25 mg/kg q24h), DIP2 (dipyrone 25 mg/kg q12h) and DIP3 (dipyrone 25 mg/kg q8h). All animals received tramadol (2 mg/kg q8h). Pain was assessed by visual analog (VAS), multidimensional UNESP and Glasgow pain scales for cats preoperatively and at 3, 6, 12, 24, 36 and 48 h after extubation. Venous blood was collected daily for 5 days, and on day 10, to perform a complete blood count (CBC) and determine the percentage of Heinz bodies (HBs). Serum biochemistry was evaluated preoperatively and on days 5 and 10; superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) and lipoperoxidation were evaluated preoperatively and on days 3, 5 and 10. RESULTS: Control cats had higher pain scores than DIP3 cats by UNESP (P = 0.0065), and DIP2 (P = 0.0035) and DIP3 cats (P = 0.0108) by VAS 3 h postoperatively. Rescue analgesia was required by two animals in the control group and one each in the DIP1 and DIP2 groups. There was no difference in SOD or CAT among groups. On day 5, MPO was more active in DIP2 than in DIP3 cats (P = 0.0274). No difference in lipoperoxidation among treatment and control cats was found. CBC remained constant and without statistical difference among groups. Control, DIP2 and DIP3 cats presented a similar percentage of HBs on day 10. Biochemical variables were similar among groups and times. CONCLUSIONS AND RELEVANCE: The administration of dipyrone in cats, when used in combination with tramadol, did not ensure better analgesia than tramadol alone. Dipyrone did not significantly affect biochemical variables and oxidative markers, despite minimal, clinically irrelevant, hematological differences between groups.

[Perioperative hypothermia in dogs receiving combined administration of acepromazin and metamizol]. / Untersuchung der perioperativen Hypothermie bei kombinierter Gabe von Acepromazin und Metamizol beim Hund.

OBJECTIVE: Evaluation the development of perioperative body temperature while administrating a combination of acepromazine and metamizol (AM) versus anesthesia with acepromazine (A) alone. MATERIAL AND METHODS: In this prospective, quasi-randomized controlled study 20 dogs undergoing standardized tibial plateau leveling osteotomy were alternatingly assigned to group A or group AM (n = 10 each). The patients' body temperature values were recorded from the time of premedication up to its post-surgical return to reference values. RESULTS: Body temperature decreases during anesthesia in both groups were comparable (p = 0.12). Postoperatively on the other hand, temperature development differed significantly between the two groups (p = 0.0455). In 6 dogs of the group AM, body temperature continued to decrease following extubation prior to returning to normothermic values. CONCLUSION: Intraoperatively, all patients developed hypothermia, regardless of the investigated anesthetic medication administered. Postoperatively, patients not receiving metamizol reached normothermia more rapidly.

The use of analgesics and risk of self-medication in an urban population sample: cross-sectional study / Uso de analgésicos e o risco da automedicação em amostra de população urbana: estudo transversal

Abstract Background and objectives: There are few data in the literature characterizing the pattern of analgesic use in Latin American countries, including Brazil. Little is known about the undertreatment of pain and its influence on the habit of self-medication with analgesics. The aim of this study is to define the pattern of analgesic use among chronic pain patients and its potential association with self-medication with analgesics. Method: Cross-sectional observational study with an urban population sample. Chronic pain was defined as a pain lasting for at least 90 days. The study was approved by the Research Ethics Committee of the institution. Results: 416 subjects were included; 45.7 % (n = 190) had chronic pain, with females (72.3 %; p = 0.04) being the most affected. Self-medication with analgesics is practiced by 78.4% of patients with chronic pain. The most common current analgesic treatment consists of non-steroidal anti-inflammatory drugs (dipyrone and acetaminophen). Weak opioids are rarely used and only 2.6% of subjects with chronic pain were taking these analgesics. None of the subjects were taking potent opioids. Conclusions: The practice of self-medication with analgesics is frequent among patients with chronic pain, which may be due to the underprescription of more potent analgesics, such as opioids. It can also be said that, given the data presented, there is no crisis of recreational opioid use in the studied population.

Resumo Justificativa e objetivos: Há poucos dados na literatura que caracterizam o padrão de uso de analgésicos na América Latina e no Brasil. Também se sabe pouco sobre o subtratamento da dor e sua influência no hábito de automedicação analgésica. O objetivo desta pesquisa é definir o padrão de uso de analgésicos entre os portadores de dor crônica (DC) e a sua potencial associação à automedicação analgésica. Método: Estudo observacional transversal com amostra de população urbana. A dor crônica foi definida como aquela presente por pelo menos 90 dias. A pesquisa foi aprovada pelo Comitê de Ética em Pesquisa institucional. Resultados: Foram incluídos 416 indivíduos; 45,7% (n = 190) portadores de dor crônica, sendo os do sexo feminino (72,3%; p = 0,04) os mais acometidos. A automedicação analgésica é praticada por 78,4% dos portadores de dor crônica. O tratamento analgésico vigente mais frequente é composto pelos anti-inflamatórios não esteroides (AINES), dipirona e paracetamol. Os opioides fracos são pouco usados e apenas 2,6% dos indivíduos com dor crônica fazem uso desses analgésicos. Nenhum dos indivíduos estava em uso de opioides potentes. Conclusões: A prática de automedicação analgésica é frequente entre os portadores de dor crônica, o que pode ser consequência da pouca prescrição de analgésicos mais potentes, como os opioides. Pode-se também dizer que, pelos dados apresentados, não ocorre uma crise de uso recreativo de opioides na população estudada.

Implantação de um protocolo de manejo de dor e redução do consumo de opioides na unidade de terapia intensiva: análise de série temporal interrompida / Pain management protocol implementation and opioid consumption in critical care: an interrupted time series analysis

RESUMO Objetivo: Avaliar o impacto de um protocolo de manejo da dor e redução do consumo de opioides no consumo geral de opioides e nos desfechos clínicos. Métodos: Estudo em centro único, quasi-experimental, retrospectivo, de coortes antes e depois. Utilizamos uma série temporal interrompida para analisar as alterações no nível e na tendência de utilização de diferentes analgésicos. Foram usadas comparações bivariadas nas coortes antes e depois, regressão logística e regressão quantílica para estimativas ajustadas. Resultados: Incluímos 988 pacientes no período pré-intervenção e 1.838 no período pós-intervenção. O consumo de fentanil teve ligeiro aumento gradual antes da intervenção (β = 16; IC95% 7 - 25; p = 0,002), porém diminuiu substancialmente em nível com a intervenção (β = - 128; IC95% -195 - -62; p = 0,001) e, a partir de então, caiu progressivamente (β = - 24; IC95% -35 - -13; p < 0,001). Houve tendência crescente de utilização de dipirona. A duração da ventilação mecânica foi significantemente menor (diferença mediana: - 1 dia; IC95% -1 - 0; p < 0,001), especialmente para pacientes mecanicamente ventilados por períodos mais longos (diferença no 50º percentil: -0,78; IC95% -1,51 - -0,05; p = 0,036; diferença no 75º percentil: -2,23; IC95% -3,47 - -0,98; p < 0,001). Conclusão: Um protocolo de manejo da dor conseguiu reduzir o consumo de fentanil na unidade de terapia intensiva. Esta estratégia se associou com menor duração da ventilação mecânica.

ABSTRACT Objective: To evaluate the impact of an opioid-sparing pain management protocol on overall opioid consumption and clinical outcomes. Methods: This was a single-center, quasi-experimental, retrospective, before and after cohort study. We used an interrupted time series to analyze changes in the levels and trends of the utilization of different analgesics. We used bivariate comparisons in the before and after cohorts as well as logistic regression and quantile regression for adjusted estimates. Results: We included 988 patients in the preintervention period and 1,838 in the postintervention period. Fentanyl consumption was slightly increasing before the intervention (β = 16; 95%CI 7 - 25; p = 0.002) but substantially decreased in level with the intervention (β = - 128; 95%CI -195 - -62; p = 0.001) and then progressively decreased (β = - 24; 95%CI -35 - -13; p < 0.001). There was an increasing trend in the utilization of dipyrone. The mechanical ventilation duration was significantly lower (median difference: - 1 day; 95%CI -1 - 0; p < 0.001), especially for patients who were mechanically ventilated for a longer time (50th percentile difference: -0.78; 95%CI -1.51 - -0.05; p = 0.036; 75th percentile difference: -2.23; 95%CI -3.47 - -0.98; p < 0.001). Conclusion: A pain management protocol could reduce the intensive care unit consumption of fentanyl. This strategy was associated with a shorter mechanical ventilation duration.

[The use of analgesics and risk of self-medication in an urban population sample: cross-sectional study]. / Uso de analgésicos e o risco da automedicação em amostra de população urbana: estudo transversal.

BACKGROUND AND OBJECTIVES: There are few data in the literature characterizing the pattern of analgesic use in Latin American countries, including Brazil. Little is known about the undertreatment of pain and its influence on the habit of self-medication with analgesics. The aim of this study is to define the pattern of analgesic use among chronic pain patients and its potential association with self-medication with analgesics. METHOD: Cross-sectional observational study with an urban population sample. Chronic pain was defined as a pain lasting for at least 90 days. The study was approved by the Research Ethics Committee of the institution. RESULTS: 416 subjects were included; 45.7% (n=190) had chronic pain, with females (72.3%; p=0.04) being the most affected. Self-medication with analgesics is practiced by 78.4% of patients with chronic pain. The most common current analgesic treatment consists of non-steroidal anti-inflammatory drugs (dipyrone and acetaminophen). Weak opioids are rarely used and only 2.6% of subjects with chronic pain were taking these analgesics. None of the subjects were taking potent opioids. CONCLUSIONS: The practice of self-medication with analgesics is frequent among patients with chronic pain, which may be due to the underprescription of more potent analgesics, such as opioids. It can also be said that, given the data presented, there is no crisis of recreational opioid use in the studied population.

Acute intermittent porphyria: analgesia can be dangerous.

Acute intermittent porphyria (AIP) is a rare condition, a metabolic disorder of the haem biosynthesis. An acute crisis of AIP can present as a combination of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness and neurological symptoms in the absence of others obvious causes. We report the case of a 53-year-old woman, who was previously diagnosed with AIP 5 weeks after therapeutic suspension has developed an acute disease exacerbation. During hospitalisation, further exacerbation has occurred after analgesia with metamizole. Glucose and hemin infusions resulted in slow improvement. Physical rehabilitation was crucial to peripheral polyneuropathy recovery. Taking into account the porphyrinogenic effect described for metamizole, this drug might have triggered the second attack. Clinical history was sufficient to suspect the diagnosis and to start the treatment immediately, preventing important sequelae.

Reparación multicapa de la fístula palatina con interposición de matriz de colágeno / Multilayer repair of palatal fistula with an interpositional collagen matrix

Objetivo. La fístula palatina tras la reparación del paladar fisurado aparece en un 7,7- 35% de pacientes. Presentamos dos casos de fístula palatina, detallando la técnica de reparación multicapa con injerto in-terposicional de colágeno. Material y métodos. Paciente 1: niña con fisura de paladar blando, operada mediante técnica de Furlow. Se programa reintervención por fístula secundaria tipo III de Pittsburgh. Paciente 2: varón con fisura de paladar blando, operado mediante técnica de Furlow. Se programa reintervención por fístula secundaria tipo V. Resultados. Reparación multicapa mediante flap rotacional y matriz de colágeno entre las capas nasal y oral. Refuerzo con adhesivo hemostático de fibrina. Ausencia de recidiva tras 2 años de seguimiento. Conclusiones. El cierre en tres capas es sencillo y efectivo a la hora de evitar refistulizaciones. Los injertos interposicionales de membrana reabsorbible de colágeno proporcionan un "andamio" para el crecimiento de los tejidos, revascularización y epitelialización de la mucosa

Objective. Palatal fistula after the repair of cleft palate appears in 7.7-35% of patients. We present two cases of palatal fistula, detailing a multi-layer repair with an interpositional collagen graft. Material and methods. Patient 1: girl with a cleft palate operated using a Furlow technique. A reintervention was performed due to a Pittsburgh type III fistula Patient 2: male with cleft palate operated using a Furlow technique. A reintervention was performed due to a type V fistula. Results. We used a multilayer repair with a local rotational flap and the interposition of a collagen matrix between the nasal and oral layers. The suture was reinforced with a fibrin hemostatic adhesive. No recurrence of the fistula after 2 years. Conclusions. The three-layer closure is simple, safe, effective and avoids refistulizations. Interpositional grafts of a resorbable collagen membrane provide a "scaffold" for tissue growth, revascularization and epithelialization of the mucosa

Dose evaluation of intravenous metamizole (dipyrone) in infants and children: a prospective population pharmacokinetic study.

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. AUC0-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 (AUCref). 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. AUC0-inf of 4-methylaminoantipyrine in children 2-6 years was 29.9 mg/L/h (95% CI 23.4-38.2), significantly lower than AUCref (80-125% range 39.2-61.2 mg/L/h). AUC0-inf of 4-methylaminoantipyrine in infants < 2 years was 43.6 mg/L/h (95% CI 15.8-119.0), comparable with AUCref, 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 .