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This retrospective study analyzed 230 pediatric opioid exposures from a statewide poison control center over a 5-year period. Most exposures involved pharmaceutical opioids and children below 2-years-old. Narrative details were reviewed to identify uncommon sources of opioids involved in poisoning and highlight the need for tailored prevention strategies and guidance.
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PURPOSE: Sex differences play a crucial role in understanding vulnerability to opioid addiction, yet there have been limited preclinical investigations of this effect during the transition from adolescence to adulthood. The present study compared the behaviors of male and female rodents in response to fentanyl treatment and targeted molecular correlates in the striatum and medial prefrontal cortex. MATERIALS AND METHODS: Thirty adolescent C57BL/6J mice underwent a 1-week fentanyl treatment with an escalating dose. In addition to evaluating locomotor activity and anxiety-related parameters, we also assessed naloxone-induced fentanyl acute withdrawal jumps. We employed real-time quantitative PCR (qPCR) to assess overall gene expression of dopaminergic receptors (Drd1, Drd2, Drd4 and Drd5) and the µ-opioid receptor Oprm1. The levels of epigenetic base modifications including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) were assessed on CpG islands of relevant genes. RESULTS: Females had higher locomotor activity than males after chronic fentanyl treatment, and they exhibited higher fentanyl withdrawal jumping behavior induced by naloxone. Females also presented lower Drd4 gene expression and DNA methylation (5mC + 5hmC) in the striatum. We found that locomotor activity and fentanyl withdrawal jumps were negatively correlated with Drd4 methylation and gene expression in the striatum, respectively. CONCLUSIONS: The findings suggested that female mice displayed heightened sensitivity to the effects of fentanyl treatment during the transition from adolescence to adulthood. This effect may be associated with molecular alterations related to the Drd4 gene.
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Fentanila , Camundongos Endogâmicos C57BL , Receptores Opioides mu , Caracteres Sexuais , Animais , Fentanila/farmacologia , Masculino , Feminino , Receptores Opioides mu/genética , Receptores Opioides mu/metabolismo , Camundongos , Metilação de DNA/efeitos dos fármacos , Analgésicos Opioides/farmacologia , Corpo Estriado/metabolismo , Corpo Estriado/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Receptores Dopaminérgicos/genética , Receptores Dopaminérgicos/metabolismo , Naloxona/farmacologia , Comportamento Animal/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/genética , Síndrome de Abstinência a Substâncias/metabolismo , Epigênese Genética/efeitos dos fármacosRESUMO
OBJECTIVE: This systematic literature review aims to evaluate the effectiveness of transdermal opioids in managing cancer pain and their impact on the quality of life (QoL) of patients. DATA SOURCES: A systematic literature review conducted following the PRISMA protocol, focusing on randomized clinical trials found in the Lilacs, Embase, PubMed, and SciELO databases over the last 20 years. STUDY SELECTION AND DATA EXTRACTION: We included randomized clinical trials, published in English, Portuguese, or Spanish, which assessed the impact of transdermal opioids on the QoL. Data extraction was facilitated using the Rayyan app. DATA SYNTHESIS: Six articles meeting the inclusion and exclusion criteria were analyzed. These studies covered a population ranging from 24 to 422 cancer patients experiencing moderate to severe pain. The risk of bias was assessed in each study, generally being categorized as uncertain or high. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The findings indicate that the analgesic effectiveness and side effects of transdermal formulations (specifically buprenorphine and fentanyl) for managing moderate to severe cancer pain are comparable to, or in some cases superior to, those of oral opioids traditionally employed. CONCLUSIONS: Transdermal therapy was suggested to have several advantages over oral opioid therapy in enhancing cancer patients' QoL. These benefits span various dimensions, including pain management, physical functioning, mental health, vitality, overall patient improvement, anger/aversion, strength/activity, general QoL, cognitive and emotional functions, fatigue, and insomnia.
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Abstract Background: Many adjuvants are added to prolong the effects of spinal analgesia. We investigated the postoperative analgesic efficacy of the addition of midazolam or fentanyl to intrathe-cal levobupivacaine in women undergoing cesarean delivery. Methods: Eighty patients were randomly assigned to two groups (n = 40). Group M received 10 mg of 0.5% levobupivacaine plus 2 mg of midazolam. Group F received 10 mg of 0.5% levobupivacaine plus 25 μg of fentanyl. Assessments included motor and sensory block, APGAR score, time to first request for analgesia, postoperative pain score, total consumption of rescue analgesics, and adverse effects. Results: Sensory blockade was prolonged in Group M compared with Group F (215.58 ± 27.94 vs. 199.43 ± 19.77 min; p = 0.004), with no differences in other characteristics of the spinal block in intraoperative hemodynamics or APGAR score. The mean time to first request for rescue analgesia was longer in Group M (351.45 ± 11.05 min) than in Group F (268.83 ± 10.35 min; p = 0.000). The median total consumption of rescue analgesics in the first 24 hours postoperatively was 30 mg in Group M vs. 60 mg in Group F (p = 0.003). The median Visual Analog Scale (VAS) scores were lower in Group Ethan in Group F from the 8th to the 12th hour postoperatively, with no differences between the groups at other time points. The incidence of adverse effects was higher in Group F than in Group M. Conclusion: Intrathecal midazolam (2 mg) was superior to intrathecal fentanyl (25 μg) in increasing the duration of the sensory blockade and postoperative analgesia with lower postoperative pain scores and decreasing the incidence of adverse effects.
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Abstract Background and objective: Anesthesia induction can produce severe propofol dose-dependent hypotension. Fentanyl coadministration reduces the catecholaminergic response to orotracheal intubation allowing propofol dose reduction. The aim of this study is to determine whether the hemodynamic response is improved by increasing the time between fentanyl and propofol administration and reducing the dose of the latter without increasing the time to achieve optimal hypnosis. Methods: After approval by the Research Ethics Committee, patients undergoing non-cardiac surgery with endotracheal intubation were randomized by a computer-generated table into six time-dose groups (1 or 2 minutes/1, 1.5, or 2mg.kg-1 of propofol). Patients with high bronchoaspiration risk, a difficult airway, hemodynamic instability, or anesthetic allergies were excluded. After giving intravenous fentanyl (2 μg.kg-1 ), each group received different doses of propofol after 1 or 2 minutes. Non-invasive blood pressure (BP) and heart rate (HR) were measured at pre-induction, pre-intubation, and post-intubation. Time to hypnosis (bispectral index < 60) was also recorded. Results: Of the 192 recruited patients, 186 completed the study (1 min group n = 94; 2 min group n = 92). It was observed that HR and BP decreased after propofol administration and increased after intubation in all groups (p<0.0001). In patients over 55 years, the 2 min - 2 mg.kg-1 group showed the greatest systolic BP reduction (36 ± 12%) at pre-intubation, while the 1 min - 1.5 mg.kg-1 group showed the least hemodynamic alteration between pre- and post-intubation (-4 ± 13%). No significant differences were found in younger patients or in the time to reach hypnosis between the six groups. While no cases of severe bradycardia were recorded, 5,4% of the sample required vasopressors. Conclusion: Increasing the time between the administration of fentanyl and propofol by up to two minutes results in greater hypotension in patients over 55 years.
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BACKGROUND: Perception of drug adulteration has increased in Mexico, but there is little research on adulterants and toxicity. The aim of this study was to identify drug composition in an electronic music outdoor festival nearby Mexico City. METHODS: The participants completed a questionnaire with demographic data, harm reduction strategies, drug-use patterns, history, and the drug they expected to find. We took a small sample of each substance and prepared it for drug checking. A two-section drug testing station was placed within the grounds of the festival. Interaction with participants occurred at the front part. Drug checking was conducted at the rear part. The service was free of charge, voluntary and confidential. Forty persons aged 22 to 48 years participated (mode = 28), of which 92.5% were male, most (82.5%) were single. Through the Substance Analysis Program of "ReverdeSer Collective," we conducted the testing with the attendants that provided 51 drug samples, following ethical and biosafety protocols. We used colorimetry, Fourier Transform Infrared Spectroscopy, and fentanyl immunoassay strips for sample analysis. RESULTS: Substances of choice among attendants were psychostimulants (MDMA and other amphetamine-like drugs) and hallucinogens. Most samples contained what the users expected plus adulterants. Main adulterants were methylene-dioxy-ethyl-amphetamine, methylene-dioxy-propyl-amphetamine, hydroxyamphetamine, and the selective serotonin reuptake inhibitor venlafaxine. Fentanyl was present in 2 out of 4 cocaine samples and in 14 of the 22 confirmed MDMA samples. CONCLUSIONS: Some of the adulterants found pose serious health risks, especially fentanyl, amphetamine-like substances, and venlafaxine. Therefore, it is urgent to monitor these adulterants at electronic music festivals and to implement prevention, treatment, and harm reduction public policies. Naloxone distribution and drug-assisted therapies should be part of government programs in Mexico.
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Drogas Ilícitas , N-Metil-3,4-Metilenodioxianfetamina , Humanos , Masculino , Feminino , Drogas Ilícitas/análise , Fentanila/análise , Férias e Feriados , México , Cloridrato de Venlafaxina , AnfetaminaRESUMO
OBJECTIVES: To assess the efficacy and adverse events linked to the utilization of fentanyl for perioperative pain management in dentistry. METHODS: This systematic review of randomized clinical trials (RCTs) adhered to the PRISMA guidelines and incorporated various databases. RESULTS: Eleven RCTs studying 674 patients were analyzed. Perioperative pain was predominantly evaluated in patients undergoing surgery for impacted molars, although some studies also included patients with other conditions such as oral submucous fibrosis, maxillary cancer, bony temporomandibular joint ankylosis, irreversible pulpitis, among others. Combined with dexmedetomidine, fentanyl produced enhanced analgesic effects. It demonstrated comparable efficacy when compared to nefopam and nalbuphine. Both intranasal and intravenous administration routes proved equally effective. In four RCTs, the transdermal fentanyl patch outperformed the control group, except in the clinical trial where it was compared to ropivacaine. The main adverse events associated with the use of fentanyl included nausea, vomiting, drowsiness, delirium, and respiratory depression; however, they were like those reported in the comparison groups. CONCLUSIONS: While fentanyl demonstrated satisfactory perioperative analgesic efficacy, there were other alternatives that displayed better or comparable outcomes. Due to the risks and potential for misuse of fentanyl, these alternatives must be considered although adverse events were also reported.
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BACKGROUND: Fentanyl is commonly laced with xylazine. People who use this combination report heightened effects, but it also increases death risk. Although no medication has been approved to counteract overdoses produced by fentanyl and xylazine, naloxone is frequently used. This paper studies the preclinical rewarding and lethal effects of fentanyl combined with xylazine and the efficacy of yohimbine or naloxone to prevent death. METHODS: Male Swiss Webster mice were treated with (in mg/kg, i.p.) xylazine (0.3, 1, 3, or 5.6), fentanyl (0.01, 0.3, or 0.1), or 1 xylazine plus 0.01 (non-effective) or 0.1 (effective) fentanyl doses during the conditioned-place preference (CPP) test. In addition, independent groups received (in mg/kg, i.p.): xylazine (31.6, 60, 74.2, or 100), fentanyl (3.1 or 10), or both substances at two doses: 31.6 xylazine + 3.1 fentanyl, or 60 xylazine + 10 fentanyl to analyze lethal effects. We determined whether yohimbine or naloxone (each medication tested at 10 or 30mg/kg) could prevent the lethality produced by fentanyl/xylazine combinations. Female mice were also tested in key experiments. RESULTS: Xylazine neither induced CPP nor altered fentanyl's rewarding effects. In contrast, lethality was potentiated when fentanyl was combined with xylazine. Naloxone, but not yohimbine, effectively prevented the lethality of the fentanyl/xylazine combinations. CONCLUSIONS: At the doses tested, xylazine does not increase the rewarding effect of fentanyl on the CPP in male mice but potentiates the risk of fatal overdose in male and female mice. A high naloxone dose prevents death induced by coadministration of fentanyl and xylazine in both sexes.
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Overdose de Drogas , Xilazina , Humanos , Masculino , Feminino , Camundongos , Animais , Xilazina/farmacologia , Fentanila/farmacologia , Ioimbina/farmacologia , Naloxona/farmacologia , Analgésicos OpioidesRESUMO
Resumen: Introducción: la concentración y velocidad en la administración de la anestesia multimodal intratecal con fentanilo en cesáreas mejoran la eficacia anestésica manteniendo buen control hemodinámico. Objetivo: evaluar si algunos cambios en la anestesia multimodal intratecal mejoran su eficacia y seguridad en cesáreas. Material y métodos: ensayo clínico, controlado, aleatorizado, doble ciego en mujeres embarazadas programadas para cesárea, distribuidas en tres grupos: grupo F6B2: fentanilo 65 μg + bupivacaína hiperbárica 2.5 mg + morfina 10 μg + dexmedetomidina 5 μg; grupo F6B3: fentanilo 60 μg + bupivacaína hiperbárica 3 mg+ morfina 100 μg+ dexmedetomidina 5 μg; y grupo F7B2: fentanilo 70 μg + bupivacaína hiperbárica 2 mg + morfina 100 μg + dexmedetomidina 5 μg. Se evaluó la eficacia anestésica previo a la incisión, durante la disección de la pared abdominal, al ingreso a cavidad abdominal, en la revisión de correderas parietocólicas y en el postquirúrgico inmediato, así como los signos vitales. Resultados: los grupos F6B2 y F6B3 resultaron tener mayor eficacia anestésica en la revisión de correderas parietocólicas (p = 0.02) y el grupo F7B2 el de mayor seguridad con mejor control hemodinámico a los minutos 1 y 10 (p = 0.03 y p = 0.03 respectivamente). Conclusiones: los cambios en la administración de la anestesia multimodal intratecal con fentanilo mejoraron la eficacia anestésica, pero disminuyen la seguridad sobre el control hemodinámico.
Abstract: Introduction: the concentration and speed in the administration of intrathecal multimodal anesthesia with fentanyl in cesareans section improve anesthetic efficacy while maintaining good hemodynamic control. Objective: to evaluate if some changes in intrathecal multimodal anesthesia improve its efficacy and safety in cesareans section. Material and methods: clinical trial, controlled, randomized, double blind; in pregnant women scheduled for cesarean section, divided into 3 groups: group F6B2: fentanyl 65 μg + hyperbaric bupivacaine 2.5 mg+ morphine 100 μg+ dexmedetomidine 5 μg; group F6B3: fentanyl 60 μg + hyperbaric bupivacaine 3 mg + morphine 100 μg + dexmedetomidine 5 μg; and group F7B2: fentanyl 70 μg + hyperbaric bupivacaine 2 mg + morphine 100 μg + dexmedetomidine 5 μg. The anesthetic efficacy was evaluated prior to the incision, during the dissection of the abdominal wall, upon the admission to the abdominal cavity, in the review of paracolic slides and in the immediate postoperative period, as well as the vital signs. Results: the F6B2 and F6B3 groups turned out to have greater anesthetic efficacy in the revision of paracolic slides (p = 0.02) and the F7B2 group had the highest safety with better hemodynamic control at 1 and 10 minutes (p = 0.03 and p = 0.03, respectively). Conclusions: changes in the administration of intrathecal multimodal anesthesia with fentanyl improved anesthetic efficacy, but decreased safety over hemodynamyc control.
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This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.
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3,4-Metilenodioxianfetamina , Estimulantes do Sistema Nervoso Central , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Humanos , Anfetamina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Metanfetamina/efeitos adversosRESUMO
Synthetic opioids have played a significant role in the current opioid crisis in the United States (U.S.) and Canada and are a matter of concern worldwide. New psychoactive opioids (NPOs) are classified in the internationally recognized new psychoactive substances (NPSs) category. This group comprises compounds that may have been synthesized decades ago but appeared only recently in the illicit drug market. Such is the case of fentanyl, fentanyl analogs, and non-fentanyl opioids. Most NPOs have effects similar to morphine, including euphoria and analgesia, and can produce fatal respiratory depression. Here, we present an overview of the systemic and molecular effects of main NPOs, their classification, and their pharmacological properties. We first review the fentanyl group of NPOs, including the four compounds of clinical use (fentanyl, alfentanil, sufentanil, and remifentanil) and the veterinary drug carfentanil. We also provide essential information on non-medical fentanyl analogs and other synthetic opioids such as brorphine, etonitazene, and MT-45, used as adulterants in commonly misused drugs. This paper also summarizes the scarce literature on the use of NPOs in Mexico. It concludes with a brief review of the challenges to prevention and treatment posed by NPOs and some recommendations to face them.
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Analgésicos Opioides , Humanos , Estados Unidos , Analgésicos Opioides/efeitos adversos , Remifentanil , Canadá , MéxicoRESUMO
BACKGROUND: Fentanyl- and methamphetamine-based counterfeit prescription drugs have driven escalating overdose death rates in the US, however their presence in Mexico has not been assessed. Our ethnographic team has conducted longitudinal research focused on illicit drug markets in Northern Mexico since 2018. In 2021-2022, study participants described the arrival of new, unusually potent tablets sold as ostensibly controlled substances, without a prescription, directly from pharmacies that cater to US tourists. AIMS: To characterize the availability of counterfeit and authentic controlled substances at pharmacies in Northern Mexico available to English-speaking tourists without a prescription. METHODS: We employed an iterative, exploratory, mixed methods design. Longitudinal ethnographic data was used to characterize tourist-oriented micro-neighborhoods and guide the selection of n=40 pharmacies in n=4 cities in Northern Mexico. In each pharmacy, samples of "oxycodone", "Xanax", and "Adderall" were sought as single pills, during English-language encounters, after which detailed ethnographic accounts were recorded. We employed immunoassay-based testing strips to check each pill for the presence of fentanyls, benzodiazepines, amphetamines, and methamphetamines. We used Fourier-Transform Infrared Spectroscopy to further characterize drug contents. RESULTS: Of n=40 pharmacies, one or more of the requested controlled substances could be obtained with no prescription (as single pills or in bottles) at 28 (70.0%) and as single pills at 19 (47.5%). Counterfeit pills were obtained at 11 pharmacies (27.5%). Of n=45 samples sold as one-off controlled substances, 18 were counterfeit. 7 of 11 (63.6%) samples sold as "Adderall" contained methamphetamine, 8 of 27 (29.6%) samples sold as "Oxycodone" contained fentanyl, and 3 "Oxycodone" samples contained heroin. Pharmacies providing counterfeit drugs were uniformly located in tourist-serving micro-neighborhoods, and generally featured English-language advertisements for erectile dysfunction medications and "painkillers". Pharmacy employees occasionally expressed concern about overdose risk and provided harm reduction guidance. DISCUSSION: The availability of fentanyl-, heroin-, and methamphetamine-based counterfeit medications in tourist-oriented independent pharmacies in Northern Mexico represents a public health risk, and occurs in the context of 1) the normalization of medical tourism as a response to rising unaffordability of healthcare in the US, 2) plummeting rates of opioid prescription in the US, affecting both chronic pain patients and the availability of legitimate pharmaceuticals on the unregulated market, 3) the rise of fentanyl-based counterfeit opioids as a key driver of the fourth, and deadliest-to-date, wave of the opioid crisis. It was not possible to distinguish counterfeit medications based on appearance of pills or geography of pharmacies, because identically-appearing authentic and counterfeit versions were often sold in close geographic proximity. Nevertheless, people who consume drugs may be more trusting of controlled substances purchased directly from pharmacies. Due to Mexico's limited opioid overdose surveillance infrastructure, the current death rate from these substances remains unknown.
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Overdose de Drogas , Metanfetamina , Farmácias , Masculino , Humanos , Heroína , Fentanila , Substâncias Controladas , México , Analgésicos Opioides , Overdose de Drogas/epidemiologia , OxicodonaRESUMO
Resumen: Introducción: El fentanilo ofrece buena eficacia anestésica, con menores efectos sobre el sistema nervioso simpático, al mantener un mejor estado hemodinámico, pero su efecto en combinación con otros anestésicos en embarazadas no está del todo descrito. Objetivo: Evaluar la eficacia anestésica y seguridad de la anestesia multimodal con fentanilo en mujeres embarazadas durante la cesárea. Material y métodos: Ensayo clínico, controlado, aleatorizado, doble ciego; en mujeres embarazadas programadas para cesárea, distribuidas en tres grupos: grupo FBMD: fentanilo 70 μg + bupivacaína hiperbárica 0.1%, 2 mg, + morfina 100 μg + dexmedetomidina 5 μg; grupo BFM: bupivacaína hiperbárica 0.25%, 5 mg, + fentanilo 25 μg + morfina 100 μg, y el grupo BM: bupivacaína hiperbárica 0.375%, 7.5 mg, + morfina 100 μg. Se evaluó la eficacia anestésica previo a la incisión, durante la disección de la pared abdominal, al ingreso a cavidad abdominal, en la revisión de correderas parietocólicas y en el postquirúrgico inmediato, así como, los signos vitales. Resultados: Se analizaron 180 mujeres. El grupo FBMD mostró mayor eficacia anestésica en la revisión de correderas parietocólicas (p = 0.01) y en el postquirúrgico inmediato (p = 0.0001), así como mayor seguridad con mejor control hemodinámico a los minutos uno y 10 (p = 0.02 y p = 0.03, respectivamente). Conclusiones: La anestesia multimodal con FBMD demuestra mejor eficacia anestésica y seguridad sobre el control hemodinámico.
Abstract: Introduction: Fentanyl offers good anesthetic efficacy and fewer effects on the sympathetic nervous system with better hemodynamic status, but its effect in combination with other anesthetics in pregnant women has not been fully described. Objective: To evaluate the anesthetic efficacy and safety of multimodal anesthesia with fentanyl in pregnant women undergoing caesarean section. Material and methods: Controlled, randomized, double blinded clinical trial; in pregnant women scheduled for cesarean section distributed in 3 groups: FBMD group: fentanyl 70 μg + hyperbaric bupivacaine 0.1%, 2 mg, + morphine 100 μg + dexmedetomidine 5 μg; BFM group: hyperbaric bupivaine 0.25%, 5 mg, + fentanyl 25 μg + morphine 100 μg, and group BM: hyperbaric bupivacaine 0.375%, 7.5 mg, + morphine 100 μg. The anesthetic efficacy was evaluated: prior to the incision, during the dissection of the abdominal wall, upon entry to the abdominal cavity, in the revision of parietocolic slides and in the immediate postoperative period, as well as the vital signs. Results: 180 women were analyzed. The FBMD group showed greater anesthetic efficacy in the revision of parietocolic slides (p = 0.01) and in the immediate postoperative period (p = 0.0001) and greater safety, showing better hemodynamic control at minutes 1 and 10 (p = 0.02 y p = 0.03 respectively). Conclusions: Multimodal anesthesia with FMBD shows better anesthetic efficacy and safety over hemodynamic control.
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ABSTRACT Synthetic opioids have played a significant role in the current opioid crisis in the United States (U.S.) and Canada and are a matter of concern worldwide. New psychoactive opioids (NPOs) are classified in the internationally recognized new psychoactive substances (NPSs) category. This group comprises compounds that may have been synthesized decades ago but appeared only recently in the illicit drug market. Such is the case of fentanyl, fentanyl analogs, and non-fentanyl opioids. Most NPOs have effects similar to morphine, including euphoria and analgesia, and can produce fatal respiratory depression. Here, we present an overview of the systemic and molecular effects of main NPOs, their classification, and their pharmacological properties. We first review the fentanyl group of NPOs, including the four compounds of clinical use (fentanyl, alfentanil, sufentanil, and remifentanil) and the veterinary drug carfentanil. We also provide essential information on non-medical fentanyl analogs and other synthetic opioids such as brorphine, etonitazene, and MT-45, used as adulterants in commonly misused drugs. This paper also summarizes the scarce literature on the use of NPOs in Mexico. It concludes with a brief review of the challenges to prevention and treatment posed by NPOs and some recommendations to face them.
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ABSTRACT This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.
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Abstract Introduction Spinal infusions of either fentanyl or sufentanil have been reported in international reports, articles, and scientific events worldwide. This study aimed to determine whether intrathecal fentanyl or sufentanil offers safety in mortality and perioperative adverse events. Methods MEDLINE (via PubMed), EMBASE, CENTRAL (Cochrane library databases), gray literature, hand-searching, and clinicaltrials.gov were systematically searched. Randomized controlled trials with no language, data, or status restrictions were included, comparing the effectiveness and safety of adding spinal lipophilic opioid to local anesthetics (LAs). Data were pooled using the random-effects models or fixed-effect models based on heterogeneity. Results The initial search retrieved 4469 records; 3241 records were eligible, and 3152 articles were excluded after reading titles and abstracts, with a high agreement rate (98.6%). After reading the full texts, 76 articles remained. Spinal fentanyl and sufentanil significantly reduced postoperative pain and opioid consumption, increased analgesia and pruritus. Fentanyl, but not sufentanil, significantly reduced both postoperative nausea and vomiting, and postoperative shivering; compared to LAs alone. The analyzed studies did not report any case of in-hospital mortality related to spinal lipophilic opioids. The rate of respiratory depression was 0.7% and 0.8% when spinal fentanyl or sufentanil was added and when it was not, respectively. Episodes of respiratory depression were rare, uneventful, occurred intraoperatively, and were easily manageable. Conclusion There is moderate to high quality certainty that there is evidence regarding the safety and effectiveness of adding lipophilic opioids to LAs in spinal anesthesia.
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Humanos , Fentanila/efeitos adversos , Raquianestesia/efeitos adversos , Dor Pós-Operatória , Sufentanil/efeitos adversos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Analgésicos Opioides/efeitos adversos , Anestésicos Locais/efeitos adversosRESUMO
INTRODUCTION: Spinal infusions of either fentanyl or sufentanil have been reported in international reports, articles, and scientific events worldwide. This study aimed to determine whether intrathecal fentanyl or sufentanil offers safety in mortality and perioperative adverse events. METHODS: MEDLINE (via PubMed), EMBASE, CENTRAL (Cochrane library databases), gray literature, hand-searching, and clinicaltrials.gov were systematically searched. Randomized controlled trials with no language, data, or status restrictions were included, comparing the effectiveness and safety of adding spinal lipophilic opioid to local anesthetics (LAs). Data were pooled using the random-effects models or fixed-effect models based on heterogeneity. RESULTS: The initial search retrieved 4469 records; 3241 records were eligible, and 3152 articles were excluded after reading titles and abstracts, with a high agreement rate (98.6%). After reading the full texts, 76 articles remained. Spinal fentanyl and sufentanil significantly reduced postoperative pain and opioid consumption, increased analgesia and pruritus. Fentanyl, but not sufentanil, significantly reduced both postoperative nausea and vomiting, and postoperative shivering; compared to LAs alone. The analyzed studies did not report any case of in-hospital mortality related to spinal lipophilic opioids. The rate of respiratory depression was 0.7% and 0.8% when spinal fentanyl or sufentanil was added and when it was not, respectively. Episodes of respiratory depression were rare, uneventful, occurred intraoperatively, and were easily manageable. CONCLUSION: There is moderate to high quality certainty that there is evidence regarding the safety and effectiveness of adding lipophilic opioids to LAs in spinal anesthesia.
Assuntos
Raquianestesia , Fentanila , Humanos , Fentanila/efeitos adversos , Raquianestesia/efeitos adversos , Analgésicos Opioides/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sufentanil/efeitos adversos , Anestésicos Locais/efeitos adversos , Dor Pós-OperatóriaRESUMO
Introducción: Los procedimientos anestésicos fuera de quirófano se han incrementado. Ahora se añade el reto del manejo del paciente con COVID-19, dentro de estos esta la colonoscopia que debe realizarse bajo sedoanalgesia, no se cuenta con un fármaco ideal por lo que se realizan combinaciones para la seguridad del paciente y personal de salud. Objetivo: Comparar la seguridad de sedoanalgesia con propofol-fentanilo vs propofol-ketamina en pacientes con COVID-19 sometidos a colonoscopia. Material y métodos: Se realizó un estudio experimental, transversal, comparativo con 60 pacientes sometidos a colonoscopia, estos fueron seleccionados por sucesión en 2 grupos: grupo A (propofol-fentanil) y grupo B (propofol-ketamina). Grupo A: fentanil 1 ug/kg y posteriormente propofol a 0,5 a 1,5 mg/kg, y mantenimiento con bolos de propofol a 0,5 mg/kg. Grupo B: se preparó mezcla de propofol-ketamina a proporción de 4:1, en la inducción se utilizó propofol (1mg/kg) y ketamina (0,25mg/kg), mantenimiento propofol (5 mg/kg/h) y ketamina (1,25 mg/kg/h). La información fue recolectada de fuentes primarias, se empleó el programa estadístico SPSS versión 22.0. Resultados: El grupo A tuvo tendencia a la bradicardia e hipotensión, además de mayor depresión respiratoria con una frecuencia de 4 (13,3%) en relación a 1 (3,3%) en el grupo ketofol. Conclusión: el ketofol demostró ser más seguro en comparación a propofol- fentanil para la sedoanalgesia en colonoscopia de pacientes COVID-19.
Introduction: Anesthetic procedures outside the operating room have increased. Now the challenge of managing patients with COVID-19 is included, within these is the colonoscopy that must be performed under sedo-analgesia, there is no an ideal drug so combinations are made for the safety of the patient and the health staff. Objective: To compare the safety of sedo-analgesia with propofol-fentanyl vs propofol-ketamine in patients with COVID-19 undergoing colonoscopy. Material and methods: An experimental, cross-sectional, comparative study was carried out in 60 patients submitted to colonoscopy, these were selected by succession into 2 groups: group A (propofol-fentanyl) and group B (propofol- ketamine). Group A: fentanyl 1 ug/kg and later propofol at 0.5 to 1.5 mg/kg, and maintenance with propofol boluses at 0.5 mg/kg. Group B: a mixture of propofol- ketamine was prepared at a ratio of 4:1, in induction propofol (1 mg/kg) and ketamine (0.25 mg/kg) were used, propofol maintenance (5 mg/kg/h) and ketamine (1.25 mg/ kg/h). The information was collected from primary sources, the statistical program SPSS version 22.0 was used. Results: Group A had a tendency to bradycardia and hypotension, as well as greater respiratory depression with a frequency of 4 (13.3%) in relation to 1 (3.3%) in the ketofol group. Conclusion: Ketofol has shown to be safer compared to propofol-fentanyl for colonoscopy sedo-analgesia in COVID-19 patients.
RESUMO
Post-operative nausea and vomiting (PONV) is an event of multifactorial origin with an incidence of 30% in the general population. Opioids such as fentanyl are being used as adjuvant to local anesthetic for its antiemetic effect. In this context, with this study we aimed to evaluate the impact of spinal fentanyl as an adjuvant on the incidence of PONV compared with a placebo, and shivering. A systematic search of randomized controlled trials that evaluated the use of spinal fentanyl in the prevention of PONV and shivering was conducted in different databases, of which 32 studies met the inclusion criteria. A total of 2116 patients scheduled for various surgeries, including cesarean section, orthopedic surgery in the lower limb, hysterectomy, and transurethral resection of the prostate, were included in the final analysis. The meta-analysis estimated the relative risk of incidence of PONV in the first 24 hours after surgery and secondary outcomes included the shivering symptom. The use of intrathecal fentanyl was associated with lower incidence of PONV, but not statistically significant when compared to the placebo (RR: 0.74 CI95%: 0.55-1.01 P = 0.06). Subgroup analysis showed a statistically significant reduction in PONV incidences with lower doses between 10 and 15 µg (RR: 0.44 CI95%: 0.35-0.55 P < 0.00001, I2 = 0%) but not with higher doses 20-25 µg. Secondary outcomes showed a decrease in incidence with the use of fentanyl vs the placebo (RR: 0.49, CI95% 0.33-0.72 P = 0.0003). Current evidence shows that the use of spinal fentanyl decreases the incidence of PONV, an effect favored using low doses.
RESUMO
Introducción: La comodidad durante la colonoscopia es una condición importante si se quiere que el paciente acepte procedimientos repetidos. Por lo tanto, se necesita de una buena sedación que pudiera combinar la analgesia con amnesia. Objetivo: Describir la utilidad de la analgosedación balanceada con propofol/fentanilo en colonoscopia ambulatoria. Métodos: Se realizó un estudio observacional descriptivo longitudinal prospectivo en pacientes a los que se les realizó colonoscopia de forma ambulatoria en el Hospital General Universitario Dr. Gustavo Aldereguía Lima en el período entre enero de 2017 y diciembre de 2018. Resultados: El 34,2 por ciento de los pacientes tenía entre 50 y 59 años, el 62,9 por ciento eran mujeres. El 73,3 por ciento de los pacientes se clasificó como ASA II según el estado físico. Los valores medios de frecuencia cardiaca y tensión arterial media tuvieron una disminución ligera después de aplicada la anestesia y se mantuvieron constantes en el resto de los momentos evaluados. Los valores medios de saturación de oxígeno de la hemoglobina se mantuvieron relativamente constantes en todos los momentos y resultaron algo superiores a la llegada del paciente a recuperación. La calidad de la sedación fue adecuada en 86,2 por ciento de los pacientes. La calidad de la analgesia y la recuperación fue buena en 88,4 por ciento y 96,2 por ciento , respectivamente. Se presentaron complicaciones en el 16,5 por ciento de los pacientes. Conclusiones: La analgosedación con propofol y fentanilo resultó una alternativa anestésica de utilidad en los pacientes a los que se les realizó colonoscopia ambulatoria con gran estabilidad hemodinámica en la serie estudiada(AU)
Introduction: Comfort during colonoscopy is an important condition if the patient is expected to accept repeated procedures. Therefore, good sedation that could combine analgesia with amnesia is needed. Objective: To describe the usefulness of balanced analgosedation with propofol/fentanyl in outpatient colonoscopy. Methods: A prospective, longitudinal, descriptive and observational study was carried out with patients who received outpatient colonoscopy at Dr. Gustavo Aldereguía Lima General University Hospital in the period between January 2017 and December 2018. Results: 34.2 percent of the patients were between 50 and 59 years old, while 62.9 percent were women. 73.3 percent of patients were classified as ASA II, according to their physical status. The mean values for heart rate and mean arterial blood pressure had a slight decrease after anesthesia was applied and remained constant for the rest of the evaluated times. The mean values of hemoglobin-oxygen saturation remained relatively constant at all the evaluated times and were slightly higher on the patient's arrival to recovery. The quality of sedation was adequate in 86.2 percent of the patients. The quality of analgesia and recovery was good in 88.4 percent and 96.2 percent, respectively. Complications occurred in 16.5 percent of the patients. Conclusions: Analgosedation with propofol and fentanyl proved to be a useful anesthetic alternative in patients undergoing outpatient colonoscopy, with high hemodynamic stability in the studied series(AU)