Manifestaciones clínicas post supresión de sedoanalgesia en pacientes adultos de una terapia intensiva / Clinical manifestations after suppression of sedoanalgesia in adult patients in intensive care

Introducción: en la unidad de cuidados intensivos (UCI), las personas asistidas con patologías relevantes se encuentran bajo sedación, una vez que estas se encuentran bajo los principios de supresión de la sedación, es importante identificar cuáles son las manifestaciones que presentan, propias de las sedaciones. Objetivo: describir las manifestaciones clínicas del síndrome de supresión de la sedoanalgesia presentes en pacientes asistidos en un Hospital Público de la Ciudad de Corrientes de enero a diciembre del 2022. Metodología: estudio cuantitativo, descriptivo, transversal y observacional. La muestra incluyó pacientes adultos de UCI. El cálculo del tamaño muestral se realizó a través del método probabilístico aleatorio simple resultando de éste una muestra de 100 historias clínicas. Para la recolección de datos se utilizó la observación y como instrumento un formulario semiestructurado, de carácter anónimo. Cada formulario contenía datos específicos donde se categorizan las variables en estudio como ser edad, sexo, comorbilidades, tiempo de sedoanalgesia, tipo de sedación, sedoanalgesia utilizada, agitación, confusión, alucinación, diaforesis, taquicardia. Resultados: en cuanto a la edad se obtuvo un promedio de 49 años, el sexo predominante fue el masculino con 52%, en cuanto a las comorbilidades más frecuentes, el 20% presentó Insuficiencia Respiratoria Aguda y el 16% Insuficiencia renal. El motivo de ingreso a UCI en mayor medida con el 33% fue por dificultad respiratoria y Post Quirúrgicos complicados 32%. Los fármacos de mayor elección fueron midazolam 94%, seguido del fentanilo 80%. En cuanto al tiempo de sedación de los pacientes, se encontró una media de 1265 horas. Las manifestaciones clínicas que se observaron en la muestra en mayor medida corresponden a taquicardia 70%, agitación 52%, un 37% confusión e hipertensión y un 24% alucinación. Conclusión: las manifestaciones que se presentaron con mayor frecuencia fueron taquicardia, agitación, confusión, hipertensión y con menor frecuencia alucinación[AU]

Introduction: in the intensive care unit (ICU), people treated with relevant pathologies are under sedation. Once they are under the principles of sedation suppression, it is important to identify the manifestations they present, typical of sedations. Objective: To describe the clinical manifestations of sedation suppression syndrome present in patients treated at a Public Hospital in the City of Corrientes from January to December 2022. Methodology: quantitative, descriptive, cross-sectional and observational study. The sample included adult ICU patients. The calculation of the sample size was carried out through the simple random probabilistic method, resulting in a sample of 100 medical records. Manifestaciones clínicas post supresión de sedoanalgesia en pacientes adultos de una terapia intensiva. Observation was used to collect data and a semi-structured, anonymous form was used as an instrument. Each form contained specific data where the variables under study were categorized, such as age, sex, comorbidities, sedation time, type of sedation, sedation used, agitation, confusion, hallucination, diaphoresis, tachycardia. Results: regarding age, an average of 49 years was obtained, the predominant sex was male with 52%, regarding the most frequent comorbidities, 20% presented Acute Respiratory Failure and 16% Renal failure. The reason for admission to the ICU to a greater extent with 33% was due to respiratory difficulty and complicated Post-Surgeries 32%. The drugs of greatest choice were midazolam 94%, followed by fentanyl 80%. Regarding the sedation time of the patients, an average of 1265 hours was found. The clinical manifestations that were observed in the sample to a greater extent correspond to tachycardia 70%, agitation 52%, confusion and hypertension 37% and hallucination 24%. Conclusion: the manifestations that occurred most frequently were tachycardia, agitation, confusion, hypertension and, less frequently, hallucination[AU]

Introdução: na unidade de terapia intensiva (UTI), as pessoas tratadas com patologias relevantes estão sob sedação. Uma vez sob os princípios da supressão da sedação, é importante identificar as manifestações que apresentam, típicas das sedações. Objetivo: Descrever as manifestações clínicas da síndrome de supressão da sedação presentes em pacientes atendidos em um Hospital Público da Cidade de Corrientes no período de janeiro a dezembro de 2022. Metodologia: estudo quantitativo, descritivo, transversal e observacional. A amostra incluiu pacientes adultos internados em UTI. O cálculo do tamanho amostral foi realizado pelo método probabilístico aleatório simples, resultando em uma amostra de 100 prontuários. A observação foi utilizada para a coleta de dados e um formulário semiestruturado e anônimo foi utilizado como instrumento. Cada formulário continha dados específicos onde foram categorizadas as variáveis em estudo, como idade, sexo, comorbidades, tempo de sedação, tipo de sedação, sedação utilizada, agitação, confusão, alucinação, sudorese, taquicardia. Resultados: em relação à idade obteve-se uma média de 49 anos, o sexo predominante foi o masculino com 52%, quanto às comorbidades mais frequentes, 20% apresentavam Insuficiência Respiratória Aguda e 16% Insuficiência Renal. O motivo de internação na UTI em maior proporção com 33% foi por dificuldade respiratória e pós-cirúrgicos complicados 32%. Os medicamentos de maior escolha foram midazolam 94%, seguido de fentanil 80%. Quanto ao tempo de sedação dos pacientes, foi encontrada uma média de 1265 horas. As manifestações clínicas mais observadas na amostra correspondem a taquicardia 70%, agitação 52%, confusão e hipertensão 37% e alucinação 24%. Conclusão: as manifestações que ocorreram com maior frequência foram taquicardia, agitação, confusão, hipertensão e, menos frequentemente, alucinação[AU]

Sex differences in sensitivity to fentanyl effects in mice: Behavioral and molecular findings during late adolescence.

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.

Influence of intravenous fentanyl or dexmedetomidine infusions, combined with lidocaine and ketamine, on cardiovascular response, sevoflurane requirement and postoperative pain in dogs anesthetized for unilateral mastectomy.

OBJECTIVE: To compare the effects of constant rate infusions (CRI) of fentanyl or dexmedetomidine, combined with lidocaine and ketamine, on cardiovascular response during surgery, sevoflurane requirement and postoperative pain in dogs undergoing mastectomy. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A total of 29 female dogs with mammary tumors. METHODS: Premedication consisted of intramuscular acepromazine and morphine. General anesthesia was induced with intravenous propofol and maintained with sevoflurane. Dogs were randomized to be administered intravenous DLK [dexmedetomidine 1 µg kg-1 loading dose (LD) and 1 µg kg-1 hour-1; lidocaine 2 mg kg-1 LD and 3 mg kg-1 hour-1; ketamine 1 mg kg-1 LD and 0.6 mg kg-1 hour-1; n = 14] or FLK (fentanyl 5 µg kg-1 LD and 9 µg kg-1 hour-1; same doses of lidocaine and ketamine; n = 15) during anesthesia. Cardiorespiratory variables and end-tidal sevoflurane (Fe'Sevo) were recorded during surgery. The number of dogs administered ephedrine to treat arterial hypotension [mean arterial pressure (MAP) < 60 mmHg] was recorded. Meloxicam was administered to both groups. Postoperative pain and rescue analgesia requirement were assessed for 24 hours using the short form of the Glasgow Composite Measure Pain Scale. Data were compared using a mixed effects model or a Mann-Whitney test. RESULTS: More dogs required ephedrine in FLK than in DLK (67% versus 7%). Heart rate was not significantly different between groups, whereas lower values of MAP (p ≤ 0.01) and Fe'Sevo (p = 0.018) were observed in FLK than in DLK. Rescue analgesia was administered to 2/15 dogs in FLK and 0/14 dogs in DLK. CONCLUSIONS AND CLINICAL RELEVANCE: Based on the cardiovascular response during surgery, intraoperative infusions of FLK and DLK provided adequate antinociception. Infusion of DLK provided greater stability of blood pressure. Both protocols resulted in minimal need for additional analgesia within 24 hours postoperatively.

Maternal and neonatal effects of epidural levobupivacaine combined with fentanyl or sufentanil for elective cesarean-section in brachycephalic breeds.

The aim of this study was to compare the safety and clinical efficacy of epidural levobupivacaine combined with fentanyl or sufentanil for bitches undergoing elective cesarean-section and the impact of these anesthetic protocols on neonatal viability. The anesthetic protocol consisted of intramuscular morphine (0.2 mg/kg), followed by an intravenous bolus of propofol, in a dose sufficient to allowed the puncture of the lumbosacral space. The dogs were randomly allocated to receive 0.5 % levobupivacaine plus fentanyl (2.5 µg/kg; LF: n = 9) or sufentanil (1 µg/kg; LS; n = 11). Maternal cardiorespiratory parameters were monitored at specific time points during surgery. Intraoperative propofol supplementation was based on the presence of head and/or thoracic limb movements. Neonatal reflex responses and the Apgar score (range 0-10 points) were assessed at 5 and 60 minutes after birth. Puppy mortality rate was recorded until 24 hours after birth. Data were analyzed using two-way ANOVA, Tukey's test, Wilcoxon signed rank test, and Fisher's exact test (P < 0.05). Intraoperatively, maternal cardiorespiratory variables and propofol requirements were similar between groups, with no detection of anesthetic complications. The puppy reflex responses did not differ between groups at any time point. The medians (range) of Apgar scores were lower (P = 0.016) in the LF [5 (1-9)] at 5 minutes in comparison with LS [6 (2-9)], while no intergroup differences were recorded at 60 minutes [LF = 8 (2-10); LS = 9 (6-10]. The total mortality rate was 4.1 %. In the LS group, no puppies died, while in the LF 8 % of the puppies died in the first 24 hours after birth (P = 0.11). Epidural levobupivacaine combined with fentanyl or sufentanil provided minimal maternal and neonatal adverse effects, but neither protocol enabled the performance of a C-section in 100 % of the French and English bulldogs, without propofol supplementation.

Expiratory Muscle Activity Counteracts Positive End-Expiratory Pressure and Is Associated with Fentanyl Dose in Patients with Acute Respiratory Distress Syndrome.

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

Evaluation of pharmacological alternatives to reduce the pain and discomfort produced by electroejaculation in rams.

Electroejaculation (EE) represents the main technique for semen collection from domestic and wild animals independently of libido. However, the technique is associated with intense involuntary muscle contractions, vocalization, ataxia and lying down, caused by the electric stimulation of the nerves in the caudal epigastric region. These clinical manifestations represent important indicators of discomfort. In this context, the objective of this study was to evaluate two protocols of local anaesthetic blockade and two anatomical access for pharmacological desensitization of the caudal epigastric innervation as alternatives to promote comfort and reduce stress associated with EE in rams. For the study, four clinically healthy Dorper rams were selected. All animals were subjected to a design consisting of five semen collection treatments (n = 3 collections per treatment): T1-control, conventional EE without local anaesthetic blockade; T2, EE with ventral blockade (VB) of epigastric innervation using lidocaine hydrochloride 2%; T3, EE with VB of epigastric innervation using a combination of lidocaine hydrochloride 2% and fentanyl citrate; T4, EE with blockade of epigastric innervation through the perineal access using lidocaine hydrochloride 2%; T5, EE with blockade of epigastric innervation through the perineal access using a combination of lidocaine hydrochloride and fentanyl citrate. Seminal samples resulting from EE were subjectively evaluated for sperm motility and concentration, vigour and volume. Additionally, blood serum samples were collected for quantification of cortisol and creatine kinase (CK) enzyme. Assessments of stress and discomfort were conducted by measuring blood pressure, heart rate (HR) and respiratory rate (RR), as well as observing involuntary muscle contractions, ataxia and animal vocalization. No variations in blood pressure, sperm motility, vigour, CK, and cortisol were observed among the treatments. Individual variations were observed for the occurrence of vocalization (p = .0066), but there were no differences between the groups. Anaesthetic blockades conducted using the combination of lidocaine and fentanyl resulted in a lower incidence of ataxia during EE (p < .0001). It is concluded that the combination of fentanyl citrate and lidocaine hydrochloride results in less discomfort for animals undergoing EE, regardless of the anatomical access used for local anaesthetic blockades.

Long-term Effects of Cannabidiol and/or Fentanyl Exposure in Rats Submitted to Neonatal Pain.

The current study aimed to evaluate anxiety behavior, hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) and cannabinoid receptor 1 (CB1) gene expression, and nociceptive response in adulthood after a combination of fentanyl and cannabidiol (CBD) for nociceptive stimuli induced during the first week of life in rats. Complete Freund's adjuvant-induced inflammatory nociceptive insult on postnatal day (PN) 1 and PN3. Both fentanyl and CBD were used alone or in combination from PN1 to PN7. Behavioral and nociceptive tests were performed at PN60 and PN62. The expression of the microglial calcium-binding proteins Iba1 and CB1 was detected in the hippocampus using reverse Quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Our results suggest that the anxiety behavior response and immune activation in adult life depend on the CBD dose combined with fentanyl for the nociceptive stimuli induced during the first week of life. Treatment of neonatal nociceptive insult with CBD and opioids showed significant dose-dependent and male-female differences. The increased gene expression in the hippocampus of the analyzed cannabinoid gene supports this data. In addition, treatment with fentanyl led to an increase in CB1 protein expression. Moreover, the expression of Iba1 varied according to the administered dose of CBD and may or may not be associated with the opioid. A lower dose of CBD during the inflammatory period was associated with enhanced anxiety in adult life. PERSPECTIVE: The treatment of nociceptive stimuli with CBD and opioids during the first week of life demonstrated significant sex differences in adult life on anxiety behavior and supraspinal pain sensitivity.

First drug-checking study at an electronic festival and fentanyl detection in the central region of Mexico.

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.

Shift in hospital opioid use during the COVID-19 pandemic in Brazil: a time-series analysis of one million prescriptions.

The pronounced change in the profile of hospitalized patients during COVID-19 and the severe respiratory component of this disease, with a great need for mechanical ventilation, led to changes in the consumption pattern of some medicines and supplies. This time-series study analyzed the in-hospital consumption of opioids during the COVID-19 pandemic in 24 Brazilian hospitals compared to the pre-pandemic period. Data included 711,883 adult patients who had opioids prescribed. In 2020, the mean consumption was significantly higher compared to 2019 for parenteral fentanyl, enteral methadone, and parenteral methadone. It was significantly lower for parenteral morphine parenteral sufentanil, and parenteral tramadol. For remifentanil, it did not differ. The number of patients in 2020 was lower but the mean consumption was higher for fentanyl, parenteral methadone, and remifentanil. It was lower for enteral methadone and parenteral sufentanil. The consumption of parenteral morphine and parenteral tramadol was stable. There was a relevant increase in hospital consumption of some potent opioids during the COVID-19 pandemic in Brazil. These results reinforce the concern about epidemiological surveillance of opioid use after periods of increased hospital use since in-hospital consumption can be the gateway to the misuse or other than the prescribed use of opioids after discharge.

Xylazine potentiates the lethal but not the rewarding effects of fentanyl in mice.

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.

A comparison of intra and postoperative analgesic effects of sacrococcygeal and lumbosacral epidural levobupivacaine in cats undergoing ovariohysterectomy.

The aim of this study was to compare the intra and postoperative analgesic effects of sacrococcygeal epidural levobupivacaine with those of lumbosacral levobupivacaine in feline ovariohysterectomy. Thirty-six cats were premedicated with intramuscular acepromazine (0.05 mg/kg) and meperidine (6 mg/kg). Anesthesia was induced with intravenous propofol and maintained with isoflurane in oxygen. The cats were randomly assigned one of the three treatments receiving 0.33% levobupivacaine (0.3 mL/kg) into the sacrococcygeal (S-C group, n=12) or lumbosacral (L-S group, n=12) epidural space, or the same volume of 0.9% saline solution into one of the epidural approaches (Control group, n=12). Intraoperatively, cardiorespiratory variables, end-tidal isoflurane concentration (FE´ISO), and fentanyl requirements were recorded. Postoperative pain was assessed by the UNESP (Universidade Estadual Paulista)-Botucatu multidimensional composite pain scale and the Glasgow feline composite measure pain scale up to 8 hr post-extubation. Morphine was administered as rescue analgesia. Overall FE´ISO and fentanyl requirements were lower in the L-S and S-C compared to the Control (P=0.002-0.048, respectively). There was no significant difference in the cardiorespiratory variables during anesthesia, postoperative pain and rescue analgesia among groups. The time to standing after anesthesia was prolonged in the L-S and S-C groups than in the Control (P<0.001). Lumbosacral and sacrococcygeal epidural levobupivacaine resulted in similar decreases in isoflurane requirements and intraoperative fentanyl supplementation in the cats, with no postoperative benefits.

Fentanyl, heroin, and methamphetamine-based counterfeit pills sold at tourist-oriented pharmacies in Mexico: An ethnographic and drug checking study.

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.

Safety and effectiveness of adding fentanyl or sufentanil to spinal anesthesia: systematic review and meta-analysis of randomized controlled trials

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.

Effect of magnesium sulfate with ketamine infusions on intraoperative and postoperative analgesia in cancer breast surgeries: a randomized double-blind trial

Abstract Background Opioids are the cornerstone in managing postoperative pain; however, they have many side effects. Ketamine and Magnesium (Mg) are NMDA receptor antagonists used as adjuvant analgesics to decrease postoperative opioid consumption. Objective We assumed that adding Mg to ketamine infusion can improve the intraoperative and postoperative analgesic efficacy of ketamine infusion alone in cancer breast surgeries. Methods Ninety patients aged between 18 and 65 years and undergoing elective cancer breast surgery were included in this prospective randomized, double-blind study. Group K received ketamine 0.5 mg.kg-1 bolus then 0.12 mg.kg-1.h-1 infusion for the first 24 hours postoperatively. Group KM: received ketamine 0.5 mg.kg-1 and Mg sulfate 50 mg.kg-1, then ketamine 0.12 mg.kg-1.h-1 and Mg sulfate 8 mg.kg-1.h-1 infusions for the first 24 hours postoperative. The primary outcome was the morphine consumption in the first 24 hours postoperative, while the secondary outcomes were: intraoperative fentanyl consumption, NRS, side effects, and chronic postoperative pain. Results Group KM had less postoperative opioid consumption (14.12 ± 5.11 mg) than Group K (19.43 ± 6.8 mg). Also, Group KM had less intraoperative fentanyl consumption. Both groups were similar in postoperative NRS scores, the incidence of side effects related to opioids, and chronic neuropathic pain. Conclusion Adding Mg to ketamine infusion can safely improve intraoperative and postoperative analgesia with opioid-sparing effect in cancer breast surgery.

Anesthetic effects of isoflurane and fentanyl infusion in capuchin monkeys (Sapajus sp) undergoing salpingectomy or deferentectomy, previously chemically restrained with ketamine-midazolam or ketamine-dexmedetomidine.

BACKGROUND: This study evaluated the anesthetic and cardiorespiratory effects of two anesthetic protocols for salpingectomy or deferentectomy in capuchin monkeys (Sapajus sp). MATERIALS AND METHODS: Five capuchin monkeys (5 per group) received ketamine (20 mg/kg) combined with midazolam (0.5 mg/kg; group KM) or dexmedetomidine (5 µg/kg; group KD) intramuscularly. Anesthesia is induced with propofol intravenously and maintained with isoflurane. Before the start of surgery, fentanyl 3 µg/kg was administered IV, and continuous infusion (10 µg/kg/min) IV was started. Times and quality of anesthetic recovery were evaluated postoperatively. RESULTS: KM and KD resulted in adequate chemical restraint. KD resulted in bradycardia. Intraoperative heart rate and systolic blood pressure were higher in KM than in KD. Both groups had smooth recovery. Time to standing was longer in KM than in KD. CONCLUSION: Both protocols allowed the performance of surgeries, with few cardiorespiratory effects. Anesthetic recovery was smooth and shorter in KD group.

Influence of Constant Rate Infusions of Fentanyl Alone or in Combination With Lidocaine and Ketamine on the Response to Surgery and Postoperative Pain in Isoflurane Anesthetized Dogs Undergoing Unilateral Mastectomy: A Randomized Clinical Trial.

The aim of this study was to compare the effects of constant rate infusions (CRI) of fentanyl alone or combined with lidocaine and ketamine (FLK), on physiological parameters, isoflurane requirements and the number of postoperative analgesic rescues in dogs undergoing unilateral mastectomy. Twenty-two dogs were premedicated with acepromazine 0.02 mg/kg and morphine 0.5 mg/kg and anesthetized with propofol and isoflurane. Dogs were randomly assigned to 1 of 2 groups: Fentanyl group (fentanyl 5 µg/kg loading dose [LD] and 9 µg/kg/h CRI; n = 11); FLK group (fentanyl [same doses]; lidocaine 2 mg/kg LD and 3 mg/kg/h CRI; ketamine 1.0 mg/kg LD and 0.6 mg/kg/h CRI; = 11). Intraoperative evaluations were performed before the start of surgery and administration of the treatments (T0); three minutes after the LD (T1); during incision and tissue divulsion (T2); during closure of the surgical wound (T3). Meloxicam (0.1 mg/kg) was administered at T3. Blood samples were collected for determination of plasma concentrations of fentanyl, lidocaine and ketamine. Pain scores and the number of postoperative analgesic rescues with morphine (0.5 mg/kg) were evaluated for 24 hours postoperatively using the short form of the Glasgow Composite Measure Pain Scale. Compared to T0, significant decreases in heart rate (from 84 ± 28 to 53 ± 16 bpm in the Fentanyl group and from 93 ± 16 to 63 ± 15 bpm in FLK) and mean arterial pressure (from 61 ± 5 to 49 ± 10 mmHg in Fentanyl and from 59 ± 3 to 38 ± 6 mmHg in FLK) were observed at T1. Arterial hypotension was transient, with normalization of values at T2 and T3. The expired fraction of isoflurane did not differ significantly between the groups. Plasma concentrations of fentanyl, lidocaine and ketamine remained within the therapeutic range. Postoperatively, the number of dogs requiring analgesic rescue was significantly lower in the FLK (0/11, 0%) than in the Fentanyl group (5/11, 45%). In dogs administered morphine and meloxicam as part of the anesthesia protocol, an intraoperative CRI of FLK abolished the requirement for postoperative analgesic rescue for 24 hours in dogs undergoing mastectomy.

Usefulness of Inhaled Sedation in Patients With Severe ARDS Due to COVID-19.

BACKGROUND: Sedation in intensive care is fundamental for optimizing clinical outcomes. For many years the world has been facing high rates of opioid use, and to combat the increasing opioid addiction plans at both national and international level have been implemented.1 The COVID-19 pandemic posed a major challenge for health systems and also increased the use of sedatives and opioid analgesia for prolonged periods of time, and at high doses, in a significant proportion of patients. In our institutions, the shortage of many drugs for intravenous (IV) analgosedation forces us to alternatives to replace out-of-stock drugs or to seek sedation goals, which are difficult to obtain with traditional drugs at high doses.2 METHODS: This was an analytical retrospective cohort study evaluating the follow-up of subjects with inclusion criteria from ICU admission to discharge (alive or dead). Five end points were measured: need for high-dose opioids (≥ 200 µg/h), comparison of inhaled versus IV sedation of opioid analgesic doses, midazolam dose, need for muscle relaxant, and risk of delirium. RESULTS: A total of 283 subjects were included in the study, of whom 230 were administered IV sedation and 53 inhaled sedation. In the inhaled sedation group, the relative risks (RRs) were 0.5 (95% CI 0.4-0.8, P = .045) for need of high-dose fentanyl, 0.3 (95% CI 0.20-0.45, P < .001) for need of muscle relaxant, and 0.8 (95% CI 0.61-1.15, P = .25) for risk of delirium. The median difference of fentanyl dose between the inhaled sedation and IV sedation groups was 61 µg/h or 1,200 µg/d (2.2 ampules/d, P < .001), and that of midazolam dose was 5.7 mg/h. CONCLUSIONS: Inhaled sedation was associated with lower doses of opioids, benzodiazepines, and muscle relaxants compared to IV sedation. This therapy should be considered as an alternative in critically ill patients requiring prolonged ventilatory support and where IV sedation is not possible, always under adequate supervision of ICU staff.

Safety and effectiveness of adding fentanyl or sufentanil to spinal anesthesia: systematic review and meta-analysis of randomized controlled trials.

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.

Role of melatonin in attenuation of hemodynamic response to intubation and anesthetic requirements: a randomized, controlled, double-blind study.

BACKGROUND: Melatonin has been studied to have anxiolytic, sedative, and analgesic effects. However, there is limited data on the effect of melatonin in the attenuation of hemodynamic response to intubation. We aimed to study whether preanesthetic oral melatonin attenuates hemodynamic responses to intubation and anesthetic requirements. METHODS: Sixty-four patients scheduled for laparoscopic cholecystectomy were randomized into melatonin or placebo group (n...=...32 each). Melatonin group received two tablets (3...mg each) of melatonin, and the placebo group received two tablets of vitamin D3 120...min before induction. Hemodynamic parameters were recorded during induction and postintubation for 15...minutes. Total induction dose of propofol, total intraoperative fentanyl consumption, and adverse effects of melatonin were also noted. RESULTS: Postintubation rise in heart rate (HR) was less in the melatonin group compared to the placebo group (10.59% vs. 37.08% at 1...min, respectively) (p...<...0.0001). Maximum percentage increase in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) was lesser in melatonin group than placebo group (SBP 9.25% vs. 37.73%, DBP 10.58% vs. 35.51%, MBP 9.99% vs. 36.45% at 1 min postintubation. respectively) (p...<...0.0001). Induction dose of propofol (1.42 mg.kg-1 vs. 2.01...mg.kg-1) and the number of patients requiring additional fentanyl intraoperatively (3 vs. 11) were also significantly reduced in the melatonin group. CONCLUSION: Premedication with 6...mg of oral melatonin resulted in significant attenuation of postintubation rise in HR, SBP, DBP, and MBP. It also reduced the induction dose of propofol, total intraoperative fentanyl consumption without any adverse effects.

Effect of magnesium sulfate with ketamine infusions on intraoperative and postoperative analgesia in cancer breast surgeries: a randomized double-blind trial.

BACKGROUND: Opioids are the cornerstone in managing postoperative pain; however, they have many side effects. Ketamine and Magnesium (Mg) are NMDA receptor antagonists used as adjuvant analgesics to decrease postoperative opioid consumption. OBJECTIVE: We assumed that adding Mg to ketamine infusion can improve the intraoperative and postoperative analgesic efficacy of ketamine infusion alone in cancer breast surgeries. METHODS: Ninety patients aged between 18 and 65 years and undergoing elective cancer breast surgery were included in this prospective randomized, double-blind study. Group K received ketamine 0.5.ßmg.kg...1 bolus then 0.12.ßmg.kg...1.h...1 infusion for the first 24.ßhours postoperatively. Group KM: received ketamine 0.5.ßmg.kg...1 and Mg sulfate 50.ßmg.kg...1, then ketamine 0.12.ßmg.kg...1.h...1 and Mg sulfate 8.ßmg.kg...1.h...1 infusions for the first 24.ßhours postoperative. The primary outcome was the morphine consumption in the first 24.ßhours postoperative, while the secondary outcomes were: intraoperative fentanyl consumption, NRS, side effects, and chronic postoperative pain. RESULTS: Group KM had less postoperative opioid consumption (14.12.ß...ß5.11.ßmg) than Group K (19.43.ß...ß6.8.ßmg). Also, Group KM had less intraoperative fentanyl consumption. Both groups were similar in postoperative NRS scores, the incidence of side effects related to opioids, and chronic neuropathic pain. CONCLUSION: Adding Mg to ketamine infusion can safely improve intraoperative and postoperative analgesia with opioid-sparing effect in cancer breast surgery.