BACKGROUND: Ketamine and fentanyl are commonly used for sedation and induction of anesthesia in critically ill patients. This study aimed to compare the hemodynamic effects of ketamine versus fentanyl bolus in patients with septic shock.
METHODS: This randomized controlled trial included mechanically ventilated adults with septic shock receiving sedation. Patients were randomized to receive either 1 mg/kg ketamine bolus or 1 mcg/kg fentanyl bolus. Cardiac output (CO), stroke volume (SV), heart rate (HR), and mean arterial pressure (MAP) were measured at the baseline, 3, 6, 10, and 15 min after the intervention. Delta CO was calculated as the change in CO at each time point in relation to baseline measurement. The primary outcome was delta CO 6 min after administration of the study drug. Other outcomes included CO, SV, HR, and MAP.
RESULTS: Eighty-six patients were analyzed. The median (quartiles) delta CO 6 min after drug injection was 71(37, 116)% in the ketamine group versus - 31(- 43, - 12)% in the fentanyl group, P value < 0.001. The CO, SV, HR, and MAP increased in the ketamine group and decreased in the fentanyl group in relation to the baseline reading; and all were higher in the ketamine group than the fentanyl group.
CONCLUSIONS: In patients with septic shock, ketamine bolus was associated with higher CO and SV compared to fentanyl bolus.
BACKGROUND: Date of registration: 24/07/2023.
RESULTS: gov Identifier: NCT05957302. URL: https://clinicaltrials.gov/study/NCT05957302 .

OBJECTIVE: Fueled by the prescription opioid overdose crisis and increased influx of illicitly manufactured fentanyl, fentanyl overdoses continue to be a public health crisis that has cost the US economy over $1 trillion in reduced productivity, health care, family assistance, criminal justice, and accounted for over 74,000 deaths in 2023. A recent demographic shift in the opioid crisis has led to a rise in overdose deaths among the Latinx population. Harm reduction interventions, including the use of naloxone and fentanyl test strips, have been shown to be effective measures at reducing the number of opioid overdose deaths. The aim of this scoping review is to summarize naloxone and fentanyl test strip interventions and public health policies targeted to Latinx communities.
METHODS: PubMed, CINHAL, Web of Science, Embase, and PsycINFO research databases using the keywords \"fentanyl,\" \"Latinx,\" \"Harm Reduction,\" \"Naloxone,\" and \"Fentanyl Test Strips\'\' to identify studies published between January 1, 2013 and December 31, 2023. Endnote and Covidence software were used to catalog and manage citations for review of studies. Subsequently, studies that met inclusion criteria were then summarized using resulting themes.
RESULTS: Twenty-seven articles met the inclusion criteria and were further abstracted for the scoping review. Of these articles, 77.7% (n = 21) included a naloxone intervention, while only 11.1% (n = 3) included a fentanyl test strip intervention. Furthermore, 30.1% (n = 8) of these studies were Latinx targeted, and 7.7% (n = 2) of the studies were adapted for Latinx populations. Four themes, including an overall lack of knowledge and awareness, a lack of access to harm reduction or opioid overdose prevention resources, an overall lack of culturally adapted and/or targeted interventions, and restrictive and punitive policies that limit the effectiveness of protective factors were highlighted in this scoping review.
CONCLUSIONS: Limited published research exists on the use of emerging harm reduction behaviors, such as the use of naloxone and fentanyl test strips as community intervention strategies to prevent opioid overdose deaths. Even fewer publications exist on the targeting and cultural adaptation of harm reduction interventions responsive to Latinx communities, especially those using theoretical approaches or frameworks to support these interventions. Future research is needed to assess the unique needs of Latinx populations and to develop culturally responsive programs to prevent opioid-related overdose deaths among this population.

BACKGROUND: Xylazine is increasingly prevalent in the unregulated opioid supply in the United States. Exposure to this adulterant can lead to significant harm, including prolonged sedation and necrotic wounds. In the absence of literature describing healthcare providers\' experiences with treating patients who have been exposed to xylazine, we aimed to explore what gaps must be addressed to improve healthcare education and best practices.
METHODS: From October 2023 to February 2024, we conducted a sequential explanatory mixed-methods study, with (1) a quantitative survey phase utilizing convenience sampling of healthcare providers treating patients in Connecticut and (2) a qualitative semi-structured interview phase utilizing purposive sampling of providers with experience treating patients with xylazine exposure. Summary statistics from the survey were tabulated; interview transcripts were analyzed using thematic analysis.
RESULTS: Seventy-eight eligible healthcare providers participated in our survey. Most participants had heard of xylazine (n = 69, 95.8%) and had some knowledge about this adulterant; however, fewer reported seeing one or more patients exposed to xylazine (n = 46, 59.8%). After sampling from this subgroup, we conducted fifteen in-depth interviews. This qualitative phase revealed five themes: (1) while xylazine is novel and of concern, this is not necessarily exceptional (i.e., there are other emerging issues for patients who use drugs); (2) participants perceived that xylazine was increasingly prevalent in the drug supply, even if they were not necessarily seeing more patients with xylazine-related outcomes (XROs); (3) patients primarily presented with non-XROs, making it difficult to know when conversations about xylazine were appropriate; (4) patients with XROs may experience issues accessing healthcare; (5) providers and their patients are learning together about how to minimize XROs and reduce the sense of helplessness in the face of a novel adulterant.
CONCLUSIONS: Xylazine-specific education for healthcare providers is currently insufficient. Improving this education, as well as resources (e.g., drug checking technologies) and data (e.g., research on prevention and treatment of XROs), is crucial to improve care for patients who use drugs.

OBJECTIVE: To examine the effect of ketanserin and naloxone on fentanyl-induced motor activity in isoflurane-anaesthetized pigs.
METHODS: Randomized, blinded, prospective two-group study.
METHODS: A group of 12 crossbred pigs weighing 22-31 kg.
METHODS: Fentanyl was administered to isoflurane-anaesthetized pigs at 7.5 μg kg-1 hour-1 for 40 minutes intravenously, followed by an intravenous injection of naloxone 0.1 mg kg-1 or ketanserin 1 mg kg-1. Electromyography (EMG) and accelerometry were used to record motor unit activity and tremors, respectively. To test the effect of drug administration on motor activity, data from a 5 minute period at baseline, immediately before and after antagonist injection were compared in a mixed model; p < 0.05.
RESULTS: Results are reported with the median difference, 95% confidence intervals and corresponding p-values in brackets. Fentanyl significantly increased EMG activity [30.51 (1.84-81.02) μV, p = 0.004] and induced tremors [0.09 (0.02-0.18) m s-2, p < 0.001] in 10 of 12 pigs. Ketanserin significantly reduced EMG [32.22 (6.29-136.80) μV, p = 0.001] and tremor [0.10 (0.03-0.15) m s-2, p = 0.007] activity. No significant effect was found for naloxone on EMG [26.76 (-13.28-91.17) μV, p = 0.4] or tremors [0.08 (-0.01-0.19) m s-2, p = 0.08].
CONCLUSIONS: Fentanyl can induce motor activity in anaesthetized pigs, with a suggested link to the serotonergic system. This study shows that ketanserin can antagonize this activity, which supports the role of serotonin. This knowledge contributes to the general understanding of the motor effects of fentanyl and especially the problem of tremors in anaesthetized pigs.

In the United States, illicit fentanyl is often trafficked as blue tablets mimicking the legitimate M-30 oxycodone tablet produced by Mallinckrodt. The analysis of dyes extracted from seized fentanyl tablets could provide a useful tool for law enforcement to establish linkages between cases and could prove useful for attributing a seizure to a given trafficking organization. Fentanyl tablet seizures associated with a particular drug trafficking organization (DTO), either through investigative or intelligence information, were used as the sample set for this study. The blue dye from the tablets was isolated by solid phase extraction and then qualitatively and quantitatively analyzed via ultraviolet-visible spectroscopy. This research revealed that the illicit tableting facilities use a different dye than several known pharmaceutical companies. The concentration of dye in individual tablets within a seizure proved to be very minimal, and the small sample size made it difficult to draw linkages from case to case. Analysis of the dyes could not effectively differentiate between the drug trafficking organizations in the tested population due to each DTO using the same dye; however, it is important to note that the dye found was consistent between illicit tablets.

BACKGROUND: Illicit opioid overdose continues to rise in North America and is a leading cause of death. Mathematical modeling is a valuable tool to investigate the epidemiology of this public health issue, as it can characterize key features of population outcomes and quantify the broader effect of structural and interventional changes on overdose mortality. The aim of this study is to quantify and predict the impact of key harm reduction strategies at differing levels of scale-up on fatal and nonfatal overdose among a population of people engaging in unregulated opioid use in Toronto.
METHODS: An individual-based model for opioid overdose was built featuring demographic and behavioural variation among members of the population. Key individual attributes known to scale the risk of fatal and nonfatal overdose were identified and incorporated into a dynamic modeling framework, wherein every member of the simulated population encompasses a set of distinct characteristics that govern demographics, intervention usage, and overdose incidence. The model was parametrized to fatal and nonfatal overdose events reported in Toronto in 2019. The interventions considered were opioid agonist therapy (OAT), supervised consumption sites (SCS), take-home naloxone (THN), drug-checking, and reducing fentanyl in the drug supply. Harm reduction scenarios were explored relative to a baseline model to examine the impact of each intervention being scaled from 0% use to 100% use on overdose events.
RESULTS: Model simulations resulted in 3690.6 nonfatal and 295.4 fatal overdoses, coinciding with 2019 data from Toronto. From this baseline, at full scale-up, 290 deaths were averted by THN, 248 from eliminating fentanyl from the drug supply, 124 from SCS use, 173 from OAT, and 100 by drug-checking services. Drug-checking and reducing fentanyl in the drug supply were the only harm reduction strategies that reduced the number of nonfatal overdoses.
CONCLUSIONS: Within a multi-faceted harm reduction approach, scaling up take-home naloxone, and reducing fentanyl in the drug supply led to the largest reduction in opioid overdose fatality in Toronto. Detailed model simulation studies provide an additional tool to assess and inform public health policy on harm reduction.

UNASSIGNED: In postoperative patients in the intensive care units (ICUs), not only analgesics are needed but also sedation so that the patient can remain calm during treatment, especially patients with mechanical ventilation. By using the measurement parameters of the quantum consciousness index (qCON) and quantum noxious index (qNOX) in measuring the depth of sedation and adequacy of analgesics, the use of subdose ketamine instead of fentanyl and midazolam as sedative, analgesic agents can be performed as a new alternative to nociceptive monitoring methods with more objective results. This study aims to obtain results of comparing qCON and qNOX in postoperative patients by administering subdose ketamine compared with a combination of fentanyl and midazolam in RSUP Haji Adam Malik Medan.
UNASSIGNED: A randomized clinical trial with a double-blind approach has been used in this study. A total of 44 experimental samples were gathered and randomly split into two groups after meeting the criteria for inclusion. Group A administered a ketamine subdose, whereas Group B administered a mixture of fentanyl and midazolam. The research data obtained were tested using Statistical Product and Science Service (SPSS).
UNASSIGNED: There were differences in the median, minimum, and maximum values of qCON and qNOX in the groups given subdose ketamine and fentanyl and midazolam, but these were not statistically significant (p > 0.05) at T0, T1, and T2.
UNASSIGNED: Administering a subdose of ketamine can provide sedation and analgesia comparable to fentanyl and midazolam.
UNASSIGNED: Masharto AR, Lubis AP, Bangun CG, Wahyuni AS. Quantium Consciousness Index and Quantium Noxious Index in Ketamine Subdose Administration Compared with Fentanyl and Midazolam in Postoperative ICU Patients: A Prospective, Observational Study. Indian J Crit Care Med 2024;28(6):581-586.

How to cite this article: Gupta A, Tomar DS. Am I Sedated or in Pain? Please Monitor by Brain. Indian J Crit Care Med 2024;28(6):531-532.

For the past decade, illicitly manufactured fentanyl has been a primary contributor in drug overdose deaths regardless of age. The pediatric population is particularly vulnerable to fentanyl exposure, yet there are limited case reports involving this population. Postmortem cases from 2019 to 2023 were retrospectively analyzed to determine the prevalence of fentanyl in decedents between 0 and 12 years of age. Over this time frame, the fentanyl positivity rate increased from 2.6 to 6.2% (n = 632). The most commonly reported age group was 0-4 years, with a peak around 1 year of age for toddlers. Fentanyl concentrations in blood (n = 573) ranged from 0.19 to 360 ng/mL (mean 18 ng/mL, median 6.9 ng/mL). Polydrug use was present in 428 cases; midazolam (n = 96) and methamphetamine (n = 66) were the most common drugs found concurrently in blood with fentanyl, followed by markers of illicitly manufactured fentanyl, such as xylazine (n = 23), para-fluorofentanyl (n = 18), and acetyl fentanyl (n = 17). This report contrasts the differences in postmortem pediatric fentanyl toxicology results for three groups of case histories: likely medical intervention (n = 113), pregnancy/birth related (n = 136), and inadvertent/intentional exposure (n = 196). Overall, this study provides a retrospective review of postmortem pediatric fentanyl concentrations in a variety of biological matrices and highlights the need for comprehensive toxicology testing in postmortem pediatric casework.

Fentanyl is a potent synthetic opioid widely used in medicine for its effective analgesic properties, particularly in surgical procedures and in the treatment of severe, chronic pain. In recent decades, however, there has been a worrying increase in the illicit use of fentanyl, particularly in North America. This rise in illicit use is concerning because fentanyl is associated with polydrug abuse, which adds layers of complexity and dangerous. This review provides a comprehensive examination of fentanyl, focusing on its synthesis and medical use. It also discusses the significance of the piperidine ring in medicinal chemistry as well as the critical role of fentanyl in pain management and anesthesia. Furthermore, it addresses the challenges associated with the abuse potential of fentanyl and the resulting public health concerns. The study aims to strike a balance between the clinical benefits and risks of fentanyl by advocating for innovative uses while addressing public health issues. It examines the chemistry, pharmacokinetics and pharmacodynamics of fentanyl and highlights the importance of personalized medicine in the administration of opioids. The review underscores the necessity of continuous research and adaptation in both clinical use and public health strategies.