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Background: Accidental hypothermia is associated with high morbidity and mortality. Research on treatment strategies for accidental hypothermia is complicated by the low incidence and heterogeneous patient population. We have developed a new method for clinical trials of experimental hypothermia, to enable further studies of active rewarming. If cold ambient air is effective as a cooling method, this would mimic the most frequent clinical setting of hypothermic patients and provide a feasible cooling method for field studies. We aimed to induce mild hypothermia in healthy volunteers by exposure to cold ambient air, and tested the hypothesis that drug-induced suppression of endogenous thermoregulation would be required. Methods: In a randomized, double-blind, crossover design, 15 healthy volunteers wearing wet clothes were put in a windy climate chamber set to 5 °C. Each participant completed the experimental procedure twice, once receiving active drugs (meperidine and buspirone) and once receiving placebo. The experiments were separated by a one-week wash-out period. Primary outcome was core temperature at termination, defined as 3 h of exposure or 35 °C. The between-groups difference was assessed using analysis of covariance (ANCOVA) with left censoring (Tobit model) and individual random intercept. Secondary outcomes were trajectory of core temperature and reduction of shivering. Results: At termination, the active drug vs placebo group differed in temperature by 1.4 °C. With adjustment for the removal of participants reaching 35 °C, the estimated mean difference was 1.7 °C (1.4–2.0, p < 0.001). Shivering was effectively reduced, but not completely inhibited by the drug regimen, and core temperature declined at a rate of − 0.82 °C per hour. Conclusion: The novel protocol utilizing cold air as a cooling method and drug-induced suppression of endogenous thermoregulation, is effective and enables future research projects. We have provided suggestions for minor alterations. Trial registration: EudraCT ID 2023–506020-81–00. [ABSTRACT FROM AUTHOR]

Medications for opioid use disorder (OUD) and overdose have been available for decades, yet nearly 70% of fatal drug overdoses in the United States are attributed to the opioid receptor agonist fentanyl and its analogs. There is a pressing need for more and better medications that reduce fentanyl use and prevent overdose. A humanized (h) monoclonal antibody (mAb) targeting fentanyl, hHY6-F9, was tested for attenuating intravenous fentanyl self-administration and reversing and preventing fentanyl-induced ventilatory depression in rhesus monkeys. A single administration of hHY6-F9 significantly decreased fentanyl, but not heroin or cocaine, self-administration. In some monkeys, fentanyl self-administration remained decreased for ~ 2 weeks. hHY6-F9 was as effective as 32 µg/kg naloxone in reversing fentanyl-induced ventilatory depression, with a single administration protecting against fentanyl-induced ventilatory depression for 2-3 weeks. Moreover, pharmacokinetic analyses indicate that hHY6-F9 continued to sequester fentanyl in the serum for 2 weeks. This study demonstrates that hHY6-F9 selectively attenuates the positive reinforcing and ventilatory depressant effects of fentanyl, indicating its possible utility for preventing relapse and overdose., Competing Interests: Declarations. Competing interests: The mAb described herein has been disclosed through patent applications (inventors: Pravetoni, Baehr, Hicks). M. Pravetoni is the founder of CounterX Therapeutics, Inc. Other authors have no financial conflicts or competing interests to declare., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Alpha2-adrenoceptor agonists (α2-agonists) are widely used in animals as sedatives and for pre-anaesthetic medication. Medetomidine has often been given subcutaneously (SC) to rats, although its absorption rate is slow and the individual variation in serum drug concentrations is high via this route. In addition, α2-agonists have various effects on metabolic and endocrine functions such as hypoinsulinaemia, hyperglycaemia and diuresis. Vatinoxan is a peripherally acting α2-adrenoceptor antagonist that, as a hydrophilic molecule, does not cross the blood-brain barrier in significant quantities and thus alleviates peripheral cardiovascular effects and adverse metabolic effects of α2-agonists. Aim of this study was to evaluate the effects of vatinoxan on sedation, blood glucose concentration, voiding and heart and respiratory rates and arterial oxygen saturation in rats sedated with subcutaneous medetomidine, midazolam and fentanyl. Results: Onset of sedation and loss of righting reflex occurred significantly faster with vatinoxan [5.35 ± 1.08 (mean ± SD) versus 12.97 ± 6.18 min and 6.53 ± 2.18 versus 14.47 ± 7.28 min, respectively]. No significant differences were detected in heart and respiratory rates and arterial oxygen saturation between treatments. Blood glucose concentration (18.3 ± 3.6 versus 11.8 ± 1.2 mmol/L) and spontaneous urinary voiding [35.9 (15.1–41.6), range (median) versus 0.9 (0–8.0) mL /kg/min] were significantly higher without vatinoxan. Conclusions: Acceleration of induction of sedation, alleviation of hyperglycaemia and prevention of profuse diuresis by vatinoxan may be beneficial when sedating rats for clinical and experimental purposes with subcutaneous medetomidine, midazolam and fentanyl. [ABSTRACT FROM AUTHOR]

Background: During scoliosis surgery, motor evoked potentials (MEP), and somatosensory evoked potentials (SSEP) have been reported to be affected by the use of higher doses of anesthetic agents. Dexmedetomidine, a sympatholytic agent, an alpha‐2 receptor agonist, has been used as an adjunctive agent to lower anesthetic dose. However, there is conflicting evidence regarding the effects of dexmedetomidine on the intraoperative neurophysiological monitoring of MEP and SSEP during surgery, particularly among pediatric patients. Objectives: This systematic review aimed to determine whether, during spinal fusion surgery in pediatric patients with scoliosis, dexmedetomidine alters MEP amplitude or SSEP latency and amplitude and, if so, whether different doses of dexmedetomidine display different effects (PROSPERO registration number CRD42022300562). Methods: We searched PubMed, Scopus, and Cochrane Library on January 1, 2022 and included randomized controlled trials, observational cohort and case–control studies and case series investigating dexmedetomidine in the population of interest and comparing against a standardized anesthesia regimen without dexmedetomidine or comparing multiple doses of dexmedetomidine. Animal and in vitro studies and conference abstracts were excluded. Results: We found substantial heterogeneity in the risk of bias (per Cochrane‐preferred tools) of the included articles (n = 5); results are summarized without meta‐analysis. Articles with the lowest risk of bias indicated that dexmedetomidine was associated with MEP loss and that higher doses of dexmedetomidine increased risk. In contrast, articles reporting no association between dexmedetomidine and MEP loss suffered from higher risk of bias, including suspected or confirmed problems with confounding, outcome measurement, participant selection, results reporting, and lack of statistical transparency and power. Conclusion: Given the limitations of the studies available in the literature, it would be advisable to conduct rigorous randomized controlled trials with larger sample sizes to assess the effects of dexmedetomidine use of in scoliosis surgery in pediatric patients. [ABSTRACT FROM AUTHOR]

Background: Intravenous adenosine induces pharmacological stress by causing vasodilatation and thus carries the risk of severe hypotension when combined with vasodilatory effects of anesthetic agents. Objective: This study describes our experience with a reduced dose adenosine cardiac magnetic resonance imaging (MRI) protocol in young children under general anesthesia (GA). Materials and methods: This is a retrospective report of all patients from birth to 18 years who underwent adenosine stress cardiac MRI under GA between August 2018 and November 2022. Based on our anecdotal experience of severe adverse effects in patients receiving adenosine infusion under GA and in discussion with the pediatric anesthesia team, we developed a modified protocol starting at a dose of 110 mcg/kg/min with incremental escalation to a full dose of 140 mcg/kg/min to achieve desired hemodynamic effect. Results: Twenty-two children (mean age 6.5 years, mean weight 28 kg) satisfied the inclusion criteria. The diagnoses included Kawasaki disease (7), anomalous aortic origin of left coronary artery (3), anomalous aortic origin of right coronary artery (2), coronary fistula (3), repaired d-transposition of great arteries (2), repaired anomalous left coronary artery from pulmonary artery (2), repaired truncus arteriosus with left coronary artery occlusion (1), extracardiac-Fontan with left coronary artery myocardial bridge (1), and post heart transplantation (1). Nine patients needed dose escalation beyond 110 mcg/kg/min. Two patients had transient hypotension during testing (systemic blood pressure drop > 25 mmHg). No patient developed significant heart block or bronchospasm. Six patients (repeat study in one) demonstrated inducible perfusion defects (27%) on stress perfusion sequences—5 of whom had confirmed significant coronary abnormalities on angiography or direct surgical inspection. Conclusion: A reduced/incremental dose adenosine stress cardiac MRI protocol under GA in children is safe and feasible. This avoids severe hypotension which is both unsafe and may result in inaccurate data. [ABSTRACT FROM AUTHOR]

Purpose of Review: To review the blood pressure (BP) effects of pain and analgesic medications and to help interpret BP changes in people suffering from acute or chronic pain. Recent Findings: Acute pain evokes a stress response which prompts a transient BP increase. Chronic pain is associated with impaired regulation of cardiovascular and analgesia systems, which may predispose to persistent BP elevation. Also analgesics may have BP effects, which vary according to the drug class considered. Data on paracetamol are controversial, while multiple studies indicate that non-steroidal anti-inflammatory drugs may increase BP, with celecoxib showing a lesser impact. Hypotension has been reported with opioid drugs. Among adjuvants, tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors could be pro-hypertensive due to potentiation of adrenergic transmission. Summary: Pain and analgesics may induce a clinically significant BP destabilization. The implications on hypertension incidence and BP control remain unclear and should be explored in future studies. [ABSTRACT FROM AUTHOR]

Rationale: Rapidly evolving e-cigarette technology developed for self-administering nicotine aerosol has the potential to be utilized to self-administer other aerosolized drugs of abuse. Rodent models which mirror characteristics of human e-cigarette use are necessary to explore the degree to which this may be a public health concern. Objectives: Our goal was to develop a highly translational model of discrete nose-only aerosol puff drug delivery to explore the reinforcing effects of fentanyl and sufentanil aerosols in rats. Methods: Male and female Sprague–Dawley rats were trained to perform a multiple schedule FR1 lever-press, 4-s (second) nose hold operant during which the subject's orofacial areas were exposed to drug-free glycerol/propylene glycol aerosol produced by a commercial e-cigarette at a power setting of 18 watts. Each completed 4-s drug-free vehicle aerosol exposure resulted in a 3-s presentation of a 0.1-ml dipper of sweetened milk solution. After training, rats were then allowed to self-administer 4-s nose-only puffs of fentanyl (100–6000 µg/ml) or sufentanil (30–500 µg/ml) aerosol in the absence of paired milk dipper reinforcers. Results: All 31 rats learned the lever-press/nose-poke multiple schedule for milk dippers alone and 25 accepted exposure to 4 s of 18 watts of drug-free vehicle aerosol when paired with milk dipper presentations. In the absence of paired milk dipper presentations, fentanyl aerosol puffs at concentrations of 1000 and 3000 µg/ml as well as 100 µg/ml puffs of sufentanil served as reinforcers compared to both air puffs and drug-free vehicle aerosol puffs. There were no significant differences between males and females in number of fentanyl or sufentanil puffs self-administered. Conclusions: Discrete nose-only puffs of two potent opioids under exposure conditions comparable to puff durations in human e-cigarette users serve as reinforcers in rats. This outcome suggests that under appropriate conditions e-cigarettes might be a potential alternative delivery mechanism for illicit opioids. [ABSTRACT FROM AUTHOR]

Thiamylal is an ultrashort‐acting barbiturate used for intravenous administration or general anesthesia induction. However, some cases of poisoning and suicide with thiamylal administration have been reported. Additionally, there are few reports on its analysis in the organs and adipose tissue, which requires purification by column chromatography and evaporation. A rapid and sensitive method was developed for quantifying thiamylal and its metabolite, secobarbital, in the adipose tissue, serum, and liver using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Samples were prepared using modified QuEChERS extraction. For adipose tissue samples, an acetonitrile–hexane partitioning step was added to the extraction. This method was applied to investigate a suspected self‐poisoning autopsy case. The quantitation accuracy for thiamylal added to porcine pericardial fat (0.18 µg/g), human serum (0.015 µg/mL), and porcine liver (0.18 µg/g) was 103%, 113%, and 95.3%, respectively. The quantitation limits calculated for porcine pericardial fat, human serum, and porcine liver at a signal‐to‐noise ratio of 10 were 0.06 µg/g, 0.005 µg/mL, and 0.06 µg/g, respectively. In addition, the thiamylal and secobarbital levels in the forensic autopsy case were 140 and 1.5 µg/g, respectively, in myocardial fat; 3.5–4.9 and 0.12–0.20 µg/mL, respectively, in serum; and 6.2–42 and 0.58–1.1 µg/g, respectively, in liver tissue. Thiamylal is especially distributed in the adipose tissue. The thiamylal‐to‐fat ratio may help estimate the time from administration to death. The developed modified QuEChERS extraction method with acetonitrile–hexane partitioning is suitable for analyzing hydrophobic compounds, such as thiamylal, in the adipose tissue. [ABSTRACT FROM AUTHOR]