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17 pages, 318 KB  
Article
Retrospective Evaluation of Anesthetic–Analgesic Protocols in Cats with and Without Transient Myocardial Thickening Following Gonadectomy
by Claire Pollak and Laura J. Ruys
Animals 2026, 16(13), 1979; https://doi.org/10.3390/ani16131979 - 26 Jun 2026
Viewed by 209
Abstract
Transient myocardial thickening (TMT) is considered a reversible feline cardiac disease that initially mimics hypertrophic cardiomyopathy. The exact etiopathogenesis remains unknown and is likely multifactorial. General anesthesia and surgery may contribute to the development of TMT in predisposed patients due to systemic inflammation, [...] Read more.
Transient myocardial thickening (TMT) is considered a reversible feline cardiac disease that initially mimics hypertrophic cardiomyopathy. The exact etiopathogenesis remains unknown and is likely multifactorial. General anesthesia and surgery may contribute to the development of TMT in predisposed patients due to systemic inflammation, perioperative stress, surgery itself, anesthetic management, and individual susceptibility. Additionally, inadequate analgesia could result in pain, which triggers a stress response. This stress response could stimulate endogenous catecholamine release and facilitate the development of TMT. In this retrospective study, anesthetic and analgesic protocols were compared between cats with and without TMT following gonadectomy. The study group consisted of 15 cats that presented with congestive heart failure after recent anesthesia and were later suspected of or diagnosed with TMT. The control group consisted of 300 cats without TMT after gonadectomy. All cats were considered healthy prior to gonadectomy based on physical examination; no echocardiography was performed prior to anesthesia. All cats in the TMT group were anesthetized with ketamine and an alpha-2 agonist, which was medetomidine in 14/15 (93.3%) and dexmedetomidine in 1/15 (6.7%) of the cats. In the control group, all cats were anesthetized with ketamine and dexmedetomidine. The ketamine dose was significantly higher (p < 0.001) in the TMT group compared to the control group, with a median dose of 6.78 mg/kg (4.52–10.34) and 4.29 mg/kg (2.08–6.45), respectively. The doses of the alpha-2 agonist and atipamezole were not significantly different. The most commonly administered non-steroidal anti-inflammatory drug was meloxicam in 83.3% of the study group cats and 98.7% of the control group cats. The dose of meloxicam was significantly lower (p < 0.001) in the study group compared to the control group, with median doses of 0.2 mg/kg (0–0.3) and 0.29 mg/kg (0–0.38), respectively. In the control group, 93.0% of the cats received buprenorphine, and 75.0% of males received intratesticular lidocaine. None of the cats in the study group received buprenorphine or intratesticular lidocaine during the procedure. Additionally, oxygen supplementation was significantly different (p < 0.017), and lack of oxygen was associated with the development of TMT. Anesthetic protocols between the two groups were significantly different. However, it is important to note that not all observed complications can solely be attributed to anesthetic or analgesic differences; effects might also be due to different perioperative circumstances. Full article
(This article belongs to the Section Companion Animals)
25 pages, 347 KB  
Article
Physiological Responses and Safety Evaluation of Combined Fremont™ Snare and Medetomidine–Ketamine–Acepromazine Immobilization in Free-Ranging Apennine Wolves (Canis lupus italicus)
by Simone Angelucci, Fabrizia Di Tana, Catarina Oliveira, José M. Almeida, Marco Carafa, Marta Gandolfi, Lorenzo Petrizzelli, Giovanna Di Domenico, Cristina E. Di Francesco, Camilla Smoglica and Antonio Antonucci
Animals 2026, 16(11), 1735; https://doi.org/10.3390/ani16111735 - 4 Jun 2026
Viewed by 585
Abstract
The Apennine wolf (Canis lupus italicus) is a distinct subspecies whose ongoing population recovery in Italy has progressively increased the demand for live capture protocols validated for scientific monitoring and conservation management. Despite the widespread use of mechanical and chemical immobilization [...] Read more.
The Apennine wolf (Canis lupus italicus) is a distinct subspecies whose ongoing population recovery in Italy has progressively increased the demand for live capture protocols validated for scientific monitoring and conservation management. Despite the widespread use of mechanical and chemical immobilization in European wolf management, no study has to date systematically evaluated the combined use of the Fremont™ humane foot snare with a medetomidine-ketamine-acepromazine (MKA) protocol in this subspecies, nor characterized the associated cardiorespiratory, thermal, and hematobiochemical parameters under operational field conditions. Between June 2010 and July 2017, thirteen free-ranging Apennine wolves were captured in Maiella National Park (central Apennines, Italy) using the Fremont™ snare and immobilized with a standardized MKA protocol; only animals immobilized with this protocol are reported here, as three additional capture events employed different drug combinations. Cardiorespiratory parameters, body temperature, peripheral oxygen saturation, venous blood gas values, and a comprehensive hematological and serum biochemical panel were recorded during immobilization. Mean heart rate was 100 ± 15 bpm, respiratory rate 24 ± 13 breaths/min, body temperature 38.1 ± 1.3 °C, and mean SpO2 88 ± 11% (range: 66–97%; n = 12). No clinically significant hyperthermia requiring active intervention was recorded in the cohort as a whole. Hematological and biochemical values were broadly consistent with published reference ranges for the species, with condition-specific deviations identified in two individuals—one pregnant female and one juvenile presenting signs of transient capture-related myopathy—both of which resolved without clinical sequelae. No capture-related mortality occurred. All thirteen individuals survived the minimum post-capture monitoring period. Preliminary GPS observations in a subset of individuals (n = 3) suggest a transient reduction in movement activity in the immediate post-release period. These findings support the safety and operational feasibility of the combined Fremont™ snare–MKA protocol for the Apennine wolf, and provide baseline physiological and hematobiochemical reference data for Canis lupus italicus relevant to future capture and conservation management programmes. Full article
8 pages, 269 KB  
Case Report
Dyspnea Induced by Alpha 2-Adrenergic Agonists and Dissociative Anesthetics Combination in Dogs and Cats
by Taehoon Sung, Won-gyun Son, Junghee Yoon, Cheol-yong Hwang and Inhyung Lee
Animals 2026, 16(7), 1100; https://doi.org/10.3390/ani16071100 - 3 Apr 2026
Viewed by 1286
Abstract
This case report describes the potential adverse effects of the combination of alpha 2-adrenergic agonists and dissociative anesthetics and discusses its prevention. The cases of 2 dogs and 3 cats, including 4 juvenile (<7 months old) animals and 1 adult cat (2 years [...] Read more.
This case report describes the potential adverse effects of the combination of alpha 2-adrenergic agonists and dissociative anesthetics and discusses its prevention. The cases of 2 dogs and 3 cats, including 4 juvenile (<7 months old) animals and 1 adult cat (2 years old), that presented with dyspnea immediately after induction at local veterinary clinics and were referred to the Seoul National University Veterinary Medicine Teaching Hospital are described. Four animals were premedicated with atropine, and all were anesthetized intravenously using a combination of an alpha 2-adrenergic agonist (medetomidine or xylazine) and a dissociative anesthetic (ketamine or Zoletil®). Both dogs developed immediate epistaxis, dyspnea, and radiographic evidence of diffuse alveolar infiltration. One dog was euthanized after experiencing seizures. All 3 cats developed anorexia followed by dyspnea within 24 to 48 h post-anesthesia, resulting in death in 2 cats, while 1 cat recovered with symptomatic treatment. The sympathomimetic effects of dissociative anesthetics and vasoconstrictive alpha 2-adrenergic agonists can cause transient hypertension, which can precipitate pulmonary edema and hemorrhage, leading to dyspnea. Either juvenile or atropine-premedicated patients may be at an increased risk, warranting dose adjustment, route selection, and careful monitoring during anesthesia. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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15 pages, 855 KB  
Review
The Emergence of Fentanyl + Medetomidine Overdose: Pharmacology, Toxicology, and Need for Poly-Drug Reversal Therapeutics
by Robert B. Raffa, Eugene Vortsman, Joseph V. Pergolizzi, Krista Casazza and Morgan King
Future Pharmacol. 2026, 6(1), 11; https://doi.org/10.3390/futurepharmacol6010011 - 15 Feb 2026
Viewed by 1345
Abstract
The overdose mortality landscape has shifted from predominantly opioid exposures to a polysubstance epidemic increasingly driven by illicit fentanyl and fentanyl analogs combined with other centrally active agents. Among the co-intoxicants, veterinary α2-adrenoceptor (α2AR) agonists such as xylazine have [...] Read more.
The overdose mortality landscape has shifted from predominantly opioid exposures to a polysubstance epidemic increasingly driven by illicit fentanyl and fentanyl analogs combined with other centrally active agents. Among the co-intoxicants, veterinary α2-adrenoceptor (α2AR) agonists such as xylazine have emerged as clinically confounding adulterants. Recent reports from forensic toxicology, medical examiners, and border/interdiction agencies indicate that medetomidine, a veterinary sedative racemate with the highly selective α2AR agonist enantiomer dexmedetomidine, is increasingly being detected together with fentanyl and its analogs in seized materials and postmortem assays. Prior reviews have covered these aspects. The current review synthesizes current evidence and clinical experience relevant to fentanyl + medetomidine co-exposure-induced respiratory depression—a primary cause of death. We focus on convergent µ-opioid receptor (MOR) and α2AR signaling within key physiological substrates, including respiratory rhythm-generating networks, ascending arousal pathways, chemosensory reflex control of ventilation, and autonomic cardiovascular regulation, integrating mechanistic pharmacology, respiratory and cardiovascular toxicology, emergency-room treatment, and emerging public-health implications. Available evidence supports a model in which combined MOR and α2AR activation produces additive-to-synergistic suppression of ventilation and consciousness, attenuation of hypoxic ventilatory drive and CO2 responsiveness, with marked sympatholysis manifested as bradycardia and hypotension, all of which can persist beyond presumptive opioid reversal with a MOR antagonist. We discuss the implications for prehospital and emergency care. In sum, the increasing detection of medetomidine in the illicit fentanyl supply represents an emerging and potentially high-risk co-exposure pattern that may be only partially naloxone-responsive. Lastly, we highlight potential future pharmacologic countermeasures for polysubstance overdose, such as the BK-channel antagonist ENA-001, which may address naloxone-insensitive ventilatory suppression in opioid-dominant polysubstance overdose. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2026)
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13 pages, 267 KB  
Article
Perceptions and Experiences of Xylazine, Disparities in Xylazine Awareness, and Correlates of Xylazine-Attributed Wounds Among People Who Use Opioids
by Carl A. Latkin, Lauren Dayton, Haley Bonneau, Melissa A. Davey-Rothwell, Danielle German, Ananya Bhaktaram and Oluwaseun Falade-Nwulia
Int. J. Environ. Res. Public Health 2026, 23(1), 70; https://doi.org/10.3390/ijerph23010070 - 2 Jan 2026
Viewed by 1608
Abstract
Background: Xylazine, an adulterant in the illicit opioid supply, heightens the risks of overdose, withdrawal severity, and severe wounds among people who use opioids (PWUO). Despite increasing prevalence, gaps remain regarding xylazine awareness in the drug supply and effective harm reduction interventions to [...] Read more.
Background: Xylazine, an adulterant in the illicit opioid supply, heightens the risks of overdose, withdrawal severity, and severe wounds among people who use opioids (PWUO). Despite increasing prevalence, gaps remain regarding xylazine awareness in the drug supply and effective harm reduction interventions to address it. Methods: We conducted a cross-sectional survey of 703 PWUO in Baltimore, MD (2023–2025), to assess xylazine awareness, perceptions, and experiences. Multivariable logistic regression models examined correlates of xylazine awareness and self-reported xylazine-attributed wounds. Results: 84.8% of White participants, 48.6% Black participants, 64.3% of males, and 51.4% females had heard of xylazine. Nearly half (45%) of those who used xylazine reported that it caused more severe withdrawal symptoms. In the multivariable model of xylazine awareness, the largest odds ratios were year of survey administration (2024 vs. 2023: aOR = 4.30, 95% CI = 2.91–6.37; 2025 vs. 2023: aOR = 6.32, 95% CI = 3.31–12.07) and White race (aOR = 3.22, 95% CI = 1.85–5.57). Other significant demographic variables included education and gender. In the multivariable model of xylazine-attributed wounds, survey year 2025 vs. 2023 (aOR = 2.65, 95% CI = 1.06–6.61) and injection drug use in the prior year (aOR = 17.74, 95% CI = 5.58–56.39) were statistically significant. Conclusions: Awareness of xylazine in the drug supply remains incomplete among PWUO, with differences by race, age, and gender. The finding of a strong association of xylazine-attributed wounds and injection drug use should be the focus of future research. These findings underscore the need for enhanced surveillance systems, peer education, and community-based harm reduction strategies. Real-time monitoring and rapid response strategies are essential to protect against health risks of toxic adulterants, such as xylazine, medetomidine, and BTMP, in the drug supply. Full article
11 pages, 862 KB  
Article
Comparison of Cardiorespiratory Effects of Two Balanced Anesthesia Protocols in Baboons (Papio hamadryas) Undergoing Laparoscopic Salpingectomy
by Roberta Pizzi, Claudia Piemontese, Caterina Vicenti, Elena Barazia, Marzia Stabile, Claudia Acquafredda, Luca Lacitignola, Marta Guadalupi, Pietro Laricchiuta and Francesco Staffieri
Vet. Sci. 2025, 12(12), 1134; https://doi.org/10.3390/vetsci12121134 - 29 Nov 2025
Viewed by 745
Abstract
Laparoscopic salpingectomy is a minimally invasive surgery that requires careful anesthetic management due to the effects of intra-abdominal gas insufflation. In this retrospective study, baboons (Papio hamadryas) were treated with two induction protocols: medetomidine–ketamine (MK; n = 16) and medetomidine–tiletamine–zolazepam (MZ; n = [...] Read more.
Laparoscopic salpingectomy is a minimally invasive surgery that requires careful anesthetic management due to the effects of intra-abdominal gas insufflation. In this retrospective study, baboons (Papio hamadryas) were treated with two induction protocols: medetomidine–ketamine (MK; n = 16) and medetomidine–tiletamine–zolazepam (MZ; n = 12) via intramuscular injection. A laryngeal mask (LMA) was used for airway management and anesthesia was maintained with isoflurane in 100% oxygen. For statistical analysis, the following parameters were analyzed via two-way ANOVA: heart rate (HR), respiratory rate (RR), systolic, diastolic, and mean arterial blood pressure (SAP, DAP, and MAP), end-tidal carbon dioxide (EtCO2), and peripheral oxygen saturation (SpO2) recorded five minutes before pneumoperitoneum (PREP), after abdominal insufflation (PP1), at 10 (PP2) and 20 (PP3) minutes post-insufflation, and 5 min after pneumoperitoneum interruption (POSTP). HR and RR were statistically significantly higher (p < 0.05) in the MK group compared to the MZ group at all time points of the study. EtCO2 was significantly higher (p < 0.05) in the MZ group at PP2, PP3, and POSTP time points. The incidence of hypotension was significantly greater in the MZ group (45.5%) compared to the MK group (6.25%). Hypercapnia was observed in all baboons sedated with the MZ protocol compared to 12.5% of the MK group. As a result, the MK protocol provided greater cardiorespiratory stability during laparoscopic surgery. Full article
(This article belongs to the Special Issue Emerging Trends in Veterinary Anesthesia and Analgesia)
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14 pages, 1014 KB  
Article
Evaluation of Medetomidine Dose Variations on Tiletamine-Zolazepam and Tramadol Anesthetic Combination in Dogs
by Donghwi Shin, Won-gyun Son, Jong-pil Seo, Min Jang and Inhyung Lee
Animals 2025, 15(23), 3419; https://doi.org/10.3390/ani15233419 - 26 Nov 2025
Cited by 1 | Viewed by 1467
Abstract
This study evaluated the effects of varying medetomidine doses on a tiletamine-zolazepam and tramadol anesthetic combination in dogs. The objective was to assess how medetomidine influences anesthesia depth, cardiovascular function, and recovery quality. Dogs were assigned to one of three treatment groups: tiletamine-zolazepam [...] Read more.
This study evaluated the effects of varying medetomidine doses on a tiletamine-zolazepam and tramadol anesthetic combination in dogs. The objective was to assess how medetomidine influences anesthesia depth, cardiovascular function, and recovery quality. Dogs were assigned to one of three treatment groups: tiletamine-zolazepam and tramadol without medetomidine (TZT), additional 10 µg/kg medetomidine (TZTM10), or additional 20 µg/kg medetomidine (TZTM20). Each dog received an intramuscular injection of 0.1 mL/kg of the designated solution. The formulation for TZT contained 25 mg/mL tiletamine and zolazepam and 40 mg/mL tramadol, while TZTM10 and TZTM20 received the same solution with additional medetomidine at 100 and 200 µg/mL, respectively. Onset time, anesthetic time, analgesic time, recovery quality, and physiological parameters, including heart rate, blood pressure, respiratory rate, oxygen saturation, and body temperature, were evaluated. Medetomidine extended analgesic time in a dose-dependent manner and improved recovery quality while maintaining stable respiratory function. While TZT provided adequate anesthesia for minor non-invasive procedures, the inclusion of medetomidine in TZTM resulted in enhanced anesthetic stability for simple surgical procedures such as gonadectomy. These findings suggest that TZTM20 is a viable anesthetic protocol, though careful patient monitoring remains essential due to its cardiovascular effects. Full article
(This article belongs to the Special Issue Developments in Therapeutic Drugs for Pain Management in Animals)
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17 pages, 1031 KB  
Case Report
Profound Opioid and Medetomidine Withdrawal: A Case Series and Narrative Review of Available Literature
by Phil Durney, Elise Paquin, Gamal Fitzpatrick, Drew Lockstein, TaReva Warrick-Stone, Maeve Montesi, Sejal H. Patel-Francis, Jamal Rashid, Oluwarotimi Vaughan-Ogunlusi, Kelly Goodsell, Jennifer L. Kahoud, Christopher Martin, Keira Chism, Paul Goebel, Karen Alexander, Dennis Goodstein and Kory S. London
Psychoactives 2025, 4(4), 37; https://doi.org/10.3390/psychoactives4040037 - 23 Oct 2025
Cited by 3 | Viewed by 5509
Abstract
Medetomidine, a potent central acting α2 agonist, has emerged as a fentanyl adulterant in the non-medical opioid supply. Its use has been linked to a novel withdrawal syndrome that is often resistant to conventional treatment protocols. Four cases are presented exemplifying extreme, but [...] Read more.
Medetomidine, a potent central acting α2 agonist, has emerged as a fentanyl adulterant in the non-medical opioid supply. Its use has been linked to a novel withdrawal syndrome that is often resistant to conventional treatment protocols. Four cases are presented exemplifying extreme, but increasingly common forms of this withdrawal syndrome. A literature review is provided demonstrating both the paucity of available literature as well as potential avenues for treatment and future research. As adulterants continue to proliferate in the illicit drug supply, clinicians should anticipate atypical withdrawal phenotypes and consider early intervention. Full article
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14 pages, 5237 KB  
Case Report
Enucleation Due to Ocular Abscess in a Captive Chimpanzee (Pan troglodytes): A Case Report from the Republic of Congo
by Manuel Fuertes-Recuero, José L. López-Hernández, Alejandra Ramírez-Lago, Luna Gutiérrez-Cepeda, Juan A. De Pablo-Moreno, Pablo Morón-Elorza, Luis Revuelta and Rebeca Atencia
Vet. Sci. 2025, 12(9), 805; https://doi.org/10.3390/vetsci12090805 - 25 Aug 2025
Cited by 1 | Viewed by 1969
Abstract
Chimpanzees (Pan troglodytes) rescued from the illegal wildlife trade often suffer from chronic, traumatic injuries that require specialized and prolonged medical treatment in wildlife rehabilitation centers. We present the case report of a two-year-old male chimpanzee admitted at the Tchimpounga Chimpanzee [...] Read more.
Chimpanzees (Pan troglodytes) rescued from the illegal wildlife trade often suffer from chronic, traumatic injuries that require specialized and prolonged medical treatment in wildlife rehabilitation centers. We present the case report of a two-year-old male chimpanzee admitted at the Tchimpounga Chimpanzee Rehabilitation Center in the Republic of Congo with a chronic periorbital abscess, likely caused by a machete wound sustained during the poaching of his mother. Despite receiving extended antimicrobial therapy, his condition was never fully controlled and progressed to a chronic orbital infection, causing him discomfort and producing chronic purulent discharge. Enucleation was performed under general anesthesia using ketamine and medetomidine, with surgical approach adapted to the distinctive orbital anatomy of chimpanzees. During the procedure, ligation of the optic nerve and ophthalmic vessels was required due to the confined orbital apex and extensive vascularization, ensuring adequate haemostasias and procedural safety. The chimpanzee made an uneventful postoperative recovery, resuming normal feeding and social behavior within 48 h, with complete wound healing occurring within two weeks. This case report highlights the importance of prompt surgical intervention when conservative medical management fails to resolve refractory ocular infections in chimpanzees. It also emphasizes the importance of specific anesthetic protocols, refined surgical techniques and tailored postoperative care in wildlife rehabilitation centers. Documenting and sharing detailed case reports such as this contributes to the limited veterinary literature on great ape surgery and supports evidence-based clinical decision-making to improve the welfare and treatment outcomes of rescued chimpanzees. Full article
(This article belongs to the Special Issue Advances in Zoo, Aquatic, and Wild Animal Medicine)
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22 pages, 1875 KB  
Article
Biochemical Identification and Clinical Description of Medetomidine Exposure in People Who Use Fentanyl in Philadelphia, PA
by Phil Durney, Jennifer L. Kahoud, TaReva Warrick-Stone, Maeve Montesi, Meg Carter, Sabrina Butt, Alberto Martinez Mencia, Louisa Omoregie, Monali Shah, Mariah Bloomfield, Nicholas Tomasko, Rebecca Jaffe, Allison Herens, Warren R. Korn, Karen Alexander, Douglas Stickle, Dennis Goodstein, Lara Carson Weinstein and Kory S. London
Int. J. Mol. Sci. 2025, 26(14), 6715; https://doi.org/10.3390/ijms26146715 - 13 Jul 2025
Cited by 12 | Viewed by 3742
Abstract
Medetomidine, a veterinary α2-adrenergic agonist, has recently emerged as an adulterant in the non-medical opioid supply, yet human exposure has remained poorly characterized. We conducted a pragmatic retrospective cohort analysis utilizing chart review and liquid chromatography–tandem mass spectrometry (LC-MS/MS) toxicology testing on available [...] Read more.
Medetomidine, a veterinary α2-adrenergic agonist, has recently emerged as an adulterant in the non-medical opioid supply, yet human exposure has remained poorly characterized. We conducted a pragmatic retrospective cohort analysis utilizing chart review and liquid chromatography–tandem mass spectrometry (LC-MS/MS) toxicology testing on available urine samples from patients presenting to two hospitals in Philadelphia, PA, who fit two clinical phenotypes, intoxication or withdrawal. Samples also underwent glucuronidase pre-treatment to assess impact on the yield of medetomidine and xylazine metabolite detection. Testing identified universal exposure to medetomidine (58/58 samples) via the 3-hydroxy-medetomidine (3-OH-M) metabolite, post glucuronidase treatment and variable xylazine exposure (40/58 samples). Importantly, 32% of medetomidine exposures would have been missed without enzymatic pre-treatment. Patients exhibited two distinct clinical phenotypes: intoxication, characterized primarily by sedation; bradycardia; and often hypotension, and withdrawal, presenting with life-threatening tachycardia; hypertension and often encephalopathy. Notably, clinical phenotype correlated with urinary concentrations of 3-OH-M but not xylazine. These findings underscore the critical need for heightened clinical awareness and need for contemporaneous toxicologic screening mechanisms for medetomidine exposure, emphasizing its distinct clinical presentations and the potential public health implications posed by its widespread adulteration in illicit opioids. Full article
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14 pages, 1369 KB  
Article
Development of a System to Deliver Inhalational Antibiotics to Marmosets
by Rachel E. Ireland, Stuart J. Armstrong, Carwyn Davies, James D. Blanchard, Francis Dayton, Igor Gonda, Sarah V. Harding and Michelle Nelson
Antibiotics 2025, 14(6), 554; https://doi.org/10.3390/antibiotics14060554 - 29 May 2025
Cited by 1 | Viewed by 1188
Abstract
Background: Inhalational antibiotics have been used effectively to treat chronic diseases such as Pseudomonas aeruginosa infections associated with cystic fibrosis. This approach may enhance treatment options for difficult-to-treat, acute pneumonic diseases. Liposomal encapsulated ciprofloxacin (Lipoquin and/or Apulmiq) has provided protection in murine models [...] Read more.
Background: Inhalational antibiotics have been used effectively to treat chronic diseases such as Pseudomonas aeruginosa infections associated with cystic fibrosis. This approach may enhance treatment options for difficult-to-treat, acute pneumonic diseases. Liposomal encapsulated ciprofloxacin (Lipoquin and/or Apulmiq) has provided protection in murine models of plague, anthrax, Q fever and tularemia. Development of the ability to deliver these drugs to nonhuman primates (NHPs) would enable further extrapolation of the data observed in small animal models of infection to humans. Methods: In this study, the methodology was established to deliver Apulmiq to common marmosets (Callithrix jacchus). Marmosets were anaesthetised with a novel, reversible anaesthetic comprising fentanyl, medetomidine and midazolam (FMM). They were placed into plethysmography tubes with their heads in an exposure chamber. The LC Sprint jet nebuliser or Pari eFlow Rapid nebuliser were used to aerosolise Apulmiq into the exposure chamber. Animals were euthanised after dosing and the concentration of ciprofloxacin was assessed in the plasma and lungs of the animals. Results: Non-compartmental pharmacokinetic analysis determined that a 30 min exposure of drug was required to reach a human-equivalent target dose of 0.8 mg/kg body weight in the lungs. Conclusions: This approach can now be used to assess the efficacy of inhalational liposomal ciprofloxacin in NHP infection models. Full article
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18 pages, 1392 KB  
Article
Decreased Effectiveness of a Novel Opioid Withdrawal Protocol Following the Emergence of Medetomidine as a Fentanyl Adulterant
by Kory S. London, Philip Durney, TaReva Warrick-Stone, Karen Alexander and Jennifer L. Kahoud
BioMed 2025, 5(2), 13; https://doi.org/10.3390/biomed5020013 - 23 May 2025
Cited by 6 | Viewed by 5046
Abstract
Background/Objectives: Philadelphia has experienced a surge in illicit fentanyl adulterated with alpha-2 agonist sedatives. Initially, xylazine (“tranq”) was the predominant adulterant, and a novel multimodal withdrawal protocol was effective at mitigating symptoms. However, since mid-2024, medetomidine—a more potent sedative—has largely supplanted xylazine. Clinicians [...] Read more.
Background/Objectives: Philadelphia has experienced a surge in illicit fentanyl adulterated with alpha-2 agonist sedatives. Initially, xylazine (“tranq”) was the predominant adulterant, and a novel multimodal withdrawal protocol was effective at mitigating symptoms. However, since mid-2024, medetomidine—a more potent sedative—has largely supplanted xylazine. Clinicians have reported more severe, treatment-resistant opioid withdrawal during this transition. To assess whether a previously effective withdrawal management protocol retained efficacy after the emergence of medetomidine as the primary fentanyl adulterant in a community. Methods: We conducted a retrospective cohort study of patients receiving protocol-based opioid withdrawal treatment at two emergency departments in Philadelphia between September 2022 and April 2025. Patients were divided into the xylazine era (September 2022–July 2024) and medetomidine era (August 2024–April 2025). The primary outcome was a change in Clinical Opioid Withdrawal Scale (COWS) score from pre- to post-treatment. Secondary outcomes included rates of discharge against medical advice (AMA) and ICU admission, as well as the impact of a revised treatment protocol. Results: Among 1269 encounters with full data, 616 occurred during the xylazine era and 770 during the medetomidine era. Median COWS reduction was greater in the xylazine group (−9.0 vs. −4.0 points, p < 0.001), with more patients achieving symptom relief (COWS ≤ 4: 65.6% vs. 14.2%, p < 0.001). ICU admission occurred in 8.5% of xylazine era patients and 16.8% of medetomidine era patients (p < 0.001). Rates of AMA were higher during the medetomidine era as well (6.5% vs. 3.6%) (p = 0.038). Revision of treatment protocols showed promise. Conclusions: The protocol was significantly less effective during the medetomidine era, though a protocol change may be helping. Findings highlight the need to adapt withdrawal treatment protocols in response to changes in the illicit drug supply. Full article
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14 pages, 859 KB  
Article
The Suitability of Dried Blood Spot Sampling for Pharmacokinetic Studies in Veterinary Medicine
by Anisa Bardhi, Andrea Barbarossa, Andrè Joubert, Ronette Gehring, Carlotta Lambertini and Noemi Romagnoli
Vet. Sci. 2025, 12(5), 488; https://doi.org/10.3390/vetsci12050488 - 18 May 2025
Cited by 1 | Viewed by 3095
Abstract
Dried blood spot (DBS) sampling has emerged as a promising microsampling technique in biomedical and clinical research, offering advantages such as reduced invasiveness, minimal blood volume requirements, and enhanced analyte stability. Although well established in human medicine for neonatal screening and diagnostic applications, [...] Read more.
Dried blood spot (DBS) sampling has emerged as a promising microsampling technique in biomedical and clinical research, offering advantages such as reduced invasiveness, minimal blood volume requirements, and enhanced analyte stability. Although well established in human medicine for neonatal screening and diagnostic applications, its potential in veterinary pharmacology remains underexplored. This study investigated the feasibility of using DBS samples to quantify anesthetic agents—ketamine and medetomidine in cats and lidocaine in horses—during routine surgical procedures at a veterinary teaching hospital. A standardized DBS collection protocol was developed, and LC-MS/MS methods were validated for the quantification of target analytes in both DBS and plasma samples. These methods were subsequently applied to real samples collected during anesthesia to conduct pharmacokinetic analyses. Comparative evaluations, including Bland–Altman analysis, assessed the suitability of DBS samples for pharmacokinetic studies in veterinary medicine. Preliminary results indicated satisfactory agreement for medetomidine, meeting EMA guidelines, with 75.6% of mean values falling within ±20% of paired measurements. Results for ketamine (46.9%) were promising but require further optimization, while those for lidocaine (21.4%) highlighted the need for additional investigation. These findings underscore the potential of DBS sampling as a minimally invasive alternative for pharmacokinetic studies in veterinary medicine, particularly for medetomidine, while identifying areas for further methodological refinement. Future research should optimize DBS techniques and expand their application to other drugs and species, broadening their impact on veterinary pharmacology. Full article
(This article belongs to the Section Veterinary Physiology, Pharmacology, and Toxicology)
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21 pages, 10581 KB  
Article
Evaluation of Echocardiographic, Conventional Electrocardiographic, and Holter Variables in Jaguars (Panthera Onca) Anesthetized with Medetomidine and Ketamine: Implications for Management and Conservation
by Murillo Daparé Kirnew, Matheus Folgearini Silveira, Roberto Andres Navarrete Ampuero, Ana Paula Rodrigues Simões, Felippe Azzolini, Gediendson Ribeiro de Araújo, Pedro Nacib Jorge-Neto, Sofia Regina Polizelle, Juliane Patrícia Sipp, Cristiane Schilbach Pizzutto, Thyara Deco-Souza and Aparecido Antonio Camacho
J. Zool. Bot. Gard. 2025, 6(1), 13; https://doi.org/10.3390/jzbg6010013 - 13 Feb 2025
Cited by 1 | Viewed by 3321
Abstract
Jaguars play a crucial role in population control across multiple biomes. They are endangered and protected by in situ and ex situ conservation mechanisms to ensure their conservation. Cardiovascular diseases in wild mammals, including jaguars, often have unclear etiopathogenies, underscoring the need for [...] Read more.
Jaguars play a crucial role in population control across multiple biomes. They are endangered and protected by in situ and ex situ conservation mechanisms to ensure their conservation. Cardiovascular diseases in wild mammals, including jaguars, often have unclear etiopathogenies, underscoring the need for research into novel hemodynamic parameters. This study evaluates the cardiovascular health of fifteen clinically healthy jaguars using conventional and Holter electrocardiography, non-invasive systemic blood pressure measurement, and echocardiography. Chemical restraint was achieved with medetomidine (0.08–0.1 mg/kg) and ketamine (5 mg/kg), with anesthesia reversed using atipamezole (0.25 mg/kg). The average heart rate was 72 ± 18 bpm, with sinus rhythm in ten animals and sinus arrhythmia in five. Six animals exhibited first and second-degree atrioventricular blocks, one had supraventricular complexes, and another had premature ventricular complexes. Non-invasive systolic blood pressure remained stable at 163 ± 29 mmHg during anesthesia. Echocardiographic examination revealed mitral, tricuspid, pulmonary, and aortic valve insufficiencies via color Doppler. The transmitral flow showed a normal E/A ratio and E` < A`, suggesting a pseudonormal ventricular filling pattern. No significant anesthetic complications were observed, affirming the protocol’s safety. This study provides valuable data, validating the anesthetic protocol and establishing reference cardiovascular values for jaguars, thus paving the way for future research in other veterinary species. Full article
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Article
Effect of Medetomidine and Dexmedetomidine at Different Dosages on Cat Semen Quality Using Urethral Catheterization After Pharmacological Induction (UrCaPI)
by Marco Cunto, Giulia Ballotta, Alberto Contri, Alessia Gloria and Daniele Zambelli
Animals 2025, 15(4), 504; https://doi.org/10.3390/ani15040504 - 11 Feb 2025
Cited by 1 | Viewed by 1794
Abstract
The aim of this study was to evaluate the effectiveness of different anesthetic protocols for semen collection from healthy tomcats using Urethral Catheterization after Pharmacological Induction (UrCaPI). Twenty sexually mature tomcats (Felis catus) were included in the study, in which high and low [...] Read more.
The aim of this study was to evaluate the effectiveness of different anesthetic protocols for semen collection from healthy tomcats using Urethral Catheterization after Pharmacological Induction (UrCaPI). Twenty sexually mature tomcats (Felis catus) were included in the study, in which high and low dosages of medetomidine or dexmedetomidine were administrated to collect semen. Ten healthy mature tomcats (Group A) received high dosages of the drugs, and, in particular, five of them were i.m. injected with 120 μg/kg of medetomidine (HMED) on day 1 and with 60 μg/kg of dexmedetomidine (HDEX) after 24 h (day 2). The remaining five tomcats of this group were i.m. injected with 60 μg/kg of dexmedetomidine on day 1 and with 120 μg/kg of medetomidine on day 2. The other ten healthy mature tomcats (Group B) received a low dosage of the same drugs; the first five tomcats were i.m. injected with 50 μg/kg of medetomidine (LMED) on day 1 and with 25 μg/kg of dexmedetomidine (LDEX) on day 2; the others were i.m. injected with 25 μg/kg of dexmedetomidine on day 1 and with 50 μg/kg of medetomidine after 24 h. In both groups, semen collection was performed as soon as the pharmacological effect of the drug was reached. All protocols permitted sperm collection, even if with different results in quality for volume, concentration, total number of spermatozoa, and movement score. Results suggest that both a high dosage of medetomidine and a high dosage of dexmedetomidine could be used for the collection of good-quality semen. Semen volume μL: HMED = 32 μL (25.75–37.5), HDEX = 23 μL (15.25–28). Concentration HMED = 670 × 106/mL (576–990.5), HDEX = 670.5 × 106/mL (536–790). Total number of spermatozoa = 23.24 × 106 (18.37–32.05). Total number of spermatozoa = 13.121 × 106 (10.116–16.83). However, the protocol with dexmedetomidine could not always guarantee an adequate sedation for urethral catheterization, so using a high dosage of medetomidine is still the better way to collect high quality semen with the UrCaPI technique. The outcome of the LMED and LDEX protocols was generally unsatisfactory regarding both level of sedation and semen collection in terms of volume (LMED = 3 μL (4–7.5); LDEX = 6 μL (4–7)), concentration (LMED = 215 × 106/mL (157–248); LDEX = 27.05 × 106/mL (0.040–110), total number of spermatozoa (LMED = 0.88 × 106 (0.581–1.38); LDEX = 0.16 × 106 (0.0001–0.80), and movement score (LMED = 3 (2–3); LDEX = 2 (0–2.75)). Full article
(This article belongs to the Special Issue Developments in Therapeutic Drugs for Pain Management in Animals)
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