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Article ; Online: Development and optimization of a fentanyl pharmacokinetic model for target-controlled infusion in anaesthetized dogs

Cattai, Andrea / Merlanti, Roberta / Bizzotto, Roberto / Lucatello, Lorena / Capolongo, Francesca / Franci, Paolo

Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia Veterinary Anaesthesia and Analgesia. 2023 Jan., v. 50, no. 1 p.31-40

2023

Abstract: To investigate pharmacokinetics (PK) of fentanyl administered by target-controlled infusion (TCI), and to develop a PK model optimized by covariates for TCI in anaesthetized dogs. Prospective clinical study. A group of 20 client-owned dogs with spinal ... ...

Abstract	To investigate pharmacokinetics (PK) of fentanyl administered by target-controlled infusion (TCI), and to develop a PK model optimized by covariates for TCI in anaesthetized dogs. Prospective clinical study. A group of 20 client-owned dogs with spinal pain undergoing anaesthesia for magnetic resonance imaging. Fentanyl was administered as an infusion to 20 anaesthetized dogs using a TCI system incorporating a previously described fentanyl two-compartment PK. Arterial blood samples were collected at specific time points during the infusion and over 60 minutes post-infusion for measurement of fentanyl plasma concentrations. The predictive performance of the Sano PK model was assessed by comparing predicted and measured plasma concentrations. A population PK analysis was then performed using a nonlinear mixed-effect modelling approach, allowing inter- and intra-individual variability estimation. Finally, a quantitative stepwise evaluation of the influence of various covariates such as weight, body condition score, size, size-related age, sex and type of premedication on the PK model was considered. Overall predictive performance of the Sano PK set of variables was not clinically acceptable in anaesthetized dogs. Fentanyl PK was best described by a three-compartment model. Weight and sex were found to affect the volume of distribution of the central compartment. Addition of these two covariate/variable associations resulted in a reduction of the objective function value (OFV) from –340.18 to –448.34, and of the median population weighted residual and the median population absolute weighted residual from 16.1% and 38.6% to 3.9% and 20.3%, respectively. Fentanyl infusions at measured concentrations up to 5.4 ng mL–¹ in sevoflurane-anaesthetized dogs resulted in stable anaesthesia and smooth recoveries without complications. A population three-compartment PK model for fentanyl TCI in anaesthetized dogs was developed. Weight and sex have been detected and incorporated as significant covariates.
Keywords	analgesia ; anesthesia ; blood ; body condition ; fentanyl ; magnetism ; models ; pain ; pharmacokinetics ; anaesthesia ; dogs ; target-controlled infusion ; TCI
Language	English
Dates of publication	2023-01
Size	p. 31-40.
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	2020582-X
ISSN	1467-2995 ; 1467-2987
ISSN (online)	1467-2995
ISSN	1467-2987
DOI	10.1016/j.vaa.2021.08.049
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Resumption of ovarian activity following removal of a 4.7 mg deslorelin implant in queens.

Ferré-Dolcet, L / Ferro, S / Contiero, B / Andretta, F / Cattai, A / Fontaine, C / Romagnoli, S

Reproduction in domestic animals = Zuchthygiene

2021 Volume 57, Issue 1, Page(s) 3–9

Abstract: Deslorelin implants are widely used in felines. Due to their prolonged duration cat breeders frequently request early implant removal. The interval between deslorelin implant removal and resumption of ovarian function in queens is unknown. The aim of ... ...

Abstract	Deslorelin implants are widely used in felines. Due to their prolonged duration cat breeders frequently request early implant removal. The interval between deslorelin implant removal and resumption of ovarian function in queens is unknown. The aim of this study was to evaluate the interval between the removal of a deslorelin implant and the resumption of ovarian activity in adult queens. Twenty-three queens were treated with a 4.7 mg deslorelin implant placed in the periumbilical area. In the 16 queens completing the study implants were surgically removed at 3, 6 or 9 months (n = 6, 4 and 6 queens, respectively). Queens received a GnRH stimulation test as part of their pre-treatment general and reproductive health check. Following implantation treatment, all queens in inter-oestrus-anoestrus at the time of treatment came in oestrus within 2-5 days. Starting 7-14 days following implant removal queens were checked every 1-2 weeks with reproductive ultrasonography, a vaginal smear and blood collection. The interval to resumption of ovarian function ranged from 3 to 7 weeks irrespective of treatment length and age of the queen but was longer when the implant was removed at decreasing photoperiod (p < .05). In conclusion, at least 3 weeks post-removal are needed during increasing photoperiod to achieve follicular development and oestrogen production sufficient to support oestrous behaviour in queens following removal of a 4.7 mg deslorelin implant, while this time may increase up to 7 weeks during decreasing photoperiod. Further studies are needed to assess the interval between removal of a deslorelin implant and occurrence of ovulation as well as fertility at the first oestrus after a deslorelin treatment.
MeSH term(s)	Animals ; Cats ; Drug Implants ; Estrus ; Female ; Gonadotropin-Releasing Hormone ; Ovary ; Triptorelin Pamoate/analogs & derivatives ; Triptorelin Pamoate/pharmacology
Chemical Substances	Drug Implants ; Triptorelin Pamoate (08AN7WA2G0) ; Gonadotropin-Releasing Hormone (33515-09-2) ; deslorelin (TKG3I66TVE)
Language	English
Publishing date	2021-10-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1015187-4
ISSN	1439-0531 ; 0936-6768
ISSN (online)	1439-0531
ISSN	0936-6768
DOI	10.1111/rda.14023
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Article ; Online: Development and optimization of a fentanyl pharmacokinetic model for target-controlled infusion in anaesthetized dogs.

Cattai, Andrea / Merlanti, Roberta / Bizzotto, Roberto / Lucatello, Lorena / Capolongo, Francesca / Franci, Paolo

Veterinary anaesthesia and analgesia

2022 Volume 50, Issue 1, Page(s) 31–40

Abstract: Objective: To investigate pharmacokinetics (PK) of fentanyl administered by target-controlled infusion (TCI), and to develop a PK model optimized by covariates for TCI in anaesthetized dogs.: Study design: Prospective clinical study.: Animals: A ... ...

Abstract	Objective: To investigate pharmacokinetics (PK) of fentanyl administered by target-controlled infusion (TCI), and to develop a PK model optimized by covariates for TCI in anaesthetized dogs. Study design: Prospective clinical study. Animals: A group of 20 client-owned dogs with spinal pain undergoing anaesthesia for magnetic resonance imaging. Methods: Fentanyl was administered as an infusion to 20 anaesthetized dogs using a TCI system incorporating a previously described fentanyl two-compartment PK. Arterial blood samples were collected at specific time points during the infusion and over 60 minutes post-infusion for measurement of fentanyl plasma concentrations. The predictive performance of the Sano PK model was assessed by comparing predicted and measured plasma concentrations. A population PK analysis was then performed using a nonlinear mixed-effect modelling approach, allowing inter- and intra-individual variability estimation. Finally, a quantitative stepwise evaluation of the influence of various covariates such as weight, body condition score, size, size-related age, sex and type of premedication on the PK model was considered. Results: Overall predictive performance of the Sano PK set of variables was not clinically acceptable in anaesthetized dogs. Fentanyl PK was best described by a three-compartment model. Weight and sex were found to affect the volume of distribution of the central compartment. Addition of these two covariate/variable associations resulted in a reduction of the objective function value (OFV) from -340.18 to -448.34, and of the median population weighted residual and the median population absolute weighted residual from 16.1% and 38.6% to 3.9% and 20.3%, respectively. Fentanyl infusions at measured concentrations up to 5.4 ng mL Conclusions and clinical relevance: A population three-compartment PK model for fentanyl TCI in anaesthetized dogs was developed. Weight and sex have been detected and incorporated as significant covariates.
MeSH term(s)	Dogs ; Animals ; Fentanyl ; Anesthetics, Intravenous ; Prospective Studies ; Infusions, Intravenous/veterinary ; Anesthesia/veterinary
Chemical Substances	Fentanyl (UF599785JZ) ; Anesthetics, Intravenous
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2020582-X
ISSN	1467-2995 ; 1467-2987
ISSN (online)	1467-2995
ISSN	1467-2987
DOI	10.1016/j.vaa.2021.08.049
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Article ; Online: Lethal septic shock after dental scaling in a healthy dog due to Ochrobactrum anthropi-contaminated propofol.

Franci, P / Dotto, G / Cattai, A / Pasotto, D

The Journal of small animal practice

2015 Volume 56, Issue 5, Page(s) 345–347

Abstract: A 10-year-old, 6-kg male Yorkshire terrier dog was scheduled for routine dental cleaning. No significant problem was observed either during anaesthesia, which was induced with propofol, or during recovery. However, 2 hours after discharge, the dog's ... ...

Abstract	A 10-year-old, 6-kg male Yorkshire terrier dog was scheduled for routine dental cleaning. No significant problem was observed either during anaesthesia, which was induced with propofol, or during recovery. However, 2 hours after discharge, the dog's owner returned to the clinic, complaining that the animal was lethargic and had had bloody diarrhoea. On physical examination the dog was depressed, dyspnoeic, tachycardic and hypoglycaemic. Despite supportive treatment, the dog deteriorated and died within a few hours.A presumed diagnosis of sepsis was confirmed by laboratory testing. Bacteriological and molecular examinations of both premortem blood samples and the anaesthetic, highlighted the presence of Ochrobactrum anthropi, an opportunistic pathogen usually associated with immunocompromised hosts with indwelling medical devices. To the authors’ knowledge, this is the first case of sepsis in a healthy dog due to contamination of an anaesthetic solution by O. anthropi, suggesting a potential role of this microorganism as an emerging pathogen.
MeSH term(s)	Anesthesia, Intravenous/adverse effects ; Anesthesia, Intravenous/veterinary ; Anesthetics, Intravenous/adverse effects ; Animals ; Dental Scaling/adverse effects ; Dental Scaling/veterinary ; Dog Diseases/etiology ; Dog Diseases/microbiology ; Dogs ; Drug Contamination ; Fatal Outcome ; Gram-Negative Bacterial Infections/etiology ; Gram-Negative Bacterial Infections/veterinary ; Male ; Ochrobactrum anthropi ; Propofol/adverse effects ; Shock, Septic/etiology ; Shock, Septic/microbiology ; Shock, Septic/veterinary
Chemical Substances	Anesthetics, Intravenous ; Propofol (YI7VU623SF)
Language	English
Publishing date	2015-05
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	410743-3
ISSN	1748-5827 ; 0022-4510 ; 1748-5827
ISSN (online)	1748-5827
ISSN	0022-4510 ; 1748-5827
DOI	10.1111/jsap.12284
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Article: Resumption of ovarian activity following removal of a 4.7 mg deslorelin implant in queens

Ferré‐Dolcet, L. / Ferro, S. / Contiero, B. / Andretta, F. / Cattai, A. / Fontaine, C. / Romagnoli, S.

Reproduction in domestic animals. 2022 Jan., v. 57, no. 1

2022

Abstract	Deslorelin implants are widely used in felines. Due to their prolonged duration cat breeders frequently request early implant removal. The interval between deslorelin implant removal and resumption of ovarian function in queens is unknown. The aim of this study was to evaluate the interval between the removal of a deslorelin implant and the resumption of ovarian activity in adult queens. Twenty‐three queens were treated with a 4.7 mg deslorelin implant placed in the periumbilical area. In the 16 queens completing the study implants were surgically removed at 3, 6 or 9 months (n = 6, 4 and 6 queens, respectively). Queens received a GnRH stimulation test as part of their pre‐treatment general and reproductive health check. Following implantation treatment, all queens in inter‐oestrus–anoestrus at the time of treatment came in oestrus within 2–5 days. Starting 7–14 days following implant removal queens were checked every 1–2 weeks with reproductive ultrasonography, a vaginal smear and blood collection. The interval to resumption of ovarian function ranged from 3 to 7 weeks irrespective of treatment length and age of the queen but was longer when the implant was removed at decreasing photoperiod (p < .05). In conclusion, at least 3 weeks post‐removal are needed during increasing photoperiod to achieve follicular development and oestrogen production sufficient to support oestrous behaviour in queens following removal of a 4.7 mg deslorelin implant, while this time may increase up to 7 weeks during decreasing photoperiod. Further studies are needed to assess the interval between removal of a deslorelin implant and occurrence of ovulation as well as fertility at the first oestrus after a deslorelin treatment.
Keywords	adults ; blood sampling ; deslorelin acetate ; estrogens ; estrus ; follicular development ; ovulation ; ultrasonography
Language	English
Dates of publication	2022-01
Size	p. 3-9.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	1015187-4
ISSN	1439-0531 ; 0936-6768
ISSN (online)	1439-0531
ISSN	0936-6768
DOI	10.1111/rda.14023
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Article ; Online: Progesterone-responsive vaginal leiomyoma and hyperprogesteronemia due to ovarian luteoma in an older bitch.

Ferré-Dolcet, L / Romagnoli, S / Banzato, T / Cavicchioli, L / Di Maggio, R / Cattai, A / Berlanda, M / Schrank, M / Mollo, A

BMC veterinary research

2020 Volume 16, Issue 1, Page(s) 284

Abstract: Background: This is the first report about a vaginal leiomyoma concomitant with an ovarian luteoma in a bitch.: Case presentation: A 11-year-old intact female Labrador retriever was referred because of anuria, constipation and protrusion of a vaginal ...

Abstract	Background: This is the first report about a vaginal leiomyoma concomitant with an ovarian luteoma in a bitch. Case presentation: A 11-year-old intact female Labrador retriever was referred because of anuria, constipation and protrusion of a vaginal mass through the vulvar commissure. The bitch had high serum progesterone concentration (4.94 ng/ml). Because of the possibility of progesterone responsiveness causing further increase of the vaginal mass and since the bitch was a poor surgical candidate a 10 mg/kg aglepristone treatment was started SC on referral day 1. A computerized tomography showed a 12.7 × 6.5 × 8.3 cm mass causing urethral and rectal compression, ureteral dilation and hydronephrosis. A vaginal leiomyoma was diagnosed on histology. As serum progesterone concentration kept increasing despite aglepristone treatment, a 0.02 ng/mL twice daily IM alfaprostol treatment was started on day 18. As neither treatment showed remission of clinical signs or luteolysis, ovariohysterectomy was performed on referral day 35. Multiple corpora lutea were found on both ovaries. On histology a luteoma was diagnosed on the left ovary. P4 levels were undetectable 7 days after surgery. Recovery was uneventful and 12 weeks after surgery tomography showed a reduction of 86.7% of the vaginal mass. The bitch has been in good health and able to urinate without any complication ever since. Conclusions: This case demonstrates the importance of identifying progesterone related conditions as well as the importance of judiciously using a combined medical and surgical approach.
MeSH term(s)	Animals ; Dog Diseases/pathology ; Dogs ; Estrenes/therapeutic use ; Female ; Hysterectomy/veterinary ; Leiomyoma/drug therapy ; Leiomyoma/surgery ; Leiomyoma/veterinary ; Luteoma/veterinary ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/surgery ; Ovarian Neoplasms/veterinary ; Ovariectomy/veterinary ; Progesterone/antagonists & inhibitors ; Progesterone/blood ; Prostaglandins F/therapeutic use ; Vaginal Neoplasms/drug therapy ; Vaginal Neoplasms/surgery ; Vaginal Neoplasms/veterinary
Chemical Substances	Estrenes ; Prostaglandins F ; aglepristone (0UT4JLE1CM) ; Progesterone (4G7DS2Q64Y) ; alfaprostol (4XKL2JJ08I)
Language	English
Publishing date	2020-08-10
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1746-6148
ISSN (online)	1746-6148
DOI	10.1186/s12917-020-02507-z
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Article ; Online: Evaluation and optimisation of propofol pharmacokinetic parameters in cats for target-controlled infusion.

Cattai, A / Pilla, T / Cagnardi, P / Zonca, A / Franci, P

The Veterinary record

2016 Volume 178, Issue 20, Page(s) 503

Abstract: The aim of this study was to develop and evaluate a pharmacokinetic model-driven infusion of propofol in premedicated cats. In a first step, propofol (10 mg/kg) was administered intravenously over 60 seconds to induce anaesthesia for the elective ... ...

Abstract	The aim of this study was to develop and evaluate a pharmacokinetic model-driven infusion of propofol in premedicated cats. In a first step, propofol (10 mg/kg) was administered intravenously over 60 seconds to induce anaesthesia for the elective neutering of seven healthy cats, premedicated intramuscularly with 0.3 mg/kg methadone, 0.01 mg/kg medetomidine and 2 mg/kg ketamine. Venous blood samples were collected over 240 minutes, and propofol concentrations were measured via a validated high-performance liquid chromatography assay. Selected pharmacokinetic parameters, determined by a three-compartment open linear model, were entered into a computer-controlled infusion pump (target-controlled infusion-1 (TCI-1)). In a second step, TCI-1 was used to induce and maintain general anaesthesia in nine cats undergoing neutering. Predicted and measured plasma concentrations of propofol were compared at specific time points. In a third step, the pharmacokinetic parameters were modified according to the results from the use of TCI-1 and were evaluated again in six cats. For this TCI-2 group, the median values of median performance error and median absolute performance error were -1.85 per cent and 29.67 per cent, respectively, indicating that it performed adequately. Neither hypotension nor respiratory depression was observed during TCI-1 and TCI-2. Mean anaesthesia time and time to extubation in the TCI-2 group were 73.90 (±20.29) and 8.04 (±5.46) minutes, respectively.
MeSH term(s)	Anesthetics, Intravenous/administration & dosage ; Anesthetics, Intravenous/pharmacokinetics ; Animals ; Cats ; Female ; Infusion Pumps/veterinary ; Infusions, Intravenous/methods ; Infusions, Intravenous/veterinary ; Male ; Propofol/administration & dosage ; Propofol/pharmacokinetics
Chemical Substances	Anesthetics, Intravenous ; Propofol (YI7VU623SF)
Language	English
Publishing date	2016-05-14
Publishing country	England
Document type	Evaluation Studies ; Journal Article
ZDB-ID	390015-0
ISSN	2042-7670 ; 0042-4900
ISSN (online)	2042-7670
ISSN	0042-4900
DOI	10.1136/vr.103560
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Article ; Online: Combined spinal and general anaesthesia in 58 cats undergoing various surgical procedures: description of technique and retrospective perioperative evaluation.

Sarotti, Diego / Cattai, Andrea / Franci, Paolo

Journal of feline medicine and surgery

2018 Volume 21, Issue 12, Page(s) 1127–1133

Abstract: Objectives: The aim of this retrospective study was to describe the spinal anaesthesia (SA) technique and evaluate the incidence of perioperative complications in cats.: Methods: The anaesthetic records of cats of American Society of ... ...

Abstract	Objectives: The aim of this retrospective study was to describe the spinal anaesthesia (SA) technique and evaluate the incidence of perioperative complications in cats. Methods: The anaesthetic records of cats of American Society of Anaesthesiologists physical status I, II and III, which received general and SA for different surgeries between 2012 and 2016, were examined. SA was administered through a 25 G Quincke needle, using an isobaric solution of bupivacaine and morphine at the level of either the L Results: A total of 58 anaesthetic records met the inclusion criteria and were analysed. PFR related to the space of injection (L Conclusions and relevance: SA was characterised by a low PFR when performed at the L
MeSH term(s)	Analgesia/veterinary ; Analgesics, Opioid/administration & dosage ; Anesthesia, General/methods ; Anesthesia, General/veterinary ; Anesthesia, Spinal/methods ; Anesthesia, Spinal/veterinary ; Anesthetics, Local/administration & dosage ; Animals ; Bupivacaine/administration & dosage ; Cats/surgery ; Intraoperative Complications/veterinary ; Morphine/administration & dosage ; Perioperative Period/veterinary ; Retrospective Studies
Chemical Substances	Analgesics, Opioid ; Anesthetics, Local ; Morphine (76I7G6D29C) ; Bupivacaine (Y8335394RO)
Language	English
Publishing date	2018-12-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2049047-1
ISSN	1532-2750 ; 1098-612X
ISSN (online)	1532-2750
ISSN	1098-612X
DOI	10.1177/1098612X18819496
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Article: Interval between Removal of a 4.7 mg Deslorelin Implant after a 3-, 6-, and 9-Month Treatment and Restoration of Testicular Function in Tomcats.

Ferré-Dolcet, Lluis / Carniello, Lisa / Ferro, Silvia / Cattai, Andrea / Romagnoli, Stefano / Mollo, Antonio

Animals : an open access journal from MDPI

2020 Volume 10, Issue 9

Abstract: Deslorelin implants have been used to produce a reversible sterilization in several species. In cats, the prolonged duration (12-15 months in tomcats and 18-22 months in queen) is often too much for cat breeders who request early implant removal. The ... ...

Abstract	Deslorelin implants have been used to produce a reversible sterilization in several species. In cats, the prolonged duration (12-15 months in tomcats and 18-22 months in queen) is often too much for cat breeders who request early implant removal. The interval between implant removal and resumption of reproductive function in cats has never been investigated. Eighteen tomcats received a 4.7 mg deslorelin implant placed in the periumbilical area and surgically removed during all seasons of the year after 3, 6, or 9 months (n = 6, 6, and 6 cats, respectively). Following implant removal, all cats received a clinical exam every two weeks, including testicular ultrasonographic measurement, observation of penile spikes, and blood collection for serum testosterone assay. Restoration of serum testosterone secretion occurred after 23 ± 6, 23 ± 6, and 22 ± 7 days in the 3-, 6-, and 9-month groups, respectively. Restoration of testicular function was confirmed by histology in 13/15 cats undergoing orchiectomy at the end of the study while the owners of the remaining two cats opted to maintain their animals intact. Removal of a 4.7 mg deslorelin implant after 3, 6, or 9 months is followed by resumption of serum testosterone secretion after about 3 weeks independent of age or season.
Language	English
Publishing date	2020-09-02
Publishing country	Switzerland
Document type	Journal Article
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani10091559
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Article: Ultrasound-Guided Hook-Wire Localization for Surgical Excision of Non-Palpable Superficial Inguinal Lymph Nodes in Dogs: A Pilot Study.

Pierini, Alessio / Marchetti, Veronica / Rossanese, Matteo / Finotello, Riccardo / Cattai, Andrea / Pisani, Guido

Animals : an open access journal from MDPI

2020 Volume 10, Issue 12

Abstract: The evaluation of loco-regional lymph nodes (LN) plays an important prognostic role and assists the clinical decision making in canine cancer patients. Excision of non-palpable LN can be challenging. The aim of the study was to evaluate surgical time, ... ...

Abstract	The evaluation of loco-regional lymph nodes (LN) plays an important prognostic role and assists the clinical decision making in canine cancer patients. Excision of non-palpable LN can be challenging. The aim of the study was to evaluate surgical time, successful excision rate and surgical complications associated with the use of an ultrasound-guided hook-wire (UGHW) LN localization method for non-palpable superficial inguinal LN (SILN) in dogs. Dogs that presented for excision of non-palpable SILN, performed with the aid of an UGHW placement, were enrolled. Information including signalment, SILN width, UGHW placement and surgical procedure time, hook-wire position, successful excision and intra- and post-operative complications were reviewed. Seventeen dogs were enrolled. Median LN width was 3 mm (range 2-11). Median time of preoperative UGHW placement and surgical LN excision was 8 min and 15 min, respectively. Successful SILN excision was achieved in all cases. Two minor intra-operative (hook migration and wire fragmentation) and one minor post-operative complications (seroma) were observed. No major intraoperative or post-operative complications occurred. The UGHW LN localization method is safe and effective and may allow a high rate of successful SILN excisions in dogs. This method has the potential to facilitate LN excision for other superficial LN locations.
Language	English
Publishing date	2020-12-07
Publishing country	Switzerland
Document type	Journal Article
ISSN	2076-2615
ISSN	2076-2615
DOI	10.3390/ani10122314
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