meredith sheil - Academia.edu (original) (raw)

Papers by meredith sheil

Anaesthesia and Intensive Care, Dec 1, 1999

We report out initial experience with intraoperative transoesophageal echocardiography (TOE) in 2... more We report out initial experience with intraoperative transoesophageal echocardiography (TOE) in 200 patients undergoing repair of congenital heart disease. Complications associated with probe insertion precluded a full study in 11 patients (5.5%) and included airway obstruction (n=6), inability to pass the probe (n=4) and vascular compression (n=1). The preoperative diagnosis was confirmed by TOE in 176 of 189 cases (93%) with minor variances in 12 (6.3%) and one major variance (additional large muscular ventricular septal defect (VSD)). Unexpected abnormalities not diagnosed preoperatively were found at surgery in four cases (2%) and were all of trivial operative significance. Postoperative studies showed no residual defect in 96 (51%) and trivial or mild residual defects in 72 patients (38%). There were moderate or severe residual defects in 21 cases (11%). Ten cases (5.3%) returned to bypass for further surgery, with eight achieving complete or adequate amelioration. In six of the 10 cases, return to bypass was prompted by the TOE examination alone. There was one re-operation in the postoperative period for a VSD patch dehiscence. Routine TOE offers significant advantages in the management of patients undergoing repair of congenital heart disease, particularly in postoperative assessment. Careful monitoring of perfusion and ventilation is required, particularly during probe insertion in children weighing 5 kg or less.

Berliner Und Munchener Tierarztliche Wochenschrift, 2021

Australian Veterinary Journal, 2013

Objective To investigate the effect of topical anaesthesia on 'mothering up' of lambs after mules... more Objective To investigate the effect of topical anaesthesia on 'mothering up' of lambs after mulesing and marking, and for pain alleviation over a 24-h period. Design Two separate trials were performed on Merino lambs undergoing the mules procedure for flystrike prevention, to assess the efficacy of immediate postoperative topical anaesthetic wound dressing containing lignocaine (hydrochloride) 40.6 g/L, bupivacaine (hydrochloride) 4.5 g/L, adrenaline (tartrate) 24.8 mg/L and cetrimide 5.0 g/L in a gel base (Bayer Animal Health, Gordon, NSW, Australia). Methods In both trials, lambs were assigned to one of three treatment regimens: control, mules procedure with topical anaesthetic (0.5 mL/kg) and mules procedure without topical anaesthetic treatment. Parameters measured included body weight, assessment of skin and wound sensitivity to light touch and pain stimulation, behavioural responses and time to mother up and to feed. Results In both trials there was rapid (1 min) and prolonged (up to 24 h) wound analgesia as shown by lower scores for light touch (P < 0.001) and pain responses (P < 0.001), with absent or significantly diminished primary and secondary hyperalgesia (P Յ 0.05) and significant reduction in pain-related behaviours (P < 0.001) in treated versus untreated lambs. Conclusion Significant pain alleviation and improved recovery can be achieved in lambs for at least 24 h after mulesing through the use of topical anaesthesia. It is suggested that the haemostatic action of adrenalin, together with inhibition of the inflammatory cascade and the barrier effect of the gel within the product, may explain the prolonged anaesthesia up to 24 h observed in the present study. These results suggest that topical anaesthesia has the capacity to dramatically improve the welfare of lambs undergoing mulesing.

This session covers eleven papers from different authors: The Sheep Room 1. Analgesia for Surgica... more This session covers eleven papers from different authors: The Sheep Room 1. Analgesia for Surgical Husbandry Procedures in Sheep and Other Livestock, Dr Meredith L. Sheil, Animal Ethics Pty Ltd, Associate Sydney University Faculty of Veterinary Science The Wool Enterprise 2. Unmulsed sheep - implications for chemical use, Di Evans & Brown Besier, Department of Agriculture and Food WA 3. Are Damara and Dorper sheep better adapted than Merinos to nutritional stress? - Growth rates, Tim Scanlon1, Andre Martinho de Almeida2, Johan Greeff1, Tanya Kilminster1, John Milton3, Chris Oldham1, Department of Agriculture and Food WA1, Instituto de Investigacao Cientifica Tropical, Lisbon, Portugal2, University of Western Australia3 4. Are Damara and Dorper sheep better adapted than Merinos to nutritional stress? - Carcass attributes, Tanya Kilminster1, Andre Martinho de Almeida2, Johan Greeff1, John Milton3, Chris Oldham1, Tim Scanlon1, Department of Agriculture and Food WA1, Instituto de Invest...

Australian Veterinary Journal, 2020

Objective There is a critical need for safe and effective analgesic treatments to address pain re... more Objective There is a critical need for safe and effective analgesic treatments to address pain resulting from surgical husbandry procedures in livestock. Piglet castration results in acute pain and stress to the animal; however, it is performed globally on millions of piglets annually, often without any analgesia what-so-ever. Tri-Solfen® (Animal Ethics Pty Ltd, Yarra Glen, Victoria, Australia) is a combination local anaesthetic and antiseptic formulation which, applied topically to wounds, has proven effective, and is registered for use to alleviate pain associated with castration (and other wounds) in lambs and calves in Australia and New Zealand. It is also reported to be effective to reduce pain in piglets following castration. Design This randomised, blinded, placebo-controlled study examined the safety and efficacy of the formulation, administered via an adapted wound instillation method, to control pain both during and following piglet castration. Method Piglets received Tri-Solfen or placebo, instilled to the wound immediately following skin incision. A 30 s wait period was then observed prior to completing castration. Pain mitigation was assessed by grading nociceptive resistance movements and piglet vocal response during castration, as well as by grading response to mechanical sensory stimulation of the wound (von Frey and needlestick) following castration. Results There was a significant reduction in nociceptive motor and vocal response during castration and in response to mechanical sensory wound stimulation up to and including 2 h following castration. There were no adverse events. Conclusion Administered via this method, Tri-Solfen is effective to mitigate acute peri-operative castration pain in piglets.

Academic Radiology, 1996

FIGURE 1. Two-dimensional echocardiographic short-axis view (chordal level) of the left ventricle... more FIGURE 1. Two-dimensional echocardiographic short-axis view (chordal level) of the left ventricle before (A) and after (B) intracoronary injection of a hand-agitated mixture of diatrizoate meglumine and saline.

The American Journal of Cardiology, 1995

Two-dimensional e&cardiography is commonly used as a method of monitoring aarlic root dimensions ... more Two-dimensional e&cardiography is commonly used as a method of monitoring aarlic root dimensions in cl?i~ Q&h crmnedivp) tisswe dbeuse. it4fsusummellts are usually standatxked to % w#cioKaeomQc~~ account for grov&. t!oWver, am saveWill theoretical and prcaclkal diidunan approach, and there has been From the Adol ph

Australian Veterinary Journal, 2008

Objective To investigate the impact of using the topical anaesthetic preparation Tri-Solfen® on p... more Objective To investigate the impact of using the topical anaesthetic preparation Tri-Solfen® on pain alleviation and wound healing in lambs undergoing mulesing. Design Three separate trials, placebo controlled and/or randomised, were carried out over a 5 month period on three mobs of between 60 and 263 merino lambs undergoing routine mulesing. Procedure Wound pain was assessed using 10 and 75 g calibrated Von-Frey monofilaments to determine sensitivity to light touch and pain stimulation over a 4 to 8 h period. Pain-related behaviour was documented by trained, blinded observers using a numerical rating scale. Wound healing rates were determined using scaled digital photography and image analysis software to calculate contraction in wound surface area 2 and 4 weeks after mulesing. Results There was rapid (3 min) and prolonged (up to 8 h) wound analgesia as shown by pain response scores (P ≤ 0.01), with absent or significantly diminished primary and secondary hyperalgesia (P ≤ 0.01) and significant reduction in pain-related behaviour (P < 0.001) in treated versus untreated lambs. In addition there was improved wound healing in the treated lambs (P ≤ 0.05). Conclusion Tri-Solfen® effects rapid and prolonged wound analgesia, reduction in pain-related behaviour and improved wound healing in lambs undergoing routine mulesing, providing effective alleviation of pain associated with routine mulesing in sheep.

Small Ruminant Research, 2009

Mulesing (removal of breech skin for blowfly strike control), castration, tail-docking and ear-kn... more Mulesing (removal of breech skin for blowfly strike control), castration, tail-docking and ear-knotching are routine husbandry procedures conducted on many millions of lambs annually in Australia, causing considerable pain and suffering. However, establishing an effective alternative to mulesing is proving to be a difficult and prolonged process. This is particularly so for producers of high-quality fine wool from Merino sheep

Australian Veterinary Journal, 2010

Objective To investigate the effect of a topical anaesthetic formulation on pain alleviation, wou... more Objective To investigate the effect of a topical anaesthetic formulation on pain alleviation, wound healing and systemic levels of local anaesthetic actives in lambs undergoing castration and tail docking. Design Three placebo-controlled and/or randomised experiments were conducted using three groups of Merino lambs (n = 62, 68 and 19) undergoing routine castration and tail docking. Procedure Surgical castration, with either surgical or hot-iron tail docking, was performed with and without the application of topical anaesthetic (Tri-Solfen®) or placebo. The effects of this procedure were compared with those of rubber ring castration and tail docking, and of the handled but unmarked controls. Wound pain was assessed using calibrated Von-Frey monofilaments over a 4-h period, pain-related behaviour was assessed over 5 h, wound healing was assessed at 14 and 28 days, and the plasma levels of lignocaine and bupivacaine were determined. Results Rapid and up to 4 h primary hyperalgesia developed following surgical castration and tail docking in the untreated and placebo-treated lambs. It was absent in the castration wounds, and significantly reduced in the tail-docking wounds, of the treated lambs. Hot-iron docking was associated with mild and transient secondary hyperalgesia, which was abolished by the topical anaesthesia. There was a significant reduction in pain-related behaviours in treated lambs, which were not significantly different in their behaviour to the sham-operation handled controls. Plasma lignocaine and bupivacaine levels were below the toxic thresholds in all tested lambs. Conclusion Topical anaesthesia alleviates wound pain and significantly reduces pain-related behaviours in lambs undergoing surgical castration plus surgical or hot-iron tail docking, without a negative effect on wound healing or a risk of systemic toxicity.

Journal of Applied Animal Welfare Science, 2009

Regulatory Toxicology and Pharmacology, 2021

Lidocaine has not been associated with cancer in humans despite 8 decades of therapeutic use. Its... more Lidocaine has not been associated with cancer in humans despite 8 decades of therapeutic use. Its metabolite, 2,6-xylidine, is a rat carcinogen, believed to induce genotoxicity via N-hydroxylation and DNA adduct formation, a non-threshold mechanism of action. To better understand this dichotomy, we review literature pertaining to metabolic activation and genotoxicity of 2,6-xylidine, identifying that it appears resistant to N-hydroxylation and instead metabolises almost exclusively to DMAP (an aminophenol). At high exposures (sufficient to saturate phase 2 metabolism), this may undergo metabolic threshold-dependent activation to a quinone-imine with potential to redox cycle producing ROS, inducing cytotoxicity and genotoxicity. A new rat study found no evidence of genotoxicity in vivo based on micronuclei in bone marrow, comets in nasal tissue or female liver, despite high level exposure to 2,6-xylidine (including metabolites). In male liver, weak dose-related comet increases, within the historical control range, were associated with metabolic overload and acute systemic toxicity. Benchmark dose analysis confirmed a non-linear dose response. The weight of evidence indicates 2,6-xylidine is a non-direct acting (metabolic threshold-dependent) genotoxin, and is not genotoxic in vivo in rats in the absence of acute systemic toxic effects, which occur at levels 35 × beyond lidocaine-related exposure in humans.

The Journal of Thoracic and Cardiovascular Surgery, 2005

Animals

Tri-Solfen® is a combination topical anaesthetic and antiseptic solution containing lidocaine, bu... more Tri-Solfen® is a combination topical anaesthetic and antiseptic solution containing lidocaine, bupivacaine, adrenaline and cetrimide. Applied to wounds, it is reported to reduce the pain experienced by calves following thermocautery disbudding. While lidocaine and bupivacaine are widely used in medicine, conflicting data exist on the impact of these compounds when applied directly to the surgical wound. To investigate the safety of Tri-Solfen® applied to thermocautery disbudding wounds of calves, experiments were performed to measure (i) the safety of Tri-Solfen® (including in overdose situations); and (ii) the impact of Tri-Solfen® application at recommended doses on disbudding wound healing under field conditions. Haematological, biochemical and urinalysis parameters did not show clinically significant differences between placebo and Tri-Solfen® groups (1×, 3× and 5× dose). No adverse health impacts were reported. Histopathological analysis of wounds noted a reduction in bacterial...

Animals

Piglet castration results in acute pain and stress to the animal. There is a critical need for ef... more Piglet castration results in acute pain and stress to the animal. There is a critical need for effective on-farm methods of pain mitigation. Local anaesthesia using Tri-Solfen® (Animal Ethics Pty Ltd., Melbourne, Australia), a topical local anaesthetic and antiseptic formulation instilled to the wound during surgery, is a newly evolving on-farm method to mitigate castration pain. To investigate the efficacy of Tri-Solfen®, instilled to the wound during the procedure, to alleviate subsequent castration-related pain in neonatal piglets, we performed a large, negatively controlled, randomised field trial in two commercial pig farms in Europe. Piglets (173) were enrolled and randomised to undergo castration with or without Tri-Solfen®, instilled to the wound immediately following skin incision. A 30 s wait period was then observed prior to completing castration. Efficacy was investigated by measuring pain-induced motor and vocal responses during the subsequent procedure and post-operati...

Analgesic products for piglet castration are critically needed. This requires extensive animal ex... more Analgesic products for piglet castration are critically needed. This requires extensive animal experimentation such as to meet regulatory-required proof of efficacy. At present, there are no validated methods of assessing pain in neonatal piglets. This poses challenges for investigators to optimize trial design and to meet ethical obligations to minimize the number of animals needed. Pain in neonatal piglets may be subtle, transient and / or variably expressed and, in the absence of validated methods, investigators must rely on using a range of biochemical, physiological and behavioural variables, many of which appear to have very low (or unknown) sensitivity or specificity for documenting pain, or pain-relieving effects. A previous systematic review of this subject was hampered by the high degree of variability in the literature base both in terms of methods used to assess pain and pain mitigation, as well as in outcomes reported. In this setting we provide a narrative review, to a...

Anaesthesia and Intensive Care, Dec 1, 1999

We report out initial experience with intraoperative transoesophageal echocardiography (TOE) in 2... more We report out initial experience with intraoperative transoesophageal echocardiography (TOE) in 200 patients undergoing repair of congenital heart disease. Complications associated with probe insertion precluded a full study in 11 patients (5.5%) and included airway obstruction (n=6), inability to pass the probe (n=4) and vascular compression (n=1). The preoperative diagnosis was confirmed by TOE in 176 of 189 cases (93%) with minor variances in 12 (6.3%) and one major variance (additional large muscular ventricular septal defect (VSD)). Unexpected abnormalities not diagnosed preoperatively were found at surgery in four cases (2%) and were all of trivial operative significance. Postoperative studies showed no residual defect in 96 (51%) and trivial or mild residual defects in 72 patients (38%). There were moderate or severe residual defects in 21 cases (11%). Ten cases (5.3%) returned to bypass for further surgery, with eight achieving complete or adequate amelioration. In six of the 10 cases, return to bypass was prompted by the TOE examination alone. There was one re-operation in the postoperative period for a VSD patch dehiscence. Routine TOE offers significant advantages in the management of patients undergoing repair of congenital heart disease, particularly in postoperative assessment. Careful monitoring of perfusion and ventilation is required, particularly during probe insertion in children weighing 5 kg or less.

Berliner Und Munchener Tierarztliche Wochenschrift, 2021

Australian Veterinary Journal, 2013

Objective To investigate the effect of topical anaesthesia on 'mothering up' of lambs after mules... more Objective To investigate the effect of topical anaesthesia on 'mothering up' of lambs after mulesing and marking, and for pain alleviation over a 24-h period. Design Two separate trials were performed on Merino lambs undergoing the mules procedure for flystrike prevention, to assess the efficacy of immediate postoperative topical anaesthetic wound dressing containing lignocaine (hydrochloride) 40.6 g/L, bupivacaine (hydrochloride) 4.5 g/L, adrenaline (tartrate) 24.8 mg/L and cetrimide 5.0 g/L in a gel base (Bayer Animal Health, Gordon, NSW, Australia). Methods In both trials, lambs were assigned to one of three treatment regimens: control, mules procedure with topical anaesthetic (0.5 mL/kg) and mules procedure without topical anaesthetic treatment. Parameters measured included body weight, assessment of skin and wound sensitivity to light touch and pain stimulation, behavioural responses and time to mother up and to feed. Results In both trials there was rapid (1 min) and prolonged (up to 24 h) wound analgesia as shown by lower scores for light touch (P < 0.001) and pain responses (P < 0.001), with absent or significantly diminished primary and secondary hyperalgesia (P Յ 0.05) and significant reduction in pain-related behaviours (P < 0.001) in treated versus untreated lambs. Conclusion Significant pain alleviation and improved recovery can be achieved in lambs for at least 24 h after mulesing through the use of topical anaesthesia. It is suggested that the haemostatic action of adrenalin, together with inhibition of the inflammatory cascade and the barrier effect of the gel within the product, may explain the prolonged anaesthesia up to 24 h observed in the present study. These results suggest that topical anaesthesia has the capacity to dramatically improve the welfare of lambs undergoing mulesing.

This session covers eleven papers from different authors: The Sheep Room 1. Analgesia for Surgica... more This session covers eleven papers from different authors: The Sheep Room 1. Analgesia for Surgical Husbandry Procedures in Sheep and Other Livestock, Dr Meredith L. Sheil, Animal Ethics Pty Ltd, Associate Sydney University Faculty of Veterinary Science The Wool Enterprise 2. Unmulsed sheep - implications for chemical use, Di Evans & Brown Besier, Department of Agriculture and Food WA 3. Are Damara and Dorper sheep better adapted than Merinos to nutritional stress? - Growth rates, Tim Scanlon1, Andre Martinho de Almeida2, Johan Greeff1, Tanya Kilminster1, John Milton3, Chris Oldham1, Department of Agriculture and Food WA1, Instituto de Investigacao Cientifica Tropical, Lisbon, Portugal2, University of Western Australia3 4. Are Damara and Dorper sheep better adapted than Merinos to nutritional stress? - Carcass attributes, Tanya Kilminster1, Andre Martinho de Almeida2, Johan Greeff1, John Milton3, Chris Oldham1, Tim Scanlon1, Department of Agriculture and Food WA1, Instituto de Invest...

Australian Veterinary Journal, 2020

Objective There is a critical need for safe and effective analgesic treatments to address pain re... more Objective There is a critical need for safe and effective analgesic treatments to address pain resulting from surgical husbandry procedures in livestock. Piglet castration results in acute pain and stress to the animal; however, it is performed globally on millions of piglets annually, often without any analgesia what-so-ever. Tri-Solfen® (Animal Ethics Pty Ltd, Yarra Glen, Victoria, Australia) is a combination local anaesthetic and antiseptic formulation which, applied topically to wounds, has proven effective, and is registered for use to alleviate pain associated with castration (and other wounds) in lambs and calves in Australia and New Zealand. It is also reported to be effective to reduce pain in piglets following castration. Design This randomised, blinded, placebo-controlled study examined the safety and efficacy of the formulation, administered via an adapted wound instillation method, to control pain both during and following piglet castration. Method Piglets received Tri-Solfen or placebo, instilled to the wound immediately following skin incision. A 30 s wait period was then observed prior to completing castration. Pain mitigation was assessed by grading nociceptive resistance movements and piglet vocal response during castration, as well as by grading response to mechanical sensory stimulation of the wound (von Frey and needlestick) following castration. Results There was a significant reduction in nociceptive motor and vocal response during castration and in response to mechanical sensory wound stimulation up to and including 2 h following castration. There were no adverse events. Conclusion Administered via this method, Tri-Solfen is effective to mitigate acute peri-operative castration pain in piglets.

Academic Radiology, 1996

FIGURE 1. Two-dimensional echocardiographic short-axis view (chordal level) of the left ventricle... more FIGURE 1. Two-dimensional echocardiographic short-axis view (chordal level) of the left ventricle before (A) and after (B) intracoronary injection of a hand-agitated mixture of diatrizoate meglumine and saline.

The American Journal of Cardiology, 1995

Two-dimensional e&cardiography is commonly used as a method of monitoring aarlic root dimensions ... more Two-dimensional e&cardiography is commonly used as a method of monitoring aarlic root dimensions in cl?i~ Q&h crmnedivp) tisswe dbeuse. it4fsusummellts are usually standatxked to % w#cioKaeomQc~~ account for grov&. t!oWver, am saveWill theoretical and prcaclkal diidunan approach, and there has been From the Adol ph

Australian Veterinary Journal, 2008

Objective To investigate the impact of using the topical anaesthetic preparation Tri-Solfen® on p... more Objective To investigate the impact of using the topical anaesthetic preparation Tri-Solfen® on pain alleviation and wound healing in lambs undergoing mulesing. Design Three separate trials, placebo controlled and/or randomised, were carried out over a 5 month period on three mobs of between 60 and 263 merino lambs undergoing routine mulesing. Procedure Wound pain was assessed using 10 and 75 g calibrated Von-Frey monofilaments to determine sensitivity to light touch and pain stimulation over a 4 to 8 h period. Pain-related behaviour was documented by trained, blinded observers using a numerical rating scale. Wound healing rates were determined using scaled digital photography and image analysis software to calculate contraction in wound surface area 2 and 4 weeks after mulesing. Results There was rapid (3 min) and prolonged (up to 8 h) wound analgesia as shown by pain response scores (P ≤ 0.01), with absent or significantly diminished primary and secondary hyperalgesia (P ≤ 0.01) and significant reduction in pain-related behaviour (P < 0.001) in treated versus untreated lambs. In addition there was improved wound healing in the treated lambs (P ≤ 0.05). Conclusion Tri-Solfen® effects rapid and prolonged wound analgesia, reduction in pain-related behaviour and improved wound healing in lambs undergoing routine mulesing, providing effective alleviation of pain associated with routine mulesing in sheep.

Small Ruminant Research, 2009

Mulesing (removal of breech skin for blowfly strike control), castration, tail-docking and ear-kn... more Mulesing (removal of breech skin for blowfly strike control), castration, tail-docking and ear-knotching are routine husbandry procedures conducted on many millions of lambs annually in Australia, causing considerable pain and suffering. However, establishing an effective alternative to mulesing is proving to be a difficult and prolonged process. This is particularly so for producers of high-quality fine wool from Merino sheep

Australian Veterinary Journal, 2010

Objective To investigate the effect of a topical anaesthetic formulation on pain alleviation, wou... more Objective To investigate the effect of a topical anaesthetic formulation on pain alleviation, wound healing and systemic levels of local anaesthetic actives in lambs undergoing castration and tail docking. Design Three placebo-controlled and/or randomised experiments were conducted using three groups of Merino lambs (n = 62, 68 and 19) undergoing routine castration and tail docking. Procedure Surgical castration, with either surgical or hot-iron tail docking, was performed with and without the application of topical anaesthetic (Tri-Solfen®) or placebo. The effects of this procedure were compared with those of rubber ring castration and tail docking, and of the handled but unmarked controls. Wound pain was assessed using calibrated Von-Frey monofilaments over a 4-h period, pain-related behaviour was assessed over 5 h, wound healing was assessed at 14 and 28 days, and the plasma levels of lignocaine and bupivacaine were determined. Results Rapid and up to 4 h primary hyperalgesia developed following surgical castration and tail docking in the untreated and placebo-treated lambs. It was absent in the castration wounds, and significantly reduced in the tail-docking wounds, of the treated lambs. Hot-iron docking was associated with mild and transient secondary hyperalgesia, which was abolished by the topical anaesthesia. There was a significant reduction in pain-related behaviours in treated lambs, which were not significantly different in their behaviour to the sham-operation handled controls. Plasma lignocaine and bupivacaine levels were below the toxic thresholds in all tested lambs. Conclusion Topical anaesthesia alleviates wound pain and significantly reduces pain-related behaviours in lambs undergoing surgical castration plus surgical or hot-iron tail docking, without a negative effect on wound healing or a risk of systemic toxicity.

Journal of Applied Animal Welfare Science, 2009

Regulatory Toxicology and Pharmacology, 2021

Lidocaine has not been associated with cancer in humans despite 8 decades of therapeutic use. Its... more Lidocaine has not been associated with cancer in humans despite 8 decades of therapeutic use. Its metabolite, 2,6-xylidine, is a rat carcinogen, believed to induce genotoxicity via N-hydroxylation and DNA adduct formation, a non-threshold mechanism of action. To better understand this dichotomy, we review literature pertaining to metabolic activation and genotoxicity of 2,6-xylidine, identifying that it appears resistant to N-hydroxylation and instead metabolises almost exclusively to DMAP (an aminophenol). At high exposures (sufficient to saturate phase 2 metabolism), this may undergo metabolic threshold-dependent activation to a quinone-imine with potential to redox cycle producing ROS, inducing cytotoxicity and genotoxicity. A new rat study found no evidence of genotoxicity in vivo based on micronuclei in bone marrow, comets in nasal tissue or female liver, despite high level exposure to 2,6-xylidine (including metabolites). In male liver, weak dose-related comet increases, within the historical control range, were associated with metabolic overload and acute systemic toxicity. Benchmark dose analysis confirmed a non-linear dose response. The weight of evidence indicates 2,6-xylidine is a non-direct acting (metabolic threshold-dependent) genotoxin, and is not genotoxic in vivo in rats in the absence of acute systemic toxic effects, which occur at levels 35 × beyond lidocaine-related exposure in humans.

The Journal of Thoracic and Cardiovascular Surgery, 2005

Animals

Tri-Solfen® is a combination topical anaesthetic and antiseptic solution containing lidocaine, bu... more Tri-Solfen® is a combination topical anaesthetic and antiseptic solution containing lidocaine, bupivacaine, adrenaline and cetrimide. Applied to wounds, it is reported to reduce the pain experienced by calves following thermocautery disbudding. While lidocaine and bupivacaine are widely used in medicine, conflicting data exist on the impact of these compounds when applied directly to the surgical wound. To investigate the safety of Tri-Solfen® applied to thermocautery disbudding wounds of calves, experiments were performed to measure (i) the safety of Tri-Solfen® (including in overdose situations); and (ii) the impact of Tri-Solfen® application at recommended doses on disbudding wound healing under field conditions. Haematological, biochemical and urinalysis parameters did not show clinically significant differences between placebo and Tri-Solfen® groups (1×, 3× and 5× dose). No adverse health impacts were reported. Histopathological analysis of wounds noted a reduction in bacterial...

Animals

Piglet castration results in acute pain and stress to the animal. There is a critical need for ef... more Piglet castration results in acute pain and stress to the animal. There is a critical need for effective on-farm methods of pain mitigation. Local anaesthesia using Tri-Solfen® (Animal Ethics Pty Ltd., Melbourne, Australia), a topical local anaesthetic and antiseptic formulation instilled to the wound during surgery, is a newly evolving on-farm method to mitigate castration pain. To investigate the efficacy of Tri-Solfen®, instilled to the wound during the procedure, to alleviate subsequent castration-related pain in neonatal piglets, we performed a large, negatively controlled, randomised field trial in two commercial pig farms in Europe. Piglets (173) were enrolled and randomised to undergo castration with or without Tri-Solfen®, instilled to the wound immediately following skin incision. A 30 s wait period was then observed prior to completing castration. Efficacy was investigated by measuring pain-induced motor and vocal responses during the subsequent procedure and post-operati...

Analgesic products for piglet castration are critically needed. This requires extensive animal ex... more Analgesic products for piglet castration are critically needed. This requires extensive animal experimentation such as to meet regulatory-required proof of efficacy. At present, there are no validated methods of assessing pain in neonatal piglets. This poses challenges for investigators to optimize trial design and to meet ethical obligations to minimize the number of animals needed. Pain in neonatal piglets may be subtle, transient and / or variably expressed and, in the absence of validated methods, investigators must rely on using a range of biochemical, physiological and behavioural variables, many of which appear to have very low (or unknown) sensitivity or specificity for documenting pain, or pain-relieving effects. A previous systematic review of this subject was hampered by the high degree of variability in the literature base both in terms of methods used to assess pain and pain mitigation, as well as in outcomes reported. In this setting we provide a narrative review, to a...