Hedley, J

Monticelli, P

Pinelas, R

English

RVC Repository (Royal Veterinary College)

Accepted ManuscriptHaemodynamic changes occurring in a loggerhead sea turtle (Caretta caretta) duringmechanical ventilation under general anaesthesiaPaolo Monticelli, Joanna Hedley, Rui PinelasPII: S1467-2987(17)30138-1DOI: 10.1016/j.vaa.2016.08.010Reference: VAA 126To appear in: Veterinary Anaesthesia and AnalgesiaReceived Date: 16 February 2016Revised Date: 4 July 2016Accepted Date: 2 August 2016Please cite this article as: Monticelli P, Hedley J, Pinelas R, Haemodynamic changes occurring ina loggerhead sea turtle (Caretta caretta) during mechanical ventilation under general anaesthesia,Veterinary Anaesthesia and Analgesia (2017), doi: 10.1016/j.vaa.2016.08.010.This is a PDF file of an unedited manuscript that has been accepted for publication. As a service toour customers we are providing this early version of the manuscript. The manuscript will undergocopyediting, typesetting, and review of the resulting proof before it is published in its final form. Pleasenote that during the production process errors may be discovered which could affect the content, and alllegal disclaimers that apply to the journal pertain.MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTLETTER TO THE EDITOR 1 Haemodynamic changes occurring in a loggerhead sea turtle (Caretta caretta) during 2 mechanical ventilation under general anaesthesia  3  4 We wish to report the occurrence of significant haemodynamic changes during mechanical 5 ventilation in a sea turtle under general anaesthesia. 6 A 67-year-old loggerhead sea turtle (Caretta caretta), weighing 94 kg, was referred for a 16-7 week period of inappetence. Physical appearance was unremarkable. A computed tomography 8 scan revealed the presence of an enterolith causing intestinal obstruction, requiring surgical 9 intervention. The patient was anaesthetised with 6 mg kg-1 of ketamine (Anaestamine; 10 Animalcare, UK) and 0.025 mg kg-1 of dexmedetomidine (Dexdomitor; Vetoquinol, UK), 11 injected into the left cervical sinus. An additional 2 mg kg-1 of propofol (PropoFlo Plus, Abbott, 12 UK) was administered via this route to allow for orotracheal intubation with a size 9 13 endotracheal tube. The latter was connected to a circle breathing system (Model 2800C; Mallard 14 Medical, USA) and mechanical ventilation was initiated with a tidal volume of 5 mL kg-1 and a 15 respiratory rate ranging between 8 and 12 breaths minute-1. Anaesthesia was maintained with 16 desflurane (Suprane; Baxter, UK) vaporized in oxygen (end-tidal percentage: 7.4% -8.4%). 17 Morphine [0.3 mg kg-1 (Morphine Sulphate; Martindale Pharmaceuticals, UK)] was 18 administered intramuscularly before performing the celiotomy. Intravenous access was obtained 19 in the left cervical sinus and 2 mL kg-1 hour-1 of Hartmann’s solution was administered 20 throughout the anaesthesia. A Datex-Ohmeda S/5 multiparametric monitor was used to monitor 21 physiological parameters. Throughout the anaesthetic end-tidal carbon dioxide partial pressure 22 ranged from 15 to 27 mmHg (2.00‒3.60 kPa) and the heart rate (HR) varied between 12 and 20 23 beats minute-1. Pulsed Wave Doppler ultrasonography was performed int rmittently through the 24 left cervicobrachial acoustic window (Valente et al. 2008) using an ultrasound machine (S9v 25 Sonoscape, China) with a 8-4 MHz micro-curved probe set to cardiology mode (Fig. 1). The 26 MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTanimal was initially positioned in ventral recumbency to perform a colonoscopy, and then turned 27 into the dorsal position to allow for pre-femoral ce iotomy. After changing the recumbency, the 28 peak airway pressure increased from 8 to 15 cm H2O and a concurrent increase in the peak 29 aortic systolic velocity from 0.35 to 0.49 m s-1 was observed. The presence of diffuse yolk 30 coelomitis, together with the severely compromised appearance of the intestines, prompted 31 euthanasia. 32 The HR recorded during anaesthesia were lower than the physiological reference intervals 33 reported for this species [29 (23-36) beats minute-1], whose values seem to correlate negatively 34 with the body mass (Valente et al. 2008). The administration of dexmedetomidine and morphine 35 could have caused bradycardia. Unfortunately, since bas line physiological  parameters were 36 not obtained before premedication, this hypothesis cannot be confirmed.  37 During the anaesthetic we recorded peaks in aortic systolic velocity higher than the values 38 reported in the literature for the species (0.22 ± 0.08 m s-1; Valente et al., 2008), and these values 39 further increased when the turtle was repositioned. This finding was unexpected and it is 40 challenging to propose a reasonable explanation.  41 The cardiovascular effects of α2-agonists in chelonians are comparable to the ones in mammals 42 (Dennis & Heard 2002), and the administration of dexm detomidine and opioids was found to 43 consistently decrease the aortic peak flow velocity in dogs (Kellihan et al. 2015). Therefore, the 44 administration of these agents to this sea turtle was expected to decrease, rather than increase, 45 the aortic flow velocity, and, consequently, the origin of our findings should be sought 46 elsewhere.  47 One potential reason could be cardiovascular changes associated with mechanical ventilation, 48 possibly exacerbated by dorsal recumbency. Chelonians are known to have broad systolic peaks, 49 as well as high velocity peaks in diastole, which generate a continuous flow throughout the 50 cardiac cycle (Valente et al. 2008). However, blood fl w distribution between the lungs and 51 systemic circulation is mainly controlled by changes in vascular resistances (Skovgaard & Wang 52 MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPT2006). Furthermore, lungs actively expand and contract due the action of the trunk muscles on 53 the ventral postpulmonary septum. Previous investigators (Shelton & Burggren 1976) observed 54 considerable changes in vascular resistances, cardia  output and flow throughout spontaneous 55 ventilation, with both pulmonary and systemic flow increasing during inspiration when the 56 intrapulmonary pressure is lower.  It is therefore plausible to hypothesize that mechanical 57 ventilation might have altered the entire vascular resistance increasing the intrapulmonary 58 pressure.  This would have resulted in a cardiac right-to-left shunt and therefore an increased 59 aortic flow. As corroborated by the dramatic increas  in peak airway pressures observed after 60 the turtle was repositioned, it is also likely that dorsal recumbency enhanced these 61 haemodynamic changes, by applying a direct pressure on the airways as well as on the aorta. 62 To the best of the authors’ knowledge, there are no published guidelines with respect to 63 mechanical ventilation in reptiles, although it is common belief that low respiratory rates and 64 pressures should be applied. We decided to administer conservative tidal volumes to this turtle, 65 because chelonians are known to have highly compliant lungs (Herman et al. 1997). As a result, 66 in order to maintain minute ventilation, relatively high respiratory rates were required. 67 Further clinical evaluations are necessary to improve the understanding of the interaction 68 between haemodynamics and mechanical ventilation in reptiles. 69  70 Paolo Monticelli*, Joanna Hedley† & Rui Pinelas* 71 *Clinical Science and Services, Royal Veterinary College, Hatfield, UK 72 †RVC Exotics Service, Royal Veterinary College, Lond, UK 73 Email: pmonticelli@rvc.ac.uk 74  75 Acknowledgements 76 The authors would like to thank Dr. Sue Thornton for her kind advice 77  78 MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTReferences 79 Dennis PM, Heard DJ (2002) Cardiopulmonary effects of a medetomidine-ketamine 80 combination administered intravenously in gopher tortoises. J Am Vet Med Assoc 81 220, 1516–1519.  82 Kellihan HB, Stepien RL, Hassen KM et al. (2015) Sedative and echocardiographic effects 83 of dexmedetomidine combined with butorphanol in healt y dogs. J Vet Cardiol 17, 84 282-292. 85 Shelton G, Burggren W (1976) Cardiovascular dynamics of the chelonia during apnoea and 86 lung ventilation. J Exp Biol 64, 323–343. 87 Skovgaard N, Wang T (2006) Local control of pulmonary blood flow and lung structure in 88 reptiles: implications for ventilation perfusion matching. Respir Physiol Neurobiol 89 154, 107-117. 90 Valente AL, Parga ML, Espada Y et al. (2008) Evaluation of Doppler ultrasonography for 91 the measurement of blood flow in young loggerhead sea turtles (Caretta 92 caretta).Vet J 176, 385-392. 93  94 Figure Legend 95 Figure 1 Aortic peak flow in the left aortic artery of a 67-year-old loggerhead sea turtle 96 (Caretta caretta). The Pulse Wave Doppler ultrasonography was performed with the 97 machine (S9v Sonoscape, China) set on cardiology mode using a 8-4 MHz micro-curved 98 probe through the left cervicobrachial acoustic window. Identification of the left aortic 99 artery was based on the position, shape, large diameter and caudal blood flow direction; 100 parameters reported by Valente and others in 2008. 101 MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPT 

Haemodynamic changes occurring in a loggerhead sea turtle (Caretta caretta) during mechanical ventilation under general anaesthesia

Paolo Monticelli

Joanna Hedley

Rui Pinelas

Crossref

Veterinary Anaesthesia and Analgesia

RVC Research Online

Accepted ManuscriptHaemodynamic changes occurring in a loggerhead sea turtle (Caretta caretta) duringmechanical ventilation under general anaesthesiaPaolo Monticelli, Joanna Hedley, Rui PinelasPII: S1467-2987(17)30138-1DOI: 10.1016/j.vaa.2016.08.010Reference: VAA 126To appear in: Veterinary Anaesthesia and AnalgesiaReceived Date: 16 February 2016Revised Date: 4 July 2016Accepted Date: 2 August 2016Please cite this article as: Monticelli P, Hedley J, Pinelas R, Haemodynamic changes occurring ina loggerhead sea turtle (Caretta caretta) during mechanical ventilation under general anaesthesia,Veterinary Anaesthesia and Analgesia (2017), doi: 10.1016/j.vaa.2016.08.010.This is a PDF file of an unedited manuscript that has been accepted for publication. As a service toour customers we are providing this early version of the manuscript. The manuscript will undergocopyediting, typesetting, and review of the resulting proof before it is published in its final form. Pleasenote that during the production process errors may be discovered which could affect the content, and alllegal disclaimers that apply to the journal pertain.MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTLETTER TO THE EDITOR 1 Haemodynamic changes occurring in a loggerhead sea turtle (Caretta caretta) during 2 mechanical ventilation under general anaesthesia  3  4 We wish to report the occurrence of significant haemodynamic changes during mechanical 5 ventilation in a sea turtle under general anaesthesia. 6 A 67-year-old loggerhead sea turtle (Caretta caretta), weighing 94 kg, was referred for a 16-7 week period of inappetence. Physical appearance was unremarkable. A computed tomography 8 scan revealed the presence of an enterolith causing intestinal obstruction, requiring surgical 9 intervention. The patient was anaesthetised with 6 mg kg-1 of ketamine (Anaestamine; 10 Animalcare, UK) and 0.025 mg kg-1 of dexmedetomidine (Dexdomitor; Vetoquinol, UK), 11 injected into the left cervical sinus. An additional 2 mg kg-1 of propofol (PropoFlo Plus, Abbott, 12 UK) was administered via this route to allow for orotracheal intubation with a size 9 13 endotracheal tube. The latter was connected to a circle breathing system (Model 2800C; Mallard 14 Medical, USA) and mechanical ventilation was initiated with a tidal volume of 5 mL kg-1 and a 15 respiratory rate ranging between 8 and 12 breaths minute-1. Anaesthesia was maintained with 16 desflurane (Suprane; Baxter, UK) vaporized in oxygen (end-tidal percentage: 7.4% -8.4%). 17 Morphine [0.3 mg kg-1 (Morphine Sulphate; Martindale Pharmaceuticals, UK)] was 18 administered intramuscularly before performing the celiotomy. Intravenous access was obtained 19 in the left cervical sinus and 2 mL kg-1 hour-1 of Hartmann’s solution was administered 20 throughout the anaesthesia. A Datex-Ohmeda S/5 multiparametric monitor was used to monitor 21 physiological parameters. Throughout the anaesthetic end-tidal carbon dioxide partial pressure 22 ranged from 15 to 27 mmHg (2.00‒3.60 kPa) and the heart rate (HR) varied between 12 and 20 23 beats minute-1. Pulsed Wave Doppler ultrasonography was performed intermittently through the 24 left cervicobrachial acoustic window (Valente et al. 2008) using an ultrasound machine (S9v 25 Sonoscape, China) with a 8-4 MHz micro-curved probe set to cardiology mode (Fig. 1). The 26 MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTanimal was initially positioned in ventral recumbency to perform a colonoscopy, and then turned 27 into the dorsal position to allow for pre-femoral celiotomy. After changing the recumbency, the 28 peak airway pressure increased from 8 to 15 cm H2O and a concurrent increase in the peak 29 aortic systolic velocity from 0.35 to 0.49 m s-1 was observed. The presence of diffuse yolk 30 coelomitis, together with the severely compromised appearance of the intestines, prompted 31 euthanasia. 32 The HR recorded during anaesthesia were lower than the physiological reference intervals 33 reported for this species [29 (23-36) beats minute-1], whose values seem to correlate negatively 34 with the body mass (Valente et al. 2008). The administration of dexmedetomidine and morphine 35 could have caused bradycardia. Unfortunately, since baseline physiological  parameters were 36 not obtained before premedication, this hypothesis cannot be confirmed.  37 During the anaesthetic we recorded peaks in aortic systolic velocity higher than the values 38 reported in the literature for the species (0.22 ± 0.08 m s-1; Valente et al., 2008), and these values 39 further increased when the turtle was repositioned. This finding was unexpected and it is 40 challenging to propose a reasonable explanation.  41 The cardiovascular effects of α2-agonists in chelonians are comparable to the ones in mammals 42 (Dennis & Heard 2002), and the administration of dexmedetomidine and opioids was found to 43 consistently decrease the aortic peak flow velocity in dogs (Kellihan et al. 2015). Therefore, the 44 administration of these agents to this sea turtle was expected to decrease, rather than increase, 45 the aortic flow velocity, and, consequently, the origin of our findings should be sought 46 elsewhere.  47 One potential reason could be cardiovascular changes associated with mechanical ventilation, 48 possibly exacerbated by dorsal recumbency. Chelonians are known to have broad systolic peaks, 49 as well as high velocity peaks in diastole, which generate a continuous flow throughout the 50 cardiac cycle (Valente et al. 2008). However, blood flow distribution between the lungs and 51 systemic circulation is mainly controlled by changes in vascular resistances (Skovgaard & Wang 52 MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPT2006). Furthermore, lungs actively expand and contract due the action of the trunk muscles on 53 the ventral postpulmonary septum. Previous investigators (Shelton & Burggren 1976) observed 54 considerable changes in vascular resistances, cardiac output and flow throughout spontaneous 55 ventilation, with both pulmonary and systemic flow increasing during inspiration when the 56 intrapulmonary pressure is lower.  It is therefore plausible to hypothesize that mechanical 57 ventilation might have altered the entire vascular resistance increasing the intrapulmonary 58 pressure.  This would have resulted in a cardiac right-to-left shunt and therefore an increased 59 aortic flow. As corroborated by the dramatic increase in peak airway pressures observed after 60 the turtle was repositioned, it is also likely that dorsal recumbency enhanced these 61 haemodynamic changes, by applying a direct pressure on the airways as well as on the aorta. 62 To the best of the authors’ knowledge, there are no published guidelines with respect to 63 mechanical ventilation in reptiles, although it is common belief that low respiratory rates and 64 pressures should be applied. We decided to administer conservative tidal volumes to this turtle, 65 because chelonians are known to have highly compliant lungs (Herman et al. 1997). As a result, 66 in order to maintain minute ventilation, relatively high respiratory rates were required. 67 Further clinical evaluations are necessary to improve the understanding of the interaction 68 between haemodynamics and mechanical ventilation in reptiles. 69  70 Paolo Monticelli*, Joanna Hedley† & Rui Pinelas* 71 *Clinical Science and Services, Royal Veterinary College, Hatfield, UK 72 †RVC Exotics Service, Royal Veterinary College, London, UK 73 Email: pmonticelli@rvc.ac.uk 74  75 Acknowledgements 76 The authors would like to thank Dr. Sue Thornton for her kind advice 77  78 MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTReferences 79 Dennis PM, Heard DJ (2002) Cardiopulmonary effects of a medetomidine-ketamine 80 combination administered intravenously in gopher tortoises. J Am Vet Med Assoc 81 220, 1516–1519.  82 Kellihan HB, Stepien RL, Hassen KM et al. (2015) Sedative and echocardiographic effects 83 of dexmedetomidine combined with butorphanol in healthy dogs. J Vet Cardiol 17, 84 282-292. 85 Shelton G, Burggren W (1976) Cardiovascular dynamics of the chelonia during apnoea and 86 lung ventilation. J Exp Biol 64, 323–343. 87 Skovgaard N, Wang T (2006) Local control of pulmonary blood flow and lung structure in 88 reptiles: implications for ventilation perfusion matching. Respir Physiol Neurobiol 89 154, 107-117. 90 Valente AL, Parga ML, Espada Y et al. (2008) Evaluation of Doppler ultrasonography for 91 the measurement of blood flow in young loggerhead sea turtles (Caretta 92 caretta).Vet J 176, 385-392. 93  94 Figure Legend 95 Figure 1 Aortic peak flow in the left aortic artery of a 67-year-old loggerhead sea turtle 96 (Caretta caretta). The Pulse Wave Doppler ultrasonography was performed with the 97 machine (S9v Sonoscape, China) set on cardiology mode using a 8-4 MHz micro-curved 98 probe through the left cervicobrachial acoustic window. Identification of the left aortic 99 artery was based on the position, shape, large diameter and caudal blood flow direction; 100 parameters reported by Valente and others in 2008. 101 MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPT 

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Haemodynamic changes occurring in a loggerhead sea turtle (Caretta caretta) during mechanical ventilation under general anaesthesia

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