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Perioperative Analgesia in Experimental Small Bowel Transplantation
Perioperative Analgesia in Experimental Small Bowel Transplantation R.A.M. Camprodon and M.J. Bowles ABSTRACT Background. Despite numerous studies in experimental rat small bowel transplantation (SBT), few authors make reference to perioperative analgesia. Recent changes to the Animals (Scientific Procedures) Act 1986 in the United Kingdom have made the use of analgesia in laboratory animals compulsory because pain is unnecessary in the majority of scientific procedures. Methods. Heterotopic SBT (PVG¡DA) was performed on male rat recipients weighing 220 to 250 mg under isoflurane with a mean anesthetic time of 100 minutes. Recovery from anesthesia was usually within 15 minutes. Analgesia regimens were based on those in common use for other procedures. All drugs were administered in the 30 minutes prior to recovery from anesthesia. Group A received carprofen (2 mg/kg IM or SC). Group B was given buprenorphine (0.05 mg/kg either IM or SC). Group C received paracetamol (10 – 30 mg) rectally. An early postoperative scoring system of four criteria was used, giving a maximum (least desirable) score of 16. Sixty transplants were performed, divided between the three groups. Results. In group A animals scored a median of 1 of 16 but all except three recipients died within 3 hours. Those in group B scored a median of 8 of 16, but all animals except one died between 4 to 16 hours after surgery. Group C had a median score of 11 of 16, but there was no early mortality. Postmortem examination excluded technical failures in all but three animals. Conclusion. We recommend the use of paracetamol for perioperative analgesia in SBT because of the high mortality associated with other drugs when used in this procedure.
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ESPITE NUMEROUS STUDIES in experimental rat small bowel transplantation (SBT), few authors make reference to perioperative analgesia. Recent changes to the Animals (Scientific Procedures) Act 1986 in the United Kingdom, compiled in the 2000 revision under Chapter VI: Appendix E (sections 12, 19, 19B and 19C), have made the use of analgesia in laboratory animals compulsory because pain is unnecessary in the majority of scientific procedures.1 Minimizing animal distress derived from any surgical intervention is not only humane but essential, especially following complex major surgery such as SBT. However, there is anecdotal evidence suggesting a link between pain-free animals and unexpected high mortality rates in the early postoperative period. The aim was to assess the impact of different analgesic regimens in the early perioperative period (within first 24 hours) following experimental rat SBT.
MATERIALS AND METHODS Heterotopic SBT was performed from donor PVG rats to DA recipients under inhalation general anesthesia using a modification of an established technique.2 The mean anesthetic time was 90 to 100 minutes, and full recovery was usually within 15 minutes. Three drugs were used in this study: carprofen, buprenorphine, and paracetamol; each has a distinct analgesic profile. The analgesic regimens were based on those in common use for other procedures. All drugs were administered in the 30 minutes prior to recovery from anesthesia. Sixty transplants were performed between three groups. Group received 2 mg/kg of a nonsteroidal antiinflammatory drug (carprofen) via intramuscular or subcutaneous injection. Group B was From the Institute of Liver Studies, King’s College Hospital, Denmark Hill, London, UK. Address reprint requests to Mr. Ricardo Camprodon, Research Fellow, Liver Transplant Surgical Service, King’s College Hospital, Denmark Hill, London, SE5 9RS, UK. E-mail: ricardcamprodon@ yahoo.es
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.05.005
Transplantation Proceedings, 38, 1857–1858 (2006)
1857
1858
CAMPRODON AND BOWLES
Table 1. Early Postoperative Distress Scoring System Appearance Normal General lack of grooming Ocular and nasal discharges Piloerection, hunched up Clinical signs Normal temperature, cardiac and respiratory rates Slight changes T⫾1oC, C/R rates ⫾ 30% T⫾2oC, C/R rates ⫾ 50% Natural behaviour Normal Minor changes Less mobile and alert, isolated Vocalization, self-mutilation, restless or very still Provoked behavior Normal Minor depression or exaggerated response Moderate change in expected behaviour Reacts violently, or very weak and precomatose Score adjustment If score 3 for more than one criterion, add an extra point for each 3 scored
0 1 2 3 0 1 2 3 0 1 2 3 0 1 2 3 2–4
given 0.05 mg/kg of the opiate buprenorphine either intramuscularly or subcutaneously. Group C received paracetamol (10 –30 mg) rectally. A scoring system modified from Wolfensohn and Lloyd3 (Table 1) used four criteria to assess animal distress during the early postoperative period, with a maximum (least desirable) score of 16.
RESULTS
The animals in group A had a median distress score of 1 of 16, but 85% of recipients died within 3 hours of recovery
from anesthesia. Those in group B scored a median of 8 of 16, but 95% animals died between 4 and 16 hours from recovery. Group C had a median score of 11 of 16, but there was no early postoperative mortality. Postmortem examination excluded technical failures in all but three (5%) animals.
DISCUSSION
There is paucity of data in the literature on perioperative analgesia. The reasons for the high mortality seen in relation to some analgesics remains poorly understood. However, a synergistic interaction with anesthetic drugs coupled with long operative times may be the best explanation. In conclusion, we recommend the use of paracetamol for perioperative analgesia in SBT. Animals under this analgesic regimen seemed to be equally comfortable at 16 hours from surgery when compared to the few survivors treated with other analgesic regimens.
REFERENCES 1. Available from http://scienceandresearch.homeoffice.gov.uk/ animal-research/legislation/. Accessed: May 20, 2005 2. Monchik GJ, Russell PS: Transplantation of small bowel in the rat: Technical and immunological considerations. Surgery 70: 693, 1971 3. Wolfensohn S, Lloyd M: Introduction To The Principles Of Animal Care And Use. Handbook of Laboratory Animal Management and Welfare. 2nd ed. Malfden, Mass: Blackwell Science; 1998, p 59
D
ESPITE NUMEROUS STUDIES in experimental rat small bowel transplantation (SBT), few authors make reference to perioperative analgesia. Recent changes to the Animals (Scientific Procedures) Act 1986 in the United Kingdom, compiled in the 2000 revision under Chapter VI: Appendix E (sections 12, 19, 19B and 19C), have made the use of analgesia in laboratory animals compulsory because pain is unnecessary in the majority of scientific procedures.1 Minimizing animal distress derived from any surgical intervention is not only humane but essential, especially following complex major surgery such as SBT. However, there is anecdotal evidence suggesting a link between pain-free animals and unexpected high mortality rates in the early postoperative period. The aim was to assess the impact of different analgesic regimens in the early perioperative period (within first 24 hours) following experimental rat SBT.
MATERIALS AND METHODS Heterotopic SBT was performed from donor PVG rats to DA recipients under inhalation general anesthesia using a modification of an established technique.2 The mean anesthetic time was 90 to 100 minutes, and full recovery was usually within 15 minutes. Three drugs were used in this study: carprofen, buprenorphine, and paracetamol; each has a distinct analgesic profile. The analgesic regimens were based on those in common use for other procedures. All drugs were administered in the 30 minutes prior to recovery from anesthesia. Sixty transplants were performed between three groups. Group received 2 mg/kg of a nonsteroidal antiinflammatory drug (carprofen) via intramuscular or subcutaneous injection. Group B was From the Institute of Liver Studies, King’s College Hospital, Denmark Hill, London, UK. Address reprint requests to Mr. Ricardo Camprodon, Research Fellow, Liver Transplant Surgical Service, King’s College Hospital, Denmark Hill, London, SE5 9RS, UK. E-mail: ricardcamprodon@ yahoo.es
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.05.005
Transplantation Proceedings, 38, 1857–1858 (2006)
1857
1858
CAMPRODON AND BOWLES
Table 1. Early Postoperative Distress Scoring System Appearance Normal General lack of grooming Ocular and nasal discharges Piloerection, hunched up Clinical signs Normal temperature, cardiac and respiratory rates Slight changes T⫾1oC, C/R rates ⫾ 30% T⫾2oC, C/R rates ⫾ 50% Natural behaviour Normal Minor changes Less mobile and alert, isolated Vocalization, self-mutilation, restless or very still Provoked behavior Normal Minor depression or exaggerated response Moderate change in expected behaviour Reacts violently, or very weak and precomatose Score adjustment If score 3 for more than one criterion, add an extra point for each 3 scored
0 1 2 3 0 1 2 3 0 1 2 3 0 1 2 3 2–4
given 0.05 mg/kg of the opiate buprenorphine either intramuscularly or subcutaneously. Group C received paracetamol (10 –30 mg) rectally. A scoring system modified from Wolfensohn and Lloyd3 (Table 1) used four criteria to assess animal distress during the early postoperative period, with a maximum (least desirable) score of 16.
RESULTS
The animals in group A had a median distress score of 1 of 16, but 85% of recipients died within 3 hours of recovery
from anesthesia. Those in group B scored a median of 8 of 16, but 95% animals died between 4 and 16 hours from recovery. Group C had a median score of 11 of 16, but there was no early postoperative mortality. Postmortem examination excluded technical failures in all but three (5%) animals.
DISCUSSION
There is paucity of data in the literature on perioperative analgesia. The reasons for the high mortality seen in relation to some analgesics remains poorly understood. However, a synergistic interaction with anesthetic drugs coupled with long operative times may be the best explanation. In conclusion, we recommend the use of paracetamol for perioperative analgesia in SBT. Animals under this analgesic regimen seemed to be equally comfortable at 16 hours from surgery when compared to the few survivors treated with other analgesic regimens.
REFERENCES 1. Available from http://scienceandresearch.homeoffice.gov.uk/ animal-research/legislation/. Accessed: May 20, 2005 2. Monchik GJ, Russell PS: Transplantation of small bowel in the rat: Technical and immunological considerations. Surgery 70: 693, 1971 3. Wolfensohn S, Lloyd M: Introduction To The Principles Of Animal Care And Use. Handbook of Laboratory Animal Management and Welfare. 2nd ed. Malfden, Mass: Blackwell Science; 1998, p 59