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Complications and prognostic factors in equine surgical colic

Sara Torfs (2012)
abstract
Gastrointestinal colic is a very common problem in the horse. Due to advances in surgical techniques and perioperative care, exploratory laparotomy has become a valuable treatment option in cases that do not respond to medical treatment. Because of improved technical possibilities, an increasing number of horses with severe pathologies can be surgically treated. However, and even in spite of better postoperative care, the incidence of postoperative complications has not decreased over the years. Numerous complications of colic surgery have been described in the literature and there are great differences in their occurrence and severity. Complications with a high morbidity and low mortality, such as surgical site infections or thrombophlebitis, primarily increase treatment costs and prolong the hospitalization period. Other complications like postoperative ileus or endotoxemic shock are potentially fatal. Compared to intraoperative elective euthanasia, postoperative death or euthanasia is associated with a much higher financial, but also emotional toll for the owner. By decreasing the occurrence of postoperative complications, colic surgery will become increasingly acceptable and affordable to a larger proportion of horse owners. Survival rates will increase and horses will have a more comfortable and faster recovery. This research project focused on two of the most important complications of colic surgery: postoperative ileus and surgical site infections. First (Chapter 3), the incidence of postoperative ileus (POI) and risk factors associated with its development were studied and the effects of two prophylactic treatments evaluated. The next part of the research focused on the pathophysiology of POI, more specifically on the plasma serotonin changes occurring in colic horses. The study of surgical site infections (SSI) occurring after equine colic surgery, is described in the final part of this dissertation (Chapter 4). Possible risk factors for SSI were analyzed, including different skin closure techniques. In Chapter 3, first the current incidence of postoperative ileus was determined. A retrospective study was conducted on colic horses operated on between March 1, 2004 through December 31, 2006 at the Ghent University equine clinic. Since POI usually onsets at the first day postoperatively and mainly occurs in small intestinal (SI) cases, the study population was limited to SI colic horses that survived surgery for at least 24h. In this group of 126 horses at risk, a POI incidence of 33% was recorded. Risk factors for POI development were preoperative reflux (> 8 liters), preoperative tachycardia and a small intestinal resection. All three of them emphasize the importance of timely referral and treatment of horses with colic, in order to prevent endotoxemia, intestinal dilation and ischemia-reperfusion lesions as much as possible. In the POI group, only 34% of horses survived to discharge, compared to 85% of non-POI horses. Postoperative ileus increased the odds for non-survival 28-fold. These results confirm that for SI colic surgery, POI is still a frequently occurring and highly fatal complication (Chapter 3.1). The effectiveness of intravenous lidocaine and intramuscular metoclopramide, both used as prophylactic drugs for POI, was evaluated in the same retrospective study (Chapter 3.1). Although metoclopramide did not exert a significant protective effect, postoperative treatment with intravenous lidocaine (a 1.3 mg/kg bolus followed by a continuous rate infusion of 0.05 mg/kg/h) led to a clear and significant decrease in POI occurrence. The odds ratio (OR) for POI in horses receiving lidocaine prophylaxis was 0.31 (95% confidence interval [CI] 0.12-0.78; P = 0.013). Lidocaine administration also exerted significant positive effects on short term survival (OR 3.33; 95% CI 1.02-11.1; P = 0.047) apart from the effects on POI. Anti-inflammatory and anti-endotoxemic properties of IV lidocaine possibly account for this positive effect on survival. The next part of the research focused on plasma serotonin changes in surgical colic horses. Serotonin is an important intestinal neurotransmitter and a major regulator of the intestinal motility. Major human prokinetic drugs, some of which are also used in horses, act on serotonin receptors. Furthermore, serotonin is involved in platelet activation and is also released by activated platelets. All of this makes serotonin an interesting molecule in POI research. A serotonin release from ischemic bowel has been demonstrated in different species and platelet activation is commonly observed in severe colic cases. Therefore we investigated changes in free plasma serotonin concentrations in surgical colic horses. This was done by determining the serotonin concentrations in platelet poor plasma (PPP) at several perioperative time points. First, a reliable method for the quantification of serotonin in equine PPP had to be developed. In Chapter 3.2, the development and validation of a suitable LC-MS/MS method is described. For this method deuterated serotonin was used as an internal standard. The sample preparation was based upon a liquid extraction into ethyl acetate and chromatographic separation was performed with an acetic acid–acetonitrile mobile phase gradient elution. The method’s linearity was demonstrated for serotonin concentrations ranging from 3 to 100 ng/ml. The limit of quantification was 3 ng/ml and the limit of detection 0.10 ng/ml. The results of a commercial human serotonin ELISA kit, more suitable for use in a clinical situation, were compared with the LC-MS/MS results. Although the ELISA serotonin recovery rates were acceptable and the correlation between the two tests was excellent, Passing–Bablok regression and Bland–Altman plotting showed a poor agreement between the methods, with an increasing difference within the higher range of measurements. This emphasizes the need for in house determination of method specific reference values. Subsequently, both quantification methods were used to study the evolution of PPP serotonin concentrations in surgical colic horses during the perioperative period (Chapter 3.3). The concentrations found in surgical colic horses preoperatively, immediately postoperatively and the next morning were compared to those in morning samples taken in healthy horses. During sample handling, measures were taken against inadvertent platelet activation and additional tests were performed to evaluate possible effects of platelet activation on serotonin concentration. Significantly lower PPP serotonin concentrations were found in all three samples of the colic horses, compared to controls. However, there were no associations with POI development or with non-survival. Free plasma serotonin concentrations are influenced by multiple mechanisms, but basically they mirror the ratio of serotonin release by enterochromaffin cells and –to a lesser extent– platelets, and plasma clearance, mainly by platelet uptake. Since findings on PPP serotonin changes are inconsistent and there is a lack of association of PPP serotonin concentrations with POI or non-survival, it can be concluded that PPP serotonin does not seem a suitable marker in POI research. It might be more useful to focus on local intestinal serotonin changes in the future. The next chapter of this dissertation (Chapter 4) describes a retrospective study of surgical site infections in the horse. A total of 356 horses that underwent colic surgery between March 1, 2004 and December 31, 2007 and survived at least 2 weeks postoperatively were included in the study. An SSI incidence of 15% was observed, with positive bacterial cultures in the majority of cases (33 out of 40). Multivariable regression analysis showed that surgical site closure by an inexperienced surgeon was a risk factor (OR 2.20 [95% CI 1.16-4.18]; P = 0.016) for SSI development. Lavage of the linea alba with sterile saline solution after closure was a protective factor (OR 0.38 [95% CI 0.20-0.74]; P = 0.004). The use of staples for skin closure was an important risk factor (OR 3.85 [95% CI 2.04-7.29]; P < 0.001) compared to monofilament sutures. Despite the fact that skin staples are easy to apply and their use may slightly decrease the total anesthesia duration, their association with SSI development makes them less suitable for use in equine celiotomies. The final chapter (Chapter 5) contains the general discussion and the main conclusions. For the treatment and prevention of POI a multimodal approach is advised. Our results emphasize, once again, the importance of early referral. The use of IV lidocaine can be advocated as a prophylactic treatment for POI. Future research should be conducted to examine its curative potential once POI has developed. Plasma serotonin did not turn out to be a suitable marker or predictor for POI. Further pathophysiologic POI research could rather focus on mucosal serotonin changes. However, the LC-MS/MS test we developed may be used for other serotonin research purposes. If LC-MS/MS is not available, ELISA is a useful alternative but rather for clinical purposes than for exact quantifications. Our work on surgical site infections revealed three factors associated with their development. Together with earlier identified risk factors and protective factors, these results could be applied in strategies for the prevention of SSI. In conclusion, the research conducted for this PhD study has led to increased knowledge on two of the most important complications after equine colic surgery. These recommendations can be implemented in evidence based protocols aimed at improving the results of colic surgery in the future.
Please use this url to cite or link to this publication:
author
promoter
UGent, UGent and UGent
organization
year
type
dissertation
publication status
published
subject
keyword
celiotomy, risk factor analysis, serotonin, equine colic, surgical site infection, complications, postoperative ileus, LC-MS/MS, ELISA
pages
217 pages
publisher
Ghent University. Faculty of Veterinary Medicine
place of publication
Merelbeke, Belgium
defense location
Merelbeke : Faculteit Diergeneeskunde (kliniekauditorium B)
defense date
2012-10-16 17:00
ISBN
9789058643117
language
English
UGent publication?
yes
classification
D1
additional info
dissertation consists of copyrighted material
copyright statement
I have transferred the copyright for this publication to the publisher
id
3158051
handle
http://hdl.handle.net/1854/LU-3158051
date created
2013-03-06 11:31:27
date last changed
2017-01-16 10:41:15
@phdthesis{3158051,
  abstract     = {Gastrointestinal colic is a very common problem in the horse. Due to advances in surgical techniques and perioperative care, exploratory laparotomy has become  a valuable treatment option in cases that do not respond to medical treatment. Because of improved technical possibilities, an increasing number of horses with severe pathologies can be surgically treated. However, and even in spite of better postoperative care, the incidence of postoperative complications has not decreased over the years. 
Numerous complications of colic surgery have been described in the literature and there are great differences in their occurrence and severity. Complications with a high morbidity and low mortality, such as surgical site infections or thrombophlebitis, primarily increase treatment costs and prolong the hospitalization period. Other complications like postoperative ileus or endotoxemic shock are potentially fatal. Compared to intraoperative elective euthanasia, postoperative death or euthanasia is associated with a much higher financial, but also emotional toll for the owner. 
By decreasing the occurrence of postoperative complications, colic surgery will become increasingly acceptable and affordable to a larger proportion of horse owners. Survival rates will increase and horses will have a more comfortable and faster recovery. This research project focused on two of the most important complications of colic surgery: postoperative ileus and surgical site infections. 
First (Chapter 3), the incidence of postoperative ileus (POI) and risk factors associated with its development were studied and the effects of two prophylactic treatments evaluated. The next part of the research focused on the pathophysiology of POI, more specifically on the plasma serotonin changes occurring in colic horses. The study of surgical site infections (SSI) occurring after equine colic surgery, is described in the final part of this dissertation (Chapter 4). Possible risk factors for SSI were analyzed, including different skin closure techniques.
In Chapter 3, first the current incidence of postoperative ileus was determined. A retrospective study was conducted on colic horses operated on between March 1, 2004 through December 31, 2006 at the Ghent University equine clinic. Since POI usually onsets at the first day postoperatively and mainly occurs in small intestinal (SI) cases, the study population was limited to SI colic horses that survived surgery for at least 24h. In this group of 126 horses at risk, a POI incidence of 33\% was recorded. Risk factors for POI development were preoperative reflux ({\textrangle} 8 liters), preoperative tachycardia and a small intestinal resection. All three of them emphasize the importance of timely referral and treatment of horses with colic, in order to prevent  endotoxemia, intestinal dilation and ischemia-reperfusion lesions as much as possible. In the POI group, only 34\% of horses survived to discharge, compared to 85\% of non-POI horses. Postoperative ileus increased the odds for non-survival 28-fold. These results confirm that for SI colic surgery, POI is still a frequently occurring and highly fatal complication (Chapter 3.1). 
The effectiveness of intravenous lidocaine and intramuscular metoclopramide, both used as prophylactic drugs for POI, was evaluated in the same retrospective study (Chapter 3.1). Although metoclopramide did not exert a significant protective effect, postoperative treatment with intravenous lidocaine (a 1.3 mg/kg bolus followed by a continuous rate infusion of 0.05 mg/kg/h) led to a clear and significant decrease in POI occurrence. The odds ratio (OR) for POI in horses receiving lidocaine prophylaxis was 0.31 (95\% confidence interval [CI] 0.12-0.78; P = 0.013). Lidocaine administration also exerted significant positive effects on short term survival (OR 3.33; 95\% CI 1.02-11.1; P = 0.047) apart from the effects on POI. Anti-inflammatory and anti-endotoxemic properties of IV lidocaine possibly account for this positive effect on survival.
The next part of the research focused on plasma serotonin changes in surgical colic horses. Serotonin is an important intestinal neurotransmitter and a major regulator of the intestinal motility. Major human prokinetic drugs, some of which are also used in horses, act on serotonin receptors. Furthermore, serotonin is involved in platelet activation and is also released by activated platelets. All of this makes serotonin an interesting molecule in POI research. A serotonin release from ischemic bowel has been demonstrated in different species and platelet activation is commonly observed in severe colic cases. Therefore we investigated changes in free plasma serotonin concentrations in surgical colic horses. This was done by determining the serotonin concentrations in platelet poor plasma (PPP) at several perioperative time points. 
First, a reliable method for the quantification of serotonin in equine PPP had to be developed. In Chapter 3.2, the development and validation of a suitable LC-MS/MS method is described. For this method deuterated serotonin was used as an internal standard. The sample preparation was based upon a liquid extraction into ethyl acetate and chromatographic separation was performed with an acetic acid--acetonitrile mobile phase gradient elution. The method{\textquoteright}s linearity was demonstrated for serotonin concentrations ranging from 3 to 100 ng/ml. The limit of quantification was 3 ng/ml and the limit of detection 0.10 ng/ml. 
The results of a commercial human serotonin ELISA kit, more suitable for use in a clinical situation, were compared with the LC-MS/MS results. Although the ELISA serotonin recovery rates were acceptable and the correlation between the two tests was excellent, Passing--Bablok regression and Bland--Altman plotting showed a poor agreement between the methods, with an increasing difference within the higher range of measurements. This emphasizes the need for in house determination of method specific reference values. 
Subsequently, both quantification methods were used to study the evolution of PPP serotonin concentrations in surgical colic horses during the perioperative period (Chapter 3.3). The concentrations found in surgical colic horses preoperatively, immediately postoperatively and the next morning were compared to those in morning samples taken in healthy horses. During sample handling, measures were taken against inadvertent platelet activation and additional tests were performed to evaluate possible effects of platelet activation on serotonin concentration. Significantly lower PPP serotonin concentrations were found in all three samples of the colic horses, compared to controls. However, there were no associations with POI development or with non-survival. Free plasma serotonin concentrations are influenced by multiple mechanisms, but basically they mirror the ratio of serotonin release by enterochromaffin cells and --to a lesser extent-- platelets, and plasma clearance, mainly by platelet uptake. Since findings on PPP serotonin changes are inconsistent and there is a lack of association of PPP serotonin concentrations with POI or non-survival, it can be concluded that PPP serotonin does not seem a suitable marker in POI research. It might be more useful to focus on local intestinal serotonin changes in the future.
The next chapter of this dissertation (Chapter 4) describes a retrospective study of surgical site infections in the horse. A total of 356 horses that underwent colic surgery between March 1, 2004 and December 31, 2007 and survived at least 2 weeks postoperatively were included in the study. An SSI incidence of 15\% was observed, with positive bacterial cultures in the majority of cases (33 out of 40). Multivariable regression analysis showed that surgical site closure by an inexperienced surgeon was a risk factor (OR 2.20 [95\% CI 1.16-4.18]; P = 0.016) for SSI development. Lavage of the linea alba with sterile saline solution after closure was a protective factor (OR 0.38 [95\% CI 0.20-0.74]; P = 0.004). The use of staples for skin closure was an important risk factor (OR 3.85 [95\% CI 2.04-7.29]; P {\textlangle} 0.001) compared to monofilament sutures. Despite the fact that skin staples are easy to apply and their use may slightly decrease the total anesthesia duration, their association with SSI development makes them less suitable for use in equine celiotomies.
The final chapter (Chapter 5) contains the general discussion and the main conclusions. For the treatment and prevention of POI a multimodal approach is advised. Our results emphasize, once again, the importance of early referral. The use of IV lidocaine can be advocated as a prophylactic treatment for POI. Future research should be conducted to examine its curative potential once POI has developed.
Plasma serotonin did not turn out to be a suitable marker or predictor for POI. Further pathophysiologic POI research could rather focus on mucosal serotonin changes. However, the LC-MS/MS test we developed may be used for other serotonin research purposes. If LC-MS/MS is not available, ELISA is a useful alternative but rather for clinical purposes than for exact quantifications.
Our work on surgical site infections revealed three factors associated with their development. Together with earlier identified risk factors and protective factors, these results could be applied in strategies for the prevention of SSI.
In conclusion, the research conducted for this PhD study has led to increased knowledge on two of the most important complications after equine colic surgery. These recommendations can be implemented in evidence based protocols aimed at improving the results of colic surgery in the future.},
  author       = {Torfs, Sara},
  isbn         = {9789058643117},
  keyword      = {celiotomy,risk factor analysis,serotonin,equine colic,surgical site infection,complications,postoperative ileus,LC-MS/MS,ELISA},
  language     = {eng},
  pages        = {217},
  publisher    = {Ghent University. Faculty of Veterinary Medicine},
  school       = {Ghent University},
  title        = {Complications and prognostic factors in equine surgical colic},
  year         = {2012},
}

Chicago
Torfs, Sara. 2012. “Complications and Prognostic Factors in Equine Surgical Colic”. Merelbeke, Belgium: Ghent University. Faculty of Veterinary Medicine.
APA
Torfs, S. (2012). Complications and prognostic factors in equine surgical colic. Ghent University. Faculty of Veterinary Medicine, Merelbeke, Belgium.
Vancouver
1.
Torfs S. Complications and prognostic factors in equine surgical colic. [Merelbeke, Belgium]: Ghent University. Faculty of Veterinary Medicine; 2012.
MLA
Torfs, Sara. “Complications and Prognostic Factors in Equine Surgical Colic.” 2012 : n. pag. Print.