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Analysis of Sodium Carboxymethylcellulose Administration and
Related Factors Associated with Postoperative Colic and Survival
in
Horses with Small Intestinal Disease
CALLIE A. FOGLE, DVM, Diplomate ACVS, MATHEW P. GERARD, BVSc,
PhD, Diplomate ACVS, YVONNE A. ELCE, DVM,Diplomate ACVS, DIANNE
LITTLE, BVSc, PhD, Diplomate ACVS, ALISON J. MORTON, DVM, MSpVM,
Diplomate ACVS, MARIA T.
CORREA, MS, PhD, and ANTHONY T. BLIKSLAGER, DVM, PhD, Diplomate
ACVS
ObjectiveTo analyze the effect of the intraoperative use of
sodium carboxymethylcellulose
(CBMC) and related perioperative factors on postoperative colic
and survival in horses that had
abdominal surgery for colic.
Study DesignRetrospective study.
AnimalsHorses (n 203) that had surgery for small intestinal
disease; 33 horses had intraop-erative administration of CBMC.
MethodsInformation was obtained from medical records for 170
horses that had surgery for colic
before use of CBMC and 33 horses that had intraoperative CBMC.
KaplanMeier survival curves
were used to estimate median survival time and a Cox
proportional hazards model was used to
estimate the hazard ratio for the effect of CBMC and other
perioperative variables on survival.
ResultsSeventy-five percent of horses administered CBMC survived
to 180 days, whereas 75% ofuntreated horses survived 8 days (median
survival time 18 days). Horses not administered CBMC
were twice as likely to die compared with horses administered
CBMC. Horses that had postop-
erative ileus (POI) were 1.4 times more likely to die than
horses without ileus. Similarly, horses with
signs of colic after surgery were 1.3 times more likely to die
than horses without postoperative signs
of colic.
ConclusionsCBMC administration is seemingly protective against
death and prolongs survival
when used intraoperatively in horses with small intestine
disease, particularly horses with postop-
erative colic or POI. Both POI and colic increased risk of death
after surgery.
Clinical RelevanceIntraoperative administration of CBMC in
horses that have surgery for small
intestinal disease may improve survival, possibly by reducing
early adhesion formation.
r Copyright 2008 by The American College of Veterinary
Surgeons
INTRODUCTION
IN HORSES, surgery for small intestinal disordersis associated
with a higher rate of postoperative
complications and consequently lower survival compared
with large intestinal surgical disease.1,2 Postoperative
colic occurred in 28.1% of horses recovering from
colic surgery and was the most frequent postoperative
Presented at the 8th International Equine Colic Research
Symposium, August 5, 2005, Quebec City, Canada.
Address reprint requests to Callie A. Fogle, DVM, Diplomate
ACVS, Department of Clinical Sciences and Population Health
&
Pathobiology, North Carolina State University College of
Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606.
E-mail:
[email protected].
Submitted February 2007; Accepted October 2007
From the Department of Clinical Sciences and Population Health
and Pathobiology, North Carolina State University College of
Veterinary Medicine, Raleigh, NC; the Department of Clinical
Sciences and Population Health and Pathobiology, Ohio State
University
College of Veterinary Medicine, Columbus, OH; the Department of
Clinical Sciences and Population Health and Pathobiology, Duke
University School of Medicine, Durham, NC; and the Department of
Clinical Sciences and Population Health and Pathobiology,
University of Florida College of Veterinary Medicine,
Gainesville, FL.
r Copyright 2008 by The American College of Veterinary
Surgeons
0161-3499/08
doi:10.1111/j.1532-950X.2008.00420.x
558
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complication before discharge.3 The definitive cause of
postoperative colic can be difficult to identify in
surviving
horses. Adhesions, stricture or obstruction at the anas-
tomosis site, ileus, and peritonitis have been
implicated.1,2
Adhesions cause a clinical problem in 1522% of horses
recovering from small intestine surgery.4 Serosal
trauma,ischemia, distension, and resulting inflammation are
common with small intestine surgery and play crucial
roles in adhesion formation.3,5 Experimental use of
carboxymethylcellulose (CBMC) suggests that it may
decrease adhesion formation in horses;6,7 however, in a
retrospective study of clinical cases where intraoperative
CBMC was used, no significant differences were found
between the treated and control groups for postoperative
colic or long-term survival.8
Other factors associated with postoperative colic and
survival in horses include small intestine resection, onset
of postoperative ileus (POI), and previous
abdominalsurgery.3,911 Small intestine resection regardless of
the
length has been associated with an increased risk of post-
operative complications, including death.12,13 Mild to
moderate abdominal pain is commonly seen in horses
with POI, especially those that have had surgery for small
intestine disorders.14 In a recent multicenter prospective
study, POI was associated with an increased risk of other
postoperative complications, such as incisional drainage,
laminitis, and death.15 Presence of postoperative colic is
associated with an increased risk of death, especially in
the short-term postoperative period.1,3,911
Our objective was to assess the association of CBMC
and other perioperative factors with postoperative colicand
survival in horses that had small intestine surgery.
MATERIALS AND METHODS
Medical records (20032005) of horses that had colic sur-
gery were selected using the following selection criteria:
(1)
exploratory celiotomy for small intestine disease; (2)
intraop-
erative CBMC administration; (3) recovered from surgery;
and (4) documented presence or absence of postoperative
colic. Thirty-three horses met these criteria. For
comparison,
horses not administered CBMC (19942002) but otherwise
using the same criteria were selected; 170 horses were
iden-tified. A selection criterion of adhesion prevention
treatment
unavoidably created 2 groups separated by the year CBMC
became available.
Information retrieved for each horse was: age, sex, breed,
year of admission, previous abdominal surgery, lesion diag-
nosis, location and method of resection, CBMC administra-
tion, and postoperative complications. Postoperative
complications were defined for 3 time points: (1) short term
to include the time from surgical recovery to hospital
discharge; (2) 1 month postoperatively; and (3) 6 months
postoperatively. Long-term postoperative complications and
survival were obtained from owner telephone interviews for
the 1- and 6-month time points. For the 1- and 6-month time
points, some horses were lost to follow-up because of loss
of
contact information or change of ownership. Information for
some horses was not available for certain variables, such as
previous abdominal surgery. Incisional drainage was defined
as any discharge from the ventral median celiotomy
incision.Postoperative colic was defined as ! 1 signs of
abdominal
discomfort (pawing, kicking at the abdomen, rolling).
POI was defined as ! 2 L of net material obtained by
nasogastric intubation.13 CBMC has been used routinely
during small intestinal surgery after it became available at
our
hospital in 2003. In all horses, it was applied topically as a
1%
solution directly onto the small intestine and its
mesentery,
before and during handling of the bowel, in volumes ranging
from 500mL to 1 L. In some instances, it was deposited into
the peritoneal cavity (250500 mL) immediately before closing
the abdomen, but this information was not recorded for each
individual horse.
Statistical Analysis
Descriptive statistics were obtained for all variables of
interest. KaplanMeier survival curves were used to obtain
median survival times (defined as time point where 50% of
the
horses were still alive) for intraoperative variable and
postop-
erative complications taking into consideration use of
CBMC.16 A Cox proportional hazards model was used to
determine effect of CBMC use on survival while accounting
for the effect of other variables of interest.16 Two models
were
defined: one model considered CBMC and postoperative
colic, and a second model considered CBMC and POI because
70% of POI cases were also classified as colic cases. Data
were
sparse for other variables such as motility treatment,
previousabdominal surgery, and resection type and therefore could
not
be included in the models. Year of admission was not con-
sidered because the use of CBMC variable and the year of
admission variable represent the same value; i.e. horses
treated
with CBMC were admitted during 20032005, and horses not
administered CBMC were admitted during 19942002. Small
intestine resection was considered as a possible confounder
and its effect was tested for in the models. Models were run
using statistical software (EGRET for Windows, 1999 version
2.0.31, Cytel Software, Cambridge, MA).
RESULTS
Mean age of horses administered CBMC was 10.1
years (range, 128 years) and was similar to horses not
administered CBMC (mean, 10.1 years; range, 0.524
years). Distribution of breeds between groups was similar
(Table 1). Sex distribution of horses administered CBMC
was 11 (33%) mares and 22 (67%) geldings and stallions
whereas in untreated horses it was 69 (41%) mares and
101 (59%) geldings and stallions. Surgical lesions
in horses administered CBMC were: ileal impaction
(17 horses), strangulating lipomas (4), mesenteric
rent entrapments (2), strangulation by adhesions (1),
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infarction (1), unknown cause of strangulation (3), small
intestinal volvulus (2), gastrosplenic entrapment (2), and
ileal mass (1). In CBMC-untreated horses, surgical
disease were: ileal impaction (76), strangulating lipomas
(30), epiploic foramen entrapment (14), mesenteric rent
entrapment (13), mesenteric hematoma (7), inguinal
hernia (6), intussusception (6), small intestine mass (6),
adhesion-related strangulations (5), unknown cause of
strangulation (5), and small intestine volvulus (2).
Mean hospitalization was 10 days for both groups
(CBMC group range, 118 days; untreated range, 127
days). Eleven of 33 horses (33%) treated with CBMC and72 of 170
untreated horses (42%) developed short-term
postoperative colic. More horses in the CBMC-untreated
group required small intestine resection (Table 2); how-
ever, fewer horses in the untreated group had POI. The
total number of horses with postoperative colic was 84,
and the total number of horses with POI from both
groups was 101. Fifty-eight horses had both postopera-
tive colic and POI.
Using KaplanMeier analyses, median survival time
for horses not administered CBMC was $18 days
(Fig 1). Median survival time for horses administered
CBMC could not be estimated because 75% of horses
survived to the 180-day follow-up compared with 75%
survival at 8 days for CBMC-untreated horses. Estimated
median survival times for horses with and without
postoperative colic was 18 and 180 days, respectively
(Fig 2). Median survival times for horses with and with-
out POI was 21 and 175 days, respectively (Fig 3).Median
survival times for horses with and without small
intestine resection were similar (22 and 29 days, respec-
tively; data not shown). Median survival time for horses
with jejunojejunosotomy and jejunocecostomy were also
similar (30 and 21 days, respectively; data not shown).
In the Cox proportional hazards models, horses
administered CBMC were less likely to die compared
with untreated horses. The estimated hazard ratio was 0.6
for the model where postoperative colic was considered
and 0.5 for POI (Tables 3 and 4). Horses that had
postoperative colic were 1.3 times more likely to die than
horses that did not. Similarly, in the model consideringPOI,
horses that had POI were 1.4 times more likely
to die compared with horses that did not have POI
(Table 3). Resection of small intestine showed no
confounding effect on the parameters estimates and it
was removed from the models.
DISCUSSION
Intraoperative use of CBMC in horses with small
intestine disease decreased the risk of death, particularly
in horses that had postoperative colic or POI. Two
separate Cox proportional hazards models were necessaryto
consider survival in horses for CBMC and POI and for
CBMC and postoperative colic. POI and presence of
abdominal pain are intricately related. Fluid distension of
both the stomach and the small intestine is a likely cause
of
abdominal pain in horses with POI. Also, tension on the
mesentery likely contributes further to abdominal pain.
The overlap between these 2 postoperative complications
in our study is consistent with a previous study where
horses with POI were significantly more likely to have
postoperative colic.17 Several studies have demonstrated an
increased risk of POI in horses that had surgery for disease
of the small intestine.17,18
POI may predispose horses toadhesions as a result of generalized
peritonitis from severe
intestinal disease and inflammation of the neuromuscular
layers of the small intestine from surgical manipula-
tion.17,19 Adhesions are also a common cause of postop-
erative colic; in 1 study adhesions and colic were the most
frequent cause of death after small intestine resection and
anastomosis in horses.9 Adhesions can cause postoperative
colic by creating a physical or functional obstruction.9
Number of days after colic surgery required to develop
clinically consequential adhesions is unknown, but it likely
begins 34 days postoperatively when development of
Table1. Breed Distribution of Horses Having Surgery for Small
Intes-
tine Disease with and without Administration of
Carboxymethylcellulose
(CBMC)
Breed CBMC (%) Not Treated (%)
Quarter horse 13 (39) 43 (25)
Thoroughbred 1 (3) 32 (19)
Arabian 4 (12) 24 (14)
Tennessee Walking horse 4 (12) 13 (8)
Warmblood 3 (9) 8 (5)
Appaloosa 2 (6) 13 (8)
Paint 2 (6) 8 (5)
Pony 2 (6) 3 (2)
Paso fino 3 (2)
Draft 1 (3) 2 (1)
Mixed breed 1 (3) 16 (9)
Morgan 3 (2)
Miniature horse 1 (0)
Mustang 1 (0)
Table2. Frequency of Small Intestine Resection and
Postoperative
Complications in Horses Undergoing Surgery for Small
Intestine
Disease with and without the Use of Carboxymethylcellulose
(CBMC)
Intraoperatively
Postoperative Complication
CBMC
(%)
Not Treated
(%)
Total
(% of Total)
Small intestine resection 13 (39) 106 (62) 119 (59)
Short-term postoperative colic 11(33) 73 (43) 84 (41)
Postoperative ileus 24 (73) 77 (45) 101 (50)
560 SODIUM CARBOXYMETHYLCELLULOSE AND POSTOPERATIVE COLIC IN
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fibrinous adhesions may lead to obstruction between
adhered segments of bowel.2 Mean hospitalization for both
groups, with and without postoperative colic, was 10 days.
In experimental studies of adhesion formation, horses are
typical euthanatized or reoperated to examine adhesions 10
days postoperatively (range, 724 days).6,7,20 The period of
postoperative hospitalization would likely include early
adhesion formation for horses undergoing surgery for dis-
ease of the small intestine; and the first 180 days postop-
eratively would likely include the formation of clinically
consequential adhesions. Surgeons involved in this studywere
well aware of potential applications of CBMC, and
standard operating procedure for small intestine surgery
was to use the product before and during handling of the
intestine intraoperatively. The exact mechanism of CBMCs
antiadhesive properties is unknown, but topical application
is thought to mechanically separate inflamed serosal
surfaces to prevent adhesion formation.6 Other possible
mechanisms include decreasing surgical trauma to the in-
testine by lubrication or by a direct anti-inflammatory
effect.5 Use of CBMC before handling small intestine
versus intra-abdominal administration before closure may
affect the frequency of adhesion formation.21
POITwenty-one (70%) CBMC horses had POI compared
with 68 (44%) non-CBMC horses. Whereas it is possible
that horses with more severe small intestine lesions were
more likely to receive CBMC there is no clinical evidence
200.0
0.1
0.2
0.3
0.4
SurvivalProbability(%)
0.5
0.6
0.7
0.8
0.9
1.0
40 60 80 100
Time (days)
CBMC=0, CBMC=1,
120 140 160 1800
Fig 1. KaplanMeier plot of survival (n 203) of horses with and
without carboxymethylcellulose (CBMC) treatment.
20
0.1
0.0
0.2
0.3
0.4
SurvivalProb
ability(%)
0.5
0.6
0.7
0.8
0.9
1.0
40 60 80 100
Time (days)
POI=0, POI=1,
120 140 160 1800
Fig 2. KaplanMeier plot of survival of horses (n 203) with and
without postoperative ileus.
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that this occurred. It is possible that instillation of a
foreign
material into the peritoneal cavity could create a low-grade
peritonitis with secondary ileus; however, experimental
studies in horses using CBMC have shown no evidence of a
low-grade peritonitis secondary to its use.68
Small Intestine Resection
Resection of small intestine alone did not significantly
increase the risk of death postoperatively, a finding incontrast
to several reports.9,19 Possible reasons for this
observation are a relatively small number of horses that
had small intestine resection, differences in small
intestine
surgical populations or differences in follow-up times
between studies.
Temporal Effect
Use of an adhesion prevention agent was a selection
criterion for the treatment group and thus cases were
separated by year of admission. It is possible that
cases admitted earlier in the study had decreased
survival times compared with more recent cases because
of advances in surgery and postoperative care; however,
in a recent study survival was improved between
1992 and 1996, compared with more recent cases,
despite therapeutic advances.22 It is also possible that
the 20032005 cases included larger numbers of more
severe cases of small intestine disease, because of a
potential surgeon tendency to treat the more severe cases
with CBMC whereas 19942002 cases, when CBMC
was unavailable, were more homogeneous. There is
no evidence to support this, as very few surgical small
intestine cases were not administered CBMC once it
became available.
Surgical Experience
Surgical experience has been shown to have an
association with short-term outcome.12 Surgeon distri-
bution was consistent between CBMC-treated and
-untreated horses except for 1 surgeon, present in the
last 2 years, who performed surgery on only 1 CBMC
case. Surgical experience is therefore unlikely to have
preferentially influenced outcome between groups.
Jejunocecostomy
Jejunocecostomy did not significantly increase risk of
death, an outcome contrary to an earlier report.23 Many
20
0.1
0.0
0.2
0.3
0.4
SurvivalProbability(%)
0.5
0.6
0.7
0.8
0.9
1.0
40 60 80 100
Time (days)
120 140 160 1800
Postoperative colic = 1Postoperative colic = 0,
Fig 3. KaplanMeier plot of survival of horses (n 203) with and
without postoperative colic.
Table3. Results of Cox Proportional Hazards Model
Considering
Postoperative Ileus and Carboxymethylcellulose (CBMC)
Variable Coefficient
Standard
Error HR 95% CI P Value
CBMC 0.61 0.20 0.55 0.370.80 .002
Postoperative
ileus
0.33 0.14 1.39 1.041.85 .02
Table4. Results of Cox Proportional Hazard Analysis Model
Consid-
ering Postoperative Colic and Carboxymethylcellulose (CBMC)
Variable Coefficient
Standard
Error HR 95% CI P Value
CBMC 0.48 0.19 0.62 0.430.90 .01
Postoperative
colic
0.29 0.14 1.34 1.011.77 .04
562 SODIUM CARBOXYMETHYLCELLULOSE AND POSTOPERATIVE COLIC IN
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horses in our study did not have small intestine resection,
which may have influenced the statistical significance of
this particular factor because of low case numbers.
Longer follow-up time may also have revealed a signif-
icant risk of decreased survival for horses with jejunoce-
costomy. The lack of significance of jejunocecostomy as arisk
factor may also reflect population differences.
POI and colic were frequent complications after small
intestine surgery in our study. Intraoperative use of
CBMC may be beneficial particularly for horses consid-
ered at increased risk of POI or colic after surgery. Based
on our results, intraoperative use of CBMC is warranted
when extensive small intestine manipulation is anticipated
because of its potential ability to reduce adhesions.
ACKNOWLEDGMENTS
Study partially funded by a grant from the North CarolinaHorse
Council.
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