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A Computer-derived Protocol Using Recursive Partitioning to Aid in Estimating Prognosis of Horses with Abdominal Pain in Referral Hospitals P.J. Pascoe, N.G. Ducharme, G.R. Ducharme and J.H. Lumsden

ABSTRACT In order to determine which variables are useful and accurate in estimating prognosis in horses with abdominal pain, data were analyzed from 231 horses presented at a veterinary teaching hospital. Using multiple stepwise discriminant analysis in a recursive partition model, we obtained a decision protocol that identified survivors and nonsurvivors. The prevalence of survivors was 61% in this population. The sensitivity, specificity, and positive and negative predictive values of this model were 71, 83, 87 and 65%, respectively. This decision protocol was validated by Jackknife classification and also by evaluation with a referral population of 100 horses in which the prevalence of survivors was 83%. This led to sensitivity, specificity, and positive and negative predictive values of 83, 78, 94 and 50%, respectively. RESUME

Le but de cette etude etait de determiner les parametres utiles dans l'estimation du pronostique chez les chevaux en colique. Utilisant les donnees de 231 chevaux presentes a un hopital veterinaire, les probabilites de classification (survie et mort) furent determinees. Ce calcul a ete fait avec un algorythme de partition utilisant l'analyse discriminante. Le taux de survie dans notre population etait de

61%. Ce modele a predit le taux de survie avec une sensitivite, une specificite, et une valeur predictive positive et negative de 71, 83, 87 et 65%. On a valide le modele utilisant la methode de Jackknife et par une reevaluation dans une autre population de 100 chevaux ayant un taux de survie de 83%. Ceci donnait une sensitivite, une specificite, et une valeur predictive positive et negative de 83, 78, 94 et 50%.

INTRODUCTION The costs of treating a horse with colic, where surgical or intensive medical management are necessary, can be very high. The owner is usually concerned about the prognosis for the horse and would like to understand the risks involved in such expensive treatment. A number of studies have addressed this issue based on both objective and subjective measurements. Objective measurements such as lactate levels (1-3), anion gap (4,5), blood pressure (6), heart rate (7), hematocrit (7-12), glucose (13,14) and other less available parameters such as coagulation tests (15,16) and phospholipase A2 (17) have been used with varying predictive values. Subjective measurements such as capillary refill time, level of pain or degree of depression, color of mucous membranes and jugular filling rate (7,18) have also been assessed as prognostic indicators. It is generally accepted that

most of these parameters reflect the degree of circulatory disturbance that has been caused by the colic and that the poorer the circulation the poorer the prognosis (19). Since no one factor indicates the complex alterations occurring during circulatory shock several studies have used combinations of the parameters to give an estimate for the prognosis (7,18,20,21). The most accurate of these studies ( 18) utilized a combination of systolic blood pressure, blood lactate, blood urea and packed cell volume. By combining these four variables using a specific formula the authors were able to predict outcome in 93% of the horses where 77% of the animals survived (Table III). The objective of this study was to assess which of the variables obtained during examination of horses with abdominal pain are significant in examining prognosis. We also wished to design a decision tree that would help clinicians in referral centers to

determine an appropriate prognosis. MATERIALS AND METHODS DATA COLLECTION

Clinical Evaluation - A prospective study was designed that included all horses with signs of abdominal pain presented to the Ontario Veterinary College (OVC) from May 1, 1983 to April 1985. Each horse was evaluated following a standard protocol. The information recorded during the clinical examination included rectal

Department of Clinical Studies (Pascoe), Department of Pathology (Lumsden), Ontario Veterinary College, University of Guelph, Guelph, Ontario NIG 2W1, Department of Clinical Sciences, Cornell University, Ithaca, New York 14853 (NG Ducharme) and Department of Mathematics and Statistics, University of Montreal, Montreal, Quebec H3C 3J7 (GR Ducharme). Present address of Dr. P.J. Pascoe: Department of Surgery, School of Veterinary Medicine, University of California, Davis, California 95616. This work was supported by a grant from the Ontario Racing Commission. Submitted May 29, 1989.

Can J Vet Res 1990; 54: 373-378

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temperature, heart rate, respiratory rate, temperature of extremities, color of mucous membranes, capillary refill time, presence and severity of signs of abdominal pain, abdominal distension, peristalsis, and the results of nasogastric intubation and rectal examination. Clinicopathological parameters evaluated included hematocrit (Hct), total plasma protein concentration (TPP), and the appearance and total protein concentration of abdominal fluid collected preoperatively by paracentesis. The data were recorded by the attending clinician according to a pretrial classification (Table I). Clinicopathological Evaluation Abdominal fluid could be obtained from 95 horses and the following information was recorded: total nucleated cells, neutrophils, band neutrophils, lymphocytes, monocytes, macrophages, eosinophils, basophils, mesothelial cells, degenerated cells, platelets, mesothelial cell clumps in tip of smear, plant material, total protein concentration and specific gravity. Turbidity, color, and inflammation (subjectively classified as absent [0] to maximum severity [4]) were also recorded. If inflammation was present, the predominant cell type was recorded. The presence of neutrophil degeneration, sepsis, erythrophagia and cytophagia was recorded and classified subjectively as absent (0) to severe (4).

CLASSIFICATION OF SURVIVAL

The records of all patients were reevaluated at the completion of the trial and the animals were grouped retrospectively as survivors and nonsurvivors. A horse was classified as surviving if it was discharged from the hospital or if it survived the episode of colic but died later from unrelated causes. Horses that were euthanized were excluded from the study. STATISTICAL ANALYSIS

The variables obtained from clinical examination were evaluated by a stepwise discriminant analysis in order to identify the most discriminant variables. All computations were done using the program 7M of the BMDP statistical package (22). The prior probabilities of being in any group were taken to be 0.5. Missing data were handled by elimination of the case from the analysis. This led to identification of a select number of discriminant variables for a reduced number of cases. The analysis was repeated using only these discriminant variables for the original data set. This led to identification of the most discriminant variable whose discriminant function was used to determine the cutoff point for the first node of the decision tree (survivors, nonsurvivors). This procedure was repeated at

each node in a recursive partitioning (23,24). Each of these two subgroups was then analyzed again as described above and the most discriminant variables for each of these two subgroups identified. This resulted in subgroups of horses which were predicted to survive or die. When no further division could be made with the variables obtained from clinical examination, the variables obtained from the clinicopathological evaluation were studied to further identify survivors and nonsurvivors. The procedure was stopped when, at each node, no further statistically significant divisions could be obtained using any of the remaining variables. The decision tree was thus formed and the overall sensitivity, specificity, positive and negative predictive values calculated. Validation of the decision tree created was carried out by reviewing the first 100 available and complete records of horses admitted for colic evaluation at the New York State College of Veterinary Medicine (NYSCVM) between January 1, 1985 and December 31, 1986. Recording of the assessment of these horses at the NYSCVM contained an almost identical scoring of all the discriminant variables as was used at the OVC. The prevalence of survivors in the NYSCVM population was 82%. Sensitivity was determined by dividing

TABLE I. Classification of the clinical parameters evaluated Rectal temperature Pulse Temperature of extremities normal normal Peripheral pulse normal Mucous membrane pink Capillary refill time Pain alert no

Peristalsis Abdominal distension Nasogastric tube Fluid pH Rectal examination Feces (if present,

consistency) Abdomen

aLarge intestine bSmall intestine 374

Likely survivor > 38.30C < 80/min increased

bright pink

pale pink

pale cyanotic

intermittent mild pain hypo

intermittent

< 3 seconds

depressed

pain hyper

normal

none

slight

none

< IL

pH 80/ min cold absent brick red

injected > 3 seconds continuous severe pain absent severe

> IL pH >5 decrease other

absent

distended SIb, distended LI

dark cyanotic

the number of horses correctly determined by the computer-derived protocol to survive by the number of horses surviving. Specificity was determined by dividing the number of horses correctly determined not to survive by the number of horses not surviving. Positive predictive value was determined by dividing the number of correct decisions for survival by the sum of the number of correct and incorrect decisions for survival. The negative predictive value was calculated by dividing the number of correct decisions for nonsurvivors by the sum of the number of correct and incorrect decisions for nonsurgical treatment.

Horses with abdominal pain (n=23 1) Hematocrit < 47 (n= 144)

Hematocrit > 47

(n=87) 4 horses

11 horses lost*

lost*

Pulse > 82

(n=42)

Pulse < 82 (n=41)

Pulse > 71 (n=4 1)

Alive 51.3%

Alive 21.5%

Alive 85.8% (n=79)

(n=2 1)

(n=9)

Pulse < 71 (n=92)

2 horse s lost*

Mucous membranes (n=39)

RESULTS Of the 260 patient examinations available in this study, only 231 horses had the most discriminant variable recorded (hematocrit), and they formed the basis for this study. Based on the hematocrit the population was divided into survivors and nonsurvivors. Of the nonsurvival and the survival groups created, "pulse rate" was the most discriminant variable again creating survival and nonsurvival subgroups. In the nonsurvival subgroup, "color of the mucous membrane" was the most discriminant variable yielding survival and nonsurvival subgroups. In the last survivors subgroup, treatment required was the most discriminating variable. The algorithm thus created is shown in Fig. 1 for the original population and in Fig. 2 for the validation population with the accuracy of each division in percentages. The sensitivity, specificity, and positive predictive values, negative predictive values of this algorithm (after validation by Jackknife classification) are compared to that of the second population in Table II.

DISCUSSION The sophisticated analysis carried out in this study involved 17 routine clinical parameters including hemato-

crit, total protein and the color and protein content of the peritoneal fluid.

pale cyanotic or brick red injected or dark cyanotic / (n= 18) Alive 33%

normal pink or bright pink or pale pink

(n=2 1)

Treatment required (n=2 1)

(n=6) Surgery (n= 7)

Medical

(n= 14)

Alive 28.6%

Alive 92.8%

(n=2)

(n= 13)

Fig. 1. Computer-derived decision algorithm for the original 231 horses with abdominal pain presented at a referral centre (OVC). The outcome is given as the percent surviving after each branching. (*Horses deleted from further evaluation because the specific parameter was not present in the data).

It also included a detailed analysis of 23 variables from peritoneal fluid obtained from 95 of the horses. It is interesting that none of the variables from the peritoneal fluid proved to be discriminating with respect to prognosis. We speculate that a horse with 1 m of dead or dying bowel is likely to show a similar response in the peritoneal fluid as a horse with 12 m of dead or dying bowel. The prognosis for these two animals is likely to be different, and although both lesions are severe, the horse with more dead bowel will probably have a greater circulatory compromise earlier and, therefore the outcome may be predicted on this basis. The analysis of the peritoneal fluid on an individual case

may be useful in confirming a diagnosis and thereby establishing prognosis, but in this study, none of the parameters analysed was discriminating for a majority of cases. The outcome of this study in terms of sensitivity and specificiity is comparable to several others (Table

III). It would appear to be less accurate than the measurement of systolic pressure alone (6) or in combination with other variables (18). It was more accurate than either lactate levels or anion gap measurements with respect to predicting survival (positive predictive value) but the negative predictive value indicates that an animal which has been predicted to die might still live. All of

375

Horses with abdominal pain (n= 100)

Hematocrit > 47

Herrnato ocrit < 47

(n= 15)

(n:=85)

Pulse > 82 (n= 11)

Pulse < 82 (n=4)

(n=72)

Alive 94.4%

Alive 69.2% (n=9)

Alive 27.3% (n=3)

Pulse < 71

Pulse > 71 (n= 1 3)

(n=68)

Mucous membranes (n=4)

normal pink or bright pink or pale pink

pale cyanotic or brick red injected or dark cyanotic (n=2) 4 Alive 50%

(n=2)

/

Treatment required (n=2)

(n= 1)

Surgery (n=2)

Medical

(n=O)

Alive 50%

(n= 1) Fig. 2 Computer-derived decision algorithm for 100 horses with abdominal pain presented at a referral centre (NYSCVM) used as the validation population. The outcome is given as the percent surviving after each branching.

the other studies showed better negative predictive values (2,4,6,18,21). None of these other studies has been validated in another population, however, and therefore, their true sensitivity and specificity is likely to be lower when

The discriminant variables are, as seen in other studies, (7,18,21,25) consistent with the progression of shock. An elevated hematocrit is usually seen in the severely dehydrated animal as well as being caused by

applied to a new population.

sympathetic stimulation associated

TABLE II. Comparison of the sensitivity, specificity and positive and negative predictive values of the computer derived decision tree for the primary (214 cases from OVC) and validation (100 cases from NYSCVM) populations of horses with colic. This is for the prediction of survival Positive

predictive No. of cases 231

100

376

Survivors % 61 82

Sensitivity % 71 83

Specificity % 83 78

value 87 94

Negative predictive value 65

with shock or excitement. Since the hematocrit of the horse is so labile, it is important to obtain the blood sample with the animal in as calm a state as possible (26). Many horses with colic are in such distress that this objective is not attainable and so the clinician must interpret the value obtained with respect to the known behaviour of the horse. It is also possible that drugs will affect the hematocrit. In this study no attempt was made to analyse specific cases with respect to prior drug therapy but it is known that acepromazine and xylazine will tend to reduce the hematocrit in the horse (27,28). It is therefore necessary to take into account the previous drugs which the horse has received when looking at the measurement of hematocrit. No attempt was made to account for breed and it is well known that the normal hematological values vary between breeds (29). Heart rate is similarly a very labile parameter and so it should be taken when the horse is as calm as possible. In general higher heart rates are associated with pain and shock. In the early stages of colic the heart rate may be elevated, due to pain, and as the condition progesses and shock ensues the heart rate may be elevated still further. This makes it a discriminant variable because the heart rate has some direct correlation with the progression of the condition. As a comparison the intensity of the pain may progress from an intermittent mild pain through to a severe continuous pain but as shock ensues the horse can become depressed. Pain may therefore be seen to increase initially and then decrease later in the progression of the condition making it a less discriminating variable when oniy one point in time is assessed. Heart rate will be significantly affected by analgesics. Drugs such as flunixin give analgesia and reduce the response to endotoxin which will reduce the heart rate (30). Opiates are analgesics and reduction in heart rate has been seen with the use of drugs such as butorphanol (31). The alpha2 agonists, such as xylazine and detomidine are not only profound analgesics but also can produce a significant and long lasting bradycardia (32,33). It is important to look at the drugs which the horse has received and the time

TABLE III. Comparison of the sensitivity, specificity, and positive and negative predictive values from various studies predicting survival

Prognostic indicator(s) Systolic blood pressure Anion gap Blood lactate Systolic blood pressure Hematocrit Blood urea Blood lactate Capillary refill time Hematocrit Heart Rate Surgical case Capillary refill time Serum bicarbonate Serum chloride Respiratory rate Surgical case

Number of horses 33 85 85 42 73

Indication of nonsurvivors > 100 mm Hg < 20 mmol/L < 24.9 mmol/ L < 8.4 mmol/L survivor equation greater than nonsurvivor equation

Prevalence of survivors

94

Positive predictive value % 95 81 72 85 98

Negative predictive value % 67 76 100 78 80

Ref. (6) (4) (4) (2) (18)

71 77

Sensitivity % 83 81 100 93 93

Specificity N 89 76 49 58

% 73 56

257

probability of death equation greater than 0.5

61

82

82

75

88

(21)

138

probability of death equation greater

52

82

82

81

83

(21)

than 0.5

since the last administration to interpret the effect of such therapy on heart rate. As another indicator of shock the color of the mucous membranes is important. Cyanosis may indicate severe ventilatory compromise associated with excessive abdominal distension, but is more likely to be caused by poor circulation. Under these conditions the red cells take so long to pass through the tissues that more oxygen is extracted and the blue color of deoxygenated hemoglobin becomes more evident. A dark red/ injected mucous membrane is associated with sepsis or endotoxemia, and the more toxic the animal becomes, the worse the prognosis. The last factor on this decision tree was whether the therapy required involved surgery. Although at this point in the tree there are very few horses left, this dichotomy is not unexpected. In general, the decision to treat a colicky horse without surgery is made on the basis that the animal will survive using medical therapy without further investigation of the lesion. It is therefore expected that horses requiring surgery will have a higher mortality rate since the lesion may involve dead or dying bowel and inevitably there will be some lesions which cannot be corrected. In addition there is a risk of death or fatal injury during the anesthesia and recovery which would not be present in the horse managed with medical therapy alone (34). This

variable was also shown to be significant in determining prognosis in the study by Reeves et al (21). The decision tree presented is therefore very dependent on the quality of information which is applied in using it. The prevalence of mortality in the population to which the tree is applied is also important. Using the results from the validation population, and assuming that the sensitivity and specificity of the tree remained the same, the positive and negative predictive values would alter to 97 and 35% with a 90% survival and to 99 and 20% with a 95% survival. This would suggest that if the decision tree predicted survival the result would be believable but that if the horse was predicted to die the accuracy of this result is highly questionable. The above assumption with respect to the sensitivity and specificity remaining constant is predicated on the nature of the population to which the test is being applied. Although the nature of colic seen at a referral centre is different from that seen in practice it is likely that the sensitivity and specificity would not change greatly because the test population is still colicky horses and the parameters measured relate to the circulatory changes. The circulation shows a continuum of response according to the severity of the injury and so even in a population with a low mortality these discriminant variables are still important.

ACKNOWLEDGMENTS We would like to thank the large animal clinicians at the Ontario Veterinary College (Drs. M. Arighi, J.D. Baird, F.D. Horney, M.H. Hurtig, M.A Livesey, P. PhysickSheard, H. Staempfli and L Viel) and at the New York State College of Veterinary Medicine (Drs. S. Dill, S.L Fubini, R.P. Hackett and W.R. Rebuhn) who have performed and recorded the results of physical examination.

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