A Fresh Look at the Process of Arriving at a Clinical Prognosis Part 2: Colic

Journal of Equine Veterinary Science 31 (2011) 370-378

Journal of Equine Veterinary Science journal homepage: www.j-evs.com

Clinical Technique

A Fresh Look at the Process of Arriving at a Clinical Prognosis Part 2: Colic James A. Orsini DVM, ACVS Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA

a b s t r a c t Keywords: Colic Equine Prognosis Homeostasis Survival

Generating an accurate prognosis in a horse with colic involves identifying and determining the severity of homeostatic derangements, particularly aberrations in cardiorespiratory, metabolic, and hemostatic functions. The basic questions to be answered are as follows: How sick is the horse?, How healthy was he to begin with?, and How well has he responded to treatment? Although laboratory data are very helpful in making such determinations, a thorough physical examination can suffice if necessary, particularly when repeated to obtain serial data. By reframing the serious colic case in terms of how the horse’s system is respondingdor failingdas a whole in its attempts to restore homeostasis, we are better equipped to act preemptively or promptly enough to avert a fatal result and to ensure minimal short- and long-term complications. Ó 2011 Elsevier Inc. All rights reserved.

1. Introduction In Part 1 of this series, we began exploring the concept of homeostasis and clinical assessment of homeostatic derangements as the foundation for predicting the outcome in any given case [1]. To recap, the ways and degree to which homeostasis has been disturbed is essentially what we are endeavoring to determine with our physical examination and diagnostic tests. Generally, the further a particular disorder is from the center of homeostatic balance, the more severe the clinical signs would be, the more immediate and intense our response needs to be, the longer it will take for the patient to recover, and the prognosis would be worse for complete recovery. The first article in this series focused on laminitis. Here, we continue with the topic as we examine the available data on colic. (For the purpose of this discussion, we will confine our exploration to gastrointestinal causes of colic.) Probably, better than any other disease we are called upon to treat in horses, colic highlights the importance of promptly identifying and correcting homeostatic derangements. The urgency of the typical “surgical” colic Corresponding author at: James A. Orsini, DVM, ACVS, Department of Clinical Studies, New Bolton Center, University of Pennsylvania, 382 West Street Road, Kennett Square, PA 19348. E-mail address: [email protected]. 0737-0806/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jevs.2011.05.018

brings into sharp focus the principle that the degree to which homeostasis is disturbed dictates the immediacy and intensity of our response, and also predicts the outcome. Colic in horses has long been an active area of clinical and laboratory research, and collectively we have amassed hundreds of studies over the years. Dukti and White recently published a thorough review of the literature on colic outcomes from the past three decades [2]. There are few surprises in that review, as the various studies confirm what most of us have learned through experience:
Most cases of colic are mild and resolve either on their own or with simple medical treatmentdin one large epidemiological study, about 80% of all colic cases fit this profile [3].
Relatively few cases of colic require more intensive medical care or surgerydin the aforementioned study, only about 20% of all colic cases comprised serious medical or surgical colics [3]; <10% of all colic cases require surgery [3,4].
The prognosis for serious medical and surgical colics is good with prompt and appropriate treatmentdalthough published survival rates across the board range from 35% to 100%, most are in the 60% to 90% range [2].

J.A. Orsini / Journal of Equine Veterinary Science 31 (2011) 370-378

The overall mortality rate for colic in the epidemiological study by Tinker et al was only 6.7% [3]. Even so, we tend to approach colic with a general air of concern because, as uncommon as it is, when colic goes bad, it can go really bad, really fast. Colic moves us to action because we never quite know in advance what we are getting into, whether it will be one of the many that will be fine or one of the critical few. Time is of the essence in horses with severe colic because at some point the outcome may be taken “out of our hands” and determined solely by the resources and resilience of the horse’s system. Study after study, and experience after experience, indicate that gut compromise sufficient to incite a systemic responsedrepresented by homeostatic derangementdcan quickly tip over into systemic failure, multiple organ dysfunction syndrome (MODS)dhomeostatic collapsedwhich profoundly worsens the prognosis. Thus, there are three basic components for determining the prognosis in a horse with an acute abdomen: 1. The type of disorderdthat is, the degree of compromise to the gut barrier, and therefore, whether and to what extent a systemic response is elicited. 2. The adequacy of corrective measuresdsurgical and/or medical. 3. The inherent wherewithal of the patientdthat is, the patient’s response to treatment, to restore order, and repair any gut damage. Looking at it another way, the questions to be answered are: What has gone wrong?; How badly has it gone wrong?; How badly is the system compromised as a result?; How much has human intervention been able to help?;- and How well has the patient responded to treatment? 2. Type of Disorder The specific type of gastrointestinal disorder is important in determining the prognosis because it pertains to the probability and severity of compromise to the intestinal barrier. This is important because the degree of compromise to the gut barrier predicts the intensity of the systemic response, which may vary from a mild and transient stress response if the gut barrier remains intact, to an eventual fatal systemic collapse if the gut barrier is fundamentally damaged. It is no simple exercise in semantics that we classify the gastrointestinal causes of colic, first and foremost, as strangulating or nonstrangulating lesions. This distinction illustrates the preeminence of blood supply to the bowel in determining disease severity and therefore our treatment response, and ultimately the outcome. Strangulating lesions generally have a lower survival rate than nonstrangulating lesions because they more profoundly compromise the gut barrier. Survival rates for the various types of nonstrangulating lesions are generally higher, but individually are related to the presence and severity of compromise to the gut barrier. Unlike strangulating obstructions, any compromise to the gut barrier with these lesions typically begins with an intraluminal event, such as an abnormal accumulation of gas, fluid, ingesta, sand, concretions, foreign objects,

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parasites, or microbial toxins, and whether the problem was precipitated by a motility disorder. Compromise to the gut barrier is not inevitable in these cases, but rather its presence and extent are a function of the severity and duration of the underlying condition. 2.1. Intestine Barrier An accumulation of research in humans and animals points to the gut as the prime mover of the systemic response in serious illness [5-36]; thus, a brief review of gastrointestinal physiology is warranted. A healthy gut barrier is essential for a healthy body. The gut barrier is a seemingly simple structure, but it comprises multiple cell types and performs many functions [5]. The three primary components are as follows:
Epitheliumdconsisting of enterocytes, goblet cells, enteroendocrine cells, Paneth cells, and specialized M cells, with tight junctions between cells forming a crucial element of the intact gut barrier.
Mucosal immune systemdincluding intraepithelial lymphocytes, Peyer’s patches, leukocytes in the lamina propria, and the mesenteric lymph nodes.
Commensal microfloradinvolving several hundred species of enteric bacteria and other microbes, which aid in digestion and in protection against more pathogenic microbes. The enteric nervous system can be added as a fourth component of the gut barrier because normal gut motility can be considered a functional element of maintaining a healthy gut barrier. Gut stasis on its own can quickly cause or exacerbate a systemic disorder [9,12,30,33]. Furthermore, sympathetic fibers innervate the gut mucosa and gut-associated lymphoid tissue where, among other functions, they have pro- and anti-inflammatory actions, depending on the prevailing conditions [20,23,35]. In addition, the parasympathetic vagus nerve inhibits inflammatory cytokine release in various experimental models of critical illness [25], and its stimulation has been shown to improve postoperative ileus in mice [16]. All of these components of the intestinal barrier are in intricate communication with one another in what one author described as “crosstalk.” This crosstalk or intercommunication is essential for the maintenance and function of a healthy gut barrier and for the various normal processes of the gutdbut it also seems to be what makes the gut the “motor” of critical illness [5]. In fact, owing to its structural complexity and functional intricacy, with potentially harmful luminal contents interfaced with local concentrations of lymphocytes and other immune system cells, the gut can become both “architect” and “prey” in the systemic inflammatory response that may ensue when the gut barrier is compromised. Far from “simple mucosa,” the gut barrier is both a receptive and defensive interface with the “outside world,” acting as a discriminating gatekeeper for all substances entering the body through the alimentary tract. It continuously sorts among “beneficial,” “benign,” and “harmful” because it must allow the absorption of beneficial substances such as water and nutrients, and repel or

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J.A. Orsini / Journal of Equine Veterinary Science 31 (2011) 370-378

Table 1 Organ systems most affected in SIRS and MODS System

Specific Homeostatic Derangements

Circulatory

Vascular dysregulation causes reductions in venous return, cardiac output, and blood pressure, and thus worsening of tissue perfusion; reduced myocardial contractility and compartmental fluid shifts further compromise cardiac output and tissue perfusion; reduced splanchnic perfusion can cause or worsen damage to the gut barrier, which incites or exacerbates SIRS Reduction in tissue oxygenation initially as a consequence of circulatory failure, and terminally as alveolar diffusion fails (the lung is a shock organ); metabolic acidosis develops and worsens as it exceeds respiratory countermeasures Initial hypercoagulable state, followed by consumptive coagulopathy; aka disseminated intravascular coagulation (DIC); the resulting microthrombosis worsens tissue perfusion Activated leukocytes can cause considerable local damage and incite further proinflammatory chemokine and cytokine release, helping to fuel ongoing SIRS; the systemic anti-inflammatory response syndrome of MODS compromises leukocyte potency, rendering the patient more vulnerable to infection Renal hypoperfusion as a consequence of circulatory failure initially causes prerenal azotemia, but acute renal failure develops with MODS Elevations in cortisol, norepinephrine, and other stress hormones result in insulin resistance and glucose dysregulation, as well as interfering with immune system regulation; other endocrine abnormalities are likely in horses, similar to those seen in humans and other animals (eg, thyroid, other adrenal hormones, pancreatic) Various biochemicals involved in SIRS can alter the patient’s mental status, causing lethargy, depression, and altered responsiveness, and in severe SIRS may interfere with central control of essential functions Hypoperfusion further compromises the gut barrier. The gut is now considered the “motor” of the systemic inflammatory response, being both casualty and architect in a potentially deadly cycle of gut barrier compromise and inflammatory response. In fact, the gut may be considered the primary “shock organ.”

Respiratory/ pulmonary Hemostatic Immune

Renal Endocrine

Central nervous system Digestive

SIRS, systemic inflammatory response syndrome; MODS, multiple organ dysfunction syndrome. For each organ system, the specific homeostatic derangements reflect a basic pattern of initial attempts to control the problem, which worsens local conditions, leading to collapse of local regulation. SIRS is this same pattern played out at the systemic level.

otherwise protect against harmful substances such as metabolic and microbial toxins and the enteric microbes themselves. As one of their primary functions, the host cells of the gut barrier maintain a symbiotic relationship with the resident microflora, which can be beneficial, benign, or harmful, depending on the existing conditions [5,17,30,32,37]. These various processes and the very integrity of the gut barrier itself require a constant supply of energy; thus, any decrease in blood supply to a part of the gut for any reason, for even a short time, can result in failure of the gut barrier at that location [7-14,24,28,29]. Various intraluminal events, if severe or prolonged, can also damage the gut barrier at that location. Depending on the extent of the damage, the consequences may be disastrous, as the potentially harmful contents of the intestinal lumen may enter the systemic circulation through the bloodstream, the regional lymphatics, or both. Potentially, pathogenic luminal contents include not only the well known endotoxin, or gram-negative bacterial cell wall lipopolysaccharide (LPS), but also various microbial exotoxins, organic acids, vasoactive amines, and other by-products of microbial activities in the gut, incompletely digested food, and the microbes themselves. In fact, bacterial translocation from gut lumen to mesenteric lymph nodes through the gut lymph is considered one of the primary triggers or amplifiers of the systemic inflammatory response [5,15,21,24,34]. After these normally prohibited luminal contents cross the compromised gut barrier, the gut-associated lymphoid tissue mounts a vigorous local inflammatory response which may be locally destructive and may spill over into a systemic inflammatory response, potentially causing significant collateral damage along the way, including further damage to the gut itself [5]. In this way, the gut can get caught up in an inadvertently self-destructive cycle, with potentially fatal results.

2.2. Systemic Response Systemic inflammatory response syndrome (SIRS) has been the focus of much research in human medicine [6-14,16-36] because it has a significant effect on both morbidity and mortality in the critically ill patient (Table 1). MODS and later multiple organ failure (MOF) is a potential consequence of SIRS, occurring if the patient’s inherent assets and the medical interventions are unable to restore or at least adequately improve homeostasis. Simply defined, SIRS is a local activation of the inflammatory cascade which then “gets away” from itself, using the analogy of a bolting horse or a brush fire that becomes a forest fire. However, although graphic, these analogies are a little too simple. With SIRS, there are concerted attempts to control the problem, in the form of regulatory countermeasures, including activation of anti-inflammatory mechanisms, and these defensive responses become part of the problem. After cell or tissue damage, the initial attempt to contain the damage locally can cause aggravation of local conditions, which ends up resulting in collapse of local regulation. The problem then “spills over” into a system-wide concern, where initial attempts to contain it can cause worsening conditions, particularly in the most vulnerable organs or tissues, and may ultimately result in collapse of the entire system [20]. In other words, SIRS is the spillingover of inflammation and its responsive regulatory countermeasures from one organ or tissue to all. It is inflammationeanti-inflammation on a systemic scale inadequately regulated and ultimately more destructive than protective or reparative. Initially, activation of neutrophils, lymphocytes, and other leukocytes is an appropriate response when the gut barrier has been breached and bacteria and toxic substances cross the gut mucosa. However, for some reason that is still not well understood, this process sometimes

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defies the normal regulatory checks-and-balances and trips a destructive cycle of system-wide inflammation, tissue damage, and more inflammation. It may simply be a mathematical probability, where the numbers of bacteria and toxic molecules crossing the gut barrier exceed the containment resources of the immune system, necessitating an all-out assault, with inevitable collateral damage. However, there may be more to it than that. For example, if the patient, or specifically its gut, is already in an inflammatory or proinflammatory state before the onset of illness, then SIRS may be more likely, proceed more rapidly, or be less responsive to treatment. Thus, the patient’s immune, nutritional, endocrine, and circulatory status may also play a role, along with genetic effects. Why some patients develop SIRS and others do not, and why some patients with SIRS survive and others do not remain a mystery. As one report states, “we still don’t know why people die when they’re critically ill” [5]. As the gut is now considered the epicenter for the systemic inflammatory response, it may ultimately come down to how responsive the “crosstalk” is among the components of the gut barrier, and whether relations between the host and its microbes at the onset of illness could best be described as mutually beneficial, passively symbiotic, or frankly hostile. A chronic, low-level “struggle” is more likely to flare up into a major divergence than in an environment, where the “groups” are on generally good terms. This aspect of host-microbe interaction and interdependencedor gut ecology and its homeostasis [37]dis too little studied to be able to draw firm conclusions and clinical implications at this time. Although, as discussed later, research on the enteral administration of particular microbial species and certain nutrients in patients with SIRS suggests that host-microbe relations and the gut environment play a vital role here.

2.3. Clinical Assessment SIRS and multiple organ dysfunction/failure have been studied in horses [38-44], but until recently, research was largely limited to the study of endotoxemia, with the methodology often involving intravenous infusion of purified LPS. Endotoxin certainly is a potent trigger for SIRS in any species, but bacterial translocation is an equally important trigger, and other luminal contents may also be involved in “tripping” or worsening SIRS and MODS [5]. There has been more research on practical prognostic indicators in horses with colic [45-77]. Indirectly, this research relates to the presence and severity of SIRS and the development of MODS in horses with severe colic, and it correlates the associated homeostatic derangements with reduced survival rates. Although specific conclusions and the resulting clinical recommendations vary somewhat among studies, there are two findings that are so consistent that they could be considered foundational: 1. Indices of cardiopulmonary, metabolic, and hemostatic dysfunctionsdthat is, indicators of systemic homeostatic derangementdare of primary prognostic value.

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2. The more severe a particular abnormality and the greater the number of individual abnormalitiesdthat is, the more severe the homeostatic derangementdthe more likely the horse will die. Specific physical and laboratory indices of prognostic value are summarized in Tables 2 and 3. Although numerous studies have attempted to provide us with a defined set of parameters [48,52,53,57,60-62,64,65,67, 70,76,77], in practical terms, it just comes down to the following: the further outside the normal range any one clinical or laboratory value is, and the greater the number of abnormal values, the poorer the prognosis. For the most part, the physical and laboratory indices customarily used in the assessment of the colic patient pertain to the type and degree of homeostatic derangement and the body’s attempts to correct it. Therefore, they all have some prognostic value. To expand on point 2 mentioned earlier in the text, a consistent finding among the various studies of colic outcome is that no single parameter is of sufficient prognostic value to stand alone. Combinations of physical and laboratory findings repeatedly outperformed single and even laboratory indices. In fact, the predictive models that performed the best, all included at least some physical indices, most often heart rate, color of the mucous membranes, and capillary refill timedthat is, physical indicators of cardiopulmonary function. Because the specific combinations of prognostic indicators differ among studies, it points neither to any specific problem in the individual studies nor to any weakness of individual indices, but rather to the dynamics of the process. Specific to this point, it lets the clinician know that there are multiple ways and many opportunities to arrive at the same conclusion. In other words, it is neither about a specific set of findings nor whether one test or group of tests is superior to another, but about determining how “sick” the individual horse is, using whatever means are available. As discussed in the previous article on laminitis, it is encouraging to know that one can arrive at an accurate prognosis based primarily or exclusively on physical examination findings when circumstances dictate. Of course, supporting diagnostic tests such as laboratory tests and ultrasound can be very helpful, but when they are unavailable, it is possible to proceed without this data, based on the clinical picture, that is, on one’s clinical assessment of how ill the equine patient is at the time of the examination. 3. Corrective Measures Without question, the prognosis in horses with serious medical or surgical colic hinges on prompt and appropriate medical intervention. The longer a clinical condition compromising the intestinal barrier is left untreated, the poorer the prognosis. Therefore, prompt identification and correction of the problem is essential for a good outcome. However, if research and clinical experience relating to SIRS has taught us anything, it is that vigilance is also important. Measurements aimed at preventing and, when they do occur, promptly recognizing and correcting the

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Table 2 Physical examination findings of prognostic value in horses with colic Index

Comments

Mentation, activity

Restlessness, anxiety, and behavioral indicators of abdominal pain increase with lesion severity; however, lethargy/ depression or stupor typically indicates severe systemic compromise and is particularly disturbing when it follows a period of severe pain Superficial abrasions or swellings are indicative of self trauma and usually indicate a severe and protracted problem Prognosis typically worsens with increasing pain severity (mild, moderate, severe) and with response to analgesics (lasting response to one dose, temporary response requiring repeated dosing, or minimal response to any dose); however, absence of pain does not necessarily indicate resolution of the problem, being seen in cases with necrotic bowel or bowel rupture; worsening systemic compromise will be present in such cases HR increases with both pain severity and cardiopulmonary (CP) compromise; bradycardia may occur with large colon volvulus, probably as a vagal reflex; survival drops significantly at HR >80 beats/min Subjectively, pulse strength decreases with CP compromise; indirect measurement of arterial BP, while a useful prognostic indicator, may not add much in clinical practice; hypotension (coccygeal mean arterial BP <80 mm Hg) is correlated with nonsurvival RR is not a particularly strong prognostic indicator, as it is affected by pain as well as by CP compromise, but it increases with lesion severity; marked changes in RR and/or respiratory character are seen with systemic collapse While fever is an uncommon and worrisome sign in a horse with colic, hypothermia is even more concerning, as it typically indicates cardiovascular collapse Gum color is a consistently reliable indicator of outcome, as it indicates peripheral perfusion and thus changes with the severity of systemic compromise; abnormalities range from pale (indicative of peripheral vasoconstriction unless anemia is present) to strong pink/brick red, bluish-purple, and finally grey as CP function progressively fails CRT becomes delayed (3 seconds) as CP function worsens; CRT is a good prognostic indicator, although its measurement is somewhat imprecise, so it must be combined with other indices of CP function With progressive CP compromise and compartmental fluid shifts, MM moistness may change from moist to tacky to dry Skin turgor is an imprecise indicator of hydration status, particularly in foals and older horses; palpably cool or cold extremities inappropriate for the ambient conditions is often found with circulatory collapse; a “cold sweat” is a poor prognostic sign Enophthalmos is a poor prognostic sign, indicating circulatory collapse The presence of auscultable gut sounds generally is a positive sign; complete absence of gut sounds, while not pathognomonic for a surgical lesion, is not a good sign Visible bloating or distention of the abdomen is not always easy to appreciate in the adult horse, but when present suggests considerable colonic distention Significant findings include distended bowel, displacement with entrapment (eg, nephrosplenic entrapment), abnormal masses, and a gritty or rough feel to the serosal surfaces (indicative of peritonitis or bowel rupture) Reflux of fluid from the stomach, either spontaneous or elicited via NG intubation, suggests a surgical lesion (eg, complete intestinal obstruction) or one requiring intensive medical intervention (eg, ileus, proximal enteritis); volumes of >5 L are associated with a poorer outcome, although recurrence of large volumes perhaps is a more telling sign

Signs of trauma Pain

Heart rate Pulse strength, jugular fill, blood pressure Respiratory rate Rectal temperature Mucous membrane color

Capillary refill time MM moistness Skin turgor, temperature, sweating Eyes Gut sounds Abdominal contour Rectal exam findings Nasogastric reflux

HR, heart rate; BP, blood pressure; RR, repiratory rate; MM, mucos membrane; CRT, capillary refill time; NG, nasogastric.

cardiopulmonary, metabolic, and hemostatic disorders characteristic of SIRS also are essential for a good outcome. In fact, failure to do so may very well result in death even though one may claim that surgery was a success. These measurements include frequent reassessment of the patient, maintenance of good hydration, tissue perfusion, and electrolyte and acid-base balance, with intravenous fluid therapy as the mainstay of the medical treatment, and anti-inflammatory, anticoagulant, and vasopressor therapy when indicated, although these latter measurements have not been critically evaluated in research studies. Interestingly, in human medicine, current research emphasis is on restoring a normal gut environment and microflora in patients with SIRS, rather than focusing just on the downstream effects of the systemic inflammatory response. In short, the intestinal environment and its resident microbial population are significantly altered in patients with SIRS, and the clinical outcome can be improved with therapy aimed at restoring the normal gut environment and microflora. In humans, severe SIRS causes an absolute decrease in fecal levels of short-chain fatty acids such as acetate, propionate, and butyrate, a relative increase in succinate and lactate, and an overall increase in pH compared with healthy subjects. In addition, there is a decrease in obligate

anaerobes such as Bacteroides, Bifidobacterium, and Lactobacillus species, and an increase in pathogenic species such as Staphylococcus, Enterococcus, and Pseudomonas species in the feces of patients with SIRS [22,30-32]. The fact that these changes in gut environment and microflora are detrimental is illustrated by companion studies which showed positive effects of enteral treatment with synbiotics (selected “beneficial” bacterial species), with or without immunonutrition. For example, in one study of human patients with severe SIRS, enteral treatment with a combination of Bifidobacterium breve, Lactobacillus casei, and galacto-oligosaccharides corrected the deteriorated gut environment and microflora and reduced the incidence of infectious complications, such as enteritis, pneumonia, and bacteremia [27]. In other studies, the addition of “immunonutrients,” which typically include glutamine or arginine, omega-3 fatty acids, and various nucleotidesdand when combined with synbiotics has been called “ecoimmunonutrition”dprotected gut barrier function [19] and reduced the severity and duration of SIRS and the incidence of MOF [14,24,36]. We have yet to perform such studies in horses with SIRS, or even to determine the best treatment protocols in these patients. At present, what seems clear from empirical evidence is that tissue perfusion, and specifically gut perfusion, is of prime concern. Correction of the surgical

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Table 3 Laboratory abnormalities of prognostic value in horses with colic Index Blood Hematocrit or packed cell volume White cell count and differential Platelet count Fibrinogen

Total protein

BUN, creatinine Glucose

Lactate, anion gap Chloride and other electrolytes Calcium Coagulation panel

Special tests

Peritoneal fluid Gross appearance Total protein Cellularity

Lac Alkaline phosphatase

Comments Hemoconcentration occurs as a consequence of both pain/stress (ie, splenic injection/contraction of stored RBCs into circulation) and CP compromise (ie, compartmental fluid shifts); generally, the higher the PCV, the poorer the outcome; survival drops significantly above a PCV of 50%; hemoglobin concentration and erythrocyte count follow the same pattern but do not appear to add much more than PCV Initially, the WCC and differential either are normal or merely reflect a stress response (mature neutrophilia, lymphopenia, eosinopenia), unless the colic is complicated by an infectious agent; with SIRS, leucopenia typically develops; a degenerative left shift is a poor prognostic sign Initially, the platelet count usually is normal or, with hemoconcentration, slightly elevated; with severe or protracted SIRS, the platelet count may drop, particularly if DIC develops; a platelet count of <100,000/mL is a poor prognostic sign Initially, the fibrinogen concentration usually is normal unless the colic is complicated by chronic infection (eg, intraabdominal abscess); the fibrinogen may rise moderately during hospitalization as part of the acute-phase inflammatory response, but it does not appear to have major prognostic value Unless the colic is accompanied by albumin loss or end-stage liver disease, the TP typically rises with the PCV as a function of hemoconcentration; it does not, however, appear to be significantly affected by pain/stress, so can be useful in interpreting elevations in PCV Prerenal azotemia often develops with CP compromise, as renal blood flow is reduced; acute renal failure is a sign of MODS; the greater the azotemia and the poorer the response to fluid therapy, the poorer the prognosis Hyperglycemia is common in horses with serious medical or surgical colic and is correlated with outcome; hypoglycemia is uncommon except in neonates, and often indicates a poor outcome, as it is associated with strangulating lesions; blood glucose values >200 mg/dL or <60 mg/dL carry a poor prognosis; a return to normoglycemia during hospitalization is a good sign, but persistent hyperglycemia or the development of hypoglycemia usually signals a poor outcome Lac and AG increase with decreasing tissue perfusion; the greater the lactic acidosis, the poorer the outcome; Lac and AG consistently are strong prognostic indicators; survival drops significantly when LAC is >75 mg/dL or >8 mmol/L and AG is >20 mEq/L Chloride concentration on its own is not a strong prognostic indicator, but a substantial drop in Cl is a poor prognostic sign; changes in other electrolyte concentrations may be found in horses with colic but, with the exception of calcium, they appear to have limited prognostic value Hypocalcemia is common in horses with severe colic, and it increases the likelihood of ileus; correction of hypocalcemia increases the probability of survival, and lack of response to Caþþ supplementation is a poor prognostic sign Abnormalities of coagulation are a hallmark of SIRS and MODS; there is an initial hypercoagulable state, followed by a consumptive coagulopathy if SIRS is severe, improperly treated, or unresponsive; the more individual coagulation abnormalities a patient has, the worse the prognosis; those of greatest prognostic value are reduced plasma AT III, increased clotting time and PT, and increased FDP; survival drops significantly when AT III is <60% of normal A D-dimer concentration of >1.5 mg/dL has good prognostic value. Various measures of specific inflammatory cytokines and chemokines, and even blood endotoxin concentration, have prognostic value, but their utility is limited by availability and expense, and they appear not to add much that may not be obtained from a thorough physical examination and routine laboratory testing The gross appearance of the peritoneal fluid can have prognostic significance if it is discolored red (severe gut compromise with red cell leakage), turbid (increased cell and/or protein content), or flocculent (septic peritonitis or bowel rupture, in which case it may also be discolored brown or green) Peritoneal fluid TP is correlated with the severity of gut compromise and thus with outcome; survival drops significantly when the peritoneal fluid TP is >3.5 g/dL Peritoneal fluid RBC and total nucleated cell counts are a reflection of gut compromise; both increase with the severity and duration particularly of strangulating lesions; survival drops significantly when the peritoneal fluid WCC is >10,000/mL; the presence of bacteria or fecal material is a poor sign As with blood/plasma Lac, peritoneal fluid Lac increases with decreasing tissue perfusion; peritoneal fluid Lac may be a more sensitive indicator of gut compromise than blood Lac, increasing earlier than blood Lac with strangulating lesions Peritoneal fluid AP is correlated with the severity of intestinal damage and thus with prognosis; values >60 IU/L indicate significant intestinal damage

PCV, packed cell volume; WCC, white cell count; TP, total protein; Lac, lactate; AG, anion gap; AP, alkaline phosphatase; RBC, red blood cell; CP, cardiopulmonary; SIRS, systemic inflammatory response syndrome; DIC, disseminated intravascular coagulation; MODS, multiple organ dysfunction syndrome; BUN, blood urea nitrogen; AT III, antithrombin III; FDP, fibrin degradation products; PT, prothrombin time. Anion gap (AG): the mathematical difference between the major anions (chloride and bicarbonate) and the major cations (sodium and potassium) in the blood; AG ¼ ([Naþ] þ [Kþ])  ([CI] þ ([HCO3]); some authors use just Naþ, Cl, and HCO3, as Kþ adds relatively little; the AG is an index of acid-base balance, and it rises with increasing metabolic acidosis.

lesion and decompression of the distended gut in medical colics, and provision of supportive fluid therapy go a long way toward restoring and maintaining adequate tissue perfusion to preserve the residual gut barrier and begin repair of the damaged portion. Additionally, ischemiareperfusion injury in this light may be viewed as the sudden decompartmentalization of a localized inflammatory response to ischemic cell and tissue damage. Anticipating reperfusion injury helps to prevent some of its regional and systemic effects.

What the patient requires from theredand to what extent the patient is able to respond to the medical and surgical interventionsddepends on the individual horse. 4. Patient Resources By now, it should be clear that the patient factor which has the greatest influence on outcome, in serious medical or surgical colics, is the presence and severity of SIRS. However, it is not simply a matter of “SIRS ¼ poor

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outcome.” Most patients with SIRS survive if treated promptly and appropriately for their various homeostatic derangements and the underlying condition. However, some die of MOF, despite aggressive medical treatment. One of the most intriguing aspects of MODS, a consequence of severe or unresponsive SIRS, is that it comprises a compensatory anti-inflammatory response syndrome [20,29]. However, this response is either “too little, too late” or it also is so poorly regulated that it provides no benefit. It seems neither to adequately control the runaway inflammation nor improve the consequent organ dysfunction. One possible reason is that it harms leukocyte function, rendering the patient even more vulnerable to infection [20]. Another reason is because blood flow and various other processes essential to cell viability and proper function rely on the balance of pro- and anti-inflammatory chemokines, cytokines, and other messenger molecules, and on the tight regulation of other counterbalancing processes such as apoptosis and mitosis. In summary, homeostasis has been almost irrevocably lost in these patients. There appears to be a “tipping point” at which the system completely collapses and is unable to restore order and normal functions even with intensive medical help. Although there are some measurable indices that warn of this impending fate (depicted in Tables 2 and 3), both if and when a patient arrives at this “point of no return” seems to be a highly individual thing, as does response to treatment. Again, most horses survive with the medical interventions provided to address SIRS and MODS, but some die regardless. The reason why one patient survives and another dies fundamentally seems to be a function of a robust and resilient system before the onset of disease. Thus, it is not just a matter of “how sick is the patient now?” but “how healthy was the patient to begin with?” That question may still be unanswerable from the available evidence, but every experienced clinician is able to answer it for an individual horse with little hesitation. Health is not merely the absence of clinical signs of disease, but also an index of the robust and resilience of the body. Health is one of those indefinable yet unmistakable qualities of a body for which we develop good judgment with experience. The healthier the horse before the onset of colic, the better the outcome. All else being equal, the difference between survivors and nonsurvivors seems to be that the survivors typically were healthier at the start. Of course, prompt and appropriate treatment is essential for a good outcome, but the ability of the horse’s system to respond to treatment appears to be the deciding factor. In other words, even when prompt and appropriate treatment is provided, the outcome is determined by the individual’s inherent resources for preventing and, when needed, correcting homeostatic derangement. By the time the horse is presented for colic, our ability to influence this element of the equation is essentially zero; and in this regard, our ability to accurately predict the outcome is limited to assessing how the horse responds to treatment. The better the response, the better the prognosis. 4.1. Age and Breed Abnormalities of cardiopulmonary, metabolic, and hemostatic functions are unarguably the most important

prognostic indicators in horses with colic. However, factors of lesser importance overall may assume greater significance, or perhaps may simply complicate the picture, in individual patients or circumstances. Age and breed are just two such factors. Generally, survival rates in young foals and geriatric horses [78-82] tend to be lower than in all other age groups. This age effect may, in part, be because the very young and the very old are systemically and immunologically more vulnerable. Equally substantial factors are the types of lesions to which these particular age groups are prone and the financial constraints that the owners often place on these cases. For example, one study of surgical colic in horses examined old age (20 years of age) as a primary prognostic factor and found two main reasons for this age effect: strangulating obstructions (specifically, strangulating lipomas) were more prevalent in older horses than in younger adults, and more older horses are euthanized during surgery as much for financial reasons as for the medical reasons [82]. The short-term survival rate (i.e., survival to hospital discharge) in the geriatric horses was only 50%, whereas it was 72% for the younger adult horses. The long-term survival rates (survival for >1 year after surgery) were less divergent, being 70% for the geriatric horses and 84% for the younger adults. Other studies have found no significant effect of age on short- or long-term survival rates [70,83,84]. The survival rate has been reported to be lower for Thoroughbreds and draft breeds than for other breeds [81,85]. Specifically with the draft breeds, survival and recovery from anesthesia may be as much a factor as the presenting complaint and surgery [85]. In one Spanish study, Andalusians were more prone to develop laminitis as a complication of colic surgery than were other breeds [86].

4.2. Complications No discussion of colic prognosis would be complete without at least a brief mention of complications because they contribute to the increased morbidity and mortality rates in serious medical and surgical colics. It is no stretch to reframe the common complications of severe gut compromise and abdominal surgery as a reflection of local/ regional damage caused by unregulated systemic inflammation and poor tissue perfusion. Laminitis, ileus, diarrhea, recurrent or persistent abdominal pain, incisional infection or dehiscence, and intra-abdominal adhesions in these patients may all be “laid at the door” of a dysregulated inflammatory response, and may also be dependent on the individual patient’s vulnerability. If research proves this true, then prevention and early treatment to limit both the severity and duration of SIRS should lower the incidence of these various complications. Subjectively, there has been a general reduction in postoperative complications over time, coincidently no doubt with the greater attention to perioperative medical support of the surgical colic patient. What the next few years bring is exciting to contemplate.

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5. Conclusions Finally, arriving at an accurate prognosis in a horse with colic involves identifying and determining the severity of homeostatic derangements, particularly aberrations in cardiopulmonary, metabolic, and hemostatic functions. The basic questions to be answered are: How sick is the patient?, What was the general health initially?, and What has been the response to treatment? Although laboratory data can be instrumental in guiding such determinations, a thorough physical examination can be enough, particularly when the time needed to obtain serial data may delay the decision to proceed with surgery, which may be definitive. SIRS and its consequencesdMODS and MOFdare recent additions to our lexicon, but these systemic states of homeostatic disorder have always been present in our examination rooms, surgical suites, and hospital wards. We know them well, just not by the names and perhaps not as discrete entities. By reframing the serious colic case in terms of how the horse’s system is respondingdor failingdas a whole in its attempts to restore homeostasis, we are better equipped to act preemptively or rapidly enough to avert a fatal outcome and to ensure minimal short- and long-term complications. Survival rates in “colicking” horses have been steadily improving ever since veterinary surgeons first started perfecting abdominal exploratory surgery in an attempt to correct the presenting problem. With better research and clinical focus on how the body maintains homeostasis and restores it in the face of overwhelming challenges, we will confidently turn colic into a condition that may still cause us “sweat and anxiety,” but far less often brings us to “tears.”

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