Topics in Compan An Med 29 (2014) 67–70
Topical Review
Cardiovascular and Systemic Effects of Gastric Dilatation and Volvulus in Dogs Claire R. Sharp, BVMS, MS, DACVECCn, Elizabeth A. Rozanski, DVM, DACVIM, DACVECC Keywords: acute kidney injury disseminated intravascular coagulation ischemic reperfusion injury multiple organ dysfunction system systemic inflammatory response syndrome Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA n
Address reprint requests to: Claire R. Sharp, BVMS, MS, DACVECC, Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA, USA. E-mail: [email protected] (C.R. Sharp)
Gastric dilatation and volvulus (GDV) is a common emergency condition in large and giant breed dogs that is associated with high morbidity and mortality. Dogs with GDV classically fulfill the criteria for the systemic inflammatory response syndrome (SIRS) and can go on to develop multiple organ dysfunction syndrome (MODS). Previously reported organ dysfunctions in dogs with GDV include cardiovascular, respiratory, gastrointestinal, coagulation and renal dysfunction. Cardiovascular manifestations of GDV include shock, cardiac arrhythmias and myocardial dysfunction. Respiratory dysfunction is also multifactorial, with contributory factors including decreased respiratory excursion due to gastric dilatation, decreased pulmonary perfusion and aspiration pneumonia. Gastrointestinal dysfunction includes gastric necrosis and post-operative gastrointestinal upset such as regurgitation, vomiting, and ileus. Coagulation dysfunction is another common feature of MODS in dogs with GDV. Disseminated intravascular coagulation can occur, putting them at risk of complications associated with thrombosis in the early hypercoagulable state and hemorrhage in the subsequent hypocoagulable state. Acute kidney injury, acid-base and electrolyte disturbances are also reported in dogs with GDV. Understanding the potential for systemic effects of GDV allows the clinician to monitor patients astutely and detect such complications early, facilitating early intervention to maximize the chance of successful management. & 2014 Elsevier Inc. All rights reserved.
Introduction Gastric dilatation volvulus (GDV), commonly referred to as bloat, is a common condition in large and giant breed dogs presenting for emergency care that is associated with high morbidity and the potential for mortality. Although the pathogenesis of GDV is incompletely understood, a lot is known about the potential cardiovascular and systemic side effects of the condition. GDV results in development of the systemic inflammatory response syndrome (SIRS) and potentially multiple organ dysfunction syndrome (MODS). Organ dysfunctions that have been documented as part of MODS in dogs with GDV include cardiovascular, respiratory, gastrointestinal (GI), coagulation, and renal dysfunction. Hepatic, central nervous system, and endocrine system dysfunction have not been specifically evaluated in dogs with GDV, although are considered other important organ systems involved in MODS.1 The multisystemic effects of GDV will be discussed here with a focus on pathophysiology. The final article in this special issue discusses management of the postoperative GDV patient, with a special focus on management of complications and organ dysfunctions.2
Pathophysiology The pathogenesis of GDV is complex and multifactorial, with apparent genetic and environmental influences. The first article in this special issue discusses the genetic predispositions to GDV in dogs,3 whereas the second article discusses the role of GI motility disturbances in the development of GDV.4 It is unknown whether dilatation or volvulus occurs first in dogs with GDV, but either is possible as dilatation in the absence of volvulus and volvulus in the absence of dilatation are both reported. Dogs with GDV classically fulfill criteria for SIRS, although this has not been formally evaluated to the knowledge of the authors.5,6 Although no consensus definition exists, in general, in veterinary studies, dogs are considered to have SIRS, if they have http://dx.doi.org/10.1053/j.tcam.2014.09.007 1527-3369/& 2014 Topics in Companion Animal Medicine. Published by Elsevier Inc.
an underlying disease that could predispose to SIRS in addition to having abnormalities of a least 2 of the following 4 abnormalities: body temperature, heart rate (HR), respiratory rate (RR), and white blood cell count or differential. There are many potential triggers for SIRS and subsequently MODS in dogs with GDV, including global tissue hypoperfusion and cellular ischemia, gastric ischemia and reperfusion, gastric necrosis, and GI translocation of bacteria and bacterial products. Ischemia reperfusion injury (IRI) have been discussed extensively in the context of GDV.5,7,8 Tissue injury and cell death leading to the release of damage-associated molecular patterns into circulation, in addition to the potential for translocation of microbial pathogen-associated molecular patterns (PAMPS), trigger the innate immune response, resulting in the production of proinflammatory cytokines, activation of the complement cascade, activation of coagulation, and associated downstream effects. Inflammation is also exacerbated by the reactive oxygen species produced as a consequence of IRI. In addition, general anesthesia required for surgical correction of GDV may be a “second hit” that exacerbates SIRS and contributes to MODS in these patients. The potentially deleterious components or effects of general anesthesia are thought to include administration of 100% oxygen (albeit for a relatively short period of time), positive pressure ventilation, vasodilation and hypotension, and the immunomodulatory effects of opioid analgesics.9 Dysregulation of the immune system and mitochondrial dysfunction are also thought to be key to the initiation of the MODS in people with sepsis and SIRS1; however, these pathologies have not yet been explored in dogs with GDV.
Cardiovascular Dysfunction Cardiovascular manifestations of GDV include shock, cardiac arrhythmias, and myocardial dysfunction. Cardiovascular compromise is thought to be the primary systemic side effect that contributes to early morbidity and mortality in dogs with GDV.
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The end result of cardiovascular dysfunction is decreased tissue oxygen delivery (DO2) and the clinical manifestations of shock. Decreased DO2 contributes to the development of MODS, with consequences on the cardiovascular, respiratory, renal, GI, and central nervous systems. Dogs with GDV likely have a combination of obstructive, distributive, hypovolemic, and cardiogenic shock. Obstructive Shock Marked gastric dilatation results in the compression of the lowpressure intra-abdominal veins, including the portal vein, splenic veins, and caudal vena cava. As a consequence, venous return to the heart, and subsequently stroke volume, is reduced. HR will increase to compensate for reduced stroke volume; however, usually this compensation is inadequate and cardiac output too is reduced. Distributive Shock Decreased venous return and increased venous pressure result in splanchnic pooling of blood. Compromise of splenic blood flow tends to result in splenic congestion and splenomegaly. Splanchnic vasodilation is likely also exacerbated by production of the potent endogenous vasodilator nitric oxide via inducible nitric oxide synthase, further exacerbating peripheral vasodilation and splanchnic pooling of blood. Hypovolemic Shock Absolute hypovolemia is likely a relatively small component of the shock syndrome in dogs with GDV, although they may well have a relative hypovolemia. In one study, 34% of dogs with GDV had microcardia on thoracic radiographs suggestive of hypovolemia, although obstructive and distributive shock could also account for this.10 Loss of intravascular volume can occur via abdominal hemorrhage, third spacing of fluids, and GI secretions. Concurrently gastric inflow obstruction prevents oral intake of water. Blood loss associated with GDV is generally relatively minor and typically occurs as a result of the rupture of small gastric vessels as gastric volvulus occurs. For this reason, a small volume hemoabdomen is often noted at the time of abdominal surgery. Splanchnic pooling of blood and portal hypertension can contribute to third spacing of fluid and interstitial edema particularly in the abdominal viscera. Cardiogenic Shock Cardiogenic shock can occur as a result of myocardial dysfunction and cardiac arrhythmias. Cardiac arrhythmias, predominantly ventricular arrhythmias, occur in approximately 40% of dogs with GDV, likely as a result of myocardial ischemia.11,12 Significant reductions in coronary blood flow have been documented in experimentally induced GDV in dogs, and histopathologic evidence of myocardial ischemia has been seen in both experimental and naturally occurring GDV.13 It is well known that ischemic myocardium is likely to establish ectopic foci of electrical activity. Dogs with GDV also commonly have elevated circulating concentrations of cardiac troponins, and concentrations of these biomarkers correlate with the severity of electrocardiogram abnormalities and patient outcome.14 Increased circulating concentrations of cardiostimulatory substances such as the catecholamines, and cardioinhibitory substances such as proinflammatory cytokines (e.g., tumor necrosis factor α), have also been implicated in the generation of arrhythmias.
Physical examination abnormalities in dogs presenting with GDV are generally manifestations of the circulatory and respiratory compromise they experience. Dogs often present in early decompensated shock, with tachycardia, weak pulses, and depressed mentation. Depending on the state of compensation mucus membranes may be pale or injected, and capillary refill time may be rapid or prolonged. Irregular cardiac rhythms and pulse deficits may be present. In one study, 18 of 20 dogs (90%) had tachycardia (HR Z 120), and all dogs had abnormal perfusion parameters (mucus membranes, capillary refill time, and pulses).15 Tachypnea, dyspnea, or both may be associated with discomfort and respiratory compromise as documented later. Hyperlactatemia is a common finding in dogs with GDV. Its origin is likely multifactorial, stemming from both global and local (gastric) hypoperfusion. Although multiple studies report the use of lactate as a prognostic biomarker in dogs with GDV,16-19 the true prevalence of hyperlactatemia at presentation is not always reported. One recent study documented that 58.5% of dogs (38/66) with GDV were hyperlactatemic at presentation,20 whereas another reported that 30% of dogs (30/101) had an admitting lactate level 4 6 mmol/L.10
Respiratory Dysfunction Respiratory compromise may occur in dogs with GDV as a result of gastric dilatation adversely affecting normal respiratory excursion, reduced pulmonary perfusion, and aspiration pneumonia. Gastric dilatation and increased intra-abdominal pressure will decrease the total thoracic volume and prevent the normal caudal excursion of the diaphragm to initiate inspiration, resulting in hypoventilation and ventilation-perfusion mismatching. In severe cases, lung lobe collapse can also occur. Increased RR and effort ensue so as to compensate, although these efforts may become inadequate and hypercapnea and hypoxemia can occur. Pulmonary blood flow may also be decreased in dogs with GDV due to decreased cardiac output, further contributing to ventilationperfusion mismatch. Dogs with GDV are at risk of developing both preoperative and postoperative aspiration pneumonia. In addition, multiple studies identified pneumonia in dogs with GDV as a poor prognostic indicator.11,12 As dogs with GDV often fulfill SIRS criteria and have tachypnea and dyspnea on presentation, the presence of pneumonia can be difficult to discern based on clinical signs alone. As such, preoperative thoracic radiographs are recommended to identify evidence of aspiration pneumonia and guide antimicrobial therapy.10 Of a population of 101 dogs with GDV, Green et al.10 documented that at presentation 27% were tachypneic (RR 434 breaths/min), 20% had increased respiratory effort, 2% had respiratory distress, and 14% had evidence of aspiration pneumonia on preoperative thoracic radiographs. The development of the acute respiratory distress syndrome has also been reported in dogs with GDV.19
GI Dysfunction Gastric necrosis is a feared complication of GDV, as it contributes to morbidity and mortality. In dogs with GDV, gastric blood flow is likely decreased owing to a combination of factors including compression, thrombosis, or avulsion of the splenic or short gastric arteries or both, elevated intragastric pressure, and reduced cardiac output. The degree of dilatation, and degree and duration of volvulus likely contribute to the risk of gastric and severity of necrosis. Susceptibility of the gastric mucosa to damage by
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hypoperfusion may also be exacerbated by its own high metabolic demands and gastric acidity. The gastric fundus is most commonly affected by necrosis in dogs with GDV, with progression to the body of the stomach. Necrosis of the gastric cardia also occurs and is likely due to direct vascular occlusion. Decreased gastric blood flow and gastric venous obstruction initially manifests as gastric mucosal, submucosal and serosal edema, ulceration, and hemorrhage. Left untreated, gastric injury processes to necrosis and ultimately perforation with resultant septic peritonitis. The presence and severity of gastric necrosis is generally not known until the stomach can be grossly visualized at the time of exploratory celiotomy. Although radiographic abnormalities such as gastric pneumatosis (intramural gas) and pneumoperitoneum suggest gastric necrosis and perforation, respectively, air may be introduced into the gastric wall and peritoneum if the dog is trocarized for stabilization before radiographs are taken.21 At the time of surgery, the viability of the stomach is assessed based on the gross appearance of the stomach (serosal color) as well as its texture (palpation of stomach wall thickness), and preservation of arterial bleeding if incised. Gray or black coloration and palpable thinning of the stomach are signs of necrosis. The proportion of dogs with gastric necrosis requiring partial gastrectomy ranges from 19%18 to 41%.5,16,17,19,22,23 Direct compression of the portal vein and decreased cardiac output also compromise intestinal blood flow in dogs with GDV, resulting in villous injury and compromise of the mucosal barrier. Subsequent translocation of bacterial PAMPS such as lipopolysaccharide from gram-negative bacteria contributes to the systemic inflammatory response seen in dogs with GDV. GI dysfunction may also be exacerbated by anesthetic and analgesic drugs, contributing to postoperative GI ileus that can manifest as regurgitation, vomiting, nausea, and anorexia in the postoperative period. Unfortunately, although some studies note postoperative vomiting,22 its incidence is not known. Given the presence of GI ulceration in dogs with GDV, the use of nonsteroidal anti-inflammatory drugs for analgesia is contraindicated. Pancreatitis has also been reported postoperatively in dogs with GDV; one study documented pancreatitis in 2 of 66 dogs (3%).20 Dogs with GDV also commonly experience splenic compromise, given the close anatomic association between the stomach and spleen. Splenic damage can include vascular avulsion, intravascular thrombosis, splenic torsion, and infarction, and thus intraoperative assessment of splenic viability and consideration of splenectomy are imperative. The need for splenectomy has been identified as a poor prognostic indicator in many studies of dogs with GDV. The proportion of dogs requiring splenectomy associated with GDV ranges from 10%18 to 21%.23
Coagulation Dysfunction Coagulation dysfunction including disseminated intravascular coagulation (DIC) is another of the organ dysfunctions seen frequently in dogs with GDV.24 Likely contributing factors include pooling of blood in the caudal vena cava, portal vein, or splanchnic circulation, tissue hypoxia, acidosis, systemic inflammation, endotoxemia, and potentially sepsis. Classically coagulation dysfunction has been determined on the basis of abnormalities in one or more of primary hemostasis (i.e., thrombocytopenia), secondary hemostasis (prolonged clotting times), and fibrinolysis (elevated concentrations of fibrin degradation products and D-dimers). A subset of dogs with GDV appear to have evidence of a hypocoagulable state, thought to be the result of consumption of platelets and clotting factors in DIC. The presence of 3 or more abnormal coagulation parameters (thrombocytopenia,
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prolonged prothrombin or activated partial thromboplastin time, hypofibrinogenemia, elevated fibrin degradation products concentration, and antithrombin depletion), consistent with DIC, has been shown to correlate with gastric necrosis in one study,24 and nonsurvival in another.22 The prevalence of DIC defined in this way and reported in different GDV studies varies from 7.8% (13/166),22 21.1% (14/66),20 to 40% (8/20).24 Beer et al.19 reported that 2 of 78 dogs were euthanized for DIC, but the total number of dogs in their study that developed DIC was not reported. More recently thromboelastography has also been employed to assess the coagulation status of dogs with GDV.25 Abnormalities in thromboelastography parameters also appear to be associated with nonsurvival.25 In addition to the hypocoagulable state of DIC, multiple studies have also reported macrothromboses in dogs with GDV including 2 dogs with splenic thrombosis,20 and one with aortic thromboembolism.26 Renal Dysfunction The potential for the development of renal dysfunction postoperatively in dogs with GDV has received considerably less attention than the other organ dysfunctions noted earlier. Two recent studies from the same institution documented acute kidney injury (AKI) in 9 of 112 (8%) and 3 of 130 (2.3%) dogs with GDV.5,6 These authors defined AKI as an increase in serum creatinine concentration more than 2 mg/dL after 24 hours of intravenous fluid therapy, and after exclusion of prerenal and postrenal causes of azotemia.5,6 In both studies, the development of AKI was a significant risk factor for death. The potential mechanisms of renal injury are common to many of the organ dysfunctions, including a global tissue hypoperfusion due to shock, inflammatory injury mediated by damage-associated molecular patterns, PAMPS, and IRI, as well as thromboembolic complications particularly renal microthrombosis. In addition, treatments used for dogs in GDV have the potential to exacerbate renal injury including synthetic colloids for fluid resuscitation. This is another reason that the use of nonsteroidal antiinflammatory drugs is contraindicated in dogs with GDV.
Acid-Base and Electrolyte Abnormalities Abnormalities of acid-base status are commonly seen in dogs with GDV.27,28 Mixed acid-base disorders occur frequently, and primary abnormalities may include a high anion gap (lactate), metabolic acidosis (due to low DO2), a hypochloremic metabolic alkalosis (due to sequestration of gastric HCl acid), and respiratory acidosis (due to hypoventilation and hypercapnea). Because of the potential for concurrent and opposing primary disorders, pH may be normal.28 Electrolyte abnormalities also occur variably in dogs with GDV. Several pathophysiological events may promote the development of hypokalemia, including the administration of a large volume of lowpotassium fluids, sequestration of potassium within the stomach, or loss through vomiting or lavage, hyperchloremic metabolic alkalosis with transcellular shifting, activation of the renin-angiotensinaldosterone system, and catecholamine-induced intracellular shifting of potassium.
Conclusions Preoperative mortality associated with GDV is thought to primarily occur due to shock and cardiovascular instability. Intravenous fluid resuscitation and rapid surgical gastric decompression and derotation are imperative to resolve the shock state; however,
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other organ dysfunctions can develop in the postoperative period that require specific management and can contribute to late morbidity and mortality. Awareness of the potential for MODS and aggressive supportive care are essential to maximize the chances of a successful outcome in dogs with GDV.
Acknowledgments The authors would like to acknowledge the Collie Health Foundation, Morris Animal Foundation, and American Kennel Club Canine Health Foundation for supporting current and future research in this area. References 1. Osterbur K, Mann FA, Kuroki K, DeClue A. Multiple Organ Dysfunction Syndrome in Humans and Animals. J Vet Intern Med 28:1141–1151, 2014 2. Bruchim Y, Kelmer E. Post-operative management and managing complications of gastric dilatation and volvulus. Top Comp Anim Med 29, 2014 3. Bell JS. Inherited and predisposing factors in the development of gastric dilatation and volvlus in dogs. Top Comp Anim Med 29, 2014 4. Gazzola K, Nelson L. The relationship between gastrointestinal motility and gastric dilatation-volvulus in dogs. Top Comp Anim Med 29, 2014 5. Bruchim Y, Itay S, Shira BH, et al. Evaluation of lidocaine treatment on frequency of cardiac arrhythmias, acute kidney injury, and hospitalization time in dogs with gastric dilatation volvulus. J Vet Emerg Crit Care 22:419–427, 2012 6. Buber T, Saragusty J, Ranen E, Epstein A, Bdolah-Abram T, Bruchim Y. Evaluation of lidocaine treatment and risk factors for death associated with gastric dilatation and volvulus in dogs: 112 cases (1997-2005). J Am Vet Med Assoc 230:1334–1339, 2007 7. Buber T, Saragusty J, Ranen E, Epstein A, Bdolah-Abram T, Bruchim Y. Prevention of reperfusion injury in surgically induced gastric dilatationvolvulus in dogs. Am J Vet Res 51:294–299, 1990 8. Lantz GC, Badylak SF, Hiles MC, Arkin TE. Treatment of reperfusion injury in dogs with experimentally induced gastric dilatation-volvulus. Am J Vet Res 53:1594–1598, 1992 9. Odunayo A, Dodam JR, Kerl ME, Declue AE. Immunomodulatory effects of opioids. J Vet Emerg Crit Care 20:376–385, 2010 10. Green JL, Cimino Brown D, Agnello KA. Preoperative thoracic radiographic findings in dogs presenting for gastric dilatation-volvulus (2000-2010): 101 cases. J Vet Emerg Crit Care 22:595–600, 2012 11. Brockman DJ, Washabau RJ, Drobatz KJ. Canine gastric dilatation/volvulus syndrome in a veterinary critical care unit: 295 cases (1986-1992). J Am Vet Med Assoc 207:460–464, 1995
12. Brourman JD, Schertel ER, Allen DA, Birchard SJ, DeHoff WD. Factors associated with perioperative mortality in dogs with surgically managed gastric dilatation-volvulus: 137 cases (1988-1993). J Am Vet Med Assoc 208:1855–1858, 1996 13. Horne WA, Gilmore DR, Ditze AE, Freden GO, Short CE. Effects of gastric distention-volvulus on coronary blood flow and myocardial oxygen consumption in the dog. Am J Vet Res 46:98–104, 1985 14. Schober KE, Cornand C, Kirbach B, Aupperle H, Oechtering G. Serum cardiac troponin I and cardiac troponin T concentrations in dogs with gastric dilatation-volvulus. J Am Vet Med Assoc 221:381–388, 2002 15. Haak CE, Rudloff E, Kirby R. Comparison of Hb-200 and 6% hetastarch 450/0.7 during initial fluid resuscitation of 20 dogs with gastric dilatation-volvulus. J Vet Emerg Crit Care 22:201–210, 2012 16. de Papp E, Drobatz KH, Hughes D. Plasma lactate concentration as a predictor of gastric necrosis and survival among dogs with gastric dilatation-volvulus: 102 cases (1995-1998). J Am Vet Med Assoc 215:49–52, 1999 17. Zacher LA, Berg J, Shaw SP, Kudej RK. Association between outcome and changes in plasma lactate concentration during presurgical treatment in dogs with gastric dilatation-volvulus: 64 cases (2002-2008). J Am Vet Med Assoc 236:892–897, 2010 18. Green TI, Tonozzi CC, Kirby R, Rudloff E. Evaluation of initial plasma lactate values as a predictor of gastric necrosis and initial and subsequent plasma lactate values as a predictor of survival in dogs with gastric dilatation-volvulus: 84 dogs (2003-2007). J Vet Emerg Crit Care 21:36–44, 2011 19. Beer KA, Syring RS, Drobatz KJ. Evaluation of plasma lactate concentration and base excess at the time of hospital admission as predictors of gastric necrosis and outcome and correlation between those variables in dogs with gastric dilatation-volvulus: 78 cases (2004-2009). J Am Vet Med Assoc 242:54–58, 2013 20. Israeli I, Steiner J, Segev G, et al. Serum pepsinogen-A, canine pancreatic lipase immunoreactivity, and C-reactive protein as prognostic markers in dogs with gastric dilatation-volvulus. J Vet Intern Med 26:920–928, 2012 21. Fischetti AJ, Saunders HM, Drobatz KJ. Pneumatosis in canine gastric dilatationvolvulus syndrome. Vet Radiol Ultrasound 45:205–209, 2004 22. Beck JJ, Staatz AJ, Pelsue DH, et al. Risk factors associated with short-term outcome and development of perioperative complications in dogs undergoing surgery because of gastric dilatation-volvulus: 166 cases (1992-2003). J Am Vet Med Assoc 229:1934–1939, 2006 23. Mackenzie G, Barnhart M, Kennedy S, DeHoff W, Schertel E. A retrospective study of factors influencing survival following surgery for gastric dilatationvolvulus syndrome in 306 dogs. J Am Anim Hosp Assoc 46:97–102, 2010 24. Millis DL, Hauptman JG, Fulton Jr RB. Abnormal hemostatic profiles and gastric necrosis in canine gastric dilatation-volvulus. Vet Surg 22:93–97, 1993 25. Bucknoff M, deLaforcade AM, Sharp CR, Meola D, Rozanski EA. Thromboelastography in dogs with gastric dilatation-volvulus, presented at the ACVIM Forum, 2013 26. Carter WO. Aortic thromboembolism as a complication of gastric dilatation/ volvulus in a dog. J Am Vet Med Assoc 196:1829–1830, 1990 27. Muir WW. Acid-base and electrolyte disturbances in dogs with gastric dilatation-volvulus. J Am Vet Med Assoc 181:229–231, 1982 28. Wingfield WE, Twedt DC, Moore RW, Leib MS, Wright M. Acid-base and electrolyte values in dogs with acute gastric dilatation-volvulus. J Am Vet Med Assoc 180:1070–1072, 1982
Topical Review
Cardiovascular and Systemic Effects of Gastric Dilatation and Volvulus in Dogs Claire R. Sharp, BVMS, MS, DACVECCn, Elizabeth A. Rozanski, DVM, DACVIM, DACVECC Keywords: acute kidney injury disseminated intravascular coagulation ischemic reperfusion injury multiple organ dysfunction system systemic inflammatory response syndrome Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA n
Address reprint requests to: Claire R. Sharp, BVMS, MS, DACVECC, Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA, USA. E-mail: [email protected] (C.R. Sharp)
Gastric dilatation and volvulus (GDV) is a common emergency condition in large and giant breed dogs that is associated with high morbidity and mortality. Dogs with GDV classically fulfill the criteria for the systemic inflammatory response syndrome (SIRS) and can go on to develop multiple organ dysfunction syndrome (MODS). Previously reported organ dysfunctions in dogs with GDV include cardiovascular, respiratory, gastrointestinal, coagulation and renal dysfunction. Cardiovascular manifestations of GDV include shock, cardiac arrhythmias and myocardial dysfunction. Respiratory dysfunction is also multifactorial, with contributory factors including decreased respiratory excursion due to gastric dilatation, decreased pulmonary perfusion and aspiration pneumonia. Gastrointestinal dysfunction includes gastric necrosis and post-operative gastrointestinal upset such as regurgitation, vomiting, and ileus. Coagulation dysfunction is another common feature of MODS in dogs with GDV. Disseminated intravascular coagulation can occur, putting them at risk of complications associated with thrombosis in the early hypercoagulable state and hemorrhage in the subsequent hypocoagulable state. Acute kidney injury, acid-base and electrolyte disturbances are also reported in dogs with GDV. Understanding the potential for systemic effects of GDV allows the clinician to monitor patients astutely and detect such complications early, facilitating early intervention to maximize the chance of successful management. & 2014 Elsevier Inc. All rights reserved.
Introduction Gastric dilatation volvulus (GDV), commonly referred to as bloat, is a common condition in large and giant breed dogs presenting for emergency care that is associated with high morbidity and the potential for mortality. Although the pathogenesis of GDV is incompletely understood, a lot is known about the potential cardiovascular and systemic side effects of the condition. GDV results in development of the systemic inflammatory response syndrome (SIRS) and potentially multiple organ dysfunction syndrome (MODS). Organ dysfunctions that have been documented as part of MODS in dogs with GDV include cardiovascular, respiratory, gastrointestinal (GI), coagulation, and renal dysfunction. Hepatic, central nervous system, and endocrine system dysfunction have not been specifically evaluated in dogs with GDV, although are considered other important organ systems involved in MODS.1 The multisystemic effects of GDV will be discussed here with a focus on pathophysiology. The final article in this special issue discusses management of the postoperative GDV patient, with a special focus on management of complications and organ dysfunctions.2
Pathophysiology The pathogenesis of GDV is complex and multifactorial, with apparent genetic and environmental influences. The first article in this special issue discusses the genetic predispositions to GDV in dogs,3 whereas the second article discusses the role of GI motility disturbances in the development of GDV.4 It is unknown whether dilatation or volvulus occurs first in dogs with GDV, but either is possible as dilatation in the absence of volvulus and volvulus in the absence of dilatation are both reported. Dogs with GDV classically fulfill criteria for SIRS, although this has not been formally evaluated to the knowledge of the authors.5,6 Although no consensus definition exists, in general, in veterinary studies, dogs are considered to have SIRS, if they have http://dx.doi.org/10.1053/j.tcam.2014.09.007 1527-3369/& 2014 Topics in Companion Animal Medicine. Published by Elsevier Inc.
an underlying disease that could predispose to SIRS in addition to having abnormalities of a least 2 of the following 4 abnormalities: body temperature, heart rate (HR), respiratory rate (RR), and white blood cell count or differential. There are many potential triggers for SIRS and subsequently MODS in dogs with GDV, including global tissue hypoperfusion and cellular ischemia, gastric ischemia and reperfusion, gastric necrosis, and GI translocation of bacteria and bacterial products. Ischemia reperfusion injury (IRI) have been discussed extensively in the context of GDV.5,7,8 Tissue injury and cell death leading to the release of damage-associated molecular patterns into circulation, in addition to the potential for translocation of microbial pathogen-associated molecular patterns (PAMPS), trigger the innate immune response, resulting in the production of proinflammatory cytokines, activation of the complement cascade, activation of coagulation, and associated downstream effects. Inflammation is also exacerbated by the reactive oxygen species produced as a consequence of IRI. In addition, general anesthesia required for surgical correction of GDV may be a “second hit” that exacerbates SIRS and contributes to MODS in these patients. The potentially deleterious components or effects of general anesthesia are thought to include administration of 100% oxygen (albeit for a relatively short period of time), positive pressure ventilation, vasodilation and hypotension, and the immunomodulatory effects of opioid analgesics.9 Dysregulation of the immune system and mitochondrial dysfunction are also thought to be key to the initiation of the MODS in people with sepsis and SIRS1; however, these pathologies have not yet been explored in dogs with GDV.
Cardiovascular Dysfunction Cardiovascular manifestations of GDV include shock, cardiac arrhythmias, and myocardial dysfunction. Cardiovascular compromise is thought to be the primary systemic side effect that contributes to early morbidity and mortality in dogs with GDV.
68
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The end result of cardiovascular dysfunction is decreased tissue oxygen delivery (DO2) and the clinical manifestations of shock. Decreased DO2 contributes to the development of MODS, with consequences on the cardiovascular, respiratory, renal, GI, and central nervous systems. Dogs with GDV likely have a combination of obstructive, distributive, hypovolemic, and cardiogenic shock. Obstructive Shock Marked gastric dilatation results in the compression of the lowpressure intra-abdominal veins, including the portal vein, splenic veins, and caudal vena cava. As a consequence, venous return to the heart, and subsequently stroke volume, is reduced. HR will increase to compensate for reduced stroke volume; however, usually this compensation is inadequate and cardiac output too is reduced. Distributive Shock Decreased venous return and increased venous pressure result in splanchnic pooling of blood. Compromise of splenic blood flow tends to result in splenic congestion and splenomegaly. Splanchnic vasodilation is likely also exacerbated by production of the potent endogenous vasodilator nitric oxide via inducible nitric oxide synthase, further exacerbating peripheral vasodilation and splanchnic pooling of blood. Hypovolemic Shock Absolute hypovolemia is likely a relatively small component of the shock syndrome in dogs with GDV, although they may well have a relative hypovolemia. In one study, 34% of dogs with GDV had microcardia on thoracic radiographs suggestive of hypovolemia, although obstructive and distributive shock could also account for this.10 Loss of intravascular volume can occur via abdominal hemorrhage, third spacing of fluids, and GI secretions. Concurrently gastric inflow obstruction prevents oral intake of water. Blood loss associated with GDV is generally relatively minor and typically occurs as a result of the rupture of small gastric vessels as gastric volvulus occurs. For this reason, a small volume hemoabdomen is often noted at the time of abdominal surgery. Splanchnic pooling of blood and portal hypertension can contribute to third spacing of fluid and interstitial edema particularly in the abdominal viscera. Cardiogenic Shock Cardiogenic shock can occur as a result of myocardial dysfunction and cardiac arrhythmias. Cardiac arrhythmias, predominantly ventricular arrhythmias, occur in approximately 40% of dogs with GDV, likely as a result of myocardial ischemia.11,12 Significant reductions in coronary blood flow have been documented in experimentally induced GDV in dogs, and histopathologic evidence of myocardial ischemia has been seen in both experimental and naturally occurring GDV.13 It is well known that ischemic myocardium is likely to establish ectopic foci of electrical activity. Dogs with GDV also commonly have elevated circulating concentrations of cardiac troponins, and concentrations of these biomarkers correlate with the severity of electrocardiogram abnormalities and patient outcome.14 Increased circulating concentrations of cardiostimulatory substances such as the catecholamines, and cardioinhibitory substances such as proinflammatory cytokines (e.g., tumor necrosis factor α), have also been implicated in the generation of arrhythmias.
Physical examination abnormalities in dogs presenting with GDV are generally manifestations of the circulatory and respiratory compromise they experience. Dogs often present in early decompensated shock, with tachycardia, weak pulses, and depressed mentation. Depending on the state of compensation mucus membranes may be pale or injected, and capillary refill time may be rapid or prolonged. Irregular cardiac rhythms and pulse deficits may be present. In one study, 18 of 20 dogs (90%) had tachycardia (HR Z 120), and all dogs had abnormal perfusion parameters (mucus membranes, capillary refill time, and pulses).15 Tachypnea, dyspnea, or both may be associated with discomfort and respiratory compromise as documented later. Hyperlactatemia is a common finding in dogs with GDV. Its origin is likely multifactorial, stemming from both global and local (gastric) hypoperfusion. Although multiple studies report the use of lactate as a prognostic biomarker in dogs with GDV,16-19 the true prevalence of hyperlactatemia at presentation is not always reported. One recent study documented that 58.5% of dogs (38/66) with GDV were hyperlactatemic at presentation,20 whereas another reported that 30% of dogs (30/101) had an admitting lactate level 4 6 mmol/L.10
Respiratory Dysfunction Respiratory compromise may occur in dogs with GDV as a result of gastric dilatation adversely affecting normal respiratory excursion, reduced pulmonary perfusion, and aspiration pneumonia. Gastric dilatation and increased intra-abdominal pressure will decrease the total thoracic volume and prevent the normal caudal excursion of the diaphragm to initiate inspiration, resulting in hypoventilation and ventilation-perfusion mismatching. In severe cases, lung lobe collapse can also occur. Increased RR and effort ensue so as to compensate, although these efforts may become inadequate and hypercapnea and hypoxemia can occur. Pulmonary blood flow may also be decreased in dogs with GDV due to decreased cardiac output, further contributing to ventilationperfusion mismatch. Dogs with GDV are at risk of developing both preoperative and postoperative aspiration pneumonia. In addition, multiple studies identified pneumonia in dogs with GDV as a poor prognostic indicator.11,12 As dogs with GDV often fulfill SIRS criteria and have tachypnea and dyspnea on presentation, the presence of pneumonia can be difficult to discern based on clinical signs alone. As such, preoperative thoracic radiographs are recommended to identify evidence of aspiration pneumonia and guide antimicrobial therapy.10 Of a population of 101 dogs with GDV, Green et al.10 documented that at presentation 27% were tachypneic (RR 434 breaths/min), 20% had increased respiratory effort, 2% had respiratory distress, and 14% had evidence of aspiration pneumonia on preoperative thoracic radiographs. The development of the acute respiratory distress syndrome has also been reported in dogs with GDV.19
GI Dysfunction Gastric necrosis is a feared complication of GDV, as it contributes to morbidity and mortality. In dogs with GDV, gastric blood flow is likely decreased owing to a combination of factors including compression, thrombosis, or avulsion of the splenic or short gastric arteries or both, elevated intragastric pressure, and reduced cardiac output. The degree of dilatation, and degree and duration of volvulus likely contribute to the risk of gastric and severity of necrosis. Susceptibility of the gastric mucosa to damage by
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hypoperfusion may also be exacerbated by its own high metabolic demands and gastric acidity. The gastric fundus is most commonly affected by necrosis in dogs with GDV, with progression to the body of the stomach. Necrosis of the gastric cardia also occurs and is likely due to direct vascular occlusion. Decreased gastric blood flow and gastric venous obstruction initially manifests as gastric mucosal, submucosal and serosal edema, ulceration, and hemorrhage. Left untreated, gastric injury processes to necrosis and ultimately perforation with resultant septic peritonitis. The presence and severity of gastric necrosis is generally not known until the stomach can be grossly visualized at the time of exploratory celiotomy. Although radiographic abnormalities such as gastric pneumatosis (intramural gas) and pneumoperitoneum suggest gastric necrosis and perforation, respectively, air may be introduced into the gastric wall and peritoneum if the dog is trocarized for stabilization before radiographs are taken.21 At the time of surgery, the viability of the stomach is assessed based on the gross appearance of the stomach (serosal color) as well as its texture (palpation of stomach wall thickness), and preservation of arterial bleeding if incised. Gray or black coloration and palpable thinning of the stomach are signs of necrosis. The proportion of dogs with gastric necrosis requiring partial gastrectomy ranges from 19%18 to 41%.5,16,17,19,22,23 Direct compression of the portal vein and decreased cardiac output also compromise intestinal blood flow in dogs with GDV, resulting in villous injury and compromise of the mucosal barrier. Subsequent translocation of bacterial PAMPS such as lipopolysaccharide from gram-negative bacteria contributes to the systemic inflammatory response seen in dogs with GDV. GI dysfunction may also be exacerbated by anesthetic and analgesic drugs, contributing to postoperative GI ileus that can manifest as regurgitation, vomiting, nausea, and anorexia in the postoperative period. Unfortunately, although some studies note postoperative vomiting,22 its incidence is not known. Given the presence of GI ulceration in dogs with GDV, the use of nonsteroidal anti-inflammatory drugs for analgesia is contraindicated. Pancreatitis has also been reported postoperatively in dogs with GDV; one study documented pancreatitis in 2 of 66 dogs (3%).20 Dogs with GDV also commonly experience splenic compromise, given the close anatomic association between the stomach and spleen. Splenic damage can include vascular avulsion, intravascular thrombosis, splenic torsion, and infarction, and thus intraoperative assessment of splenic viability and consideration of splenectomy are imperative. The need for splenectomy has been identified as a poor prognostic indicator in many studies of dogs with GDV. The proportion of dogs requiring splenectomy associated with GDV ranges from 10%18 to 21%.23
Coagulation Dysfunction Coagulation dysfunction including disseminated intravascular coagulation (DIC) is another of the organ dysfunctions seen frequently in dogs with GDV.24 Likely contributing factors include pooling of blood in the caudal vena cava, portal vein, or splanchnic circulation, tissue hypoxia, acidosis, systemic inflammation, endotoxemia, and potentially sepsis. Classically coagulation dysfunction has been determined on the basis of abnormalities in one or more of primary hemostasis (i.e., thrombocytopenia), secondary hemostasis (prolonged clotting times), and fibrinolysis (elevated concentrations of fibrin degradation products and D-dimers). A subset of dogs with GDV appear to have evidence of a hypocoagulable state, thought to be the result of consumption of platelets and clotting factors in DIC. The presence of 3 or more abnormal coagulation parameters (thrombocytopenia,
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prolonged prothrombin or activated partial thromboplastin time, hypofibrinogenemia, elevated fibrin degradation products concentration, and antithrombin depletion), consistent with DIC, has been shown to correlate with gastric necrosis in one study,24 and nonsurvival in another.22 The prevalence of DIC defined in this way and reported in different GDV studies varies from 7.8% (13/166),22 21.1% (14/66),20 to 40% (8/20).24 Beer et al.19 reported that 2 of 78 dogs were euthanized for DIC, but the total number of dogs in their study that developed DIC was not reported. More recently thromboelastography has also been employed to assess the coagulation status of dogs with GDV.25 Abnormalities in thromboelastography parameters also appear to be associated with nonsurvival.25 In addition to the hypocoagulable state of DIC, multiple studies have also reported macrothromboses in dogs with GDV including 2 dogs with splenic thrombosis,20 and one with aortic thromboembolism.26 Renal Dysfunction The potential for the development of renal dysfunction postoperatively in dogs with GDV has received considerably less attention than the other organ dysfunctions noted earlier. Two recent studies from the same institution documented acute kidney injury (AKI) in 9 of 112 (8%) and 3 of 130 (2.3%) dogs with GDV.5,6 These authors defined AKI as an increase in serum creatinine concentration more than 2 mg/dL after 24 hours of intravenous fluid therapy, and after exclusion of prerenal and postrenal causes of azotemia.5,6 In both studies, the development of AKI was a significant risk factor for death. The potential mechanisms of renal injury are common to many of the organ dysfunctions, including a global tissue hypoperfusion due to shock, inflammatory injury mediated by damage-associated molecular patterns, PAMPS, and IRI, as well as thromboembolic complications particularly renal microthrombosis. In addition, treatments used for dogs in GDV have the potential to exacerbate renal injury including synthetic colloids for fluid resuscitation. This is another reason that the use of nonsteroidal antiinflammatory drugs is contraindicated in dogs with GDV.
Acid-Base and Electrolyte Abnormalities Abnormalities of acid-base status are commonly seen in dogs with GDV.27,28 Mixed acid-base disorders occur frequently, and primary abnormalities may include a high anion gap (lactate), metabolic acidosis (due to low DO2), a hypochloremic metabolic alkalosis (due to sequestration of gastric HCl acid), and respiratory acidosis (due to hypoventilation and hypercapnea). Because of the potential for concurrent and opposing primary disorders, pH may be normal.28 Electrolyte abnormalities also occur variably in dogs with GDV. Several pathophysiological events may promote the development of hypokalemia, including the administration of a large volume of lowpotassium fluids, sequestration of potassium within the stomach, or loss through vomiting or lavage, hyperchloremic metabolic alkalosis with transcellular shifting, activation of the renin-angiotensinaldosterone system, and catecholamine-induced intracellular shifting of potassium.
Conclusions Preoperative mortality associated with GDV is thought to primarily occur due to shock and cardiovascular instability. Intravenous fluid resuscitation and rapid surgical gastric decompression and derotation are imperative to resolve the shock state; however,
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other organ dysfunctions can develop in the postoperative period that require specific management and can contribute to late morbidity and mortality. Awareness of the potential for MODS and aggressive supportive care are essential to maximize the chances of a successful outcome in dogs with GDV.
Acknowledgments The authors would like to acknowledge the Collie Health Foundation, Morris Animal Foundation, and American Kennel Club Canine Health Foundation for supporting current and future research in this area. References 1. Osterbur K, Mann FA, Kuroki K, DeClue A. Multiple Organ Dysfunction Syndrome in Humans and Animals. J Vet Intern Med 28:1141–1151, 2014 2. Bruchim Y, Kelmer E. Post-operative management and managing complications of gastric dilatation and volvulus. Top Comp Anim Med 29, 2014 3. Bell JS. Inherited and predisposing factors in the development of gastric dilatation and volvlus in dogs. Top Comp Anim Med 29, 2014 4. Gazzola K, Nelson L. The relationship between gastrointestinal motility and gastric dilatation-volvulus in dogs. Top Comp Anim Med 29, 2014 5. Bruchim Y, Itay S, Shira BH, et al. Evaluation of lidocaine treatment on frequency of cardiac arrhythmias, acute kidney injury, and hospitalization time in dogs with gastric dilatation volvulus. J Vet Emerg Crit Care 22:419–427, 2012 6. Buber T, Saragusty J, Ranen E, Epstein A, Bdolah-Abram T, Bruchim Y. Evaluation of lidocaine treatment and risk factors for death associated with gastric dilatation and volvulus in dogs: 112 cases (1997-2005). J Am Vet Med Assoc 230:1334–1339, 2007 7. Buber T, Saragusty J, Ranen E, Epstein A, Bdolah-Abram T, Bruchim Y. Prevention of reperfusion injury in surgically induced gastric dilatationvolvulus in dogs. Am J Vet Res 51:294–299, 1990 8. Lantz GC, Badylak SF, Hiles MC, Arkin TE. Treatment of reperfusion injury in dogs with experimentally induced gastric dilatation-volvulus. Am J Vet Res 53:1594–1598, 1992 9. Odunayo A, Dodam JR, Kerl ME, Declue AE. Immunomodulatory effects of opioids. J Vet Emerg Crit Care 20:376–385, 2010 10. Green JL, Cimino Brown D, Agnello KA. Preoperative thoracic radiographic findings in dogs presenting for gastric dilatation-volvulus (2000-2010): 101 cases. J Vet Emerg Crit Care 22:595–600, 2012 11. Brockman DJ, Washabau RJ, Drobatz KJ. Canine gastric dilatation/volvulus syndrome in a veterinary critical care unit: 295 cases (1986-1992). J Am Vet Med Assoc 207:460–464, 1995
12. Brourman JD, Schertel ER, Allen DA, Birchard SJ, DeHoff WD. Factors associated with perioperative mortality in dogs with surgically managed gastric dilatation-volvulus: 137 cases (1988-1993). J Am Vet Med Assoc 208:1855–1858, 1996 13. Horne WA, Gilmore DR, Ditze AE, Freden GO, Short CE. Effects of gastric distention-volvulus on coronary blood flow and myocardial oxygen consumption in the dog. Am J Vet Res 46:98–104, 1985 14. Schober KE, Cornand C, Kirbach B, Aupperle H, Oechtering G. Serum cardiac troponin I and cardiac troponin T concentrations in dogs with gastric dilatation-volvulus. J Am Vet Med Assoc 221:381–388, 2002 15. Haak CE, Rudloff E, Kirby R. Comparison of Hb-200 and 6% hetastarch 450/0.7 during initial fluid resuscitation of 20 dogs with gastric dilatation-volvulus. J Vet Emerg Crit Care 22:201–210, 2012 16. de Papp E, Drobatz KH, Hughes D. Plasma lactate concentration as a predictor of gastric necrosis and survival among dogs with gastric dilatation-volvulus: 102 cases (1995-1998). J Am Vet Med Assoc 215:49–52, 1999 17. Zacher LA, Berg J, Shaw SP, Kudej RK. Association between outcome and changes in plasma lactate concentration during presurgical treatment in dogs with gastric dilatation-volvulus: 64 cases (2002-2008). J Am Vet Med Assoc 236:892–897, 2010 18. Green TI, Tonozzi CC, Kirby R, Rudloff E. Evaluation of initial plasma lactate values as a predictor of gastric necrosis and initial and subsequent plasma lactate values as a predictor of survival in dogs with gastric dilatation-volvulus: 84 dogs (2003-2007). J Vet Emerg Crit Care 21:36–44, 2011 19. Beer KA, Syring RS, Drobatz KJ. Evaluation of plasma lactate concentration and base excess at the time of hospital admission as predictors of gastric necrosis and outcome and correlation between those variables in dogs with gastric dilatation-volvulus: 78 cases (2004-2009). J Am Vet Med Assoc 242:54–58, 2013 20. Israeli I, Steiner J, Segev G, et al. Serum pepsinogen-A, canine pancreatic lipase immunoreactivity, and C-reactive protein as prognostic markers in dogs with gastric dilatation-volvulus. J Vet Intern Med 26:920–928, 2012 21. Fischetti AJ, Saunders HM, Drobatz KJ. Pneumatosis in canine gastric dilatationvolvulus syndrome. Vet Radiol Ultrasound 45:205–209, 2004 22. Beck JJ, Staatz AJ, Pelsue DH, et al. Risk factors associated with short-term outcome and development of perioperative complications in dogs undergoing surgery because of gastric dilatation-volvulus: 166 cases (1992-2003). J Am Vet Med Assoc 229:1934–1939, 2006 23. Mackenzie G, Barnhart M, Kennedy S, DeHoff W, Schertel E. A retrospective study of factors influencing survival following surgery for gastric dilatationvolvulus syndrome in 306 dogs. J Am Anim Hosp Assoc 46:97–102, 2010 24. Millis DL, Hauptman JG, Fulton Jr RB. Abnormal hemostatic profiles and gastric necrosis in canine gastric dilatation-volvulus. Vet Surg 22:93–97, 1993 25. Bucknoff M, deLaforcade AM, Sharp CR, Meola D, Rozanski EA. Thromboelastography in dogs with gastric dilatation-volvulus, presented at the ACVIM Forum, 2013 26. Carter WO. Aortic thromboembolism as a complication of gastric dilatation/ volvulus in a dog. J Am Vet Med Assoc 196:1829–1830, 1990 27. Muir WW. Acid-base and electrolyte disturbances in dogs with gastric dilatation-volvulus. J Am Vet Med Assoc 181:229–231, 1982 28. Wingfield WE, Twedt DC, Moore RW, Leib MS, Wright M. Acid-base and electrolyte values in dogs with acute gastric dilatation-volvulus. J Am Vet Med Assoc 180:1070–1072, 1982
