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Evaluation of lidocaine treatment and risk factors for death associated with gastric dilatation and volvulus in dogs: 112 cases (1997–2005) Tali Buber, bsc; Joseph Saragusty, dvm; Eyal Ranen, dvm; Ana Epstein, dvm; Tali Bdolah-Abram, msc; Yaron Bruchim, dvm

Objective—To determine clinical features, outcome, risk factors for death, and efficacy of IV administration of lidocaine as a prophylactic treatment for ischemic reperfusion injury in gastric dilatation and volvulus (GDV) in dogs. Design—Retrospective case series. Animals—112 dogs with GDV. Procedures—Data pertaining to breed; time lag to admission; clinical, clinicopathologic, and surgical findings; lidocaine treatment; and postoperative complications were assessed for association with outcome. Results—German Shepherd Dogs (28.6%) and Great Danes (17%) were significantly overrepresented. Risk factors for death included time lag (≥ 5 hours vs < 5 hours) from onset of clinical signs to admission (46.0% vs 11.3%), rectal temperature (≤ 38oC vs > 38oC [< 100.4oF vs > 100.4oF]) at admission (40.0% vs 14.9%), presence or absence of ARF (67.0% vs 23.3%), presence or absence of suspected gastric wall necrosis (59.3% vs 16.0%), and untreated gastric wall necrosis, compared with treated gastric wall necrosis (100% vs 47.6%). Overall mortality rate was 26.8%; no significant differences were detected in mortality rate or postoperative complications between dogs that received lidocaine IV prior to surgical intervention (52.0%) and dogs that did not (48.0%). Mean ± SD hospitalization time was longer in the lidocaine treatment group (3.5 ± 1.9 days vs 2.5 ± 1.4 days). Conclusions and Clinical Relevance—Presence of the identified risk factors should warrant aggressive treatment. Lidocaine treatment was not associated with mortality rate or postoperative complications, but was associated with prolonged hospitalization time. (J Am Vet Med Assoc 2007;230:1334–1339)

G

astric dilatation and volvulus is an acute, lifethreatening syndrome that requires immediate medical and surgical treatment as well as intensive postoperative care.1 Rapid accumulation of gas in the stomach, gastric displacement, increased intragastric pressure, and decreased venous return occur. Gastric dilatation and volvulus is characterized principally by cardiogenic shock, during which the entire body may be subjected to inadequate tissue perfusion and ischemia.2-5 The most serious complications of GDV are associated with IRI and consequent SIRS. These include hypotension, ARF, DIC, and cardiac arrhythmias.1,6 Despite appropriate medical and surgical treatment, the reported mortality rate in GDV is high (15% to 28%).4,7,8 Gastric necrosis and high serum lactate concentration were found as predictors of postoperative complications and death in GDV, indicating the imFrom the School of Veterinary Medicine (Buber, Ranen, Epstein, Bdolah-Abram, Bruchim) and the Department of Animal Sciences (Saragusty), Faculty of Agricultural, Food & Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel. Dr. Bruchim’s present address is Emergency and Critical Care Unit, School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot 76100, Israel. Presented at the European Emergency and Critical Care Association Conference, Edinburgh, June 2006. Address correspondence to Dr. Bruchim. 1334

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Abbreviations GDV IRI SIRS ARF DIC ROS HUVTH CRI PT aPTT ROC

Gastric dilatation and volvulus Ischemic reperfusion injury Systemic inflammatory response syndrome Acute renal failure Disseminated intravascular coagulation Reactive oxygen species Hebrew University Veterinary Medicine Teaching Hospital Constant rate infusion Prothrombin time Activated partial thromboplastin time Receiver operating characteristic

portant role of ischemic hypoperfusion in the progression of this disease.2,7-12 Standard treatment includes gastric decompression and intensive treatment for hypovolemic circulatory shock, followed by repositioning of the stomach and surgical removal of necrotic tissue, with intensive postoperative monitoring.1,2,5,9,12 The initial goal of treatment is reversal of shock by increasing venous return to the heart and reperfusion of transiently ischemic tissues.1,2,12 However, reperfusion may result in paradoxical tissue damage and destruction caused by ROS that are formed in previously ischemic tissues.13-17 During JAVMA, Vol 230, No. 9, May 1, 2007

Criteria for Selection of Cases The medical records of all dogs admitted to the Emergency and Critical Care Unit of the HUVTH from 1997 through 2005 were retrospectively reviewed. Inclusion criteria were diagnosis of GDV on the basis of history, clinical findings, and at least one of the following: radiographic findings and rotated stomach, gastric wall necrosis, or both diagnosed during surgery. Identification of gastric wall necrosis was made on the basis of altered serosal coloration and lack of arterial pulsation. Only dogs that were treated surgically were selected for the present study. Procedures One dog was excluded from the present study because of concurrent mesenteric root volvulus, even though gastric wall necrosis was diagnosed during surgery. Time lag from clinical signs to admission was obtained from the owners. Breed prevalence in the hospital population was obtained from the HUVTH database and was compared with breed prevalence in the present study. Surgical treatment included gastrotomy, resection or invagination of the stomach wall, complete or parJAVMA, Vol 230, No. 9, May 1, 2007

tial spleen removal when indicated, and gastropexy in all dogs. Surgeons followed the general guideline to use resection when large necrotic areas were found and invagination for small necrotic areas. Gastropexy methods included incisional gastropexy, belt loop gastropexy, tube gastropexy, and circumcostal gastropexy. The decision regarding gastrotomy and gastropexy methods was made according to the surgeon’s personal preferences, amount of necrosis on the stomach wall, or both. Nonsurvivors were dogs that died naturally or were euthanized during hospitalization either because of severe gastric wall necrosis found during surgery or postsurgical complications. Lidocaine administration protocol—Dogs were allocated into a lidocaine-treated group and a nontreated group on the basis of whether dogs were treated IV with lidocaine prior to surgical intervention. Fourteen dogs that received lidocaine IV to treat cardiac arrhythmias after surgery were excluded from analysis of lidocaine treatment. Therefore, the remaining 98 dogs constituted the lidocaine-treated group (n = 51 dogs) and nontreated group (47). The clinical status of the dog had no effect on the decision whether to treat it with lidocaine. In the lidocaine-treated group, the 2 protocols used were IV administration of a bolus (2 mg/kg [0.91 mg/ lb]), followed by CRI of 0.05 mg/kg/min (0.023 mg/lb/ min) for at least 3 hours (8/51 dogs), or CRI IV administration of lidocaine (0.05 mg/kg/min) for at least 3 hours. The decision regarding choice of treatment regimen was based on the clinician’s personal preference. Definition of secondary complications—Acute renal failure was diagnosed when dogs had serum creatinine concentration > 2 mg/dL after 24 hours of fluid administration. Disseminated intravascular coagulation was diagnosed when dogs had a combination of thrombocytopenia (< 150,000 cells/µL) and 2 of the following: prolongation (> 25%) of the PT or aPTT and clinical signs of DIC (petechiae, ecchymoses, hematochezia, melena, hematemesis, and hematuria). Cardiac arrhythmias included ventricular premature complexes, ventricular tachycardia, idioventricular rhythm, and atrial fibrillation. Laboratory tests—Blood samples for hematologic tests were collected in evacuated blood tubes that contained potassium-EDTA and analyzed within 30 minutes of collection. Blood samples for coagulation tests were collected in evacuated tubes that contained trisodiumcitrate and analyzed within 30 minutes of collection. Prothrombin time and aPTT were determined by use of analyzers calibrated for canine serum. Complete blood counts were performed by use of an automatic blood impedance analyzer calibrated for canine blood.a,b Packed cell volume was measured via centrifugation of heparinized capillary tubes at 12,000 X g, and total plasma protein was determined by use of a standard refractometer. Differential WBC counts were performed manually by counting 100 leukocytes in Giemsa-stained blood smears. Blood for serum biochemical analyses was collected in plain tubes and centrifuged within 30 minutes from collection, and sera were refrigerated (4oC [39.2oF]) Scientific Reports: Retrospective Study

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ischemia, 2 major changes occur in the cells including ATP degradation, which results in accumulation of its by-product, hypoxanthine, and conversion of xanthine dehydrogenase into xanthine oxidase. As oxygen enters previously ischemic tissues, it serves as a substrate for xanthine oxidase, which then transforms excess hypoxanthine into ROS.16,17 When ROS interact with cells, they inflict damage to proteins, DNA, and RNA and cause membrane lipid peroxidation, often leading to cell death.15 Treatment of IRI in experimentally induced GDV in dogs, with deferoxamine (iron chilator) and dimethyl sulfoxide (a free radical scavenger), is reported to reduce mortality rate but has never been used in clinical settings.2 Lidocaine, a local anesthetic and antiarrhythmic agent, has traditionally been used for treatment of ventricular dysrhythmias.18-20 Recently, the IV use of lidocaine to prevent IRI and SIRS was described in humans and laboratory animals.20-26 In veterinary medicine, IV administration of lidocaine was found to be effective in postoperative ileus or enteritis in horses and improved the clinical course in horses with gastric reflux for > 24 hours or volume > 20 L, with minimal adverse effects.27 Although no clinical experiments with prophylactic IV administration of lidocaine to prevent IRI in veterinary medicine have been reported, there is a large body of evidence that supports the use of lidocaine. Possible mechanisms of action of such administration include inhibition of Na+/Ca++ exchange and Ca++ accumulation during ischemia, scavenging of hydroxyl radical, decreasing the release of superoxide from granulocytes, decreasing neutrophil activation, migration into ischemic tissue, and subsequent endothelial dysfunction.3,28,29 The purposes of the study reported here were to determine progression and outcome, identify risk factors for death, and evaluate IV administration of lidocaine as a prophylactic treatment for IRI in GDV in dogs.

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pending analysis that was performed within 24 hours of collection by use of an autoanalyzer.c Blood samples for individual specific, dry biochemical analyses were collected in heparin-treated tubes and analyzed within 30 minutes of collection by use of a dry biochemical analyzer.d Electrolyte analysis was performed from heparinized blood within 30 minutes of collection by use of a specific-electrode electrolyte analyzer.e,f Pre- and postoperative treatment—Preoperative treatment included aggressive IV administration of lactated Ringer’s solution, gastric decompression with stomach tube or trocar, gastric lavage, and IM administration of meperidine. Postoperative treatments included IV administration of lactated Ringer’s solution, fresh frozen plasma (34/112 dogs), and packed RBCs (15/112). Other common medications included antimicrobials, H2-receptor blockers (42/112 dogs), furosemideg (37/112), mannitolh (18/112), and dopaminei (13/112). A urinary catheter was placed in all dogs and urine production was monitored closely. Statistical analysis—Statistical analyses were performed by use of software.j To test the association between 2 categoric variables, the χ2 test and the Fisher exact test were used. The 2-sample t test and the MannWhitney nonparametric test were used to compare quantitative variables between 2 groups. Overall assessment of the association between continuous variables and survival was analyzed by use of the ROC procedure. This was done by calculation of the area under the curve with its 95% confidence interval by use of the nonparametric method. The cutoff points that optimized the overall correct predictors of survival and nonsurvival on the ROC curve were selected for division of continuous variables and their dichotomous transformation. Because no difference was found via analysis based on dogs that were euthanized and dogs that died naturally, these 2 subgroups were combined for the purpose of analysis. Certain variables had not been recorded for some dogs, so denominators for calculation of proportions varied among variables. All tests used were 2-tailed, and P ≤ 0.05 was considered significant. Results One hundred twelve dogs admitted to the HUVTH from 1997 through 2005 with a diagnosis of GDV were included in this study. Median time lag from onset of clinical signs to admission was 3.5 hours (n = 89; SD, 5.85; range, 0.5 to 30 hours). The dogs were allocated into 2 time lag groups via ROC curve analysis (≥ 5 hours [37/89 {41.6%} dogs] and < 5 hours [52/89 {58.4%} dogs]). The mortality rate was significantly (P < 0.001) higher in dogs with time lag of ≥ 5 hours, compared with dogs with time lag of < 5 hours (45.9% vs 11.5%, respectively). Signalment—There was no difference between the prevalence of males and females (60/112 [53.6%] dogs vs 52/112 [46.4%] dogs, respectively). Median age was 8.0 years (n = 112; SD, 3.575; range, 1 to 16 years). German Shepherd Dogs (28.6%) and Great Danes 1336

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(17%) were significantly (P < 0.001) overrepresented, compared with the general hospital population (8% and 1%, respectively). Median body weight was 38.0 kg (83.6 lb; n = 100; SD, 12.8; range, 20 to 80 kg [44 to 176 lb]). Clinical signs—Median rectal temperature at admission was 38.5oC (101.3oF; n = 72; SD, 1.03; range, 35.0o to 40.2oC [95o to 104.4oF]), which was at the lower limit of normothermia (38.5o to 39.5oC [101.3o to 103.1oF]). By use of ROC curve analysis, dogs were allocated into 2 rectal temperature groups (> 38.0oC [> 100.4oF]; 47/72 [65.3%] dogs and ≤ 38.0oC; 25/72 [34.7%] dogs). Mortality rate was significantly (P = 0.019) higher in dogs with a body temperature ≤ 38.0oC (≤ 100.4oF [40.0% vs 14.9% of dogs]). Mean rectal temperature at admission in nonsurvivors (38.0oC [100.4oF]; 17/72 [23.6%] dogs) was significantly (P = 0.032) lower, compared with survivors (38.6oC [101.5oF]; 55/72 [76.4%] dogs). The most common historical and physical examination findings were nonproductive retching (83/99 [83.8%] dogs), hypovolemic shock (79/101 [78.2%]), tachypnea (45/81 [55.6%]), and collapse (23/101 [22.8%]). Only 11 of 99 (11.1%) dogs had a history of productive vomiting. Median heart rate at admission was 140 beats/min (n = 84; SD, 43.9; range, 28 to 240 beats/min). Tachycardia (> 120 beats/min) was recorded in 58 of 84 (69.0%) dogs. Hematologic and coagulation tests—Thrombocytopenia (< 150 X 103 thrombocytes/µL) detected at admission was recorded in 23 of 100 (23.0%) dogs and was not found to be a significant risk factor for death. Coagulation tests were performed in 21 of 112 (18.8%) dogs at admission and in 27 of 112 (24.1%) dogs within 12 hours of admission. Prolongation of PT and aPTT at admission was not a significant risk factor for death. However, prolongation of PT within 12 hours from admission, found in 7 of 27 (25.9%) dogs, was a significant (P = 0.009) risk factor for death, compared with dogs without this finding (57.1% vs 5.0%, respectively). Median serum potassium concentration at admission was 3.85 mmol/L (n = 91; SD, 0.59; range, 2.75 to 7.2 mmol/L). Potassium concentration among survivors (3.84 mmol/L; 21/91 [23.1%] dogs) was significantly (P = 0.009) lower, compared with nonsurvivors (4.23 mmol/L; 70/91 [76.9%] dogs). Median serum creatinine concentration at admission was 1.25 mg/dL (n = 70; SD, 0.55; range, 0.55 to 3.94 mg/dL). High creatinine concentration (> 2.0 mg/ dL) at admission was found in 7 of 70 (10.0%) dogs and was not a risk factor for death. Treatment—Mean duration of lidocaine CRI was 20.8 hours (SD, 19.5; range, 3 to 72 hours). There were no significant differences in prevalence of complications (ARF, DIC, and cardiac arrhythmias) or survival between lidocaine-treated and nontreated groups. There was also no significant difference when the treated and nontreated groups were compared for age, body weight, rectal temperature at admission, or time lag from onset of signs to admission. However, mean hospitalization time was significantly (P = 0.008) longer in the treated group (data available for 48/51 dogs), compared with JAVMA, Vol 230, No. 9, May 1, 2007

Complications—Disseminated intravascular coagulation and cardiac arrhythmias were diagnosed in 18 of 112 (16.1%) and 51 of 112 (45.5%) dogs, respectively. Neither was a risk factor for death. Acute renal failure, diagnosed in 9 of 112 (8.0%) dogs, was a significant (P = 0.005) risk factor for death, compared with dogs without ARF (66.6% vs 23.3%, respectively). The overall mortality rate was 26.8%. Of these, 6 dogs were euthanized during surgery because of severe gastric wall necrosis and 1 dog that deteriorated clinically was euthanized at the owner’s request. Nonsurvivors that were not euthanized during surgery survived for up to 10 days. Discussion Results of this study indicated the importance of the time lag to initiation of treatment as well as resection of suspected necrotic tissue in canine GDV. Initiation of treatment with lidocaine prior to surgery was not associated with reduced risk for complications or improved prognosis but was associated with prolonged hospitalization time. Lidocaine is effective in halting the formation of ROS and membrane lipid peroxidation and in reducing IRI.3,20-25 Canine GDV is an excellent model for intestinal and cardiac reperfusion injury because hydroxyl radical production and neutrophil infiltration of ischemic tissues are implicated as causes of cardiac and gastric necrosis. Previous studies30-33 in experimentally induced GDV in dogs and rats reveal that pre-ischemic lidocaine treatment reduces gastric and cardiac histologic and ultrastructural tissue damage and cardiac arrhythmias. In the present study, the overall mortality rate (26.8%) was similar to that in previous reports.4,7-9 No significant differences were found in mortality rates and prevalence of postoperative complications between dogs that were treated IV with lidocaine prior to surgical intervention and those that were not. Lidocaine treatment was initiated in all treated dogs prior to surgical repositioning of the stomach but JAVMA, Vol 230, No. 9, May 1, 2007

after the initiation of medical treatment and gastric decompression. Reperfusion injury may have commenced by the time lidocaine treatment was initiated, and its severity may have even been exacerbated by aggressive fluid administration, which would have helped distribute the ROS throughout the body. Thus, treatment with lidocaine at this point in the course of the disease may not contribute substantially as a prophylactic measure. Furthermore, following IV bolus administration of lidocaine, onset of action is generally within 2 minutes and duration of action is 10 to 20 minutes, whereas if lidocaine CRI is begun without an initial bolus administered IV, it may take up to an hour for therapeutic concentrations to be reached.34 In the present study, only 8 dogs received IV administration of a lidocaine bolus prior to lidocaine CRI, which may have affected efficacy of the treatment and may explain its failure to improve survival rate and reduce complication rate. The fact that hospitalization time was significantly longer in the lidocaine treatment group was surprising. We speculate that the sedative effects of IV administration of lidocaine may have caused a delay in recovery35 and that prolonged lidocaine CRI may have resulted in temporary immune suppression, as in an experimental study in mice.36 The significant overrepresentation of German Shepherd Dogs (28.6%) and Great Danes (17%) found in this study was similar to that in previous reports.4,7,9,37 Reasons for overrepresentation of large breeds are described and include genetic predisposition, aging, temperament, hormonal influences, feeding regimens, and body conformation.7,37,38 In contrast to a previous report7 in which no difference was found in the survival rates of dogs with different time lags from the commencement of clinical signs to admission, in the present study, mortality rate was significantly higher in dogs with time lag ≥ 5 hours. It can be hypothesized that the severity of gastric wall necrosis, accumulation of ROS, and consequent IRI correlated with the duration of gastric dilatation and volvulus and the severity of vascular obstruction. Thus, gastric decompression and its surgical repositioning and the consequent restoration of blood flow are crucial factors influencing survival rate in dogs with GDV. We believe that these factors are important in improving the prognosis of dogs with GDV, and the sooner these dogs are treated the better. Rectal temperature at admission was significantly higher among survivors than nonsurvivors. Low body temperature can be caused by poor systemic perfusion39 associated with reduced venous return and consequent shock. It may be that lower body temperature reflects the severity of venous obstruction caused by the rotation and dilatation of the stomach and the duration of hypoperfusion. Therefore, body temperature at admission can serve as an indicator of the severity of the patient’s clinical condition. Disseminated intravascular coagulation, diagnosed in 18 of 112 (16.1%) dogs, was not a risk factor for death in the present study. This was in contrast to DIC caused by other etiologies, such as a heat stroke, in which DIC is a significant risk factor for death.40 Thus, it seems that DIC in dogs with GDV can be treated successfully with plasma or, when indicated, with whole blood. The occurrence of DIC was lower in our study (16.1%), compared with a previous report (40%).6 The probable explanation for this difference Scientific Reports: Retrospective Study

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the nontreated group (data available for 45/47 dogs; 3.47 ± 1.93 days vs 2.51 ± 1.42 days, respectively). Gastric decompression was performed prior to surgery in 76 of 112 (67.9%) dogs by use of a trocar or stomach tube (56/112 and 20/112 dogs, respectively). Gastric decompression did not improve survival rate. All dogs were treated surgically. Gastric wall necrosis was suspected during surgery in 27 of 108 (25.0%) dogs for which data were available and was a significant (P < 0.001) risk factor for death, compared with the remaining 81 dogs (59.3% vs 16.0%, respectively). Of the 27 dogs with suspected gastric wall necrosis, 21 of 108 (19.4%) dogs underwent partial gastrectomy whereas the other 6 of 108 (5.6%) dogs were left untreated because of technical difficulty in removing the necrotic tissue. The suspected necrosis in these dogs was located in the stomach fundus (6/6 dogs) and around the cardia (2/6). Untreated suspected necrosis was a significant risk factor for death, compared with surgically treated suspected necrosis (100% vs 47.6%, respectively). Additional findings during surgery included rupture of the stomach wall (4/109 dogs) and volvulus of the stomach to various degrees (90o [6/103]; 180o [59/103]; 270o [22/103]; and 360o [7/103]). In the remaining 9 dogs, no gastric volvulus was found during surgery. Neither rupture of the stomach nor volvulus was a risk factor for death.

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is that in the present study, the definition of DIC included only 3 laboratory variables (platelet count, PT, and aPTT) plus clinical signs, whereas in the other report, the definition of DIC included 6 variables (platelet count, PT, aPTT, antithrombin concentration, fibrinogen concentration, and concentration of fibrin degradation products). We assume that if additional tests had been used, DIC might have been diagnosed more frequently in the present study as well. Although prolongation of PT within 12 hours of admission was found in the present study to be a significant risk factor for death, this finding might have been biased. At least for some of the dogs for which the clinician decided to conduct the PT test, either at admission or within 12 hours, clinical signs suggested a coagulopathy. These tests may, therefore, have not been conducted at random. In the present study, similar to a previous study,7 cardiac arrhythmias were the most frequent complication (45% of dogs). These arrhythmias are the result of myocardial ischemia caused by extracardiac factors, such as hypoperfusion, lactic acidosis, electrolyte imbalance, and IRI.5,18,41 Moreover, under ischemic conditions, the pancreas produces myocardial depressant factor, which, combined with production of oxygen free radicals, further compromises cardiac function.5 Serum concentrations of cardiac troponins are specific markers for myocardial infarction in humans and dogs.41 In that study, dogs with GDV had a highly significant increase in cardiac troponins after 24 and 48 hours, indicating the important role of IRI in the pathogenesis of myocardial damage.41 Because cardiac arrhythmia in the present study was not found as a risk factor for death, antiarrhythmic therapy should probably be considered only if the patient has related clinical signs such as reduced arterial blood pressure, poor perfusion, or both. Bacterial translocation, endotoxemia, sustained reduction of peripheral perfusion, and IRI all contribute to renal damage.5 High serum concentration of creatinine at admission was not a risk factor for death, whereas 24 hours later it was. Therefore, careful monitoring of urine output and serum creatinine concentration as well as fluid treatment is essential for at least 24 hours after surgery. Ischemic reperfusion injury plays a major role in the pathophysiologic features of GDV and its consequent complications. It is therefore imperative to monitor and treat affected dogs for at least 24 hours after surgery. Risk factors for death in the present study included late admission, low body temperature at admission, ARF, and gastric wall necrosis, whether treated or not. Therefore, the presence of these risk factors for death should alert the clinician and warrant aggressive treatment that includes fluid administration; early surgical treatment of gastric wall necrosis; and close postsurgical monitoring for early identification of indictors of DIC, renal failure, and sepsis. Although lidocaine administration to prevent IRI was not effective in the present study, other lidocaine treatment protocols in a prospective study should be investigated.

g. h. i. j.

References 1. 2. 3. 4. 5. 6. 7. 8.

9.

10. 11. 12.

13. 14. 15. 16. 17. 18. 19. 20.

21. a. b. c. d. e. f.

Minos, ST-Vet, Montpelier, France. Abacus, Diatron Messtechnik GmbH, Vienna, Austria. Kone Progress Selective Chemistry Analyzer, Kone Corp Instrument Group, Espoo, Helsinki, Finland. Reflotron, Boehringer, Mannheim, Germany. Nova 8, Nova Biomedical, Waltham, Mass. KC 1A micro, Amelung, Germany, or ACL 200, Instrumentation Laboratory, Tenerife, Spain.

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Fusid, Teva Pharmaceutical Industries Ltd, Jerusalem, Israel. Osmitrol, Baxter Healthcare Corp, Deerfield, Ill. Docard, Dexon Ltd, Hadera, Israel. SPSS for Windows, version 13, SPSS Inc, Chicago, Ill.

22.

23.

Brockman DJ, Holt DE. Management protocol for acute gastric dilatation-volvulus syndrome in dogs. Compend Contin Educ Pract Vet 2000;22:1025–1034. Lantz GC, Badylak SF, Hiles MC, et al. Treatment of reperfusion injury in dogs with experimentally induced gastric dilatationvolvulus. Am J Vet Res 1992;53:1594–1598. Cassutto BH, Gfeller RW. Use of intravenous lidocaine to prevent reperfusion injury and subsequent multiple organ dysfunction syndrome. J Vet Emerg Crit Care 2003;13:137–148. Glickman LT, Glickman NW, Perez CM, et al. Analysis of risk factors for gastric dilatation and dilatation-volvulus in dogs. J Am Vet Med Assoc 1994;204:1465–1471. Monnet E. Gastric dilatation-volvulus syndrome in dogs. Vet Clin North Am Small Anim Pract 2003;33:987–1005. Millis DL, Hauptman JG, Fulton RBJ. Abnormal hemostatic profiles of gastric necrosis in canine gastric dilatation-volvulus. Vet Surg 1993;22:93–97. 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 1995;207:460–464. Brourman JD, Schertel ER, Allen DA, et al. Factors associated with perioperative mortality in dogs with surgically managed gastric dilatation-volvulus: 137 cases (1988–1993). J Am Vet Med Assoc 1996;208:1855–1858. Glickman LT, Lantz GC, Schellenberg DB, et al. A prospective study of survival and recurrence following the acute gastric dilatation-volvulus syndrome in 136 dogs. J Am Anim Hosp Assoc 1998;34:253–259. Matthiesen D. Partial gastrectomy as treatment of gastric volvulus: results in 30 dogs. Vet Surg 1985;14:185–193. Matthiesen D. The gastric dilatation-volvulus complex: medical and surgical considerations. J Am Anim Hosp Assoc 1983;19:922–932. de Papp E, Drobatz KJ, 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 1999;215:49–52. McCord JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 1985;312:159–163. Flaherty JT, Weisfeldt ML. Reperfusion injury. Free Radic Biol Med 1988;5:409–419. Rochat MC. An introduction to reperfusion injury. Compend Contin Educ Pract Vet 1991;13:923–930. Collard CD, Gelman S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology 2001;94:1133–1138. Maxwell SR, Lip GY. Reperfusion injury: a review of the pathophysiology, clinical manifestations and therapeutic options. Int J Cardiol 1997;58:95–117. Knight DH, Allen CL. Ventricular arrhythmias in ICU patients: prevalence, management and outcome assessment, in Proceedings. 15th Am Coll Vet Intern Med Forum 1997;205–207. Barthel H, Ebel D, Mullenheim J, et al. Effect of lidocaine on ischaemic preconditioning in isolated rat heart. Br J Anaesth 2004;93:698–704. Canyon SJ, Dobson GP. Protection against ventricular arrhythmias and cardiac death using adenosine and lidocaine during regional ischemia in the in vivo rat. Am J Physiol Heart Circ Physiol 2004;287:H1286–H1295. Cao H, Kass IS, Cottrell JE, et al. Pre- or post-insult administration of lidocaine or thiopental attenuates cell death in rat hippocampal slice cultures caused by oxygen-glucose deprivation. Anesth Analg 2005;101:1163–1169. Chen MY, Li CH, Huang ZQ, et al. Protective effects of lidocaine injected into the hepatoduodenal ligament on warm ischemia-reperfusion injury to the rat liver. Chin Med J (Engl) 2004;117:275–279. Das KC, Misra HP. Prevention of reperfusion lung injury by liJAVMA, Vol 230, No. 9, May 1, 2007

25. 26.

27. 28.

29.

30. 31.

32.

33. 34. 35.

36.

37. 38. 39.

40. 41.

tric lesions and key role of plasma bicarbonate concentration in dogs with experimentally induced gastric dilatation. Am J Vet Res 1987;48:262–267. Pfeiffer CJ, Keith JC, Cho CH, et al. Gastric and cardiac organoprotection by lidocaine. Acta Physiol Hung 1989;73:129–136. Plumb DC. Lidocaine HCl. In: Veterinary drug handbook. 4th ed. Ames, Iowa: Iowa State University Press, 2002;504. Valverde A, Gunkelt C, Doherty TJ, et al. Effect of a constant rate infusion of lidocaine on the quality of recovery from sevoflurane or isoflurane general anaesthesia in horses. Equine Vet J 2005;37:559–564. Dickstein R, Kiremidjian-Schumacher L, Stotzky G. Effect of lidocaine on the function of immunocompetent cells. II. Chronic in vivo exposure and its effects on mouse lymphocyte activation and expression of immunity. Immunopharmacology 1985;9: 127–139. Glickman LT, Glickman NW, Schellenberg DB, et al. Incidence of and breed-related risk factors for gastric dilatation-volvulus in dogs. J Am Vet Med Assoc 2000;216:40–45. Brockman DJ, Holt DE, Washabau RJ. Pathogenesis of acute canine gastric dilatation-volvulus syndrome: is there a unifying hypothesis? Compend Contin Educ Pract Vet 2000;22:1108–1114. Smith SA, Tobias AH, Jacob KA, et al. Arterial thromboembolism in cats: acute crisis in 127 cases (1992–2001) and longterm management with low-dose aspirin in 24 cases. J Vet Intern Med 2003;17:73–83. Bruchim Y, Klement E, Saragusty J, et al. Heat stroke in dogs: a retrospective study of 54 cases (1999–2004) and analysis of risk factors for death. J Vet Intern Med 2006;20:38–46. Burgener IA, Kovacevic A, Mauldin GN, et al. Cardiac troponins as indicators of acute myocardial damage in dogs. J Vet Intern Med 2006;20:277–283.

Selected abstract for JAVMA readers from the American Journal of Veterinary Research Effect of low doses of cosyntropin on serum cortisol concentrations in clinically normal dogs Linda G. Martin et al Objective—To determine the lowest of 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, or 0.01 µg/kg) administered IV that stimulates maximal cortisol secretion in clinically normal dogs. Animals—10 clinically normal dogs. Procedures—5 dose-response experiments were performed in each of the dogs. Each dog received 5 doses of cosyntropin (1.0, 0.5, 0.1, 0.05, and 0.01 µg/kg) IV in random order (2-week interval between each dose). Serum samples for determination of cortisol concentrations were obtained before (baseline) and at 10, 20, 30, 40, 50, 60, 120, and 240 minutes after cosyntropin administration. Results—Compared with baseline values, mean serum cortisol concentration in the study dogs increased significantly after administration of each of the 5 cosyntropin doses. Mean peak serum cortisol concentration was significantly lower after administration of 0.01, 0.05, and 0.1 µg of cosyntropin/kg, compared with findings after administration of 0.5 and 1.0 µg of cosyntropin/kg. After administration of 0.5 and 1.0 µg of cosyntropin/kg, mean peak serum cortisol concentration did not differ significantly; higher doses of cosyntropin resulted in more sustained increases in serum cortisol concentration, and peak response developed after a longer interval. Conclusions and Clinical Relevance—Administration of cosyntropin IV at a dose of 0.5 µg/kg induced maximal cortisol secretion in healthy dogs. Serum cortisol concentration was reliably increased in all dogs after the administration of each of the 5 doses of cosyntropin. These data should be useful in subsequent studies to evaluate the hypothalamic-pituitary-adrenal axis in healthy and critically ill dogs. (Am J Vet Res 2007;68:555–560)

JAVMA, Vol 230, No. 9, May 1, 2007

May 2007

See the midmonth issues of JAVMA for the expanded table of contents for the AJVR or log on to avmajournals.avma.org for access to all the abstracts.

Scientific Reports: Retrospective Study

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docaine in isolated rat lung ventilated with higher oxygen levels. J Postgrad Med 2003;49:17–20. de Klaver MJ, Buckingham MG, Rich GF. Lidocaine attenuates cytokine-induced cell injury in endothelial and vascular smooth muscle cells. Anesth Analg 2003;97:465–470. Lei B, Popp S, Capuano-Waters C, et al. Effects of delayed administration of low-dose lidocaine on transient focal cerebral ischemia in rats. Anesthesiology 2002;97:1534–1540. Alexander JH, Granger CB, Sadowski Z, et al. Prophylactic lidocaine use in acute myocardial infarction: incidence and outcomes from two international trials. The GUSTO-I and GUSTOIIb Investigators. Am Heart J 1999;137:799–805. Malone E, Ensink J, Turner T, et al. Intravenous continuous infusion of lidocaine for treatment of equine ileus. Vet Surg 2006;35:60–66. Lan W, Harmon D, Wang JH, et al. The effect of lidocaine on in vitro neutrophil and endothelial adhesion molecule expression induced by plasma obtained during tourniquet-induced ischaemia and reperfusion. Eur J Anaesthesiol 2004;21: 892–897. Lan W, Harmon D, Wang JH, et al. The effect of lidocaine on neutrophil CD11b/CD18 and endothelial ICAM-1 expression and IL-1beta concentrations induced by hypoxia-reoxygenation. Eur J Anaesthesiol 2004;21:967–972. Kamiyama T, Tanonaka K, Harada H, et al. Mexiletine and lidocaine reduce post-ischemic functional and biochemical dysfunction of perfused hearts. Eur J Pharmacol 1995;272:151–158. van Emous JG, Nederhoff MG, Ruigrok TJ, et al. The role of the Na+ channel in the accumulation of intracellular Na+ during myocardial ischemia: consequences for post-ischemic recovery. J Mol Cell Cardiol 1997;29:85–96. Pfeiffer CJ, Keith JC Jr, April M. Topographic localization of gas-