GDV: Past Present and Future Mauricio Dujowich, DVM, DACVS Veterinary Specialty Hospital Management Absolute Emergency! Medical management alone is not enough Need to stabilize as much as possible by treating shock and decompressing stomach Emergency surgery Gastric Dilatation Volvulus Abnormal rotation of stomach Results in obstruction of blood flow Systemic Shock Necrosis of stomach Damage to spleen Death Management Catheterize patient (front limbs) Bolus fluids/blood Pressure Decompress Stomach Blood work (CBC, Chem, Lactate) ECG Any other supportive care you deem necessary Clinical Signs Wretching Bloat/Abdominal Distension Lethargy Anorexia Collapse GDV Surgery Main goal is to de-rotate stomach Assess damage and determine if stomach is viable Check viability of the spleen Perform a gastropexy to prevent recurrence 1
GDV Survival Survival depends on degree of shock and damage to the patient 10-25% mortality rate (was as high as 42%) Post-operative care is intensive and patients may die despite surviving surgery GDV Survival Lactate < 6mmol/L associated with 00% survival Lactate >6mmol/L associated with 58% survival Lactate < 9mmol/L associated with 90% survival Lactate > 9mmol/L associated with 54% survival If you have a high initial lactate (>9mmol/L) your survival rate is better if your final concentration is <6.4mmol/L, you have an absolute change of lactate concentration of > 4mmol/L or a percentage change of > 42.5% GDV Survival If recumbent 4.4 times more likely to die If comatose 36 times more likely to die If gastric necrosis is present there is an 11 fold increase in death Gastric necrosis is associated with 46% mortality Increased time from presentation to surgery associated with lower mortality Who is predisposed Large and Giant Breed Dogs Anxious Dogs Dogs that eat very fast Sibling of dog that had a GDV GDV Survival If you need to perform a gastrectomy you have a 9-35% higher likelihood of death If you need to perform a splenectomy then there is a 15-32% increase in death If you need to perform both there is a 20% increase in death If there are cardiac arrhythmias present there is a 38% increase in likelihood of death What Are My Dog s Chances of Getting a GDV? Somewhere between 4-37% lifetime likelihood that your dog will develop a GDV Depends on the breed Great Dane is most likely 2
Treatment Re-dilatation cannot occur Stomach is decompressed and blood supply returned Concentrate on the animal s cardiovascular needs Shock Any arrhythmias that develop Corrective surgery when stable!!!!! Prevention Small frequent meals Reduce speed of eating Do not feed in elevated bowl Avoid foods with particle diameter <30mm Avoid increased stress in anxious animals Do not breed animals with a first degree relative that has had a GDV Prophylactic gastropexy Surgery Release the Temporary Gastrostomy Amputate exposed stomach Gastrotomy closure Cranial Abdominal Exploratory Gastric Repositioning Most are repositioned Good blood supply Current Options Incisional Belt-loop Incorporating Circumcostal Grid-approach Laparoscopic assisted Total laparoscopic Surgery Gastric evaluation for necrosis 24-48 hours have allowed the compromised areas to delineate themselves Gastric resection decisions are made easier Antral gastropexy procedure Incisional gastropexy Objective Identify surgical failure in clinical patients Identify immediate complications Identify long term complications 3
Methods 24 client owned animals Randomly split in two groups Group A laparoscopically evaluated 1 month after procedure Group B laparoscopically evaluated 6 months after procedure Complications No immediate surgical complications Two dogs experience vomiting within 4 weeks of surgery Vomiting resolved with conservative therapy (famotidine) Four dogs experienced diarrhea within 4 weeks of surgery Diarrhea resolved without medical intervention Surgical Procedure Previously validated 12 research dogs euthanized for other reasons Complications included needle bending and breaking which resolved after proper needle selection Laparoscopic Results 10 dogs underwent recheck at one month 9 dogs underwent recheck at six months All gastropexies found to be sutured at the level of the pyloric antrum in both groups All gastropexies were strongly adhered to the body wall Dujowich M, Reimer SB: evaluation of an endoscopically assisted gastropexy technique in dogs. Am J vet Res 69:537 541, 2008 Results 24 dogs underwent procedure 10 Great Danes, all others were also considered predisposed to GDV based on signalment Age 2.3 ± 1.9 yr (range 0.3-8.3 yr) Weight 41.5 ± 17.3 kg (range 12.5 79.1 kg) Mean gastropexy length 4.5 ± 0.9 cm Mean duration of surgery 22 ± 5 min (range 15 35 min) Laparoscopic Recheck Results Biopsy of gastropexies for both groups showed one or more of the following: Mature granulation tissue Fibrous connective tissue Tunica muscularis 4
Long Term Outcome No GDV episodes in 1.4 ± 0.3 yrs in 23 dogs available for follow-up Endoscopically Assisted Gastropexy Advantages Minimally invasive Easy to perform Can be performed quickly Inexpensive Disadvantages Endoscope may not be readily available Patient positioning may be a hassle Unknown failure rate Discussion Technique likely results in a very strong fibrous adhesion Procedure maximizes the benefits associated with minimally invasive surgery Discussion Rapid, inexpensive, and reliable method for performing an endoscopically assisted gastropexy in dogs 5
The Neurological Examination Robin Levitski-Osgood, DVM, DACVIM (Neurology) The neurological examination, in combination with the patient s signalment and history, is used to document neurological disease and to localize the lesion. Perfoming the exam in the same order each time helps to ensure certain tests are not forgotten and minor deficits are not missed. At the end of the exam, the abnormal findings are used to localize the lesion. Once the lesion has been localized, a list of differential diagnoses can be constructed and the appropriate diagnostic procedures can be recommended. The mentation of the patient can be evaluated while taking the history. There are many different degrees of awareness: normal, obtunded (dull), stuporous (responds to moderate stimulation), semi-comatose (patient can be aroused with vigorous stimulation), and comatose (nonrousable). Some patients may act demented, hyper-excitable, hyper-aggressive, stand with their head pressed into the corner, or pace compulsively. Posture can also be evaluated at the same time. Evaluate the head (head tilt, head turn, head bobbing/tremors, wide excursions of the head), tail (low tail carriage, flaccid) and limb (knuckling on paw, holding limb up, wide based vs. narrow based, crouched) position. If the patient is recumbent, are they exhibiting Schiff-Sherrington (normal mentation, paraplegia, extensor rigidity thoracic limbs), decerebellate (normal mentation, dorsoflexion of the neck, extensor rigidity thoracic limbs, flexion pelvic limbs), or decerebrate (comatose, dorsoflexion of the neck, extensor rigidity all limbs) posture? All three of these postures can look similar when the patient is in lateral recumbency. Watching the patient ambulate on a non-slippery surface, turn to the left and right, and navigate a few steps or a curb is a very important part of the exam. The gait is examined for both strength and coordination. Watching the patient walk in a small exam room is not enough to fully evaluate the gait. Weakness is termed paresis. The patient may be monoparetic (one leg), paraparetic (pelvic limbs), hemiparetic (thoracic and pelvic on one side), or tetraparetic (all four legs). Absence of voluntary motion is paralysis/plegia. Again, the patient may have a mono, para, hemi or tetraplegia. A withdrawal of the leg when the toes are pinched is not considered voluntary motion. Lameness, ataxia, dysmetria, hypermetria, scuffing of the toe nails, and circling are other signs that may be observed during the gait evaluation. Cranial nerves are examined in order from CN I to CN XII. These tests evaluate the function of the cranial peripheral nerve and the specific area of the brain stem from which the nerve arises. Common cranial nerve tests include visual tracking, menace, pupillary light reflex, comparing pupil size, presence of normal physiologic nystagmus, strabismus, size of muscles of mastication,
sensation to the face, corneal reflex, palpebral, vibrissae and auricular reflex, head tilt, head turn, resting or spontaneous nystagmus, gag reflex, presence of stridor, and unilateral atrophy of the tongue. When testing conscious proprioception the patient must be supported properly when lifting and turning the paw over, and then observed to see if they correct the abnormal position. Wheelbarrowing, hopping, extensor postural thrust with the pelvic limbs, visual placing and tactile placing can be performed to evaluate postural reactions in the cat and small to medium sized dogs. The common spinal reflexes that are tested include the bicep, tricep, patellar, gastrocnemius, withdrawal reflexes. The limbs should be relaxed when testing. The reflex is either absent, decreased, or present/brisk. The patellar reflex is the most useful and easy to grade monosynaptic reflex, while the tricep reflex is the least useful. The withdrawal reflex is tested by lightly pinching or wiggling your fingers in the interdigital tissue and observing flexion of the limb. The opposite limb is observed for an exaggerated crossed extensor reflex which indicates upper motor neuron damage. The withdrawal reflex is a spinal reflex only, and does not evaluate voluntary motion or the presence or absence of deep pain. The cutaneous trunci (CT) or panniculus reflex is twitching of the skin in response to pinching. It can be tested from the L4 region up to T2 along both sides of the spine. The area where the CT response changes from being absent to being intact is an indicator of where the spinal cord white matter is damaged. The CT can be helpful in localizing T3-L3 lesions. The perineal reflex can be evaluated when the patient s temperature is taken. The spine is palpated for areas of increased sensitivity or pain. Support under the thorax and abdomen when palpating the thoracolumbar spine. Cervical range of motion can be evaluated by having the patient follow a treat to both sides and then up and down. Muscle size, tone and symmetry is also evaluated. Somatosensory function is typically tested by applying a painful stimulus and watching for a behavioral response such as turning the head, crying, trying to bite, pupillary dilation, or cessation of panting. This is usually tested at the end of the exam. Pinch the skin to check for superficial pain and pinch the bone of the digit for deep pain. If a patient has voluntary motion, you do not need to test for superficial or deep pain sensation.
Current Trends in Veterinary Orthopedics Locking Plate Technology Fluoroscopic Assisted Surgery Current Trends in Veterinary Orthopedics Arthroscopic Assisted Surgery Hip Resurfacing Scapulohumeral Joint Medial Shoulder Instability (MSI) Previously diagnosed only in performance dogs, MSI is being diagnosed with increasing frequency Lameness can range from decreased performance to intermittently non-weightbearing Pathology can affect the medial glenohumeral ligament, subscapularis tendon or occasional the biceps tenon 1
Scapulohumeral Joint Medial Shoulder Instability (MSI) Differs from rotator cuff injury in that injury generally affects the ligaments of the canine shoulder and not the musculotendinous component Anatomic differences in the scapulohumeral articualtion and range of motion are contributing factors Scapulohumeral Joint Medial Shoulder Instability Canine Shoulder Human Shoulder Medial Shoulder Instability 2
MSI Diagnosis Abduction angle MSI Diagnosis (MRI) Parenchymal Hemorrhage Normal Biceps Tendon Medial Compartment Pathology (Subscapularis Tear) 3
MSI Diagnosis Arthroscopy MSI Repair Scapulohumeral Joint Tightrope 4
Shoulder Hobbles for MSI www.dogleggs.com Arthroscopic Assisted Surgery (Glenoid Avulsion) Glenoid Avulsion 5
Glenoid Avulsion Glenoid Avulsion Immediate Postoperative Glenoid Avulsion 8 week postoperative 6
Fracture Management For decades, anatomic reconstruction / reduction using a dynamic compression plate has been the gold standard for fracture repair In recent years, a paradigm shift has occurred towards minimally invasive approaches and biologically friendly internal fixation for complex fracture repair Fracture Management Biologically friendly internal fixation minimizes the soft-tissue stripping that can further contribute to biologic insult largely through vascular compromise The identification of growth factors and their presence in the fracture hematoma have reiterated the biologic fixation theory Look but don t touch Locking Plate Technology Locking technology involves both securing the screw to the fracture and locking the screw to the plate. The technique differs from tradition bone plating in which friction between the bone plate and bone cortex provided stability. Locking the screw to the bone plate greatly increases the stability of the repair and helps decrease the potential for implant loosening and fragment translocation. The locking plates act similar to an external fixator but is placed adjacent to the bone 7
Locking Plate Technology Locking plate systems offer is the ability to allow potential for minimally invasive fracture fixation (percutaneous plating) Joint preservation vs replacement Joint preservation vs replacement 8
Biologic Fixation Maxillofacial Surgery Spinal fractures / Stabilization 9
Advanced Osteotomy Techniques (Sliding Humeral Osteotomy) Hip Resurfacing Clinical Trial Starting Soon 10
CH 3 8/16/2010 H 3 CO NH H3C CH 3 N. HO 2 C CO 2 H HO CO 2 H. H 2 O Keith Richter, DVM, Diplomate ACVIM Veterinary Specialty Hospital of San Diego Cerebral Cortex α2, ENKμ, GABA CRTZ D2, α2, ENK, H1 5-HT3, M1, NK1 Emetic Center (EC) 5-HT, α2, NK1 Abdominal Organs 5-HT3, 5-HT4 M1, NK1 Emetic Receptors Higher Brain Vestibular apparatus Metoclopramide works here on dopamine receptors CRTZ VA Emetic Center CERENIA works in both places 1
8/16/2010 Only maropitant has anti-emetic properties that block vomiting caused by two powerful emetogens 20 2.0 Mean Number 1.5 of Emetic Events 1.0 Efficacy in Preventing Vomiting Induced by Known Emetogens 2.5 Ipecac ** Apomorphine 0.5 ** ** 0.0 Placebo Maropitant Metoclopramide Chlorpromazine Ondansetron **Statistically different from maropitant at P<0.05 Statistically different from maropitant at P<0.05 Pfizer studies 1961R-60-05-715 and 1961R-60-05-716 Cerenia 2 mg/kg orally 100% enter GIT Drug Portal vein Liver CYP Absorption efflux P-gP Metabolism CYP CYP CYP CYP CYP CYP CYP CYP Bioavailability 24% Out (Oral bioavailability) To feces Gut wall First Pass metabolism Cerenia is the first FDA approved product to prevent and treat emesis in the dog and launched in the US in 2007 Since launch, roughly 2.8 million dogs have been treated with Cerenia Adverse events with Cerenia have been mild and similar to those seen during the registration trials with the exception of injection-related stinging Mechanism: NK-1 antagonist Neurotransmitter: Substance P 2
8/16/2010 Common current use is prevention and treatment of chemotherapy- related emesis There has been a label change in Europe; indication for use for nausea secondary to chemotherapy Was not reported in a large number of dogs in clinical studies Occurrence in pre-approval studies similar to saline and metoclopramide Therefore the stinging i reported postapproval was unexpected The injectable product is primarily sterile water and maropitant but includes an agent to increase solubility and a preservative Post approval investigation More maropitant is bound to solubility agent at refrigerated temperatures versus room temperature A laboratory study demonstrated t d reduced d stinging when product is administered directly from refrigerator versus at room temperature Suggests that increased amount of unbound maropitant results in higher rate of stinging Narishetty ST, Glavan B, Coscaelli E, Aleo M, Fleck T, Humphrey, W, McCall, RB: Effect of Refrigeration of the Antiemetic Cerenia (Maropitant) on Pain on Injection. Vet Therapeutics: Vol 10, No3, Fall 2009, 93-100. 3
8/16/2010 Stability studies support use of refrigerated product Portions of the field studies in the US and EU were conducted with refrigerated product with no effect on efficacy At product launch, broached vial shelf life was listed on the label for 28 days Label reflected stability study conducted for global approval EU restricts broached vials for 28 days Pfizer conducted a 90 day broached vial stability study and submitted the results to FDA/CVM data was accepted and label was changed Well tolerated at anti-emetic doses 15 days at up to 5 mg/kg sid T1/2 = 13-17 hours: once daily dosing Clearance much slower than dogs No drug accumulation (vs. early suggestion in dogs) Bioavailability ~50% (oral); ~100% SQ Efficacy demonstrated against emesis induced by xylazine and motion Ferris wheel! 1 mg/kg sid PO or SQ Hickman, et al. J Vet Pharmacol Therap 31 2008 4
8/16/2010 Three studies conducted using different methods in healthy adult laboratory dogs Studies conducted with a placebo group and positive control groups dosed with cisapride, erythromycin and metoclopramide No difference was detected between treatment groups; unclear what effect NK1 antagonism has on abdominal organ NK1 receptors and GI motility Dog to dog variability was high in all studies; does not appear to be a good healthy dog model to evaluate for pro-kinetic effect of any medication Study by Twedt, et al was presented as an abstract at the 2009 ACVIM meeting Definitive studies demonstrating safety in puppies < 16 weeks was not available at product launch Three studies were conducted prior to approval and showed histopathologic evidence of bone marrow suppression in both maropitant and placebo treated puppies Changes were observed at higher frequency and greater severity in maropitant-treated puppies Confounding factors such as coccidiosis, parvovirus, early weaning / stress prevented conclusions Dosing was at 1, 3 and 5 times the label dose for 15 days Additional study conducted post-launch; to be submitted for publication Included 40 puppies 9-10 weeks of age Five treatment groups (8 puppies/treatment): Placebo orally X 2 days Placebo subcutaneously X 5 days Maropitant 1 mg/kg subcutaneously X 5 days Maropitant 2 mg/kg orally X 5 days Maropitant 8 mg/kg orally X 2 days All bone marrow samples were normal Puppies were dosed according to label only 5
8/16/2010 Maropitant at 1 mg/kg reduces anes requirement 25%. This compares favorably with morphine (35%), and much better than butorphanol (8%) and carprofen (12%) There are NK-1 receptors throughout the nervous system Many examples demonstrating the role of substance P in nociception Pedro Boscan; Gutski 2010 Laparoscopic Spay Model: Maropitant decreased the anesthetic requirements during stimulation of the ovarian ligament in dogs: 24% at 1 mg/kg; 30% at 5 mg/kg This suggests for the first time the use of an NK-1 receptor antagonist to treat visceral pain Pedro Boscan; Gutski 2010 Chronic use beyond 5 continuous days I have personally used in this way for the past year w/o apparent negative impact Original recommendation based on pharmacokinetic modeling, not drug accumulation study Splitting of pills Is stable and no loss of efficacy is expected; I have used split pills when reasonable since approval w/o no apparent change in efficacy 6