2016 FALL: Negative Pressure Wound Therapy | Degenerative Valve Disease | Platelet Transfusions | New Doctors | Continuing Education
Negative Pressure Wound Therapy (NPWT):
A Better Solution for Complex Wounds
Jennifer Weh, DVM, DACVS-SA
Wounds are a common cause of morbidity in our patients, and management of complex wounds can be prolonged and debilitating, leading to long hospital stays, painful and labor-intensive bandaging, and significant financial hardship. The most successful wound care plan takes into consideration all of the components of a wound (depth, degree of contamination, size, location, chronicity) as well as the clinical presentation of the patient (systemic health, personality, age). We have come a long way from the time of the wet-to-dry bandage, and today there are a number of moist wound care products to choose from that follow the typical course of healing through inflammation, proliferation, and finally maturation.
Jennifer Weh, DVM, DACVS-SA
Negative pressure wound therapy (NPWT) is a wound healing modality that intervenes at the proliferation stage of healing and has some pretty amazing results. Functionally, NPWT is the application of subatmospheric pressure to a wound bed, open or closed, through foam dressing. This results in decreased interstitial edema, reduced bacterial load, the creation of a closed environment, improved circulation and enhanced granulation bed formation. While there’s never only one way to treat a wound, I have found that in some cases NPWT is the most efficient path to resolution. Faster granulation bed formation means fewer trips to the hospital, fewer bandage changes and often sets the stage for earlier delayed primary closure.
Nuts and bolts of bandage application
NPWT bandages have to be applied at the right time to the right wounds. They have no part in the debridement phase of a dirty, devitalized or infected wound. After adequate debridement (that may take several days), the bandage is applied. This consists of open cell foam covered by adaptic dressing placed within the wound bed. Skin edges can be advanced to the foam edges as determined by the wound configuration. Adhesive drape material covers the entire dressing and tubing that connects the foam to a vacuum pump and collection reservoir. Negative 125 mmHg is an adequate setting for most applications, and the bandage can stay in place for up to 72 hours. Most commonly, NPWT therapy is used for 3 to 6 days, but the bandage is often only changed once under moderate sedation. This results in a hospitalized patient who needs less sedation or anesthesia, gets more consistent nutrition, and is more comfortable and amenable to treatment.
Photo 1: Placement of foam dressing within a septic incisional dehiscence wound
Photo 2: After placement of tubing and adhesive dressing
Photo 3: After 6 days of NPWT
Photo 4: Closure
Photo 1: Multiple wounds, such as these bite wounds, can be treated in one bandage.
Photo 2: Foam bridges connect wound dressings.
Photo 3: After placement of the adhesive
Photo 4: Patients are comfortable with the NPWT bandage in place.
How does it work?
The application of uniform negative pressure to a wound bed removes from the area interstitial fluid that contains high levels of inflammatory cytokines and proteases in chronic wounds. It also helps to decrease the local pressure which can increase perfusion pressure and restore blood flow to previously collapsed capillaries and lymphatics.1 Negative pressure also has a direct effect on blood vessels by increasing vascular diameter and blood velocity and by initiating earlier angiogenesis – within the first hours of the application of negative pressure.2,3 Negative pressure also deforms tissue by deforming the skin edges and limiting the loss of domain that happens when wound edges naturally retract. On a microscopic level, the mechanical force of microdeformation has a fundamental role in regulating tissue growth by placing traction on the extracellular matrix and thereby turning on growth factors that regulate cellular proliferation.4 This is similar to the Ilizarov technique of distraction osteogenesis, which is based on the principal that tissue, in this case bone, responds to mechanical tension. Finally, NPWT stabilizes the wound environment by creating a semipermeable membrane that keeps ongoing contamination out, provides an appropriate electrolyte balance, and maintains body temperature. Under these conditions and through these mechanisms, granulation tissue forms more quickly.
NPWT was developed for humans to treat diabetic ulcers and open fractures. Since its inception over 500 peer-reviewed articles have been published in the human literature reporting its efficacy. Veterinarians have adapted the use of NPWT to our patients over the past 15 or so years, but evidence of efficacy is sporadic. Excellent evidence supports the use of NPWT in early treatment of distal extremity shearing wounds5 and to stabilize full thickness skin grafts.6 It was confirmed to speed the formation of smooth, nonexuberant granulation tissue in acute wounds7 and as an acceptable modality in treating traumatic wounds.8 Veterinarians at the University of Florida have reported its successful use in other applications including skin avulsions, degloving injuries, abdominal and thoracic wounds, surgical dehiscence, chronic nonhealing wounds, to prevent postoperative edema, and myofascial compartment syndrome.9 NPWT is contraindicated in a few cases in which cancer cells or overexposed vessels are present in the wound bed, in the face of active bleeding, or in devitalized tissue beds. Complications are few and are usually technical issues related to the application or use of the system. Mild skin irritation of surrounding skin can develop from the tissue adhesive and drape. In my experience, as with any wound care tool, NPWT works best in carefully selected wounds. It has proven significantly effective in our patients in many traumatic wounds resulting in more comfortable and earlier wound closure. Let us help you to determine if NPWT may be helpful in your complicated wound cases.
1Morykwas MJ, Argenta LC, Shelton-Brown EI, et al. Vacuum-assisted closure: A new method for wound control and treatment: Animal studies and basic foundation. Ann Plast Surg. 83(6): 553-562. 1997.
2Huang S, Chen CS, and Ingber DE. Control of cyclin D1, p27 (Kip1), and cell cycle progression in human capillary endothelial cells by cell shape and cytoskeletal tension. Mol Biol Cell. 9:3179-3193, 1998.
3Chen S, et al. Asian J Surg, 2005.
4Pietramaggiori G, Liu P, Scherer SS, Kaipainen A, Prsa MJ, Mayber H, et al. Tensile forces stimulate vascular remodeling and epidermal cell proliferation. Ann Surg. Nov;246(5):896-902. 2007.
5Ben-Amotz R, Lanz O, Miller JM, et al. The use of vacuum-assisted closure therapy for the treatment of distal extremity wounds in 15 dogs. Vet Surg. 36(7):684-690. 2007.
6Stanley BJ, Pitt KA, Weder CD, et al. Effects of negative pressure wound therapy on healing of free full-thickness skin grafts in dogs. Vet Surg. 42(5): 511-522. 2013.
7Demaria M, Stanley, BJ, Hauptman JG, et al. Effects of negative pressure wound therapy on healing of open wounds in dogs. Vet Surg. 40(6): 658-669. 2011.
8Pitt KA and Stanley BJ. Negative pressure wound therapy: Experience in 45 dogs. Vet Surg. 43(4): 380-387. 2014.
9Kirby KA, Wheeler JL, Farese JP, et al. Vacuum-assisted wound closure: Clinical applications. Compendium. 2010.
Treating the “In-Between” Patients with Degenerative Valve Disease
Mikaela Mueller, DVM, DACVIM-Cardiology
Degenerative valve disease, or endocardiosis, is a disease that affects many canine patients, particularly small-breed dogs. The vast majority of our patients with degenerative valve disease are at the “in-between” stage, where they have a heart murmur and various levels of left-sided cardiomegaly, but are not yet in congestive heart failure. Many patients stay in this preclinical, in-between stage for their entire lives, but there is still the unlucky handful that do progress to congestive heart failure, typically with pulmonary edema. Studies such as the PREDICT cohort study, along with some common sense, indicate that left atrial enlargement and biomarkers such as NT-proBNP, can signal patients that are at a higher risk of developing congestive heart failure in the near future. However, it is more difficult to predict the clinical course that patients will experience when they are still in the more mild stages of the disease.
Mikaela Mueller, DVM, DACVIM-Cardiology
As doctors, we want to be able to fix problems for our patients. Sadly, this is one disease that we cannot fix (yet). We have been frustrated alongside our clients with nothing to offer them in this common preclinical stage. One intervention that has gotten a lot of research attention is ACE-inhibitors. We seem to really want them to make a difference in delaying the time to onset of congestive heart failure, maybe because we can make physiological justifications for why ACE-inhibitors should, theoretically, help. Multiple studies have shown “trends” to improvement, but no statistical significance (VETPROOF, SVEP). Many arguments suggest that we simply haven’t performed the right study to find the benefit, but one could also argue that if multiple different studies didn’t show a statistical difference, then the true benefit is likely modest, at best. That said, I think many of us have prescribed ACE-inhibitors in the preclinical stage just in case it does help. It makes us, and our clients, feel like we are doing something that may possibly help, while we are, in all honesty, in a position where our hands are tied. All of that changed with the release of the EPIC study results at ACVIM in June 2016.
Historically, we have found that pimobendan out-performs ACE-inhibitors after the onset of congestive heart failure by reducing heart size and retention of free water (QUEST study). The EPIC study (Evaluation of Pimobendan in Dogs with Cardiomegaly) was a prospective, double-blind, randomized, placebo-controlled, international, multi-center study that was started in June 2010. Pimobendan (or placebo) was administered chronically to small-breed (4.1-15 kg) canine patients with cardiomegaly due to degenerative valve disease (ACVIM Stage B2) to determine if it could delay the onset of congestive heart failure. For the study, 360 patients were enrolled – 180 dogs in the pimobendan group and 180 dogs in the placebo group. The primary endpoint was the development of left-sided congestive heart failure or death due to a cardiac cause.
A planned interim analysis was conducted, showing a significant benefit in the administration of pimobendan prior to the onset of clinical signs, and no concerns over safety were found. The investigators found that the time to the primary endpoint was increased by over a year. Patients in the pimobendan group did not live as long as the placebo group after the onset of congestive heart failure, but overall survival time (all-cause mortality) was increased. Said another way, patients that receive pimobendan starting in the preclinical stage (ACVIM Stage B2) live longer than those who don’t and spend less of their life battling clinical signs of congestive heart failure. The results were significant enough that the study was prematurely discontinued in March 2015.
One of the major concerns with the EPIC study is that many dogs with only mild enlargement never experience clinical signs of congestive heart failure in the first place, so treating them long-term with pimobendan does not change their clinical outcome. Luckily, it appears to be a very safe medication for the majority of patients, but it is not a cheap medication to give for years when it does not change the outcome. Since we do not have a good way of predicting which dogs with mild disease will progress to clinical signs, it becomes difficult to decide whether or not to recommend pimobendan for some patients.
This is where the art of clinical practice comes into play. Each patient is an individual who deserves personalized thought and attention. If a patient has mild cardiomegaly and is already 16 years old, it is far less likely that the patient will progress to congestive heart failure during his or her lifetime than a different patient with similar disease who is only 5 years old. Also, does the patient have other clinical diseases that otherwise limit its lifetime? Potentially, these patients will not be expected to benefit from chronic pimobendan administration. Since the EPIC study was announced, I have started to recommend giving pimobendan with increased urgency to patients of mine with progressive cardiomegaly. When in doubt, I often take the approach of educating the owners on the potential benefits and the downfalls of starting their dog on pimobendan at any given time, empowering them to make the decision that is best for them and their companion.
Questions still remain about the best way to treat patients at various stages of degenerative valve disease, and I imagine that questions will always remain since each patient is a different case to consider. Like the rest of us, I anxiously await publication of the EPIC study results. I have to admit, though, it feels good to have something to offer many of my clients when their patients are “in-between.”
Platelet Transfusions: Do We Use Them?
Beth Davidow, DVM, DACVECC
Platelets are cytoplasmic fragments that circulate in the blood and are crucial for the initial formation of a clot. Platelets bind to exposed factors in damaged blood vessels and then bind to fibrinogen to form a clot. When activated, platelets also bind coagulation proteins to keep them at the site of the injury.
Beth Davidow, DVM, DACVECC
Platelets are short-lived and much more fragile than red blood cells or plasma proteins. Average platelet life span in the dog is 5-7 days. Platelets are quickly activated and no longer useable when refrigerated. Thus, platelet products for transfusion must be stored at room temperature, constantly agitated, and due to the risk of bacterial contamination, can only be stored for 5 days.
Thrombocytopenia, or low platelet count, is seen commonly in emergent veterinary patients but because of the complexity of storage and distribution, platelet transfusions are not often used in veterinary medicine.
Thrombocytopenia can be caused by decreased production, accelerated removal, increased consumption, loss, or dilution of platelets. The most common cause of thrombocytopenia in dogs is immune-mediated thrombocytopenia (ITP).3,4 Other causes include infectious diseases such as ehrlichiosis, bone marrow insults, neoplasia, disseminated intravascular coagulation (DIC) and blood loss.
Therapy with certain drugs can also result in thrombocytopenia. Azathioprine and chloramphenicol can lead to thrombocytopenia through a dose-related effect on the bone marrow. In people, heparin can cause thrombocytopenia. Drug therapy with potentiated sulfonamides can also result in an immune-related thrombocytopenia in both dogs and people.
In the inherited macrothrombocytopenia of cavalier King Charles spaniels, a genetic mutation in the beta-tubulin protein of the microtubules is known to be the cause. Cavaliers affected with this condition can have platelet counts as low as 50,000/ul but often have no signs of bleeding. It is important to distinguish this condition from immune causes of platelet destruction as these animals do not require treatment.
In thrombocytopathic conditions, platelet numbers are normal but function is impaired. Acquired loss of platelet function is associated with medications and certain disease states. Non-steroidal anti-inflammatory drugs such as aspirin can decrease platelet function. Animals with both hepatic disease and uremia can also have platelet function issues.
We count on donor dogs like Wilson to help us maintain our supply of blood products.
Several hereditary thrombocytopathias have been identified in dogs and cats.8 Glanzmann thrombasthenia is a genetic disease that has been documented in great Pyrenees and otterhounds. Basset hounds can also have a genetic issue with platelet function.
Indications for platelet transfusions
In humans, platelets are recommended for prophylaxis in any patient with a count less than 10,000/ul and in patients who need an invasive procedure with counts less than 50,000/ul. Platelets are recommended therapeutically in any actively bleeding patient with a count less than 20,000/ul. Platelets are also recommended in patients with drug or hereditary impairment of platelet function that need an invasive procedure. However, ITP is considered a unique situation due to the rapid clearance of any administered platelets. In addition, platelets in ITP are often younger and hyperfunctional so that bleeding may not occur until counts are extremely low. Platelet transfusions are usually NOT recommended for prophylaxis in this disease.
The risk of bleeding with thrombocytopenia is affected by the degree of anemia. A higher packed cell volume reduces the risk of bleeding. Thus, in cases of moderate thrombocytopenia and concurrent anemia, the risk of bleeding may be lessened with packed RBC transfusion alone.
The risk of bleeding from thrombocytopenia must be weighed against the risk of transfusion reaction especially when prophylactic platelet transfusions are considered. The reported rate of febrile reactions in people is 38% while 2% have a severe adverse reaction.
The standard fresh platelet concentrate dose of 1 U per 10 kg was derived to aim for a 40,000/ul increase in platelet count. Some investigators have looked at whether the interval between transfusions could be extended by using a higher dose initially. A meta-analysis in humans did show an increase in the interval between transfusions when a higher initial dose was used.
Currently Available Products
Fresh whole blood is the product most veterinarians use when platelets are needed. A 500 ml unit of fresh whole blood obtained from a canine donor is estimated to contain 7 X 1010 platelets. A dose of 10ml/kg of whole blood would be expected to raise the platelet count about 10,000/ul. The advantage of fresh whole blood is that no platelets are lost during separation. In addition, the platelets are less activated than in platelets obtained via centrifugation for concentrate. Fresh whole blood at room temperature is considered safe for use for 4-8 hours. As mentioned above, refrigeration of blood rapidly renders the platelets unusable for coagulation.
Fresh platelet concentrate has traditionally been made when initially processing whole blood. Whole blood is spun using a “soft” spin which separates the platelets into the plasma component, which is expressed into a separate bag. This plasma is then known as platelet rich plasma (PRP). The PRP is then spun again to create a platelet concentrate (PC), and the plasma is removed and stored as fresh frozen plasma. One unit of PC is the amount made from one unit (500 ml) of whole blood but will contain a lower amount of platelets. A recent study showed a maximum in vivo platelet recovery of 80%. The dose is normally calculated as 1 unit/10 kg. Fresh platelets must be stored in gas soluble bags at room temperature to remain active. They must also be constantly agitated and thus are kept on continuous rockers. Bacterial contamination is a concern at room temperature and storage is limited to 5 days. Because of the paucity of use and complexity of storage, the ACCES Blood Bank makes platelet rich plasma only on an as needed basis. This product cannot be easily shipped.
Frozen platelet concentrate is made by stabilizing apheresed platelets with 6% DMSO or with 2% DMSO and ThromboSol. In the original studies, canine platelet recovery after freezing with 6% DMSO at -80° F was shown to be 70% with a halfl-life of 2 days versus 3.5 days for fresh platelets.19 The platelets were shown to be effective in halting active bleeding in thrombocytopenic dogs. A more recent study comparing 6% DMSO to 2% DMSO and ThromboSol showed only 49% and 44% platelet recovery, respectively. Platelet half-life was confirmed to be about 2 days.18 The frozen product must be thawed at room temperature. This product can be obtained from Animal Blood Resources International (ABRI).
We are always happy to help if you have transfusion questions.
References are available on request.
FROM THE MEDICAL DIRECTORS
Summer always brings change, and ours came in the form of some great new additions to the BluePearl team.
Dr. Lauren Devine
We are excited to introduce the newest member of our internal medicine team in Renton, Dr. Lauren Devine, who grew up in Arizona and is excited to be back in the west. Dr. Devine attended veterinary school at Kansas State, completed an internship at University of Minnesota and just finished her residency at North Carolina State University. She is interested in all aspects of internal medicine but especially enjoys complex endocrine diseases, chronic urinary conditions, gastrointestinal disease and endoscopy. Adding Dr. Devine to our internal medicine team allows us to now provide internal medicine services 6 days a week in both Seattle and Renton. Dr. Devine is available for consultations and referrals Wednesday through Saturday at BluePearl in Renton.
In June, we said good-bye to two of our emergency clinicians. Victoria Miller was accepted into an emergency and critical care residency in Wisconsin, and Mary Ellen Finley was accepted as a radiology resident at Washington State University. Fortunately, two new emergency clinicians have joined us.
Beth Davidow, DVM, DACVECC
Linda Barton, DVM, DACVECC
Many of you know John Fiddler who worked for 10 years with the emergency service at Veterinary Specialty Center in Lynnwood and then as part of the ACCES team from 2010-2013. Over the last several years, Dr. Fiddler has traveled throughout the world both exploring and volunteering his veterinary services, and we are excited to have him back on our team.
Elizabeth Mansi moved to the Seattle area last summer after completing military service that included a tour in Naples, Italy and another at Dog Center Europe, a large military veterinary specialty and emergency hospital in Germany that treats over 12,000 pets and military working dogs each year. Over the past year, she has worked with us as a relief clinician and is now joining us full time.
We are committed to sharing our specialized knowledge with family veterinarians and veterinary technicians in the region by providing continuing education programs throughout the year. Our CE is free of charge and includes dinner and two hours of CE credit. Registration is required for each CE. Please RSVP to Amiellia Johnston at firstname.lastname@example.org or call 206.364.1660 as space is limited.
|Oct 12||7-9:00PM||Doctor||Palliative Cancer Care|
Megan Breit, DVM, MS, DACVIM-Oncology
4130 Lind Ave SW
|Nov 1||7-9:00PM||Tech||Radiology Position and Safety|
Carmen King, LVT, VTS (ECC)
|North Seattle College|
9600 College Way N
|Nov 9||7-9:00PM||Doctor||Oral Chemotherapy|
Karri Meleo, DVM, DACVIM-Oncology, DACVR-RO
|North Seattle College|
9600 College Way N
|Nov 15||7-9:00PM||Tech||Fluid Therapy: What You Should Know|
Beth Davidow, DVM, DACVECC
4130 Lind Ave SW