Extracorporeal Therapy at BluePearl New York
Dear Colleagues:We hope that you had an enjoyable summer. We would like to take this time to let you know about exciting new therapies we offer in Forest Hills.
Relatively new to the veterinary world, extracorporeal renal replacement therapy has become a highly advanced and potentially life-saving medical treatment for pets with acute kidney failure (including toxin exposures, fulminant infections, and ureteral obstructions) and difficult to manage immune-mediated diseases. Extracorporeal therapies include both intermittent hemodialysis (IHD) and therapeutic plasma exchange (TPE). Currently, BluePearl Veterinary Partners in Queens is the only veterinary facility in New York City to offer these services for pets.
Consultation with Dr. Christine Iacovetta and Dr. Yuki Tse is encouraged as soon as you suspect a patient may benefit from dialysis. Candidacy for dialysis for dogs and cats, prognosis and potential complications will be determined by a brief review of the pet’s history, blood work and current condition.Extracorporeal Therapies Available at BluePearl
- Hemodialysis is the process of removing metabolic waste products from a patient’s blood stream while restoring and maintaining normal fluid and electrolyte balances. While dialysis is lifesaving in cases of fulminant kidney disease, it can also be employed early in the course of disease to prevent, rather than reverse, some of the life-threatening complications associated with renal failure. The ultimate goal in hemodialysis is not to “fix” the kidneys but rather to buy time for the patient to determine if their kidney function will recover.
- Hemoperfusion is hemodialysis performed with the addition of a charcoal filter to remove certain toxins.
- Therapeutic Plasma Exchange is the process of removing a patient’s plasma through a filter while replacing the loss with donated plasma. The goal is to remove autoantibodies from the patient in order to get better control over their immune disease. In addition, the same process can be used to remove protein bound toxins in order to prevent a toxic insult from occurring or progressing further.
Indications for hemodialysis
Acute Kidney Injury
Acute injury to the kidneys may occur for various reasons (e.g.: Leptospirosis, pyelonephritis, ischemic damage etc.). Although the underlying etiology will determine therapy, the mainstay of medical therapy for all cases is intravenous fluid.
Reasons for referral:
Azotemia that is severe or not improving
Anuria despite correcting dehydration
If you have any questions about whether a patient would benefit from hemodialysis please call for advice. We are happy to discuss any patient case, as early intervention is often beneficial.
There are many toxins that may be removed by hemodialysis alone, hemoperfusion or therapeutic plasma exchange. Referral as soon as possible after exposure is best.
Some commonly dialyzable toxins:
- Ethylene Glycol
- Many Chemotherapeutics
Therapeutic Plasma Exchange (TPE) is available for select cases of immune dysfunction refractory to conventional therapy. Beneficial effects can be seen in immune-mediated hemolytic anemia patients that require multiple transfusions or are becoming neurologic from high total bilirubin content. TPE can also be used in Myasthenia gravis patients with severe weakness or aspiration pneumonia or pre-operatively to help stabilize the disease. Other cases include dermatologic conditions such as pemphigus as well as immune-mediated thrombocytopenia (ITP).
If You Are Considering Referral
Avoid using the jugular veins in any patient that may be a candidate for dialysis. The blood flow rates necessary to perform dialysis require placement of a large-bore jugular catheter. Dogs and cats have limited options for vascular access, and the jugular veins should be protected if possible.
Any previous lab work is helpful in determining acute versus chronic disease if it is available. Diagnostics and medical therapy provided along with any imaging should also be sent with the patient.
Open Fractures and Treatment Approaches in Orthopedic Trauma Cases
Duane A. Robinson, DVM, PhD, DACVS-SA
- Open fractures are generally considered an orthopedic emergency.
- Proper assessment and initial treatment are key to a successful outcome.
- Classification systems are used to help with prognosis.
- Choose an antimicrobial with efficacy against Gram-positive, Gram-negative, aerobic and anaerobic organisms.
- Grade I and II fracture – cephalexin/cefazolin, amoxicillin + clavulanic acid
- Grade III and IV– as above and a fluoroquinolone (e.g. enrofloxacin)
- Cultures at initial presentation add little value unless there has been more than 24 hours since injury.
Open fractures are common in veterinary medicine, often affecting bones of the appendicular skeleton. These cases represent a unique combination of soft tissue and orthopedic injuries.
In a recent cross-sectional and case-control study the risk factors for open fractures of the appendicular skeleton in dogs and cats were evaluated.3 The authors found that sexually intact, younger dogs were at a higher risk. Interestingly, toy-breed dogs had a lower risk of open fractures when compared to other breeds in the case group. Bone segments with a higher risk included the scapula, radius or ulna, tibia or fibula and tarsus. Comminuted fractures were strongly associated with an open fracture followed by short oblique fractures. Similarly, sexually intact and younger cats were at a higher risk of open fractures.
Classification systems exist in the human literature and have been used to classify these fractures in veterinary medicine (figures 1 and 2).2 The goal of using such a system is to help provide a prognosis and guide treatment. The use of this system can also help during conversations with a referral surgeon as it provides an understanding of the degree of injury.
As with all trauma cases it is essential to assess the entire patient as, in many cases, comorbidities may prove more life threating than the orthopedic injury. The goals of successful management of an open fracture include preventing infection, promoting fracture healing and restoring function to the affected extremity. Key steps in achieving these goals include prompt and aggressive debridement of contaminated material and nonviable tissue; vigorous irrigation; administration of antimicrobials and restoration of soft tissue coverage to healing bone, tendons, ligaments and neurovascular structures.
The overriding goals of wound treatment in these patients are centered around prevention of further contamination and soft tissue trauma/injury. In many cases sedation and/or general anesthesia is essential, so thorough assessment of the overall patient stability is necessary. The wound should be packed with sterile, water-soluble lubricant. The hair should be clipped widely around the wound to give the surgeon the most flexibility in treating the wound. Gross debris is removed, nonviable soft tissues are debrided judiciously and the wound is lavaged.
The general recommendation for lavage is to use a sterile isotonic fluid at a pressure of 7 to 8 psi which is thought to limit trauma to the viable tissues. Such a pressure can be achieved using a 1-litre fluid bag placed in a pressure sleeve, attached to IV fluid tubing and a 22 to 16-gauge needle with the pressure in the sleeve raised to 300 mm Hg.1,2 In cases of severe contamination, tap water, although not ideal, can be used to remove gross debris prior to lavage. Similarly, the use of a 0.05% chlorhexidine solution has been described. Once the wound is clean a sterile dressing and bandage, often with rigid external fixation (e.g. fiberglass cast splint, aluminum rod) is placed.
The choice of antimicrobial in these cases can be a challenge. One must consider not only the commensal organisms of the patient but also those that have contaminated the wound. It is also prudent to realize that contamination of a wound does not necessarily mean the wound will become colonized and develop an active infection. Similarly, the population of a given wound is not static and can change in relation to many patient and environmental factors. In general, the antimicrobial chosen should be broad spectrum with efficacy against Gram-positive, Gram-negative, aerobic and anaerobic organisms. Some more common isolates include Staphylococcus spp., Streptococcus spp., Klebsiella spp., Pseudomonas spp., Enterobacter spp., and Escherichia coli.
In a prospective study of 1104 open fractures in humans there was a significant decrease in infection rate when antibiotics were administered within 3 hours after injury (4.7%), compared with 4 hours or longer after injury (7.4%).5 The authors also noted that the lowest infection rates occurred when the antimicrobial drugs provided coverage against Gram-positive, Gram-negative, aerobic and anaerobic organisms. Finally, an increased risk of infection was noted when there was a lack of antimicrobial administration; when it was > 4 hours from injury until initiation of antimicrobials; when there was extensive soft tissue trauma; when resistant organisms were present; and when the post debridement-irrigation culture was positive.5
The final consideration regarding the use of antimicrobials in these cases is that surgical site infections are increasingly the result of pathogens acquired in a hospital setting; pathogens that often have some degree of antimicrobial resistance. In attempts to avoid this complication it is best to avoid unnecessarily maintaining an open fracture as this likely increases the rate of nosocomial infection.
Definitive Surgical Treatment
The goals of definitive surgical treatment include preventing infection, promoting bony union, repair of soft tissue damage, and restoring function. Restoration of the soft tissue element is essential for fracture healing and the use of vacuum-assisted closure techniques may be beneficial.2 The Gustilo-Anderson classification scheme can be used to help determine the best surgical treatment. In general, Type I open fractures can usually be treated using the same method of fixation as would be used for a closed fracture of similar configuration. Type II open fractures require the proper management as outlined above and can be treated using the same method of fixation as would be used for closed fractures. Type III open fractures have extensive soft tissue damage which may preclude internal fixation.2 In every case, appropriate, experienced judgment is necessary.
Complications (figures 3 and 4) can occur and counselling owners regarding this potential is important. Widely described complications include: superficial infections, deep-seated infections (may require implant removal), delayed union or nonunion, necrosis of soft tissue with subsequent breakdown of soft tissue repair techniques, and temporary or permanent neurologic damage from the initial injury. In severecases amputation may be necessary and septicemia and death may result from infections treated inappropriately.
These cases can be challenging and at times daunting, but with appropriate and timely treatment, a successful outcome is achievable. If you are unsure or would like to consult on a case, please give our surgery service a call.
- Gall TT, Monnet E: Evaluation of fluid pressures of common wound-flushing techniques. Am J Vet Res 71:1384-1386, 2010.
- Millard RP, Towle HA: Open Fractures, in Tobias KM, Johnston SA (eds): Veterinary Surgery: Small Animal, Vol 1. St. Louis, MO, Elscervier Saunders, 2012, pp 572-575.
- Millard RP, Weng HY: Proportion of and risk factors for open fractures of the appendicular skeleton in dogs and cats. J Am Vet Med Assoc 245:663-668, 2014.
- Orthopaedic Trauma Association: Open Fracture Study G: A new classification scheme for open fractures. J Orthop Trauma 24:457-464, 2010.
- Patzakis MJ, Wilkins J: Factors influencing infection rate in open fracture wounds. Clin Orthop Relat Res:36-40, 1989.
Lauren Harris, DVM, DACVECC
BluePearl Tampa Bay
Serotonin syndrome is a life-threatening, drug-induced condition resulting from excessive serotonergic agonism at the serotonin receptors of the central and peripheral nervous system. This syndrome is characterized by mentation changes (depression, hyperactivity, agitation, delirium), autonomic instability (diarrhea, mydriasis, tachycardia, borborygmous) and neuromuscular abnormalities (hyperreflexia, myoclonus, tremors, rigidity, ataxia). It can occur secondary to overdose of a single serotonergic drug, or secondary to concurrent administration of two or more serotonergic drugs. In animals, this syndrome most commonly occurs due to accidental ingestion of one or more antidepressant medications prescribed to their caregivers.
Serotonergic medications targeted to increase levels of serotonin (5-hydroxytryptamine, 5-HT) in the brain include:
- Drugs that increase serotonin production
- Drugs that inhibit the metabolism of serotonin
-Monoamine oxidase inhibitors (MAOIs) such as moclobemide, selegiline, clorgyline, tranylcypromine
- Drugs that increase serotonin release
-Amphetamines, ecstasy, cocaine
- Drugs that inhibit the reuptake of serotonin
-Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, citalopram, paroxetine, sertraline, venlafaxine
-Tramadol, fentanyl, methadone, meperidine
-Tricyclic antidepressants (TCAs) such as amitriptyline, clomipramine, doxepin, imipramine
- Drugs that stimulate serotonin receptors
-LSD, lithium, buspirone, sumatriptan
In veterinary medicine, SSRIs are gaining popularity for the treatment of behavioral issues such as aggression and urine spraying.
Serotonin is formed in the body from the essential amino acid, tryptophan. Most serotonin in the body is synthesized and stored in the enterochromaffin cells and the myenteric plexus of the gastrointestinal tract, exerting its effects on the central and peripheral nervous systems. Because serotonin cannot cross the blood-brain barrier, it must also be synthesized in the brain by nuclei in the lower pons and medulla. It is removed from the circulation by the lungs. Once serotonin is synthesized in the cytosol of neurons, it is stored in transport vesicles at the nerve terminal. When serotonin is released from these vesicles into the synaptic cleft, neurotransmission occurs as serotonin binds to the postsynaptic receptor.
Serotonin’s effects on the peripheral nervous system include bronchoconstriction, vasoconstriction, platelet aggregation, intestinal peristalsis and uterine contraction. In the central nervous system, serotonin influences mood, sleep, thermoregulation, aggression, vomiting and the perception of pain.
The clinical signs of serotonin syndrome are variable and may be seen within 10 minutes to 4 hours following accidental ingestion. Mild signs may include diarrhea, whereas more severe signs may include neuromuscular rigidity and severe hyperthermia. Cardiac arrhythmias, transient blindness, disseminated intravascular coagulation and acute renal failure have also been reported as sequelae to this syndrome.
In a recent retrospective study of SSRI ingestion in 313 dogs, 76.3% of dogs that ingested SSRIs were asymptomatic. In dogs that developed clinical signs, the median time to develop clinical signs was 2 hours, and the most common signs were neurological or gastrointestinal in nature. Four patients in this study displayed signs consistent with “serotonin syndrome,” which was described as demonstrating multiple signs (such as mental status changes, agitation, myoclonus, hyperreflexia, shivering, tremors, diarrhea, incoordination, hyperthermia, etc.).
Another recent retrospective study evaluated SSRI toxicosis in 33 cats. Only 24% of cats were symptomatic, with the most common clinical sign being sedation (in 75% of symptomatic cats). Gastrointestinal signs such as vomiting, diarrhea and drooling were seen in 50% of symptomatic cats. Central nervous system stimulation, hyperthermia, and cardiovascular signs were rarely seen.
SSRIs, TCAs and MAOIs are rapidly absorbed from the gastrointestinal tract after ingestion. TCAs seem to have the narrowest margin of safety with a toxic dose of 15 mg/kg; however, clinical signs can be seen at much lower dosages. Alternatively, SSRIs are considered relatively safe, with a minimum lethal dosage reported as 100 mg/kg in the dog and 50 mg/kg in the cat.
Diagnosis is typically based on clinical signs and potential for exposure to medications known to increase serotonin in the peripheral or central nervous system. Toxicology screens are available.
If ingestion is known and the patient is not yet symptomatic, decontamination with emesis should be performed. As these drugs are rapidly absorbed through the GI tract, emesis should be induced within 15 minutes of ingestion (however this is not always possible). Emesis should not be induced in cases that are already symptomatic due to the risk of aspiration. Activated charcoal can be used to minimize further drug absorption; however, like emesis, this should be done within 15 minutes of ingestion and before clinical signs are present.
In patients that are symptomatic, emergency treatment should be aimed at assessing patency of the airway, breathing, circulation, and neurological status. In mild reactions, supportive care will be all that is needed. IV fluids should be used to maintain hydration; however, IV fluids will not assist with elimination of the drugs more quickly, as serotonergic drugs are highly protein bound. In patients with neurological signs such as seizures or tremors, diazepam can be given as an IV bolus at 0.5 mg/kg with CRI as needed. In cases of refractory seizures, phenobarbital or propofol infusion may be considered. Hyperthermic animals should receive passive and active cooling measures. In patients with autonomic instability, treatment considerations may include sympathomimetic medications (norepinephrine, epinephrine) or short acting beta blockers (such as esmolol), depending on the clinical signs experienced.
Serotonin receptor antagonists such as cyproheptadine and chlorpromazine may be beneficial in the management of serotonin syndrome. Cyproheptadine may be administered by mouth or crushed and given rectally at 1.1 mg/kg in dogs or 2-4 mg (total dose) in cats every 4-6 hours. Chlorpromazine may be given at 0.5 mg/kg IV, IM, or SC every 6 hours; however, side effects such as sedation and hypotension are common with this drug, so close monitoring is needed.
More recently, intravenous lipid emulsion (ILE) therapy has been used as an adjunctive treatment for serotonin syndrome in people; however, no reports of its use in veterinary medicine for serotonin syndrome have been reported. If ILE therapy is to be considered, it should only be considered in cases that are refractory to conventional therapy. Intralipid 20% emulsion can be given IV (using sterile technique) as a 1.5 mL/kg slow bolus, followed by a CRI of 0.25-0.5 ml/kg/min for 30-60 minutes.
Prognosis for serotonin syndrome is variable, and depends on the amount of serotonergic medication ingested, the clinical signs experienced by the animal, and the individual animal’s response to treatment. In patients that survive, most are asymptomatic by 36 hours post-ingestion. In two recent retrospective studies of SSRI toxicosis in dogs and cats, 100% of animals that received veterinary attention and treatment survived to discharge; however, death has been reported in other studies.
- Mohammad-Zadeh LF, Moses L, Gwaltney-Brant SM. Serotonin: a review. J Vet Pharmacol Therap 2008; 31:187-199.
- Reineke EL: Serotonin Syndrome. p 464. In Silverstein DC, Hopper K (eds): Small Animal Critical Care Medicine. 2nd Ed. Elsevier, St Louis, 2015.
- Thomas DE, Lee JA, Hovda LR. Retrospective evaluation of toxicosis from selective serotonin reuptake inhibitor antidepressants: 313 dogs (2005-2010). J Vet Emerg Crit Care 2012; 22(6);674-681.
- Pugh CM, Sweeney JT, Bloch CP, et al. Selective serotonin reuptake inhibitor (SSRI) toxicosis in cats: 33 cases (2004-2010). J Vet Emerg Crit Care 2013; 23(5):565-570.
- Isbister GK, Buckley NA. The Pathophysiology of Serotonin Toxicity in Animals and Humans. Clin Neuropharmacol 2005; 28(5):205-214.
Jamie Etish, DVM, DACVIM
BluePearl Philadelphia (VSEC)
Unfortunately, immune-mediated diseases are all too common in veterinary medicine. However, there are some medications that have shown promise in the treatment of these conditions. These medications include leflunomide, mycophenolate mofetil and intravenous immunoglobulin.
Leflunomide is an immunosuppressant drug that has been used in human medicine for years and is becoming more popular in veterinary medicine more recently. The drug inhibits pyrimidine synthesis in the S phase of the lymphocyte cell cycle. This action reduces production of T- and B-cells, decreases production of immunoglobulins, and interferes with leukocyte adhesion. The activity of the drug is focused on lymphocytes because non-lymphoid cells are able to synthesize pyrimidine through alternate pathways. Leflunomide can be used as an initial therapy (most often in combination with prednisone) for the treatment of immune-mediated polyarthritis (IMPA). It may also be used for treatment of immune-mediated thrombocytopenia (ITP) or immune-mediated hemolytic anemia (IMHA).
The recommended starting dosages in dogs are 2-4 mg/kg once a day. In cats, we use 2 mg/kg once a day as the initial dose.
Potential side effects include decreased appetite, vomiting, and diarrhea. A cutaneous, ulcerative drug eruption can also be seen with this drug, which should resolve if leflunomide therapy is discontinued. Liver enzyme elevations may be seen in some patients, but these are typically reversed with dose reduction or discontinuation of the medication. Additionally, decreases in leukocytes, red blood cells and platelets can be seen. Monitoring of CBCs on a monthly basis is recommended.
Another immunosuppressant is mycophenolate mofetil. This drug inhibits purine biosynthesis in lymphocytes, which inhibits antibody formation by B-cells and inhibits cell-mediated responses by T-cells. Mycophenolate may be used in the treatment of immune-mediated hemolytic anemia and thrombocytopenia, polyarthropathies, glomerulonephropathies, and possibly autoimmune skin disease. Mycophenolate may cause gastrointestinal side effects, which consist mostly of anorexia and diarrhea. Dose reductions may help to decrease side effects. The recommended starting dose is approximately 10-15mg/kg BID. This drug is absorbed better on an empty stomach.
Intravenous immunoglobulin (IVIG) is a fractionated sample of human plasma that contains primarily IgG. The mechanisms of action include: Fc receptor blockade on phagocytes, which decreases phagocytosis by mononuclear cells; interference with complement-mediated damage; increase in anti-inflammatory cytokines; increase in clearance of IgG; and modulation of B- and T-cell function. IVIG has been used in treatment of IMHA and ITP in dogs.
Previous studies have shown improved platelet recovery time and duration of hospitalization when a single injection of IVIG is given in patients with ITP.
IVIG can be quite an expensive drug, however, so use of this drug may be limited in certain cases. Side effects of IVIG may include an increased risk of thromboembolism, facial swelling, and pruritus. This medication should be given under close hospital supervision given the possible side effects.
Despite the many different treatment options available, immune-mediated diseases are often quite difficult to treat, and appropriate medications should be chosen based on individual patient needs. If you have any questions about immune-related diseases, and possible treatments, please feel free to contact the nearest BluePearl internal medicine service.
BluePearl is strongly committed to the veterinary community. One of the ways we demonstrate this commitment is through our continuing education program, which is subsidized in part by our Partners in Education.
All BluePearl lectures are free and include a light dinner at 7:00pm. Presentation begins at 7:30 pm.