Application of Airway Pressure Therapy in Veterinary Critical Care: Part I: Respiratory Mechanics and Hypoxemia

Over the past several decades, recognition of acute respiratory failure as the cause of death in patients suffering from various clinical conditions has prompted aggressiv investigation into the area of respiratory physiology and supportive respiratory care. With the evolution of emergency medicine and critical care services in both human and veterinary medicine, many patients previously considered unsalvageable due to the severity of their underlying disease are now being resuscitated and successfully supported, creating a new population of critically ill patients. Where only a decade ago these patients would have succumbed to their underlying disease, they now survive long enough to manifest the complications of shock and tissue injury in the form of acute respiratory failure. Investigation into the pathophysiology and treatment of this acute respiratory distress syndrom (ARDS) has facilitated increased clinical application of respiratory theerapy and machanical ventilation.¹ The purpose of this paper is to provide a basic review of respiratory mechanics and the pathophysiology of hypoxemia as they relate to airway pressure therapy in veterinary patients and to review the use of airway pressure therapy in veterinary patients This paper is divided into two parts; part I reviews respiratory mechanics and hypoxemia as they apply to respiratory therapy, while part II deals specifically with airway pressure therapy andits use in clinical cases.     

Role of Lung Surfactant in Respiratory Disease: Current Knowledge in Large Animal Medicine

Lung surfactant is produced by type II alveolar cells as a mixture of phospholipids, surfactant proteins, and neutral lipids. Surfactant lowers alveolar surface tension and is crucial for the prevention of alveolar collapse. In addition, surfactant contributes to smaller airway patency and improves mucociliary clearance. Surfactant-specific proteins are part of the innate immune defense mechanisms of the lung. Lung surfactant alterations have been described in a number of respiratory diseases. Surfactant deficiency (quantitative deficit of surfactant) in premature animals causes neonatal respiratory distress syndrome. Surfactant dysfunction (qualitative changes in surfactant) has been implicated in the pathophysiology of acute respiratory distress syndrome and asthma. Analysis of surfactant from amniotic fluid allows assessment of fetal lung maturity (FLM) in the human fetus and exogenous surfactant replacement therapy is part of the standard care in premature human infants. In contrast to human medicine, use and success of FLM testing or surfactant replacement therapy remain limited in veterinary medicine. Lung surfactant has been studied in large animal models of human disease. However, only a few reports exist on lung surfactant alterations in naturally occurring respiratory disease in large animals. This article gives a general review on the role of lung surfactant in respiratory disease followed by an overview of our current knowledge on surfactant in large animal veterinary medicine.     

Thrombolytic Therapy in Dogs and Cats

Objective: To review the thrombolytic agents most commonly used in humans, their mechanisms of action, potential uses, adverse effects, and reports of their use in dogs and cats.
Human data synthesis: Thrombolytic agents avaliable in human medicine include streptokinase, urokinase, tissueplasminogen activator (t-PA), single-chain urokinase plasma activator (scu-PA) and anisoylated plasminogen-strep-tokinase activator complex (APSAC). These agents were originally used for the management of proximal deep vein thrombosis and severe pulmonary embolism but more recently, use of these drugs has been extended to include the treatment of acute peripheral arterial disease, cerebrovascular disease (stroke) and acute coronary thrombosis. The most predictable side effect associated with the use of thrombolytic therapy is hemorrhage.
Veterinary data synthesis: Clinical experience with thrombolytic agents in small animals is limited to streptokinase and t-PA. It is possible, that as in humans, canine and feline patients with PTE and right ventricular dysfunction may benefit from thrombolytic therapy but there are no veterinary studies to support this theory to date. Successful use of streptokinase has been documented in a small number of canine patients with systemic thromboembolism. ⁶³ Thrombolytic therapy is relatively efficacious in cats with aortic thromboemboli but is associated with a high mortality rate. ^59,60,64 With regard to use of t-PA in veterinary medicine, the small number of animals treated with varying protocols makes it impossible to provide safe and effective dose recommendations at this time.
Conclusions: Future goals for thrombolytic therapy in veterinary medicine include determination of more specific clinical indications, as well as design of effective protocols that minimize mortality and morbidity.     

Acute lung injury and acute respiratory distress syndromes in veterinary medicine: consensus definitions: The Dorothy Russell Havemeyer Working Group on ALI and ARDS in Veterinary Medicine

Background: As veterinary medicine has become more sophisticated, with greater numbers of veterinary patients receiving intensive care, more patients with an acute respiratory distress (ARDS)‐like syndrome have been recognized. Methods: A consensus definition meeting was held for the purpose of developing veterinary‐specific definitions for acute lung injury (ALI) and ARDS. Results/conclusions: Three clinically based definitions for acute lung injury and acute respiratory distress‐like syndromes occurring in veterinary patients were described. Neonatal equine respiratory distress syndrome (NERDS) was defined separately due to the specific requirement for primary developmental surfactant dysfunction and lack of an inflammatory component. Five diagnostic criteria categories were established for Veterinary ALI/ARDS (Vet ALI/ARDS) with 4 required and a fifth highly recommended criteria. A strong consensus was reached that onset of respiratory distress must have been acute and that known risk factors must be present. Additional criteria included evidence of pulmonary capillary leak with no evidence of increased pulmonary capillary pressure, evidence of inefficient gas exchange and, finally, evidence of inflammation. Some features of ALI/ARDS in the neonatal horse were recognized as unique, therefore, equine neonatal ALI/ARDS (EqNALI/EqNARDS) was similarly defined but with a graded gas exchange inefficiency table to allow for normal developmental changes in gas exchange. Use of these definitions in planning prospective studies of these problems in veterinary patients should allow for more direct comparisons of studies and clinical trials, with a larger goal of improving outcome in veterinary patients.     

Veterinary hemodialysis: advances in management and technology.

Hemodialysis (HD) is a renal replacement therapy that can enable recovery of patients in acute kidney failure and prolong survival for patients with end-stage kidney failure. HD is also uniquely suited for management of refractory volume overload and removal of certain toxins from the bloodstream. Over the last decade, veterinary experience with HD has deepened and refined and its geographic availability has increased. As awareness of the usefulness and availability of dialytic therapy increases among veterinarians and pet owners and the number of veterinary dialysis facilities increases, dialytic management will become the standard of advanced care for animals with severe intractable uremia.     

Helium‐oxygen gas‐carrier mixture (heliox): a review of physics and potential applications in veterinary medicine

Background – To review the physics of helium with regard to airway physiology, as well as known human and potential veterinary applications of administration of inhaled helium‐oxygen gas‐carrier mixture (heliox). Data Sources – Human and veterinary studies. Human Data Synthesis – Helium‐oxygen mixtures have been used in human medicine for over 70 years as an adjunct therapy in various upper and lower respiratory disorders. Helium's low density promotes laminar flow through partially obstructed airways, resulting in a decreased work of breathing. Veterinary Data Synthesis – Little to no evidence‐based medicine exists to support or oppose the use of heliox in veterinary species. However, domestic animal species and humans share several common pathophysiologic aspects of various obstructive airway disorders. Thus, veterinary patients may also ultimately and significantly benefit from this novel therapy. Conclusion – Prospective studies are needed in veterinary medicine to determine the utility of heliox in clinical scenarios.     

Photobiomodulation Therapy in Veterinary Medicine: A Review

Laser therapy, or photobiomodulation, has rapidly grown in popularity in human and veterinary medicine. With a number of proposed indications and broad, sometimes anecdotal, use in practice, research interest has expanded aimed at providing scientific support. Recent studies have shown that laser therapy alters the inflammatory and immune response as well as promotes healing for a variety of tissue types. This review will cover the history of the modality, basic principles, proposed mechanisms of action, evidence-based clinical indications, and will guide the practitioner through its application in practice.     

CLINICAL TECHNIQUE: Negative Pressure Wound Therapy-General Principles and Use in Avian Species

Negative pressure wound therapy (NPWT) is an adjunctive wound management modality that has been shown to augment the treatment of acute and chronic dermal and subdermal wounds in human and veterinary medicine. The proposed effects of NPWT are multifactorial and include improvement of wound perfusion, reduction of interstitial edema and substances inhibitory to wound healing, enhancement of granulation tissue formation, and reduction in bacterial contamination from a wound bed. Together, the proposed benefits of NWPT can lead to enhanced efficiency of wound healing when this treatment modality is applied to a wound. In this article, the authors provide an overview of the mechanism of action of NPWT. Case selection, system application and management, as well as contraindications to NPWT therapy are presented. Potential uses, practical application, and limitations of use of NPWT in avian species are discussed.     

Use of dopamine in acute renal failure

Objective: To review the current understanding of dopamine and its use in the prevention and treatment of acute renal failure (ARF). Data sources: Original research articles and scientific reviews. Human data synthesis: Low‐dose dopamine administration has been shown to increase natriuresis and urinary output in both healthy individuals and in a few small studies in human patients with renal insufficiency. However, in several large meta‐analyses, dopamine treatment did not change mortality or the need for dialysis. Due to the potential side effects, the use of dopamine for prevention and treatment of ARF is no longer recommended in human medicine. Veterinary data synthesis: Low‐dose dopamine increases urinary output in healthy animals and animal models of ARF if given before the insult. There are no available studies looking at the effect of low‐dose dopamine therapy in naturally occurring ARF in dogs or cats. Conclusion: Due to the potential side effects of low‐dose dopamine therapy, the results from large human trials, and the lack of information in veterinary medicine, the use of dopamine for treatment of ARF in veterinary patients should be further evaluated.     

An overview of positive pressure ventilation

Objective: The purpose of this article is to give the reader a brief overview of the indications for positive pressure ventilation (PPV). Data sources: Current human and veterinary literature. Summary: There are numerous indications for PPV in veterinary medicine. These include both pulmonary parenchymal disease and diseases that affect ventilation. When choosing PPV, a clinician must have a comprehensive understanding of the different ventilation mode options available and the physiologic effects of ventilation on the patient. Conclusions: PPV is becoming more widely used in veterinary medicine and is improving the survival of animals with hypoxemic and hypercapnic respiratory failure.     

Veterinary Neurologic Rehabilitation: The Rationale for a Comprehensive Approach

The increase in client willingness to pursue surgical procedures, the heightened perceived value of veterinary patients, and the desire to provide comprehensive medical care have driven the recent demand of using an integrative treatment approach in veterinary rehabilitation. Physical therapy following neurologic injury has been the standard of care in human medicine for decades, whereas similar rehabilitation techniques have only recently been adapted and utilized in veterinary medicine. Spinal cord injury is the most common neurologic disease currently addressed by veterinary rehabilitation specialists and will be the primary focus of this review; however, research in other neurologic conditions will also be discussed. Of particular interest, to clients and veterinarians are techniques and modalities used to promote functional recovery after neurologic injury, which can mean the difference between life and death for many veterinary patients.The trend in human neurologic rehabilitation, often regardless of etiology, is a multimodal approach to therapy. Evidence supports faster and improved recoveries in people after neurologic injury using a combination of rehabilitation techniques. Although the primary neurological disorders researched tend to be spinal cord injury, peripheral neuropathies, allodynia, multiple sclerosis, and strokes—many correlations can be made to common veterinary neurological disorders. Such comprehensive protocols entail gait training activities in combination with neuromuscular electrical stimulation and directed exercises. Additionally, pain-relieving and functional benefits are bolstered when acupuncture is used in addition to rehabilitation. Studies, both laboratory and clinical, support the use of acupuncture in the management of neurologic conditions in small animals, specifically in cases of intervertebral disc disease, other myelopathies, and neuropathic pain conditions. Acupuncture’s ability to promote analgesia, stimulate trophic factors, and decrease inflammation, including neuroinflammation, make it an alluring adjunct therapy after neurologic injury.Although there is limited research in veterinary medicine on physical techniques that expedite recovery after neurologic injury, there are sparse publications on clinical veterinary research suggesting the benefits of acupuncture, rehabilitation, and LASER in dogs with intervertebral disk disease. Accordingly, due to the relative lack of evidence-based studies in veterinary neurologic rehabilitation, much of the data available is human or laboratory-animal based, however, evidence supports the utilization of an early, comprehensive treatment protocol for optimal neurologic recovery. The rationale for why an integrative approach is critical will be detailed in this review; in addition, literature on specific physical rehabilitation techniques that have evidence of improved recoveries after neurologic injury, will be addressed.     

Phosphorus and phosphate metabolism in veterinary patients

Objective: To review phosphorus and phosphate metabolism and the importance of phosphate abnormalities in veterinary patients. Data sources: A review of recent human and veterinary medical literature. Human data synthesis: There is a significant amount of original research on human patients with phosphate abnormalities. Hypophosphatemia has been studied in patients with diabetic ketoacidosis (DKA), head trauma, refeeding syndrome, hypothermia and in ventilator patients that fail to wean. Hyperphosphatemia has been studied in patients with renal failure and malignancy. Phosphate levels have also been evaluated for prognostic value in sepsis and acute liver failure. Veterinary data synthesis: Although animal models were used in early experimental research, fewer studies have been published on the effects of phosphate abnormalities in veterinary patients. Hypophosphatemia has been studied in animals with DKA, with refeeding syndrome and with hyperparathyroidism. Hyperphosphatemia has been studied in animals with renal failure and with secondary hypoparathyroidism. Conclusion: Phosphorus and phosphate are important in many biological functions. This paper is a review of their role in normal metabolism and the clinical importance of phosphate imbalances for our emergency and critical care patients.     

Therapy of systemic fungal infections: a pharmacologic perspective

An increase in the incidence of severe, invasive, systemic fungal infections has been noted over the last decade in human and veterinary medicine. Reports of drug resistance and therapeutic failure to currently available antifungal agents have also been on the rise. Many factors are likely to be involved in these trends, including immune suppression and the use of broad-spectrum antibiotics. The use of fungistatic drugs, suboptimal doses, compounded drugs, poorly absorbed drug formulations, and inadequate tissue penetrations of antifungals also contribute to the development of acquired resistance. Because of the unique chemical complexities of the antifungal agents, drug/drug and drug/food interactions may also play a significant role in poor therapeutic outcome. This review summarizes the pharmacology and toxicology of the antifungal agents in current use for systemic mycosis and introduces some of the newer antifungal agents that anecdotally show very promising results.     

Endotracheal stenting therapy in dogs with tracheal collapse

Tracheal collapse in dogs is a common respiratory disorder, typically presenting with a history of chronic cough, increasing respiratory difficulties, and episodes of dyspnoea. Medical treatment is the therapy of choice and surgical repair is considered when patients do not respond well. Minimally invasive endotracheal stenting is a promising new therapy under investigation, but there remain significant challenges to overcome potential complications. The purpose of this article is to provide a comparative overview of intra-luminal stenting of the trachea in human and veterinary medicine. The currently available stents and their potential clinical application to the veterinary patient will be discussed.     

Effects of a pilot training program on veterinary students' pain knowledge, attitude, and assessment skills

The prevention and management of pain is fundamental to the practice of both human and veterinary medicine. The recognition and treatment of pain represents an important indicator of the quality of care delivered in human hospitals and veterinary hospitals. Yet, both human and veterinary health care professionals have cited inadequate knowledge as a significant barrier to effective pain management. The aims of this pilot study were twofold: (1) to gauge veterinary medical students' current attitudes regarding their training in pain management and (2) to assess the impact of training and practice on the use of a canine acute pain assessment teaching tool. Participants, third-year professional veterinary medical students, completed a 16-item survey questionnaire before a 30-minute training session on pain assessment using the teaching tool and completed it again after training and a one-week practice period. Questions related to canine pain, assessment of canine pain, pain management education in the professional veterinary curriculum, and an example case presentation (video) were included in the survey. The analysis of survey results indicated that professional veterinary medicine students find value in didactic and clinical training in canine pain assessment. Additionally, use of the canine acute pain teaching tool in conjunction with a training program improved students' knowledge and skill in assessment while pointing out the importance of further training. Differences with regard to gender and tracking were found and warrant further exploration.     

Adult respiratory distress syndrome (ARDS). Incidence, clinical findings, pathomorphology and pathogenesis. A review

Acute and progressive respiratory distress ("shock lung") is a well known and feared complication in human patients with a variety of underlying disorders, even though the lungs are not involved primarily. In spite of the fact that dogs, and other animals, very often have been used in experimental models studying this syndrome, "shock lungs" have not received much attention in veterinary medicine. With the improved and more intensive treatment of severely diseased animals during the last years, especially pet animals, it is reasonable to assume that the lungs will be more important as an end organ also in veterinary practice. Animals in shock, particularly if complicated with sepsis, are prone to develop progressive respiratory distress. This paper reviews the current knowledge about the clinical picture, pathology and pathogenesis of acute respiratory disease, with main emphasize on the pathogenetic mechanism.     

A Candidate Second‐Generation Photosensitizer for Photodynamic Therapy in Veterinary Medicine

Introduction:  Photodynamic therapy (PDT) involves the light activation of a drug within a tumor causing selective tumor cell death. Unfortunately, some photosensitizing drugs have been associated with adverse reactions in veterinary patients. Zinc phthalocyanine tetrasulfonate (ZnPcS4) is a promising second‐generation photosensitizer for use in veterinary medicine, however, it cannot be applied clinically until safety and efficacy data are available.
Methods:  Increasing intraperitoneal doses of ZnPcS4 were given to Swiss Webster mice to assess acute toxicity. Based on mouse toxicity data, a phase I clinical trial of ZnPcS4‐based PDT in tumor‐bearing dogs was designed, using an accelerated titration scheme starting at 0.5% of the minimum toxic dose in mice. 24‐hours after ZnPcS4 administration tumors were irradiated with 675 nm light and dogs were evaluated by routine hematology and serum biochemistry at regular intervals after PDT.
Results:  Doses >125 mg/kg were associated with acute toxicity and mortality in Swiss Webster mice, suggesting the minimum toxic dose is 120–125 mg/kg. One dog, a Golden retriever with a massive malignant fibrous histiocytoma, has been entered into the phase I clinical trial. No deleterious effects were noted after ZnPcS4 administration. Within 48 hours of PDT, the tumor was dark and necrotic, with no grossly visible changes to the surrounding normal tissues. Histological examination of the PDT‐treated tumor confirmed widespread necrosis and thrombosis consistent with PDT‐mediated damage. The owner reported no adverse effects after treatment.
Conclusions:  Although preliminary data are encouraging, additional evaluation of ZnPcS4‐based PDT is required to determine its role in veterinary medicine.     

Veterinary intensive care

The term ‘intensive care’ is becoming increasingly popular in veterinary medicine to describe those techniques employed in caring for the critically ill animal. Application of the techniques required for intensive care is not difficult and can be employed in any veterinary practice. The purpose of intensive care is the uncomplicated conversion of a dramatic disease process into an uneventful one, not the performance of life-saving heroics. Critically ill patients share several common features, particularly the need for diligent monitoring and nursing. Regardless of the primary disease, the function of many organs is frequently impaired in these patients and they require total body care. Critically ill animals may have fluid, acid-base and electrolyte imbalances, increased caloric requirements and an increased susceptibility to infection. This paper describes the equipping and staffing of an intensive care unit and the various techniques for monitoring critically ill animals. It also reviews aspects of fluid and electrolyte disturbances and therapy, and the unusual respiratory problems and nutritional requirements of these patients.