Revisiting the use of hydroxyethyl starch solutions in equine fluid therapy

The last decade has led to major shifts in opinions on the use of hydroxyethyl starch (HES) solutions in fluid therapy, specifically in human patients with sepsis. The majority of evidence documenting adverse effects of HES solutions on coagulation and renal health come from studies in people. However, these findings have led to investigation into the safety of HES solutions in veterinary species. While there are now studies investigating the effects of HES solutions on coagulation and renal health in dogs, cats and horses, information regarding long-term follow-up, clinical significance of these changes and use of these solutions in critically ill animals is still lacking. The information presented here serves to review the physiology of oncotic pressure and the rationale behind colloid use, specifically HES solutions. Additionally, the foundation of arguments against the use of HES and the available literature regarding HES use in animals will be summarised.     

Responsible antimicrobial use in critically ill adult horses

Due to increasing antimicrobial resistance, pressure on veterinarians is mounting to adhere to responsible use of antimicrobial drugs. Antimicrobials are frequently included in the treatment of systemically ill horses due to the strong likelihood of an infection and the innate difficulties in differentiating systemic inflammation secondary to noninfectious from infectious causes. In light of increasing antimicrobial drug resistance and the potential negative impact of antimicrobials on equine patients, every attempt should be made to identify noninfectious disease, choose first-line antimicrobials and discontinue treatment as soon as possible. In most cases, a short duration of antimicrobial therapy ranging from a single dose (e.g. preoperatively) to 24–72 h might be sufficient with long-term treatment being rarely required. This article aims to provide practical guidelines for antimicrobial drug usage in critically ill adult horses by describing ancillary diagnostic aids that can help establishing whether or not an infection is present, discussing commonly encountered pathogens and their typical antimicrobial drug sensitivity patterns, and providing some guidance how to safely shorten the duration of antimicrobial therapy.     

The use of 25% human serum albumin: outcome and efficacy in raising serum albumin and systemic blood pressure in critically ill dogs and cats

Objective: To report on the use of 25% human serum albumin (25% HSA) (Plasbumin®), associated outcome, and efficacy in raising serum albumin and systemic blood pressure (BP) in critically ill dogs and cats. Design: Retrospective clinical study. Animals: Client‐owned cats and dogs. Interventions: Administration of 25% HSA. Measurements and main results: The medical records of 66 animals (64 dogs, 2 cats) at the Ontario Veterinary College, which received 25% HSA (Plasbumin®) from June 1997 to December 2001 were reviewed for age, body weight, clinical problems, albumin and globulin (g/L) levels pre‐ and within 18‐hour post‐transfusion and upon discharge from hospital, total solids (TS), systolic and diastolic BP pre‐ and post‐transfusion total volume administered, adverse reactions, blood products and synthetic colloids used, and outcome. Twenty‐five percent HSA was prescribed for a range of clinical problems, which were grouped into 6 categories for analysis. The age range was 4 months–12 years and body weight range 1.4–65 kg. The maximum volume administered to any dog was 25 mL/kg, mean volume administered was 5 mL/kg, maximum volume given as a slow push or bolus was 4 mL/kg with a mean of 2 mL/kg volume. The range for a constant rate infusion (CRI) was 0.1–1.7 mL/kg/hr over 4–72 hours. Forty‐seven (71%) animals survived to discharge; 11(16%) were euthanized, and 8 (12%) died. Serum albumin and TS increased significantly (P<0.0001) above pre‐transfusion levels as did systolic BP (P<0.01). Conclusions: Twenty‐five percent HSA can be safely administered to critically ill animals, and an increase in albumin levels and systemic BP can be expected.     

Fluid therapy in the critically ill patient

Fluid therapy products for use in the critically ill patient are described. Various specific clinical syndromes are described in detail, including shock, hypoalbuminemia, heart failure, liver failure, diabetic keto-acidosis and pancreatitis. Pathophysiology and specific therapeutic recommendations are given for these clinical syndromes.     

Hypocalcemia in a critically ill patient

Objective: To present a case of clinical hypocalcemia in a critically ill septic dog. Case summary: A 12‐year old, female spayed English sheepdog presented in septic shock 5 days following hemilaminectomy surgery. Streptococcus canis was cultured from the incision site. Seven days after surgery, muscle tremors were noted and a subsequent low serum ionized calcium level was measured and treated. Intensive monitoring, fluid therapy, and antibiotic treatment were continued because of the sepsis and hypocalcemia, but the dog was euthanized 2 weeks after surgery. New or unique information provided: Low serum ionized calcium levels are a common finding in critically ill human patients, especially in cases of sepsis, pancreatitis, and rhabdomyolysis. In veterinary patients, sepsis or streptococcal infections are not commonly thought of as a contributing factor for hypocalcemia. Potential mechanisms of low serum ionized calcium levels in critically ill patients include intracellular accumulation of calcium ions, altered sensitivity and function of the parathyroid gland, alterations in Vitamin D levels or activity, renal loss of calcium, and severe hypomagnesemia. Pro‐inflammatory cytokines and calcitonin have also been proposed to contribute to low ionized calcium in the critically ill. Many veterinarians rely on total calcium levels instead of serum ionized calcium levels to assess critical patients and may be missing the development of hypocalcemia. Serum ionized calcium levels are recommended over total calcium levels to evaluate critically ill veterinary patients.     

Coagulopathy of the critically ill equine patient

Objective – To review the hemostasis literature relevant to development of coagulopathy in the critically ill equine patient.
Data Source – Original scientific and review articles.
Human Data Synthesis – Inflammation plays a critical role in the activation and amplification of clot formation, as well as the impairment of physiologic anticoagulant mechanisms, and fibrinolysis. Earlier identification of coagulopathy in patients at risk and restoration of physiologic hemostasis may result in better outcome. Development of scoring systems based on information other than coagulation markers alone may better identify patients with subclinical coagulopathy.
Veterinary Data Synthesis – Critically ill equine patients commonly at risk for coagulopathy include those with severe gastrointestinal disease, septic foals, and adults subjected to severe systemic inflammatory response syndrome. Publications provide information regarding coagulation markers helpful for identification of hemostatic dysfunction in specific patient populations, as well as information regarding the influence of coagulopathy on outcome. Data regarding clinically relevant information on therapeutic intervention are lacking.
Conclusions – The relationship between inflammation and endotoxemia and development of coagulopathy is better understood in both human patients and the critically ill equine patient. Prospective clinical trials evaluating clinically relevant and financially feasible approaches to treatment are still needed.     

Nutritional requirements of the critically ill patient

The presence or development of malnutrition during critical illness has been unequivocally associated with increased morbidity and mortality in people. Recognition that malnutrition may similarly affect veterinary patients emphasizes the need to properly address the nutritional requirements of hospitalized dogs and cats. Because of a lack in veterinary studies evaluating the nutritional requirements of critically ill small animals, current recommendations for nutritional support of veterinary patients are based largely on sound clinical judgment and the best information available, including data from experimental animal models and human studies. This, however, should not discourage the veterinary practitioner from implementing nutritional support in critically ill patients. Similar to many supportive measures of critically ill patients, nutritional interventions can have a significant impact on patient morbidity and may even improve survival. The first step of nutritional support is to identify patients most likely to benefit from nutritional intervention. Careful assessment of the patient and appraisal of its nutritional needs provide the basis for a nutritional plan, which includes choosing the optimal route of nutritional support, determining the number of calories to provide, and determining the composition of the diet. Ultimately, the success of the nutritional management of critically ill dogs and cats will depend on close monitoring and frequent reassessment.     

Anesthesia of the critically ill equine patient.

There is a plethora of information regarding anesthetic management of horses; however, controlled studies of the critically ill equine patient are few.These patients should be managed like any equine anesthetic candidate but much more stringently:I. Preoperative evaluation and appropriate therapy may represent the difference between life and death during the intraoperative and recovery periods. 2. The anesthetic induction and maintenance protocol should be based on the individual situation of the veterinary facility and personnel("comfort zone"). 3. Appropriate monitoring and intraoperative supportive measures are essential. 4. The anesthetic period is a significant perturbation to homeostasis. Even if the horse seems to have done well (ie, as indicated by the cardiopulmonary values), a problem-free anesthetic period does not guarantee a successful recovery, and close monitoring should continue until the horse is ambulatory. 5. Critically ill patients are often in a negative energy balance. Supportive measures to ensure an adequate caloric intake, such as enteral or parenteral nutrition, facilitate healing and return of homeostasis.     

Colloid Oncotic Pressure and the Clinical Use of Colloidal Solutions

The synthetic colloids, dextran and hydroxyethyl starch, have only recently enjoyed widespread use in critically ill veterinary patients. Plasma proteins normally provide colloid oncotic pressure and, thereby, are the primary force responsible for retaining fluid within the vasculature. Abnormally low plasma protein concentrations, common in the critically ill patient, are associated with excessive fluid loss from capillaries and development of peripheral or pulmonary edema. Infusion of colloid solutions decreases the potential for and severity of edema in hypooncotic states. Dextran and hydroxyethyl starch solutions also provide other positive hemodynamic benefits and are a preferable alternative to crystalloid usage in the resuscitation of selected patients from hypotensive and hypovolemic states. Potential side effects of synthetic colloid infusion include anaphylactoid reactions, increased risk of bleeding, interference with cross matching, and acute renal failure. Knowledge of the mechanisms responsible for these adverse effects minimizes their occurrence.     

The therapeutic use of 25% human serum albumin in critically ill dogs and cats.

Twenty-five percent human serum albumin (HSA) is a foreign protein and can potentially cause immune-mediated reactions. For this reason, the author only recommends 25% HSA use after risk analysis shows that the benefits outweigh the potential risks of adverse events. If it is apparent that a critically ill animal may succumb to its illness because of the problems associated with severe hypoalbuminemia, the benefit outweighs the risk. The veterinarian must inform the owner of potential delayed immune-mediated reactions, describe these lesions, and follow the case weekly to ensure that no reaction has occurred. Although there are many positive attributes to the administration of 25% HSA, there seems to be specific situations in which 25% HSA may be indicated and others in which it may not be indicated.     

Effects of isovolemic resuscitation with hemoglobin-based oxygen carrier Hemoglobin glutamer-200 (bovine) on systemic and mesenteric perfusion and oxygenation in a canine model of hemorrhagic shock: a comparison with 6% hetastarch solution and shed blood

OBJECTIVE: To study Hemoglobin glutamer-200 bovine (Hb-200), 6% hetastarch (HES) and shed whole blood (WB) resuscitation in canine hemorrhagic shock. STUDY DESIGN: Prospective laboratory investigation. Animals Twelve adult dogs [29 +/- 1 kg (mean +/- SD)]. METHODS: Anesthetized dogs were instrumented for recording systemic and mesenteric hemodynamic parameters and withdrawal of arterial, mixed and mesenteric venous blood, in which hematological, oxygenation, blood gas and acid-bases variables were determined. Recordings were made before [baseline (BL)], after 1 hour of hypovolemia and immediately and 3 hours post-resuscitation with 30 mL kg(-1) of either Hb-200, HES, or WB. RESULTS: Blood withdrawal (average 34 +/- 2 mL kg(-1)) caused significant hemodynamic changes, metabolic acidosis and hyperlactatemia characteristic for hemorrhagic shock. Only WB transfusion restored all variables. Hemoglobin glutamer-200 bovine infusion returned most hemodynamic parameters including cardiac output and mesenteric arterial blood flow to BL but increased mean arterial pressure above BL (p < 0.05). However, Hb-200 failed to restore total Hb and arterial oxygen content (CaO2), leaving systemic (DO2I) and mesenteric O2 delivery (DO2Im) below BL (p < 0.05). Nevertheless, acid-base variables recovered completely after Hb-200 resuscitation, and met-hemoglobin (Met-Hb) levels increased (p < 0.05). Hetastarch resuscitation returned hemodynamic variables to or above BL but further decreased total Hb and CaO2, preventing recovery of sDO2I and mDO2I (p < 0.05). Thus, systemic and mesenteric O2 extraction stayed above BL (p < 0.05) while acid-base variables recovered to BL, although slower than in Hb-200 and WB groups (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Resuscitation with Hb-200 seemed to resolve metabolic acidosis and lactatemia more rapidly than HES, but not WB; yet it is not superior to HES in improving DO2I and DO2Im. The hyperoncotic property of solutions like Hb-200 that results in rapid volume expansion with more homogenous microvascular perfusion and the ability to facilitate diffusive O2 transfer accelerating metabolic recovery may be the key mechanisms underlying their beneficial effects as resuscitants.