Complications in Equine Surgery. Группа авторов

Associated with Administration of Colloid Therapy

      A colloid is a large (high molecular weight, MW) hydrophilic molecule. Colloids do not freely permeate the capillary membrane and remain in the vasculature bed where they are responsible for plasma colloid oncotic (COP) pressure. Proteins, particularly albumin, are natural colloids. Hydroxyethylstarch (HES) is the parent name of a group of synthetic colloids. Other synthetic colloids include gelatins and dextrans, which are not widely used and have been mostly replaced by HES. There are different types (generations) of HES solutions available. They differ in concentration, MW, and molar substitution ratio and pattern of the hydroxyethyl molecules (C₂/C₆ ratio).

       Definition

       Volume overload

       Coagulopathies

       Acute kidney injury

       Pro‐inflammatory cytokine release

       Allergic reactions. Allergic reactions are very rare as the HES molecule is similar in structure to glycogen. The side effects of HES are due to the cumulative effects of therapy over several days, rather than a single 24‐hour dose. In human medicine there is currently not enough evidence to support a consistent difference between HES generations with regard to morbidity, mortality, hemorrhage and acute kidney injury.

       Risk factors

      The MW and pattern of substitution determines the pharmacokinetics and pharmacodynamics of the colloid but is also responsible for the severity of side effects [37]. Currently, hetastarch, hexastarch, pentastarch and tetrastarch preparations are available on the market.

       Pathogenesis

      In human medicine delayed onset pruritus, due to cutaneous deposition of HES in the dendritic cells of the skin (Langerhans cells), is reported in up to 54% of patients and is refractory to treatment. Clinical pruritus occurs usually several weeks after HES administration and may persist for 12–24 months. Side effects include acute renal injury with underlying mechanisms being unclear. Osmotic nephrosis, altered oncotic forces in the glomerulus, lead to a change in glomerular filtration rates and a decrease in reno‐protective albumin have been discussed as a potential cause [38–40]. Some studies have suggested that certain HES generations are associated with a higher risk for renal injury; however, a meta‐analysis of these studies in humans showed insufficient evidence to support this [41]. Human clinical trials and meta‐analysis have shown that the need for receiving renal replacement therapy due to renal failure is higher in patients treated with HES compared to other fluids, particularly in septic patients [42, 43]. No side effects have been noted in the few studies on colloid use in horses. A 10 mL/kg dose did not have a significant effect on serum creatinine, urine specific gravity, urine gammaglutamyltransferase (GGT), creatinine ratio and urine sediment examination in healthy ponies [44]. Care has to be taken to extrapolate human data to horses with signs of disease.

Dilutional coagulopathy, platelet dysfunction, and decreased concentration of von Willebrandt factor and factor VIII have been reported in humans. The clinical significance of HES‐induced coagulopathies is unclear [45]. Side effects are associated with the dose administered. The administration of a single dose (25 mL/kg) is generally accepted to be safe in humans and dogs. Incisional bleeding and bleeding into body cavities has occurred in dogs treated with large doses of HES (>30 mL). Daily or weekly hetastarch infusion over long periods did not result in significant coagulation abnormalities in humans [38]. Several studies have evaluated the effect of administration of HES on coagulation times. A minimal effect on platelet count, concentrations of von Willebrandt factor and factor VIII, as well as coagulation times, was noted after administration of 10 mL/kg HES to healthy horses in several studies [44, 46, 47]. Higher doses of HES (20 ml/kg) led to more changes in equine platelet function and factor concentrations compared to lower doses (10 mL/kg) [48]. The clinical significance of these findings is not clear at this stage.

       Prevention

      Avoid unnecessary use of colloids. Over the past few years the use of hydroxyethyl starches in humans has been associated with higher mortality rates and kidney injury. The Food and Drug Authority and European Medicine Agency (EMA) currently do not recommend the use of colloids in critically ill adult men, including those with sepsis (www.fda.gov, www.ema.europa.eu). However, the use of colloids is ]still recommended for specific subgroups of patients, such as volume resuscitation for acute blood loss.

      Many of the side effects seen in humans have to date not been observed in horses; however, adequately sized clinical trials are missing. The extrapolation of human data to animals has to be performed with caution, as there are differences in species physiology and treatment protocols. Acute kidney injuries and significant bleeding have also not been observed in dogs and cats treated with HES. As there is a lack of additional therapeutic options in horses, the use of HES is justifiable in selected cases. However, equine clinicians should carefully weigh the necessity of colloid use in horses. Horses with preexisting renal disease, coagulopathies and sepsis should be especially carefully monitored for side effects of HES infusions.

      Colloids were widely used in human and veterinary medicine over the last decades, as a means of increasing COP. The Starling Landis equation described the forces responsible for the fluid equilibrium between interstitium and capillaries. The main factors are the capillary oncotic pressure (COP), the capillary hydrostatic pressure and the hydrostatic pressure of the interstitium and the colloid oncotic pressure of the interstitium [5]. Until recently, the COP was believed to counteract the outward movement of fluid from the vascular space and to be the main factor responsible for maintaining intravascular fluid volume. However, recently the no absorption rule has been added to the traditional Starling equation, stating that net absorption back into the capillaries does not occur, even with increased plasma COP. Administering a hyperoncotic fluid is therefore thought unlikely to increase the movement of fluid from the interstitial space to the capillaries. The main driving force for fluid shifts is thought to be the interstitial hydrostatic pressure [5], questioning the use of colloids.

      In horses, colloids are used to expand plasma volume. They are used in healthy horses undergoing anesthesia and horses with disease resulting in decreased plasma oncotic pressure. In prticular, animals with gastrointestinal disease often suffer from hypoproteinemia and are being treated with colloids to restore COP [46, 49, 50]. The benefits include volume resuscitation with smaller volumes of fluid, shorter infusion times, longer intravascular duration of infused fluids, maintenance of intravascular volume despite low serum albumin concentrations, and reduced need for pressure medication during anesthesia.

      The recommendations for use of HES in human medicine have drastically changed in the recent past. New insights into physiology of fluid movements have questioned the benefit of an increased capillary COP. Additionally, HES administration has been associated with more reports of side effects and increased mortality rates in humans. Furthermore, several studies which initially described the beneficial effects of HES had to be withdrawn due to a conflict of interest of the authors [51].

      There is little data on use of colloids in veterinary medicine, particularly horses. Treatment protocols differ from human medicine, with respect to dosage, product, MS ratio and pattern, administration technique and concurrent fluid therapy. Extrapolation of data therefore has to be made with caution.

Complications of Enteral Fluid Therapy

Enteral fluid therapy is the administration of fluids into the gastrointestinal tract using a nasogastric tube or feeding tube. This technique is commonly used in human medicine, as a natural way of administering fluids, and is reasonably safe and cost effective. This is less commonly used in horses but can be an effective method for providing large amounts of fluids to a horse, especially under field conditions. Unfortunately lack of patient cooperation often limits its use. Horses cannot usually be stimulated to drink excessive amounts of fluids and forced oral feeding can lead to aspiration pneumonia.