Shock: Fluid therapy remains a basic tenet for successful resuscitation

Q. Please review shock fluid therapy for small animals.

A. Dr. Deborah Silverstein at the 2005 American College of Veterinary Internal Medicine Forum in Baltimore gave a lecture on shock fluid therapy. Some relevant points in this lecture are provided below.

Shock fluid therapy remains a basic tenet of therapy for the resuscitation of animals with non-cardiogenic shock. Volume replacement for the treatment of non-cardiogenic shock helps to restore tissue perfusion, attenuate the cytokine response, and reverse cellular swelling and injury that commonly occurs. The perfect fluid does not exist, but science has progressed in helping clinicians to better understand the use and abuse of fluid therapy for the treatment of shock. By reviewing the past, present and future of shock fluid therapy, the veterinarian might better understand the art of fluid resuscitation.

The past

During and after World War I, shock was thought to be secondary to an excessive neurogenic discharge, thus the word "shock". It was considered an over-response to the popular concept of "fight or flight". In 1960, Fogelman and Wilson found that dogs subjected to two hours of hemorrhagic hypotension followed by resuscitation with reinfusion of shed blood had 80 percent mortality. If these dogs were also given lactated Ringer's solution during resuscitation, mortality decreased to only 40 percent. Thus, the beginning of resuscitative fluid therapy commenced. Initially, blood-volume replacers not only included isotonic crystalloids but also exotic substances such as gum acacia, bovine and human plasma, plasma fractions and albumin.

The main therapeutic strategies include the arrest of bleeding and replacement of circulating blood volume. During most of the second half of the 20th century, aggressive fluid administration was recommended. The last decade re-examined this practice, and the adverse consequences of overaggressive fluid resuscitation have been recognized.

"Supranormal" endpoints of resuscitation will not increase survival and may actually do the opposite. Overzealous fluid administration to the bleeding patient may exacerbate bleeding tendencies and lead to clot disruption from increased blood flow, decreased viscosity and increased perfusion pressure. The goal is to restore effective circulating blood volume while minimizing the risk of further bleeding.

In addition, vigorous fluid resuscitation may potentiate the cellular injury caused by hemorrhagic shock and may predispose patients to interstitial edema throughout the body.

Normotensive versus hypotensive resuscitation

Hypotensive resuscitation has been advocated in order to prevent the resuscitation injury mentioned above. This technique calls for fluid administration to a goal mean arterial pressure of 60 mm Hg or systolic pressure of 90 mm Hg, the minimum pressure necessary to maintain vital organ perfusion.

It would appear that bolus administration of large quantities of crystalloids (the only fluid that is dosed using a full-blood volume) might increase blood pressure excessively and cause bleeding problems. One more recently proposed strategy for hypotensive resuscitation uses the presence or absence of a palpable peripheral pulse as a guide for fluid therapy. The British and American armed forces currently recommend that fluids be administered to maintain the presence of a radial pulse in soldiers with ongoing hemorrhage. It is important to keep in mind that the long-term effects of permissive hypotension are still unknown.

Early versus delayed resuscitation for hemorrhagic shock

The potential risks of early intravenous fluid therapy before surgical control of bleeding continue to be investigated. In an attempt to avoid the disruption of an early clot at the site of vascular injury, delayed resuscitation has been studied.

Although there is evidence to support both early and delayed resuscitation techniques, early resuscitation does appear to cause marked hepatic stability, an increase in urine output, decreased IL-6 levels and a lower mortality rate than delayed resuscitation strategies. However, the volume of fluid delivered is obviously very important. Not only are larger volumes of crystalloids more likely to dislodge early clots, but overzealous fluid administration may also lead to an increased inflammatory cytokine response and mortality.

A study performed by Siegel et al examined 40 dogs that were bled to a mean oxygen debt of 104 mL/kg and partial resuscitation strategies were investigated.

Animals that survived the shock were given 0 percent, 8.4 percent, 15 percent, 30 percent or 120 percent of the shed volume (as 5 percent albumin), held for two hours, and then administered the remaining portion of resuscitation fluid.

The oxygen debt response correlated significantly with base deficit and lactate, but not blood pressure. The dogs that received the 30 percent immediate resuscitation showed the mildest organ dysfunction with a complete recovery at seven days. Early, small volume, hypotensive resuscitation may prove to be the best treatment for resuscitation in patients with hemorrhagic shock.

Colloids versus crystalloids

The debate over colloids versus crystalloids for resuscitation has existed for more than five decades now and will likely not be over anytime soon. Although evidence-based medicine is the preferable method of making therapeutic decisions for patients, it is the vulnerability of the present evidence on this matter that intensifies the controversy. There are enough studies on the issue to sustain 11 systematic reviews or meta-analyses or quantitative data syntheses. However, the suboptimal quality of most of the primary studies, which is subsequently imparted to the systematic reviews, does nothing to ameliorate the situation. In reality, the use of colloid or crystalloid fluids varies considerably and depends primarily on personal choices, availability, clinical experience and cost.

If a review of the literature examining colloid versus crystalloid resuscitation for the critically ill patient is performed, the combined results suggest that the choice of resuscitative fluid has a small or no effect on mortality. In contrast, however, considering only trauma patients, the results suggest that the use of colloids carries an increase in mortality. Should crystalloids therefore remain preferable in the initial treatment of animals with traumatic shock?

The use of synthetic colloids has been shown to alter the coagulation profile and immune response. There has been extensive research in Europe investigating novel synthetic colloid products that do not interfere with coagulation and perhaps even positively modulate the inflammatory response following infusion and prevent or correct capillary leak syndromes. By increasing the C2:C6 ratio and decreasing the molar substitution to 0.4, a new hydroxyethyl starch (HES) product with a molecular weight of 130,000 has been introduced in Europe (Voluven®).

This solution has minimal effects on coagulation, does not accumulate in plasma after multiple dosing, and may help to minimize endothelial damage and "seal the leaks" in the capillaries, as other HES preparations have also claimed to do.

Small volume resuscitation

The use of hypertonic saline (HS) for resuscitation has been studied extensively. HS increases the blood volume by 2.5- to 3-times the volume infused and HSD by 3- to 4-times the volume infused, making these fluids impressively efficient compared to isotonic crystalloids (0.8 times volume infused) or even synthetic colloids (about 2 times the volume infused for Hetastarch and Dextran 70). The benefits of hypertonic, small volume resuscitation have repeatedly been shown to restore hemodynamic stability, restore splanchnic organ perfusion, attenuate neutrophil migration, reduce increases in post-resuscitation intracranial pressure, decrease cardiac troponin-I levels and lower pulmonary capillary wedge pressures.

There have been numerous studies in both experimental and clinical dogs examining the use of HSD for resuscitation from severe burns, pyometra with septic shock, traumatic shock, endotoxemia, hemorrhagic shock and gastric dilatation volvulus. Results are favorable overall, with an increase in mean arterial blood pressure, cardiac output, oxygen delivery and consumption, superoxide dismutase levels and minimal side effects were noted.

Future strategies and directions

Shock-induced depletion of energy stores was first recognized in the 1940s by Le Page. It is clear that the ATP levels in the liver, kidney and gastrointestinal tract are depleted rapidly, and correspondingly the metabolites are elevated during and after resuscitation from shock. Since hypoxanthine and xanthine are well-known substrates for xanthine oxidase, their accumulation during ischemia indubitably contributes to a burst of free-radical activity during reperfusion of the tissues. Thus, it is well proven that lipid peroxidation by oxygen-derived free radicals plays a large role in the morbidity and mortality associated with shock. Much of the current research is focusing on pharmacologic agents that might be used in conjunction with fluid therapy to limit the extent of depletion of cellular and tissue ATP by increasing ATP levels in the tissues and lowering xanthine and hypoxanthine levels during, and after, resuscitation. These include glutamine, crocein, ketone bodies and pyruvate-containing fluid strategies.

Perfluorochemicals are chemically synthetic molecules that consist primarily of carbon and fluorine atoms, and have been used to dissolve oxygen since 1966. The use of perfluorocarbon solutions to replace red blood cells for oxygen delivery was first demonstrated in 1968. Subsequent studies in 1994 and 1995 have looked at these solutions for the treatment of hemorrhagic shock in dogs. The use of perfluorocarbon resuscitation resulted in greater survival compared to lactated Ringer's solution. Further research may shed more light on these fluids.

The use of self-assembling amphophilic lipids or liposomes has been studied experimentally. Liposomes-encapsulated hemoglobin and red blood-cell enzymes such as superoxide dismutase are underway. The physiology and toxicity profiles thus far suggest that further research is needed before these products can be safely recommended.

The concept of freeze-drying blood products is not new but has led to continued investigations. Freeze-dried plasma products maintain undamaged protein constituents, even after 10 years of storage in a freeze-dried stage. The powder can be quickly reconstituted and even dissolved in a small volume of solvent that would yield a hyperoncotic, hypertonic fluid. Freeze-dried plasma might prove to be a method of resuscitation that prevents immune overactivation and allows for an easily stored, rapidly reconstituted resuscitation fluid of the future.

Conclusions

There is still ample room for research investigating the role of fluid type, quantity and fluid additives for resuscitation of animals with cardiovascular shock. The type of shock and stage of shock (compensatory, early decompensatory or late decompensatory) plays a major role in the approach to treatment.

The inflammatory response following hemorrhage is not the same as the inflammatory response following septic shock, so trying to use the same resuscitation strategy could prove fruitless.

The decision to use one class of fluid over another should be subjected to the same critical thought process and dependence on scientific evidence that takes place when choosing a drug to administer to a patient. Recent meta-analyses are beneficial but have not settled the debate and are fraught with their own weaknesses.

There is no "magic bullet" intravenous fluid solution for all patients with shock.

Dr. Hoskins is owner of DocuTech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200, or e-mail: jdhoskins@mindspring.com.