Volumen
8 Número 3 Mayo - Junio 1996
Artículo de Revisión
| Jean-François Baron, MD |
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El mantenimiento de un adecuado volumen intravascular es de máxima prioridad durante el periodo perioperatorio. En la actualidad, los coloides sintéticos y los cristaloides son comúnmente utilizados para mantener la normovolemia en la práctica cotidiana. Esta revisión intenta proporcionar algunos lineamientos para una adecuada expansión de volumen en diversas situaciones clínicas durante la anestesia y en el perioperatorio. Se discuten los cambios fisiopatológicos condicionados por hemodilución, al igual que los cambios ultraestructurales condicionados por el estado de choque hemorrágico.
En general, son discutidos varios puntos, considerando que el análisis de la mayor parte de las situaciones clínicas durante la anestesia y el periodo perioperatorio demuestra que los cristaloides, los hidroxietilalmidones, las gelatinas y aún los dextranos, cuando se emplean en forma apropiada, pueden ser una alternativa económica y segura en casi todas las situaciones clínicas anestésicas y perioperatorias.
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Maintenance of an adequate plasma volume is an important clinical priority during the perioperative period- Today, natural and synthetic colloids and crystaloids are generally used to maintain normovolemia in standard clinical practice. This review intents to draw guidelines for plasma volume expansion in various clinical situations during anesthesia and postoperative care. Physiopathologic changes confered by hemodilution are discussed and ultrastructural changes due to hemorrhagic shock are also contemplated.
In general, several points are discussed, considering that the analysis of the most common clinical situations during anesthesia and postoperative care demonstrates that crystalloids, hydroxiethyl starches, gelatines and even dextrans, when appropriately used, could be an economic and safe alternative in almost all clinical situations, as far as anesthetic and postoperative care is concerned.
Palabras clave: anestesia, complicaciones anestésicas, hemorragia, hemodilución, choque, tratamiento.
Key words: anesthesia, anesthetic complications, hemorrhage, hemodilution, shock treatment.
Maintenance of an adequate plasma volume is an important clinical priority during the perioperative period. Most clinicians have eliminated the use of blood products for this purpose because of growing concerns about transmission of hepatitis and AIDS. Nowadays, natural and synthetic colloids and crystalloids are generally used to maintain normovolemia in standard clinical practice.
This chapter will intent to draw guidelines for plasma volume expansion in various clinical situations during anesthesia and postoperative care.
Plasma Volume Expanders Expendidure
The balance sheet of the expenditure of plasma substitutes in Europe is not easy to draw since first there is some variability in clinical practice from one country to another and second available synthetic colloids are not exactly the same in all European countries. Even if non extrapolable to standard European practice, the expediture of plasma substitutes in a big French hospital could be helpful to determine the ratio between the use in natural and synthetic colloids and to focus on the potential problems related to this practice.
From 1986 to 1990, the main change in the expenditure of plasma volume expanders was a fivefold increase in the use of human serum albumin. This increased expenditure in human serum albumin was timely associated with a decrease in the use of fresh frozen plasma, which was still largely used as a plasma volume expander until 1986. During the same period of time, no significant change in the use of either synthetic colloids or crystalloids was observed. During the year of 1990, the total number of albumin units infused is three times higher than the total number of synthetic colloids units. Despite a progressive decrease, the price of human serum albumin remains much higher than that of synthetic colloids. The economic consequences of such a strategy are obviously highly significant. Indeed, the total cost of plasma volume expansion with albumin is more than fifty times higher than that of synthetic colloids. Even if this balance sheet of plasma volume expanders expenditure cannot be extrapolated to European practice, the following point could be probably generalized: the cost of plasma volume expansion with human serum albumin is so high that the medical care system cannot afford it anymore.
Accordingly, a strategy for plasma volume expansion during anesthesia and postoperative must define safe and economic alternatives to the use of human serum albumin. In anesthetic practice and protoperative care, the most common clinical situations that require plasma volume expansion are: intentional preoperative hemodilution, hemorrhagic shock, intraoperative blood loss, anesthesia-induced relative hypovolemia and postoperative hypovolemia.
Intentional Preoperative Hemodilution
Preoperative intentional hemodilution is induced by an isovolemic exchange of whole blood with plasma substitutes to save autologous blood while maintaining normovolemia. Intentional hemodilution is commonly used as a simple autologous transfusion technique before orthopedic, urologic and vascular surgery. The pathophysiology of normovolemic hemodilution has been extensively studied. Briefly, it has been established that a reduction in hematocrit and, as a result, in arterial oxygen content, is not deleterious until a 25-30 % hematocrit, since compensatory mechanisms are involved to maintain oxygen supply and consumption. Indeed, the decrease in hematocrit induces an improvement in blood rheologic properties and especially in blood viscosity. In normovolemic conditions, the decreased blood viscosity induces an increased venous return and cardiac output. Despite the decreased oxygen carrying capacity, system oxygen supply is not compromised in relation to the increased cardiac output. Based on theoretical considerations, Hint first predicted that systemic oxygen transport may be at least maintained until hematocrit reaches 25%. These results have been fully corroborated by many experimental and clinical studies. The key point of the tolerance of hemodilution is the achievement and maintenance of normovolemia that points out the major importance of the choice and volume of a plasma substitute to infuse during and after the exchange. This issue was recently addressed by a recent study published by our group. In patients scheduled for abdominal aortic surgery, intentional normovolemic hemodilution was performed using either a 6% low molecular weight hydroxyethyl starch, HES 200/0.6, Elohes 6% or albumin 4%. The study runs over the plasma exchange period for 24 hours. After basal measurements, blood have been withdrawn from a large venous catheters and collected into standard citrate-phosphate-dextrose blood storage bags. Simultaneously, colloid solution was infused in a ratio of 1, 2 ml of colloid for each ml of blood withdrawn. Hemodilution was continued until the large vessel hematocrit reached approximately 30% as controlled by repeated micro-hematocrit measurements. An additional infusion of 500 ml of colloids was performed from 30 min to 3 hours after the exchange. Hemodynamic blood oxygen gas and hormonal plasma levels were determined before hemodilution, then 30 min, 1-2-3 and 24 hours after the end of hemodilution. As in both groups, the decrease in blood cells volume was exactly compensated by the increase in plasma volume no significant changes in total blood volume were observed. Throughout the study, in both groups, the common cardiovascular and metabolic effects of hemodilution were observed since after hemodilution, the decrease in arterial oxygen O2 content was compensated by an increased cardiac output to maintain systemic oxygen transport until the 24th hour. An increase in O2 extraction was observed after the exchange, but no further increase was observed until the 24th hour. No significant changes either in global O2 consumption or in lactate concentration were detected. Plasma renin activity (PRA) decreased in both groups while atrial natriuetic factor (ANF) rised with a peak value at the 2nd hour. The plasma levels of vasopressine (ADH) and catecholamines remained unchanged. ANF increased immediately after the exchange while the measured blood volume is unchanged when compared to basal values; in this context, two mechanisms may explain the change in ANF: increased heart rate or venous return. It has been demonstrated that tachycardia per se may induce a release in ANF. However, in our study, changes in heart rate were very limited. The increase of intravenous return most likely explains the increase in ANF. Indeed, during hemodilution, the decrease in whole blood viscosity induced an increase in venous return and cardiac output, which in turn may increase atrial wall stress and induce a release in ANF.. The increase in ANF was associated with a decrease in PRA. The same mechanisms as those discussed for ANF may have determined these last hormonal changes. In addition, a direct or indirect effect of ANF on the reninangiotensin system may have played a role in the decrease in PRA. The modulation of the ADH secretion mainly determined by changes in osmolality and carotid baroreceptors probably explained the non or undetectable variation of this hormone throughout the different events of this study.
The changes in ANF and ARP could have determined an increase in diuresis and natriuresis during normovolemic hemodilution. This hypothesis has not been checked in our study. One should remark that these hormonal changes do not facilitate the maintenance of normovolemia during hemodilution and may be a justification first for the choice of a long-acting plasma substitute, and second, for a secondary infusion of colloids after the exchange. When compared to 4% albumin, the HES 200/0.6 has at least the same efficacy to maintain normovolemia during 24 hours after intentional hemodilution.
Hemorrhagic Shock
The effects of hemorrhagy may markedly vary with the nature, duration, severity of blood loss, patient status, and with the speed, adequacy and nature of resuscitation.
Even though a decreased blood volume is obviously the first consequence of hemorrhage, there are other abnormalities in water repartition. A decreased interstitial volume is generally associated and result from a negative net water flux between the intravascular space and the interstitial space. A third space development could secondarily contribute to decrease the exchangeable interstitial space. A third potential abnormality is the development of intracellular hyperosmolarity secondary to an altered energy metabolism which is an essential source for ionic pump. The absence of the high energy phosphate as a consequence of tissular hypoxia leads to depression of pump function and cell swelling. Thus, the resulting effects of hemorrhagic shock are a decreased interstitial volume, an intracellular hyperosmolarity and hydratation.
Although the restitution of intravascular, interstitial and intracellular fluid volumes is the main objective of hemorrhagic shock treatment, based on the pathophysiological course of events in shock, other objectives, such as restoration of the oxygen transporting capacity of blood, improvement in microvascular blood flow, correction of acid-base disturbances, prevention of cell injury at reperfusion and inhibition of activation cascade system (complement activation, release of mediators), have been outlined by some authors. There is still a dispute as to the selection of fluid for resuscitation, the so-called colloid versus crystalloid controversy. Arguments on both sides have been outlined in a number of major reviews. More recently, the above given objectives for the treatment led some authors to recommend the use of a combination of crystalloids and colloids. Some major arguments have to be emphasized.
As previously discussed, an extracellular dehydration is logical during hemorrhagic shock and the use of crystalloids to rehydrate this extracellular space seems to be logical. However, Cervera have demonstrated theoretically and experimentally that the ratio of crystalloids to infuse over the volume of blood loss is not a linear relationship and that there is an exponential increase in this ratio with the severity of hemorrhage.
Indeed, this ratio is about 4-5 for blood loss lower than 40% of blood mass and could be as high as 12 for bloodloss greater than 70% of blood mass. This phenomenon is directly related to the progressive development of an interstitial edema that is the consequence of the non linear relationship between interstitial pressure and volume. Indeed, during rehydratation with crystalloids, the interstitial volume progressively increases until insterstitial pressure rises from a negative value to zero. At this pressure, two phenomenons simultaneously occur and are responsible for the development of massive edema in the loose binding connective tissue. First, lymphatic flow is maximal, second, the perimicrovascular interstitial space is saturated with water. These phenomenons explain the exponential increase in the ratio of crystalloids to infuse over blood loss with the severity of hemorrhage. Even though the use of crystalloids seems logical during hemorrhagic shock, the volume of crystalloids to infuse is a real limitation to the exclusive use of crystalloids, especially during severe hemorrhage. Since a quick restoration of global and regional hemodynamics is a major determinant of prognosis to prevent cell injury and activation cascade system (complement activation, release of mediators), it could be suggested that an administration of long acting colloids plus crystalloids is logical to achieve both goals, rehydration of the interstitial space and a quick restoration of global and regional hemodynamics.
Compensation of Intraoperative Blood Loss
While intentional hemodilution and hemorrhagic shock have been extensively investigated, the compensation of intraoperative blood loss has not been studied as well. Actually, the problem of compensation of intraoperative blood loss could be most likely assimilated to "intentional hemodilution" rather than to hemorrhagic shock. However, some specific points have to be outlined: pharmacokinetics of plasma substitutes adapted to compensate blood loss and side effects of plasma substitute on coagulation.
As already mentioned about intentional hemodilution, it seems logical to compensate intraoperative blood loss using long lasting plasma substitute. This point could be further illustrated by the study of Kolher and coworkers. In normal volunteers, blood have been withdrawn (400 ml) and secondarily compensated by the infusion of 500 ml of various plasma substitutes, gelatins, hydroxyethyl starches or dextrans. All of them were initially efficient to restore blood volume. However, when considering the maintenance of normovolemia during the hours following the compensation, some major differences between the plasma substitutes could be pointed out. One or two hours after the infusion, the volunteers who received gelatins were slightly hypovolemic. After infusion of HES 200/ 0.5 or dextrans, normovolemia was maintained during a maximum of 12 hours. Thus, even normal volunteers who were supposed to be able to maintain normovolemia were slightly hypovolemic after a limited blood loss and an initial efficient compensation. The onset of this secondary hypovolemia seems to be highly dependent on pharmacokinetics of plasma substitutes. Accordingly, it seems logical to recommend the use of a long-lasting plasma substitute to compensate blood loss.
Side-effects of plasma substitutes on hemostasis have to be considered, especially when hemorrhagic surgery is concerned. High molecular weight hydroxyethyl starches and dextrans are the plasma substitutes that induce significant side-effects on hemostasis. This point has been reviewed elsewhere. Briefly, these colloids and especially dextrans 60.70 and hydroxyethyl starches 450 could induce a type I Von Willebrand-like syndrome that can be responsible for abnormal clinical bleeding. Gelatins are probably the synthetic colloids that induce the loose (or even none) side-effects on hemostasis. Accordingly, when bleeding is very active and responsible for blood loss greater than 1.5 or 2 liters, it seems logical to recommend the use of gelatins during the acute phase of bleeding and to secondarily infuse long-lastin colloids to maintain normovolemia postoperatively
Anesthesia - Induced Relative Hypovolemia
General or regional anesthesia induces a relative hypovolemia, generally in relation to an increased venous compliance. As a result, a decreased venous return is one of the major mechanisms responsible for the hemodynamic effects of anesthesia. These effects are highly dependent on the type of anesthesia, on the anesthetic drug and on the preoperative state of hydratation.
Patients coming to the operating room may be grouped according to whether they are undergoing routine scheduled operations or require emergency procedures. After midnight prior to the day of the surgical procedure, oral intake is withheld for elective surgery. This hydric deficit, nearly one-half of their daily maintenance fluid requirements, is increased by other losses from nasogastric suction, diarrhea, or intestinal preparation. The volume status of patients undergoing emergency procedures can be even more complex and severe. Protein and extracellular fluid loss into the peritoneal cavity or the intestinal insterstitium. is frequently associated with abdominal lesions such as perforated viscue, bowel obstruction, and vascular obstruction. In addition, the body water status could be compromised not only by the surgical problem itself, but also by preexiting medical derangements of therapy such as hyperthermia and sweating, diabetic ketacidosis, diabetes insipidus, hepatic cirrhosis or diuretic therapy.
During the immediate preoperative and intraoperative periods, fluids are required to compensate a preoperative hydric deficit and to compensate the cardiovascular effects of anesthesia. Rehydration of the extracellular space is the main objective of the preoperative fluid infusion. Most of the times, crystalloids are required to rehydrate the extracellular space. However in emergency procedures, when normovolemia must be rapidly corrected before induction of anesthesia synthetic colloids could be preferred, leaving temporarily the interstitial space deficit.
The standard practice that consists to compensate the cardiovascular effects of anesthesia with a plasm substitute is admitted by most anesthesiologists. Most of the times, crystalloids infusion is preferred, a choice based on limited requirements in volume and in duration, a perfect tolerance and low cost. In fact, there is a lot of various clinical situations in which coloids could be preferred to crystalloids, especially when larger initial volume effect is expected. Side-effects on hemostasis and allergic reactions are probably the major criteria of choice. Although allergic reaction are a cause of concern, gelatins are commonly used in these clinical situations. Allergic reactions can be prevented with dextrans, but side-effects on coagulation could be a limit to their use. Hydroxyethyl starches (HES 200-250), which induce few sever allergic reactions and very limited effects on hemostasis, could be another alternative.
Postoperative Hypovolemia
There are several reasons for continuing fluid an blood loss in the postoperative period. The usual cause is active bleeding from an open vessel. Other source of volume depletion are continued loss into traumatize tissues and bleeding associated with coagulopathies Patients having major operations may be either volume depleted preoperatively or received partial replacement of blood, plasma and fluid loss intraoperatively. I addition, they often continue to lose volume in the postoperative period in relation to insensible loss that could be increased by postoperative fever, and to nasogastric suction, drainage from fistulas, to tubes pleural and peritoneal drains. A third space developmen as a consequence of surgical trauma or due to increase capillary membrane permeability is also a common cause of postoperative hypovolemia. A progressive elimination of synthetic colloids infused intraoperatively contributes to induce postoperative hypovolemia.
Fortunately, most patients are able to compensate for these deficiencies and require only minor volume adjustments. Indeed, clinically stable patients may have appreciable blood volume deficits. Routine measurements of vital signs have been shown to correlate poorly with volume deficits. Although it could be the physiological result of various etiologies, an important indicator of postoperative hypovolemia is oliguria, which is defined as urine production of less than 15 ml per hour. When related to hypovolemia, oliguria is associated with a low urinary sodium (<30 mEq/1), a high urinary osmolality and a high urine creatinine concentration.
Thus, postoperative hypovolemia is common and generally easily diagnosed. When considering postoperative hypovolemia and potential mechanisms that could be responsible for it, the use of a long acting plasma substitute seems to be logical. The pharmacokinetics properties and limited side-effects of human serum albumin have certainly promoted its use in this indication. Indeed, even if non extrapolable to standard European practice, the expenditure of plasma substitutes in a big French hospital could be helpful to define a strategy. The breakdown of the albumine by type of use shows that nearly 50% of the albumine is used postoperatively. The economic consequences of such a strategy are obviously highly significant and since the use of a longlasting plasma substitute is logical in this indication, long-acting hydroxyethyl starches with a molar substitution ratio greater than 0.6 or high molecular weight dextrans could be better recommended.
Dextrans would be preferred in countries where deep venous thrombosis prevention is not performed using heparine. Several studies have demonstrated that dextrane significantly reduced the incidence on deep venous thrombosis. Several comparative studies with vitamin K antagonists, unfractionated heparin and low molecular weight heparin have demonstrated the efficacy of dextrans in deep venous thrombosis prevention, especially when associated with graded compression stockings.
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