Chapter 2. Crystalloid fluids

Crystalloid electrolyte solutions include isotonic saline, Ringer’s lactate, Ringer’s acetate, and Plasma-Lyte. In the perioperative period these fluids are used to compensate for anesthesia-induced vasodilatation, small to moderate blood losses, and urinary excretion. Although evaporation consists of electrolyte-free water, such fluid losses are relatively small during short-term surgery and may also be compensated by a crystalloid electrolyte solution.

These fluids expand the plasma volume to a lesser degree than colloid fluids as they hydrate both the plasma and the interstitial fluid space. However, the distribution to the interstitial fluid space takes 25–30 min to be completed, which is probably due to the restriction of fluid movement by the finer filaments in the interstitial gel. The slow distribution gives crystalloid electrolyte solutions a fairly good plasma volume-expanding effect as long as the infusion continues and shortly thereafter.

Isotonic saline is widely used, but has an electrolyte composition that deviates from that of the extracellular fluid (“unbalanced”). This fluid is best reserved for special indications, such as hyponatremia, hypochloremic metabolic alkalosis, and disease states associated with vomiting. Isotonic saline may also be considered in trauma and in children undergoing surgery. Hypertonic saline might be considered in neurosurgery and, possibly, in preoperative emergency care.

Ringer’s lactate, Ringer’s acetate, and Plasma-Lyte have been formulated to bemore similar to the composition of the ECF (“balanced fluids”). They are the mainstay of fluid administration in the perioperative period and should be used in all situationswhere isotonic saline is not indicated.

Chapter 3. Colloid fluids

Colloid fluids are crystalloid electrolyte solutions with a macromolecule added that binds water by its colloid osmotic pressure. As macromolecules escape the plasma only with difficulty, the resulting plasma volume expansion is strong and has a duration of many hours. Clinically used colloid fluids include albumin, hydroxyethyl starch, gelatin, and dextran.

The plasma volume expansion shows one-compartment kinetics, which means that colloids, in contrast to crystalloids, have no detectable distribution phase. Marketed fluids are usually composed so that the infused volume expands the plasma volume by the infused amount. Exceptions include rarely used hyperoncotic variants and mixtures with hypertonic saline.

The main indication for colloid fluids is as secondline treatment of hemorrhage. Because of inherent allergenic properties, crystalloid electrolyte fluids should be used when the hemorrhage is small. A changeover to a colloid should be performed only when the crystalloid volume is so large that adverse effects may ensue (mild effects at 3 liters, severe at 6 liters). The only other clinical indication is that dextran can be prescribed to improve microcirculatory flow.

There has been lively debate about clinical use of colloid fluids after studies in septic patients have shown that hydroxyethyl starch increases the need for renal replacement therapy. This problem has not been found in the perioperative setting but the use of starch has still been restricted.

The colloids have defined maximum amounts that can be infused before adverse effects, usually arising from the coagulation system, become a problem.

Chapter 4. Glucose solutions

Glucose 5% is given after surgery to prevent starvation and to provide free water for hydration of the intracellular fluid space. Glucose is sometimes infused before surgery as well, in particular when surgery is started late during the day, and, in some hospitals, also as a 2.5% solution during the surgical procedure. Glucose infusion has also been used together with insulin to improve outcome in cardiac surgery and in intensive care.

Because of the risk of hyperglycemia, intravenous glucose infusions need to be managed with knowledge, attention, and responsibility. Hyperglycemia promotes wound infection and osmotic diuresis, by which the kidneys lose control of the urine composition. The anesthetist has to consider a four-fold modification in infusion rate of glucose to account for the perioperative change in glucose tolerance. The suitable rate of infusion when a glucose infusion is initiated can be predicted by pharmacokinetic simulation. A control plasma sample taken one hour later shows whether the prediction was correct, and also that plasma glucose will only rise by another 25% if no adjustment of the infusion rate is made.

Glucose solution is contraindicated in acute stroke and not recommended in operations associated with a high risk of perioperative cerebral ischemia, such as carotid artery and cardiopulmonary bypass surgery. Subacute hyponatremia is a postoperative complication that is promoted by infusing >1 liter of plain 5% glucose in the perioperative setting.

Chapter 5. Hypertonic fluids¹

Hypertonic fluids have an osmotic content that is higher than in the body fluids. When this content remains in the extracellular fluid space, such as with saline, the volume effect becomes very powerful owing to osmotic allocation of fluid from the intracellular to the extracellular fluid space. These fluids have also been found to favorably modulate the inflammatory response. The most studied preparations are saline 7.5% with and without a colloid (dextran or hydroxyethyl starch) added.

This chapter reviews the current clinical evidence regarding the use of hypertonic fluids for the early resuscitation of injured patients and for perioperative indications for a variety of procedures. While there is a wealth of preclinical data suggesting potential benefit from this resuscitation strategy, the clinical trial data have failed to show any clear benefit to the prehospital administration of these fluids in trauma patients, and the data for perioperative use is limited. More study is needed to define the best use of these fluids in a variety of patient populations and surgical procedures.

Chapter 6. Fluids or blood products?

Thanks to the impressive anemia tolerance of the human body, red blood cell (RBC) transfusion may often be avoided despite even important blood losses – provided that normovolemia is maintained. While a hemoglobin (Hb) concentration of 60–70 g/l can be considered safe in young, healthy patients, older patients with preexisting cardiopulmonary morbidity should be transfused at Hb 80–100 g/l. Physiological transfusion triggers (e.g. decrease of VO₂, ST-segment depression in the ECG, arrhythmia, continuous increase in catecholamine needs, echocardiographic wall motion disturbancies, lactacidosis) appearing prior to the aforementioned Hb concentrations necessitate immediate RBC transfusion. In the case of unexpected massive blood losses and/or logistic difficulties impeding an immediate start of transfusion, the anemia tolerance of the patient can be effectively increased by several measures (e.g. hyperoxic ventilation, muscular relaxation, or adequate depth of anesthesia).

In cases of dilutional coagulopathy – often reflected by an intraoperatively diffuse bleeding tendency – a differentiated coagulation therapy can either be directed on the basis of viscoelastic coagulation tests (e.g. thromboelastometry/-graphy) or directed empirically by replacing the different components in the order of their developing deficiency (i.e. starting with fibrinogen, followed by factors of the prothrombin complex and platelets). The “global” stabilization of coagulation with fresh frozen plasma requires the application of high volumes and bears the risk of cardiac overload (TACO) and immunological alterations (TRIM).

Chapter 7. Body volumes and fluid kinetics

Body fluid volumes can be measured and estimated by using different methods. A key approach is to use a tracer by which the volume of distribution of an injected substance is measured. Useful tracers occupy a specific body fluid space only. Examples are radioactive albumin (plasma volume), iohexol (extracellular fluid space), and deuterium (total body water). The transit time from the site of injection to the site of elimination must be considered when using tracers with a rapid elimination, such as the indocyanine green dye. The volume effect of an infusion fluid can be calculated by applying a tracer method before and after the administration.

Guiding estimates of the sizes of the body volumes can be obtained by bioimpedance measurements and anthropometric equations.

The blood hemoglobin (Hb) concentration is a frequently used endogenous tracer of changes in blood volume. Hb is the inverse of the blood water concentration, and changes in Hb indicate the volume of distribution of the infused fluid volume. Certain assumptions have to be made to convert the Hb dilution to a change in blood volume. Volume kinetics is based on mathematical modeling of Hb changes over time which, together with measurements of the urinary excretion, can be used to analyze and simulate the distribution and elimination of infusion fluids.

Chapter 8. Acid–base issues in fluid therapy

Solutions such as NaCl 0.9% are an established cause of metabolic acidosis. The underlying mechanism, a reduction in plasma strong ion difference, [SID], is comprehensibly explained by the principles of the Stewart approach. Fluid-induced metabolic acidosis can be avoided by the use of so-called balanced solutions that do not cause alterations in plasma [SID]. Many balanced solutions are commercially available, their only drawback being their higher cost. Since NaCl 0.9% remains the first choice of resuscitation fluid in large parts of the world, there remains an important question over whether a large-scale upgrade to balanced solutions should be at hand. There is a lack of high-quality data at the time of writing, but there is increasing evidence that hyperchloremia has a detrimental effect on renal function and has an economic impact of its own. Therefore, until we have more definitive data, the use of balanced solutions in patients who need a relevant amount of fluid therapy seems to be a pragmatic choice.

Chapter 9. Fluids and coagulation

Infusion therapy is essential in intravascular hypovolemia and extravascular fluid deficits. Crystalloid fluids and colloidal volume replacement affect blood coagulation when infused intravenously. Questions remain over whether unspecific dilution and specific side effects of infusion therapy are clinically relevant in patients with and without bleeding manifestations, and whether fluid-induced coagulopathy is a risk factor for anemia, blood transfusion, mortality, and a driver for resource use and costs. In this chapter, pathomechanisms of dilutional coagulopathy and evidence for its clinical relevance in perioperative and critically ill patients are reviewed. Furthermore, medico-legal aspects are discussed. The dose-dependent risk of dilutional coagulopathy differs between colloids (dextran > hetastarch > pentastarch > tetrastarch > gelatins > albumin). Risk awareness includes monitoring for early signs of side effects. With rotational thromboelastometry/thromboelastography not only the deterioration in clot strength can be assessed but also in clot formation and platelet interaction. Fibrinogen concentrate administration may be considered in severe bleeding as well as relevant dilutional coagulopathy. Targeted doses of gelatins and tetrastarches seem to have no proven adverse effect on anemia and allogeneic blood transfusions. Further studies implementing goal-directed volume management and careful definition of triggers for transfusions and alternative therapies are needed.

Chapter 10. Microvascular fluid exchange

There is always a continuous leakage of plasma fluid and proteins to the interstitium, called the transcapillary escape rate (TER). The transcapillary escape rate of albumin (TERalb) corresponds to 5–6% of total plasma albumin per hour. Plasma volume is preserved mainly because of recirculation via the lymphatic system and transcapillary absorption. During inflammation and after trauma, TER may increase up to 2–3 times and exceed the recirculation capacity, resulting in hypovolemia, low plasma concentration of proteins, and tissue edema. The present chapter discusses mechanisms controlling microvascular fluid exchange under physiological and pathophysiological conditions, including possible passive and active mechanisms controlling transcapillary fluid exchange. Options to reduce the need for plasma volume expanders while still maintaining an adequate plasma volume are presented. Consequently, this may simultaneously reduce accumulation of fluid and proteins in the interstitium. The effectiveness of available plasma volume expanders is also discussed.

Chapter 11. The glycocalyx layer

Endothelial cells cover the inner surface of the vasculature and are essential for vascular homeostasis with regulation of vasodilation and vasoconstriction, permeability, inflammation, and coagulation. The endothelium is not a barren surface but is covered by a thick layer of so-called glycocalyx. The glycocalyx is built of heavily glycosylated proteins such as syndecans which are anchored in the cell membrane, freely associating proteoglycans such as hyaluronidase, and also a multitude of plasma molecules that bind and interact with the proteoglycans.

The glycoproteins collectively organize into the glycocalyx, which plays a vital role in several important vascular functions. It serves as a mechanotransductor mediating information on blood flow and cellular movement to the endothelium, it regulates permeability via its physical properties, it regulates binding of vascular factors to the endothelium, and it is the “habitat” of the resident components of the complement system and the coagulation cascade. In addition, the glycocalyx serves as a sink for small molecules and electrolytes in the plasma and generates chemokine gradients to guide leukocytes to sites of inflammation. The delicate structures of the glycocalyx can be easily disturbed and damaged by acute disease such as sepsis or ischemia, as well as chronic disease such as diabetes or hypertension. The proteoglycans and/or its sugar moieties can be shed by specific enzymes. Novel tools have been developed to better visualize the glycocalyx both in vitro and in vivo. An understanding and, possibly, a molecular manipulation of the glycocalyx will be important to improve our therapeutic strategies in patients.

Chapter 12. Monitoring of the microcirculation

Perioperative fluid management requires comprehensive training and an understanding of the physiology of oxygen transport to tissue. Administration of fluids has a limited window of efficacy. Too little fluid reduces organ perfusion and too much fluid causes organ dysfunction from edema. In addition, isotonic saline carries the danger of hyperchloremia, whereas balanced crystalloid solutions are pragmatic choices of fluid in the majority of perioperative resuscitation settings.

The prime aim of fluid therapy is to improve tissue perfusion so as to provide adequate oxygen to the tissues. Macrohemodynamical parameters and/or surrogates of tissue perfusion do not always correspond to microcirculatory functional states, and especially not in states of inflammation. Even when targets for macrohemodynamics are reached, the microcirculation may still remain damaged and dysfunctional.

Observation of the microcirculation in the perioperative setting provides a more physiologically based approach for fluid therapy by possibly avoiding the unnecessary and inappropriate administration of large volumes of fluids.

Hand-held videomicroscopy is able to visualize microcirculatory perfusion sublingually. It can be used to monitor the functional state of the microcirculation by assessment and quantification of sublingual microvascular capillary density, and thus to guide fluid therapy. The Cytocam-IDF device might provide the needed clinical platform because of its improved imaging capacity in terms of density and perfusion parameters as well as providing on-line quantification of the microcirculation.