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Year : 2016  |  Volume : 29  |  Issue : 3  |  Page : 487-494

A rationale approach to perioperative fluid therapy in adult patients

Department of Anesthesia and Intensive Care, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission14-Jun-2015
Date of Acceptance22-Jun-2015
Date of Web Publication23-Jan-2017

Correspondence Address:
Zeinab Zahran
Tolba Awida Street, Marium Building, 7th Floor, Zagazig, 44511
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1110-2098.198659

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The  aim of this study was to focus on the main fluid compartments of the body, and their relative volumes, the differences in their composition, and how these factors affect water and electrolyte balances within the body. In addition, the study aimed to highlight the different types of fluids that can be used for maintenance, replacement, and resuscitation in special situations and outline the latest British guidelines on adult perioperative fluid therapy.
Data summary
Fluid and electrolyte disturbances are extremely common in the perioperative period. Large amounts of intravenous fluids are frequently required to correct fluid deficits and compensate for blood loss during surgery. Major disturbances in fluid and electrolyte balance can rapidly alter cardiovascular, neurological, and neuromuscular functions. In this review, we summarize a clear understanding of normal water and electrolyte physiology, body's fluid compartments and common water and electrolyte derangements, their treatment, and anesthetic implications, which are essential parts of perioperative care and the management of perioperative hemodynamic instability.
Perioperative fluid therapy plays an important role in maintaining hemodynamic stability before, during, and after operation, as well as in preventing electrolyte disturbance. Although it saves life if used cautiously, it can also cause many adverse effects if used without understanding its physiology and how to be used in different situations.

Keywords: British guidelines on adult perioperative fluid therapy, fluid compartments of the body, major disturbances in fluid and electrolyte balance, perioperative fluid therapy

How to cite this article:
Helal S, Daha N, Zalat S, Zahran Z. A rationale approach to perioperative fluid therapy in adult patients. Menoufia Med J 2016;29:487-94

How to cite this URL:
Helal S, Daha N, Zalat S, Zahran Z. A rationale approach to perioperative fluid therapy in adult patients. Menoufia Med J [serial online] 2016 [cited 2020 Sep 21];29:487-94. Available from: http://www.mmj.eg.net/text.asp?2016/29/3/487/198659

  Introduction Top

Fluid and electrolyte disturbances are extremely common during the perioperative period. Large amounts of intravenous fluids are frequently required to correct fluid deficits and compensate for blood loss during surgery [1] .

Major disturbances in fluid and electrolyte balance can rapidly alter cardiovascular, neurological, and neuromuscular functions. Therefore, a clear understanding of normal water and electrolyte physiology, body's fluid compartments and common water and electrolyte derangements, their treatment, and anesthetic implications is required. Acid-base disorders and intravenous fluid therapy, as well as the ability to assess intravascular volume, are essential in perioperative care and the management of perioperative hemodynamic instability [2] .

The basic principle of maintaining adequate tissue perfusion must continue to be followed during surgery. However, this is influenced by a number of factors, including the vasodilator effects of anesthesia, blood loss, and the hormonal response to surgery, increased capillary permeability and albumin escape rate, and increased insensible losses [3] .

  Objectives Top

The aim of this study was to focus on the main fluid compartments of the body, and their relative volumes, the differences in their composition, and how these factors affect water and electrolyte balances within the body. In addition, the study aimed to highlight the different types of fluids that can be used for maintenance, replacement, and resuscitation in special situations as well and outline the latest British guidelines on adult perioperative fluid therapy.

  Data summary Top

Data source

Data were collected from previous literature, reviews, and studies as well as medical websites (PubMed, MD Consult) and Scientific Journals.

Study selection

Study selection was carried out by supervisors for studying new advancements in perioperative fluid therapy for adult patients.

Data extraction

In this review, data from published studies were manually extracted and summarized.

Data synthesis

In  this review several studies on the physiology of different types of fluids used in the perioperative period were included, in addition to studies on the different situations that direct the use of one type over another, their adverse effects, and the guidelines to adjust their use.

  Perioperative fluid therapy in adults Top

The usual concept of distribution volumes of intravenous fluids

The distribution of water and sodium in the body prompts several assumptions about the distribution of intravenous fluids. First, sodium-free water will be distributed across total body water. Second, solutions containing sodium in physiological concentrations will be distributed almost exclusively within the extracellular space. Third, solutions in which colloid osmotic pressure is similar to plasma colloid osmotic pressure will remain largely within the plasma volume. On the basis of these assumptions, less than 1/14 th of an infusion of sodium-free water in a 70-kg adult should remain within the plasma volume. If an isotonic sodium solution were infused, slightly less than 3/14ths of the fluid should remain within the plasma volume. If an iso-oncotic fluid were infused, plasma volume should expand by an amount similar to the infused volume ([Figure 1]). However, these estimates are obviously inadequate for predicting the retention of infused fluid, because they do not account for time differences in perfusion of different organs, urinary losses, or other physiological or pharmacological perturbations such as the effects of fluid deprivation, hypoproteinemia, anesthesia, hemorrhage, or septicemia [4] .
Figure 1 The distribution of total body water divided into the intracellular (ICV) and extracellular (ECV) spaces. For an adult man weighing 70 kg, the body water is equivalent to 60% of total body weight. This amounts to ∼42 l, distributed as 40% intracellular volume (28 l) and 20% extracellular volume (14 l), of which 10.5 l is interstitial and 3.5 l is plasma volume (red cell volume is a component of intracellular volume). Hb, hemoglobin.

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Regulation of water and sodium balance

Sodium is the principal solute acting to preserve water within the extracellular compartment. Total body water and extracellular volume are dependent on total body sodium. Consequently, maintenance of sodium balance is central to volume regulation. Changes in sodium balance lead to changes in plasma volume and are sensed principally through changes in the circulation. It is, therefore, not surprising that the systems regulating sodium excretion are closely integrated with those regulating blood pressure. The systems regulating salt balance, and thus volume, are essentially aimed at the preservation of tissue perfusion, which is sensed as the effective circulating volume. The potential for regional variation in perfusion, for example, with a change in posture and the primacy of certain organs, such as the brain, account for the presence of multiple volume receptors in various parts of the circulation. On examining the systems of salt and volume regulation, it is helpful to consider the concept of the effective circulating volume. The humoral and neural mechanisms involved in the regulation of water and sodium balance are illustrated in [Figure 2] [5] .
Figure 2: The humoral and neural mechanisms involved in the regulation of water and sodium balance. ACE, angiotensin converting enzyme.

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Different types of fluids are used.

  Crystalloids Top

A crystalloid fluid is a solution of small water-soluble molecules that can diffuse easily across semipermeable membranes. They are composed of low molecular weight (MW) solutes (<30 000 Da), either ionic (e.g., Na + and Cl ) or nonionic (e.g. mannitol). They are inexpensive compared with blood products and artificial colloids. The contents of a  number of commonly used crystalloids are listed in [Table 1] of Prough et al.'s [6] study.{Table 1}

Adverse effects of large-volume crystalloid infusion

There is no doubt that excess fluid accumulation can cause several problems after surgery. The extravascular accumulation of infused crystalloids will mainly occur in tissues with high compliance such as skin and connective tissue, but also in vital organs such as the lungs and kidney. Furthermore, inhibition of gastrointestinal motility and delayed healing of anastomoses are of great concern. Moreover, fluid accumulation in the lungs may predispose patients to pneumonia, respiratory problems, and delayed ventilatory support withdrawal [7] .

Effects of crystalloids on immune response

Trauma, surgery, and hemorrhage stimulate the immune system. During trauma with significant hemorrhagic shock, there is neutrophil activation, adherence, and emigration into tissues contributing to the systemic inflammatory response, which can lead to acute respiratory distress syndrome and multiorgan failure. Thus, fluid resuscitation in hemorrhagic shock must be performed with caution as it may be harmful, and the type of fluid chosen may contribute to the inflammatory syndrome and promote apoptosis in highly vulnerable tissues such as the gut [8] .

Effects of crystalloids on acid-base balance

Most crystalloid solutions are acidotic and have high chloride content. Traditionally, the saline-induced acidosis has been explained by the dilution of bicarbonate in plasma. However, studies have shown high chloride levels despite unchanged plasma volume. A more extended explanation is that the addition of saline alters the dissociation of water, leading to more free hydrogen, which is measured as a fall in pH [9] .

Thus, hyperchloremic acidosis can occur even with perioperative fluid management during stable conditions when large amounts of saline 0.9% are given [10] .

On studying acid-base disorders in the present study, metabolic acidosis was found frequently. It is also reported that hypoxia and acidosis increase cardiac excitability directly, increasing the risk for arrhythmias and cardiac arrests. Moreover, the presence of metabolic disturbances, such as hypocalcemia, hyponatremia, and acidemia, may exacerbate the effects of hyperkalemia, with subsequent serious arrhythmias [11] .

Effects on coagulation

Several studies have shown that both in-vitro and in-vivo crystalloids cause a hypercoagulability. The probable cause for this is an imbalance between naturally occurring anticoagulants and activated procoagulants, with a reduction in antithrombin III being the most important. This may occur when infusion is rapid [12] .

  Colloids Top

The ideal colloid solution would probably be a low-to-medium MW starch with a low degree of substitution, suspended in a balanced electrolyte solution. At present, no such solution exists commercially, but there are several interesting products undergoing phase III trials [13] .


These are synthetic colloids made with gelatin, commonly from bovine collagen. The MWs of the molecules are relatively small at 30-35 kDa. As a result, duration within the intravascular space is relatively short at ∼1-2 h. They are mainly excreted through the kidneys within 24 h or so. There is a significant associated incidence of anaphylaxis [14] .


Dextrans are colloids made with large glucose polymer molecules of differing MWs. They are produced by the action of the bacterium Leuconostoc mesenteroides on sucrose. Dextran 40 (MW = 40 kDa) has been used for purposes other than intravascular expansion. Dextrans with MWs of 70 kDa and  110 kDa were produced for fluid replacement but are now used infrequently. Their duration within the intravascular space is said to be longer than that of gelatins, but they are associated with a number of side effects including osmotic diuresis, renal failure secondary to deposition within the renal tubules, abnormal platelet function, coagulopathy, and interference with blood cross-matching [15] .


Hydroxyethyl starches are colloids composed of chains of amylopectin (glucose) molecules etherified and substituted with hydroxyethyl groups. Starches are effective volume expanders with a duration of action longer than that of the other synthetic colloids ranging from 4 h (lower MW fluids) up to 36 h (higher MW fluids). However, they have been associated with a number of serious adverse effects, especially the older higher substitution fluids, and are the attention of many studies [16] .


Albumin is a naturally occurring colloid with an average MW of 68 kDa. It is a product of plasma fractionation; however, because of the risk for Variant  Creutzfeldt-Jakob disease More Details transmission, the plasma used is obtained from outside the UK. The solutions produced are either 4.5, 5, or 20%. Albumin is a negatively charged molecule, which reduces its vascular permeability, and hence it can remain in the circulation for longer. The use of albumin over the last decade has been controversial [17] .

  Balanced solutions Top

Recent interest in the Stewart theory of acid-base has highlighted the effects of chloride on acid-base disturbance. Infusing large volumes of fluid with high chloride content will generate a metabolic acidosis, although the clinical impact of this is still under research. By substituting chloride with lactate, Hartmann's is considered a 'balanced' crystalloid. Balanced fluids, which contain higher physiological levels of chloride, along with a bicarbonate-precursor buffer and small amounts of other electrolytes, such as calcium, magnesium, and potassium, do not cause hyperchloremic metabolic acidosis [18] .

  Oxygen carrying plasma expanders Top

After William Harvey discovered blood pathways in 1616, many people tried to use fluids such as beer, urine, milk, and animal blood as blood substitute. The demand for more blood substitutes began during the Vietnam War as wounded soldiers were unable to be treated at hospitals due to blood shortages [19] .

Hemoglobin-based oxygen carriers (HBOCs)

Hemoglobin-based oxygen carriers (HBOCs) are an adaptation of the hemoglobin molecule, which, because of its high activity in the plasma, must be chemically modified to avoid potential deleterious outcomes. The hemoglobin tetramer (64 kDa) is unstable in solution, dissociating to αβ dimers that are rapidly cleared by the kidney. This results in a circulatory time of only a few hours and high toxicity to the renal tubular cells. The modifications have attempted to reduce renal clearance and toxicity [20] .

Intramolecular cross-linking to stabilize the tetramer [e.g. 'di-aspirin' technique (HemAssist;  Baxter) and recombinant technique (Optro; Somatogen/Baxter, U.S.A)]

Intermolecular cross-linking to polymerize to higher order oligomers [e.g. glutaraldehyde (PolyHeme; Northfield and Hemopure; Biopure) and o-raffinose (HemoLink; Hemosol)]

Surface conjugation to increase MW and diameter [e.g., polyethylene glycol (PEG Hemoglobin; Enzon and Hemospan; Sangart)].

The main sources for HBOCs are bovine blood, date-expired human blood, and biotechnological techniques. The latter have produced molecules with plasma half-lives between 12 and 36 h and several are at advanced stages of development. They do not require cross-matching, have similar oxygen dissociation curves to blood, and do not transmit bacterial or viral infections. Being cellular and of lower viscosity, they are potentially better than blood in delivering oxygen to ischemic or edematous tissues, which prevents the capillary flow of erythrocytes. However, this appears not to be the case because of induced suppression of relaxing factors within the microcirculation. Many can cause systemic vasoconstriction through endothelial nitric oxide scavenging. Primarily cleared by the reticuloendothelial system, they may cause impairment of macrophage activity and neutrophil priming, thereby reducing the subsequent release of cytotoxic effectors and the risk for multiple organ failure after trauma [21] .

The human-sourced polymer PolyHeme (six units) has been used in 21 trauma patients in a phase-II randomized study without major ill effects. Hemopure (bovine) has been given a lisence in South Africa for adult surgery. However, a randomized, controlled trial of di-aspirin cross-linked hemoglobin in trauma was stopped early because of a significant increase in mortality in the di-aspirin cross-linked hemoglobin group, possibly relating to the enhanced pressor effect [22] .

Perfluorocarbon emulsions

Perfluorocarbon emulsions were the first potential  blood substitutes to undergo clinical trials (Fluosol-DA;  Green Cross Corporation, Osaka, Japan). They are prepared as emulsions for most purposes because of their high insolubility in water. Some compounds have high solubility in oxygen, nitrogen, and carbon dioxide, although trials have shown relatively low oxygen content compared with blood. The droplets are small (<0.2, intramuscular), thus allowing better penetration in diseased vessels, and flow closer to vessel walls, thereby aiding the delivery of oxygen by mass action. The first disappointing trial led to the development of other compounds, one of which is still in a trial as an adjunct to acute normovolemic hemodilution (Oxygent; Alliance Pharmaceutical Corporation) [23] .

Liposome-encapsulated hemoglobin

Liposome-encapsulated hemoglobin is a formulation of HBOCs, in which hemoglobin is encapsulated within the lipid bilayers. It is believed that the encapsulated form of hemoglobin is the preferred means of delivering oxygen in vivo, because of the favorable toxicity profile, and efficient delivery of oxygen to the hypoxic tissue [24] .

The use of  LHb, which is a cellular hemoglobin, has been demonstrated to be beneficial in the treatment of hypohemoglobinemic shock. As a molecule of appropriate size (220 nm) that can carry oxygen, LHb may ameliorate cardiac dysfunction during lethal hemodilation [25] .

  Fluid therapy in daily practice Top

Standard fluid therapy includes replacement of fluid lost (by basal fluid requirements, perspiration through the surgical wound), loss to the third space, and blood loss and exudation through the surgical wound and maintenance of physiological functions ('preloading' of neuroaxial blockade). It is generally agreed that fluid lost by the basal fluid requirements, perspiration through the surgical wound, blood loss, and exudation should be replaced. Any disagreement as regards these losses is about the timing, the route of administration, and the type of fluid used for replacement. However, replacement of the so-called 'loss to the third space' and the 'preloading of neuroaxial blockade' are subject to much controversy, and doubts have been raised about the very existence of the third space loss. Replacement of such a third space loss, as well as the preloading of neuroaxial blockade, will inevitably cause a postoperative body weight gain (i.e. a postoperative fluid overload) [26] .

  Third space loss Top

Third space losses are more difficult to see and measure but can be extensive, continuing for 24-48 h postoperatively. Replacement of these losses is usually on a 1: 1 ratio. Current guidance recommends the use of Hartmann's or Ringer's lactate/acetate instead of 0.9% saline, unless there is hypochloremia. However, the loss to the third space is replaced according to algorithms. Volumes up to 15 ml/kg/h are recommended during the first hour of abdominal surgery, with decreasing volumes in subsequent hours [27] .

  Discussion Top

'Liberal', 'standard', or 'restrictive', it is in the eye of the beholder. Results of studies on fluid therapy will have an impact on everyday practice only if clinicians are able to accept one or more alternative regimens as being superior. Many clinicians are reluctant to change their fluid practices, impeding research on perioperative fluid handling and acceptance of protocol-based improvements. Research suffers not only from an almost unascertainable target, but traditionally from a lack of standardization, complicating the design of control and study groups. Investigators have normally named their traditional regimen the standard group and compared it with their own restrictive ideas. Consequently, a restrictive regimen in one study is often designated as liberal in another setup. In addition, studies claiming to compare restrictive versus liberal use of fluid should, in part, rather be interpreted as investigating hypovolemia versus normovolemia [28] . This shortcoming prevents even promising results from impacting daily clinical routine and makes any pooling of the data impossible. A further important limitation of the data in this field is the target of a given study. Perioperative fluid handling has been related, among other things, to nausea and vomiting, pain, tissue oxygenation, cardiopulmonary disorders, need for revision surgery, duration of hospital stay, and bowel recovery time. However, the relevance of each individual target depends on the examined type and extent of surgery, which in turn has an enormous influence on changes and significance of these outcome parameters. Avoiding postoperative nausea and vomiting in cardiopulmonary-healthy patients, for example, might be the most important goal after a 15-min knee arthroscopy. In contrast, it is merely a minor issue after a 6-h major abdominal intervention, in which cardiopulmonary complications or mortality rates are in the spotlight. Therefore, a careful differentiation between major and minor operations, as well as abdominal versus nonabdominal surgery, seems to be necessary.

The goal of perioperative fluid application differs in the cardiovascular system as we might be restrictive rather than liberal, especially in stenotic cardiac lesions. Therefore, it might be helpful to change our way of thinking from fluid 'therapy' toward fluid 'substitution'. Above that, it is only a half-truth to proclaim a more restrictive therapy to be superior to a liberal one. Rather, an adequate and timely replacement of actual losses with appropriate preparations seems to be an ideal primary approach. Therefore, we should divide fluid therapy into two components: (a) replacement of fluid losses from the body through insensible perspiration and urinary output and (b) replacement of plasma losses from the circulation due to fluid shifting or acute bleeding. Although a 'goal-directed' approach using circulatory surrogates is, in principle, possible to replace plasma losses, the extracellular compartment cannot currently be monitored. Therefore, losses from the latter should be replaced based on a protocol:

  • The extracellular deficit after usual fasting is low [29]
  • The basal fluid loss through insensible perspiration is ∼0.5 ml/kg/h, extending to 1 ml/kg/h during major abdominal surgery [30]
  • A primarily fluid-consuming third space does not exist.

Plasma losses out of the circulation have to be replaced with iso-oncotic colloids, presuming the vascular barrier to be primarily intact and acknowledging that colloidal volume effects are context sensitive. The basis should be a timely replacement of visible blood losses, possibly supplemented by a goal-directed approach. Goals depend on local and individual circumstances and can vary from the maintenance of heart rate and blood pressure within a normal range in daily routine, up to stroke volume control by means of pulse pressure variation or esophageal Doppler in special cases. Importantly, despite being helpful, extended monitoring does not primarily seem to be the diagnostic hardware we urgently need to change to apply a more rational fluid concept. Rather, it seems warranted to replace the infusion of crystalloid by colloid if we detect the patient's circulation to be in need of additional volume.

Establishing a modern approach to perioperative fluid handling is currently hindered by the claim of successful studies to have treated their patients restrictively. Until recently, this has led to skepticism among clinicians, because many believe that restrictive fluid handling means depriving patients of their actual needs, leading to dehydration, which must, logically, lead to a decreased circulatory state due to intravascular hypovolemia. A careful comparison of the applied study protocols with measured values of preoperative blood volume after overnight fasting and insensible perspiration, however, reveals that the fluid regimens were mostly not restrictive in the true sense of the word, but represented an adequate substitution of fluid needs. A measurable weight gain even in restricted study groups [30],[31] indicates that there is still room for improvements in this context. To tap the full potential will be an important challenge in the next years. Even using a worldwide regimen or guidelines for fluid replacement will make a systematic way of fluid therapy all over the world ([Figure 3]) [32] .
Figure 3: Summary guidelines for fluid therapy algorithm. BP, blood pressure; CVP, central venous line; JVP, jugular venous pulse; NG, naso-gartic; IVI, intra venous infusion.

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  Conclusion Top

It may be concluded that an 'adequate' rather than a 'liberal' or a 'restrictive' perioperative fluid approach may represent the gateway to improved patient outcome. An 'adequate' approach implies a careful 'substitution' of fluid deficits, losses, and needs, because the body normally strives to maintain its volume homeostasis. Blood should be transfused for all patients with hemoglobin less than 6 g/dl and not to be transfused for any patient with hemoglobin greater than 10 g/dl. Transfusion of blood may be withheld as long as a patient's hemoglobin remains at 7 g/dl or higher, and he is not actively bleeding. A blood 'transfusion trigger' may be 9-10 g/dl for a patient with cardiac disease to raise his or her oxygen carrying capacity. Further systematic reviews of randomized controlled trial are needed for evidence-based perioperative fluid regimens, including hemoglobin therapy [33] .

Perioperative fluid therapy may have important beneficial effects on outcome after surgery. Inappropriate fluid management is likely to harm patients, but fluid prescribing practice still varies widely. Therefore, NICE guidelines encourage a standardized approach to fluid prescription and management. Such initiatives are welcome and should be widely implemented to ensure the highest standards of patient care [34] .

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Conflicts of interest

There are no conflicts of interest.

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