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Perioperative uid therapy

Chris Marsh Jules Brown

Learning objectives
After reading this article, you should be able to: C Understand normal electrolyte and uid homeostasis and how this is impacted upon by surgery and injury C Understand the types of intravenous uid therapy and the individual indications and contra-indications for their use C Understand the importance of goal directed uid therapy and cardiac output optimisation to ensure effective oxygen delivery in the perioperative period

Precise physiological systems ensure normal uid and electrolyte homeostasis in health. These mechanisms can be disrupted by illness and injury (including surgery). Disruption results in altered cellular and organ function. An understanding of this physiology is therefore crucial to provide safe and effective uid management for these patients. Effective uid management is required to cover the full perioperative period and there is increasing evidence to support the use of cardiac output monitoring to guide uid therapy. The ultimate aim is to ensure preoperative, intraoperative and postoperative uid optimisation to maximise cardiac output and oxygen delivery at the cellular level. Such goal directed uid therapy tailors management to individual patient physiology, associated comorbidity and the degree of surgical insult and subsequent stress response with the aim of reducing mortality, morbidity and reducing the length of postoperative stay.

Fluid homeostasis
In health, 60% of total body mass is composed of water which moves freely between compartments under the inuence of osmotic forces. About 40% of this resides in the intracellular compartment. The movement of electrolytes and other molecules is dependent upon factors including ionic charge, molecular size, concentration/ ionic gradients and active processes. The composition of intravenous uids, therefore, will determine their distribution between compartments and the speed of this distribution change. Extracellular osmolality is normally maintained within a narrow range through numerous neuro-endocrine processes, despite wide variations in uid and sodium intake. Interestingly, the ability of normal human kidneys to retain sodium and water during times of paucity are far more efcient than the ability to handle and excrete excesses of sodium. The normal dietary requirements for water and electrolytes are listed in Table 1. After injury/surgery After injury or surgical insult physiological processes result in antidiuresis and oliguria mediated by vasopressin, catecholamines and the renineangiotensinealdosterone (RAAS) system. Water and sodium are retained even in the presence of uid overload. In patients with a signicant stress response following major surgery, increased capillary permeability leaks albumin into the interstitial space, resulting in intravascular hypovolaemia and further activation of the RAAS system. RAAS activation can also result in the depletion of potassium which further impairs the excretion of a sodium load. In critically unwell post-surgical patients, a catabolic state tends to ensue with a resulting increase

Keywords colloid; crystalloid; uid homeostasis; uid management;

goal-directed; perioperative Royal College of Anaesthetists CPD Matrix: 2A05

Normal uid and electrolyte homeostasis of the intracellular, extracellular, interstitial and intravascular compartments is under precise physiological control to allow efcient cellular and organ function. Any injury (including surgery) may result in changes to this physiological control resulting in the retention of sodium and water. During the perioperative period there is also a reduction in enteral intake so that intravenous uid therapy is utilized to ensure adequate volume and electrolyte status. Peri-operative uid therapy is essential to prevent the complications associated with hypovolaemia. There is an increasing amount of evidence however to suggest that excessive infusions of intravenous uid may be associated with adverse events.1 Surprisingly, the management of perioperative uid administration is often non-standardized and not individualized to patient physiology, surgical insult or perioperative environment, despite the availability of national guidelines.2

Daily water, electrolyte and uid requirements

Substrate Water Sodium Potassium Chloride Phosphate Calcium Magnesium Energy Table 1 Requirement 1.5 ml/kg/hour 1e1.5 mmol/kg 1 mmol/kg 1.5 mmol/kg 0.2e0.5 mmol/kg 0.1e0.2 mmol/kg 0.1e0.2 mmol/kg 145 kJ/kg

Chris Marsh MBChB FRCA is an ST7 in Anaesthesia at Cheltenham General Hospital, Cheltenham, UK. Conicts of interest: none declared. Jules Brown BSc MBChB MRCP FRCA DICM is a Consultant Anaesthetist at Frenchay Hospital, Bristol, UK. Conicts of interest: none declared.



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in urea and nitrogen production. The excretion of nitrogen competes with that of sodium and chloride which is often retained and further contributes to interstitial oedema.

Types of intravenous uid therapy

Crystalloids These are solutions of small water-soluble molecules that can diffuse easily across semipermeable membranes. The properties of these solutions are largely determined by their tonicity (osmolality relative to plasma) and their sodium content (affecting their distribution within body compartments e Table 2). Isotonic uids: these have an osmolality which is comparable to the physiological norm. These can either have a normal sodium content such as Hartmanns solution and sodium chloride 0.9% (normal saline) or a low sodium content such as glucose 5% or sodium chloride 0.18%/glucose 4%. Fluids with a normal sodium content distribute freely within the extracellular uid (ECF) compartment causing little change in sodium concentration and osmolality. As a result this limits the movement of water out of the ECF into the intracellular uid (ICF) compartment and vice versa. Fluids with a low sodium content essentially provide free water once the glucose component has been metabolized which is then free to move between the ICF and ECF compartments. As such they are good for rehydration but risk hyponatraemia if used in excess. Non-isotonic uids: these uids can either be hypo- or hypertonic relative to normal plasma tonicity. They are typically reserved for special situations where manipulation of plasma osmolality is required. Hypertonic saline (sodium chloride 5%) is an example of a hypertonic uid which when given raises the ECF concentration of sodium resulting in a net shift of water from the ICF into the ECF. This is benecial, for example, in the management of cerebral oedema following head injury and has been shown to be of benet in the management of some trauma patients.

Colloids These uids contain larger, more insoluble molecules that do not readily cross semipermeable membranes. Their movement out of the intravascular space depends on their molecular weight (MW), shape, ionic charge and the capillary permeability. There are several types available depending on the colloid used (Table 2). Gelatins: these are synthetic colloids made with gelatin, commonly from bovine collagen, and as such carry an associated incidence of anaphylaxis. The molecular weights of the molecules are relatively small at 30e35 kDa and duration within the intravascular space is relatively short (1e2 hours) compared to other colloids. Renal excretion occurs within 24 hours. Dextrans: these colloids are made with large glucose polymer molecules. Dextran colloids with molecular weights of 70 and 110 kDa were produced for uid replacement and due to their increased molecular weight have a longer duration of action within the intravascular space than gelatins. However, they are used infrequently due to the associated side effects which include an osmotic diuresis, renal failure secondary to deposition within the renal tubules, abnormal platelet function, coagulopathy and interference with blood cross-matching. Starches: hydroxyethyl starches (HES) are colloids composed of chains of amylopectin (glucose) molecules etheried and substituted with hydroxyethyl groups. They also range according to their molecular weight but also according to the degree of group substitution, for example HES 130/0.4 (average MW 130 kDa, 40% substitution), HES 450/0.6. They are effective volume expanders with a duration of action longer than that of the other synthetic colloids ranging from 4 to 36 hours depending on molecular weight. However, they also have been associated with a number of serious adverse effects particularly renal failure and especially with the older higher substitution uids. There is ongoing research to determine the extent of this association.

Composition of intravenous uids

Type of uid Plasma Saline 0.9% 5% Dextrose 4% Dextrose saline 0.18% Hartmanns Gelofusine HES 6% (130/0.4) Volulyte HES 6% (130/0.4) HES 10% (200/0.5) HES 6% (450/0.6) 5% Albumin
HES, hydroxyethyl starches.

NaD (mmol/litre) 136e145 154 0 30 131 154 154 137 154 154 150

KD (mmol/litre) 3.5e5.0 0 0 0 5 0 0 4 0 0 0

ClL (mmol/litre) 98e105 154 0 0 111 125 154 110 154 154 150

Osmolarity (mosm/litre) 280e300 308 278 154 275 290 308 286 308 308 300

Molecular weight (kDa) e e e e e 30,000 130,000 130,000 200,000 450,000 68,000

Table 2



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Albumin: it is a naturally occurring colloid with an average molecular weight of 68 kDa. It is a product of plasma fractionation but due to the risk of variant CreutzfeldtJakob disease 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 so it can remain in the circulation for longer. The use of albumin over the last decade has been variable due to initial concerns in its use in critically ill patients The SAFE study3 has, however, disproved concerns regarding increased mortality in this patient group.

losses. Major surgery poses a more complex picture due to uid shifts, the systemic inammatory response and subsequent neuro-endocrine sequelae. The assessment of these patients is also challenging as stand-alone clinical parameters (heart rate, blood pressure, central venous pressure etc) do not correlate well to volume status. Dynamic responses to uid challenges (e.g. 250 ml) are more useful in these patients and The National Institute for Health and Clinical Excellence (NICE) has endorsed the use of peri-operative cardiac output monitoring to optimize volume status and stroke volume.7 Preoperative uid management Every effort should be made for oral intake to be continued until the minimum time prior to theatre. The use of carbohydrateloaded drinks should be considered as part of a routine perioperative regime and may improve patient satisfaction and recovery from surgery. Bowel preparation should be avoided where at all possible and if it is required, or where uids are required for maintenance, they should be prescribed to ensure that euvolaemia and normal electrolyte levels are sustained. In the high-risk surgical patient, preoperative volume status should be optimized and management plans made regarding their intra-operative and postoperative care based around predetermined goals for cardiac output and oxygen delivery. Intraoperative uid management Signicant uid losses can occur during the perioperative period via a number of routes. These include uid loss from nasogastric aspirates, vomit and diarrhoea, volume loss into drains, blood loss from the surgical site and insensible losses. Third space losses are usually concealed and more difcult to measure but can be extensive, continuing for 24e48 hours postoperatively. In patients undergoing major orthopaedic and major abdominal surgery, evidence suggests that goal-directed uid therapy is associated with a reduced length of stay and postoperative complications.8,9 Intraoperative cardiac output monitoring (e.g. oesophageal Doppler) enables manipulation of volume status to optimize ventricular lling and stroke volume and to allow assessment of the requirement for inotropes to maximize cardiac output. In major abdominal surgery, this goal-directed uid regime has also produced an earlier return to enteral feeding and a reduced ileus.9 The evidence base for its use in emergent major surgery is more limited but does point to signicant advantages of goal-directed therapy and stroke volume optimization in this patient group. Postoperative uid management It is important to note that there is no such thing as standard postoperative uid therapy. Before discharge from the recovery unit, volume status should be assessed and an action plan documented regarding ongoing requirements. In most patients who are euvolaemic and haemodynamically stable this will include returning to oral administration as soon as possible. The majority of postoperative patients will be in a positive uid and sodium balance due to neuro-endocrine responses and uid administration. Postoperative uid management, therefore, should be aimed at restoring the patient to their normal status. If a patient is euvolaemic then regimes should be structured to allow cautious net excretion of excess salt and water. To facilitate the prescription of correct volumes and types of intravenous

Balanced solutions
The Stewart theory of acidebase balance has highlighted the effects of chloride on acidebase disturbance. Infusing large volumes of uid with high chloride content will generate a metabolic acidosis, although the clinical impact of this is debated. By substituting chloride with lactate or acetate, Hartmanns is deemed a balanced crystalloid. Whereas most colloids are suspended in 0.9% sodium chloride solutions, a number of balanced colloid solutions are now available.

Crystalloids or colloids
It is important to consider any intravenous uid as a drug which will have both benets and side effects. In addition, the type of uid given should reect the volume and electrolyte status of the patient and the clinical goal. There is no one single crystalloid or colloid that can solely provide appropriate uid and electrolyte components. In general, glucose-based uids will provide free water and sodium-based uids will provide sodium (although often in supra-physiological levels). Potassium can be provided by additional supplementation or in balanced solutions (e.g. Hartmanns). There is no evidence that resuscitation with colloids reduces the risk of morbidity or mortality compared with resuscitation using crystalloids.4 Crystalloids are cheap, easily available and are associated with a low risk of anaphylaxis. However they rapidly leave the intravascular space with only 25e35% remaining intravascularly following infusion. Colloids have a longer intravascular half-life but are more expensive, have an increased incidence of anaphylaxis and there are ongoing concerns regarding colloids with respect acute kidney injury in sepsis.5,6 As such there is ongoing research into these topics and prescription of these uids is likely to be based around personal choice and clinical indication until there is strong evidence either way.

The perioperative period

Assessment of uid status Inadequate intravascular volume in the perioperative period results in a reduced cardiac output, reduced oxygen delivery to tissues and is associated with increased morbidity and mortality. However, there is an increasing body of evidence to suggest that excessive uid administration is also associated with increased length of recovery and rates of postoperative complications. It is essential therefore to assess uid status and uid responsiveness to guide appropriate therapy. In minor surgery, uid requirements will be required to make up for uid decit and to replace



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uids in the postoperative period, monitoring should include careful uid balance charts, clinical examination, weight measurements and regular biochemical analysis. In the high-risk group or those undergoing major surgery, meticulous attention to volume status is required and there is possible evidence to support the continued use of goal-directed therapy in the immediate postoperative period.10

The management of perioperative uid balance and the prescription of perioperative uids often varies widely despite the well-recognized physiological sequelae of tissue injury. Inappropriate uid regimes are likely to result in poorer patient outcomes, whilst there is a growing body of evidence to suggest that goal directed therapies may well have signicant benets. The prescription of intravenous uid needs to be tailored to specic patient parameters and to the degree of surgical insult. Currently, no single colloid or crystalloid can be used as a solo agent. National guidelines currently attempt to set out evidence based approaches to perioperative uid management and further research should help to resolve existing dilemmas and standardize the prescription of these drugs. A

Fluid prescription in acute kidney injury

The aetiology of acute kidney injury (AKI) can be considered in terms of pre-renal, renal and post-renal. Inadequate assessment of uid balance and poor prescription of intravenous uid therapy can be a major cause of AKI in the perioperative period. AKI can be dened as a sudden reduction in renal function measured by serum creatinine (rise of 25 mmol/litre or 1.5 baseline). Patients who develop AKI have signicant increases in morbidity and mortality and present signicant clinical challenges to the management of their volume and electrolyte status. Urine output is often used as a marker of renal function with outputs less than 0.5 ml/kg/hour representing oliguria. As described above however, physiological changes in the rst 24 hours following surgery are intended to conserve sodium and water making urine output difcult to interpret in isolation. In addition if AKI is the result of hypovolaemia then there will be a further physiological effort to retain sodium and water. As such it should be interpreted in the context of other clinical and biochemical markers. The initial management of volume status in AKI should essentially be guided by the same criteria used for patients with normal renal function. It is, however, important to rule out any renal or post-renal reasons for the AKI before attributing a prerenal aetiology. In addition, meticulous attention is required to volume status and biochemical parameters (urine and blood). It is also recommended that early involvement from renal or critical care services be sought if AKI progresses or there is clinical evidence of worsening interstitial oedema and impairment of secondary organ function. There is still debate regarding the use of certain uids in AKI. There has been a long-standing reluctance to use potassiumcontaining balanced solutions (e.g. Hartmanns) in AKI due to the potential risk of precipitating hyperkalaemia. Current recommendations suggest that it can be used but only if regular plasma potassium assays can be performed (e.g. in a critical care setting).2 Colloids have also been linked with AKI. In particular, recent evidence suggests that higher molecular weight hetastarches (>200 kDa) are associated with an increased risk of AKI in critically ill patients with sepsis and current recommendations are to avoid these colloids in this group.2,6

REFERENCES 1 Guidet B, Soni N, Della Rocca G, et al. A balanced view of balanced solutions. Crit Care 2010; 14: 325. 2 Powell-Tuck J, Gostling P, Lobo DN, et al. Consensus guidelines on intravenous uid therapy for adult surgical patients (GIFTASUP). Available at: http://www.bapen.org.uk pdfs/bapen_pubs/giftasup.pdf (accessed 20 May 2012). 3 Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for uid resuscitation in the intensive care unit. N Engl J Med 2004; 350: 2247e56. 4 Perel P, Roberts I. Colloids versus crystalloids for uid resuscitation in critically ill patients. Cochrane Database Syst Rev 2011. Issue 3. Art. No.:CD000567. 5 Schortgen F, Lacherade JC, Bruneel F, et al. Effects of hydroxyethyl starch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 2001; 357: 911e6. 6 Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358: 125e39. 7 CardioQ-ODM oesophageal Doppler monitor. National Institute for Health and Clinical Excellence, 2011. 8 Abbas SM, Hill AG. Systematic review of the literature for the use of oesophageal Doppler monitor for uid replacement in major abdominal surgery. Anaesthesia 2008; 63: 44e51. 9 Walsh SR, Tang T, Bass S, Gaunt ME. Doppler-guided intra-operative uid management during major abdominal surgery: systematic review and meta- analysis. Int J Clin Pract 2008; 62: 466e70. 10 Pearse RM, Belsey J, Cole J, Bennet ED. Effect of dopexamine infusion on mortality following major surgery: individual patient data metaregression analysis of published clinical trials. Crit Care Med 2008; 36: 1323e9.



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