Avoiding common problems associated with intravenous fluid therapy

Andrew K Hilton, Vincent A Pellegrino and Carlos D Scheinkestel
Med J Aust 2008; 189 (9): 509-513. || doi: 10.5694/j.1326-5377.2008.tb02147.x
Published online: 3 November 2008

Intravenous fluid therapy has been used for almost 200 years and remains a fundamental part of hospital patient care.1 However, approaches to the administration of water and sodium vary,2,3 with justification for any particular intravenous fluid regimen being based primarily on physiological concepts rather than evidence. Inappropriate administration of intravenous fluids — either the incorrect volume (too much or too little) or the incorrect type of fluid — is a significant cause of patient morbidity and mortality. Here, we recommend strategies to avoid inappropriate intravenous fluid therapy.

Volume replacement

The goal of volume replacement is to prevent or restore impaired circulatory function secondary to ineffective vascular volume. Volume replacement is commonly guided by one of two strategies:

Algorithmic approaches

Recent evidence also suggests that volume replacement targeting a specific circulatory parameter may improve patient outcome.15-17 These targets involve invasive monitoring of cardiac chamber filling pressures (central venous pressure and pulmonary artery wedge pressure) and cardiac output. Recent ultrasound techniques, such as continuous transoesophageal Doppler, allow less invasive monitoring of circulatory parameters, such as stroke volume. These regimens are necessarily restricted to critically ill patients in intensive care units and will not be discussed further here.

Disturbances of volume

In both fixed and targeted regimens, there is a risk of either insufficient or excessive volume replacement. This risk is likely to be small in previously healthy patients with minimal acute illness. However, a patient’s tolerance to relative hypo- or hypervolaemia decreases with increasing severity of acute illness18 (Box 2 and Box 3).

Inadequate volume replacement is defined as the failure to restore an adequate vascular volume for effective nutrient, metabolite and gaseous exchange in the tissues. The consequences of hypovolaemia are likely to be related to the magnitude of volume loss, timing and adequacy of volume replacement, and clinical context.

Extreme hypovolaemia manifests clinically as shock, which may be treated with crystalloids or colloids. A recent Australian study showed that, in intensive care patients, use of either 4% albumin or 0.9% (isotonic) saline for fluid resuscitation resulted in similar outcomes at 28 days.20 Of note, the ratio of the volume of albumin to saline administered was about 1 : 1.4.

The clinical impact of a lesser degree of hypovolaemia can range from thirst and postural hypotension, increased incidence of perioperative nausea and vomiting, through to prolonged hospitalisation.21-23

There is no universally accepted definition of over-resuscitation or “fluid overload”,5,13,24 which is often understood to mean respiratory or heart failure secondary to excessive positive fluid balance.

Symptoms and signs attributed to fluid overload are likely to be determined by the magnitude of positive fluid balance, the severity of underlying cardiorespiratory disease and the nature and severity of acute illness. Limited human data exist, but volunteer studies suggest that infusion of more than 2–3 L isotonic saline in euvolaemic humans results in symptoms of mild nasal stuffiness, periorbital discomfort and a small, asymptomatic decrease in lung mechanics and gas exchange.25,26

As volume loading increases, maintenance of the plasma oncotic pressure may become important in protecting against pulmonary oedema. Acute illness is often associated with hypoalbuminaemia, and it has been shown that when filling pressure is increased, a low plasma oncotic pressure allows pulmonary oedema to develop at lower filling pressures.27

Excessive administration of saline may be tolerated by an otherwise healthy patient, but additional acute physiological changes, such as altered perioperative sodium and water metabolism, increased capillary permeability, hypoalbuminaemia, and impaired pulmonary mechanics, increase the risk of symptomatic respiratory failure.

Types of fluid administered

The type of fluid administered may be considered incorrect if it causes excessive changes in effective osmolality (tonicity).

If two solutions are separated by a barrier permeable to water only, then water will move from the compartment of low osmolality to that of higher osmolality until the fluids on either side of the barrier share the same osmolality. This redistribution of water between the intracellular and extracellular fluid (ICF and ECF) compartments leads to rapid changes in cell volume, with consequent cellular dysfunction or injury. This is particularly important in the central nervous system, where it results in clinically significant symptoms and signs.

Hypotonic fluids, such as 5% glucose and 4% glucose in 0.18% saline have low (or no) effective solutes when added to the ECF and cause net water movement into cells. Hypertonic fluids, such as 3% saline, added to the ECF cause net water movement from cells. Isotonic (0.9%) saline is isotonic to normal ECF and causes no net water movement. Hartmann’s solution is mildly hypotonic,28 having a calculated osmolality of 273 mOsm/kg, but a measured osmolality (by freezing point depression) of only 254 mOsm/kg.

Disorders of tonicity most commonly result from the accumulation or loss of total body water. Therefore, hyponatraemia usually indicates relative water overload, and hypernatraemia indicates dehydration (water depletion).


Hyponatraemia (serum sodium concentration < 135 mmol/L) is the most common electrolyte disorder in hospitalised patients.29 Symptoms of hyponatraemia include headache, lethargy, decreasing level of consciousness and seizures. Death can result from cerebral oedema. Permanent neurological abnormalities may occur with rapid decreases in sodium concentration below 125 mmol/L, or too rapid correction of sodium concentration back towards this level (osmotic demyelination syndromes).

Hypotonic fluid administration to fasting postsurgical patients is the main cause of hyponatraemia in adults and children in hospital.19,30-33 The perioperative stress response, pain, nausea and vomiting all lead to increased secretion of antidiuretic hormone (ADH) which results in inappropriate accumulation of free water from “routine” administration of hypotonic fluids in susceptible individuals. The duration of the effect is from 12 hours after minor surgery to 4 days after major surgery.13

Fatal cases of hyponatraemia in otherwise healthy patients have led to publications questioning the routine use of hypotonic intravenous fluids and proposing they be replaced with isotonic saline in hospitalised patients.34-37

Hyponatraemia should be avoided by not administering hypotonic fluids to patients while they have increased ADH secretion. Once hyponatraemia occurs, management is determined by the cause and severity, the time over which it developed, and the presence of neurological symptoms.29,38 Initial management of acute hyponatraemia without neurological symptoms includes the cessation of all fluids that can exacerbate hyponatraemia. If the patient is euvolaemic or hypervolaemic, then the hyponatraemia is likely to result from inappropriate ADH secretion (SIADH, syndrome of inappropriate ADH) or excessive free water administration. Importantly, patients with SIADH can produce hypertonic urine, and thus neither isotonic (0.9% NaCl solution) nor hypotonic fluids should be administered, as they will exacerbate the hyponatraemia.29 Acute hyponatraemia associated with severe volume depletion (eg, diarrhoea or diuretic use) often corrects spontaneously when the volume depletion is restored with isotonic saline or colloids.39 Hypertonic solutions should only be considered for asymptomatic acute hyponatraemia if a standard approach does not adequately correct the hyponatraemia. The rate of correction of serum sodium concentration in asymptomatic patients with acute hyponatraemia should be gradual and not exceed 8 mmol/L per day.29 Neurological symptoms and persistent or worsening hyponatraemia despite standard treatment should prompt referral to a physician experienced in treatment of acute hyponatraemia.

Severe acute hyponatraemia (serum sodium concentration < 125 mmol/L) associated with neurological symptoms such as headache, drowsiness or seizure is a medical emergency that may result in death from cerebral oedema. The initial treatment goal should be rapid elevation of serum sodium concentration until acute neurological symptoms are controlled, usually by the administration of hypertonic saline (eg, 3% NaCl solution). This is followed by slower correction, as per the treatment of hyponatraemia without neurological symptoms. Permanent brain injury and death due to osmotic demyelination following symptomatic hyponatraemia and its correction are well described.29,40,41 Approaches to the rate of correction of serum sodium in this setting have been recently reviewed.37,42,43

Chronic hyponatraemia is often associated with medication or severe organ failure, particularly cardiac or liver failure. Specific treatment of chronic hyponatraemia is not required provided hyponatraemia is not symptomatic or severe (serum sodium concentration < 125 mmol/L). Optimising management of the underlying condition and addressing drug causes is the mainstay of treatment in this setting.


Hypernatraemia (serum sodium concentration > 145 mmol/L) is much less common than hyponatraemia and occurs when there is either excessive water loss from the ECF (most common) or excessive sodium gain (uncommon, and associated with hypervolaemia). Normal renal concentrating function and thirst often prevent hypernatraemia developing, but these can be impaired in infants and elderly and critically ill patients, increasing the propensity for hypernatraemia.44 Usually, the onset of hypernatraemia is gradual and results from insufficient replacement of free water loss from urine, skin (eg, fever, severe exercise, burns) or bowel (severe diarrhoea). However, diabetes insipidus due to either insufficient ADH release (central diabetes insipidus) or decreased renal distal tubular response to ADH (nephrogenic diabetes insipidus) can cause more rapid rises in serum sodium concentration because of large urinary losses of free water. Brain injury (central) and chronic lithium use (nephrogenic) are the two most common causes of diabetes insipidus.

Hypernatraemia that results from sodium accumulation in excess of water is less common, but may occur in patients with trauma, burns and brain injury who are resuscitated with hypertonic saline (eg, 3% NaCl solution).

Symptoms directly attributable to hypernatraemia are neurological and range from lethargy, weakness, and irritability, to seizures, obtundation and death in severe cases. Severe or permanent neurological dysfunction is more likely to occur with acute increases in serum sodium concentration above 160 mmol/L.45,46

Hypernatraemia secondary to water loss is managed by treating the specific cause for ongoing water loss, and is corrected by the administration of hypotonic fluids. These usually contain glucose (eg, 5% glucose, or 4% glucose in 0.18% NaCl solution) and may cause hyperglycaemia in patients with diabetes or if given in excessive quantities. If hyperglycaemia and hypernatraemia are severe, sterile water can be administered intravenously, but this requires central venous access as peripheral administration leads to red cell haemolysis.47 Central diabetes insipidus requires administration of the ADH analogue desmopressin (2–4 µg intravenously) to control urinary free water loss, whereas the nephrogenic form is managed by removing the cause of renal ADH unresponsiveness, if possible, and increasing the intake of hypotonic fluids.

Hypernatraemia secondary to excessive hypertonic fluid administration is managed by ceasing hypertonic fluid intake and, if necessary, increasing urinary sodium excretion with diuretics plus hypotonic fluid replacement of urinary volume loss.


Intravenous fluid therapy is common and has frequent non-trivial complications with regard to volume and tonicity. Disorders of the two states may coexist, and we advocate considering each state separately in formulating an approach to management.

Volume complications tend to follow large errors in volume replacement and primarily relate to the cardiorespiratory system and peripheral perfusion. Disorders of tonicity may occur independently of volume state abnormalities, and complications are primarily neurological.

Avoidance of these complications is predicated on careful clinical estimation of the volume, composition and rate of intravenous fluid replacement, and diligent monitoring of clinical response, supplemented with daily estimations of electrolyte concentrations and renal function.

  • Andrew K Hilton1
  • Vincent A Pellegrino2
  • Carlos D Scheinkestel3

  • Intensive Care Unit, Alfred Hospital, Melbourne, VIC.


Competing interests:

None identified.

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