Approach

The treatment of volume depletion varies with the aetiology. History, physical examination, and accurate diagnosis are crucial in planning management. Prompt volume resuscitation is necessary to restore vascular volume and normalise venous return, cardiac output, and blood pressure.[27]

Critically ill individuals with obvious bleeding require urgent resuscitation with crystalloid solutions, followed as soon as possible by blood transfusions. The amount of resuscitation required depends on the extent of volume deficit: many litres of fluid and/or blood may be required in shock states.

When electrolyte disturbances are present, the fluid used for resuscitation should be tailored to effect appropriate correction of both volume depletion and electrolyte abnormalities.

Monitoring vital signs and their response to treatment is necessary to guide fluid resuscitation, as well as determine the severity of volume depletion. Individuals with systolic blood pressure <80 mmHg, or who are exhibiting confusion or signs of organ ischaemia, require a more rapid treatment course and greater volumes of resuscitation fluid than those with mild hypotension and tachycardia but no signs of systemic hypoperfusion. Oral therapy may be appropriate in patients with only mild volume depletion.[5][9]

Moderate to severe volume depletion

Initial fluid resuscitation: choice of fluid

Intravenous administration of isotonic crystalloid solution is the first-line treatment for volume depletion in most situations, including haemorrhage and gastrointestinal losses. When severe volume depletion is present, fluid delivery is more important than the type of fluid.[28][29] Balanced crystalloids may be preferable to normal saline in critically ill patients in intensive care, and are recommended in patients with sepsis or septic shock due to the chloride content in normal saline inducing hyperchloraemic metabolic acidosis when given in large amounts.[14][30] Patients with with sepsis-induced hypoperfusion or septic shock should receive 30 mL/kg crystalloid for hypotension within the first 3 hours of resuscitation.[14]

Isotonic crystalloid solutions are generally readily available and inexpensive, require no special handling, and have minimal complications associated with their use. There is evidence to support the use of crystalloids over colloids for the treatment of shock. In general, colloids have not been shown to further improve survival compared with crystalloids. [ Cochrane Clinical Answers logo ] Solutions containing hydroxyethyl starch (HES) are associated with adverse outcomes including kidney injury and death, particularly in critically ill patients and those with sepsis.[29][31] In view of the serious risks posed to these patient populations, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency in February 2022 recommended suspending HES solutions for infusion in Europe.[32] The Surviving Sepsis Campaign advises against the use of starches for patients with sepsis and septic shock.[14] In the US, the Food and Drug Administration (FDA) issued safety labelling changes in July 2021 for solutions containing HES stating that HES products should not be used unless adequate alternative treatment is unavailable.[33]

Sodium bicarbonate solutions

For the acute treatment of severe metabolic acidosis (arterial pH <7.10 to 7.20), sodium bicarbonate can be given either as hypertonic ampoules or as an isotonic infusion.[5][34]

Repeated administration of hypertonic ampoules will lead to hypernatraemia, a problem that can be avoided by using an isotonic sodium bicarbonate infusion. The use of bicarbonate in anion gap acidosis, such as lactic acidosis, is controversial, as its administration could theoretically increase intracellular acidosis and lactate production, and impair tissue oxygen delivery. We favour using sodium bicarbonate for severe metabolic acidosis to maintain blood pH at a safe range, such as above 7.10, with intubation and ventilation where clinically appropriate to facilitate compensatory reduction in blood pCO2.[35]

Bicarbonate is useful in the setting of hyperchloraemic acidosis arising directly from bicarbonate loss, as can occur with severe diarrhoea. Lactated Ringer's solution contains 130 mmol/L (130 mEq/L) sodium, 28 mmol/L (28 mEq/L) lactate, 4 mmol/L (4 mEq/L) potassium, as well as calcium and chloride. Lactate is converted to bicarbonate, which can be helpful in metabolic acidosis, but in lactic acidosis and liver disease this conversion is impaired, so lactate-containing fluids should be avoided in these circumstances. In renal failure, the use of lactated Ringer's solution can contribute to hyperkalaemia.

Isotonic crystalloid is the preferred initial choice for volume resuscitation over lactated Ringer's solution and sodium bicarbonate solutions.[5] In the special circumstances discussed above, bicarbonate-containing solutions can be added or substituted.

Hypernatraemia

Hypotonic saline (0.45% sodium chloride) has a concentration of 77 mmol (77 mEq) sodium per litre, and can be used after initial fluid resuscitation when there is hypernatraemia and a water deficit greater than the solute deficit. In these patients, 5% dextrose in water can be given simultaneously with the isotonic crystalloid and then hypotonic saline substituted once the patient has been stabilised. In diabetic patients on an insulin drip, 5% dextrose solution may also be added to resuscitation or replacement fluid to prevent hypoglycaemia or ketosis.[5][9]

Mild volume depletion

In cases of mild volume depletion, resuscitation can be adequately achieved with oral fluid alone. Sodium chloride tablets and electrolyte-containing solutions are often used. Glucose is typically added to these oral replacement solutions to promote uptake of sodium via the intestinal sodium/glucose co-transporter mechanism.

Solutions that are rice-based are effective in cholera, given the absorption of both protein and glucose that occurs with rice digestion.[7]

Oral electrolyte solutions are used in children, particularly with gastroenteritis. This product contains sodium, potassium, chloride, citrate, and dextrose, and is designed to replace the solute and water that is lost with vomiting or diarrhoea.[36]

Rate of volume repletion

The goal of fluid replacement is to restore haemodynamic stability and avoid shock and organ ischaemia. Fluid may be typically delivered as rapidly infused boluses of 250 to 500 mL of crystalloid, repeated as necessary.[37] As it is extremely difficult to estimate the true volume deficit accurately, frequent monitoring of vital signs and particularly systolic blood pressure is used to determine when adequate fluid replacement has been administered. Resuscitation in sepsis should be guided by dynamic over physical examination or static measures alone. Dynamic parameters include response to a passive leg raise or a fluid bolus, using stroke volume (SV), stroke volume variation (SVV), pulse pressure variation (PPV), or echocardiography, where available. Capillary refill time can guide resuscitation as an adjunct to other measures of perfusion.[14] Once enough volume has been given to effect an increase in blood pressure, such as a return to normal values for the patient (often a systolic blood pressure >100 mmHg), subsequent fluid replacement must reflect ongoing losses and be adjusted accordingly. Because excessive fluid administration can be deleterious in situations such as heart or kidney failure, close monitoring of vital signs and frequent clinical estimation of intravascular volume are essential. Some authorities recommend fluid resuscitation of 50 to 100 mL/hr more than the sum of all fluid losses (urine output, insensible losses, gastrointestinal losses, or tube drainage) as a maintenance rate once haemodynamic stability has been achieved.[5]

In acute gastrointestinal haemorrhage and with trauma, there is some evidence that relative hypotension may be appropriate during resuscitation until the bleeding can be managed by either endoscopy or surgery. Studies show that restoring blood pressure to normal or attempting to restore haemoglobin to normal may lead to more bleeding, perhaps from increased blood pressure or dilution of platelets and clotting factors that are produced in the setting of acute bleeding.[38][39][40]

Haemorrhagic losses

Blood is the definitive intravascular volume expander, especially in the setting of anaemia and active haemorrhage. It is usually transfused as packed red blood cells, and isotonic crystalloid is given in place of plasma.[5][41]

Fresh frozen plasma is appropriate to use in volume expansion in the setting of a coagulopathy.

Gastrointestinal losses

Anti-emetics, such as promethazine or ondansetron, can be given for nausea and vomiting. Antidiarrhoeals, such as diphenoxylate/atropine or loperamide, can be given in cases of non-infectious diarrhoea.

In general, intravenous vasopressors are not indicated in shock due to gastrointestinal losses, as crystalloid resuscitation is the appropriate treatment. However, if sepsis is also suspected, vasopressors are often necessary.

Excessive diuresis

Consideration should be made for modification or withholding of any diuretics being used. Oral replacement is appropriate if it is possible to maintain oral intake to match the renal losses without a resulting electrolyte abnormality or haemodynamic instability.

Sodium chloride tablets and electrolyte-containing solutions can be used. Glucose is typically added to these oral replacement solutions to promote uptake of sodium via the intestinal sodium/glucose co-transporter mechanism.

In addition to overuse of diuretics, osmotic diuresis is also caused by glycosuria due to uncontrolled diabetes; by adrenal insufficiency; or rarely by salt-wasting nephropathies. Renal water excretion can be severe in the setting of diabetes insipidus, but this primarily causes dehydration and hypernatraemia.[1][5][8][9]

If intravenous fluid replacement is required, the type of solution will depend on the electrolyte abnormalities detected by laboratory testing. Generally, isotonic crystalloid is used first-line. However, if significant hypernatraemia is present, 0.45% normal saline may be appropriate to replace the water deficit as well. As dehydration and volume depletion may occur together, 0.45% saline allows for replacement of both solute and free water loss.

Skin losses

Burns

Isotonic crystalloid will best replace the fluid that is lost through burnt skin.

The volume deficit can be many litres in severe burns covering a large surface area. The Parkland formula aims to calculate the fluid resuscitation requirement in the first 24 hours, using the formula (4 mL x bodyweight in kg x % total body surface area burn), with half the calculated volume given in the first 8 hours and the other half given over the remaining 16 hours. However, close attention should also be given to monitoring urine output per hour, and resuscitation adjusted accordingly to maintain an output of 0.5 to 1 mL/kg/hr. Too much fluid can lead to increased intra-abdominal pressure and compartment syndromes.[42]

Referral to a specialist burn centre is necessary if the burn is severe and covers a large surface area. There, definitive treatment such as debridement, wound dressing, and topical antibiotics will be used appropriately. Ultimately skin grafts can be done to cover damaged areas with exposed tissue for cosmetic purposes, as well as to limit the potential for continued fluid loss.

Profound sweating

When there has been excessive sweating but systolic blood pressure (SBP) remains >100 mmHg and pulse <100 bpm, it is reasonable to use oral replacement solutions or intravenous 0.45% sodium chloride. Sweat contains less solute than the fluid lost through burns, and, therefore, in less severe cases the deficit can be replaced with a hypotonic solution.

However, in more severe situations, with SBP <100 mmHg and/or pulse >100 bpm, isotonic crystalloid is the preferred initial choice; hypotonic saline or oral replacement solutions can then be used once the vital signs improve and patients are haemodynamically stable. When volume loss from excessive sweating is severe and leads to hypotension (SBP <100 mmHg) with symptoms such as confusion, isotonic crystalloid should be used.

As in other states of moderate to severe volume depletion, the best choice is the fluid that will expand the intravascular space.

Even if there is a component of hypernatraemia from dehydration, when volume depletion exists, isotonic crystalloid should be used.

It is rare to see severe volume depletion and hypotension from sweating alone.

Third-space sequestration

Third-space sequestration is seen when abnormal collections of fluid develop in spaces where they cannot be re-absorbed into the intravascular space. Examples include ascites due to cirrhosis or Budd-Chiari syndrome, venous obstruction, severe pancreatitis, crush injury with muscle damage, and intestinal obstruction.[5][9]

The fluid is sequestered from the intravascular space, causing symptoms of volume depletion, so resuscitation is an attempt to increase intravascular volume, and isotonic crystalloid is the best choice.

Close monitoring of vital signs and response to resuscitation is important, as the deficit in third-space sequestration can be many litres. Care must be undertaken in certain situations, such as cirrhosis, when too much fluid can be detrimental.

Management of the underlying condition needs to be considered.

  • In bowel obstruction, conservative management with nasogastric decompression is often initially attempted. However, in some patients, a surgical intervention is required to relieve the obstruction.

  • Obstruction of a large vein, such as the portal vein, can lead to ascites and fluid sequestration. In some settings of venous obstruction, anticoagulants are used and the volume deficit replaced appropriately while waiting for response to anticoagulation.

  • Pancreatitis is generally managed with liberal use of isotonic crystalloid as needed for volume losses.

  • Orthopaedic consultation for measurement of compartment pressures and fasciotomy, if indicated, should be considered for crush injury.

Pulmonary losses

Bronchorrhoea (i.e., excessive discharge of mucus from the bronchi) or draining pleural effusion are rare causes for volume depletion, but may be seen in chronically ill or hospitalised patients. Symptoms are a reflection of intravascular volume depletion, so the intravascular space must be expanded with isotonic solution. Pleurodesis may be necessary to limit continued drainage into the pleural space. If bronchorrhoea is severe enough to lead to volume loss, appropriate treatment of the infection is necessary.

Sustained inadequate oral intake

This is generally seen in infants and in older people with limited ability to communicate thirst. Inadequate oral intake must be recognised and vital signs and symptoms of volume depletion closely monitored.

Sodium chloride tablets and electrolyte-containing solutions can be used. Glucose is typically added to oral replacement solutions to promote uptake of sodium via the intestinal sodium/glucose co-transporter mechanism.

Isotonic crystalloid is the best initial choice for volume expansion. The goal of fluid replacement is to restore haemodynamic stability and avoid shock and organ ischaemia. Fluid is typically delivered as boluses of 250 to 500 mL of crystalloid, repeated as necessary. As it is extremely difficult to estimate the true volume deficit accurately, frequent monitoring of vital signs (particularly systolic blood pressure) is used to determine when adequate fluid replacement has been administered.

Once the volume deficit is replenished with isotonic crystalloid, 0.45% normal saline can be used as a maintenance fluid.

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