CHAPTER 10. INTRAVENOUS FLUIDS AND COMMONLY PRESCRIBED INFUSIONS
Commonly prescribed infusions85
Dr Thomas Aitchison Latta (circa 1790–1833) pioneered the use of intravenous saline as fluid resuscitation for cholera victims in 1832 using a small silver tube attached to a syringe.
INTRODUCTION
Fluid balance and the prescription of intravenous fluids is one of the most common duties performed by a hospital doctor. A detailed explanation of the physiology underlying fluid balance is beyond the scope of this text, but it is imperative that fluid prescriptions are based upon the individual requirements of that patient; there is no such thing as a standard fluid regimen. The patient should have their fluid status assessed through clinical history and examination prior to determining their management (Table 10.1).
| Hypovolaemia | Fluid overload | |
|---|---|---|
| Symptoms |
Thirst
Headache
Dark
concentrated urine
Oliguria
|
Dyspnoea
Orthopnoea
Frothy (white/pink) sputum
|
| Signs in order of frequency and reliability |
Tachycardia
Hypotension
Cool peripheries
Prolonged capillary refill time (>2 seconds)
Postural hypotension (systolic drop of >20 mmHg on rising)
Low jugular venous pressure
Dry mucous membranes
Increased skin turgor
Sunken eyes
|
Tachypnoea
Tachycardia
Relative hypertension
Low oxygen saturations
Raised JVP
Bilateral crepitations (initially bibasal but rising depending upon the degree of pulmonary oedema)
Third heart sound (gallop rhythm)
Peripheral oedema (dependent areas such as ankles and sacrum. Not reliable in the presence of concomitant hypoalbuminaemia)
|
| Investigations |
High urine specific gravity (concentrated urine)
Oliguria/anuria
Raised urea (initially) and creatinine (later)
Raised serum osmolality
Rising base deficit
|
Chest X-ray features of pulmonary oedema |
A strictly documented fluid balance chart, if accurate, might be helpful in assessing the prescription of intravenous fluids. However, third-space sequestration, gastrointestinal losses and febrile illnesses, for example, may lead to a gross underestimate of losses and what may appear to be a positive balance on paper due to modest fluid administration can in fact be very misleading. Remember a patient’s clinical signs never lie, and should be relied upon in preference to a fluid balance.
Furthermore, the clinical assessment should be made in the context of the patient’s acute disorder and chronic co-morbidities:
• Some common causes of hypovolaemia include:
— insensible losses, e.g. febrile illness and lack of fluid intake
— third space losses, e.g. bowel obstruction, sepsis, ascites
— acute losses, e.g. profuse diarrhoea (especially secondary to Clostridium difficile), vomiting, haemorrhage
— excessive diuresis, whether drug-induced or secondary to diabetes mellitus or insipidus.
• Chronic co-morbidities requiring judicious fluid input:
— left ventricular failure
— end-stage renal failure
— ascites.
DEHYDRATION VERSUS HYPOVOLAEMIA
While dehydration is commonly a term used to mean hypovolaemia the two are different. Dehydration is a relative loss of water that will lead to hypernatraemia and hyperuricaemia, while hypovolaemia is loss of circulating volume regardless of the fluid loss (blood, sequestration due to sepsis, GI fluid losses, etc.) and may or may not be associated with sodium and urea changes. The mechanism for urea change in hypovolaemic patients is as much related to renal hypoperfusion as it is to the composition of the fluid loss. Only the respiratory system leads to a pure water loss while diarrhoea leads to a relatively increased water loss.
Furthermore, it is possible for a patient to be normovolaemic and dehydrated or hypovolaemic and dehydrated. The former is often seen in hospitalized patients whose insensible losses are only replaced with saline. Consequently it is important for management purposes to be clear when describing dehydration, hypovolaemia or both.
INTRAVENOUS FLUIDS
Intravenous fluids can be divided into two types, namely crystalloids and colloids.
Crystalloids
Crystalloid solutions are aqueous solutions containing electrolytes that pass freely across semipermeable membranes. Crystalloids have no oncotic pressure, and so distribute readily from the intravascular compartment to the interstitium and beyond. For this reason crystalloids such as normal saline are commonly used for maintenance intravenous fluid replacement. The type of maintenance fluids prescribed needs to be tailored to the individual requirements of the patient taking into account both their volume status and electrolyte requirements (Table 10.2).
| Na+ | K+ | Cl– | Ca2+ | lactate | |
|---|---|---|---|---|---|
| Normal saline (NaCl 0.9%) | 154 | – | 154 | – | – |
| NaCl 0.45% | 77 | – | 77 | – | – |
| Dextrose–saline (NaCl 0.18%, dextrose 4%) | 30 | – | 30 | – | – |
| Dextrose 5% | – | – | – | – | – |
| Hartmann’s solution | 131 | 5 | 111 | 2 | 29 |
| Ringer’s solution | 130 | 4 | 109 | 1.5 | 28 |
• 5% dextrose is an isotonic solution that can effectively be thought of as intravenous water, because once infused the dextrose is metabolized. The dextrose serves to maintain tonicity and therefore prevents immediate red blood cell haemolysis. In effect the solution provides pure water and therefore will reduce urea and sodium concentrations. It is distributed throughout the whole body water (intracellular and extracellular). Consequently it is the least efficient fluid for intravascular volume replenishment.
• Hartmann’s solution contains less chloride than normal saline, 5 mmol/L of potassium and 29 mmol/L of lactate, which is later converted in the liver to bicarbonate. Thus Hartmann’s solution is more representative of plasma and so is described as being more ‘physiological’. This solution is distributed to the extracellular space (i.e. the interstitial and intravascular compartments).
• Normal saline is also exclusively distributed to the extracellular space and is as effective as Hartmann’s solution for restoring intravascular volume. If used exclusively it will lead to a rise in serum sodium and because of the chloride content produce hyperchloraemia, which displaces bicarbonate and thus may be responsible for a mild metabolic acidosis.
Colloids
In comparison to crystalloids, colloids are large molecules that contribute to oncotic pressure and do not cross semi-permeable membranes. In reality colloids simply remain within the intravascular compartment for longer than crystalloids, hence the use of solutions containing colloid for the rapid and acute expansion of intravascular volume (e.g. haemorrhage). In situations of increased capillary permeability, such as sepsis, colloids will eventually leak across the capillary membrane causing interstitial oedema through raising the interstitial oncotic pressure.
• Colloid solutions contain either natural colloid (e.g. blood products) or synthetic colloid.
• Gelatin-containing solutions include Haemaccel and Gelofusine, whereas Dextran contains high-molecular-weight dextrose.
• Colloids have the disadvantages of being considerably more expensive than crystalloids and can on rare occasions cause anaphylactic reactions (more so with Dextran).
• Blood is the only colloid with oxygen-carrying capacity.
CRYSTALLOID VERSUS COLLOID: WHICH FLUID TO USE IN THE CRITICALLY ILL?
Inadequate tissue perfusion in the critically ill patient leads to anaerobic metabolism within those tissues, commonly manifesting as peripherally cool and shutdown extremities with a progressively worsening base deficit. Therefore rapid volume resuscitation is required to restore adequate tissue perfusion.
Medical opinion still varies regarding the fluid of choice in these circumstances. However, the essence of managing hypovolaemia is rapid restoration of circulating volume and although the various solutions may have differing theoretical efficiencies, in practice it is ensuring the initiation of the process that matters as much as the type of fluid used. Giving orders to start administering a colloid that does not take place for an hour is significantly worse than starting immediate resuscitation with 5% dextrose!
The choice of fluid is in part influenced by what is at hand, the speed of fluid loss and the type of fluid loss. For example:
• profuse diarrhoea can be managed with moderately rapid infusions of dextrose saline and 5% dextrose
FLUID CHALLENGES
If the aim of fluid administration is to determine whether hypovolaemia is the cause of new clinical signs such as oliguria, a colloid fluid challenge of between 300 and 500 mL over 30 minutes would be more effective in restoring normality than a similar quantity of saline. Colloid fluid challenges are therefore more likely to reveal whether hypovolaemia was indeed the reason for the change in clinical signs.
DAILY FLUID REQUIREMENTS
In health an average 70- kg adult requires 3 L of fluid per day for the maintenance of euvolaemia, with approximately 40–60 mmol of potassium and 100 mmol of sodium. It is worth noting that a proportion of these fluid and electrolyte requirements come from foods as well as fluids. For example, an otherwise fit and well 70-kg individual who is nil by mouth prior to an elective surgical procedure would reasonably have a 24-hour maintenance fluid regimen as in Table 10.3.
| Date | Fluid | Quantity | Additives | Quantity | Rate | Route |
|---|---|---|---|---|---|---|
| 28/6 | 5% dextrose | 1 L | 8 hours | i.v. | ||
| 28/6 | 0.9% saline | 1 L | KCl | 40 mmol | 8 hours | i.v. |
| 28/6 | 5% dextrose | 1 L | 8 hours | i.v. |
As described above, the volume and constitution of a patient’s fluid requirements in illness will vary depending upon both their volume status and the nature of the underlying disease process.
ELECTROLYTE REQUIREMENTS: SPECIAL CIRCUMSTANCES
A detailed explanation of electrolyte physiology is again beyond the scope of this text, but it is important to appreciate certain pathological states in which important caveats exist to the prescription of electrolytes.
Heart and liver failure
These are states that exhibit pathological over-activity of the renin–angiotensin cascade. Thus sodium intake should be restricted in these groups of patients in addition to close monitoring of their overall fluid balance. Many centres advise 5% dextrose as a maintenance fluid of choice in hepatic failure.
Chronic renal failure
Patients with chronic renal failure will have an impaired ability to both produce urine and excrete potassium in their urine. Therefore potassium supplementation should be avoided in these patients (especially with end-stage renal failure) unless levels are dangerously low.
Diabetic ketoacidosis
This characteristically presents with metabolic acidosis, hyperglycaemia, hypovolaemia and dehydration due to a urinary sugar osmotic diuresis, and hyperkalaemia due to a lack of insulin. It is typically managed initially with rapid saline resuscitation and an intravenous insulin sliding scale until blood sugars come close to the normal range. Although such patients may have high initial serum potassium concentrations, overall total body potassium levels are depleted due to the osmotic diuresis. The subsequent administration of insulin and correction of metabolic acidosis will return potassium to its intracellular sites and serum potassium will fall. In this acute circumstance a potassium infusion via a central venous line with close monitoring of potassium levels will be necessary once an insulin sliding scale has been started to avoid precipitously falling potassium levels.
Large gastrointestinal losses
Patients in whom hypovolaemia and associated dehydration occurs secondary to large gastrointestinal losses will also require intravenous replacement of lost potassium and magnesium.
Large urinary losses
Patients receiving diuretics will concomitantly excrete sodium, potassium and magnesium in their urine to varying degrees. If blood levels start falling, potassium and magnesium both require replacement to avoid complications (especially arrhythmias).
• If diuretics are being administered to treat fluid overload, potassium should be supplemented orally.
• Avoid oral magnesium preparations as these are particularly prone to causing diarrhoea as a side-effect. Even in fluid overload, magnesium is more effectively replaced intravenously in very small volumes of fluid (as little as 20 mL – see Intravenous fluids section).
• In contrast, hyponatraemia secondary to diuretic use is resolved simply by cutting back on the diuretic medications rather than replacing sodium.
Arrhythmias
The prevention and treatment of arrhythmias involves ensuring that potassium and magnesium levels are adequately controlled. Both are predominantly intracellular ions closely involved in cardiac rhythm generation and conduction. Low extracellular levels (detected on blood analysis) should be corrected in the management of arrhythmias. Aim for a serum potassium of >4.5 mmol/L, with serum magnesium >1.0 mmol/L. Take care to avoid fluid overload whilst replacing these electrolytes in the presence of a tachyarrhythmia.
Refeeding syndrome
This can occur in previously starved/malnourished patients in whom enteral feeding has been resumed. Carbohydrate administration stimulates insulin release, with the depletion of extracellular potassium, magnesium and phosphate levels following their shift into the intracellular environment. Avoidance of this condition can be achieved with daily monitoring and replacement of potassium, magnesium and phosphate whilst feeding is introduced under the guidance of a dietitian.
COMMONLY PRESCRIBED INFUSIONS
INSULIN SLIDING SCALE
This is indicated in several situations:
• the treatment of diabetic ketoacidosis (DKA) or hyperosmolar non-ketosis (HONK)
• in diabetic patients who are nil by mouth pre-operatively or pre-procedure (e.g. oesophagogastroduodenoscopy (OGD))
• intercurrent illness requiring tight blood sugar control (e.g. sepsis, acute coronary syndromes).
The sliding scale in Table 10.4 is one example of how to prescribe the insulin regimen, but check to see if your hospital already has a local policy in place.
| Adjust the insulin infusion rate according to blood sugar measurement. | ||||||
| Note that in the case of DKA, the fluid regimen will be different to that attached to the above standard sliding scale regimen. | ||||||
| CBGM, capillary blood glucose monitoring; DKA, diabetic ketoacidosis. | ||||||
| Date | Fluid | Quantity | Additives | Quantity | Rate | Route |
|---|---|---|---|---|---|---|
| 28/6 | 0.9% saline | 50 mL | Actrapid | 50 units | See chart | i.v. |
| CBGM | Rate (units/hour) | |||||
| 0–4.0 | Stop | |||||
| 4.1–8.0 | 1 | |||||
| 8.1–12.0 | 2 | |||||
| 12.1–14.0 | 3 | |||||
| 14.1–16.0 | 4 | |||||
| 16.1–20.0 | 5 | |||||
| >20 | Call Dr | |||||
| 28/6 | 0.9% saline | 1 L | If BM >15 | 8 hours | i.v. | |
| 28/6 | 5% dextrose | 1 L | If BM <15 | 8 hours | i.v. | |
GLYCERYL TRINITRATE (GTN) INFUSION
See Table 10.5 for an example of a GTN infusion prescription.
| ∗GTN is a potent vasodilator. The infusion must thus be started at a low rate and be titrated against the systolic BP, which can fall precipitously with GTN. Therefore start the infusion at 1–2 mL/hour, re-check the BP and increase the infusion rate accordingly. |
||||||
| Date | Fluid | Quantity | Additives | Quantity | Rate | Route |
|---|---|---|---|---|---|---|
| 28/6 | 0.9% saline | 50 mL | GTN∗ | 50 mg | See below | i.v. |
| Titrate infusion rate to symptoms and systolic BP. Aim for systolic BP >110 | ||||||
Indications include:
• ongoing cardiac chest pain despite initial management (e.g. GTN spray)
• the management of acute pulmonary oedema.
AMIODARONE INFUSION
See Table 10.6 for an example of an amiodarone infusion prescription. Indications include:
| Date | Fluid | Quantity | Additives | Quantity | Rate | Route |
|---|---|---|---|---|---|---|
| 28/6 | 5% glucose | 100 mL | Amiodarone | 300 mg | 1 hour | i.v. |
| 28/6 | 5% glucose | IL | Amiodarone | 900 mg | 23 hours | i.v. |
| 29/6 | 5% glucose | IL | Amiodarone | 900 mg | 24 hours | i.v. |
The following points should be noted with intravenous amiodarone:
• Optimize detrolytes prior to starting anti-arrhythmic therapy.
• Telemetry is required with amiodarone infusions to monitor clinical response.
• The 1-hour intravenous loading dose of amiodarone can initially (in emergency situations) be given peripherally via a large-bore cannula, but should be continued via a central venous line.
• Check baseline liver function tests and thyroid function tests prior to starting amiodarone, as deranged liver and thyroid function may ensue.
• After the first 24 hours, subsequent 900 mg/24 hour infusions are only given if necessary according to clinical response. If clinical response has been achieved, switch to p.o. amiodarone.
PHENYTOIN INFUSION
Indications include (check with senior prior to starting):
• status epilepticus (i.e. refractory to initial benzodiazepine therapy)
• seizures (or seizure prophylaxis) in neurosurgery.
The loading dose of intravenous phenytoin is 15 mg/kg at a rate not exceeding 50 mg/min. Therefore Table 10.7 is a prescription for a phenytoin infusion for a 70-kg man.
| Date | Fluid | Quantity | Additives | Quantity | Rate | Route |
|---|---|---|---|---|---|---|
| 28/6 | 0.9% saline | 100 mL | Phenytoin | 1050 mg | 25 minutes(4 mL/minute) | i.v. |
| 28/6 | 0.9% saline | 100 mL | Phenytoin | 100 mg | 6–8 hours | i.v. |
• Telemetry is required with phenytoin infusions to monitor for arrhythmias.
• Monitor phenytoin infusions by measurement of plasma phenytoin levels.
AMINOPHYLLINE INFUSION
Indications include (check with senior prior to starting):
Note
• Patients taking oral aminophylline or theophylline should not receive intravenous aminophylline unless plasma theophylline concentration is available to guide dosage.
• In patients not previously taking aminophylline or theophylline, a loading dose is given at 5 mg/kg (between 250 and 500 mg) over at least 20 minutes. A subsequent maintenance infusion is given at 500 μg/kg/hour, adjusted according to plasma theophylline concentration.
Table 10.8 is a prescription for an aminophylline infusion for a 70-kg man not previously taking aminophylline or theophylline.
| Date | Fluid | Quantity | Additives | Quantity | Rate | Route |
|---|---|---|---|---|---|---|
| 28/6 | 0.9% saline | 100 mL | Aminophylline | 350 mg | 30 minutes | i.v. |
| 28/6 | 0.9% saline | 500 mL | Aminophylline | 280 mg | 8 hours | i.v. |
• Telemetry is required with aminophylline infusions to monitor for arrhythmias.
• Monitor aminophylline infusions by measurement of plasma aminophylline levels.
MAGNESIUM INFUSION
Indications include (check with senior prior to starting – see Table 10.9):
| Date | Fluid | Quantity | Additives | Quantity | Rate | Route |
|---|---|---|---|---|---|---|
| 28/6 | 0.9% saline | 100 mL | Magnesium | 2g (8 mmol) | 20 minutes | i.v. |
• hypomagnesaemia (commonly encountered in sepsis, diuretic use, diarrhoea, chronic alcohol excess, refeeding syndrome), a common precipitant of cardiac arrhythmias
• acute severe asthma not responding to initial nebulized bronchodilators.
