Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Hypokalaemia
The infusion of Sodium chloride 0.9% w/v and Glucose 5% w/v solution may result in hypokalaemia. Close clinical monitoring may be warranted in patients with or at risk for hypokalaemia, for example:
• Persons with metabolic alkalosis
• Persons with thyrotoxic periodic paralysis. Administration of intravenous glucose has been associated in aggravating hypokalaemia
• Persons with increased gastrointestinal losses (e.g., diarrhea, vomiting) • Prolonged low potassium diet
• Persons with primary hyperaldosteronism
• Patients treated with medications that increase the risk of hypokalaemia (e.g. diuretics, beta-2 agonists or insulin)

Sodium retention, fluid overload and oedema
Sodium chloride 0.9% w/v and Glucose 5% w/v solution should be used with particular caution in
• Patients with metabolic acidosis
• Patients at risk of o Hypernatraemia o Hyperchloraemia o Hypervolaemia
• Patients with conditions that may cause sodium retention, fluid overload and oedema (central and peripheral), such as o Primary hyperaldosteronism,
o Secondary hyperaldosteronism associated with, for example,
 hypertension,
 congestive heart failure,
 liver disease (including cirrhosis),
 renal disease (including renal artery stenosis, nephrosclerosis) o Pre-eclampsia.
Patients taking medications that may increase the risk of sodium and fluid retention, such as corticosteroids

Hyperosmolality, serum electrolytes and water imbalance
Depending on the volume, rate of infusion, the patient’s underlying clinical condition and capability to metabolize glucose, administration of Sodium chloride 0.9% w/v and Glucose 5% w/v solution can cause:
• Hyperosmolality, osmotic diuresis and dehydration
• Electrolyte disturbances such as
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o hyponatraemia (see “Sodium imbalance” below) o hypokalaemia (see above) o hypophosphataemia,
o hypomagnesaemia
• Acid-base imbalance
• Overhydration/hypervolaemia and, for example, congested states, including central (e.g.
pulmonary congestion) and peripheral oedema.
• An increase in serum glucose concentration is associated with an increase in serum osmolality. Osmotic diuresis associated with hyperglycaemia can result in or contribute to the development of dehydration and in electrolyte losses.

Electrolyte balance (see ‘Sodium imbalance’ below)
Glucose intravenous infusions are usually isotonic solutions. In the body, however, glucose containing fluids can become extremely physiologically hypotonic due to rapid glucose metabolization (see section 4.2).

Depending on the tonicity of the solution, the volume and rate of infusion and depending on a patient's underlying clinical condition and capability to metabolize glucose, intravenous administration of glucose can cause electrolyte disturbances most importantly hypo- or hyperosmotic hyponatraemia.

Hyponatraemia:
Patients with non-osmotic vasopressin release (e.g. in acute illness, pain, post-operative stress, infections, burns, and CNS diseases), patients with heart-, liver- and kidney diseases and patients exposed to vasopressin agonists (see section 4.5) are at particular risk of acute hyponatraemia upon infusion of hypotonic fluids.

Acute hyponatraemia can lead to acute hyponatraemic encephalopathy (brain oedema) characterized by headache, nausea, seizures, lethargy and vomiting. Patients with brain oedema are at particular risk of severe, irreversible and life-threatening brain injury.

Children, women in the fertile age and patients with reduced cerebral compliance (e.g.
meningitis, intracranial bleeding, and cerebral contusion) are at particular risk of the severe and life-threatening brain swelling caused by acute hyponatraemia

Clinical evaluation and periodic laboratory determinations may be necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient or the rate of administration warrants such evaluation.

Hyperglycaemia
Rapid administration of glucose solutions may produce substantial hyperglycaemia and hyperosmolar syndrome. In order to avoid hyperglycaemia the infusion rate should not exceed the patient’s ability to utilize glucose. To reduce the risk of hyperglycaemia-associated complications, the infusion rate must be adjusted and/or insulin administered if blood glucose levels exceed levels considered acceptable for the individual patient 
Intravenous glucose should be administered with caution in patients with, for example: 4 of 11
•   Impaired glucose tolerance (such as in diabetes mellitus, renal impairment, or in the presence of sepsis, trauma, or shock),
•   Severe malnutrition (risk of precipitating a refeeding syndrome, see below), •   Thiamine deficiency, e.g., in patients with chronic alcoholism (risk of severe lactic acidosis due to impaired oxidative metabolism of pyruvate),
•   Water and electrolyte disturbances that could be aggravated by increased glucose and/or free water load

Other groups of patients in whom Sodium chloride 0.9% w/v and Glucose 5% w/v solution should be used with caution include:
• Patients with ischemic stroke. Hyperglycaemia has been implicated in increasing cerebral ischemic brain damage and impairing recovery after acute ischemic strokes.
• Patients with severe traumatic brain injury (in particular during the first 24 hours following the trauma). Early hyperglycaemia has been associated with poor outcomes in patients with severe traumatic brain injury.
• Newborns (See Paediatric glycaemia-related issues).

Prolonged intravenous administration of glucose and associated hyperglycaemia may result in decreased rates of glucose-stimulated insulin secretion.

Hypersensitivity Reactions
•    Hypersensitivity/infusion reactions, including anaphylaxis, have been reported (see section 4.8).
•    Stop the infusion immediately if signs or symptoms of hypersensitivity/infusion reactions develop. Appropriate therapeutic countermeasures must be instituted as clinically indicated.

Solutions containing glucose should be used with caution in patients with known allergy to corn or corn products

Refeeding syndrome
Refeeding severely undernourished patients may result in the refeeding syndrome that is characterized by the shift of potassium, phosphorus, and magnesium intracellularly as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop. Careful monitoring and slowly increasing nutrient intake while avoiding overfeeding can prevent these complications

Severe renal impairment
Sodium chloride 0.9% w/v and Glucose 5% w/v solution should be administered with particular caution to patients at risk of (severe) renal impairment. In such patients, administration may result in sodium retention and/or fluid overload.

Paediatric use
The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy, and should be determined by a physician experienced in paediatric intravenous fluid therapy.

Paediatric glycaemia-related issues
Newborns, especially those born premature and with low birth weight, are at increased risk of developing hypo- or hyperglycaemia. Close monitoring during treatment with intravenous 5 of 11
glucose solutions is needed to ensure adequate glycaemic control, in order to avoid potential long term adverse effects.
• Hypoglycaemia in the newborn can cause, e.g., prolonged seizures, coma, and cerebral injury
• Hyperglycaemia has been associated with cerebral injury, including intraventricular hemorrhage, late onset bacterial and fungal infection, retinopathy of prematurity, necrotizing enterocolitis, increased oxygen requirements, prolonged length of hospital stay, and death.

Paediatric hyponatraemia-related issues
Children (including neonates and older children) are at increased risk of developing hyponatraemia as well as for developing hyponatraemic encephalopathy.

•    Hyponatraemia can lead to headache, nausea, seizures, lethargy, coma, cerebral oedema and death; therefore, acute symptomatic hyponatraemic encephalopathy is considered a medical emergency.
•    Plasma electrolyte concentrations should be closely monitored in the paediatric population
•    Rapid correction of hyponatraemia is potentially dangerous (risk of serious neurologic complications). Dosage, rate, and duration of administration should be determined by a physician experienced in paediatric intravenous fluid therapy.


Blood
Sodium chloride 0.9% w/v and Glucose 5% w/v solution should not be administered simultaneously with blood through the same administration set because of the possibility of pseudoagglutination or haemolysis.

Geriatric use
When selecting the volume/rate of infusion for a geriatric patient, consider that geriatric patients are generally more likely to have cardiac, renal, hepatic and other diseases or concomitant drug therapy.

Effects on Driving

4.7 Effects on ability to drive and use machines
There is no information on the effects of Sodium chloride 0.9% w/v and Glucose 5% w/v solution on the ability to operate an automobile or other heavy machinery.

Sodium chloride 0.9% w/v and Glucose 5% w/v solution should be administrated with special caution for pregnant women during labour particularly if administered in combination with oxytocin due to the risk of hyponatraemia (see section 4.4, 4.5 and 4.8).