Posology : מינונים

4.2     Posology and method of administration

Propofol 1% Fresenius must only be given in hospitals or adequately equipped day therapy units by physicians trained in anaesthesia or in the care of patients in intensive care.
Circulatory and respiratory functions should be constantly monitored (e.g. ECG, pulse oximetry) and facilities for maintenance of patient airways, artificial ventilation, and other resuscitation facilities should be immediately available at all times.

For sedation during surgical and diagnostic procedures Propofol 1% Fresenius should not be administered by the same person conducting the surgical or diagnostic procedure.


The dose of Propofol 1% Fresenius emulsion should be individualised based on the response of the patient and premedications used.
Supplementary analgesic agents are generally required in addition to Propofol 1% Fresenius.


Posology
General anaesthesia in adults

Induction of anaesthesia:

For induction of anaesthesia Propofol 1% Fresenius should be titrated (approximately 20 - 40 mg propofol every 10 seconds) against the response of the patient until clinical signs show the onset of anaesthesia.

Most adult patients aged less than 55 years are likely to require 1.5 to 2.5 mg propofol/kg bodyweight.

In patients over this age and in patients of ASA grades III and IV, especially those with impaired cardiac function, the requirements will generally be less and the total dose of Propofol 1% Fresenius may be reduced to a minimum of 1 mg propofol/kg bodyweight.
Lower rates of administration of Propofol 1% Fresenius should be used (approximately 2 ml (20 mg propofol) every 10 seconds).

Maintenance of anaesthesia:

Anaesthesia can be maintained by administering Propofol 1% Fresenius either by continuous infusion or repeat bolus injections.

For maintenance of anaesthesia generally doses of 4 to 12 mg propofol/kg bodyweight/h should be given. A reduced maintenance dose of approximately 4 mg propofol/kg bodyweight/h may be sufficient during less stressful surgical procedures such as minimal invasive surgery.

In elderly patients, patients in unstable general conditions, patients with impaired cardiac function or hypovolaemic patients and patients of ASA grades III and IV the dosage of Propofol Fresenius may be reduced further depending on the severity of the patient’s condition and on the performed anaesthetic technique.

For maintenance of anaesthesia using repeat bolus injections dose increments of 25 to 50 mg propofol (= 2.5 – 5 ml Propofol 1% Fresenius) should be given according to clinical requirements.

Rapid bolus administration (single or repeated) should not be used in the elderly as this may lead to cardiopulmonary depression.

General anaesthesia in children over 1 month of age

Induction of anaesthesia:


For induction of anaesthesia Propofol Fresenius should be titrated slowly until clinical signs show the onset of anaesthesia. The dose should be adjusted according to age and/or bodyweight. Most patients over 8 years of age require approximately 2.5 mg/kg bodyweight Propofol Fresenius for induction of anaesthesia. In younger children, especially between the age of 1 month and 3 years, dose requirements may be higher (2.5 - 4 mg/kg bodyweight).

Maintenance of general anaesthesia:

Anaesthesia can be maintained by administering Propofol Fresenius by infusion or repeated bolus injection to maintain the depth of anaesthesia required. The required rate of administration varies considerably between patients but rates in the region of 9 - 15 mg/kg/h usually achieve satisfactory anaesthesia. In younger children, especially between the age of 1 month and 3 years, dose requirements may be higher.

For ASA III and IV patients lower doses are recommended (see also section 4.4).

Sedation for diagnostic and surgical procedures in adult patients
To provide sedation during surgical and diagnostic procedures, doses and administration rates should be adjusted according to the clinical response. Most patients will require 0.5 - 1 mg propofol/kg bodyweight over 1 to 5 minutes for onset of sedation. Maintenance of sedation may be accomplished by titrating Propofol Fresenius infusion to the desired level of sedation.
Most patients will require 1.5 - 4.5 mg propofol/kg bodyweight/h. The infusion may be supplemented by bolus administration of 10 – 20 mg propofol (1 – 2 ml Propofol 1% Fresenius) if a rapid increase of the depth of sedation is required.

In patients older than 55 years and in patients of ASA grades III and IV lower doses of Propofol Fresenius may be required and the rate of administration may need to be reduced.

Sedation for diagnostic and surgical procedures in children over 1 month of age 
Doses and administration rates should be adjusted according to the required depth of sedation and the clinical response. Most paediatric patients require 1 – 2 mg/kg bodyweight propofol for onset of sedation. Maintenance of sedation may be accomplished by titrating Propofol Fresenius infusion to the desired level of sedation. Most patients require 1.5 – 9 mg/kg/h propofol. The infusion may be supplemented by bolus administration of up to 1 mg/kg bodyweight if a rapid increase of depth of sedation is required.

In ASA III and IV patients lower doses may be required.

Sedation in adults during intensive care
When used to provide sedation for ventilated patients under intensive care conditions, it is recommended that Propofol Fresenius should be given by continuous infusion. The dose should be adjusted according to the depth of sedation required. Usually satisfactory sedation is achieved with administration rates in the range of 0.3 to 4.0 mg propofol/kg bodyweight/h.
Rates of infusion greater than 4.0 mg propofol/kg bodyweight/h are not recommended (see section 4.4).

Administration of propofol by a target controlled infusion (TCI) system is not advised for sedation in the intensive care unit (ICU).
Method of administration

For intravenous use.

Propofol 1% Fresenius can be used for infusion undiluted or diluted with 5% w/v glucose intravenous infusion solution or 0.9% w/v sodium chloride intravenous infusion solution only, in glass infusion bottles.

When Propofol 1% Fresenius is infused undiluted, it is recommended that equipment such as burettes, drop counter, syringe pumps or volumetric infusion pumps should always be used to control infusion rates.

Containers should be shaken before use.
Use only homogeneous preparations and undamaged containers.

Prior to use, the ampoule neck or rubber membrane should be cleaned using an alcohol spray or a swab dipped in alcohol. After use, tapped containers must be discarded.

Propofol Fresenius is a lipid containing emulsion without antimicrobial preservatives and may support rapid growth of micro-organisms.

The emulsion must be drawn aseptically into a sterile syringe or giving set immediately after opening the ampoule or breaking the vial seal. Administration must commence without delay.

Asepsis must be maintained for both Propofol Fresenius and infusion equipment throughout the infusion period. Co-administration of other medicinal products or fluids added to the Propofol Fresenius infusion line must occur close to the cannula site using a Y-piece connector or a three-way valve.

Propofol Fresenius must not be mixed with other solutions for infusion or injection. But 5% w/v glucose solution, 0.9% w/v sodium chloride solution or 0.18% w/v sodium chloride and 4% w/v glucose solution may be administered via suitable appendages at the cannula site.

Propofol Fresenius must not be administered via a microbiological filter.

Propofol Fresenius and any infusion equipment containing Propofol 1% Fresenius are for single administration in an individual patient. After use remaining solution of Propofol 1% Fresenius has to be discarded.

Infusion of undiluted Propofol 1% Fresenius:

As usual for fat emulsions, the infusion of Propofol Fresenius via one infusion system must not exceed 12 hours. After 12 hours, the infusion system and reservoir of Propofol Fresenius must be discarded or replaced if necessary.

Infusion of diluted Propofol 1% Fresenius:

For administering infusion of diluted Propofol 1% Fresenius, burettes, drop counters or volumetric infusion pumps should always be used to control infusion rates and to avoid the risk of accidentally uncontrolled infusion of large volumes of diluted Propofol 1% Fresenius.
This risk has to be taken into account when the decision for the maximum dilution in the burette is made.

The maximum dilution must not exceed 1 part of Propofol 1% Fresenius with 4 parts of 5% w/v glucose solution or 0.9% w/v sodium chloride solution (minimum concentration 2 mg propofol per ml). The mixture should be prepared aseptically (controlled and validated conditions preserved) immediately prior to administration and must be administered within 6 hours after preparation.

Propofol 1% Fresenius must not be mixed with other solutions for infusion or injection.
However, co-administration of a 5% w/v glucose solution or 0.9% w/v sodium chloride solution or 0.18% w/v sodium chloride and 4% w/v glucose solution with Propofol 1% Fresenius is permitted via a Y-piece connector close to the injection site.

To reduce pain on the injection site, lidocaine may be injected immediately before the use of Propofol 1% Fresenius (see section 4.4). Alternatively, Propofol 1% Fresenius may be mixed, immediately for use, with preservative free lidocaine injection (20 parts of Propofol 1% Fresenius with up to 1 part of 1% lidocaine injection solution) under controlled and validated aseptical conditions. The mixture has to be administered within 6 hours after preparation.

Muscle relaxants like atracurium and mivacurium should only be administered after flush of the same infusion site used for Propofol Fresenius.

Propofol may also be used by Target Controlled Infusion. Due to the different algorithms available on the market for dosage recommendations please refer to the instructions for use leaflet of the device manufacturer.

Duration of administration

The duration of administration must not exceed 7 days.