Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Aspen Pharma Trading Limited, 3016 Lake Drive, Citywest Business Campus, Dublin 24, Ireland
Diprivan 1% is a short-acting intravenous general anaesthetic for:
For specific guidance relating to the administration of Diprivan 1% with a target controlled infusion (TCI) device, which incorporates ‘Diprifusor’ TCI Software, see Section 4.2.5. Such use is restricted to induction and maintenance of anaesthesia in adults. The ‘Diprifusor’ TCI system is not recommended for use in ICU sedation or sedation for surgical and diagnostic procedures, or in children.
In unpremedicated and premedicated patients, it is recommended that Diprivan 1% should be titrated (approximately 4 ml [40 mg] every 10 seconds in an average healthy adult by bolus injection or infusion) against the response of the patient until the clinical signs show the onset of anaesthesia. Most adult patients aged less than 55 years are likely to require 1.5–2.5 mg/kg of Diprivan 1%. The total dose required can be reduced by lower rates of administration (2–5 ml/min [20–50 mg/min]). Over this age, the requirement will generally be less. In patients of ASA Grades 3 and 4, lower rates of administration should be used (approximately 2 ml [20 mg] every 10 seconds).
In older people the dose requirement for induction of anaesthesia with Diprivan 1% is reduced. The reduction should take into account of the physical status and age of the patient. The reduced dose should be given at a slower rate and titrated against the response.
Diprivan 1% is not recommended for induction of anaesthesia in children aged less than 1 month.
For induction of anaesthesia in children over 1 month of age, Diprivan 1% should be titrated slowly until clinical signs show the onset of anaesthesia. The dose should be adjusted according to age and/or body weight. Most patients over 8 years of age require approximately 2.5 mg/kg body weight of Diprivan 1% 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 body weight).
For ASA 3 and 4 patients lower doses are recommended (see also Section 4.4).
Administration of Diprivan 1% by a ‘Diprifusor’ TCI system is not recommended for induction of general anaesthesia in children.
Anaesthesia can be maintained by administering Diprivan 1% either by continuous infusion or by repeat bolus injections to prevent the clinical signs of light anaesthesia. Recovery from anaesthesia is typically rapid and it is therefore important to maintain Diprivan 1% administration until the end of the procedure.
Continuous Infusion: The required rate of administration varies considerably between patients, but rates in the region of 4–12 mg/kg/h usually maintain satisfactory anaesthesia.
Repeat Bolus Injections: If a technique involving repeat bolus injections is used, increments of 25 mg (2.5 ml) to 50 mg (5.0 ml) may be given according to clinical need.
When Diprivan 1% is used for maintenance of anaesthesia the rate of infusion or ‘target concentration’ should also be reduced. Patients of ASA grades 3 and 4 will require further reductions in dose and dose rate. Rapid bolus administration (single or repeated) should not be used in older people as this may lead to cardiorespiratory depression.
Diprivan 1% is not recommended for maintenance of anaesthesia in children aged less than 1 month.
Anaesthesia can be maintained in children over 1 month of age by administering Diprivan 1% 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 3 and 4 patients lower doses are recommended (see also Section 4.4).
Administration of Diprivan 1% by a ‘Diprifusor’ TCI system is not recommended for maintenance of general anaesthesia in children.
For sedation during intensive care it is advised that Diprivan 1% should be administered by continuous infusion. The infusion rate should be determined by the desired depth of sedation. In most patients sufficient sedation can be obtained with a dosage of 0.3–4 mg/kg/h of Diprivan 1% (See 4.4 Special warnings and precautions for use). Diprivan 1% is not indicated for sedation in intensive care of patients of 16 years of age or younger (see 4.3 Contraindications). Administration of Diprivan 1% by Diprifusor TCI system is not advised for sedation in the intensive care unit.
Diprivan 1% may be diluted with 5% Dextrose (see “Dilution and Co-administration” table below).
It is recommended that blood lipid levels be monitored should Diprivan 1% be administered to patients thought to be at particular risk of fat overload. Administration of Diprivan 1% should be adjusted appropriately if the monitoring indicates that fat is being inadequately cleared from the body. If the patient is receiving other intravenous lipid concurrently, a reduction in quantity should be made in order to take account of the amount of lipid infused as part of the Diprivan 1% formulation; 1.0 ml of Diprivan 1% contains approximately 0.1g of fat.
If the duration of sedation is in excess of 3 days, lipids should be monitored in all patients.
When Diprivan 1% is used for sedation the rate of infusion should also be reduced. Patients of ASA grades 3 and 4 will require further reductions in dose and dose rate. Rapid bolus administration (single or repeated) should not be used in older people as this may lead to cardiorespiratory depression.
Diprivan 1% is contraindicated for the sedation of ventilated children aged 16 years or younger receiving intensive care.
To provide sedation for surgical and diagnostic procedures, rates of administration should be individualised and titrated to clinical response.
Most patients will require 0.5–1 mg/kg over 1– 5 minutes for onset of sedation.
Maintenance of sedation may be accomplished by titrating Diprivan 1% infusion to the desired level of sedation – most patients will require 1.5–4.5 mg/kg/h. In addition to the infusion, bolus administration of 10–20 mg may be used if a rapid increase in the depth of sedation is required. In patients of ASA Grades 3 and 4 the rate of administration and dosage may need to be reduced.
Administration of Diprivan 1% by a ‘Diprifusor’ TCI system is not recommended for sedation for surgical and diagnostic procedures.
When Diprivan 1% is used for sedation the rate of infusion or ‘target concentration’ should also be reduced. Patients of ASA grades 3 and 4 will require further reductions in dose and dose rate. Rapid bolus administration (single or repeated) should not be used in older people as this may lead to cardiorespiratory depression.
Diprivan 1% is not recommended for surgical and diagnostic procedures in children aged less than 1 month.
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 body weight of Diprivan 1% for onset of sedation. Maintenance of sedation may be accomplished by titrating Diprivan 1% infusion to the desired level of sedation. Most patients require 1.5–9 mg/kg/h Diprivan 1%. The infusion may be supplemented by bolus administration of up to 1 mg/kg body weight if a rapid increase of depth of sedation is required.
In ASA 3 and 4 patients lower doses may be required.
Diprivan 1% has no analgesic properties and therefore supplementary analgesic agents are generally required in addition to Diprivan 1%.
Diprivan 1% can be used for infusion undiluted from glass containers, plastic syringes or Diprivan 1% pre-filled syringes or diluted with 5% Dextrose (Intravenous Infusion BP) only, in PVC infusion bags or glass infusion bottles. Dilutions, which must not exceed 1 in 5 (2 mg propofol per ml) should be prepared aseptically immediately before administration and must be used within 6 hours of preparation.
It is recommended that, when using diluted Diprivan 1%, the volume of 5% Dextrose removed from the infusion bag during the dilution process is totally replaced in volume by Diprivan 1% emulsion. (see “Dilution and Co-administration” table below).
The dilution may be used with a variety of infusion control techniques, but a giving set used alone will not avoid the risk of accidental uncontrolled infusion of large volumes of diluted Diprivan 1%. A burette, drop counter or volumetric pump must be included in the infusion line. The risk of uncontrolled infusion must be taken into account when deciding the maximum amount of Diprivan 1% in the burette.
When Diprivan 1% is used undiluted to maintain anaesthesia, it is recommended that equipment such as syringe pumps or volumetric infusion pumps should always be used to control infusion rates.
Diprivan 1% may be administered via a Y-piece close to the injection site into infusions of the following:
The glass pre-filled syringe (PFS) has a lower frictional resistance than plastic disposable syringes and operates more easily. Therefore, if Diprivan 1% is administered using a hand held pre-filled syringe, the line between the syringe and the patient must not be left open if unattended.
When the pre-filled syringe presentation is used in a syringe pump appropriate compatibility should be ensured. In particular, the pump should be designed to prevent syphoning and should have an occlusion alarm set no greater than 1000 mm Hg. If using a programmable or equivalent pump that offers options for use of different syringes then choose only the ‘B-D’ 50/60 ml ‘PLASTIPAK’ setting when using the Diprivan 1% pre-filled syringe.
Diprivan 1% may be premixed with alfentanil injection containing 500 micrograms/ml alfentanil in the ratio of 20:1 to 50:1 v/v. Mixtures should be prepared using sterile technique and used within 6 hours of preparation.
In order to reduce pain on initial injection, Diprivan 1% may be mixed with preservative-free Lidocaine Injection 0.5% or 1%; (see “Dilution and Co-administration” table below).
Administration of Diprivan 1% by a ‘Diprifusor’ TCI system is restricted to induction and maintenance of general anaesthesia in adults. It is not recommended for use in ICU sedation or sedation for surgical and diagnostic procedures, or in children.
Diprivan 1% may be administered by TCI only with a ‘Diprifusor’ TCI system incorporating ‘Diprifusor’ TCI software. Such systems will operate only on recognition of electronically tagged pre-filled syringes containing Diprivan 1% or 2% Injection. The ‘Diprifusor’ TCI system will automatically adjust the infusion rate for the concentration of Diprivan recognised. Users must be familiar with the infusion pump users' manual, and with the administration of Diprivan 1% by TCI and with the correct use of the syringe identification system.
The Diprifusor allows the anaesthetist to achieve and control a desired speed of induction and depth of anaesthesia by setting and adjusting target (predicted) blood concentrations of propofol. An alternative effect-site mode of administration may be accessible on some Diprifusors, but its safety and efficacy have not yet been established.
The ‘Diprifusor’ TCI system assumes that the initial blood propofol concentration in the patient is zero. Therefore, in patients who have received prior propofol, there may be a need to select a lower initial target concentration when commencing ‘Diprifusor’ TCI. Similarly, the immediate recommencement of ‘Diprifusor’ TCI is not recommended if the pump has been switched off.
Guidance on propofol target concentrations is given below. In view of interpatient variability in propofol pharmacokinetics and pharmacodynamics, in both premedicated and unpremedicated patients the target propofol concentration should be titrated against the response of the patient in order to achieve the depth of anaesthesia required.
In adult patients under 55 years of age anaesthesia can usually be induced with target propofol concentrations in the region of 4–8 microgram/ml. An initial target of 4 microgram/ml is recommended in premedicated patients and in unpremedicated patients an initial target of 6 microgram/ml is advised. Induction time with these targets is generally within the range of 60–120 seconds. Higher targets will allow more rapid induction of anaesthesia but may be associated with more pronounced haemodynamic and respiratory depression.
A lower initial target concentration should be used in patients over the age of about 55 years and in patients of ASA grades 3 and 4. The target concentration can then be increased in steps of 0.5–1.0 microgram/ml at intervals of 1 minute to achieve a gradual induction of anaesthesia.
Supplementary analgesia will generally be required and the extent to which target concentrations for maintenance of anaesthesia can be reduced will be influenced by the amount of concomitant analgesia administered. Target propofol concentrations in the region of 3–6 microgram/ml usually maintain satisfactory anaesthesia.
The predicted propofol concentration on waking is generally in the region of 1.0–2.0 microgram/ml and will be influenced by the amount of analgesia given during maintenance.
Dilution and Co-Administration of Diprivan 1% with Other Drugs or Infusion Fluids (see also ‘Additional Precautions’ Section):
| Co-administration Technique | Additive or Diluent | Preparation | Precautions |
|---|---|---|---|
| Pre-mixing. | Dextrose 5% Intravenous Infusion | Mix 1 part of Diprivan 1% with up to 4 parts of Dextrose 5% Intravenous Infusion B.P in either PVC infusion bags or glass infusion bottles. When diluted in PVC bags it is recommended that the bag should be full and that the dilution be prepared by withdrawing a volume of infusion fluid and replacing it with an equal volume of Diprivan 1%. | Prepare aseptically immediately before administration. The mixture is stable for up to 6 hours. |
| Lidocaine hydrochloride injection (0.5% or 1% without preservatives). | Mix 20 parts of Diprivan 1% with up to 1 part of either 0.5% or 1% lidocaine hydrochloride injection. | Prepare mixture aseptically immediately prior to administration. Use for Induction only. | |
| Alfentanil injection (500 microgram/ml). | Mix Diprivan 1% with alfentanil injection in a ratio of 20:1 to 50:1 v/v. | Prepare mixture aseptically; use within 6 hours of preparation. | |
| Co-administration via a Y-piece connector. | Dextrose 5% intravenous infusion | Co-administer via a Y-piece connector. | Place the Y-piece connector close to the injection site. |
| Sodium chloride 0.9% intravenous infusion | As above | As above | |
| Dextrose 4% with sodium chloride 0.18% intravenous infusion | As above | As above |
Accidental overdosage is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression would require lowering of the patient’s head and, if severe, use of plasma expanders and pressor agents.
Shelf life of the product as packaged for sale:
Ampoules: 3 years.
Vials: 3 years.
Pre-filled syringe: 2 years.
Shelf life after dilution:
Use of diluted Diprivan must begin immediately following dilution.
Store between 2°C and 25°C.
Do not freeze.
a) Clear neutral glass ampoules of 20 ml in boxes of 5
b) Clear neutral glass vials of 50 ml and 100 ml
c) Type 1 glass pre-filled syringe of 50 ml
Containers should be shaken before use.
Any portion of the contents remaining after use should be discarded.
Diprivan 1% should not be mixed prior to administration with injections or infusion fluids other than 5% Dextrose or Lidocaine Injection (see Section 4.2.5).
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