Questions and Answers
Diprivan Questions and Answers - Propofol, TCI (target controlled infusion)
1. Q: What pharmaceutical methods have been used to reduce the incidence of pain on injection on induction of anaesthesia with propofol??2. Q:What are the side effects if any of inadvertent intra-arterial infusion of propofol?
4. Q: Will any electrical equipment in the OR interfere with the functioning of `Diprifusor` TCI?
5. Q: Is propofol suitable for use in asthmatic patients ?
6. Q: Can propofol be diluted in 10% glucose solution ?
7. Q: What drugs can be co-administered with `Diprivan` through a Y-piece connector ?
8. Q: Does haemodialysis or haemofiltration affect the blood concentration of propofol ?
9. Q: Propofol has been reported to turn urine green, what information is available in the medical literature ?
10. Q: Does the Diprivan pre-filled syringe contain silicone and if so how much?
11. Q: How sterile is the pre-filled syringe?
12. Q: What is the mechanism of the antimicrobial action of EDTA?
13. Q: Are there any reports of Diprivan causing corrosion of infusion equipment?
14. Q: Is there any Gluten in Diprivan?
15. Q: Does Diprivan contain any mercuric compounds or are they involved in the manufacture? Is it suitable for use in patients with a known allergy to mercury containing compounds?
16. Q: Is the dose of Diprivan, required to induce and maintain anaesthesia, affected by the alcohol intake of patients?
17. Q: How do you determine the Keo for Diprivan and what is its value?
18. Q: Can lidocaine be added to overcome pain on injection when using Diprifusor TCI?
19. Q: Should actual or lean body weight be used when inputting weight data for an obese patient into the "Diprifusor" pump?
20. Q. Will any electrical equipment in the OR interfere with the functioning of "Diprifusor" TCI?
21. Q: What is the calorific value of Diprivan?
22. Q: What non-pharmaceutical methods have been used to reduce the incidence of pain on injection on induction of anaesthesia with propofol?
23. Q: Why is it necessary to shake a vial or ampuole of Diprivan before use?
1. Q: What pharmaceutical methods have been used to reduce the incidence of pain on injection on induction of anaesthesia with propofol?
A: A number of pharmaceutical methods have been used to reduce pain on injection including local anaesthetics (lignocaine, prilocaine, procaine alizapride and possibly EMLA cream), opioids (fentanyl, alfentanyl and pethidine), labetalol, metoclopramide,ketamine, nitroglycerine, aspirin and lipids. The most commonly used methods employ either lignocaine or the opioid analgesics.
Effects of local anaesthetics
Lignocaine (Lidocaine)
Gehan et al (AN18465) showed that lignocaine at a dose of 0.1 mg/kg or greater administered with 2.5mg/kg propofol at induction significantly reduced the incidence of pain on injection. Similar results have been demonstrated in a number of studies where lignocaine has either been mixed with propofol or administered separately. Stafford et al (AN18471), Newcombe (AN17350), Johnson et al (AN15320), Ewart and Whitwam (AN14678),Morton (AN13875), Goodrum et al (AN11927), Helbo-Hansen et al (AN9548) and Barker and Kamath (AN7173).
Prilocaine
1% prilocaine reduced propofol injection pain from 89% (saline control) to 69% (Eriksson AN34612)
Procaine
Nicol et al (AN19315) showed that there was no statistical difference between 2% procaine and 2% lignocaine in their ability to reduce propofol injection pain when administered through small peripheral veins.
EMLA
EMLA cream is a topical anaesthetic commonly used for the insertion of intravenous catheters and needles in children. The patients usually receive the EMLA Cream (2.5% lignocaine, 2.5% prilocaine) 1 h prior prior to surgery. It is not known what effect this has on the incidence of pain during induction of anaesthesia with Diprivan. However it would be predicted that EMLA would have some beneficial effect on the burning sensation produced by `Diprivan` around the site of injection.
Alizapride
1% lignocaine or 25mg alizapride (a benzamide derivative structurally related to procainamide with anti-emetic properties) administered immediately before propofol injection reduced propofol injection pain from 78%(placebo) to 18% and 56% respectively. The greater effect of lignocaine was statistically significant (Zaouk et al AN27473).
Effect of opioid analgesics
Fentanyl
2mcg/Kg fentanyl given intravenously immediately before propofol reduced propofol injection pain from 93% (Saline placebo) to 36% in 28 children (Chessa AN32441).
Alfentanil
Pre-treatment with 1mg alfentanil reduced pain on injection with propofol from 67% in the placebo saline group to 24%. Premixing `Diprivan` with 40 mg lignocaine reduced the incidence to 13%. (Nathanson et al AN40670). Fletcher et al (AN30457) showed that administration of 1 mg alfentanil 15 s before propofol reduced the incidence of propofol injection pain from 84% to 36%. In contrast Dru et al (AN24543) showed that there was no noticeable reduction in pain when alfentanil was given intravenously just before or after propofol but when it was given 3 min before propofol pain was reduced. In addition Hiller and Saarnivaara (AN24063) showed that although 10-20 mcg alfentanil reduced propofol injection pain it was not as effective as 1% lignocaine.
Pethidine
Pretreatment with either 25 mg pethidine or 10 mg lignocaine reduced pain on injection with propofol from 64% in the placebo saline group to 35% and 44% in the pethidine and lignocaine groups respectively.(Lyons et al AN40473)
Effect of other drugs
Labetalol
10 mg labetalol was as effective as lignocaine, 20 mg, in reducing propofol induced pain on injection in 102 patients. 89% of patients receiving placebo saline experienced pain in contrast to 17% on labetalol and 13% on lignocaine (Khalid AN 41559).
Metoclopramide
20mg lignocaine and 10mg metoclopramide when administered intravenously after a rubber tourniquet for one minute reduced propofol injection pain from 67% in the placebo saline group to 10% and 15% respectively (Maroof et al AN35457). Mecklem (AN33333) showed that mixing propofol with 20mg metoclopramide was as effective as mixing propofol with 1% lignocaine in reducing propofol injection pain. Similar results were obtained by Ganta and Fee(AN24580)
Ketamine
20 mg ketamine injected while venous drainage was occluded for 1 min significantly reduced the incidence (and severity) of propofol injection site pain from 85% in the control group to 7%. No postoperative hallucinations were reported after ketamine (Khalid AN35329).
Nitroglycerine
A strip of ointment containing 5 mg nitroglycerine applied over the back of one hand 20 min prior to induction with propofol reduced propofol injection pain from 67% (placebo) to 36%. No patient had headache or postural hypotension (Wilkinson et al AN29819).
Aspirin
Aspirin given in the form of 1.8 g acetyl salicylate given intravenously 15 minutes before `Diprivan` reduced the incidence of severe propofol injection pain from 70% to 20% although it had little effect on the overall incidence of pain. Propofol was administered as a 1% solution in 16% Cremophor EL (Bahar et al 1982).
Effect of lipid on pain on injection
Doenicke et al (AN 34305) showed that reducing the amount of propofol in the aqueous phase by just 32% prevents most if not all pain on injection. In this study 10ml ‘Intralipid’ injected into a vein in the back of the hand together with 20ml `Diprivan` reduced propofol injection pain from 67% (`Diprivan` control) to 0%.
A fuller description of methods of reducing pain on injection may be found in the attachment below.
References.
Bahar M, Mcateer E, Dundee JW, Briggs LP
Forum. Aspirin in the prevention of painful intravenous injection of
disoprofol (ICI 35,868) and diazepam (`Valium`).
Anaesthesia 1982 37 (8) 847-848. AN 4119847
Barker-J-P; Kamath-B-S-K.
Prevention of pain on injection.
British Journal of Anaesthesia , 1988 , 60 (2) pp 243 . AN 7173
Chessa-D; Cossu-F; Serra-G.
(Il fentanyl previene il dolore nella sede di iniezione del
propofol.) Fentanyl prevents pain caused by propofol injection. (Ita,
English summary, English translation).
Minerva Anestesiologica , 1992 , 58 (12) pp 1319-1321 . AN 32441
Doenicke-A; Roizen-M-F; Kellermann-W; Rau-J; Babl-J.
Reduction of pain during injection of propofol - How does it relate
to the solvent?
Anesthesia and Analgesia , 1995 , 80 (2S) Suppl Abs S104 . Abstracts
of the International Anesthesia Research Society 69th Clinical and
Scientific Congress, Honolulu, 10-14 Mar 1995. AN 34305
Dru-M; Lory-C; Journois-D; Playe-E.
(Influence de l`alfentanil sur la douleur a l`injection de propofol,
lors de l`induction anesthesique pediatrique). Effect of alfentanil
on pain on injection with propofol during paediatric anaesthetic
induction. (Fre, English summary).
Cahiers d`Anesthesiologie , 1991 , 39 (6) pp 383-386 . AN 24543
Eriksson-M.
Prilocaine reduces injection pain caused by propofol.
Acta Anaesthesiologica Scandinavica , 1995 , 39 (2) pp 210-213 . AN 34612
Fletcher-J-E; Seavell-C-R; Bowen-D-J.
Pretreatment with alfentanil reduces pain caused by propofol.
British Journal of Anaesthesia , 1994 , 72 (3) pp 342-344 . AN 30457
Ganta-R; Fee-J-P-H.
Pain on injection of propofol: comparison of lignocaine with
metoclopramide.
British Journal of Anaesthesia , 1992 , 69 (3) pp 316-317 . AN 24580
Gehan-G; Karoubi-P; Quinet-F; Leroy-A; Rathat-C; Pourriat-J-L.
Optimal dose of lignocaine for preventing pain on injection of
propofol.
British Journal of Anaesthesia , 1991 , 66 (3) pp 324-326 . AN 18465
Goodrum-D-T; Stokes-M; Cooper-G-M.
Pain on Injection with Propofol (`Diprivan`).
Anaesthesia Points West , 1987 , 20 (2) pp 75-77 . AN 11927
Helbo-Hansen-S; Westergaard-V; Krogh-B-L; Svendsen-H-P.
The reduction of pain on injection of propofol: the effect of
addition of lignocaine.
Acta Anaesthesiologica Scandinavica , 1988 , 32 (6) pp 502-504 . AN 9548
Hiller-A; Saarnivaara-L.
Injection pain, cardiovascular changes and recovery following
induction of anaesthesia with propofol in combination with alfentanil
or lignocaine in children.
Acta Anaesthesiologica Scandinavica , 1992 , 36 (6) pp 564-568 . AN 24063
Johnson-R-A; Harper-N-J-N; Chadwick-S; Vohra-A.
Pain on injection of propofol. Methods of alleviation.
Anaesthesia , 1990 , 45 (6) pp 439-442 . AN 15320
Khalid-A.
Labetalol reduces propofol injection pain.
British Journal of Anaesthesia , 1996 , 76 Suppl 2 pp 87-88 Abs A279
European Society of Anaesthesiologists 4th Annual Congress, London,
1-5 Jun 1996. AN41559
Khalid-A.
Pretreatment with ketamine reduces propofol injection pain.
Regional Anesthesia , 1995 , 20 (2S) Suppl pp 143 Abs . 20th Annual
Meeting of the American Society of Reginal Anesthesia, Orlando, 30
Mar-2 Apr 1995. AN 35329
Lyons-B; Lohan-D; Flynn-C; McCarroll-M.
Modification of pain on injection of propofol: A comparison of
pethidine and lignocaine.
Anaesthesia , 1996 , 51 (4) pp 394-395 . AN 40473
Maroof-M; Khan-R-M; Khalid-A; Siddique-M-S-K; Rahman-Z.
Pain associated with propofol injection is abolished by pretreatment
with metoclopramide.
British Journal of Anaesthesia , 1995 , 74 Suppl 1 pp 8 Abs A26 .
Abstracts: European Society of Anaesthesiologists 3rd Annual
Congress, Paris, 29 Apr-3 May 1995. AN 35457
Mecklem-D-W-J.
Propofol Injection Pain: Comparing the Addition of Lignocaine or
Metoclopramide.
Anaesthesia and Intensive Care , 1994 , 22 (5) pp 568-570 . AN 33333
Morton-N-S.
Abolition of injection pain due to propofol in children. (Letter).
Anaesthesia , 1990 , 45 (1) pp 70 . AN 13875
Nathanson-M-H; Gajraj-N-M; Russell-J-A.
Prevention of Pain on Injection of Propofol: A Comparison of
Lidocaine with Alfentanil.
Anesthesia and Analgesia , 1996 , 82 (3) pp 469-471 . AN 40670
Newcombe-G-N.
The Effect, on Injection Pain, of Adding Lignocaine to Propofol.
Anaesthesia and Intensive Care , 1990 , 18 (1) pp 105-107 . AN 17350
Nicol-M-E; Moriarty-J; Edwards-J; Robbie-D-S; AHern-R-P.
Modification of pain on injection of propofol - a comparison between
lignocaine and procaine.
Anaesthesia , 1991 , 46 (1) pp 67-69 . AN 19315
Stafford-M-A; Hull-C-J; Wagstaff-A.
Effect of lignocaine on pain during injection of propofol.
British Journal of Anaesthesia , 1991 , 66 (3) pp 406P-407P . Proc
Anesthetic Research Society, Edinburgh, 9-10 Nov 1990. AN 18471
Wilkinson-D; Anderson-M; Gauntlett-I-S.
Pain on Injection of Propofol: Modification by Nitroglycerin.
Anesthesia and Analgesia , 1993 , 77 (6) pp 1139-1142 . AN 29819
Zaouk-G; Gilbart-E; Dubois-A; Jacobs-D; Balatoni-E.
Alizapride does reduce pain on injection of propofol: comparison with
lidocaine.
British Journal of Anaesthesia , 1993 , 70 Suppl 1 pp 6 Abs A11 .European Society of Anaesthesiologists Founding Congress Abstracts,
Brussels, 12-16 May 1993. AN 27473
2. Q: What are the side effects if any of inadvertent intra-arterial infusion of propofol?
A: Although, little information is available on subcutaneous administration, some does exist on inadvertent intra-arterial injection or extravasation This is summarised below.
Chong and Davis (1987) report the case of the inadvertent injection of 4ml of `Diprivan` 1% into the left brachial artery of a 42-year old woman. An area of blanching around the injection site occurred within 5 seconds and the patient cried out in pain, which was felt radiating down towards the palm of the hand, about 8 - 10 seconds after the injection commenced. The injection was stopped immediately and anaesthesia was induced using `Diprivan` 1% in the other arm. A hyperaemic appearance over the anterior aspect of the forearm and palm was observed postoperatively, half an hour after the initial injection, and the forearm and hand felt slightly stiff. However four hours later the patient had no complaints and she had no residual symptoms when questioned a week later.
Holley and Cuthrell (1990) report the case of an 44-year old man who was inadvertently given an intra-arterial injection of 8 ml of `Diprivan` 1% through a tube connected to an arterial catheter. The patient experienced severe pain in the left hand. Upon realisation of the error, the tubing was disconnected at the needle hub and flushed with 0.9% sodium chloride. Inspection of the hand showed a good colour and the nailbeds quickly resumed a pink colour after pressure. The patient received the remainder of the `Diprivan` 1% by i.v. injection and underwent surgery for the reduction and repair of a C6-7 cervical fracture. After recovery the patient experienced no further pain in his hand or arm and the hand and fingers perfused well. The authors conclude that, other than severe pain, the intra-arterial injection of `Diprivan` 1% caused no complications in their patient.
In a letter to the journal, "Anaesthesia and Intensive Care", Riley and Lincoln (1990) report the case of a 61-year old man, scheduled for day-case cystoscopy, who received a test dose of `Diprivan` 1%, mixed with lignocaine, via a cannula inserted in a vessel in the antecubital fossa. The patient immediately complained of pain in the hand and it was realised that an artery had been cannulated by accident. The patient had not been pretreated with lignocaine and the addition of lignocaine to the `Diprivan` 1% did not eliminate the discomfort of the arterial injection. A vein in the contralateral arm was cannulated and anaesthesia proceeded without adverse event.
A subsequent letter to the above journal by Hatch (1993), again concerns a patient undergoing outpatient cystoscopy. In this case, a 78-year old woman inadvertently received approximately 1 ml of `Diprivan` 1%, mixed with lignocaine, intra-arterially. The patient experienced "excruciating pain" radiating from the site of the injection into the thenar eminence and the radial side of the hand, associated with immediate blanching of the skin surrounding the cannula site. A vein was cannulated and anaesthesia proceeded uneventfully. Digital pulse oximetry on the affected side showed no effect on the pulse waveform at any time. During the recovery period, hyperaemia was noted on the radial side of the hand which persisted for almost two hours; however, the patient was discharged four hours post-operatively in good health. Two weeks later, on presenting for major urological surgery, the patient showed no evidence of any distal ischaemia and reported no impairment of function.
Riley and Westhoff (1993) report a case of accidental extravasation of 15 ml `Diprivan` 1%, mixed with 2 ml lignocaine 2%, into the left antecubital fossa of a 46-year old woman, scheduled for cystoscopy and retrograde urogram. Transient cyanosis of the skin in the affected area was noted but the patient denied experiencing any pain, paraesthesiae or any other sensory changes. Also, she did not become anaesthetised or even sedated. A firm cool swelling was observed on the arm, just proximal to the antecubital fossa; however, the arm remained pink and the wrist pulses were easily palpable. Pulse oximetry readings from a probe on a left finger did not change. The patient was admitted for overnight observation but no special treatment was required and recovery proceeded without adverse event.
Brimacombe et. al. (1994) reported the case of a 72 year old woman who complained of severe local pain on administration of propofol. A small hyperaemic area was noted around the cannula. The authors concluded that although blood gas analysis was not performed intra arterial placement of the cannula seemed likely. They observed that this case demonstrated that large doses can lead to a transient reduction of blood flow, but that limb morbidity remains unlikely and that specific management is probably not required.
Findlay (1994) reported the case of a 29-year-old woman undergoing minor plastic surgery. The patient`s previous medical history included mild eczema of the forearms. Anaesthesia was induced with 250 mcg alfentanil and 100 mg propofol with 5 mg lignocaine delivered via a cannula in a vein in the dorsum of the left hand. As the propofol was injected, superficial forearm veins became white. A laryngeal mask was inserted and the patient breathed enflurane in air/oxygen spontaneously. 10 min into the procedure, 5 mg morphine was given via the cannula and the forearm covered in surgical drapes. On removal of these after 45 min, the forearm veins were seen still to be white. On examination, the white colouration appeared to be in the tissue surrounding the vein and was associated with mild erythema which disappeared within 3 h. The colouration was reduced after 3 h and had disappeared within 24 h, the veins remaining soft and patent throughout. The author concluded that extravasation of propofol had occurred in the superficial forearm veins. He suggested that the increased vascular permeability could possibly be connected with the patient`s eczema.
Vohra (1995) wrote a letter about a 52-year-old hypertensive man sedated in the ICU with propofol and fentanyl for 6 days having suffered head injuries and grand mal convulsions following a fall. 6 h after the venous line through which 10 ml/h propofol was being infused had been re-sited in a forearm vein, the infusion line became accidentally disconnected and it was discovered that for the previous 6 h the propofol had been infused intra-arterially. Volume of propofol administered in this way was estimated to be 60 ml. There were no local reactions at the cannula site; no significant morbidity resulted from the intra- arterial administration and sedation was judged to be adequate. Haemodynamic parameters were similar to those before placement of the cannula and the start of propofol infusion. The patient was weaned off the ventilator over the next few days but neurological recovery was poor and he died on the 15th day. Extensive intracranial pathology was confirmed at autopsy.
Leng (1997) discusses the report by Seddon (AN 44697) regarding inadvertent intra-arterial propofol. The author also reports the case of 16 year old boy who received an inadvertent injection of propofol 1%, 14 ml, into an aberrant radial artery which resulted in a delay in discharge and hyperaethesia, edema, and hyperaemia of the hand for 2 weeks. The author suggests that intra-arterial injections of propofol should not be taken too lightly, and puncture of veins should not be encouraged, as suggested by Seddon, in the antecubital area where the incidence of anomalous arteries is high (10-13%).
Finally, animal studies have demonstrated that `Diprivan` 1% does not appear to cause any changes in vessel function, other than vasodilatation (Bentley et. al., 1989, and Ozhan et. al., 1990). MacPherson et. al. (1992) investigated the arterial responses during and after the intra-arterial administration of `Diprivan` 1% in New Zealand semi-lop-eared rabbits. The authors conclude that their results, when considered in conjunction with anecdotal clinical evidence, indicate that inadvertent intra-arterial administration of `Diprivan` 1% does not lead to local constriction or damage vessel structure and that major ischaemic sequelae are unlikely.
References
Bentley-G-N; Gent-J-P; Goodchild-C-S
Vascular effects of propofol: smooth muscle relaxation in isolated veins and arteries
Journal of Pharmacy and Pharmacology 1989; 41 (11): 797-798
AN13536
Brimacombe-J; Gandini-D; Bashford,L.
Transient decrease in arm blood flow following accidental intra-arterial injection of propofol into the left brachial artery
Anaesthesia and Intensive Care 1994; 22 (3): 291-292 AN31922
Chong-M; Davis-T-P
Accidental intra-arterial injection of propofol
Anaesthesia 1987; 42 (7): 781 AN4330
Findlay-J-Y
White veins after propofol. (Letter)
Anaesthesia 1994 49 (9) pp 838 AN32539
Hatch-P
Intra-arterial injection of propofol (Letter)
Anaesthesia and Intensive Care 1993; 21 (4): 481-482 AN28809
Holley-H-S; Cuthrell-L.
Intraarterial Injection of Propofol.
Anesthesiology 1990; 73 (1): 183-184 AN15879
Leng-S-A-B.
Inadvertent intra-arterial propofol. (Letter).
Anaesthesia 1997; 52 (11): 1122-1123 AN47662
Ozhan-M; Sill-J-C; Katusic-Z; Rorie-D
Propofol, thiopental and contractile responses in isolated pig coronary arteries and cultured vascular smooth muscle cells (Abstract)
Anesthesiology 1990; 73 (3A):Abs A583, ASA Annual Meeting, Las Vegas, 19-23 Oct 1990 AN17059
MacPherson-R-D; Rasiah-R-L; McLeod-L-J.
Intraarterial Propofol Is Not Directly Toxic to Vascular Endothelium.
Anesthesiology 1992; 76 (6): 967-971 AN24477
Riley-R-H; Lincoln-C-A.
Intra-arterial injection of propofol. (Letter).
Anaesthesia and Intensive Care 1990; 18 (2): 269-270 AN26577
Riley-R-H; Westhoff-G-P
Extravasation of propofol (Letter)
Anaesthesia and Intensive Care 1993; 21 (5): 720-721 AN29344
Seddon-S-J.
Pain on injection of propofol. (Letter).
Anaesthesia 1997; 52 (3): 288 AN44697
Vohra-S-B.
Inadvertent intra-arterial infusion of propofol. (Letter).
British Journal of Intensive Care 1995; 5 (9): 306-307 AN37391
3. Q: Are there any side effects reported for `Diprivan` when it is inadvertently administered subcutaneously?
A: A small number of cases of accidental subcutaneous administration of `Diprivan` have been reported to AstraZeneca. The majority of those that were followed up had no reaction but when a reaction occurred it was generally localised and minor with swelling, discomfort and erythema Other routes of administration e.g. intra-arterial, have also been reported to cause localised temporary pain although not associated with long term damage.
4. Q: Will any electrical equipment in the OR interfere with the functioning of `Diprifusor` TCI?
A: No. Having `Diprifusor` in your pump makes the pump no less safe than other infusion pumps.
There are numerous reports in the medical literature of propofol being used successfully to sedate patients during MRI scans. Pumps and scanners should not however be in close proximity to one another for the following reasons.
To avoid the magnetic attraction between the MRI magnet and the metallic
components of the pump it is suggested to have the pump outside of the
scanner room e.g. in the control room, with a long IV line running through a
suitable portal to the patient.
The `Diprifusor` infusion pump module reads the `Diprivan` recognition tag
on the pre-filled syringe by emitting a small radio signal. Provided the pump
is a sufficient distance from the imaging equipment this should not interfer
with the quality of the images produced by the scanner.
In terms of the scanners interfering with the `Diprifusor` software current
experience indicates that this is not a problem.
5. Q: Is propofol suitable for use in asthmatic patients ?
A: The use of `Diprivan` in asthmatics is not contraindicated althought under the warnings and precautions section of the Global prescribing information it is stated that:
"As with other intravenous anaesthetic agents, caution should be applied in patients with cardiac, respiratory, renal or hepatic impairment or in hypovolaemic or debilitated patients."
Although AstraZeneca has not undertaken trials looking at this particular group of patients, asthmatics have been included in trials with no apparent problem. However, such patients may be atopic individuals who can respond adversely to many agents.
Some small studies (Clarkson et. al., 1993, Brown et. al., 1992) and case reports have been published in this area. Clarkson et. al. (1993) studied 41 asthmatic patients undergoing day-case fiberoptic bronchoscopy, of whom 20 received midazolam and 21 received propofol. They found propofol to be equally effective as midazolam in producing reliable sedation, satisfactory bronchoscopy conditions, satisfactory amnesia, and a stable haemodynamic profile. However, propofol achieved significantly faster sedation than midazolam. Furthermore, the patients in the propofol group had returned to prebronchoscopy levels of alertness when assessed at 30 minutes, while the patients in the midazolam group were still significantly less alert at 90 minutes after bronchoscopy.
Brown et. al. (1992) investigated the incidence and relative risk of wheezing during induction of anaesthesia in asthmatics. Of the 24 asthmatic patients, 7 wheezed within 5 minutes of intubation for a total incidence of 29.2% (3 of 7 receiving thiamylal, 4 of 14 receiving methohexital, and 0 of 4 receiving propofol). The study suggested that asthmatics, even when asymptomatic, have a five-fold increased risk of wheezing on induction after intubation than nonasthmatic patients. Their preliminary results in this small study showed propofol to have a lower incidence of wheezing.
In conclusion the decision to use propofol must be one for the clinical judgement of individual anaesthetists.
References
Brown-R-H, Pizov-R, Hennes-H, Hirshman-C-A
The incidence and relative risk of wheezing during indution of anaesthesia in asthmatics - preliminary results
Anaesthesiology 1992, 77 (3A) Sep Abs A1209. Abstracts of Annual Meeting American Society of Anaesthesiologists, New Orleans, 17 - 21 October, 1992
AN25213
Clarkson-K, Power-C-K, OConnell-F, Pathmakanthan-S, Burke-C-M
A comparative evaluation of propofol and midazolam as sedative agents in fiberoptic bronchoscopy
Chest 1993, 104 (4) pp 1029 - 1031 AN29351
6. Q: Can propofol be diluted in 10% glucose solution ?
A: The Global Prescribing Information states that propofol 1% ‘Diprivan’ can be diluted in 5% dextrose and this is the dilution which the manufactures can endorse. Dilutions must not exceed 1 in 5 and the mixture is stable for upto 6 hours. It should be prepared aseptically immediately before use.
Both 5% dextrose and propofol are isotonic and so when mixed the resultant solution is also isotonic. 10% glucose is hypertonic and as such this will affect the tonicity of the resulting solution.
The use of 10% dextrose as a diluent has never been investigated by the manufacturer.
Please refer to the administration section of the current prescribing information.
7. Q: What drugs can be co-administered with `Diprivan` through a Y-piece connector ?
A: Initial studies in our laboratories have suggested that the following drugs are suitable for co-administration with `Diprivan` via a Y-piece connector:- pancuronium injection, suxamethonium chloride injection, vecuronium injection, atropine injection, hyoscine injection, fentanyl injection.
`Diprivan` has also been shown to be compatible with Rapifen (alfentanil) in pharmaceutical studies undertaken jointly by AstraZeneca and Janssen Pharmaceuticals. This study concluded that:-
`Diprivan` may be premixed with Rapifen injection in the ratio of 20:1 to 50:1 or any intermediate ratio. Mixtures should be used within six hours of preparation. It has been confirmed in a clinical study that the pharmacodynamic effects of both agents were retained in this mixture (Taylor et. al., 1992).
Other clinical studies have described the successful use of mixtures of `Diprivan` and alfentanil (Sherry, 1992; Sandin and Nordstrom, 1993). The latter authors refer to a series of 1727 patients anaesthetised with this technique. A small number of cases of awareness reported in this series were attributed to lack of experience with the technique. The findings have also been recently confirmed by Maurier and Kalhain (1994) in approximately 13 000 patients aged between 1 and 93 years. The patients received the mixture for outpatient procedures lasting from between 15 minutes to seven hours.
Recent studies in our laboratories have concluded that "co-infusion of `Diprivan` with atracurium (`Tracrium`) and mivacurium (`Mivacron`) even through a Y piece, should be avoided, as they adversely affect the physical stability of the `Diprivan` emulsion. These agents should not therefore be given through the same line as `Diprivan` without prior flushing.
Always consult the full prescribing information before mixing other agents with `Diprivan`.
References
Maurier,W.G., Kalhain,S.
Propofol and alfentanil mixture for outpatient surgery
Journal of Clinical Anaesthesia 1994; 6 (2): 166-167. AN31215
Taylor-I-N; Kenny-G-N-C; Glen-J-B.
Pharmacodynamic stability of a mixture of propofol and alfentanil.
British Journal of Anaesthesia 1992; 69 (2): 168-171. AN24247
Sandin-R; Nordstroem-O.
Awareness during total i.v anaesthesia.
British Journal of Anaesthesia 1993; 71 (6): 782-787. AN29704
Sherry-E.
Admixture of propofol and alfentanil. Use for intravenous sedation and analgesia during transvaginal oocyte retrieval.
Anaesthesia 1992; 47 (6): 477-479. AN23442
Trissel-L-A; Gilbert-D-L; Martinez-J-F
Compatibility of propofol injectable emulsion with selected drugs during simulated Y-site administration.
American Journal of Health-System Pharmacy , 1997 , 54 (11) 1st Jun pp 1287-1292 . AN 46189
Farinotti-R.
(Interactions physicochimiques et mode de conservation du `Diprivan`.) Physicochemical interactions and mode of storage of `Diprivan`. (Review, 6 refs, Fre, Eng translation).
Annales Francaises d`Anesthesie et de Reanimation , 1994 , 13 (4) pp 453-456.AN 34651
8. Q: Does haemodialysis or haemofiltration affect the blood concentration of propofol ?
A: There is little literature in the public domain on this topic. However, a paper by Harris et al (1991) concerning haemofiltration, rather than dialysis in patients with renal and hepatorenal failure, concluded that haemofiltration does not significantly affect blood propofol concentration in critically ill patients.
Unpublished work shows that there is an initial small fall in the blood propofol levels at the start of dialysis but then the blood levels remain fairly constant.
Presumably, propofol either adheres directly to the membrane or to proteins adhering to the membrane at the start of dialysis until an equilibrium state is reached. There appears to be no affect on the dialysis properties of the membrane.
A later paper by Eddelston et. al. (1995) demonstrated in a small prospective trial that during haemodiafiltration, 4 patients had no change in propofol infusion, 4 patients had a minimal change, and 1 patient required an increase in infusion rate. Propofol was
not found in filtrate or dialysate.
References
Harris-C-E; O`Donnell-C; Macmillan-R-R; Mostafa-S-B
Use of propofol by infusion for sedation of patients undergoing haemofiltration - assessment of the effect of haemofiltration on the level of sedation and on blood propofol concentration
Focus On Infusion: Intensive Care Sedation Proceedings of ICU Sessions held during a Symposium in Cannes 28 - 29 April 1991
Journal of Drug Development 4 (Suppl 3) 37 - 39 AN21291
Eddleston-J-M; Pollard-B-J; Blades-J-F; Doran-B
The use of propofol for sedation of critically ill patients undergoing haemodiafiltration.
Intensive Care Medicine 1995; 21 (4): 342-347 AN 35489
9. Q: Propofol has been reported to turn urine green, what information is available in the medical literature?
A: There have been a number of literature reports of discoloured urine in patients who have received propofol.
In most cases the discoloration is seen in the intensive care unit, where patients are receiving sedative doses by infusion, and ranges from a bright green to reddish brown (Bodenham 1987, Hughes 1988, Beller 1988, Kitson 1988, Reeve 1991, Cadier 1993, Tirosh 1996, Marinella 1997, Miyazawa 1998, ).
Green urine has been seen on catheterisation immediately following induction (Ananthanarayan 1995) and white urine has been observed in four patients during prolonged surgical procedures where propofol was used for maintenance (Nates 1995). Masuda (1996) report their experience with 9 cases of milky pink urine, which were probably the same phenomenon as that described by Nates.
Uric acid excretion has been found to increase during propofol anaesthesia (Miyazawa 1998, Masuda 1997) which is thought may cause discoloration of urine (white or cloudy).
The colour of the urine, which is pH sensitive, is thought to be due to a complex metabolite of propofol. The urinary metabolite fluoresces at an acidic pH and its occurence is therefore an indicator of an acid urine and an indirect indicator of acidosis. This metabolite has not been identified but is not a known derivative of propofol. The normal quinol metabolites have been isolated and found to be colourless.
The presence of discoloration in the urine is not thought to be clinically significant since renal function in these patients has not been affected.
References
Ananthanaranyan C, Fisher JA
Why was the urine green?
Canadian J Anaesthesia 1995 42(1) 87-89 AN34204
Beller JP, Pottecher T, Lugnier A, Mangin P, Otteni JC
Prolonged sedation with propofol in ICU patients: recovery and blood concentration changes during periodic interruptions in infusion
Br J Anaesthesia 1988 61(5) 583-588 AN9897
Bodenham A, Culank LS, Park GR
Propofol infusion and green urine
Lancet 1987 2(8561) 740 AN5247
Cadier MA, Clarke JA
Ecstasy and Whizz at a rave resulting in a major burn plus complications
Burns 1993 19(3) 239-240 AN28124
Hughes KR, Armstrong RF
Continuous infusion of propofol
Anaesthesia 1988 43(4) 331 AN7995
Kitson GE, Wauchob TD
Pulmonary oedema following carbamazepine overdose
Anaesthesia 1988 43(11) 967-969 AN10026
Marinella-M-A.
Propofol for sedation in the intensive care unit: essentials for the clinician. (Review, 52 refs).
Respiratory Medicine 1997; 91 (9): 505-510. AN47194
Masuda-A; Hirota-K; Satone-T; Ito-Y.
Pink Urine During Propofol Anesthesia. (Letter).
Anesthesia and Analgesia 1996; 83 (3): 666-667. AN42895
Masuda-A; Asahi-T; Sakamaki-M; Nakamaru-K; Hirota-K; Ito-Y.
Uric Acid Excretion Increases During Propofol Anesthesia.
Anesthesia and Analgesia 1997; 85 (1): 144-148. AN46612
Miyazawa-N; Izawa-H; Miyao-H; Takeda-J.
White urine due to uric acid during propofol anesthesia.
Anesthesia and Analgesia 1998; 86 (2S) Suppl: Abs S485. AN49120
Miyazawa-N; Takeda-J; Izawa-H.
Does propofol change uric acid metabolism?
Anesthesia and Analgesia 1998; 86 (2S) Suppl: Abs S486. AN49119
Nates J, Avidan A, Gozal Y, Gertel M
Appearance of white urine during propofol anaesthesia
Anesth Analg 1995; 81(1): 210. AN36263
Reeve WG, Wallace PGM
A survey of sedation in intensive care
Care of the Critically Ill 1991; 7(6): 238-241. AN22171
Tirosh-R; Barzilay-Z; Almog-S; Paret-G.
Propofol and green urine. (Letter).
Paediatric Anaesthesia 1996; 6 (3): 244. AN41425
10. Q: Does the Diprivan pre-filled syringe contain silicone and if so how much?
A: ‘Diprivan’ stored in a pre-filled syringe will contain less than 0.01 mg/ml silicone during its shelf life, and the amount of silicone which may be injected into a patient will be less than 0.01 mg/ml.
Ref. AstraZeneca Data on File
11. Q: How sterile is the pre-filled syringe?
A: The pre-filled syringe plunger rod and sterile luer connector are packaged in a plastic tray. The secondary packaging is not sterile, only the contents of the syringe and the luer connector are sterile. Therefore, as a precaution, the top of the syringe needs to be disinfected with alcohol before use.
Ref. AstraZeneca Data on File
12. Q: What is the mechanism of the antimicrobial action of EDTA?
A: The action of EDTA is to chelate (bind) divalent metal ions such as Ca++ and Mg++ and hence make them unavailable to the bacteria for cellular replication and growth.
Divalent metal ions are essential for the stability and replication of the outer layers of bacterial cell walls and in some cases EDTA can be used to destabilise and remove the outer lipopolysaccharide layer.
The dependance for metal ions is somewhat species specific, pseudomonas species for example have a particular dependance on Mg++ . The sensitivity of bacteria to EDTA can be used to enhance the succeptability of bacteria to antibiotics by destabilising the cell wall structure.
Although at a concentration of 0.005% the EDTA in Diprivan does not have any direct antimicrobial activity (it is not bactericidal) it is sufficiently high to bind available divalent ions and so inhibit microbial growth.
References
Pharmaceutical Microbiology. Sixth Edition. Eds W B Hugo and A D Russell. Publishers Blackwell Science
13. Q: Are there any reports of Diprivan causing corrosion of infusion equipment?
A: On the Planet literature database there are no previous reports of equipment corrosion associated with the use of Diprivan. We have received no previous reports to the company of Diprivan causing a corrosive reaction with any intravenous equipment. If there had been any previous reports it would be expected that this would have resulted in some form of warning on the current prescribing information. As with all lipid infusions, prolonged contact with some plastics occurring in infusion equipment may result in the plastic becoming softened and/or weakened. However adherence to the prescribing information recommendation to change the infusion set associated with Diprivan infusion would prevent any significant occurrence of this.
References
Prescribing Information
Planet literature database search
14. Q: Is there any Gluten in Diprivan?
A: The list of pharmaceutical excipients in Diprivan is given in the Global Prescribing Information. Diprivan does not contain Gluten.
Gluten is the protein found in wheat and other grain products which gives it elasticity.
References
Astrazeneca Pharmaceutical Department.
Global Prescribing Information
15. Q: Does Diprivan contain any mercuric compounds or are they involved in the manufacture? Is it suitable for use in patients with a known allergy to mercury containing compounds?
A: The Global Prescribing Information for Diprivan clearly states in the contraindications section (section 4.3) that Diprivan is contraindicated in patients with a known allergy to Diprivan (on one of its excipients).
Diprivan does not contain any mercuric compounds (e.g. phenylmercuric nitrate) and the hydroxybenzoates (e.g. methylhydroxybenzoate, propylhydroxybenzoate) and they are not involved in the manufacturing process. Therefore Diprivan should be suitable for use in patients if known allergy to mercury based compounds is an issue.
References
Global Prescribing Information.
Data from AstraZeneca pharmaceutical department
16. Q: Is the dose of Diprivan, required to induce and maintain anaesthesia, affected by the alcohol intake of patients?
A: A number of papers suggest that some patients who have a high alcohol intake may require higher doses of 'Diprivan'. The mechanism of this action has not been elucidated, but may possibly be due to induction of the enzymes participating in propofol metabolism thereby increasing the rate of metabolism.
Holder and Weller (1997) discuss the metabolism of alcohol, drug metabolism and cross-tolerance, pathogenicity (neurological, liver, cardiovascular, respiratory, gastrointestinal, hematological, pancreatic, renal, and metabolic), specific problems for the anaesthetist (acute intoxication, ethanol withdrawal in the chronic alcoholic, and pre- and postoperative assessment), administration of anaesthesia (rapid sequence induction, balanced technique), monitoring, recovery and regional analgesia in intoxicated patients.
Fassoulaki et. al. (1993) investigated the induction dose required in an open prospective study of 26 patients with an average ethanol consumption of 40 g/day for at least 2 years (Group 1) and 20 patients consuming alcohol occasionally or not at all (Group 2). The patients were premedicated with 1.5-2.5 mg/kg hydroxyzine and 1 mg oral atropine. All patients were undergoing ear, nose and throat surgery. 'Diprivan' was administered by an infusion pump and doses were recorded upon loss of verbal contact and when the patient dropped a syringe. Group 1 was significantly older and weighed less (48 years and 64 kg) than Group 2 (38 years, P<0.001 and 72 kg, P<0.05). There were significant differences between groups in pre-induction levels of gamma-glutamyl transpeptidase and alanine and aspartate aminotransferase. Group 1 patients required 2.7 mg/kg propofol for loss of verbal contact compared to 2.2 mg/kg for Group 2 (a significant difference, P<0.001). To drop the syringe, Group 1 required 4.2 mg/kg propofol while Group 2 required significantly less (3.2 mg/kg, P<0.001). Propofol blood levels at induction were 17.3 mcg/ml for Group 1 and 14.6 mcg/ml for Group 2. The authors conclude that "the doses of propofol required to induce anaesthesia in chronic alcoholic patients are more than in patients who drink socially".
Du Cailar et. al. (1987) present 2 case reports supporting the existence of resistance to propofol in patients with chronic alcoholism. A third case involving a man who was acutely intoxicated at the time of surgery demonstrated that alcohol can potentiate the effects of propofol.
Mackenzie and Grant (1986) studied 30 patients scheduled to undergo orthopaedic surgery under spinal anaesthesia who were premedicated with an oral benzodiazepine. An infusion of propofol was then administered into a peripheral hand vein. 2.5 to 3 ml of Bupivacaine 0.75% was used to provide spinal anaesthesia. The infusion rate of propofol was adjusted to maintain an appropriate level of sedation. All patients received an infusion of Hartmann's solution or blood and breathed oxygen enriched air. The propofol infusion was stopped 5-10 min before the end of surgery. 13 males and 17 females were studied. The first 13 patients had an initial infusion rate of 4 mg/kg/h for 30 min. The remaining 17 patients received 6 mg/kg/h for 10 min reducing to 4 mg/kg/h for the next 10 min. The average infusion rate was 3.8 mg/kg/h, patients over 65 requiring significantly less and 2 heavy drinkers requiring significantly more.
References
Du-Cailar-J; DAthis-F; Eledjam-J-J; Bonnet-M-C.
(Propofol et ethylisme). Propofol and alcoholism. (English translation).
Annales Francaises d'Anesthesie et de Reanimation 1987; 6 (4): 332-333. AN5458
Fassoulaki-A; Farinotti-R; Servin-F; Desmonts-J-M.
Chronic Alcoholism Increases the Induction Dose of Propofol in Humans.
Anesthesia and Analgesia 1993; 77 (3): 553-556. AN28869
Holder-K-J; Weller-R-M.
Southmead Hospital and Frenchay Hospital, Bristol, England.
Medicine. Alcohol consumption and anaesthesia. (Review, 13 refs).
Current Anaesthesia and Critical Care; 1997; 8 (5): 231-236. AN48088
Mackenzie-N; Grant-I-S.
Propofol for continuous intravenous sedation.
Beitraege zur Anaesthesiologie und Intensivmedizin 1986; 17 Abstracts Book 2: 303 Abs 466. 7th European Congress of Anaesthesiology, Vienna, 7-13 Sep, 1986 Editors: Bergmann H, Kramar H and Steinbereithner K, ISBN 385-175-448-2. AN1027
17. Q: How do you determine the Keo for Diprivan and what is its value?
A: TCI systems facilitate the delivery of anaesthetic agents by rapidly achieving and then maintaining a particular drug blood concentration. However, it must be appreciated that anaesthesia is induced by the effect of a drug acting on a site or sites within the brain which by their very nature are remote from the blood. There is therefore a delay between any change in the blood concentration of an anaesthetic agent and its effect in the brain [Schnider et al 1994]. The concentration at this effect site is linked to the blood concentration of a drug by a blood-brain equilibration constant (Keo). Given a measure of drug effect such as spectral edge it is possible to calculate a value for Keo for any anaesthetic agent. Using the auditory evoked response the Keo for propofol has recently been estimated to have a mean value of 0.2 min-1 [White et al 1999]. Estimation of Keo for a given drug permits calculation of the effect site concentration and this can be displayed on a TCI system. Such displays allow the anaesthetist to assess the degree to which brain and blood concentrations of propofol have equilibrated.
References
White-M; Schenkels-M-J; Engbers-F-H-M; Vletter-A; Burm-A-G-L; Bovill-J-G; Kenny-G-N-C.
Effect-site modelling of propofol using auditory evoked potentials.
British Journal of Anaesthesia , 1999 , 82 (3) pp 333-339 .
Schnider TW, Minto CF, Stanski DR
The effect compartment concept in pharmacodynamic modelling.
Anaesthesia Pharmacological Reviews 1994; 2:204-213
18. Q: Can lignocaine be added to overcome pain on injection when using Diprifusor TCI?
A: Lignocaine 1% to 2% can be administered 10-30 seconds before using 'Diprifusor' TCI in order to reduce pain on injection. Lignocaine must not be mixed with 'Diprivan'in the PFS before use.
References
Diprivan Core Data Sheet
19. Q: Should actual or lean body weight be used when inputting weight data for an obese patient into the "Diprifusor" pump?
A: Actual body weight should be used for obese subjects. Dr Servin 1993 showed that dosing schemes were the same for obese patients as for normal patients. However the anaesthetist should always titrate to effect. She compared 8 morbidly obese patients weighing 97-160 kg and undergoing elective surgery for => 2 h with a control group. She showed that in the obese group, steady state volume of distribution and total body clearance of propofol were correlated to body weight whereas distribution clearance was not. The extrapolated area under the curve (AUC) was the same for both groups (3.16%). She concluded that using an appropriate dosing scheme in morbidly obese patients there is no accumulation of propofol.
References
Servin-F; Farinotti-R; Haberer-J-P; Desmonts-J-M
Propofol Infusion for Maintenance of Anesthesia in Morbidly Obese Patients Receiving Nitrous Oxide.
Anesthesiology 1993 78 (4) pp 657-665
20. Q. Will any electrical equipment in the OR interfere with the functioning of "Diprifusor" TCI?
A: No. Having "Diprifusor" in your pump makes the pump no less safe than other infusion pumps.
There have been reports of MRI scanners and Diprifusor pumps interacting due to the strong magnetic field however it is generally considered that if the pump is placed outside of the immediate vicinity of the magnet, ie in the control room with a long infusion line leading to the patient, then there is no risk of any interaction or interference. (see AN 59781).
References
Wynnychenko TM et al
Infusion pump use in the MRI
Anesthesia and Analgesia, 2000, 91(1), 249-250 (AN 59781)
21. Q: What is the calorific value of Diprivan?
A: The calorific value of 'Diprivan' in a patient in the ICU who is sedated by an infusion of propofol at the rate of 20 ml/h would receive 528 kilocalories per day (Platt and White, 1987) eg., 1 ml of 'Diprivan' = 1.1 kcal per 1ml (or 4.6 kJ per 1ml).
References
Platt M, White DC
Calories in sedation.
Anaesthesia 1987; 42(3): 322 AN2269
22. Q: What non-pharmaceutical methods have been used to reduce the incidence of pain on injection on induction of anaesthesia with propofol?
A: A number of non-pharmaceutical methods have been used to reduce pain on injection including different routes of administration (less pain with the larger veins), use of glass rather than plastic syringe, use of either cold (4° C ) or warm (37°C ) emulsions and aspiration ( mixing patients blood with Diprivan prior to induction). The most commonly used non-pharmaceutical method is the administration of 'Diprivan' into a large vein.
A common adverse event associated with 'Diprivan' administration is ‘pain on injection’ with a reported incidence of between 5% and 74%. The following non-pharmaceutical mehods have been described in the literature for reducing the pain associated with 'Diprivan' administration.
Effects of route of administration
A summary of the effect of route of administration on the incidence on pain on injection with propofol on induction of anaesthesia is summarised below:
Route of administration / Number of patients
Mean % Incidence of Pain on Injection (range)
Injection into antecubital fossa 428/6.0
Injection into forearm 117
39.5 (4-76)
Injection into back of hand 566
63.5 (29-93)
A summary of each study is presented in the attachment below. It can be concluded that injection of propofol into the small veins at the back of the hand will give about a 63% incidence of pain on injection whilst injection into the antecubital fossa gives a low incidence of 6%.
Speed of injection
Unfortunately, few if any studies have investigated the effect of rate of administration on the incidence of pain on injection.
Use of Glass syringe
Lomax (AN32325) reported a low incidence of propofol injection pain when propofol was administered from a glass syringe at a rate of 10 ml over 10-15 s in 100 elderly patients. 84% of patients experienced no pain. He suggested that propofol strips the silicone lubricant from the inside of plastic syringes which interacts to cause pain on administration.
Effect of temperature on pain on injection
Cold
McCirrick and Hunter (AN 16987) showed a significant reduction in the incidence of pain on injection when the temperature of propofol was reduced from room temperature to 4° C without altering the efficacy of the drug as an induction agent. The incidence of pain was reduced from 46% to 24%. Similar findings have been reported by Kaya et al (AN35543) and Verlinden (AN 33697) although in the latter study 1% lidocaine was shown to be superior to cooling. Also of interest, Barker et al (AN21660) showed that propofol immediately preceded by 10ml physiological saline at 4° C injected over 15s was as effective in reducing propofol injection pain as propofol mixed with lignocaine.(There was a 75% incidence of propofol injection pain in the placebo group compared with 22% and 44% in the cold saline and lignocaine groups respectively)
Warming
Fletcher et al (AN 41039) showed that warming propofol to 37°C reduced the incidence of pain on injection from 59% to 22% in 101 healthy outpatients. In contrast Vijayakulasingham et al (AN34832) failed to show any significant differences in propofol injection pain when the temperature of propofol was raised from 32°C to 40°C.
Aspiration
McDonald and Jameson 1996 in a randomized, controlled, single-blind study, showed that aspiration of a patient's own blood into a syringe of propofol immediately before injection into a vein in the back of the hand reduced pain on injection to the same extent as lignocaine. They aspirated 2 ml of the patient's own blood into a 20 ml syringe containing 18 ml blood prior to induction of anaesthesia. They then administered 7 ml of the propofol mixtures over 7-10 s and rated any pain on a mild, moderate or severe scale.
Although a number of non-pharmaceutical methods have been used to reduce propofol injection pain, the most commonly used is the administration of 'Diprivan' into a large vein.
References
Barker-P; Langton-J-A; Murphy-P; Rowbotham-D-J.
Effect of prior administration of cold saline on pain during propofol
injection. A comparison with cold propofol and propofol with
lignocaine.
Anaesthesia , 1991 , 46 (12) pp 1069-1070 . AN 21660
Fletcher-G-C; Gillespie-J-A; Davidson-J-A-H
The effect of temperature upon pain during injection of propofol.
Anaesthesia , 1996 , 51 (5) pp 498-499 . AN 41039
Kaya-K; Oezkocak-I; Akcabay-M; Babacan-A; Izdes-S; Oecal-E;
Karadenizli-Y.
Effect of lidocain addition to cold propofol and the propofol at room
temperature on the propofol injection pain.
British Journal of Anaesthesia , 1995 , 74 Suppl 1 pp 140 Abs A462 .
Abstracts: European Society of Anaesthesiologists 3rd Annual
Congress, Paris, 29 Apr-3 May 1995. AN 35543
Lomax-D.
Propofol injection pain. (Letter).
Anaesthesia and Intensive Care , 1994 , 22 (4) pp 500-501 . AN 32325
McDonald-D-S; Jameson-P
Injection pain with propofol: Reduction with aspiration of blood.
Anaesthesia 1996 51 (9) pp 878-880 AN 0042627
McCrirrick-A; Hunter-S.
Pain on injection of propofol: the effect of injectate temperature.
Anaesthesia , 1990 , 45 pp 443-444 . AN 16987
Verlinden-B; Van-De-Put-D; De-Hert-S; Adriaenssen-H.
Pain on injection of propofol.
Acta Anaesthesiologica Belgica , 1994 , 45 (2) pp P.59-P.60 .
Proceedings of the Residents' Meeting of the Belgian Society of
Anesthesia and Reanimation, Brussels, 19 Mar 1994. AN 33697
Vijayakulasingham-V; Ratnayake-N; Saunders-P-R-I.
Propofol: Injectate Near Body Temperature and Pain on Injection.
1st International & 3rd European Congress on Ambulatory Surgery ,
1995 , Abs P112 . Brussels, 16-17th Mar 1995. AN 34832
23. Q: Why is it necessary to shake a vial or ampuole of Diprivan before use?
A: The UK and USA prescribing information states: 'Containers should be shaken before use'
This statement is included to ensure an even distribution of the formulation. After prolonged standing (weeks or months) the Diprivan emulsion will begin to form a density gradient with the less dense material accumulating at the top of the ampoule. This is a recognised characteristic of this type of emulsion and explains why very gentle shaking is recommended before use.
References
Diprivan Core Data Sheet
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