PROPOFOL

Drugs in Pregnancy and Lactation.

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Name: PROPOFOL
Class: Hypnotic
Risk Factor:    BM

Fetal Risk Summary

A number of studies have described the use during cesarean section of propofol, a hypnotic agent used for the IV induction and maintenance of anesthesia (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19 and 20). Apparently, the drug has not been used during the 1st and 2nd trimesters in humans. Reproduction studies in rats and rabbits at doses 6 times the recommended human induction dose revealed no evidence of impaired fertility or fetal harm (21).

The pharmacokinetics of propofol in women undergoing cesarean section was reported in 1990 (1). Propofol rapidly crosses the placenta and distributes in the fetus (2,3,4,5,6,7,8,9,10,11 and 12). The fetal:maternal (umbilical vein:maternal vein) ratio is approximately 0.7. Doses were administered either by IV bolus, by continuous infusion, or by both methods.

Several studies have examined the effect of maternal propofol anesthesia on infant Apgar scores, time to sustained spontaneous respiration, and Neurologic and Adaptative Capacity Score (NACS) or Early Neonatal Neurobehavioural Scale (ENNS) (1,2,4,5,7,8,11,12,13,14,15,16,17 and 18). Most investigators reported no difference in the Apgar scores of infants exposed to propofol either alone or when compared with other general anesthesia techniques, such as thiopental with enflurane or isoflurane (2,5,7,8,14,15,16,17 and 18). Moreover, no correlation was found between the Apgar scores and umbilical arterial or venous concentration of propofol (2,5,8,11,15).

In one study infants (N=20) exposed to a maternal propofol dose of 2.8 mg/kg had significantly lower Apgar scores at 1 and 5 minutes compared with infants (N=20) whose mothers were treated with thiopental 5 mg/kg (p<0.05) (13). The Apgar scores in both groups were significantly lower (p<0.002) when compared with infants born by spontaneous vaginal delivery. The induction-to-delivery and uterine incision–to-delivery intervals in the two treatment groups were nearly identical. Five propofol-exposed infants had profound muscular hypotonus at birth and at 5 minutes, and one newborn was somnolent (13). Propofol-exposed infants were evaluated using the ENNS and found to have a depression in alert state, pinprick and placing reflexes, and mean decremental count in Moro and light reflexes 1 hour after birth, but not at 4 hours (13). Five (25%) of the infants exhibited generalized irritability and continuous crying at 1 hour, but not at 4 hours.

In contrast, most studies found no difference in the NACS or time to sustained spontaneous respiration between various groups with propofol IV bolus doses of 2.5 mg/kg, or when continuous infusion doses were no higher than 6 mg/kg/hour (2,5,8,14,15 and 16). Higher doses, such as 9 mg/kg/hour, were correlated with a depressed NACS (8,12,14,15 and 16,18).

Breast Feeding Summary

Small amounts of propofol are excreted into breast milk and colostrum following use of the agent for the induction and maintenance of maternal anesthesia during cesarean section (3). Two groups of women were studied. The first group consisted of four women who had received a mean IV propofol dose of 2.55 mg/kg, a mean of 25.9 minutes before delivery. The mean total dose received by patients in this group was 155.5 mg. The second group consisted of three women who had received a mean IV dose of 2.51 mg/kg plus a mean infusion of 5.08 mg/kg/hr. The mean total dose in this group was 247.4 mg, and the mean time to delivery was 20.2 minutes. Breast milk or colostrum samples were collected at various intervals from 4 to 24 hours after delivery. Propofol concentrations in the seven patients varied between 0.048 and 0.74 µg/mL, with the highest levels predictably occurring at 4–5 hours in group 2. In one patient from group 2, the milk/colostrum concentration was 0.74 µg/mL at 5 hours and fell to 0.048 µg/mL (6% of the initial sample) at 24 hours. These amounts were considered negligible when compared with the amounts the infants received before birth from placental transfer of the drug (3).

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References

  1. Gin T, Gregory MA, Chan K, Buckley T, Oh TE. Pharmacokinetics of propofol in women undergoing elective caesarean section. Br J Anaesth 1990;64:148–53.
  2. Dailland P, Lirzin JD, Cockshott ID, Jorrot JC, Conseiller C. Placental transfer and neonatal effects of propofol administered during cesarean section (abstract). Anesthesiology 1987;67:A454.
  3. Dailland P, Cockshott ID, Lirzin JD, Jacquinot P, Jorrot JC, Devery J, Harmey JL, Conseiller C. Intravenous propofol during cesarean section: Placental transfer, concentrations in breast milk, and neonatal effects. A preliminary study. Anesthesiology 1989;71:827–34.
  4. Moore J, Bill KM, Flynn RJ, McKeating KT, Howard PJ. A comparison between propofol and thiopentone as induction agents in obstetric anaesthesia. Anaesthesia 1989;44:753–7.
  5. Dailland P, Jacquinot P, Lirzin JD, Jorrot JC. Neonatal effects of propofol administered to the mother in anesthesia in cesarean section. Can Anesthesiol 1989;37:429–33.
  6. Dailland P, Jacquinot P, Lirzin JD, Jorrot JC, Conseiller C. Comparative study of propofol with thiopental for general anesthesia in cesarean section. Ann Fr Anesth Reanim 1989;8 (Suppl):R65.
  7. Valtonen M, Kanto J, Rosenberg P. Comparison of propofol and thiopentone for induction of anaesthesia for elective caesarean section. Anaesthesia 1989;44:758–62.
  8. Gin T, Gregory MA. Propofol for caesarean section. Anaesthesia 1990;45:165.
  9. Pagnoni B, Casalino S, Monzani R, Lazzarini A, Tiengo M. Placental transfer of propofol in elective cesarean section. Minerva Anestesiol 1990;56:877–9.
  10. Maglione F, Guarini MC, Montanari A, Cirillo F, Postiglione M, Pica M, Amorena M, De Liguoro M. Determination of propofol blood levels in mothers and newborns in anesthesia for cesarean section. Minerva Anestesiol 1990;56:881–3.
  11. Gin T, Gregory MA, Chan K, Oh TE. Maternal and fetal levels of propofol at caesarean section. Anaesth Intensive Care 1990;18:180–4.
  12. Gin T, Yau G, Chan K, Gregory MA, Oh TE. Disposition of propofol infusions for caesarean section. Can J Anaesth 1991;38:31–6.
  13. Celleno D, Capogna G, Tomassetti M, Costantino P, Di Feo G, Nisini R. Neurobehavioural effects of propofol on the neonate following elective caesarean section. Br J Anaesth 1989;62:649–54.
  14. Gin T, Yau G, Gregory MA. Propofol during cesarean section. Anesthesiology 1990;73:789.
  15. Gin T, Yau G, Chan K, Gregory MA, Kotur CF. Recovery from propofol infusion anaesthesia for caesarean section. Neurosci Lett (Suppl) 1990;37:S44.
  16. Gregory MA, Gin T, Yau G, Leung RKW, Chan K, Oh TE. Propofol infusion anaesthesia for caesarean section. Can J Anaesth 1990;37:514–20.
  17. Gin T, Gregory MA, Oh TE. The haemodynamic effects of propofol and thiopentone for induction of caesarean section. Anaesth Intensive Care 1990;18:175–9.
  18. Yau G, Gin T, Ewart MC, Kotur CF, Leung RKW, Oh TE. Propofol for induction and maintenance of anaesthesia at caesarean section. Anaesthesia 1991;46:20–3.
  19. Costantino P, Emanuelli M, Muratori F, Sebastiani M. Propofol versus thiopentone as induction agents in cesarean section. Minerva Anestesiol 1990;56:865–70.
  20. Alberico FP. Propofol in anesthesia induction for cesarean section. Minerva Anestesiol 1990;56:871.
  21. Product information. Diprivan. AstraZeneca, 2000.

Index

Q&A about Propofol

kim jeong
What does Propofol really do in pur body?
Does propofol provide a state of analgesia or merely sadation?

When the GABA-A receptor is being potentiated and the neurotransmitters are being inhibited, What will happen? Will the patient's skeletal muscles relax also?

What is the PRIMARY USE of Propofol? What does it mean when you say a GENERAL ANAESTEHTIC AGENT?

IS Propofol only for sedation and nothing else?
Pangolin
Propofol is a sedative/hypnotic, and can be used for sedation or general anesthesia.

It has NO analgesic properties, so for surgery, it is administered along with analgesic drugs. That's not necessary if it's being used for sedation along with a spinal, or for a procedure that isn't going to cause any pain afterward, like a colonoscopy.

It provides NO skeletal muscle relaxation, which is great if we want our patient to breathe spontaneously during the procedure.

Primary use: general anesthesia induction agent - the "going off to sleep" drug. It provides rapid, deep anesthesia which is very short acting, about 5 minutes. That's time enough for us to get the breathing tube in (if that's our choice of airway management), and get some gas on. It's short acting enough that if we run into problems, waking up is an option.

It's also great for deep sedation/intravenous general anesthesia (you can't always tell by looking when your sedation has turned into general). Because it goes away so quickly, it's ideal for surgery tht requires the patient to wake up and cooperate during or immediately after the procedure.

I don't like it for conscious sedation, because patients get squirmy and confused, and are more likely to try to get up and leave or cause trouble in other ways.

Propofol has antiemetic properties, and small doses can be used to treat post-operative nausea and vomiting.
irish
Mom was sedated on propofol for 7 days and isnt waking up?
She had a triple bypass. The doctor said that it can take time. How long does it usually take to wake up after a long period of propofol? She has been off of it for 2 days now. He eyes are about halfway open, but she is completely unresponsive.
confuzze...
Just wait it out the doctors can tell now adays between coma and death if she were dead and just on support they would know. Which means shes alive!!!!!! I was faced with a lifethreatening illness with no cure (i made it obviously) but when i was ill i was out cold without meds so my body could repair itself in a week i spent 90% of the time asleep like a rock and this was not medically induced. My point is her body may keep her asleep to heal- only time will tell
KayGrace
For anesthesiologists: What is the difference between Propofol and Etomidate?
Are they administered the same? Why use one over the other? Does one last longer? Does one put you further under? Does one have higher risks? Have fewer side effects? How do the recovery times compare?
Surfnrg
Propofol and Etomidate fall into the sedative/hypnotic category, meaning they are both used to induce either unconsciousness or provide sedation. Propofol being the more diverse of the two drugs.

Both Propofol and Etomidate work by stimulating GABA receptors (anesthesia is all about "GABA"). GABA is one of the few major inhibitory neurotransmitters. Basically, you're creating an inhibition in the normal body responses. Etomidate also works by depressing the reticular activating system (RAS).

Clinical considerations:

---Both burn momentarily with injection due to the suspension they're prepared in. Lidocaine is typically injected just before Propofol to lessen the local irritation.

---Propofol has slightly less duration (4-10min) vs Etomidate (5-15 min). Both are very lipid soluble and redistribute quickly into fat tissues. Propofol is metabolized by the liver, and Etomidate is metabolized by enzymes in the blood (plasma esterases), along with hepatic microsomal enzymes.

---Both have serious side effects. Propofol drops your systemic vascular resistance therefore dropping BP. If you have cardiovascular issues or low blood pressure, we'll likely give Etomidate instead (being the more cardiovascular stable drug). However, Etomidate causes myoclonus (localized seizures), so it needs to be given with a paralytic or benzodiazepine. Etomidate also tends to cause nausea/vomiting, whereas Propofol actually has antiemetic effects. Etomidate can also cause serious hypotensive issues 6-8 hours later due to a drop in cortisol levels (something that does not seem to be commonly understood in many ER's or ICU's)

There has been some previous reports that if the patient has an allergy to egg whites, it would contradict Propofol due to it's egg lecithin preparation. Recent studies have found that to be inconclusive.

Bottom line: Propofol is preferred unless blood pressure or CAD limits it's use.
Jesus W
Can propofol cause changes in a ussualy normal period?
An 18 year old female had a procedure done, and they use propofol, she reffers to have had intercourse 1 week before, she used the day after pill that time, and her period had to have come 1 week after, acording to her calendar. She had not had intercourse 2 months before that, and her period was regular those months. now she says her period is 1 week late.
Joseph
Propofol does not seem to effect your period:

Side effects that you should report to your prescriber or health care professional as soon as possible:

•difficulty breathing, wheezing, swelling of the throat

•fast heartbeat, palpitations

•lightheadedness or fainting spells

•numbness or tingling in the hands or feet

•seizure (convulsion)

•skin rash, flushing (redness), or itching

•swelling or extreme pain at the injection site

•uncontrollable muscle spasm

So I guess you better wait another couple of weeks and if you do not get your period have a preganncy test done, no use having it now its too early.
julie57
what is the difference between propofol and midazalam sedative drugs?
in what way do they differ. and what are the differing effects on the body
drblonde
I can't remember very well as I'm now a GP and its been a while since I worked in Anaesthetics, but... midazolam is a benzodiazepine, which has a short duration of action. Propofol is used as a general anaesthetic agent as it has a longer duration of action. Midazolam can be given for short-term sedation, for eg. to put back a dislocated shoulder. Propofol is only given by an anaesthetist in an operating-theatre setting.

Sorry I can't remember more about modes of action.
BEACH GIRL
I have to have surgery, and they are giving me Diprivan / Propofol. What that make me feel like I am sleeping?
I don't wanna be awake or remember anything.
Jungle Jane
You may drift in and out. When I have propofol I go in and out but it's kind of like taking a cozy nap, then waking up a bit and having the lovely feeling that I can go right back to sleep instead of having to wake right up. Tell those doing the surgery that you realize you'll be drifting in and out and that you'd prefer quiet and to be unaware of what's going on so that you can drift in and out peacefully. They call propofol "Mother's Milk" (La Leche) because it's comforting and soothing!
nascargi...
Can deep sedation such as propofol be used for surgery for instance for something that lasts 1-2hrs ?
Instead of using General Anesthesia can Deep Sedation be used?
Pangolin
The line between deep sedation and general anesthesia is not something that can be easily seen or measured. (It's when you lose your protective airway reflexes)

If by "general anesthesia" you mean using gas to keep you asleep, then propofol can be used as an alternative. Propofol can be used as a general anesthetic.

Deep sedation can be used for as long as necessary, but only for surgery that is conducive to that. Some surgery requires the patient to be paralyzed, and once you take away the ability to breathe, you've crossed over to general anesthesia. There are also procedures that require a breathing tube (like laparoscopic procedures), and few people could tolerate a tube with sedation.

We routinely use deep sedation for endovascular cases, and those go on FOREVER sometimes.

Anesthesia is all about balance - we have to give just enough drug to keep the patient comfortable (and alive). For low-stimulation surgery (like endovascular cases), a little sedation goes a long way.

Hope that helps.
DG
I am allergic to soy and am scheduled for colonoscopy. What alternatives are there to propofol for me?
ajmill19...
The doctor performing the procedure should have several. A benzodiazepine is usually indicated (like midazolam), perhaps mixed with fentanyl. However, defer to your internist's opinion.
serialmo...
Is propofol safe to use on a patient with sleep apnea?
The Dr is going to use this on my girlfriend instead of that god-awful drug Versed for a colonoscopy. That drug gave me permanant brain damage from just one use....I don't want this to happen to her!!
cwgrrl7
Propofol is safely used on a daily basis to medicate patients for surgery.
emilguro...
Why Astra Zeneca warns that Propofol is contraindicated for Cesarean section but it is used for this operation
Propofol exists in every protocol for induction of anaesthesia along with commonly used Thiopental and Ketamine. One can read this in every textbook of Anaesthesia but look at the leaf-let of this product. And this is not only that company, it is the same with Finnish producers, Claris...
belfus
because fetal effects are unknown. we don't know how much propofol will get across the placenta to the baby, and we furthermore don't know what the effects would be on the unborn baby. the answer to those questions is that the risk is very likely negligible, but for ethical reasons it's impossible to conduct a study to prove its safety in unborn babies. so the manufacturer must put that warning to shift liability on to the doctor using the drug. i can tell you from personal experience that you're right, propofol is used all the time for c-sections and there haven't been any attributable problems that i can tell.