KETAMINE

Drugs in Pregnancy and Lactation.

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Name: KETAMINE
Class: General Anesthetic
Risk Factor:    B

Fetal Risk Summary

Ketamine is a rapid-acting IV general anesthetic agent related in structure and action to phencyclidine. No teratogenic or other adverse fetal effects have been observed in reproduction studies during organogenesis and near delivery with rats, mice, rabbits, and dogs (1,2,3,4 and 5). In one study with pregnant rats, a dose of 120 mg/kg/day for 5 days during organogenesis resulted in no malformations or effect on fetal weight (4).

Ketamine rapidly crosses the placenta to the fetus in animals and humans (6,7). Pregnant ewes were given 0.7 mg/kg IV, and 1 minute later the maternal and fetal concentrations of ketamine were 1230 ng/mL and 470 ng/mL (ratio 0.38), respectively (6). Maternal effects were slight, transitory increases in maternal mean arterial pressure and cardiac output, respiratory acidosis, and an increase in uterine tone without changes in uterine blood flow. In humans, the placental transfer of ketamine was documented in a study in which a dose of 250 mg IM was administered when the fetal head reached the perineum (7). The ketamine concentration in cord venous plasma at the 0- to 10-minute dose-to-delivery interval was 0.61 ΅g/mL, compared with 1.03 ΅g/mL at the 10- to 30-minute interval, reflecting absorption following the IM route.

Pregnant monkeys (Macaca nemistrina) were administered ketamine in a dose of 2 mg/kg IV (N=3) or 1 mg/kg IV (N=2) in an investigation of the anesthetic's effects on the fetus and newborn (8). No fetal effects were observed from either dose. The newborns from the mothers given 2 mg/kg, but not those exposed to lower doses, however, had profound respiratory depression.

The use of ketamine (CI-581) for obstetric anesthesia was first described in 1966 (9). Since then, a large number of References have documented its use for this purpose (10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29, 30,31,32,33,34,35,36,37 and 38). Among the maternal and newborn complications reported with ketamine are oxytocic properties, an increase in maternal blood pressure, newborn depression, and an increased tone of newborn skeletal musculature. These adverse effects were usually related to higher doses (1.5–2.2 mg/kg IV) administered during early studies rather than to the lower doses (0.2–0.5 mg/kg IV) now commonly used.

Ketamine usually demonstrates a dose-related oxytocic effect with an increase in uterine tone, and in frequency and intensity of uterine contractions (9,10,11 and 12,22,37), but one investigator reported weakened uterine contractions following a 250-mg dose administered IM when the fetal head reached the perineum (7). Uterine tetany was observed in one case (12). Low doses (0.275–1.1 mg/kg IV) of ketamine increased only uterine contractions, whereas a higher dose (2.2 mg/kg IV) resulted in a marked increase in uterine tone (22). Maximum effects were observed within 2–4 minutes of the dose. In one study, however, the effect on uterine contractions from an IV dose of 1 mg/kg, followed by succinylcholine 1 mg/kg, was no different from thiopental (14). No effect on intra-uterine pressure was measured in 12 term patients treated with ketamine 2 mg/kg IV, in contrast to a marked uterine pressure increase in patients in early pregnancy undergoing termination (39). Similarly, in 12 women given ketamine 2.2 mg/kg IV for termination of pregnancy at 8–19 weeks, uterine pressure and the intensity and frequency of contractions were increased (40).

Several investigators have noted a marked increase in maternal blood pressure, up to 30%–40% in systolic and diastolic in some series, during ketamine induction (7,10,12,13,15,23,24). An increased maternal heart rate is usually observed. These effects are dose-related with the greatest increases occurring when 2–2.2 mg/kg IV was administered, but smaller elevations of pressure and pulse have been noted with lower IV doses.

Maternal ketamine anesthesia may cause depression of the newborn (7,12, 15,16,17 and 18,21,23,26,32). As with the other complications, the use of higher doses (1.5–2.2 mg/kg IV) resulted in the highest incidence of low neonatal Apgar scores and requirements for newborn resuscitation. The induction-to-delivery (ID) interval is an important determinant for neonatal depression (7,21,32,34). In two studies, neonatal depression was markedly lower or absent if the ID interval was less than 10 minutes (7,32). In a third report, significant depression occurred with an ID interval of 9.2 minutes, but a dose of 2.1 mg/kg IV had been used (21).

The use of ketamine in low doses apparently has little effect on fetal cardiovascular status or acid-base balance as evidenced by neonatal blood gases (7,24,26, 29, 31,32 and 33). In one study, a ketamine dose of 25 mg IV administered with nitrous oxide and oxygen within 4 minutes of delivery did not adversely affect neonatal blood pressure (38).

Ketamine doses of 2 mg/kg IV have been associated with excessive neonatal muscle tone, sometimes with apnea (10,11,17). In some cases, the increased muscle tone made endotracheal intubation difficult. In contrast, lower doses (e.g., 0.25–1 mg/kg) have not been associated with this complication (24).

Neonatal neurobehavior, as measured by the Scanlon Group of Early Neonatal Neurobehavioral Tests during the first 2 days, is depressed following maternal ketamine (1 mg/kg IV) anesthesia but less than the effect measured after thiopental anesthesia (4 mg/kg IV) (41,42). In these studies, spinal anesthesia with 6–8 mg of tetracaine was associated with the best performance, general anesthesia with ketamine was intermediate, and that with thiopental was the poorest in performance.

In summary, although ketamine anesthesia close to delivery may induce dose-related, transient toxicity in the newborn, these effects are usually avoided with the use of lower maternal doses. No reports of malformations in humans (43) or in animals attributable to ketamine have been located, although experience with the anesthetic agent during human organogenesis apparently has not been published.

Breast Feeding Summary

Because ketamine is a general anesthetic agent, breast feeding would not be possible during use of the drug, and no reports have been located that measured the amount of the agent in milk. The elimination half-life of ketamine has been reported to be 2.17 hours in unpremedicated patients (31). Thus, the drug should be undetectable in the mother's plasma approximately 11 hours after a dose. Nursing after this time should not expose the infant to pharmacologically significant amounts of ketamine.

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References

  1. Nishimura H, Tanimura T. Clinical Aspects of The Teratogenicity of Drugs. New York, NY:American Elsevier, 1976:178.
  2. Schardein JL. Chemically Induced Birth Defects. 2nd ed. New York, NY:Marcel Dekker, 1993:148.
  3. Onnis A, Grella P. The Biochemical Effects of Drugs in Pregnancy. Volume 1. West Sussex, England:Ellis Norwood, 1984:18–9.
  4. El-Karum AHA, Benny R. Embryotoxic and teratogenic action of ketamine. Ain Shams Med J 1976;27:459–63.
  5. Product information. Ketalar. Parke-Davis, 1993.
  6. Craft JB Jr, Coaldrake LA, Yonekura ML, Dao SD, Co EG, Roizen MF, Mazel P, Gilman R, Shokes L, Trevor AJ. Ketamine, catecholamines, and uterine tone in pregnant ewes. Am J Obstet Gynecol 1983;146:429–34.
  7. Nishijima M. Ketamine in obstetric anesthesia: special Reference to placental transfer and its concentration in blood plasma. Acta Obstet Gynaecol Jpn 1972;19:80–93. Cited in Anonymous. Operative obstetrics and anesthesia. Obstet Gynecol Surv 1975;30:605–6.
  8. Eng M, Bonica JJ, Akamatsu TJ, Berges PU, Ueland K. Respiratory depression in newborn monkeys at caesarean section following ketamine administration. Br J Anaesth 1975;47:917–21.
  9. Chodoff P, Stella JG. Use of CI-581 a phencyclidine derivative for obstetric anesthesia. Anesth Analg 1966;45:527–30.
  10. Bovill JG, Coppel DL, Dundee JW, Moore J. Current status of ketamine anaesthesia. Lancet 1971;1:1285–8.
  11. Moore J, McNabb TG, Dundee JW. Preliminary report on ketamine in obstetrics. Br J Anaesth 1971;43:779–82.
  12. Little B, Chang T, Chucot L, Dill WA, Enrile LL, Glazko AJ, Jassani M, Kretchmer H, Sweet AY. Study of ketamine as an obstetric anesthetic agent. Am J Obstet Gynecol 1972;113:247–60.
  13. McDonald JS, Mateo CV, Reed EC. Modified nitrous oxide or ketamine hydrochloride for cesarean section. Anesth Analg 1972;51:975–83.
  14. Peltz B, Sinclair DM. Induction agents for caesarean section. A comparison of thiopentone and ketamine. Anaesthesia 1973;28:37–42.
  15. Meer FM, Downing JW, Coleman AJ. An intravenous method of anaesthesia for caesarean section. Part II: ketamine. Br J Anaesth 1973;45:191–6.
  16. Galbert MW, Gardner AE. Ketamine for obstetrical anesthesia. Anesth Analg 1973;52:926–30.
  17. Corssen G. Ketamine in obstetric anesthesia. Clin Obstet Gynecol 1974;17:249–58.
  18. Janeczko GF, El-Etr AA, Younes S. Low-dose ketamine anesthesia for obstetrical delivery. Anesth Analg 1974;53:828–31.
  19. Akamatsu TJ, Bonica JJ, Rehmet R, Eng M, Ueland K. Experiences with the use of ketamine for parturition. I. Primary anesthetic for vaginal delivery. Anesth Analg 1974;53:284–7.
  20. Krantz ML. Ketamine in obstetrics: comparison with methoxyflurane. Anesth Analg 1974;53:890–3.
  21. Downing JW, Mahomedy MC, Jeal DE, Allen PJ. Anaesthesia for caesarean section with ketamine. Anaesthesia 1976;31:883–92.
  22. Galloon S. Ketamine for obstetric delivery. Anesthesiology 1976;44:522–4.
  23. Ellingson A, Haram K, Sagen N. Ketamine and diazepam as anaesthesia for forceps delivery. A comparative study. Acta Anaesth Scand 1977;21:37–40.
  24. Maduska AL, Hajghassemali M. Arterial blood gases in mothers and infants during ketamine anesthesia for vaginal delivery. Anesth Analg 1978;57:121–3.
  25. Dich-Nielsen J, Holasek J. Ketamine as induction agent for caesarean section. Acta Anaesth Scand 1982;26:139–42.
  26. White PF, Way WL, Trevor AJ. Ketamine—its pharmacology and therapeutic uses. Anesthesiology 1982;56:119–36.
  27. Hill CR, Schultetus RR, Dharamraj CM, Banner TE, Berman LS. Wakefulness during cesarean section with thiopental, ketamine, or thiopental-ketamine combination (abstract). Anesthesiology 1993;59:A419.
  28. Schultetus RR, Paulus DA, Spohr GL. Haemodynamic effects of ketamine and thiopentone during anaesthetic induction for caesarean section. Can Anaesth Soc J 1985;32:592–6.
  29. Bernstein K, Gisselsson L, Jacobsson L, Ohrlander S. Influence of two different anaesthetic agents on the newborn and the correlation between foetal oxygenation and induction-delivery time in elective caesarean section. Acta Anaesthesiol Scand 1985;29:157–60.
  30. Schultetus RR, Hill CR, Dharamraj CM, Banner TE, Berman LS. Wakefulness during cesarean section after anesthetic induction with ketamine, thiopental, or ketamine and thiopental combined. Anesth Analg 1986;65:723–8.
  31. Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth 1989;36:186–97.
  32. Baraka A, Louis F, Dalleh R. Maternal awareness and neonatal outcome after ketamine induction of anaesthesia for caesarean section. Can J Anaesth 1990;37:641–4.
  33. Rowbottom SJ, Gin T, Cheung LP. General anaesthesia for caesarean section in a patient with uncorrected complex cyanotic heart disease. Anaesth Intens Care 1994;22:74–8.
  34. Krissel J, Dick WF, Leyser KH, Gervais H, Brockerhoff P, Schranz D. Thiopentone, thiopentone/ketamine, and ketamine for induction of anaesthesia in caesarean section. Eur J Anaesthesiol 1994;11:115–22.
  35. Conway JB, Posner M. Anaesthesia for caesarean section in a patient with Watson's syndrome. Can J Anaesth 1994;41:1113–6.
  36. Maleck W. Ketamine and thiopentone in caesarean section. Eur J Anaesthesiol 1995;12:533.
  37. Marx GF, Hwang HS, Chandra P. Postpartum uterine pressures with different doses of ketamine. Anesthesiology 1979;50:163–6.
  38. Marx GF, Cabe CM, Kim YI, Eidelman AI. Neonatal blood pressures. Anaesthesist 1976;25:318–22.
  39. Oats JN, Vasey DP, Waldron BA. Effects of ketamine on the pregnant uterus. Br J Anaesth 1979;51:1163–6.
  40. Galloon S. Ketamine and the pregnant uterus. Can Anaesth Soc J 1973;20:141–5.
  41. Hodgkinson R, Marx GF, Kim SS, Miclat NM. Neonatal neurobehavioral tests following vaginal delivery under ketamine, thiopental, and extradural anesthesia. Anesth Analg 1977;56:548–53.
  42. Hodgkinson R, Bhatt M, Kim SS, Grewal G, Marx GF. Neonatal neurobehavioral tests following cesarean section under general and spinal anesthesia. Am J Obstet Gynecol 1978;132:670–4.
  43. Friedman JM. Teratogen update: anesthetic agents. Teratology 1988;37:69–77.

Index

Q&A about Ketamine

bigcatlo...
Ketamine??
In psychology we where talking about different drugs and their effects on the body. The teacher said the ketamine use causes seizuires and hallusinations that can last for a few weeks to several months. Since ketamine is used on animals, do you think that the animals can have these hallusinations? This is just out of cariousity.
none
NO

when the aniaml is hit with injection it is knowcked out. ketamine is not only used for cats, is also used in humans..dentist now use it quite frequently for children suring surfery and hospitals as well for humans and children

as far as humans go , NO they do not have seisures... I used to do it as much as I could and i never had seisures..

yes you can halucinate, but its a differnet halucination that others...

and once you come of it within an hour or so, you will feel normal again. there are no bad feelings when you are done either, and especially anything that goes on for weeks, your teacher has NO idea what he/she is talking about....
Julie F
Can the anaesthesia drug Ketamine cause blindness in animals?
My 4 month old Burmese kitten had to have chest X-Rays and she needed an extra dose of Ketamine to sedate her. This was 18 hours ago. She has woken up but cannot see. Could she still be coming out of the sedation or has she been permanently damaged.
Go Cubs Go
Shes just coming out of the sedation. Nothing to worry about.
arlyn tg
Risks of ketamine use and medication to counter addiction to it?
I would like to know what the risks of using ketamine are and if there's a drug out there structured to treat ketamine addiction.
alianna r
Users of ketamine may have distorted perceptions of sight and sound as well as feel out of control and disconnected. The use of this drug may also cause the impairment of one's coordination, senses, and judgment for up to 24 hours after its intake. Its hallucinogenic effects, however, usually last for only 45-90 minutes. Prolonged usage of ketamine can cause delirium, amnesia, impaired motor function, and respiratory problems-- which can lead to death.

No drugs out there are used as medication for people with ketamine addiction. Treatment usually involves psychotherapy and behavior modification.
baddest_...
What are some effects of the drug ketamine and where do people transport it?
I need to know specifically what ketamine does to your body. I also need to know where people get the main ingredients to make the ketamine. *I am not doing drugs. I need it for a health project*
SoccerBo...
Ketamine is a general dissociative anaesthetic for human and veterinary use. As with many other pharmaceuticals, ketamine is used extramedically as a recreational drug. The effect of Ketamine as a depressant on the respiratory and circulatory systems is less than that of other anaesthetics. When used at anaesthetic doses, it will sometimes stimulate rather than depress the circulatory system. It is sometimes possible to perform ketamine anaesthesia without protective measures to the airways. Ketamine is also a potent analgesic and can be used in sub-anaesthetic doses to relieve acute pain; however, its psychotropic properties must be taken into account. Patients have reported vivid hallucinations, "going into other worlds" or "seeing God" while anesthetized, and these unwanted psychological side-effects have reduced the use of ketamine in human medicine. As for where people get it they usaully steal it from an vets office. Ketamine sold illicitly comes from diverted legitimate supplies or theft, primarily veterinary clinics. In the US near its border with Mexico, the drug is most commonly acquired in Mexico, where it can be bought over the counter in veterinary clinics, and smuggled across the border. In 2003, Operation TKO was a probe conducted by the U.S. Drug Enforcement Agency (DEA). As a result of operation TKO, U.S. and Mexican authorities shut down the Mexico City company, Laboratorios Ttokkyo, which was the biggest producer of ketamine in Mexico. According to the DEA, over 80% of ketamine found in the U.S. is of Mexican origin.[
opio-coc...
how often is ketamine administered as an anesthetic for surgery?
i know ketamine is used sometimes but many complain of hallucinations and dissaciation when waking up. (which is why its popular for drug users right now)

what im wondering though, is how often is ketamine administered as an alternative anethetic? what are the numbers?
Pangolin
I have no idea what the numbers are. We don't register our anesthetic drug use or anything. Some anesthesiologists don't use it all, others use it a lot, most of us are somewhere in the middle.

The incidence of hallucinations is markedly diminished by the concurrent administration of midazolam.

Ketamine is useful as an induction agent in certain situations, the most common being an emergency C-section for bleeding (abruption or previa). It's also useful for uncooperative kids or mentally challenged adults in whom we can not place an IV (the "ketamine dart") because we can get enough in IM to get them asleep or close to it. It can also be given to kids orally as pre-op sedation.

Ketamine can be a useful adjunct when we need to boost blood pressure or maintain spontaneous ventilation. It helps other pain medications work better, and has its own analgesic properties.

Thanks to the drug users, we now have to lock it up and sign it out.
unknown
What are the advanteges of Ketamine from other anestetics?
Anyone else have ever been given ketamine for anesthesia before? What was it like?
Matthew N
Never had it, but given it before. Typically, ketamine is given in a few situations. We give it intramuscularly to combative young kids who won't sit still to have an i.v. placed to sedate them so we can induce general anesthesia. It's also a very potent intravenous sedative with analgesic (pain killing) properties for adults, but adults can have severe hallucinations/nightmares with ketamine that kids don't have. So, we usually give some valium-like drugs along with it to smooth out those effects and wipe out any memory of such nightmares. Ketamine is sometimes chosen over other sedatives because it's less likely to stop your breathing or depress your cardiac system, which other sedatives can do. This is ideal in certain patients. It is actually the most widely used anesthetic in the world (not in the U.S., however), because if you give a bunch of it i.v. you can do many types of surgeries without intubating or giving other pain-killers, though the patient is still "kind of" awake. We don't do that in the U.S. because we have so many other, better drugs for full-on general anesthesia. Please keep in mind that ketamine is not without other side effects...particularly if this is a question of whether or not it should be used recreationally. You can have massive release of adrenaline from ketamine use (strokes, heart attacks), seizures are not uncommon, the hallucinations can lead to full on psychosis, and you absolutely can stop breathing if you use enough. It's a powerful drug and really should only be used by people who really know how to deal with it's effects.
anahy i
Any substance abuse treatment centers for people with ketamine addiction in Callicoon, New York?
I would like to know more about ketamine and its effects upon those who are addicted to it. I figured my best bet would be to look for patients in substance abuse treatment centers and ask them about their experience with the drug.
adamaris ns
Finding substance abuse treatment centers won't take you too much time. Just the links below will get to help you out in your search. You can also get recommendations from doctors and healthcare providers. The problem here, though, is that treatment centers are usually very stringent about the privacy of their patients. You will probably have to settle with interviewing the therapists and counselors. Nevertheless, good luck!
drjjjjdr
Can ketamine help you through a hangover?
Seriously. I become sick and terribly hungover the next day after drinking 3 lite beers!!! Would the anaesthetic effects of ketamine be preferable than a hangover? Please don't give me the (boring) typical response of not drinking. Or suggesting Chaser (a scam). I'm deperate for hangover help.
icesk8er
Ketamine will only make your hangover worse. Ketamine has serious side effects that will only make your hangover worse. Ketamine has side effects like hallucinations, dizziness, headaches, nausea, airway constriction (patients who are prescribed ketamine are usually on a ventilator), your blood pressure and heart rate can begin to go up, and depending on the dosage you can even die from the ketamine. When ketamine is mixed with alcohol the side effects can become even worse, and it is more likely to lead to death. I'd suggest finding another solution for your hangovers.
destinie...
What could be the long-term effects of Ketamine?
Once my mom and I visited our neighbor, I saw a Ketamine bottle in their medicine cabinet. My mom said not to touch it because it is dangerous. How dangerous can Ketamine be?
cherish l_l
For decades now, Ketamine is used both for human and animals as an anesthesia. However, there are those people who use this for recreational purposes. Such wrong usage of this prescription drug is very dangerous and can result to long term side effects such as impairment of the brain's pscho-motor functions, amnesia, and other respiratory and cardiovascular illnesses. It my also lead to delirium and confusion. There are times that when ketamine is injected to a person, his blood pressure gets high and erratic.