This page covers Ketamine IV Therapy including its benefits. IV League provides mobile Ketamine IV Therapy.

Ketamine, an anesthetic derivative of phencyclidine, is frequently described as a “unique drug” because it shows hypnotic (sleep producing), analgesic (pain relieving) and amnesic (short-term memory loss) effects; no other drug used in clinical practice combines these three important features at the same time.

Ketamine administration has long been known to mediate a wide variety of pharmacological eects, including dissociation, analgesia, sedation, catalepsy, and bronchodilation. Though ketamine is known most widely for its anesthetic properties, recent research has uncovered multiple novel uses for this drug, including neuroprotection, combatting inflammation and treatment of depression, seizures, chronic pain, and headache.

BENEFITS OF KETAMINE IV

HISTORY OF KETAMINE IV

In 1959 the search for a safe but potent sedative agent led pharmacologists to the phencyclidines (PCPs) (CI-395 and CI-400). Although CI-395 and CI-400 produced reliable sedation, the hallucinogenic effects that patients experienced upon reawakening were too severe to warrant widespread use, and therefore the search for related, but less hallucinogenic, compounds began (Johnson 1959). This finally led to the discovery of ketamine (CI-581), which was first synthesized in 1962 by Calvin Stevens at Parke-Davis and Co.

Ketamine showed fewer severe adverse effects of the PCPs. It was first used in humans in 1965 by Corssen and Domino and was introduced into clinical practice by 1970, in time for use during the Vietnam War.

It was originally hoped that ketamine would be used as a sole agent for anesthesia, inducing analgesia, amnesia, loss of consciousness, and immobility. However, because of its adverse psychological effects and the availability of other induction agents, its use diminished rapidly. Recently, the availability of S (+)-ketamine has regenerated interest in its clinical use, because it has greater potency and fewer side effects.

MOLECULAR STRUCTURE OF KETAMINE 

Ketamine contains a chiral center at the C-2 carbon of the cyclohexanone ring; this means there are two optical isomers; S ketamine and R ketamine. The S isomer is pharmacologically more active.

Chemical structure of ketamine. There is a chiral center in the cyclohexanone ring giving the S and R isomers

WHAT ARE THE MECHANISM OF ACTION OF KETAMINE IV?

Ketamine is a derivative of the cyclo-hexamine (phencyclidine) anesthetic agents used extensively in the 1950s. Ketamine acts on the central nervous system (CNS) and has local anesthetic properties. Its effects are mediated primarily by non-competitive antagonism at the N-Methyl-D-aspartate (NMDA) receptor Ca2 + channel pore. NMDA channel block appears to be the primary mechanism of the anesthetic and analgesic action of ketamine (at the CNS and also at spinal cord receptors). These NMDA receptors are located at the spinal, thalamic, limbic and cortical levels. In addition, it reduces the presynaptic release of glutamate.

Ketamine therefore interferes with sensory input to higher centers of the central nervous system, affecting pain and emotional responses as well as memory, hence it is referred to as a ‘‘dissociative anesthetic.’’.

Other mechanisms of action of ketamine include interaction with opioid receptors, with a preference for mu and kappa receptors; this interaction with opioid receptors is complex. The affinity of ketamine for these receptors is 10 times less than that for the NMDA channel.

Clinically, the anesthetic potency of the S (+)-isomer is approximately three to four times that of the R (-)-isomer, which is attributable to the higher affinity of the S (+)-isomer to the phencyclidine binding sites on the NMDA receptors.

Depression is known to be associated with alterations in glutamatergic neurotransmission and dysfunctional activity of the resting state network. Additionally, depression is thought to be caused by enhanced subcortical and limbic activity, which aects cognition and emotion regulation. Ketamine is thought to aect these brain areas directly through modification of glutamatergic neurotransmission, although it has also been shown to mediate its eects through modulation of dopaminergic neurotransmission and serotonergic neurotransmission. Ketamine also indirectly acts through several other neurochemical pathways

WHAT ARE THE USES OF KETAMINE IV?

  1. Ketamine and historical use for anesthesia

Ketamine has been used in the operating room for nearly 50 years.  The bronchial dilatory profile of ketamine makes the induction and maintenance of anesthesia safer in patients with asthma and life-threatening acute bronchial constriction.  Because of the favorable cardiovascular characteristics, stimulating the central sympathetic system and inhibiting neuronal catecholamine uptake, ketamine is preferred in patients with unstable hemodynamics.  Ketamine is also one of the very few drugs approved for anesthesia induction in caesarean sections.  It is considered the agent of choice in children and burn victims.

  1. Ketamine and Pain Syndromes

Ketamine has been widely used to manage acute and chronic pain, both alone and as an adjunct to opiates. The primary analgesic mechanism of ketamine is through NMDA receptor antagonism, though ketamine has also been shown to act on opioid, nicotinic, and muscarinic receptors. Ketamine’s anti-inflammatory qualities may also contribute to its ecacy in pain relief

Opioids are traditionally an integral part of therapy for acute post-operative pain.  Unfortunately, possible hyperalgesia from opioids can result in increased analgesic requirements.  However, ketamine can block these mechanisms; when administered at sub-anesthetic and repeated doses, ketamine has been shown to prevent the development of increased pain sensitivity and opioid tolerance.

  1. Non cancer chronic pain: Ketamine has been used off-label, administered topically or intravenously in small, sub anesthetic doses as an analgesic for treating chronic painful conditions. The action of ketamine on opiate tolerance and hyperalgesia combined with its direct analgesic activity has prompted its increasing use in chronic pain states.

Current literature suggests that ketamine can be used by various routes: IV, SC, and IM, epidural, intrathecal, intra articular, intranasal, oral and topical for the short-term relief of refractory neuropathic pain. Due to side-effects such as psychedelic symptoms, cardiovascular stimulation and hepatotoxicity, the use of ketamine should be restricted to patients with therapy resistant severe neuropathic pain

  1. Cancer pain: In palliative care practice, ketamine has been administered as a co-analgesic in addition to opioids and co-adjuvant drugs. Ketamine is now considered to be an essential adjuvant analgesic for refractory cancer pain, and it is on the WHO’s essential drugs list for patients who no longer respond to high doses of opioids or have predictable breakthrough pains.

Ketamine and its anti-depressive and anti-suicidal effects

Ketamine has proved to be an extremely effective treatment for major depression, bipolar disorder and suicidal behavior.  The slow onset and moderate degrees of receptor occupancy could largely be used to avoid the anesthesia effect, dissociation and psychotomimetic reactions.  However, a debate is ongoing as to whether it is the direct actions of ketamine at the phencyclidine site on the NMDA receptor that account for its actions, or the downstream stimulation of AMPA receptors.

Ketamine works incredibly fast, lifting depression in as little as two hours, which is unlike conventional anti-depressants that generally take weeks to start working. Ketamine has demonstrated rapid antidepressant efficacy in patients with treatment-resistant depression (TRD). Importantly, the effects of intravenous (IV) ketamine may last up to several weeks after repetitive infusions.

Ketamine has also been shown to rapidly reduce suicidal thoughts in depressed patients with suicidal ideation.

  1. Ketamine and sedation

The safety and efficacy of ketamine for emergency department (ED) dissociative sedation for a variety of brief painful or emotionally disturbing procedures in both children and adults is strongly supported e.g.: Laceration repair, fracture reduction, abscess drainage, emergency cardioversion, amputation, chest tube insertion. It is useful for procedures in the mentally disabled who are often uncooperative. This dissociative sedation can be readily achieved by administration of a single IV or IM loading dose of ketamine followed by titration. Intranasal ketamine is being used in a wide range of clinical doses for procedural sedation in children It is used for sedation or general anesthesia for pediatric procedures like cardiac catheterization, radiation therapy, radiological studies such as magnetic resonance imaging, dressing changes, and dental work. Ketamine in low doses in combination with low doses of propofol provides effective and safe pseudo-analgesia in pediatric emergency short surgical procedures and in adults undergoing colonoscopy and short gynecological procedures.

  1. Uses in Critical Care

Ketamine has a number of potential applications within critical care medicine, including sedation, analgesia and the treatment of persistent bronchospasm. Ketofol (ketamine and propofol in combination) has been shown to be effective for short-term sedation in a critical care population.

Ketamine was initially thought to be contraindicated in patients with traumatic brain injuries or raised intracranial pressure. However, some studies have shown that ketamine can be helpful as a sedative within these patient groups. Its use has been associated with maintenance of cerebral perfusion pressure during stimulating interventions in a critical care population with brain injuries

  1. Reactive Airways Disease

Ketamine by virtue of its bronchodilating property and profound analgesia allowing use of high oxygen concentration is considered to be the IV induction agent of choice in patients with active bronchospasm. Some researchers have found that ketamine not only protected against precipitation of asthma in asymptomatic surgical patients, but it also alleviated bronchospasm in patients with respiratory distress prior to induction of anesthesia

INTRAVENOUS KETAMINE VS ORAL SUPPLEMENTATION

Ketamine is water- and lipid-soluble, allowing it to be administered conveniently via various routes and providing extensive distribution in the body

Intravenous route is the best route for your brain to receive ketamine because of something called bioavailability. In addition, it is also more effective, more precise, and safer for use.

What is bioavailability?

It is the amount of medication that your body and brain is actually able to use, which is sometimes different than the amount of medication that your body receives.it is defined as the fraction of the active form of a drug that reaches systemic circulation unaltered.

When medications are taken, some parts of the active ingredients in them, get digested, altered into an unusable form, metabolized and excreted into the body. This is particularly prevalent in oral and intranasal medications. Receiving Ketamine in intravenous form[IV] is the only way to have 100% bioavailability.

Intravenous route gives 100% bioavailable, while taking ketamine Orally gives 16-24% bioavailability. Other route such as Intramuscular, Intranasal and sublingual gives 93%, 25-50% and 30% respectively

Ketamine IV Therapy References

  1. Gao, M., Rejaei, D. & Liu, H. Ketamine use in current clinical practice. Acta Pharmacol Sin 37, 865–872 (2016). https://doi.org/10.1038/aps.2016.5.
  2. Sinner, B., Graf, B.M. (2008). Ketamine. In: Schüttler, J., Schwilden, H. (eds) Modern Anesthetics. Handbook of Experimental Pharmacology, vol 182. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-74806-9_15
  3. Pribish, Abby & Wood, Nicole & Kalava, Arun. (2020). A Review of Nonanesthetic Uses of Ketamine. Anesthesiology Research and Practice. 2020. 1-15. 10.1155/2020/5798285.
  4. Dr Alistair Gales, Dr Stuart Maxwell. Ketamine: Recent Evidence and Current Uses. Anaesthesia Tutorial of the week. www.wfashq.org Tutorial 381.  https://resources.wfsahq.org/wp-content/uploads/381_english.pdf
  5. Wilkinson ST, Ballard ED, Bloch MH et al. The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis. Am J Psychiatry. 2018;175(2):150–158. [PMC free article] [PubMed] [Google Scholar
  6. Benefit of Ketamine. https://bostonmindcare.com/benefits-of-ketamine/.
  7. Anirudda Pai, MD DNB FRCA, Mark Heining, MD FRCA, Ketamine, Continuing Education in Anaesthesia Critical Care & Pain, Volume 7, Issue 2, April 2007, Pages 59–63, https://doi.org/10.1093/bjaceaccp/mkm008
  8. Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014 Sep-Dec;8(3):283-90. doi: 10.4103/0259-1162.143110. PMID: 25886322; PMCID: PMC4258981.
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