ketamine (ketalar) is an anesthetic and analgesic medicine that induces dissociative anesthesia.

It is used during anesthesia for sedation and analgesia.

Ketamine Uses:

• Anesthesia:

  • Making you sleep really deeply and keeping you that way for a surgery or procedure.

• Off Label Use of Ketamine in Adults:

  • Serious agitation: When someone is really upset or restless.
  • Pain Management (subanaesthetic dosing): Giving just enough medicine to help with pain without making someone unconscious.
  • Miserable episode linked with the major depressive disorder (unipolar), medication refractory: A really tough time caused by a type of depression that doesn't respond to medicine.
  • Routine tranquillity/analgesia: Calmness and pain relief as part of a normal procedure.
  • Refractory status epilepticus: A severe condition where seizures keep happening despite treatment.

ketamine (ketalar) Dose in Adults:

To reduce excessive saliva production, doctors might use drugs like atropine or scopolamine before starting anesthesia and at certain times during the procedure.

They adjust the amount of the drug you receive to get the effect they want.

ketamine (ketalar) Dose as an alternative agent in the treatment of severe agitation (off-label):

For people who don't get better with benzodiazepines or antipsychotic drugs, there's limited evidence to guide treatment:

• Injection into the muscle (IM): A single dose of 4 to 6 milligrams per kilogram of body weight.
• Injection into the vein (IV): Some experts recommend a single dose of 1 to 2 milligrams per kilogram of body weight.

ketamine (ketalar) Dose as Anesthesia:

• Induction of anesthesia:

Keep in mind to use a lower amount if you're giving this drug alongside others like midazolam.

For injections into the muscle (IM): Give between 4 to 10 milligrams per kilogram of body weight.

For injections into the vein (IV): Give between 0.5 to 2 milligrams per kilogram of body weight.

Manufacturer's recommendations might not always match current medical advice.

Here are updated guidelines: IM: Between 6.5 to 13 milligrams per kilogram.

IV: Between 1 to 4.5 milligrams per kilogram.

ketamine (ketalar) Dose as Maintenance of anesthesia:

• • You can administer it continuously through an IV at a rate of 0.1 to 0.5 milligrams per minute, according to the manufacturer's instructions.

  • You might also give half of the initial dose as an additional quick injection.

  • For maintaining anesthesia ideally, you'd use 1 to 2 milligrams per minute.

  • However, some experts suggest different doses, ranging from 15 to 90 micrograms per kilogram per minute (which translates to approximately 1 to 6 milligrams per minute in a 70-kilogram patient).

  • If you're using nitrous oxide at the same time, you'll need a lower dose.

  • Recent studies indicate better outcomes with a lower amount of ketamine.

ketamine (ketalar) Dose in the Analgesia (subanesthetic dosing) (off-label):

• Acute pain:

  • • When given through the nose (which is not the usual way), the dose is typically between 0.5 to 1 milligram per kilogram of body weight.
    • If needed, you can give another dose after 10 to 15 minutes, with a smaller amount of 0.25 to 0.5 milligrams per kilogram, until the discomfort goes away.

• Chronic pain:

  • • When given through the nose (which isn't the usual way), there are different methods available to lessen symptoms like feeling disconnected from reality.

    • Through the vein (IV): Note: Other medicines like lorazepam and glycopyrrolate can be given together to manage symptoms like excessive saliva or tears.

    • Start with: IV drip: 0.5 milligrams per kilogram over 6 hours.

    • If there's a good response (at least 50% improvement), keep the drip going at 1.5 milligrams per kilogram every day for 48 hours.

    • If there's no improvement, increase the dose to 2 milligrams per kilogram over 12 hours.

    • If the pain comes back after feeling better initially, you can increase the dose by 50% to 100% every day as needed.

    • Stop the drip if the pulse goes over 110 beats per minute, if the systolic blood pressure jumps more than 25% from baseline, if the breathing rate falls below 7 breaths per minute, or if there are signs of irritability or feeling disconnected from reality.

    • By mouth (Oral): Start with: 0.5 milligrams per kilogram as a single dose to see how it affects pain and how long it lasts.

    • You can increase the dose if needed, adding 0.5 milligrams per kilogram each time.

    • You can give it 3 to 4 times a day to keep the pain relief going.

ketamine (ketalar) Dose in the treatment of Acute on chronic episodes of severe neuropathic pain:

• Continuous IV or SubQ (off-label route) infusion:

  • The dosage range is between 2.3 to 6.7 micrograms per kilogram per minute, which is the same as 0.14 to 0.4 milligrams per kilogram per hour.

• Postoperative opioid sparing:

  • For injections into the muscle (IM), the typical dose is between 2 to 4 milligrams per kilogram.

  • If necessary, you can continue with a constant flow of the medication.

  • For injections into the vein (IV), you'd typically administer a bolus dose ranging from 0.2 to 0.8 milligrams per kilogram.

  • In one study, a maximum dose of 50 milligrams was used.

  • If needed, you can start a continuous infusion after giving the bolus dose.

• Continuous IV infusion:
  • The dosage range is between 1 to 2 micrograms per kilogram per minute, which is equivalent to 0.06 to 0.12 milligrams per kilogram per hour.

ketamine (ketalar) Dose in the treatment of Depressive episode associated with treatment-refractory major unipolar depressive disorder (off-label):

• The recommended intravenous dosage is 0.5 milligrams per kilogram, given twice a week as an IV infusion.
• Studies have investigated this treatment for up to 6 weeks.

ketamine (ketalar) Dose in the treatment of Procedural sedation/analgesia (off-label):

• For the intramuscular (IM) route:

• The intravenous (IV) route is preferred, but if not possible, you can give a single dose of 4 to 5 milligrams per kilogram.
• If sedation isn't enough after 5 to 10 minutes or if more sedation is needed, you can give another dose ranging from 2 to 5 milligrams per kilogram.
• Using a benzodiazepine like midazolam before giving ketamine can help reduce the risk of adverse reactions.

• For the intravenous (IV) route:

• The typical dose for adults is 1 to 2 milligrams per kilogram (with the usual adult dose being 100 milligrams) given over 1 to 2 minutes.
• Taking a benzodiazepine like midazolam before giving ketamine can help reduce the risk of unwanted reactions.
• If the initial sedative isn't enough or if multiple doses are needed for a longer procedure, you can give additional doses of 0.5 to 1 milligram per kilogram every 5 to 15 minutes as necessary.

ketamine (ketalar) Dose in Childrens:

Keep in mind:

• Adjust the dosage until you achieve the desired effect.
• Ketamine can help decrease saliva production when used with drugs that block acetylcholine, which is responsible for salivation.

Additionally, note that:

• The American College of Emergency Physicians strongly advises against using ketamine in newborns younger than 3 months due to the higher risk of breathing difficulties.

ketamine (ketalar) Dose in the Anesthesia:

• For pre-anesthetic sedation, the dosages for different administration routes are as follows:

  Intranasal:

• Infants aged 6 months and older: 3 milligrams per kilogram per dose, given at least 15 minutes before the procedure (half the dose in each nostril).
• Children under 2 years: Same as infants.
• Children aged 2 to 7 years: Half the dose of 3 to 6 milligrams per kilogram, given 15 to 40 minutes before the procedure.

• Oral:

• Children up to 8 years old: Administer 6 to 8 milligrams per kilogram 20 to 30 minutes before the operation.

• Rectal:

• As a single dose 15 to 45 minutes before surgery. If combined with other sedatives, consider lower doses.
• Studies comparing rectal ketamine to other drugs found effective dosages:
  • Infants aged 2 to 6 months: 8 milligrams per kilogram per dose.
  • Infants aged 7 months and older and children up to 9 years: 8 to 10 milligrams per kilogram per dose.

• Note:

• Lower doses (4 to 7 milligrams per kilogram per dose) were found to be less effective, while higher doses (10 milligrams per kilogram per dose) led to prolonged sedation after surgery in some patients.
• Combining a lower rectal dose of 3 milligrams per kilogram with midazolam has been beneficial.

ketamine (ketalar) Dose in the Induction of anesthesia:

• Infants ≥3 months, Children, and Adolescents <16 years:

  • According to expert recommendations:

  • Intramuscular (IM): 5 to 10 milligrams per kilogram. Intravenous (IV): 1 to 3 milligrams per kilogram.

• Adolescents ≥16 years:

  • For intramuscular (IM) administration: 6.5 to 13 milligrams per kilogram.
  • For intravenous (IV) administration: 1 to 4.5 milligrams per kilogram.

Dose as Maintenance of anesthesia:

• Adolescents ≥16 years:
  • If necessary, you can give additional doses ranging from half to the full dose used for the initial induction.

ketamine (ketalar) Dose in the  treatment of Endotracheal intubation:

• Infants, Children, and Adolescents:
  • For intravenous (IV) administration as part of rapid sequence sedation, the recommended dosage is 1 to 2 milligrams per kilogram.

ketamine (ketalar) Dose in the treatment of procedural sedation and analgesia:

• Infants, Children, and Adolescents:

It's important to note that ketamine should only be used in patients 3 months of age and older, as recommended by ACEP, due to the risk of airway obstruction, laryngospasm, and apnea.

Ketamine without propofol:

Intramuscular (IM):

• A single dose of 4 to 5 milligrams per kilogram.
• If sedation is inadequate after 5 to 10 minutes or if more doses are needed, a second dose ranging from 2 to 5 milligrams per kilogram can be given.
• Some suggest smaller doses (2 to 2.5 milligrams per kilogram) for certain procedures like wound suturing with local anesthesia.

Intravenous (IV):

• Administer 1 to 2 milligrams per kilogram over 30 to 60 seconds.
• Additional doses of 0.5 to 1 milligram per kilogram can be given every 5 to 15 minutes if initial sedation is insufficient or if ongoing sedation is needed for a longer procedure.

Intranasal:

• For infants 3 months and older and children: 3 to 6 milligrams per kilogram (half the dose in each nostril). This method has mainly been studied in dental or radiological procedures.

Oral:

• For children and adolescents: Administer oral midazolam 30 to 45 minutes before surgery at a dose of 5 milligrams per kilogram.

Rectal:

• For children aged 1 to 8 years: Give midazolam rectally in a single dose of 1.5 to 3 milligrams per kilogram 20 minutes before surgery.

• Ketamine with propofol ("ketofol"):

  • Infants ≥3 months, Children, and Adolescents:

    • Intravenous (IV) administration: Typically, 0.5 to 0.75 milligrams per kilogram of each agent is used in combination.
    • Using this combination has led to lower doses of each individual agent being needed.
    • It's believed that these lower doses help decrease major side effects.
    • Ketamine may reduce respiratory depression and hypotension caused by propofol, while propofol may reduce emergence reactions and nausea caused by ketamine.

ketamine (ketalar) Dose for Sedation and analgesia in critically ill patients:

• Infants ≥5 months, Children, and Adolescents:

  • The initial dose for intravenous (IV) administration is typically 0.5 to 2 milligrams per kilogram, followed by a continuous IV infusion ranging from 5 to 20 micrograms per kilogram per minute (equivalent to 0.3 to 1.2 milligrams per kilogram per hour).

  • It's recommended to start with the lowest prescribed dose and adjust as necessary.

  • In cases of severe, difficult-to-treat bronchospasm, patients have reported receiving doses as high as 60 micrograms per kilogram per minute (equivalent to 3.6 milligrams per kilogram per hour).

Pregnancy Risk Category: N

• Ketamine crosses the placenta and can affect uterine contractions, with effects varying depending on the trimester of pregnancy.

• Clearance of ketamine from the blood decreases during pregnancy.

• High doses given during delivery may lead to depression in newborns and lower Apgar scores.

• General anesthetics and sedatives that affect N-methyl D-aspartate receptors (NMDA) and/or enhance gamma-aminobutyric acid (GABA) activity may impact brain development, as shown in animal studies.

• When surgery is expected to last longer than 3 hours, the potential risks and benefits of fetal exposure to ketamine should be considered.

• Although not recommended by the manufacturer, ketamine can be used during vaginal and cesarean delivery, particularly for women who require stable blood pressure during cesarean delivery.

• Its use as an additional painkiller during cesarean sections has been explored but requires further research.

• While low doses of ketamine can be used to sedate pregnant women, other drugs are preferred.

• In rare cases of refractory epilepsy during pregnancy, ketamine infusions have been used successfully.

• According to the American College of Obstetricians and Gynecologists (ACOG), medically necessary surgery should not be denied to pregnant women, regardless of their trimester.

• However, elective procedures should be postponed until after delivery.

Use while breastfeeding

• It's uncertain whether ketamine is present in breast milk.

• The Academy of Breastfeeding Medicine advises delaying elective surgery until breastfeeding is well-established.

• Whenever possible, it's recommended to express breast milk before surgery.

• If the baby is full-term and healthy, breastfeeding can typically resume after the mother has recovered from surgery.

• Expressed milk can be stored for later use for infants at lower risk of side effects like low blood pressure, breathing problems, or muscle weakness.

• Additional doses of ketamine should not be given during cesarean deliveries.

• Breastfeeding can resume as usual once the mother is awake and stable.

• However, there isn't enough data to support using ketamine for long-term pain management during breastfeeding.

Dose in Kidney Disease:

There are no dosage modifications on  labeling.

Dose in Liver disease:

There are no dosage modifications on labeling. 

Common Side Effects of ketamine (ketalar):

• Central nervous system:

  • Prolonged emergence from anesthesia includes
    • Hallucinations
    • Delirium
    • Excitement
    • Irrational behavior
    • Dreamlike state
    • Vivid imagery
    • Confusion

Frequency of side effects not defined:

• Cardiovascular:

  • Cardiac Arrhythmia
  • Increased Blood Pressure
  • Hypotension
  • Increased Pulse
  • Bradycardia

• Central Nervous System:

  • Increased Cerebrospinal Fluid Pressure
  • Hypertonia (Tonic-Clonic Movements Sometimes Resembling Seizures)
  • Drug Dependence

• Dermatologic:

  • Rash At Injection Site
  • Morbilliform Rash
  • Erythema

• Endocrine & Metabolic:

  • Central Diabetes Insipidus.

• Gastrointestinal:

  • Sialorrhea (Hatab 2014)
  • Vomiting
  • Nausea
  • Anorexia

• Genitourinary:

  • Bladder Dysfunction (Reduced Capacity)
  • Cystitis Including
    • Cystitis Erosive
    • Cystitis Ulcerative
    • Cystitis Hemorrhagic
    • Cystitis Interstitial
    • Cystitis Noninfective
  • Urinary Incontinence
  • Hematuria
  • Urinary Urgency
  • Urinary Frequency
  • Dysuria

• Hypersensitivity:

  • Anaphylaxis

• Local:

  • Pain At Injection Site

• Neuromuscular & Skeletal:

  • Laryngospasm

• Ophthalmic:

  • Nystagmus
  • Diplopia
  • Increased Intraocular Pressure

• Renal:

  • Hydronephrosis

• Respiratory:

  • Respiratory Depression
  • Apnea
  • Airway Obstruction

Contraindications to ketamine (ketalar):

• Some absolute contraindications for using ketamine in the emergency department for procedural sedation or pain relief include:

• Infants under 3 months old.
• Known or suspected schizophrenia, even if it's being managed with medication.
• Additional contraindications listed in Canadian labeling but not in US labeling:
  • History of cerebrovascular accidents (stroke).
  • Acute cardiac decompensation (sudden worsening of heart function).
  • Surgery involving the pharynx or larynx if appropriate muscle relaxants have not been used, as it may lead to complications.

Warnings and precautions

• Complications with airways:

  • When anesthetics are needed for procedures involving the posterior pharynx (like endoscopy) or for patients with active lung diseases, there's a higher chance of laryngospasm (which includes conditions like asthma or upper respiratory diseases).

  • The risk is even higher if there's a history of airway issues, previous surgery on the windpipe, or narrowing of the windpipe.

  • The American College of Emergency Physicians advises against using ketamine in these situations due to the increased risk.

  • While the manufacturer doesn't recommend using ketamine alone for surgery, tests, or laryngoplasty, it's suggested to use ketamine alongside other medications whenever possible.

• Depression in the CNS:

  • CNS depression can lead to mental or physical impairments.

  • Patients should be aware that activities such as operating heavy machinery or driving may require mental focus.

  • For outpatient surgery, it's important for patients to have a responsible adult accompany them and oversee their care.

  • According to the manufacturer, patients should avoid driving, operating dangerous machinery, or engaging in hazardous activities for at least 24 hours after anesthesia.

• Dependence

  • Long-term use of ketamine can lead to tolerance, meaning that higher doses may be needed to achieve the same effect, and it can also lead to dependence, where the body becomes reliant on the drug.

  • When someone stops using ketamine after long-term use, they may experience withdrawal symptoms.

  • These symptoms can include psychological effects such as psychosis, which involves losing touch with reality.

  • It's important for individuals who have been using ketamine long-term to seek medical help when discontinuing its use to manage any withdrawal symptoms safely.

• Emergence reactions

  • After anesthesia, some people may experience vivid dreams, hallucinations, or delirium.

  • These reactions are more common in patients aged 16 and older when ketamine is given via intramuscular injection.

  • Using lower doses of ketamine and giving benzodiazepines beforehand may help reduce the risk of disorientation or sudden reactions.

  • Minimizing tactile (touch) and verbal stimulation during recovery can also help.

  • Patients with schizophrenia should be cautious because ketamine may worsen psychotic symptoms.

  • The American College of Emergency Physicians considers ketamine an absolute contraindication for analgesia and procedural sedation in patients with schizophrenia.

• Symptoms of the genitourinary system:

  • Patients with a history of long-term ketamine overuse or abuse may experience lower urinary tract symptoms and bladder issues such as painful urination, increased frequency or urgency, and urge incontinence.

  • These symptoms may be related to ketamine use. Diagnostic tests may also reveal conditions such as cystitis (inflammation of the bladder) and hydronephrosis (swelling of the kidneys due to urine buildup).

  • If you experience genitourinary pain or other symptoms while using ketamine, it's important to consider stopping its use and seeking medical advice.

  • These symptoms may indicate bladder dysfunction and should be addressed promptly.

• Increased intracranial pressure

  • There are conflicting reports regarding the effect of ketamine on intracranial pressure (ICP) in patients with central nervous system (CNS) conditions such as CNS masses, abnormalities, or hydrocephalus.

  • Some studies suggest that ketamine can increase ICP in these patients.

  • However, other research indicates that ketamine may not significantly affect ICP and, with appropriate ventilation, could potentially improve cerebral blood flow and reduce intracranial tension.

  • It's important for healthcare providers to carefully consider the individual patient's condition and monitor ICP closely when using ketamine in patients with CNS pathology.

  • Adjustments in dosage and monitoring techniques may be necessary to ensure safe use of ketamine in this population.

• Increased ocular pressure

  • Patients with high intraocular pressure (IOP) should use ketamine cautiously. Individuals with open eye injuries or any other eye conditions should generally avoid ketamine use.

  • However, opinions on the effects of ketamine on IOP vary.

  • While some evidence suggests that ketamine may not have a clinically significant effect on IOP, it's essential to approach its use with caution in patients with eye conditions.

  • Monitoring IOP and considering the individual patient's medical history are crucial factors in determining the safety of ketamine use in these cases.

• Porphyria

  • The American College of Emergency Physicians considers ketamine safe for individuals with porphyria because of its heightened sympathomimetic effects.

• Respiratory depression

  • Rapid intravenous (IV) infusion or an overdose of ketamine can lead to respiratory depression or apnea.

  • Therefore, it's essential to have emergency equipment readily available whenever ketamine is used.

• Thyroid disorders

  • Due to its heightened sympathomimetic effects, the American College of Emergency Physicians considers the administration of ketamine to patients with a thyroid problem or who are on thyroid medication as a relative contraindication.

• Cardiovascular disease

  • Patients with conditions such as high blood pressure, coronary artery disease, catecholamine deficiencies, or tachycardia should use ketamine with caution.

  • Those with elevated blood pressure or cardiac issues need close monitoring while receiving ketamine.

  • Ketamine can increase blood pressure, heart rate, cardiac output, and myocardial oxygen demands, although the exact mechanism of its cardiovascular effects is not fully understood.

  • Combining ketamine with benzodiazepines, inhaled anesthetics, or propofol, or administering them continuously via infusion, may help reduce these cardiovascular side effects.

  • For individuals already hypertensive or at risk of coronary artery disease, the American College of Emergency Physicians advises against using ketamine.

  • The American Heart Association's scientific statement suggests that ketamine may worsen underlying cardiac conditions to a significant extent.

• Pressure elevation of Cerebrospinal Fluid (CSF).

  • Increased cerebrospinal fluid (CSF) pressure may be considered in cases where intracranial pressure has been elevated previously.

• Use of ethanol:

  • Patients with severe alcoholism or a history of chronic drinking should be carefully administered ketamine.

Ketamine: Drug Interaction

Monitoring parameters:

• During ketamine administration, it's important to monitor for emergence reactions, changes in blood pressure, pulse oximetry (oxygen saturation levels), respiratory rate, and heart rate.
• Continuous cardiac monitoring is especially important for patients with increased blood pressure or cardiac decompensation.

How to administer ketamine (ketalar)?

• Here are the administration instructions for ketamine via different routes:

  Intranasal (using the parenteral dosage form):

• Use the 50 or 100 mg/mL solution.
• Administer undiluted or diluted to 20 mg/mL.
• Use an atomizer or syringe without a needle to deliver equal doses in both nostrils.

• Oral:

• Mix the required dose in any liquid and use it immediately.

• Intramuscular (IM):

• Administer as a deep IM injection.

• Intravenous (IV):

• Provide bolus/induction doses over a minute or at a rate of 0.5 mg/kg/minute as recommended by the manufacturer.
• Some specialists suggest administering over two to three minutes to reduce the risk of increased pressor response and respiratory depression.
• For resistant unipolar depression, administer over a 40-minute period or as a continuous infusion.

• Rectal (using the parenteral dosage form):

• Use the 50 mg/mL solution undiluted or dilute the 100 mg/mL solution further if needed.

Mechanism of action of ketamine (ketalar):

• Ketamine is a noncompetitive NMDA receptor antagonist that induces dissociative anesthesia.

• It primarily acts on the limbic system and cortex.

• Analgesia can occur with subanesthetic or lower doses of ketamine, which can also alter central sensitization, hyperalgesia, and opioid tolerance.

• The onset of action varies depending on the route of administration:

• Intravenous (IV): Anesthetic effect within 30 seconds.
• Intramuscular (IM): Anesthetic effect within 3 to 4 minutes; analgesia within 10 to 15 minutes.
• Intranasal: Analgesic effect within 10 minutes; sedation in children aged 2 to 6 years within 5 to 8 minutes.
• Oral: Analgesia within 30 minutes; sedation in children aged 2 to 8 years within 10 to 13 minutes.

• The duration of action also varies by route:

• IV: Anesthetic effect lasts 5 to 10 minutes; recovery takes 1 to 2 hours.
• IM: Anesthetic effect lasts 12 to 25 minutes; analgesia for 15 to 30 minutes; recovery in 3 to 4 hours.
• Intranasal: Analgesic effect up to 1 hour; recovery in children aged 2 to 6 years takes 30 to 45 minutes.

• Ketamine's metabolism involves liver enzymes, producing metabolites that are eventually excreted in urine and feces. Its bioavailability varies:

• IM: 93%
• Oral: 20% to 30%
• Intranasal: 35% to 50%
• Rectal: 25% in children aged 2 to 9 years.

• The half-life of ketamine elimination has two phases: alpha (10 to 15 minutes) and beta (2.5 hours).

• Time to peak plasma concentration ranges from 5 to 30 minutes for IM, 10 to 14 minutes for intranasal, approximately 30 minutes for oral, and around 45 minutes for rectal administration.

International Brand Names of Ketamine:

• Ketalar
• Aneket
• Anesject
• Brevinaze
• Calypsol
• Cost
• Dorgipain
• Etamine
• Kain
• Kanox
• Keiran
• Ketalar
• Ketalin
• Ketam
• Ketamar
• Ketamax
• Ketamin-S
• Ketamina
• Ketanest
• Ketanir
• Ketaride
• Ketashort
• Ketava
• Ketavit
• Ketmin
• Ketolar
• Ketomin
• Narkamon
• Raketiv
• Tekam
• Velonarcon
• Venilam

Ketamine Brand Names in Pakistan: