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Ketamine

Medically reviewed by Drugs.com. Last updated on Aug 4, 2020.

Pronunciation

(KEET a meen)

Index Terms

  • Ketamine HCl
  • Ketamine Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection:

Ketalar: 10 mg/mL (20 mL); 50 mg/mL (10 mL); 100 mg/mL (5 mL)

Generic: 10 mg/mL (20 mL); 50 mg/mL (10 mL); 100 mg/mL (5 mL, 10 mL)

Brand Names: U.S.

  • Ketalar

Pharmacologic Category

  • General Anesthetic

Pharmacology

Produces a cataleptic-like state in which the patient is dissociated from the surrounding environment by direct action on the cortex and limbic system. Ketamine is a noncompetitive NMDA receptor antagonist that blocks glutamate. Low (subanesthetic) doses produce analgesia, and modulate central sensitization, hyperalgesia and opioid tolerance. Reduces polysynaptic spinal reflexes.

Distribution

Vdss: 2.4 L/kg (Wagner 1997)

Metabolism

Hepatic via N-dealkylation (metabolite I [norketamine]), hydroxylation of the cyclohexone ring (metabolites III and IV), conjugation with glucuronic acid and dehydration of the hydroxylated metabolites to form the cyclohexene derivative (metabolite II); metabolite I (norketamine) is 33% as potent as parent compound. When administered orally, norketamine concentrations are higher compared to other routes of administration due to extensive first-pass metabolism in the liver (Blonk 2010; Soto 2012).

Excretion

Urine (91%); feces (3%) (Ghoneim 1977)

Onset of Action

IV: Anesthetic effect: Within 30 seconds

IM: Anesthetic effect: 3 to 4 minutes; Analgesia: Within 10 to 15 minutes

Intranasal: Analgesic effect: Within 10 minutes (Carr 2004); Sedation: Children 2 to 6 years: 5 to 8 minutes (Bahetwar 2011)

Oral: Analgesia: Within 30 minutes; Sedation: Children 2 to 8 years (Turhanoglu 2003):

4 mg/kg/dose: 12.9 ± 1.9 minutes

6 mg/kg/dose: 10.4 ± 2.9 minutes

8 mg/kg/dose: 9.5 ± 1.9 minutes

Time to Peak

Plasma:

IM: 5 to 30 minutes (Clements 1982)

Intranasal: 10 to 14 minutes (Huge 2010); Children 2 to 9 years: ~20 minutes (Malinovsky 1996)

Oral: ~30 minutes (Soto 2012)

Rectal: Children 2 to 9 years: ~45 minutes (Malinovsky 1996)

Duration of Action

IV: Anesthetic effect: 5 to 10 minutes; Recovery: 1 to 2 hours

IM: Anesthetic effect: 12 to 25 minutes; Analgesia: 15 to 30 minutes; Recovery: 3 to 4 hours

Intranasal: Analgesic effect: Up to 60 minutes (Carr 2004); Recovery: Children 2 to 6 years: 34 to 46 minutes (Bahetwar 2011)

Half-Life Elimination

Alpha: 10 to 15 minutes; Beta: 2.5 hours

Protein Binding

27% (Brunton 2006)

Use: Labeled Indications

Anesthesia: Induction and maintenance of general anesthesia.

Off Label Uses

Agitation, acute/severe or refractory

Data from open-label, prospective clinical trials suggest that IV or IM ketamine may be beneficial for the treatment of severe agitation and violent behavior [Cole 2018], [Isbister 2016], [Li 2019], [Riddell 2017].

Based on the American College of Emergency Physicians clinical policy for critical issues in the diagnosis and management of the adult psychiatric patient in the emergency department, ketamine is an option for immediate sedation of severely agitated patients in the emergency department who may become violent or aggressive and have not responded to benzodiazepines and/or antipsychotics, particularly when immediate control is required for patient and/or staff safety [Nazarian 2017].

Analgesia, subanesthetic dosing, acute and chronic pain

In a number of clinical trials evaluating IV or intranasal ketamine for the treatment of various pain syndromes (eg, central and peripheral neuropathic pain, postherpetic neuralgia, peripheral nerve injury, fibromyalgia, cancer pain, severe pain due to acute musculoskeletal injury), ketamine demonstrated effectiveness in reducing pain [Mercadante 2000], [Okon 2007], [Orhurhu 2019], [Schwenk 2018], [Shimonovich 2016], [Shrestha 2016], [Singh 2018]. Although the use of oral ketamine is not currently routine, it may be beneficial for some patients with refractory pain [Blonk 2010], [Kannan 2002], [Marchetti 2015], [Vadivelu 2016].

Based on the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists guidelines on the use of IV ketamine infusions for acute pain management, ketamine can be used as initial therapy or as an adjunct therapy in patients with acute pain [Schwenk 2018].

Based on the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists guidelines on the use of IV ketamine infusions for chronic pain, ketamine can be used in patients with chronic pain [Cohen 2018].

Depressive episode (severe, treatment resistant) associated with major depressive disorder (unipolar)

In 3 meta-analyses of double-blind, randomized, controlled trials evaluating the role of ketamine for depressive disorders, the use of a single infusion of ketamine was shown to produce a rapid antidepressant response lasting ~7 days. This effect has been seen when ketamine is used as monotherapy and as an antidepressant augmentation strategy [Fond 2014], [McGirr 2015], [Newport 2015]. Repeated infusions have been assessed in a limited number of patients in open-label and blinded studies with positive results; however, relapse rates were high within the 2 to 3 weeks following treatment in the open-label studies [aan het Rot 2010], [Murrough 2013], [Rasmussen 2013], [Shiroma 2014], [Singh 2016]. Data from a meta-analysis and 2 randomized, blinded, controlled trials support the use of single-dose ketamine infusions for temporarily decreasing suicidal ideation in patients during depressive episodes [Fan 2017], [Grunebaum 2018], [Wilkinson 2018].

Due to a lack of long-term data in patients with depressive episodes without psychotic features associated with major depressive disorder, the American Psychiatric Association Council of Research Task Force on Novel Biomarkers and Treatments recommends balancing the risk of each infusion with the risk of long-term exposure, including neurotoxicity, cystitis, and abuse potential [Sanacora 2017]. Based on the US Department of Veterans Affairs/Department of Defense clinical practice guideline for the assessment and management of patients at risk for suicide, ketamine is suggested as an adjunctive treatment in patients with suicidal ideation and major depressive disorder for short-term reduction in suicidal ideation [VA/DoD 2019].

Mechanically ventilated patients in the ICU, analgesia/sedation/agitation

Data from several retrospective studies suggest that ketamine may be beneficial as an adjunct sedative/analgesic in critically ill patients who are mechanically ventilated. Ketamine may decrease concomitant sedative and/or analgesia dose requirements [Buchheit 2019], [Garber 2019], [Groetzinger 2018].

Based on the Society of Critical Care Medicine clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU, ketamine can be used as an adjunct for analgesia in critically ill, mechanically ventilated adults [SCCM [Devlin 2018]].

Procedural sedation

Based on the American College of Emergency Physicians (ACEP) clinical policy for procedural sedation and analgesia in the emergency department, ketamine may be safely administered to patients for procedural sedation and analgesia. More specifically, the use of ketamine has been recommended for short, painful procedures, especially those requiring immobilization (eg, facial laceration, burn debridement) and examinations judged likely to produce excessive emotional disturbance (eg, pediatric sexual assault examination) [ACEP [Godwin 2014]], [ACEP [Green 2011]]. According to ACEP, the combination of ketamine and propofol may also be safely administered; however, to date, clinical trials have not shown this combination to be more efficacious than either agent alone [ACEP [Green 2011]], [Andolfatto 2012], [David 2011]. According to the Society of Critical Care Medicine clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU, ketamine may also be used as a sedative and an analgesic (as an adjunct to an opioid analgesic for non-neuropathic pain) for critically ill patients [SCCM [Devlin 2018]].

Rapid sequence intubation outside the operating room (induction)

Data from a randomized, controlled, single-blind study suggest that ketamine is safe and effective compared to etomidate for rapid sequence intubation in adult patients [Jabre 2009]. Data from a retrospective study suggest similar patient-centered outcomes with ketamine compared to etomidate for rapid sequence intubation in adult trauma patients [Upchurch 2017].

Status epilepticus, refractory

Data from a retrospective review of a limited number of patients (including children) from academic medical centers in North America and Europe and multiple case reports suggest that ketamine may be beneficial for the treatment of refractory status epilepticus [Gaspard 2013], [Kramer 2012]. A systematic review, consisting mostly of case reports and case series, suggests ketamine is effective in treating refractory status epilepticus [Rosati 2018].

Based on the Neurocritical Care Society guidelines for the evaluation and management of status epilepticus, ketamine may be used in the management of refractory status epilepticus [NCS [Brophy 2012]].

Contraindications

Hypersensitivity to ketamine or any component of the formulation; conditions in which an increase in blood pressure would be hazardous

Note: When used for procedural sedation and analgesia in the emergency department, the following additional absolute contraindications according to the American College of Emergency Physicians have been asserted (ACEP [Green 2011]): Infants <3 months of age; known or suspected schizophrenia (even if currently stable or controlled with medications)

Canadian labeling: Additional contraindications (not in US labeling): History of cerebrovascular accident; severe cardiac decompensation; surgery of the pharynx, larynx, or bronchial tree unless adequate muscle relaxants are used

Dosing: Adult

Note: Safety: To decrease risk of respiratory depression and apnea, administer IV bolus doses over >30 to 60 seconds (ACEP [Green 2011]). For obese patients, some experts use ideal body weight or adjusted body weight for initial weight-based dosing, unless otherwise indicated below (Erstad 2020).

Agitation, acute/severe or refractory (adjunct) (off-label use): Note: May be used when benzodiazepines and/or antipsychotics have failed (Cole 2018; Linder 2018; Moore 2020).

IV: Initial: 1 to 2 mg/kg once over 30 to 60 seconds; if initial sedation is inadequate, may repeat dose once 5 to 10 minutes after the initial dose using 0.5 to 1 mg/kg; however, this is not common if using the upper end of the initial dose range (ACEP [Green 2011]; Li 2019; Roberts 2019). Some experts use an initial dose of 0.5 to 1 mg/kg in the emergency department with concomitant sedatives (Li 2019; Moore 2020).

IM: Initial: 4 to 6 mg/kg once; if initial sedation is inadequate, may repeat dose once 10 to 25 minutes after the initial dose using 2 to 3 mg/kg; however, this is not common if using the upper end of the initial dose range (ACEP [Green 2011]; ACEP [Nazarian 2017]; Cole 2018; Heydari 2018; Isbister 2016; Li 2019). Some experts use an initial dose of 2 mg/kg in the emergency department with concomitant sedatives (Li 2019; O’Brien 2020).

Analgesia, subanesthetic dosing (off-label use):

Acute pain:

Note: Prior to use, consult with a pain specialist or service experienced with ketamine use in this setting. Optimal doses and regimens have not been identified; refer to institutional protocols. Recommendations provided below are examples of regimens. May be useful for moderately to severely painful procedures and conditions that do not respond optimally to standard analgesics (eg, postoperative, burn, trauma, sickle cell disease vaso-occlusive pain).

IV: Initial: 0.25 to 0.5 mg/kg bolus (maximum bolus: 35 mg), followed by 0.05 to 0.25 mg/kg/hour continuous infusion in patients who need a longer duration of analgesia; titrate to pain goal and tolerability; usual dosing range: 0.05 to 1 mg/kg/hour; may need to use doses at the higher range in patients who are opioid-tolerant or with opioid-induced hyperalgesia; duration of infusion: 48 to 72 hours (SCCM [Devlin 2018]; Schwenk 2018; Tawfic 2014).

Intranasal (off-label route): 0.2 to 1 mg/kg by administering half dose in each nostril (using 100 mg/mL solution); if necessary, may repeat after 10 to 15 minutes with 0.25 to 0.5 mg/kg; titrate to pain goal and tolerability. Doses up to 40 mg may be reliably administered intranasally; for doses >40 mg, part of the dose will be delivered to the oropharynx and ingested orally due to volume limitations, which may decrease effectiveness (Andolfatto 2013; Corrigan 2015; Shimonovich 2016; Shrestha 2016; Singh 2018; Yeaman 2014).

Chronic pain, intractable:

Note: Prior to use, consult with a pain specialist or service experienced with ketamine use in this setting. Optimal regimens, doses, and duration have not been identified; refer to institutional protocols. Long-term safety, efficacy, and timing of repeated ketamine treatments are not well established. Recommendations provided below are examples of regimens. May be used in refractory chronic pain (eg, complex regional pain syndrome, end-stage illness, neuropathies). May need to use doses at the higher range in opioid-tolerant patients (Schwenk 2018). Reduce baseline opioids by 25% to 50% when used concomitantly with ketamine (Quibell 2015).

IV intermittent infusion: Initial: 0.25 to 0.6 mg/kg (usual maximum dose: 60 mg) as a 4- to 6-hour infusion; titrate to pain goal and tolerability; repeat daily for up to 2 to 10 days as needed (Cohen 2018; Mercadante 2000; Okon 2007; Orhurhu 2019; Quibell 2015).

IV continuous infusion: Initial: 0.05 to 0.15 mg/kg/hour for 1 day outpatient or for 2 to 5 days inpatient; titrate to pain goal and tolerability; usual dosing range: 0.02 to 1 mg/kg/hour (maximum dose: 30 mg/hour; not well established) (Cohen 2018; Loveday 2015; Mercadante 2018; Orhurhu 2019; Quibell 2015).

SubQ: Initial: 0.1 to 0.6 mg/kg (usual 2.5 to 25 mg) as needed; titrate to pain goal and tolerability. In patients who need a longer duration of analgesia, follow with continuous SubQ infusion at 0.1 to 1.2 mg/kg/hour (maximum daily dose: 500 mg) (Cohen 2018; Quibell 2015).

Oral: Note: Used in refractory chronic pain (eg, advanced illness or palliative care) in a hospitalized patient when other regimens have failed.

Initial: 0.5 mg/kg/day administered in 3 to 4 divided doses as needed; then increase dose in increments of ~5 mg/dose based on pain goal and tolerability; maximum daily escalation dose: 15 to 20 mg; maximum dose: 800 mg/day (Blonk 2010; Cohen 2018; Marchetti 2015; Vadivelu 2016). Note: May administer dose as the undiluted injectable or mixed with an appropriate flavoring agent (eg, simple syrup).

Depressive episode (severe, treatment resistant) associated with major depressive disorder (unipolar) (off-label use): Note: Avoid or use with caution in patients with substance use disorder.

IV: Initial: 0.5 mg/kg administered over 40 minutes; may repeat at a frequency of 1 to 3 times weekly; may increase dose to 0.75 to 1 mg/kg based on response and tolerability. Treatment up to 6 weeks has been studied, although optimal duration of therapy is unknown (Fava 2020; Phillips 2019; Sanacora 2017; Singh 2016; Thase 2020).

General anesthesia (alternative agent): For obese patients, use adjusted body weight for initial weight-based dosing and then dose to clinical effect (Schumann 2020).

Induction of anesthesia:

Note: Useful in hypotensive patients or patients likely to develop hypotension during induction; lower doses may be used if concomitant anesthesia/sedatives (eg, midazolam) are administered (Gropper 2019; King 2020).

IV: 0.5 to 2 mg/kg or 0.5 to 1 mg/kg in patients with shock (Gropper 2019; King 2020).

IM (use only if IV access is not available): 4 to 6 mg/kg (Gropper 2019; King 2020; Roberts 2019).

Maintenance of anesthesia (adjunct with total intravenous anesthesia): Note: Adjunct to reduce requirements of other anesthetic agents. Typically reserved for opioid-tolerant patients in order to avoid or limit opioid requirements (Khorsand 2020); concurrent use of nitrous oxide reduces ketamine requirements (Gropper 2019).

IV: 0.25 to 0.35 mg/kg, followed by continuous infusion up to 1 mg/kg/hour (Khorsand 2020).

Mechanically ventilated patients in the ICU, analgesia/sedation/agitation (adjunct or alternative agent) (off-label use):

Note: Used as part of a multimodal strategy and adjunct for the reduction of opioid and sedative requirements and/or for the management of opioid-induced hyperalgesia in patients with acute/chronic pain or postsurgical pain. Pain should be monitored using validated scales (eg, behavioral pain scale, critical-care pain observation tool) in patients who are unable to self-report. If used for sedation, titrate to a light level of sedation (eg, Richmond Agitation Sedation Scale 0 to −2), unless deeper sedation is clinically indicated (SCCM [Devlin 2018]). Refer to institutional policies and procedures.

IV: Initial: 0.1 to 0.5 mg/kg bolus, followed by a 0.2 to 0.5 mg/kg/hour continuous infusion; titrate dose to pain and/or sedation goal (dosing range: 0.04 to 2.5 mg/kg/hour) (Buchheit 2019; Garber 2019; Groetzinger 2018; SCCM [Barr 2013]; SCCM [Devlin 2018]). Note: Higher initial bolus doses (eg, 1 to 2 mg/kg) can be used to manage severely agitated patients; see "Agitation, acute/severe or refractory (off-label use)" (ACEP [Green 2011]; Cole 2018).

Procedural sedation (off-label use): Note: To decrease risk of emergence reactions (although rare), may consider premedication with a benzodiazepine (eg, midazolam) (ACEP [Green 2011]; Chudnofsky 2000).

IV: Initial: 1 to 2 mg/kg over 1 to 2 minutes; if initial sedation is inadequate or for longer procedures, repeat dose (0.5 to 1 mg/kg) every 5 to 10 minutes; use lower doses (0.25 to 0.5 mg/kg) depending on concomitant sedation and clinical status (ACEP [Green 2011]; Chudnofsky 2000; Roberts 2019). Some experts use 0.5 to 0.75 mg/kg (as a 1:1 mixture) when combined with propofol (ACEP [Godwin 2014]).

IM: Note: Onset of sedation will be delayed ~5 minutes with this route.

Initial: 4 to 5 mg/kg as a single dose; if sedation is inadequate after 5 to 10 minutes, repeat dose (2 to 5 mg/kg) (ACEP [Green 2011]; Roberts 2019).

Rapid sequence intubation outside the operating room (induction) (off-label use): Note: Consider in patients with bronchospasm and/or hemodynamic compromise (Brown 2020; Caro 2020; Roberts 2019).

IV: Initial: 1 to 2 mg/kg once over 1 minute; in patients with shock, use 1 mg/kg (Brown 2020; Caro 2020; Jabre 2009; Roberts 2019; Stollings 2014; Upchurch 2017).

Intraosseous (use only if IV access is not available): Initial: 100 mg once (Barnard 2015; Davis 2016).

Status epilepticus, refractory (off-label use): Note: Used as an alternative or adjunct to midazolam, propofol, or barbiturates after conventional intermittent antiseizure therapies have failed. Mechanical ventilation and hemodynamic support generally required; continuous EEG is recommended; titrate doses to cessation of electrographic seizures or burst suppression (Legriel 2017; NCS [Brophy 2012]; Oddo 2019; Rai 2018). Optimal regimen and dose are uncertain; refer to institutional protocol.

IV:

Loading dose: Initial: 1.5 mg/kg or 0.5 to 3 mg/kg; repeat loading dose of 0.5 mg/kg every 3 to 5 minutes as needed for electrographic/burst suppression, followed by continuous infusion (Legriel 2017).

Continuous infusion: After initial loading dose and electrographic suppression, begin at a rate of 0.1 to 4 mg/kg/hour; titrate as needed for electrographic/burst suppression; maximum dose: 15 mg/kg/hour (Gaspard 2013; Legriel 2017; Rosati 2018).

Note: Generally, a period of at least 24 hours of electrographic suppression is suggested prior to down-titrating the continuous infusion; withdraw gradually by decreasing the dose by 20% every 3 hours while continuing conventional antiseizure therapies (Legriel 2017; NCS [Brophy 2012]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Titrate dose to effect. May be used in combination with anticholinergic agents to decrease hypersalivation. Note: The American College of Emergency Physicians considers the use of ketamine in infants <3 months of age to be an absolute contraindication, due to the higher risk of airway complications (ACEP [Green 2011]).

Anesthesia:

Pre-anesthetic sedation: Limited data available:

Intranasal:

Infants ≥6 months: 3 mg/kg/dose (half dose per nostril) administered at least 15 minutes prior to mask induction (Diaz 1997; Lin 1990).

Children <2 years: 3 to 5 mg/kg/dose (half dose per nostril) administered at least 15 minutes prior to mask induction (Diaz 1997; Gautam 2007; Lin 1990).

Children 2 to 7 years: 3 to 6 mg/kg/dose (half dose per nostril) administered 15 to 40 minutes prior to induction (Diaz 1997; Gautam 2007; Lin 1990; Roelofse 2004; Weksler 1993).

Oral: Children ≤8 years: 6 to 8 mg/kg/dose 20 to 30 minutes prior to surgery. Dosing based on two prospective, randomized, double-blind, placebo-controlled, dose finding trials. The larger trial compared 4 mg/kg, 6 mg/kg, and 8 mg/kg (n=20 in each group; age range: 2 to 8 years) and found that patients who received 8 mg/kg were significantly more calm, but also had slightly longer recovery times. Sedation was effective within 10 minutes of administration in 80% and 45% of the patients in the 8 mg/kg and 6 mg/kg, groups respectively, but was not effective in the 4 mg/kg group (Turhanoğlu 2003). The other study compared 3 mg/kg and 6 mg/kg (n=15 in each group, age range: 1 to 7 years) and found that patients who received 6 mg/kg had satisfactory sedation without prolonged recovery times, but the 3 mg/kg dose did not provide uniform sedation nor offer a significant improvement in premedicated emotional state compared to placebo (Gutstein 1992).

Rectal: Administer 15 to 45 minutes prior to surgery as a single agent; when used in combination with other sedatives, lower doses should be considered. Efficacy was reported in trials comparing rectal ketamine to rectal doses of other agents (fentanyl/droperidol, midazolam) (Lin 1990; Tanaka 2000; Van der Bijl 1991; Wang 2010; Zanette 2010). Reported effective range:

Infants 2 to 6 months: 8 mg/kg/dose.

Infants ≥7 months and Children ≤9 years: 8 to 10 mg/kg/dose.

Note: Although lower doses of 4 to 7 mg/kg/dose have been reported, they were less effective. In some patients, the 10 mg/kg/dose was associated with prolonged postoperative sedation. When used in combination with midazolam, a lower rectal dose of 3 mg/kg/dose has been effective (Beebe 1992).

Induction of anesthesia:

Infants ≥3 months, Children, and Adolescents <16 years: Limited data available:

IM: 5 to 10 mg/kg has been reported and suggested by experts (Coté 2013; Lin 2005; Sungur Ulke 2008).

IV: 1 to 3 mg/kg has been reported and suggested by experts (Coté 2013; Lin 2005).

Adolescents ≥16 years:

IM: 6.5 to 13 mg/kg.

IV: 1 to 4.5 mg/kg.

Maintenance of anesthesia: Adolescents ≥16 years: May administer supplemental doses of one-half to the full induction dose as needed.

Endotracheal intubation: Limited data available: Infants, Children, and Adolescents: IV: 1 to 2 mg/kg as part of rapid sequence sedation (AAP [Hegenbarth 2008]; Ballow 2012; Fuhrman 2011).

Sedation/analgesia, procedural: Limited data available: Infants, Children, and Adolescents: Note: Due to risk of airway obstruction, laryngospasm, and apnea, ACEP only recommends use in patients ≥3 months of age (ACEP [Green 2011]).

Ketamine without propofol:

IM: 4 to 5 mg/kg as a single dose; may give a repeat dose (range: 2 to 5 mg/kg) if sedation inadequate after 5 to 10 minutes or if additional doses are required (ACEP [Green 2011]). Some have recommended smaller doses (2 to 2.5 mg/kg) for minor procedures (eg, wound suture with local anesthetic) (McGlone 2004).

IV: 1 to 2 mg/kg over 30 to 60 seconds. If initial sedation inadequate or repeated doses are necessary to accomplish a longer procedure, may administer additional doses of 0.5 to 1 mg/kg every 5 to 15 minutes as needed (ACEP [Green 2011]; Asadi 2013; Berkenbosch 2004, Koruk 2010).

Intranasal: Infants ≥3 months and Children: 3 to 6 mg/kg (half dose per nostril). Studies have primarily used this route in the dental or radiology setting. In the largest, randomized, placebo-controlled, double-blind trial, intranasal ketamine was compared to intranasal dexmedetomidine for use prior to propofol for MRI sedation. The ketamine group (n=52, mean age: 4.9 ± 2.4 years) received 5 mg/kg intranasally 30 minutes prior to IV cannulation. Both treatment groups required significantly less propofol during the MRI than the placebo group and had high rates of satisfaction from anesthesiologists and parents (Gyanesh 2014). Another study in the radiology setting was a prospective, observational trial of sedation prior to CT scan. Patients (n=30, mean age: 2.15 years; range: 3 months to 12 years) received intranasal ketamine 5 mg/kg in combination with midazolam. For patients who remained uncooperative after 20 minutes, an IV dose of ketamine was administered. Intranasal therapy alone was effective for 83% of patients (Louon 1994). In the dental setting, three randomized, blinded, comparative studies have found intranasal ketamine (3 to 6 mg/kg) as monotherapy in children (ages 17 months to 11 years) to be either as effective or more effective than intranasal midazolam (Abrams 1993, Bahetwar 2011, Surendar 2014). In all of these studies, intranasal ketamine was well tolerated with no significant adverse effects.

Oral: Children and Adolescents: 5 mg/kg with oral midazolam given 30 to 45 minutes before the procedure. Dosing based on two prospective, randomized, blinded studies involving patients aged 1 to 10 years with either laceration repair or burn wound care (Barkan 2014; Norambuena 2013). A lower dose (3 mg/kg) in addition to midazolam was effective in a study comparing different routes (IV, oral, rectal) of ketamine plus midazolam for invasive procedures in oncology patients. The oral group included 24 patients (mean age: 3.9 ± 1.3 years); incidence of optimal sedation was similar between groups (75% for the oral group) (Ozdemir 2004). Note: A higher dose (10 mg/kg) has been used successfully as monotherapy prior to procedures in pediatric oncology patients (n=35, age: 14 months to 17 years; mean age: 6.5 years) (Tobias 1992).

Rectal: Children 1 to 8 years: 1.5 to 3 mg/kg with midazolam as a single dose 20 minutes prior to painful procedure. Dosing based on two studies. The first was completed in children with burns requiring dressing changes (n=47 procedures in 30 patients, mean age: 1.9 years, range: 10 months to 7.3 years). Patients received 0.75 mg/kg of the S(+) isomer (equivalent to 1.5 mg/kg of racemic ketamine) along with rectal midazolam 20 minutes prior to dressing changes; 94% of the procedures were reported to have good or excellent analgesia (Heinrich 2004). The second study compared different routes (IV, oral, rectal) of ketamine plus midazolam for invasive procedures in oncology patients. The rectal group included 24 patients (mean age: 3.7 ± 1.1 years) who received 3 mg/kg of ketamine in addition to midazolam. Incidence of optimal sedation was similar between groups (79% for the rectal group) (Ozdemir 2004). In both of these studies, rectal ketamine was well tolerated.

Ketamine with propofol ("ketofol"): Infants ≥3 months, Children, and Adolescents: IV: 0.5 to 0.75 mg/kg of each agent. This combination has been used to decrease the dose of each agent required. It has been proposed that these lower doses help decrease adverse effects, ketamine may decrease the propofol-related hypotension and respiratory depression, and propofol may decrease the ketamine associated nausea and emergence reactions (ACEP [Godwin 2014]; Alletag 2012; Shah 2011; Willman 2007).

Sedation/analgesia, critically ill patients: Very limited data available: Infants ≥5 months, Children, and Adolescents: Initial dose: IV: 0.5 to 2 mg/kg, then continuous IV infusion: 5 to 20 mcg/kg/minute (0.3 to 1.2 mg/kg/hour); start at lower dosage listed and titrate to effect (Denmark 2006; Rock 1986; Tobias 1990; White 1982); doses as high as 60 mcg/kg/minute (3.6 mg/kg/hour) have been reported in patients with refractory bronchospasm (Youssef-Ahmed 1996).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Reconstitution

Injection: The 50 mg/mL and 100 mg/mL vials may be further diluted in D5W or NS to prepare a maintenance infusion with a final concentration of 1 mg/mL (or 2 mg/mL in patients with fluid restrictions); mix well. The 10 mg/mL vials are not recommended to be further diluted. Do not mix with barbiturates or diazepam (precipitation may occur). Note: The 100 mg/mL concentration should not be administered IV unless properly diluted with an equal volume of SWFI, NS, or D5W.

Intranasal (off label): Use the 50 or 100 mg/mL injectable solution; may administer undiluted or further diluted in NS to a concentration of 20 mg/mL (Bahetwar 2011; Louon 1994; Surendar 2014; Yeaman 2014).

Oral solution (off label): Use the 100 mg/mL injectable solution (10 mL vial); may administer undiluted or further dilute with simple syrup, purified water (90 mL), or may add own flavoring agent (eg, fruit cordial) to prepare 100 mL concentration of 50 mg per 5 mL; dilute immediately before administration (Quibell 2015).

Administration

Intranasal (off label): Administer half dose in each nostril using a needleless syringe or mucosal atomizer device. Note: Intranasal use for adults for procedural sedation is not recommended since volume limits an adequate dose (Rech 2017).

Oral (off label): May administer undiluted or mix the appropriate dose (using the injectable solution) in a flavoring agent (eg, simple syrup), cola, or other beverage; administer immediately after preparation (Gutstein 1992; Quibell 2015).

IM: Inject deep IM into large muscle mass.

IV: According to the manufacturer, administer bolus/induction doses over 1 minute or at a rate of 0.5 mg/kg/minute; more rapid administration may result in respiratory depression and enhanced pressor response. Some experts suggest administration over 2 to 3 minutes (Miller 2010). When used for treatment refractory unipolar depression, administer over 40 minutes (Sanacora 2017). May also be administered as a continuous infusion.

Rectal (off label): May use the 50 mg/mL solution undiluted or use the 100 mg/mL solution and further dilute prior to administration (Tanaka 2000; Van der Bijl 1991).

SubQ (off label): May administer as a subcutaneous continuous infusion (Cohen 2018; Hocking 2003).

Storage

Vials: Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Oral solution (off label): Store prepared oral solution at 2°C to 8°C (36°F to 46°F) for up to 1 week from preparation (Quibell 2015).

Drug Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Abametapir: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Consider therapy modification

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP2B6 Inducers (Moderate): May decrease the serum concentration of Ketamine. Monitor therapy

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Memantine: NMDA Receptor Antagonists may enhance the adverse/toxic effect of Memantine. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiopental: Ketamine may enhance the adverse/toxic effect of Thiopental. Monitor therapy

Thiotepa: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Monitor therapy

Ticlopidine: May increase the serum concentration of Ketamine. Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Test Interactions

May interfere with urine detection of phencyclidine (false-positive).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Central nervous system: Prolonged emergence from anesthesia (12%; includes confusion, delirium, dreamlike state, excitement, hallucinations, irrational behavior, vivid imagery)

Frequency not defined:

Cardiovascular: Bradycardia, cardiac arrhythmia, hypotension, increased blood pressure, increased pulse

Central nervous system: Drug dependence, hypertonia (tonic-clonic movements sometimes resembling seizures), increased cerebrospinal fluid pressure

Dermatologic: Erythema, morbilliform rash, rash at injection site

Endocrine & metabolic: Central diabetes insipidus (Hatab 2014)

Gastrointestinal: Anorexia, nausea, sialorrhea (Hatab 2014), vomiting

Genitourinary: Bladder dysfunction (reduced capacity), cystitis (including cystitis noninfective, cystitis interstitial, cystitis ulcerative, cystitis erosive, cystitis hemorrhagic), dysuria, hematuria, urinary frequency, urinary incontinence, urinary urgency

Hypersensitivity: Anaphylaxis

Local: Pain at injection site

Neuromuscular & skeletal: Laryngospasm

Ophthalmic: Diplopia, increased intraocular pressure, nystagmus

Renal: Hydronephrosis

Respiratory: Airway obstruction, apnea, respiratory depression

Warnings/Precautions

Concerns related to adverse effects:

• Airway complications: When used for procedural sedation for major procedures involving the posterior pharynx (eg, endoscopy) or when used for patients with an active pulmonary infection or disease (including upper respiratory disease or asthma), the use of ketamine increases the risk of laryngospasm. Patients with a history of airway instability, tracheal surgery, or tracheal stenosis may be at a higher risk of airway complications. The American College of Emergency Physicians (ACEP) considers these situations relative contraindications for the use of ketamine (ACEP [Green 2011]). The manufacturer recommends against the use of ketamine alone in surgery or diagnostic procedures of the pharynx, larynx, or bronchial tree; mechanical stimulation of the pharynx should be avoided, whenever possible, if ketamine is used alone.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). When used for outpatient surgery, the patient should be accompanied by a responsible adult. Driving, operating hazardous machinery, or engaging in hazardous activities should not be undertaken for ≥24 hours after anesthesia, according to the manufacturer.

• Dependence: May cause dependence (withdrawal symptoms on discontinuation) and tolerance with prolonged use. A withdrawal syndrome with psychotic features has been described following discontinuation of long-term use.

• Emergence reactions: Postanesthetic emergence reactions, which can manifest as vivid dreams, hallucinations, and/or frank delirium, occur. These reactions are less common in patients <16 years of age and >65 years of age and when given IM (White 1982); incidence may be reduced when given at subanesthetic analgesic doses (Quibell 2015). Emergence reactions, confusion, or irrational behavior may occur up to 24 hours postoperatively and may be reduced by pretreatment with a benzodiazepine, use of ketamine at the lower end of the dosing range, and minimizing verbal and tactile stimulation of the patient during the recovery period.

• Genitourinary symptoms: Lower urinary tract and bladder symptoms, including dysuria, increased frequency/urgency, urge incontinence, and hematuria have been reported in patients with a history of chronic ketamine use or abuse and may be related to ketamine treatment, not the underlying condition. Additional findings from diagnostic studies have included cystitis, hydronephrosis, and reduced bladder capacity. Consider discontinuation of ketamine for continued genitourinary pain in the setting of other genitourinary symptoms.

• Increased intracranial pressure: Some consider the use of ketamine in patients with CNS masses, CNS abnormalities, or hydrocephalus a relative contraindication due to multiple reports that ketamine may increase intracranial pressure in these patients; use caution, especially at higher doses (ACEP [Green 2011]; Cohen 2018). However, assuming adequate ventilation, some evidence suggests that ketamine has minimal effects on intracranial pressure and may even improve cerebral perfusion and reduce intracranial pressure (Albanese 1997; Bowles 2012; Quibell 2015; Zeiler 2014).

• Increased ocular pressure: Use with caution in patients with increased intraocular pressure (IOP). Some recommend avoiding use in patients with an open eye injury or other ophthalmologic disorder where an increase in IOP would prove to be detrimental; however, the effects of ketamine on IOP is mixed with some evidence demonstrating no clinically significant effect on IOP (ACEP [Green 2011]; Cunningham 1986; Drayna 2012; Miller 2010; Nagdeve 2006).

• Liver injury: Recurrent use (eg, abuse/misuse, medically supervised unapproved use) may cause hepatobiliary dysfunction (usually a cholestatic pattern); monitor LFTs, including alkaline phosphatase and gamma glutamyl transferase.

• Porphyria: The ACEP considers the use of ketamine in patients with porphyria a relative contraindication due to enhanced sympathomimetic effect produced by ketamine (ACEP [Green 2011]).

• Respiratory depression: Rapid IV administration or overdose may cause respiratory depression or apnea. Resuscitative equipment should be available during use.

• Thyroid disorders: The ACEP considers the use of ketamine in patients with a thyroid disorder or receiving a thyroid medication a relative contraindication due to enhanced sympathomimetic effect produced by ketamine (ACEP [Green 2011]).

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with coronary artery disease, catecholamine depletion, hypertension, and tachycardia. Cardiac function should be monitored in patients with increased BP or cardiac decompensation. Ketamine increases BP, heart rate, and cardiac output, thereby increasing myocardial oxygen demand; arrhythmias, cardiac decompensation, and decreases in BP and heart rate have also been reported. The mechanism by which ketamine causes a sympathetic surge to stimulate the cardiovascular system has yet to be elucidated. The use of concurrent benzodiazepine, inhaled anesthetics, and propofol or administration of ketamine as a continuous infusion may reduce these cardiovascular effects (Miller 2010). The ACEP recommends avoidance in patients who are already hypertensive and in older adults with risk factors for coronary artery disease (ACEP [Green 2011]). In a scientific statement from the American Heart Association, ketamine has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• Cerebrospinal fluid pressure elevation: Use with caution in patients with cerebrospinal fluid (CSF) pressure elevation; an increase in CSF pressure may be associated with use.

• Ethanol use: Use with caution in the chronic alcoholic or acutely alcohol-intoxicated.

Special populations:

• Pediatric neurotoxicity: In pediatric and neonatal patients <3 years of age and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on child or fetal brain development and may contribute to various cognitive and behavioral problems. Epidemiological studies in humans have reported various cognitive and behavioral problems, including neurodevelopmental delay (and related diagnoses), learning disabilities, and attention deficit hyperactivity disorder. Human clinical data suggest that single, relatively short exposures are not likely to have similar negative effects. No specific anesthetic/sedative has been found to be safer. For elective procedures, risk versus benefits should be evaluated and discussed with parents/caregivers/patients; critical surgeries should not be delayed (FDA 2016).

Other warnings/precautions:

• Experienced personnel: Use requires careful patient monitoring, should only be used by experienced personnel who are not actively engaged in the procedure or surgery. If used in a nonintubated and/or nonmechanically ventilated patient, qualified personnel and appropriate equipment for rapid institution of respiratory and/or cardiovascular support must be immediately available. Use to induce moderate (conscious) sedation in patients warrants monitoring equivalent to that seen with deep anesthesia. Consult local regulations and individual institutional policies and procedures.

Monitoring Parameters

Heart rate, BP, respiratory rate, transcutaneous O2 saturation, emergence reactions; cardiac function (continuously monitored in patients with increased BP or cardiac decompensation); LFTs, alkaline phosphatase, and gamma glutamyl transferase (baseline and then at periodic intervals).

Continuous IV infusion: Monitor BP at baseline and then hourly (Quibell 2015).

Vital signs and pain level should be monitored at 30 minutes and 60 minutes post-dose (Geiger-Hayes 2018).

Pregnancy Considerations

Ketamine crosses the placenta (Ellingson 1977; Little 1972).

Ketamine produces dose dependent increases in uterine contractions; effects may vary by trimester. The plasma clearance of ketamine is reduced during pregnancy. Dose related neonatal depression and decreased Apgar scores have been reported with large doses administered at delivery (Little 1972; Neuman 2013; White 1982).

Based on animal data, repeated or prolonged use of general anesthetic and sedation medications that block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity may affect brain development. Evaluate benefits and potential risks of fetal exposure to ketamine when duration of surgery is expected to be >3 hours (Olutoye 2018).

Although obstetric use is not recommended by the manufacturer, ketamine has been evaluated for use during cesarean and vaginal delivery (ACOG 209 2019; Akamatsu 1974; Galbert 1973). Ketamine may be considered as an alternative induction agent in females requiring general anesthesia for cesarean delivery who are hemodynamically unstable (Devroe 2015). Use of ketamine as an adjunctive analgesic in cesarean section has also been evaluated; however, use for this purpose may require additional studies (Carvalho 2017; Heesen 2015). When sedation and analgesia is needed for other procedures during pregnancy, low doses of ketamine may be used, but other agents are preferred (Neuman 2013; Schwenk 2018). Use of ketamine infusion for the treatment of refractory status epilepticus in a pregnant patient has been noted in a case report (Talahma 2018).

The ACOG recommends that pregnant women should not be denied medically necessary surgery, regardless of trimester. If the procedure is elective, it should be delayed until after delivery (ACOG 775 2019).

Patient Education

What is this drug used for?

• It is used to cause sleep during a procedure.

• It is used to put you to sleep for surgery.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling sleepy

• Not hungry

• Upset stomach or throwing up

• Irritation where this drug is given

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• High or low blood pressure like very bad headache or dizziness, passing out, or change in eyesight

• Liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes

• Trouble breathing, slow breathing, or shallow breathing

• Fast, slow, or abnormal heartbeat

• Shortness of breath, a big weight gain, or swelling in the arms or legs

• Feeling confused

• Hallucinations (seeing or hearing things that are not there)

• Change in how you act

• Muscle stiffness

• Seizures

• Change in eyesight

• Not able to control eye movements

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.