ketamine

introduction

ketamine is a unique anaesthetic agent in that rather than causing general depression of neuronal activity, it causes dissociative anaesthesia which generally maintains airway reflexes and is generally safer that other anaesthetic agents, although it has it's own adverse effect profile and its relatively long duration of action means it may not be as suitable for very brief procedural sedation such as DC reversion, shoulder relocation, etc.
appears to act on the GluN1-2B-2D NMDA receptor in the mammalian brain¹⁾ - this receptor is critical for promoting physiological synaptic plasticity and neuronal viability.²⁾
ketofol (ketamine + propofol) does not appear to have any advantages over propofol +/- fentanyl for short procedures or ketamine for longer procedures
as with all procedural sedation, one must be ready and able to ventilate +/- intubate if needed, and be able to manage the rare occurrence of potentially life threatening laryngospasm
it is also useful in the induction of patients with severe life threatening asthma who need intubation as it assists in relieving bronchospasm and does not depress respiratory drive
it is also being trialled to Rx depression as it appears to produce good results within 24hrs
- studies in zebra fish suggest this action may be due to a noradrenaline mediated affect on astrocyte activity ³⁾
- a 2025 study suggests that ketamine's antidepressant effect at low doses is mediated via opioid receptors as giving naltrexone prior to ketamine reduced both the brain's glutamatergic response and the antidepressant effects observed the following day ⁴⁾
a 2025 Cochrane concluded there was little evidence to support use of IV ketamine for chronic pain Mx but it does increase adverse events⁵⁾

contraindications

absolute

age < 3 months
schizophrenia

relative

children under 12 months
food within last 4 hours
poorly controlled seizure disorder
upper airway surgical procedures or airway compromise such as tracheal stenosis, etc
increased pharyngeal secretions (eg. URTI, chest infection or acute asthma) as increased risk of laryngeal spasm from secretions on the cords
avoid in patients in whom you do not want raised heart rate or raised blood pressure (eg. consider risk benefit in those with cardiovascular disease, thyroid disease)
historically it has been C/I in patients at risk of raised intracranial pressure (eg. head injury patients, CNS masses, hydrocephalus), or raised intra-ocular pressure (eg. eye trauma, glaucoma), however, this has become controversial and many use it even in patients with head injury
porphyria

dose

The four stages of the ketamine brain continuum have overlapping dose ranges that are highly variable among patients. Unfortunately, the patient will pass through all these stages as it wears off - hence the emergence phenomenon which can result in severe dysphoria
- emergence issues are more likely in adults and adolescents, but can be reduced by:
  - pre-induction coaching (expect vivid dreams, etc)
  - adequate analgesia prior to sedation
  - ensuring quite surroundings during emergence with minimal external stimuli
  - may require midazolam or even propofol to treat until the ketamine is no longer causing partial dissociation
consider a dose of ondansetron pre or during Rx to prevent vomiting
higher doses once dissociated do not produce any further effect - a dissociated patient does not become more dissociated with more ketamine, higher doses only prolong duration of action

dissociative anaesthesia dose:
- each patient should have pulse oximetry and cardiac monitoring, and a nurse in attendance until recovery is well established.
- close observation of the airway and chest movements is necessary
- iv route:
  - onset: ~1 minutes
  - effective sedation: 10-20minutes
  - time to discharge (young children): 90-120 minutes on average
  - iv 0.7-2mg/kg (most give 1.0-1.5mg/kg) given over 60 secs (fast bolus may cause apnoea)
  - further incremental doses of 0.5mg/kg may be given if sedation is inadequate or longer sedation is necessary.
- im route to avoid iv pre-sedation in children:
  - onset: ~5 minutes
  - effective sedation: 15-30minutes
  - time to discharge (young children): 100-140 minutes on average
  - for children, im 4mg/kg is a usual recommended dose for procedural “sedation”
  - a repeat dose of 2-4 mg/kg may be given after 10 minutes if sedation is inadequate
- atropine and midazolam may be given prior to or with the ketamine (can be mixed in same syringe if giving it im)
  - atropine 0.02mg/kg to a maximum of 0.6mg can be used to diminish hypersalivation
  - midazolam 0.02 mg/kg may be added to ameliorate emergence phenomena in children over 5 years old

analgesic infusion dose:
- using 5mL of ketamine 50mg/mL added to 250ml 0.9% saline (makes 1mg/ml ketamine infusion):
  - initial bolus dose of 0.3mg/kg over 10 minutes
  - maintenance dose: 0.3mg/kg/hr
  - doses can be titrated up or down - consider increasing by 50% if severe pain or poor response
  - dissociative anaesthesia will not occur at doses < 100mg/hr in a normal sized adult and thus at the above doses, monitoring as per procedural sedation is not required.⁶⁾
  - some patients may experience “recreational” phase effects
- usual analgesic iv infusion doses as used by chronic pain specialists:
  - Western Health pain team ketamine procedure (docx)
  - acute pain: 200mg ketamine in 100mL 0.9% saline = 2mg/mL given at 0.1-0.2mg/kg/hr
  - prolonged infusions for chronic pain: 400mg ketamine in 100mL 0.9% saline = 4mg/mL given at 4mg/hr initially
  - PCA: 200mg ketamine in 100mL 0.9% saline = 2mg/mL; 1-2mg bolus; 5 min lockout, no background infusion.

4 dose dependent phases of action

these “phases” have overlapping dose ranges that are highly variable among patients.
effects are consistent at small analgesic dose (<0.1 mg/kg) or large dissociative dose (>2 mg/kg), anything in between is unpredictable

analgesic

at doses around 0.1-0.3 mg/kg, ketamine has minimal effect on perception or emotion but is a powerful analgesic

"recreational"

at doses of 0.2-0.5 mg/kg, ketamine has analgesic actions plus hallucinatory effects with distortions of preception
patient is aware of surroundings and can converse and follow commands

partial dissociation

at doses of 0.4-0.8 mg/kg, ketamine causes only partial dissociative effects leaving the patient with some awareness of external stimuli, and can make purposeful actions although may not be able to move, see, hear or talk.
this phase can be very frightening and is the main cause of the “emergence phenomenon”

full dissociative anaesthesia

this is the desired phase for procedural sedation and occurs with doses > 0.7mg/kg iv
patient passes into a trance like state with the eyes open but not responding
catalepsy
excellent analgesia
usual total amnesia
maintenance of airway reflexes
BP and HR tend to increase
most have nystagmus and staring open eyes
tends to cause hypersalivation and vomiting
may lower seizure threshold
rapid bolus doses will cause transient apnoea