Ketamine for primary care providers in remote medicine

Ketamine for primary care providers in remote settings
By Dr Minh Le Cong
MBBS, FRACGP, FACRRM, FARGP, FACAsM, GEM, GradDipAeroRTM
Disclaimer : I have provided the recommended dosages of medication and preparations as a guide only. Final decisions on dosing and drug preparation must be your own responsibility as a medical/health practitioner working within your nation’s laws and professional scope of practice.

Indications
-acute sedation for painful procedures
-acute analgesia for moderate to severe pain not responding to opioids
-emergency general anaesthesia

How to prepare an injection, different concentrations, how to dilute
Ketamine hydrochloride comes as a clear liquid in dilutions of 50mg/ml or 100mg/ml. Typically a 200mg in 2 ml ampoule is available. It can be given undiluted for intramuscular administration or mixed with normal saline or dextrose solutions.

When to give iv vs im. Where to give. How to give. What not to do.
Intravenous administration is preferred, in particular if repeated dosages are expected. Slow IV push is preferred as rapid bolus can lead to apnoea. Preparing a ketamine drip by injecting 500mg into a 1000ml bag of saline will allow a gravity fed infusion to be started for general anaesthesia.

Intramuscular or intranasal administration is reasonable for short procedures when repeated doses are not expected to be required or if intravenous access is difficult to gain initially. 5mg/kg IMI or Intranasal will provide adequate analgesia and some sedation to allow a quick procedure to be performed or the gaining of IV access. Intranasal ketamine must be delivered in an atomised spray or mist to be effective, otherwise it becomes an oral dose. Simplest way to produce a mist is to connect a 3 way tap IV connector to oxygen tubing then connect a 18G peripheral IV cannula to the distal connector and the ketamine in a syringe to the side port connector. Deliver 4 L/min O2 down the tubing and squirt in the premeasured ketamine via the 3 way tap. This oxygen flow produces a jet mist via the 18 G cannula.

Equipment and preparation.
Ketamine is an anaesthetic agent so care must be taken when administering it.

The basic setup for ketamine sedation /anaesthesia should be :
Bag/face mask manual resuscitator
Oral and nasal airways
Suction
Oxygen if at all possible
IV access equipment
Blood pressure cuff
An assistant for airway technique and monitoring assessments

It would be nice to have :
Oxygen saturation monitor
Cardiac monitor
Intubation drugs : suxamethonium, thiopentone, midazolam

. Contraindications. Adverse events, how to prepare and how to treat
There is good evidence to support the use of ketamine sedation in children and adults for emergency procedures. The use of ketamine anaesthesia in adults is extensive and its utility and safety in remote settings is well recorded.
Whilst there is no strict age limit to ketamine use as an anaesthetic, analgesic or sedative, many guidelines indicate the expert opinion of avoiding ketamine use below the age of 6 months for elective procedures. This is due to animal model research findings of neurodevelopmental abnormalities despite a complete lack of human evidence for such problems. In the event of emergency, life threatening cases, the balance of risk vs benefit in using ketamine for any age group must be weighed by the provider.
Ketamine will produce elevated blood pressure and pulse. Any condition that will worsen with such a change , one needs to be extremely cautious in using ketamine. For example, severe pre-eclampsia or aortic dissection will be seriously worsened by ketamine in the usual doses. Cardiac ischemia, angina and myocardial infarction may get worse with ketamine induced tachycardia and hypertension. This sympathomimetic effect of ketamine can be blunted with co-administration of morphine, diazepam, midazolam or droperidol.

Ketamine produces nystagmus and so is not ideal for ocular procedures. Hypersalivation is common but usually not an issue in short procedures. Longer procedures may benefit from an anticholinergic agent to dry secretions, atropine 300mcg in adult IV or 10mcg/kg IV in children.
Common adverse events also include nausea and vomiting with higher dosing range >;;;;;4mg/kg boluses.

The most serious adverse events are hallucinations/delirium and laryngospasm. Whilst uncommon they do occur and a provider must be prepared to manage them

Laryngospasm is the sudden spasming of the vocal cords and leads to acute airway obstruction. The patient will be making chest wall movements but no airway noise or a stridor indicating partial closure of the vocal cords. Immediate action is to provide positive pressure ventilation with oxygen via a manual bag/face mask resuscitator. A jaw thrust by an assistant will greatly help the alleviation of the spasm. If this does not relax the spasm then administration of IV (1mg/kg) or IMI(4mg/kg) suxamethonium should resolve the issue and allow emergent intubation to occur to secure the airway. If the laryngospasm resolves adequately to allow effective face mask ventilation then tracheal intubation maybe deferred if the procedure is short and the aim is to recover the patient quickly.

Emergency delirium/hallucinations are frightening perceptual experiences during ketamine sedation/anaesthesia and often occur during the recovery phase. They are uncommon as many experience complete amnesia with ketamine. To minimise the risk of their occurrence then co-administration of midazolam 1-2mg IV or diazepam 5mg IV is helpful. The same benzodiazepines can be used to treat emergence delirium as well. This problem is almost exclusively seen in adults rather than children.

low dose for pain control vs higher dose for sedation vs induction dose. compatability with other drugs like morphine, pethidine, propofol.
Ketamine is an excellent analgesic at low doses 0.5mg/kg IV. Sedation for procedures can usually be achieved with 1mg/kg IV dosing whereas induction and general anaesthesia doses are typically 2mg/kg with maintenance 2-4mg/kg/hr IV infusion. Ketamine is compatible with all other anaesthetic drugs and analgesics. It has an opioid sparing effect. Ketofol is an alternative cocktail of ketamine and propofol usually in a 1:1 ratio but increasingly providers use separate syringes of each and give small boluses of both drugs to provide a balanced form of anaesthesia/sedation. I personally see no advantage over plain ketamine.

How long will the effect last? Can you repeat?
IV ketamine will last 10-20minutes then require repeat dosing or an infusion to maintain. IMI ketamine will last 30-40 minutes depending upon the dosing. IV ketamine can be repeated multiple times. IMI ketamine you should not repeat unless absolutely necessary as it will lead to prolonged sedation and recovery. If you need to repeat ketamine after IMI dose, better to gain IV access and administer smaller IV dose

Long term side effects
The only recognised long term side effect of ketamine is in chronic abuse of the drug for recreational purposes. Daily long term use of illicit ketamine for recreation has lead to a significant number of users developing a chronic uropathy characterised by bladder wall dysfunction and lower urinary tract inflammatory symptoms.
There is no evidence that medical use of ketamine leads to this uropathy. Studies into the effects of ketamine on psychotic disorders have never revealed a long term increase in the development of chronic schizophrenia or mental illness as a result of ketamine.

References:
Ketamine, a review by a Medecins Sans Frontieres anaesthetist<;;
Basic ketamine infusion anaesthesia
laryngospasm after ketmine