Ketamine infusion: high dependency and intensive care units only

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Introduction

Ketamine is a phencyclidine derivative which acts as a dissociative anaesthetic agent with analgesic properties. Sub anaesthetic doses of ketamine, given as low dose infusion prevent central sensitisation associated with the development of chronic pain, reduce post operative opioid requirements and hyperalgesia. Low dose ketamine thus provides safe and effective analgesia, usually as part of a multi-modal approach. Evidence suggests use of ketamine reduces pain scores across different patient groups with a lower requirement for post operative opioids.

Ketamine is a non competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, therefore reducing the action of the excitatory neurotransmitter glutamate in the central nervous system. Evidence from a growing number of trials suggests that ketamine attenuates the “wind-up” phenomenon in early post operative patients, associated with a reduction in the development of chronic pain as well as reducing overall post operative opioid requirements. Post operative nausea and vomiting is generally reduced with ketamine treatment, partly due to the reduction in opioid requirements and partly due to NMDA receptor antagonism. Studies show the greatest reduction in opioid requirements in patients undergoing orthopaedic (both limb and spine), intra-abdominal or lower abdominal surgeries. Ketamine is not efficacious in patients undergoing dental or head and neck surgery.

A 2010 Cochrane Review of perioperative ketamine in acute postoperative pain concluded that in sub anaesthetic dose ketamine:

  • Is effective in reducing opioid requirements in the first 24hours following surgery
  • Reduces postoperative nausea and vomiting
  • Is generally well tolerated with mild or absent adverse effects

Respiratory depression is minimal with ketamine but clinical use is limited due to its potential to cause hallucinations and dissociative mental state. Although uncommon these side effects generally limit the use of ketamine to patients who’s pain is likely to be difficult to manage with opioids alone. Ketamine has no role in surgery known to produce only mild pain.

Ketamine prescriptions should only be made following consultation with the acute pain service or the on call anaesthetist out of hours. The infusion should be prepared by two nurses with adequate training and knowledge of infusion pumps. Other prescribed analgesics should continue as prescribed following review by the anaesthetic team. The requirement for ketamine infusion should be reviewed daily by the parent team with input from the acute pain service/on call anaesthetist. Ketamine should be considered for short term use only and require anaesthetic consultant review if exceeding 72 hours.

Indications
  • Rescue analgesia for ongoing acute pain uncontrolled with opioids alone
  • Post amputation pain not responding to opioids
  • Acute on chronic pain in an opioid tolerant individual with usual opioid requirements in excess of 120mg morphine equivalents. Including (but not limited to):
    • Fibromyalgia patients with high opioid usage
    • Chronic low back pain attending for spinal surgery
    • Acute on chronic pancreatitis
  • Uncontrolled ischaemic pain such as in critical limb ischaemia
  • Acute pain with underlying debilitating chronic pain disorder, eg complex regional pain syndrome
Contraindications
  • Allergy to ketamine / previous significant adverse effects
  • Paediatrics/Obstetric patients (including breastfeeding mothers
  • Psychiatric illness or history of psychosis (excluding depression without psychotic features)
  • Known epilepsy or recent history of unexplained seizures
  • Severe uncontrolled hypertension
  • Severe/end stage cardiac failure (NYHA class 3 or 4)
  • Raised intracranial pressure (use with caution in those with known space occupying lesions)
  • Glaucoma / Raised intraocular pressure
  • Patient not consenting

Ketamine is safe for use in asthmatic patients but care should be taken in patients treated with theophylline due to known drug interactions.

Drug Interactions

Ketamine has known interactions with

  • Theophylline (tachycardia, reduced seizure threshold with resulting seizures)
  • Levothyroxine (hypotension, tachycardia)
  • Diazepam (increased plasma concentrations of ketamine, consider reducing ketamine infusion dose)
Equipment

An Asena syringe driver with lock box should be obtained. Use a luer lock 50ml syringe attached to an anti siphon line (which must be labelled as per NHS Highland guidelines) and a dedicated IV cannula.  Standard aseptic precautions should be deployed.

Dose and Drug Preparation

A new drug syringe should be prepared and discarded every 24 hours. Ketamine should be prepared to a concentration of 5mg/ml using these instructions:

  • Obtain ketamine hydrochloride (Ketolar) at a concentration of 10mg/ml.
  • Draw 20ml of ketamine into a 50ml syringe (20ml x 10mg = 200mg).  The addition of 20ml 0.9% saline gives a total of 40ml volume and a final concentration of 5mg/ml (200mg ketamine in 40ml = 5mg/ml).
  • Infusions should be commenced at 1ml per hour (5mg/hour) and titrated to effect (see below for maximal infusion rates) or until side effects are experienced.
  • In patients weighing >50kg the infusion rate should not be increased more frequently than hourly and should never exceed 5ml/25mg per hour.
  • If weight <50kg the infusion rate should not be increased more frequently than hourly and should never exceed 3ml/15mg per hour.
  • Consider an initial dosage of 0.5ml (2.5mg) per hour in the frail and elderly with cautious dose titration.

Loading doses are not recommended.

Ketamine undergoes renal excretion however there is no requirement for dose adjustment in patients with renal dysfunction in the dose ranges suggested in this guideline.

Paracetamol and NSAIDS should be continued unless specifically contraindicated.

Concurrent prescription of adequate antiemetics should be available prior to starting the infusion to ameliorate any side effects.

A dedicated ketamine prescription chart must be used and can be obtained from the acute pain team or the intranet. The prescription is not valid unless signed by the treating anaesthetist or acute pain service.

Ketamine infusions should ideally be commenced before 2pm allowing for close monitoring for side effects and toxicity within day time working hours.

Side effects

Side effects are minimal at the initial dosages in this guideline but may limit usage at higher doses. These include:

  • Cardiovascular stimulation causing hypertension and tachycardia
  • Hallucinations and dysphoria (may be alleviated with benzodiazepines under anaesthetic direction)
  • Rise in intra-cranial pressure, cerebral metabolic rate and cerebral blood flow
  • Excessive sedation

If the patient develops disturbing hallucinations or other concerning symptoms the infusion should be stopped and the acute pain service or on call anaesthetist out of hours should be notified urgently.

Respiratory depression and hypotension are not typical features of ketamine however consider the use of naloxone in compromised patients with concurrent opioid treatment.

Patient Observation
Monitoring parameter 1st hour During dose titration Thereafter
Respiratory Rate and Oxygen Saturations 15 mins Half Hourly Hourly
Blood Pressure 15 mins Half Hourly Hourly
Heart rate 15 mins Half Hourly Hourly
Pain Score 15 mins Half Hourly Hourly
Sedation Score 15 mins Half Hourly Hourly
Dysphoria and hallucinations 15 mins Half Hourly Hourly

Patients should be nursed in a critical care environment such as an HDU or ICU only.  Ketamine infusions are not suitable for ward level care.  Patients may be mobilised with care.

Patients should have supplemental oxygen prescribed for the duration of the infusion. Increasing oxygen requirements should prompt medical review with particular focus on assessment for concurrent opioid toxicity.

Treatment of potential issues

Hypotension is unusual with ketamine due to its positive inotropic effects. Persistent hypotension should prompt urgent medical review and consideration of other potential causes eg sepsis, acute coronary syndromes, haemorrhage/ hypotension, post operative complications.

Respiratory depression is not a typical feature of ketamine however any respiratory depression should prompt an increase in monitoring of vital signs and urgent medical review. In the event of respiratory compromise the on call ward doctor should be contacted immediately if the respiratory rate drops below 9/minute and the infusion should be stopped. Administer high flow oxygen via a reservoir mask. If in doubt summon emergency help by calling 2222.

Naloxone has NO effect on ketamine however should be considered in any patient with significant respiratory depression or excessive sedation who is receiving concurrent opioids.

In the event of suspected opioid toxicity with resulting respiratory depression, respiratory rate of 8 or less and difficult to rouse, observe the following actions:

  • Stop ketamine infusion and withhold further doses of opioids
  • Ensure a clear airway and administer high flow, 15 litres per minute, oxygen using a reservoir face mask
  • Contact the on call ward doctor, ICU anaesthetist and acute pain nurse
  • Prepare naloxone 400micrograms (1ml) in with 3mls sodium chloride in a 5ml syringe
  • Administer naloxone in 100microgram increments until the respiratory rate is greater than 10 or sedation score is 0 or 1
  • Naloxone should be administered to a maximal dose of 400micrograms. If no response seek other causes of sedation/respiratory depression, consider surgical causes
  • DO NOT give further doses of ketamine or opioids until reviewed by the acute pain nurse or ICU anaesthetist

In the event of excessive sedation with ketamine alone WITHOUT respiratory compromise:

  • Stop ketamine infusion and withhold further doses of opioids
  • Ensure a clear airway and administer high flow, 10 litres per minute, oxygen using a reservoir face mask
  • Contact the acute pain nurse or ICU anaesthetist out of hours to reassess analgesia

Nausea and vomiting should be treated with regular antiemetics with escalation to the anaesthetic team as detailed below.

Guidance for escalation to the acute pain service / on call anaesthetist in the event of:

  • Ineffective pain relief
  • Persistent nausea and vomiting despite regular antiemetics
  • Seizures
  • Acute agitation/dysphoria
  • Acute change in vital signs, the acute pain service of on call anaesthetist out of hours should be notified urgently and the infusion stopped in the event of any of the following:
    • Drop in systolic blood pressure of 30%
    • Drop in respiratory rate to 8 or less
    • Profound sedation or difficulty in waking
Follow Up

Patients treated with ketamine infusion should be reviewed at least daily by the acute pain service or on call anaesthetist out of hours. Discontinuation of the infusion will be guided by clinical response under the direction of the acute pain service/on call anaesthetist. Infusions lasting more than 72 hours require are by anaesthetic consultant discretion only following patient review.

Editorial Information

Last reviewed: 30 November 2018

Next review: 30 November 2020

Author(s): Acute pain team

Version: 2

Approved By: TAM Subgroup of ADTC

Reviewer Name(s): Acute Pain Nurse Specialists

Document Id: TAM111