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Sedatives and Analgaesia

An important aspect of the management of critically ill patients is appropriate sedation and analgesia.

 

The goals of these agents may be to:

  • Control pain associated with illness and/or ICU interventions

  • Allow the patient to tolerate various invasive interventions

    • For example, endotracheal intubation, mechanical ventilation​

  • Minimise distress and anxiety

  • Manage agitation or delirium

  • Reduce patient oxygen consumption

  • Reduce intracranial pressure

  • Facilitate rest/sleep

​

This article provides an introduction to commonly used medications within the ICU and how to approach their use.

 

It is not expected that junior medical staff will manage sedation/analgesia on their own. 

  • Make a sedation/analgesia plan for patients in conjunction with more senior staff and be confident to ask for help if you are unsure or require assistance.

Key Terms
​
Assessment of Sedation
 
Agents:
​
Approach to Sedation

Key Terms

  • Analgaesia

    • Relief of pain​

  • Sedation

    • ​Depression of a patient's awareness to the environment and reduction of their responsiveness to external stimulation

  • Hypnosis

    • Drowsiness associated with the onset and maintenance of sleep
    • Extension of sedation

  • Anxiolysis

    • Level of sedation associated with relaxation and relief of anxiety/agitation

  • Amnesia

    • Period of memory loss​

​

​

Assessment of Sedation

  • There are various sedation assessment tools

  • Western Health ICU uses the RIKER agitation-sedation scale

    • Usually aiming for a level of 3-4​

    • Sometimes 1-2 may be required for the critically unwell

​

Key Terms
Assessment of Sedation

  • Another commonly used score in Australia ICUs is the Richmond Agitation-Sedation Scale (RASS)

    • Usually aiming for a level of 0 to -2.​

Commonly Used Agents

Propofol

  • Preparation

    • White oil-in-water emulsion​

    • 10 mg/ml

    • Administered neat (ie. does not require dilution)

  • Mechanism of action

    • Exact mechanism unclear​

    • Potentiates inhibitory neurotransmitters (Glycine and GABA)

  • Effects

    • Hypnosis​

    • Anxiolysis

    • DOES NOT provide any analgaesia

    • DOES NOT provide physiologic sleep

  • Route

    • Intravenous (peripheral or central)​

  • Dose

    • Infusion: 10 - 200 mg/hr​

      • Commonly commence at 50 mg/hr​

      • Titrate up or down by 10 - 20 mg/hr as necessary

    • Bolus: 10 - 20 mg

      • Repeat every 30 - 60 seconds as required​

      • Indicated for intubated patients with inappropriate ventilation or acute agitation

  • Adverse Effects

    • Vasodilation -> Hypotension​

    • Negative inotrope (decreased cardiac contractility)

    • Apnoea

    • Suppression of airway reflexes

    • Propofol infusion syndrome

      • Refractory bradycardia associated with:​

        • Metabolic acidosis​

        • Rhabdomyolysis

        • Multi-organ failure

      • Associated with prolonged/large doses of propofol

    • Green discolouration of urine (harmless effect)

Propofol

Midazolam

  • Preparation

    • Clear solution​

    • Infusions made up as:

      • 100mg in 100ml OR 250mg in 250ml​ (1 mg/ml)

      • Diluted in 0.9% NaCl or 5% dextrose solutions

  • Mechanism of action

    • Benzodiazepine receptor agonist​

    • Potentiates activity of endogenous GABA

  • Effects

    • Sedation​/hypnosis

    • Anxiolysis

    • Amnesia

    • Anti-emesis

    • Anti-convulsant

    • DOES NOT provide any analgaesia

  • Route

    • Intravenous (peripheral or central)​

  • Dose

    • Infusion: 1 - 10 mg/hr​

      • Commonly commenced at 1 - 3 mg/hr​

      • Titrate up/down by 1 mg/hr as required

  • Adverse effects

    • Hypotension​

    • Respiratory depression

    • Withdrawal syndrome following prolonged infusion

    • May accumulate in renal impairment

  • Antidote:​

    • Flumazenil

    • 500 mcg

    • Intravenous

    • Short duration of action (minutes)

Midazolam

Ketamine

  • Preparation

    • Clear solution​

    • Infusions made up as:

      • 200mg in 100ml​ (2 mg/ml)

      • Diluted in 0.9% NaCl solution

  • Mechanism of action

    • NMDA receptor antagonist​

    • Inhibits activity of excitatory neurotransmitter​ glutamate

  • Effects

    • Sedation/hypnosis​

      • Dissociative anaesthesia​

    • Anxiolysis

    • Analgaesia

    • Bronchodilation

  • Route

    • IV (peripheral or central)​

  • Dose

    • Infusion: 4 - 20 mg/hr​

      • Commonly​ commenced at 4 mg/hr

      • Titrate up/down by 2 - 4 mg/hr as appropriate

    • Bolus: 10 - 20 mg

  • Adverse effects

    • Hallucinations/nightmares​

    • Nausea and vomiting

    • Tachycardia

    • Myocardial depression

      • The commonly held notion that ketamine is a 'cardiac stable' anaesthetic agent ​refers to its sympathomimetic activity via increased catecholamine release

      • In the critically ill patient with depleted catecholamine reserves, ketamine has a direct myocardial depressant effect, which will result in haemodynamic instability

Ketamine

Dexmedetomidine (Precedex)

  • Preparation

    • Clear solution​ 

    • Infusions made up as:

      • 400mcg in 100 ml​ (4 mcg/ml)

      • Diluted in 5% dextrose solution

  • Mechanism of action

    • Central alpha-2 adrenoceptor agonist​

  • Effects

    • Sedation​

      • Of all sedatives, most closely resembles physiologic sleep​

    • Anxiolysis

    • Analgaesia

  • Route

    • Intravenous (central or peripheral)​

  • Dose

    • Infusion: 0.2 - 1.0 mcg/kg/hr​

  • Adverse effects

    • Bradycardia​

    • Hypotension

      • May cause initial transient hypertension due to peripheral alpha-1 adrenoceptor agonism​

    • Rebound tachycardia/hypertension on infusion cessation

    • Mild respiratory depression

    • Nausea

    • Xerostomia (dry mouth)

Dexmedetomidine

Fentanyl

  • Preparation

    • Clear solution​

    • Infusions made up as:

      • 1000 mcg in 100ml (10 mcg/ml)

      • Diluted in 0.9% NaCl or 5% dextrose solutions

    • Vial comes as 50 mcg/ml

  • Mechanism of action

    • CNS and spinal cord opioid receptor agonist

  • Effects​

    • Analgaesia​

    • Sedation

  • Route

    • Intravenous (peripheral or central)​

  • Dose

    • Infusion: 10 - 100 mcg/hr​

      • Commence at 10 - 30 mcg/hr​

      • Up/down titrate by 10 mcg/hr as indicated

    • Bolus: 10 - 50 mcg

      • 10 mcg fentanyl = 1mg morphine (IV)​

  • Adverse effects

    • Respiratory depression​

    • Bradycardia

    • Nausea and vomiting

    • Facial itch

    • Constipation

  • Antidote

    • Naloxone​

    • 200 - 400 mcg

    • Intravenous or intramuscular

    • Duration of action: 20 - 40 minutes

  • Hepatic metabolism to inactive metabolites

    • Safer than morphine in renal impairment​

Fentanyl

Morphine

  • Preparation

    • Clear solution​

    • Infusions made up as:

      • 100mg in 100ml OR 250mg in 250 ml (1 mg/ml)​

      • Diluted in 0.9% NaCl or 5% dextrose solution

  • Mechanism of action

    • CNS and spinal cord opioid receptor agonist

  • Effects​

    • Analgaesia​

    • Sedation

  • Route

    • Intravenous (peripheral or central)​

  • Dose

    • Infusion: 1 - 10 mg/hr

      • Commence at 1 - 3 mg/hr​

      • Up/down titrate by 1 mg/hr as indicated

    • Bolus: 1 - 5 mg

      • 1 mg morphine = 10 mcg fentanyl

  • Adverse effects

    • Respiratory depression​

    • Bronchospasm

    • Bradycardia

    • Hypotension

    • Nausea and vomiting

    • Pruritis

    • Constipation

    • Caution in renal impairment - active metabolites will accumulate

  • Antidote

    • Naloxone​

    • 200 - 400 mcg

    • Intravenous or intramuscular

    • Duration of action: 20 - 40 minutes

Morphine
Approach to Sedation
Approach to Sedation

There are many different approaches to sedation/analgesia for critically ill patients

  • This can be confusing at times for junior staff as senior clinician experience and preference impacts choice of medication regimes

  • Using a combination of sedatives/analgesics results in a reduction in dose requirement of each medication (reduced side effect profile) and improves patient comfort by providing hypnosis, anxiolysis, amnesia and analgesia

​​

Hypnosis

  • Propofol

    • First line sedative

    • Maximum 200mg/hr

    • Usually run in combination with opioid

  • Benzodiazepines

    • If propofol/opioid combination not providing adequate sedation, midazolam infusion commonly added

​

Analgesia

  • As mentioned, propofol has no analgesic properties therefore it is commonly used in combination with opioids

    • Combination of propofol AND fentanyl OR morphine most commonly used practice in Western Health

  • Fentanyl

    • Commence at lower dose 10 - 30 mcg/hr and up titrate as required

    • Common maximum dose of 100mcg/hr, however not a hard limit

  • Morphine

    • Used less commonly than Fentanyl​

    • Commenced at lower dose 2 - 4 mg/hr and up titrate as required

    • Common maximum dose of 10mg/hr, however not a hard limit

​​

Other

  • In rare event that the above medications are not providing adequate sedation/analgesia other agents can be used

    • Ketamine

    • Dexmedetomidine

  • Discussion with senior staff must occur prior to initiation of these medications

       Author: Matt Guest, Peer Reviewer: James Douglas, Date: 31/03/20

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