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Anaesthesia - introduction to anaesthetic drugs

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Introduction

These notes are intended as an introduction to some of the commonly used anaesthetic agents and techniques used in PICU. They are guidelines only and do not replace the more comprehensive texts available, or the need for skilled assistance from senior colleagues.

The agents described are usually used to facilitate intubation, control seizure activity, decrease CMRO2 (and consequently ICP) or provide sedation.

Monitoring - pulse oximetry/capnography/ECG/BP/agent monitoring
Intubation - ETTs/laryngoscopes/introducers/suction/assistance

See also related guidelines above - Emergency intubation checklist and Difficult intubation

Drugs

Induction Agents

Propofol (Diprivan) - Solvent is an intralipid-like substance consisting 10% soyabean oil, 2.25% glycerol, 1.2% egg phosphatide.
  Patients allergic to eggs should be able to
 tolerate propofol as egg allergies usually arise to egg albumen
- Causes hypotension due to vasodilatation
- Respiratory depressant
- Pain on injection common especially small hand veins
- Infusion for sedation ≈ 4 mg/kg/h (titrate to effect). Note: unexplained metabolic  acidosis (PRIS) reported with
   prolonged infusion at dose rates >4mg/kg/h.
Ketamine  (Ketalar) - Dissociative agent
- Stimulates sympathetic system but direct myocardial depressant
- Increases secretions
- Bronchodilator
- May increase muscle tone
- Patient may appear to be awake
- Usual dose 2mg/kg induction then 1mg/kg every 20-30 mins for anaesthesia
- Facilitates simple painful procedures (eg chest drain removal) 0.5mg/kg
- Powerful analgesic and can be used by infusion in low doses to provide analgesia (0.2-1 mg/kg/h)
- Concerns that may increase ICP unfounded if pCO2 controlled
Midazolam (Hypnovel) - 0.1-0.2 mg/kg, infusion 2 mcg/min/kg
- Cardiorespiratory depression in compromised patient ESPECIALLY if given with opioids
- Not painful in peripheral IV (cf. diazepam)
Etomidate - Very CVS stable steroid derivative
- Causes adrenal suppression with repeat dose or infusion
- Induction dose is 0.3 mg/kg


Neuromuscular Blocking Drugs (NMBDs)

Depolarising Agents
Cause activation at neuromuscular junction then stay bound causing muscle relaxation
Succinylcholine - Dose is age dependent:
        - Neonate 3 mg/kg
        - Child 2 mg/kg
        - Adult 1 mg/kg
- Structure and action similar to acetylcholine
- Produces initial muscle twitching and fasciculation followed by paralysis for 2-4 min
- Can cause bradycardia, especially after 2nd dose, atropine (0.01 mg/kg, max 0.6 mg) will ameliorate effect
- Transient small increase in K+ 2° to fasciculation. This effect may be associated with hyperkalaemic arrhythmias
  and arrest in patients with pre-existing hyperkalaemia / gross tissue damage (e.g. burns, crush injuries)
  /immobilisation /myopathies /stroke. Avoid using in these patients.
- Succinylcholine is metabolised by pseudocholinesterase in plasma. The occasional patient is deficient and
   neuromuscular block is prolonged for hours.
- Contraindicated in MH
Competitive/non-depolarising relaxants
Compete with Ach at neuromuscular junction
Rocuronium - Rapid onset vecuronium derivative
- Very CVS stable. Can give 1mg/kg to speed onset but lasts approx 60min.
- Dose = 0.6 mg/kg (onset approx 1 min)
- Intermediate duration action (10 min)
- Can be reversed with sugammadex 16 mg/kg for immediate reversal, sugammadex 4mg/kg if 1-2 post-tetanic
  counts
Pancuronium - Dose 0.1 mg/kg
- Duration of action ≈ 30-45 min
- Usually minimal effect on circulation (mild tachycardia & hypertension)
  O
ccasionally profound tachycardia.
- Urinary excretion (prolonged effect in renal failure)
Atracurium - Dose 0.5 mg/kg
- Duration of action ≈ 20-30 min
- Mild hypotension, occasional histamine release
- Not dependent on kidneys or liver for metabolism
Vecuronium - Dose 0.1 mg/kg
- Duration of action ≈ 20-30 min
- Occasional mild bradycardia
- Partly metabolised in liver and small amounts excreted in urine
- Sugammadex may partially reverse neuromuscular blockade


Opioids

Morphine - 0.1-0.2 mg/kg, infusion 10-50 mcg/min/kg
- Cardiorespiratory depression, nausea, vomiting, histamine release
- Duration ≈ 1 h
Fentanyl - Related chemically to pethidine
- 0.1 mg fentanyl ≈ 10 mg morphine: dose 1-2 mcg/kg IV
- Infusion 2-4 mcg/kg/h
- Duration of analgesia 20-30 min
- Respiratory depression, nausea, vomiting
- Can use for induction - dose 10 mcg/kg (beware chest wall or glottis rigidity)

Clinical Situations

  • Usual induction agent is propofol 2mg/kg in stable patients.
  • Usual muscle relaxant is succinylcholine 1-2 mg/kg in children, higher doses (3 mg/kg used in neonates)

Some clinical situations require a different approach as outlined below:

Upper Airway Obstruction - croup / epiglottitis / tracheitis

Problem  airway obstruction/inability to ventilate using PPV/inability to intubate.
Preferred technique  gaseous induction with sevoflurane. Senior anaesthetic assistance + ENT assistance is always required.
Breathing System Ayers T-piece with Jackson Rees modification
- Flow 6-8 L/min
- FiO2=1
Technique Sevoflurane 0.5% in 100% O2 is administered using an appropriate  sized face mask. Sevoflurane concentration is increased every 5 breaths to a maximum of 8%. Partial occlusion of the open rebreathing bag adds CPAP which is  often needed as the child initially loses consciousness. CPAP maintains FRC and helps splint the upper airway open. Gentle assisted breathing may be helpful but make sure that it is timed to patient effort. A Guedel airway may be necessary but great  care must be taken to avoid laryngospasm by inserting it while the patient is lightly anaesthetised.  Anaesthesia is satisfactory when pupils are central and breathing is regular and diaphragmatic…at this stage it is often wise to wait a further 2 minutes before attempting intubation. Induction of anaesthesia is slow and can take over 15 min.
Sevoflurane - Non-irritant
- Rapid induction/emergence
- MAC 2.5%
- Hepatic metabolism 3-4%
- Respiratory and circulatory depressant effects

The Convulsing Child

Problems - Obtunded child (post ictal/hypoxia/anti-convulsant medication e.g. diazepam, phenobarbitone, phenytoin, levoteracitam)
- Aspiration due to potential full stomach
Technique - Depends on degree of obtundation - always maintain airway and oxygenate. This includes cricoid pressure and skilled
  assistance

- If unresponsive - intubate with no further CNS depressants
- If seizing - rapid sequence induction with propofol 2-3 mg/kg, succinylcholine 1 mg/kg
NB Long acting NMBDs given to fitting children may mask seizure activity.

Asthma

  • Intubation in these situations is a last resort after ineffective medical management using sympathomimetics and bronchodilators
  • Ketamine 2 mg/kg or propofol 1-2 mg/kg are useful for induction
  • Succinylcholine 1 mg/kg or rocuronium 0.6 mg/kg achieve good intubating conditions within 60 sec

Head Injury

Problems - Other associated trauma, especially to airway and cervical spine
- Hypotension due to blood loss
- Prevention of secondary injury (hypotension, hypoxia, ↑CMRO2 e.g. fitting)
- Prevention ↑ICP, maintain CPP
Technique - Rapid sequence induction with propofol 1-2 mg/kg (dose titrated to clinical scenario, e.g. reduce in face of hypotension)
  and succinylcholine (1 mg/kg). This technique achieves rapid control of the airway without massive rises in ICP
- May require in line stabilisation of cervical spine during intubation
- Always give thought to possible intubation difficulties prior to rushing into a rapid sequence induction


Burns, Crush Injury, Hyperkalaemia, Spinal Injuries, Myopathies

  • Avoid succinylcholine because of massive K+ release that can occur after administration
  • Alternatives:
    • Rocuronium for rapid sequence induction
    • If no concern about airway/full stomach then a longer acting NMBD can be used (e.g. vecuronium, atracurium, pancuronium)
    • Gaseous induction using sevoflurane
    • Rarely awake intubation under local anaesthesia in older children

Neonatal Intubation

Neonates in PICU are usually given the benefit of anaesthesia during intubation. Awake intubation is rarely performed. The drugs used are individualised depending on pathology, but invariably include an induction agent (propofol, ketamine, fentanyl) and a neuromuscular blocking drug (succinylcholine, rocuronium, atracurium, vecuronium, pancuronium)

Trauma

Problems relate to nature of trauma, secondary insult and pre-existing pathology. 
Always consider:

  • Head injury/cervical spine
  • Hypovolaemia
  • Crush injury
  • Difficult airway
  • Full stomach

and give anaesthetic drugs accordingly.

A rapid sequence induction using preoxygenation, cricoid pressure, propofol 1-2 mg/kg and succinylcholine 1 mg/kg remains popular. However, the induction technique must be adapted to each patient's particular circumstances.

Shocked Child

These children have obvious cardiovascular compromise and the use of drugs such as propofol can cause profound CVS collapse. Ketamine 1-2mg/kg is a useful alternative in this situation. It maintains blood pressure indirectly by stimulating the sympathetic nervous system, but it is in fact a myocardial depressant.

A safer alternative for induction is fentanyl 10 mcg/kg. This will maintain CVS stability but fentanyl is an analgesic and not an induction agent and it can cause muscle rigidity (resolves with NMBD administration). If available etomidate is a reasonable drug to use.

When intubating these children you need to have IV fluids and vasopressor and/or inotrope immediately available because any induction agent plus positive pressure ventilation can precipitate CVS collapse. Remember that they will all have a slow circulation time which means that drugs will take longer to act when given.

Rapid control of the airway and ventilation is often required in these patients as it decreases the work of breathing and facilitates line placement.

NOTE: These notes are GUIDELINES only and do not replace skilled advice from colleagues with airway maintenance experience.

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Document Control

  • Date last published: 04 July 2017
  • Document type: Clinical Guideline
  • Services responsible: Paediatric Intensive Care Unit
  • Author(s): Brian Anderson
  • Editor: John Beca
  • Review frequency: 2 years