Drugs and Sedation

, Amy Gospel2, Andrew Griffiths3 and Jeremy Henning4



(1)
Intensive Care Unit, James Cook University Hospital, Middlesbrough, UK

(2)
Tyne and Wear, UK

(3)
The York Hospital, Middlesbrough, UK

(4)
James Cook University Hospital, Middlesbrough, UK

 



By the end of this chapter you should:



  • Know the dilution, dosing and indications of the drugs routinely used within PHA


  • Appreciate the main side effects of these agents


  • Understand the aim of sedation and sedation end points

The safety of pre-hospital anaesthesia (PHA) is very dependent on the familiarity of personnel with the techniques and drugs that they are using. Therefore, it is usual for well-developed pre-hospital systems to use a consistent technique and a limited number of drugs. All individuals involved with the drawing up and administration of these drugs should have an understanding of their pharmacology and pharmacokinetics.

The ‘ideal’ recipe for pre-hospital rapid sequence intubation (PRSI) is yet to be determined. Lyon et al. (2015) report the use of Fentanyl (3 mcg/kg), Ketamine (2 mg/kg) and Rocuronium (1 mg/kg) for the PRSI of trauma patients. This combination produced good conditions for laryngoscopy within 60 s, whilst maintaining favourable physiological parameters. The doses were reduced to Fentanyl 1 mcg/kg and Ketamine 1 mg/kg in those with haemodynamic compromise.

GNAAS advocates doses of 1–2 mcg/kg Fentanyl, 1–2 mg/kg Ketamine and 1.2 mg/kg Rocuronium (with the lower dose, or omission, of Fentanyl and lower dose of Ketamine in hypotensive patients). A dose of 3 mcg/kg of Fentanyl is used in hypertensive patients with an isolated head injury.


7.1 Pre-treatment


Various drugs can be used to reduce the unwanted sympathetic response to laryngoscopy (hypertension, raised intracranial pressure (ICP)). Fentanyl 2 mcg/kg is a reasonable first choice, but should be used with caution in patients with cardiovascular instability, hypovolaemia or a systolic blood pressure (SBP) <120 mmHg. It has a peak effect at around 3 min, so would ideally be given 3 min prior to laryngoscopy. Unfortunately, it can cause respiratory depression and so there is potential for a period of hypoventilation between administration and induction if given early. To avoid this problem, whilst still obtunding the pressor response to laryngoscopy, it is possible to give Fentanyl in a higher dose (e.g. 3 mcg/kg) immediately prior to the induction agent. This allows a rapid induction whilst providing a similar effect to a lower dose even though the drug has not yet reached its peak effect. This risks delayed hypotension after the stimulation of laryngoscopy has receded. Lyon et al. (2015) reported the successful use of this higher dose, however they did note a higher number of patients with a 20 % reduction in blood pressure and hence advocated a reduced dose of 1 mcg/kg in patients with haemodynamic compromise.

Alfentanil has a peak effect within approximately 90 s and as such is theoretically a better choice than Fentanyl, however it is more prone to causing bradycardia and, more importantly, most clinicians are less familiar with Alfentanil and there is much less evidence of its use in RSI compared to Fentanyl. As Fentanyl is also useful as an analgesic in pre-hospital medicine, it seems sensible to only carry one potent opioid to cover both induction and analgesia.

There is little evidence of benefit from the use of Lidocaine to prevent an increase in ICP during RSI (Butler and Jackson 2002) and none in the pre-hospital environment, nor in comparison to Fentanyl. Lidocaine is therefore not recommended.


7.1.1 Fentanyl


This is a synthetic opioid. It is approximately 100 times more potent than Morphine.































Indication

Attenuate response to laryngoscopy e.g. in isolated head injury

Rapid acting (but relatively short-lived) analgesia

Presentation

Clear solution containing 50 mcg/mL (2 mL amp)

Dilution for use

Neat

Dose

1–2 mcg/kg IV for analgesia, 1–3 mcg/kg IV for induction

Onset

Peak effect 3 min

Offset

10–20 min

Side effects

Respiratory depression, bradycardia, hypotension

Chest rigidity (high doses)


7.1.2 Alfentanil


This is a synthetic opioid. More rapid onset than Fentanyl.



























Indications

Attenuate response to laryngoscopy

Presentation

Clear solution containing 500 mcg/mL (2 mL amp)

Dilution for use

Neat

Dose

20 mcg/kg IV

Onset

Peak effect 90 s

Offset

5–10 min

Side effects

Same as Fentanyl


7.2 Induction Agents


Ketamine and Propofol are probably now the most commonly used induction agents for PRSI within the UK. Ketamine has certainly become the first choice induction agent for trauma patients for both GNAAS and London HEMS.

Ketamine has gained in popularity in recent years encouraged by the number of British military doctors working in UK HEMS who have worked in Afghanistan as part of the Medical Emergency Response Team (MERT). Ketamine was the standard induction agent for PRSI within the MERT from 2008. It was selected as the safest induction agent in young patients who were often hypovolaemic following massive trauma. The beta-1 and alpha-1 effects can help to maintain blood pressure, whereas Propofol (which is the most frequently used induction agent in hospitals in the developed world), causes vasodilation and an element of myocardial depression. Together with the sudden reduction in endogenous catecholamines following anaesthesia, this can cause profound hypotension. Due to its sympathomimetic effect on beta-2 receptors, Ketamine is also particularly useful for induction of patients with severe bronchospasm.

For many years there was a widely held belief that Ketamine increased ICP and was therefore unsuitable for use in patients with head injury. This misconception appears to stem from early studies that reported increased ICP in patients breathing spontaneously; the effect was almost certainly due to an increase in PaCO2 rather than a direct effect of Ketamine. In ventilated patients, Ketamine often decreases the ICP (Zeiler et al. 2014). It is unclear whether the N-methyl-D-aspartate (NMDA) receptor antagonist effect of Ketamine is beneficial or not. In some studies on developing animals, higher doses of Ketamine appeared to have a neurotoxic effect, although these effects were prevented by the co-administration of a Gamma-aminobutyric acid (GABA) receptor agonist (this may be another reason for using Midazolam for ongoing sedation following a Ketamine based RSI) (Himmelsher and Durieux 2005). Overall; the maintenance of blood pressure following induction and a stable or reduced ICP (which results in a stable or increased cerebral perfusion pressure (CPP)) leads to a recommendation to use Ketamine in patients with head injuries requiring PRSI.

In elderly patients who are not shocked, the hypertension and tachycardia following Ketamine may potentially risk myocardial stress and ischaemia, however, with a lower induction dose and pretreatment with Fentanyl, this is probably less of an issue than the potential for hypotension which may result from using Propofol. Tachycardia following Ketamine induction also has the potential to cause some confusion regarding depth of anaesthesia, as both tachycardia and hypertension are usually signs of inadequate anaesthesia. Those who do not routinely using Ketamine in their clinical practice should keep this factor in mind.

Propofol or Thiopentone would normally be the induction agents of choice for a patient with status epilepticus. Ketamine is not recommended in these patients.

Etomidate was previously advocated as the best induction agent for PRSI (EMS Physicians 2006), and was the standard induction agent used by both GNAAS and London HEMS for almost a decade. The benefit of Etomidate is that when compared to most other agents, it is relatively cardiostable. It causes less hypotension than Propofol and Thiopentone, without the tachycardia of Ketamine. Etomidate also reduces ICP and cerebral metabolism. These effects result in a stable CPP and a reduction in cerebral oxygen requirements. This made it a seemingly ideal induction agent for most pre-hospital patients requiring PRSI. Unfortunately it is now clear that Etomidate induces temporary (12–24 h) adrenocortical dysfunction. It has been shown to inhibit 11-beta hydroxylase production of cortisol, leading to decreased serum cortical levels. This is associated with an increased mortality when used in patients with sepsis and may potentially have detrimental effects on trauma patients (Chan et al. 2012; Warner et al. 2009). Combined with the general acceptance that Ketamine does not cause an increase in ICP, Etomidate has therefore fallen out of favour.


7.2.1 Ketamine


This is a phencyclidine derivative.











































Indications

Induction of anaesthesia in patients with hypotension or asthma

Potent analgesic; ideal for facilitating extrication

Presentation

Clear colourless solution containing 10, 50, or 100 mg/mL (Beware using the incorrect concentration)

Dilution for use

10 mg/mL (e.g. 200 mg made up to 20 mL with 0.9 % NaCl) IV

50 mg/mL when used IM

Dose

Profound analgesia 0.25–0.5 mg/kg IV (1–4 mg/kg IM)

IV induction 1–2 mg/kg IV (5–10 mg/kg IM)

Onset

30 s

Offset

5–10 min

Side effects

Emergence phenomenon hallucinations or unpleasant dreams during recovery. Incidence reduced by Midazolam and recovery in a stimuli free environment

Tachycardia and hypertension

Relative contraindication in ischaemic heart disease

Masseter spasm

Increased salivation

Increased upper airway reflexes. Instrumentation of the upper airway without muscle relaxant may lead to laryngospasm


7.2.2 Propofol (2,6-Diisopropylphenol)


This is now the most commonly used induction agent in UK hospitals and is also widely used for sedation in critically ill patients.





























Indications

Induction and maintenance of general anaesthesia

Presentation

White oil in water emulsion containing 10 mg/mL (1 %) (20 mg/mL (2 %) is also available)

Dilution for use

Neat

Dose

1.5–2.5 mg/kg IV induction (up to 4 mg/kg in Paeds)

IV maintenance of sedation at a dose of 2–6 mg/kg/h

Onset

15–20 s

Offset

5–10 min

Side effects

Pain on injection (reduced by adding Lidocaine)

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Sep 22, 2016 | Posted by in ANESTHESIA | Comments Off on Drugs and Sedation
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