Healthcare and Medicine Reference
In-Depth Information
The sedative and anxiolytic effects of these drugs are normally
apparent at a much lower dose than that needed to cause respi-
ratory and cardiovascular depression; in comparison to propofol,
they have a wider margin of safety in this respect.
Each agent has slightly differing properties, in terms of half-life,
dose range, metabolites and physicochemical properties. The clinical
properties are summarised for the agents in common use in Table 4.2.
Arguably the most appropriate agent to use as fi rst choice is midazo-
lam, due to its relatively short half-life. It is also water-soluble and
therefore less painful to administer intravenously than diazepam.
Most benzodiazepines have active metabolites, frequently with
longer half-lives than the parent drug. For this reason, this group of
drugs should only be used for sedation in the short term in normal
circumstances.
Benzodiazepines are Class C controlled drugs.
diazepam. Patients may occasionally develop paradoxical excite-
ment and aggression. Dependence and idiosyncratic reactions can
occur, but are rare in the context of single-event sedation.
Antagonist
Flumazenil is a competitive inhibitor at the benzodiazepine binding
site. It is available in 5-mL ampoules containing 500 microgrammes
(µg) of drug. A dose of 200 µg should be administered over 15 seconds
in suspected benzodiazepine overdose, with supplementary boluses
of 100 µg if the patient fails to respond. It should be remembered
that fl umazenil has a short half-life compared with most benzodi-
azepines; the patient should be continually monitored for recurring
sedation and the practitioner prepared to give additional doses.
NB Flumazenil is not suitable for administration to reverse pur-
poseful patient-led overdose of benzodiazepine-based medication.
Side-effects
All benzodiazepines have the potential to cause respiratory and
cardiovascular system depression. Prolonged confusion and ataxia
may be problematic, particularly with longer-acting agents such as
Anaesthetic agents
Propofol
Propofol is a drug commonly used to induce anaesthesia and to
maintain sedation on critical care units. It has a narrower window
of safety than benzodiazepines in that it causes respiratory depres-
sion and hypotension at doses only marginally greater than those
causing sedation. It should therefore only be administered by those
expert in providing airway, ventilatory and cardiovascular support.
Despite this, in experienced hands, propofol has a number of
advantages over benzodiazepines. It is less likely to cause residual
sedation, since it has a short duration of action and no active
metabolites. Similarly, it does not accumulate to a great extent with
repeated doses. Amnesia does not occur at subhypnotic doses.
CI
β
GABA
α
β
GABA
α
BDZ
Extracellular
γ
Dose
Propofol is available in 1% (10 mg/mL) and 2% strengths. It is a
white emulsion, formulated with egg protein and soybean oil, or in
synthetic lipid suspension. An initial appropriate bolus for an aver-
age adult to achieve conscious sedation is 30-50 mg (3-5 mL of 1%),
with further 10-mg boluses to achieve and maintain the desired
effect (see Figure 4.4). This should be reduced in the very elderly.
Intracellular
Ion channel
Side-effects
Propofol causes respiratory depression and hypotension com-
monly, and may cause bradycardia. It may precipitate hiccups and
Figure 4.3 Diagram of the 5-subunit GABA
receptor, showing
α
benzodiazepine-specifi c binding site (BDZ).
Table 4.2 Clinical properties of intravenous benzodiazepines used in conscious sedation.
Agent
Suggested
initial IV dose
Suggested
'top-up' dose
Time to
peak effect
Duration
Amnesia
Active metabolites?
Comments
Midazolam
1-2 mg
0.5-1 mg
Wait 2 min
1-5 min
15-60 min
+++
None
Water soluble (at pH<4), less
pain on injection
Diazepam
2.5-5 mg
1-2.5 mg
Wait 5 min
2-10 min
30-90 min
+
Nordiazepam
Temazepam
Oxazepam
Pain on injection. Diazemuls
(emulsion in lipid) less
painful
Lorazepam
0.5-2 mg
0.25-1 mg
Wait 15 min
10-20 min
2-6 h
++
None
Dilute before injection to
reduce irritation
 
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