What new information this study adds
Age and total dose volume of topicalised lidocaine have a significant
relationship with plasma lidocaine levels. A dose of 5mg/kg topicalised
lidocaine for paediatric airway endoscopy is safe and provides good
operating conditions. Lower patient weights trend toward higher peak
lidocaine plasma concentrations and require further investigation.
Introduction
Airway endoscopy is a diagnostic and therapeutic procedure involving
instrumentation of the airway. Anaesthesia is typically performed using
a spontaneous ventilation technique with topical lidocaine applied under
direct vision to the supra- and sub-glottis. Local anaesthetic is
applied to the airway to provide a good operative field, minimise the
risk of complications such as laryngospasm and apnoeas, but also
to minimise the peak blood concentration of anaesthetic agent and
facilitate a spontaneous ventilation technique1.
Despite not being licensed for airway topicalisation, lidocaine has been
used for over three decades in paediatric airway examination under
general anaesthesia2, 3. Its use is established
practice in many specialist institutions including [removed for blind
peer review]. The administered dose of topical lidocaine varies
between practitioners from 3-5mg/Kg. The maximum topical dosage of
5mg/Kg is extrapolated from the manufacturers guidance regarding
intravenous administration. Since intravenous administration is presumed
to have 100% bioavailability, the topical route of
administration potentially will result in reduced plasma lidocaine
concentrations due to swallowing, surgical suction and application of
vasoconstrictors such as adrenaline8. This then poses
a clinical quandary as to the safe dose of topically administered
lidocaine, and whether a larger dose will result in increased clinical
effectiveness and complications such as toxicity.
Currently there is little data from well-controlled paediatric studies
regarding peak lidocaine plasma concentrations in airway
endoscopy1,2,3,5,6. Further dosing studies
are required to ensure peak plasma levels do not exceed 5000ng/ml,
as this concentration may potentially be harmful5. In
this study we measured sequential plasma lidocaine levels in order to
ascertain the peak plasma concentration of lidocaine following airway
topicalisation. This would allow us to ensure the safety of our current
dosing regimen, and guide us to any future changes.
Methodology
Study location
Written approval was sought and obtained from the [removed for blind
peer review] in November 2015 and [removed for blind peer review]
in March 2016. Data was prospectively collected over an 18-month period
from January 2017 to June 2018 at [removed for blind peer review].
Study Design
This was a prospective Type A, single arm dosing study aimed at
informing future interventions. There was no modification to standard
clinical care. This trial adhered to the principles outlined in the
[removed for blind peer review]. It is also compliant with
[removed for blind peer review] requirements.
Participants
Participants were recruited on a voluntary basis. Children aged 0-8
years undergoing an elective diagnostic or therapeutic airway endoscopy
were eligible.
Individuals were excluded if there had been any pre-operative exposure
to lidocaine, taking medication that interfered with lidocaine
metabolism or clearance (for example phenytoin, beta blockers or
cimetidine) or informed consent was not obtained from a parent or
guardian. Patients were also excluded from the study if there was a
contra-indication or inability to insert a second intravenous (IV)
cannula for blood sampling.
Eligible patients were identified by a nominated investigator on the
hospital management system greater than 24 hours prior to the
procedure. Individuals with parental responsibility were contacted via
telephone and a trial information sheet sent either via post or
email. On the day of surgery, those that had received trial information
were approached and inclusion within the study discussed. Written,
informed consent was obtained from persons with parental
responsibility.
Any subject could withdraw from the study at any point.
Intra-operative procedure
Individual investigators were trained in standardised sampling
techniques by the project leads [removed for blind peer review].
Standard pre-operative care was delivered, with induction and
maintenance of anaesthesia achieved either by inhalational or
intravenous techniques.
Lidocaine was applied under direct visualization to the airway using a
mucosal atomization device (MAD) at a dose of 3-5mg/kg with standardised
2% solution across all study participants. Once the lidocaine was
delivered to the patient, a stopwatch was commenced and the
investigator inserted an IV cannula for blood sampling (using aseptic
technique as per trust policy). No more than 3 sites were attempted and
if the investigator was unable to cannulate, the subject was excluded
from trial. The supplementary cannula was reserved only for blood
aspiration, and therefore no drugs were administered via this route.
Venous blood was taken at 5, 10, 15 and 20 minutes post
lidocaine administration. Sampling procedure required aspiration of
0.5ml blood from the cannula to exclude dead space, which was then
discarded. The 1ml sample was then withdrawn, stored in a plain
bottle and the cannula flushed with 1ml normal saline.
A 2-minute window was allowed for the taking of blood samples. If
this elapsed, the sample was omitted. For example, if the 10-minute
sample was not taken by twelve-minutes, it was omitted, and the next
sample taken at fifteen-minutes. If a participant had an incomplete set
of samples due to untimely sampling or cannula failure, they remained
within the study and their results were analysed for plasma lidocaine
levels. They were then transferred to [removed for blind peer
review] for preparation, freezing and storage, and then later
transferred to [removed for blind peer review] for
analysis. Analysis was conducted using a validated LC-MS/MS method. The
validation was performed over the lidocaine concentration range 0.5 to
250 ng/mL.
The supplementary cannula was removed at end of case prior to emergence,
unless clinical need suggested otherwise.
The case report form was completed with patient details such as weight
and DOB and procedure details: administered lidocaine dose and
volume, anaesthetic technique and supplementary drugs administered,
intra-operative IV fluid administration, surgical technique including
any endotracheal suction and topical application of adrenaline. We also
recorded any clinical adverse events to include laryngospasm, coughing,
desaturation and evidence of local anaesthetic toxicity.