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.