Discussion/Analysis
Our study has demonstrated that 5mg/kg dosing of lidocaine for airway
topicalisation in paediatric airway endoscopy is safe. We had no
incidences of clinical adverse events, symptoms of local anaesthetic
toxicity and maintained good surgical conditions for the required
procedure. This qualitative data supports the safety profile of this
pilot study.
Our study primary outcome achieved significant results. We successfully
demonstrated a quadratic correlation between higher peak lidocaine
plasma levels and ages <18 months (p=0.00973) as shown in
Figure 2. Previous studies have demonstrated similar findings with
younger patients achieving higher peak lidocaine plasma levels. In 1978
Eyres et al found higher peak lignocaine plasma levels following topical
application to mucous membranes in children under 3 years old, with
those under 1 year occurring earliest at 2 minutes5.
The median time to peak lidocaine plasma level in our study was found to
be 10 minutes as demonstrated in Table 1. This is significantly longer
than the 2 minutes demonstrated in 19785. Whilst we
did not record the average length of the surgical procedures, our
lidocaine plasma levels would most likely peak during the surgical
procedure or following completion of the endoscopy in the recovery room.
In 1983 Eyres et al repeated their 1978 study and again showed a
variation in the time to peak level in different age groups2,5. In children less than 1 year of age the time to
peak lignocaine plasma level was 5.8 minutes, increasing to 6.5 minutes
between 1-3 years, and over 10 minutes in the 5 plus group. We did not
demonstrate a significant relationship between age and time to peak
lidocaine plasma level as our secondary outcome measure.
Whilst our covariates for patients’ with smaller weights achieving
higher peak lidocaine plasma levels did not reach significance level
(p=0.0516), it suggests an area for further review whilst supporting the
safety profile of this pilot study. Figure 3 illustrates a trend for
higher peak plasma lidocaine levels in patients weighing between 10 and
12kg. This correlates well with ages up to 18 months as shown in Figure
1. Extremes of weight are a known risk factor for local anaesthetic
toxicity. Many previous studies2,5 have focused on age
of patients rather than weight. Sitbon1 et al altered
the dose administered dependent on weight as well as age. The dosing
used was much smaller (0.9 and 2.6 mg/kg) with corresponding lower
maximum peak levels of 1.05 mcg/ml. They concluded that younger children
less than 6 months old did not present with peak levels earlier,
although they did not analyse the relationship of weight versus
lidocaine levels in more detail.
Our study cohort did not have extreme outliers regarding weight for age
as indicated by Figure 1. As an urban tertiary paediatric hospital, our
results can therefore reliably be extrapolated to a wider paediatric
population ensuring the external validity of the study.
In 2016 Roberts and Gildersleve aimed to review practice amongst
paediatric anaesthetists regarding their use of topical
lignocaine4. As demonstrated in our study, variation
in the dose of lidocaine was recognised with a range of 1-10 mg/kg
(median dose 4 mg/kg). Amongst the respondents the most commonly
documented dose was 3mg/kg as per the British National Formulary for
Children10. In our study anaesthetic participants did
not alter their usual practice. The median dose at [removed for blind
peer review] was 5mg/kg. Despite this no significant adverse effects
were recorded. Roberts and Gildersleve did note some respondents using
significantly higher doses in line with adult bronchoscopy practice.
Previous rationale for this was that some of the lidocaine would be
suctioned by the surgeons or swallowed. We found no change in plasma
lidocaine levels with the use of surgical suction, topical
vasoconstrictors or by surgical procedure group.
An interesting and significant result from this study is shown in Figure
4. We demonstrated higher peak plasma lidocaine levels when utilising
total dose volumes between 2 and 3mls of 2% lidocaine local anaesthetic
(p=0.0352) when compared with volumes less than 2mls. The relationship
between volume and time to peak lidocaine plasma levels however was not
significant (p=0.68). This would suggest higher concentrations of local
anaesthetic solution at lower total dose volumes could achieve a better
safety profile. However whether this would affect surgical conditions or
lead to clinical adverse effects would be an area for investigation in a
larger future study.
A non-significant, but noteworthy result from this pilot study was the
reduced IQR variation of peak plasma lidocaine levels when lidocaine
dosing was <5mg/kg. With dosing <5mg/kg we again
demonstrated no occurrences of clinical adverse events, signs of local
anaesthetic (LA) toxicity or compromise of surgical conditions.
Most importantly, despite four patients exceeding recommended toxic
levels of >5000ng/ml, no symptoms of LA toxicity or
clinical adverse effects occurred. It is therefore possible differing
toxic levels exist for mucosal application versus intravenous
application of LA agents. Studies have previously failed to show
clinical signs of toxicity in anaesthetised adults with serum lidocaine
levels over 5000ng/ml2,7. One theory is some
protection is offered by general anaesthesia8. Further
research is needed to extrapolate this to the paediatric population.
Pharmacological research has shown extremes of age including neonates
and infants are at greatest risk of LA toxicity9. This
age group have reduced plasma concentration of the proteins that bind
the anaesthetic agents (alpha1- acid glycoprotein). The unbound portion
undergoes metabolism and determines toxicity.
A limitation of our study was not standardising the dose and volume of
lidocaine used. As this was a pilot study with an aim to avoid changes
in usual practice variations were expected. The small sample size is
acknowledged but felt to be adequate to allow relationships between
outcomes and variables to be analysed. Further studies with larger
samples sizes are planned.