Comparison of Nasopharyngeal and Lower Oesophageal Temperatures Under General Anaesthesia With an Endotracheal Tube With Leak
Phase: NA
Conditions: Child
Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust

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CLINICAL STUDY PROTOCOL 
 
R&D registration number = 14SG04 
 
Title 
Correlation of nasopharyngeal and lower oesophageal temperatures in children ventilated 
with an endotracheal tube with leak  
Purpose 
Non-commercial study to find agreement between methods 
Study investigators 
Dr Emily Haberman – Locum Consultant, Great Ormond Street Hospital Department of 
Anaesthesia 
Phone: 07890549924 
Email: Emily.Haberman@gosh.nhs.uk 
 
 
-  
Dr Aarjan Snoek – Research Fellow, Great Ormond Street Hospital Department of 
Anaesthesia  
Phone: 07910716106 
Email: Aarjan.Snoek@gosh.nhs.uk 

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Background 
During surgery under general anaesthesia a patient tends to cool down due to radiation, 
convection, evaporation and conduction (1). Under anaesthesia a patient loses their ability to 
regulate their own body temperature and solely relies on the anaesthetist to control their 
temperature with warming and cooling devices. Perioperative hypothermia is known to cause 
multiple complications such as surgical wound infection, coagulopathy, prolonged drug 
metabolism, shivering and increased oxygen consumption, all of which can affect patient 
outcome (2). However, hyperthermia in children also comes with risks such as febrile 
seizures or increased metabolic activity, so it is important to find a balance of maintaining 
normothermia (36.5˚C to 37.5˚C) accurately. In order to achieve this, temperature is routinely 
monitored under anaesthesia. NICE guidelines (3) recommend that temperature be monitored 
at least every 30 minutes. Continuous temperature monitoring devices such as those based on 
a thermistor design are commonly placed by anaesthetists, and indeed anaesthetic machines 
are routinely equipped to be compatible with this technology. NICE also recommends that 
when using a device to measure temperature, anaesthetists should be aware of adjustments 
that may need to be made to estimate core temperature from recorded temperature. Different 
sites of temperature measurement correlate to varying degrees with actual core temperature. 
Measuring core temperature in the patient's heart is the gold standard upon which to base 
decisions regarding temperature management, but measurement is invasive with a risk of 
complications (4) and is thus inappropriate in the vast majority of cases. Therefore alternative 
sites are generally used as surrogates of core temperature and it is important to identify a site 
that precisely reflects temperature of the core. 
 
Oesophageal temperature accurately reflects core temperature (5) when a probe is positioned 
in the lower oesophagus (excluding open heart or lung surgery). However, the position of this 
probe must accurately be in the lower third of the oesophagus, lest a higher location is 
influenced by the cooler tracheal temperature (6-9). Compared to an adult, the short distance 
between the stomach, lower and middle oesophagus in a child makes reliable placement 
challenging.  In order to achieve the precise placement of oesophageal temperature probes in 
adults and children, some formulas (10, 11) have been devised with varying success but none 
is perfect and accurate oesophageal temperature probe placement remains elusive, limiting 
the usefulness of the site.  
 
The nasopharynx receives a good blood supply via the external carotid artery and therefore 
could correlate well with core temperature.  The nasopharyngeal temperature probe confers 
the advantage of simplicity of placement compared to its oesophageal counterpart. The value 
of nasopharyngeal temperature’s correlation with that of the core is generally regarded as 
accurate (12-14) in adults. In children undergoing anaesthesia often uncuffed endotracheal 
tubes are utilized, as historically in paediatric anaesthesia there have been concerns about 
subglottic stenosis and postoperative stridor (15) but to date there is no evidence that newer 
Microcuff®  tubes are any less safe in children than uncuffed tubes (19). The use of uncuffed 
tubes is in direct contrast to adults, in whom cuffed endotracheal tubes are placed by 
anaesthetists. In the paediatric population very little evidence exists, although in small, poor 
quality trials findings are favourable for nasopharyngeal temperature comparisons to core 
(16). When a patient is ventilated during general anaesthesia, a humidity and moisture 
exchange filter (HMEF) assists in warming inspired gases administered from an anaesthetic 
machine, but does so incompletely (not achieving body temperature). With an uncuffed 

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endotracheal tube an escape of ventilated gases from the trachea upwards towards the mouth 
and nose occurs via the nasopharynx. With a temperature that is lower than body temperature, 
even at low flows, (17) these gases could possibly have a cooling effect on temperature in the 
nasopharynx (18). The question remains, thus, whether or not nasopharyngeal temperature is 
influenced by the cooling effects of these escaped gases or not.  
 
Study objectives 
 
This study will seek to find an agreement of methods (lower oesophageal and nasopharyngeal 
sites) to measure temperature in children undergoing general anaesthesia with an 
endotracheal tube that has a leak. This is an important question to answer because it is not 
known whether or not oesophageal and nasopharyngeal temperatures correlate in children 
ventilated with an uncuffed endotracheal tube, and would allow clinicians to confidently use 
the more feasible nasopharyngeal temperature probes if this were the case. 
Study Design 
 
Prospective, unblinded, cross-sectional (observational) agreement study 
Approval will be obtained from the Research Ethics Committee 
Written parental informed consent will be obtained prior to investigation. Parents will be 
informed of their right to withdraw at any stage of the trial without compromising their 
clinical care.  
Inclusion criteria 
Age: 8 months to 7 years 
Patient requires general anaesthesia with endotracheal intubation for a procedure assisted by 
radiography (e.g. line insertion, line change)  
Patient requires chest radiograph for procedure 
Expected anaesthetic time more than 30 minutes 

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Exclusion criteria 
No written parental written consent  
Known oesophageal pathology (e.g. tracheo-oesophageal fistula, oesophageal strictures, 
oesophageal varices, oesophageal atresia) 
Known base of skull or midface fractures 
Previous gastric bypass surgery or nasal surgery 
Known coagulopathy  
Previous alkaline ingestion 
High aspiration risk 
Significant respiratory co-morbidity requiring anticipated peak airway pressures > 25 cmH2O 
ASA 4 – 5 
Tracheostomy in situ 
Severe sepsis or septic shock or other other condition (such as bronchopulmonary fistula) that 
precludes use of tidal volume ventilation over 7 ml/kg 
Known airway abnormalities (e.g. subglottic stenosis) that preclude placement of a 
MicroCuff® endotracheal tube 
Oesophageal or nasopharyngeal probe contraindicated for reasons related to surgery / 
procedure  
 
Feasibility of study/ number of patients 
Statistical advice and analysis has been sought from the Great Ormond Street Hospital/ 
Institute for Child Health (ICH) statistical support team. 100 patients would suffice to be able 
to estimate agreement between methods, giving a 95% CI about +/- (0.34 x standard 
deviation).  
At GOSH approximately 1500 radiography-assisted procedures are performed on children 
annually. Of these it is estimated that about 1000 are performed on children between the ages 
of 8 months and 7 years old. Of these it is anticipated that about 750 would meet inclusion 
criteria without exclusion criteria, meaning that this study would be suitable for a single 
centre (GOSH). 

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Patient management and intervention 
Patient management for general anaesthesia will continue according to usual paediatric 
anaesthetic standards. Anaesthesia will be induced by an intravenous or inhalational method. 
After administration of muscle relaxant, the patient will be intubated with a cuffed 
MicroCuff® endotracheal tube, which has been shown to be safe in children (19) and is even 
recommended by some experts as superior to an uncuffed endotracheal tube (20). 
The size of the low-pressure, high-volume endotracheal tube shall be determined according to 
manufacturer’s instructions (21). The anaesthetist will confirm the presence of an audible 
leak at <15 cmH2O pressure as is typical in paediatric anaesthesia, and in the unlikely event 
that this does not exist then the endotracheal tube will be changed to one size smaller. Once a 
leak has been confirmed the cuff of the endotracheal tube will be inflated under guidance of a 
cuff manometer. The in-built ventilator’s spirometric equipment will be used to measure 
expired tidal volumes and these will later be compared to set inspired volume to calculate the 
leak during cuff deflation.  
An oesophageal and nasopharyngeal temperature probe will be inserted prior to 
commencement of the actual procedure (after anaesthesia has been established). The insertion 
depth of the nasopharyngeal probe will be estimated by a formula previously described (9): 
Length (cm) = (distance from tragus to nostril) – 2          
This length will then be adjusted at the discretion of the operator inserting the probe in order 
to achieve the level of the posterior border of the soft palate (position confirmed with 
laryngoscope). 
The oesophageal probe will initially be inserted to a depth determined by a formula slightly 
adjusted from a previously described method to calculate the distance to the lower 
oesophageal sphincter in children (22): 
 
Length (cm) = (0.226 x height)   + 5 
Once the initial radiograph has been taken (timing of which shall be dictated by the surgical 
team as this radiograph will assist with the procedure), the intervertebral space between the 
8th and 9th thoracic vertebrae will be identified and the distance between the end of the 
oesophageal probe and this landmark will be measured. The position of the end of the 
temperature probe will be adjusted to the level of T8/ T9, which corresponds to the lower 
third of the oesophagus.  
The anaesthetic gas mixture flow will be set at 2L /min in order to standardize the flow of this 
potentially cooling factor between patients. The anaesthetist will set the ventilator mode to 
volume control ventilation (VCV) without leak compensation with a Peak End Expiratory 
Pressure (PEEP) of 5 and a tidal volume of 7 – 9 ml/kg. The inspiratory: expiratory (I:E) ratio 
will be set to 1:2. Approximately 1 minute following satisfactory positioning of the 
temperature probe, the temperature of the oesophageal and nasopharyngeal probes will be 
recorded over a period of 20 breath cycles (approximately 1 minute), while the ventilator’s 

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spirometric equipment will be utilized to measure expired tidal volume and peak airway 
pressure.. 
The endotracheal tube cuff will now be deflated to allow an anaesthetic gas leak, thus 
simulating the use of an uncuffed endotracheal tube. The volume of air in the cuff will be 
adjusted by the anaesthetist to achieve a clinically soft audible leak (whilst on the ventilator). 
Temperature and spirometry measurements will recommence approximately 1 minute 
hereafter (simulating an uncuffed endotracheal tube scenario), again over a period of 20 
breath cycles. Once this is completed the anaesthetist will use their discretion whether or not 
they wish to fully re-inflate (with cuff manometry) the endotracheal tube cuff or not for the 
remainder of the procedure.  
As is usual during anaesthesia, standard body warming measures (aiming for normothermia) 
will be taken, guided by the measured temperatures.   
  
Data collection 
The following data will be collected: 
Demographics – including date of procedure, date of birth, age, height, ASA status 
Initial distance that oesophageal probe is inserted, based on formula described above 
Distance of oesophageal probe tip away from T8/T9 intervertebral space 
Temperature of nasopharyngeal probe at a point approximately 1 minute after satisfactory 
positioning at T8/T9 level and again 1 minute after cuff deflation to a clinically soft audible 
leak 
During the periods of cuff inflation as well as cuff deflation, inspired and expired tidal 
volumes will be measured by spirometry over a 20 breath cycle, and these will later be used 
to calculate Fractional volume loss (FVL).  
Ventilator settings including I:E ratio, PEEP, Peak AirWay Pressure (PAWP) 
Distance of nasopharyngeal probe insertion 
Complications of nasopharyngeal probe insertion (bleeding, failure) 
Complications of oesophageal probe insertion (failure) 
Cuff pressure utilized 

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Duration of study 
It is estimated that about 1000 radiography-assisted procedures are performed annually on 
children between the ages of 8 months and 7 years old at GOSH. Of these, it is anticipated 
that about 750 would meet inclusion criteria without exclusion criteria. If a parental consent 
rate of 50% is achieved, then the study would estimate to run for 6 months (allowing for 40% 
of patients missed due to researcher unavailability) in order to recruit 100 patients. 
Risks of study 
Recruitment of patients will include only those who would anyway have received an 
endotracheal tube for anaesthesia (as opposed to an alternative anaesthetic airway such as a 
supraglottic airway device). The study population will be those children undergoing a 
procedure that requires radiography (e.g line insertion) ie there is a need for X-rays for 
surgical reasons. These X-rays will simultaneously be used to confirm optimal oesophageal 
probe position, and no radiation risk will be added for probe X-ray. Position will initially 
have been estimated with a formula and adjusted according to radiograph. 
It is usual in anaesthesia to measure temperature intraoperatively, and common practice is to 
use a nasopharyngeal (23) or oesophageal probe when anaesthesia is expected to last longer 
than 30 minutes (24). As nasopharyngeal and oesophageal temperature probes are commonly 
inserted during general anaesthesia (25-27), practice will be little changed from standard 
during this study. Children will be recruited if they are expected to undergo anaesthesia for 
greater than 30 minutes. Insertion of an oesophageal temperature probe as well as a 
nasopharyngeal probe is expected to add only 1 minute to total anaesthetic time, meaning that 
the child will be kept asleep only fractionally longer than would otherwise have been the case 
if they were not recruited into the study. This short prolongation of anaesthesia will not have 
any significant clinical effects. 
The insertion of a nasopharyngeal temperature probe can cause nasal bleeding (28) but this is 
self-limiting in the overwhelming majority of cases. Those with a known coagulopathy will 
not be recruited into this study due to risk of nasal bleeding. Failure to insert a 
nasopharyngeal probe can occasionally occur, for example due to previous nasal trauma, in 
which case success in the other nare is usually possible. Very rarely will a nasopharyngeal 
probe be unable to be inserted in both nares, in which case recruitment of the patient into the 
study will be abandoned. There is a possibility that the nasopharyngeal probe will be placed 
too deep, reaching the mouth. In this case, there is a possibility that ambient temperature may 
reduce the recorded temperature, causing inaccuracy. This risk will be minimized by the 
insertion of the temperature probe being done by the researchers, aiming to insert the probe’s 
end to the level of the posterior border of the soft palate (under laryngoscopic view after 
estimating depth required by formula). Very rarely have other complications occurred with 
nasopharyngeal probes, including one case report relating to too deep insertion of 
nasopharyngeal probe during surgery on the oesophagus (29) and a report on defective 
nasopharyngeal probes (30), both scenarios of which are highly unlikely to be relevant in our 
proposed study. 

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The insertion of the oesophageal probe is a safe procedure, with very few side-effects 
reported in the literature. Rarely has an oesophageal temperature probe been inadvertently 
inserted intratracheally (31). If this were to occur, early diagnosis would be possible due to 
accompanying radiography, noting the probe to cross the carina. Rarely will oesophageal 
probe insertion fail, in which case recruitment into the study will terminate. 
Statistics and data analysis 
We consider a clinically unacceptable difference as a difference of greater than 0.5˚C 
between methods. 
The study recruitment rate will be assessed by recording patients successfully entered into the 
study as well as those for whom parental consent was not achieved. Demographic data will be 
appropriately recorded and analysed in terms of means and medians. Temperature 
measurements with the oesophageal probe will be compared to temperature measurements 
with the nasopharyngeal probe and mean differences, standard deviations, and 95% 
confidence intervals will be calculated and tabulated. Bland-Altman plots of the esophageal-
nasopharyngeal temperature differences will be drawn. Differences will be checked for 
normality. Differences against mean will also be checked for variability (making sure that 
differences do not increase with mean). Linear regression analysis shall be utilized with 
scatter plot diagrams and r values calculated. A paired t-test will be performed to exclude 
systematic bias. Endotracheal leak, as measured by spirometry and fractional volume loss, 
will be measured, analysed and tabulated for means and standard deviations. It is anticipated 
that a clinically audible leak will correspond to a FVL of approximately 12.4 – 29.3% (based 
on data received directly from study author regarding IQR from a previous study (32)) for 
50% of patients. 
After the study has been completed we also plan to do a subgroup analysis for agreement 
between methods on 2 subgroups of patients: (1) those with FVL < 21.1% (2) those with FVL 
> 21.1%. This is in order to determine if there is any potential effect of leak size that might 
affect temperature differences.  
Data handling 
After parental written consent on recruitment, a data form with study number will be used (no 
hospital number or name of patient). Once completed, these patient data forms will be 
securely stored in a filing cabinet in the Anaesthetic office (access to which is controlled by 
GOSH swipe card). Each form will also be scanned and stored into a password-protected 
folder on the GOSH intranet “i drive”.  Patient confidentiality will be ensured at all stages.   

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Study finances & disclosures 
In order to meet the costs of consumables that would not routinely otherwise have been used 
in normal clinical management: 
For oesophaegeal temperature probes: 100 probes would cost £330.70  
For MicroCuff® endotracheal tubes: 100 tubes would cost £600 
The cost for uncuffed Portex tubes that would otherwise have been used anyway is £123 
We expect a possible extra 10% of consumables to be used for patients that might be 
recruited into the trial but are unable to complete the trial. 
Total required =  (110% x £993.70)  -  £123  ≈  £900  
Further savings will also occur due to minimal use of sevoflurane.  
Discussions have taken place within the anaesthetic department (via the clinical lead in 
anaesthesia Dr Scuplak) and funding has been internally arranged. 
No authors shall be remunerated for their efforts and no conflicts of interest are declared.  
Representatives from Covidien and Philips assisted in education of study authors regarding 
recording and retrieving temperature data 
 
Publication plan 
Following the study, the findings will be submitted to journal editors for consideration for 
publication in a peer-reviewed journal. Failing that, submissions will be made to conference 
or congress organisers with a view to present the findings in poster or oral presentation 
format. Raw data will be safely stored so that any potential future investigators can have 
access to this. 

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