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June 2024

This issue features contributors from Townsville Hospital in Queensland, and covers journal articles in the paediatric anaesthesia literature published in January and February 2024

Anesthesia Analgesia

Submitted June 2024 by Dr Mark Moll

Read by 188 Journal Watch subscribers

Background:

Childhood obesity is a significant problem. Obesity may alter the pharmacokinetics (PKs) of many medications. Fentanyl is commonly used in paediatric anaesthesia, but there is a paucity in the pharmacokinetics of bolus dose fentanyl data in obese children.

Study:

30 children aged between 2 to 12 years of age, half of whom presented with obesity (defined as >95th percentile body mass index (BMI) for their age and sex) undergoing elective tonsillectomy & adenoidectomy.

After induction, subjects had two intravenous lines placed in two different extremities:
One for medications and IV fluids and one for obtaining blood aliquots for fentanyl concentration analysis. After administration of 1mcg/kg of fentanyl based on total body weight (TBW), blood sample collections for fentanyl concentration analysis were attempted at 5, 15, 30, 60, 90, and 120 minutes.

Population PK analysis to examine the differences between obese and nonobese children was performed and included various body size descriptors, such as TBW, BMI, and fat-free mass (FFM), to examine their influence on model parameters.

Mean fentanyl concentrations at 5 minutes was 0.53 ng/mL for the nonobese group and 0.88 ng/mL for the obese group, a difference of 0.35 ng/mL (95% CI, 0.08–0.61 ng/mL; P = .01).

Population PK analysis showed that FFM was a significant covariate for the central volume of distribution. 1 mcg/kg fentanyl dose based on TBW resulted in approximately a 60% higher peak fentanyl effect site concentration than dosing based on FFM.

A few salient points and confounders need to be mentioned here:
- The primary preoperative indication for the procedure was sleep-disordered breathing, excluded patients who had previously documented hypersensitivity to opioids, preexisting respiratory disease with the exception of sleep disordered breathing, hepatic disease, renal disease, pregnancy, Tanner stages 2 to 5, and chromosomal abnormalities.
- The mean age of the obese cohort was 8.9 years with mean TBW of 38 kg. The mean age of the nonobese cohort was 3.9 years with mean TBW of 15.8 kg.
- No additional doses of fentanyl for the procedure or in the post-anaesthesia care unit.
- Additional opioid and anaesthetic medications were administered at the discretion of the anaesthetist. Additional opioids administered during the case and in the post anaesthesia care unit were tracked and converted to morphine milligram equivalents for analysis.
- Adverse respiratory events requiring bag mask ventilation were concurrently recorded.

Commentry:

Adenotonsillectomy is one of the most common surgeries performed in children. Fentanyl is one of most common analgesics used in these surgeries and there is a well known interplay between children with obesity related co-morbid disease and adverse post operative consequences namely respiratory depression of which opioids have a significant role.

The study has achieved its aim of determining the peak concretions of fentanyl in obese and non-obese children. Finding that at 5 minutes after the bolus dose there is approximately 60% greater concentration. It appears that recommendation dosing of lipophilic drugs like fentanyl have many differing opinions in the literature, some suggesting that dosing based on ideal body weight, total body weight and adjusted body weight being the more common ones. In my opinion this study is useful in the clinical context of choosing a bolus dose of fentanyl in which it is preferential to keep the patient breathing i.e. remain below the apneic threshold threshold as seen in the below figure. This of course comes with the acknowledgement of the confounders: the difference in age between obese and non-obese children and its effect on PK; the change physiology of the respiratory drive system in obesity and how that influences propensity for apnea; and interplay with other medications.

Whilst not a major aim of the study the authors do note some clinical effects of dosing based on TBW—adverse respiratory events requiring bag mask ventilation and additional opioid administration. They note no difference in bag mask ventilation but do note that the non obese children required higher average amount of additional opioids - as represented by morphine milligram equivalents per kilogram - than obese subjects through the procedure and into their recovery time in the post anaesthesia care unit.

This may just indicate that obese children with higher effect site concentrations are just better analgesed due to the higher peak concentrations. There was no mention of comparing non-opioid medications between the two groups, such as ketamine, alpha-2 agonists etc.

The authors concluded that dosing based on FFM was the most likely to not “overshoot” goal analgesic concentrations. One of the major problems is that the calculation of FFM is not a common calculation and requires the input of many variables limiting its use in clinical anaesthesia.

The authors rightly conclude that more research into this topic to develop FFM based calculations and protocols to bolus dose fentanyl in the obese child.

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Pediatric Anesthesia

Submitted June 2024 by Dr Laura Panizza

Read by 87 Journal Watch subscribers

Summary:

This study by Jock et al assessed the effect of intraoperative cerebral oxygen desaturation on postoperative cerebral oxygen metabolism in neonates and infants undergoing non-cardiac surgery (1). It is a prospective single-centre pilot study from Germany and was published in Pediatric Anesthesia in 2024.

Thirty-seven neonates and infants undergoing general anaesthesia for greater than 30 minutes and necessitating invasive arterial blood pressure monitoring were enrolled. A non-invasive device called Oxygen-to-See (O2C), which combines laser Doppler flowmetry and white-light spectrometry, was placed over the right forehead to continuously measure regional blood flow. Cerebral fractional tissue oxygen extraction (cFTOE) and approximated cerebral metabolic rate of oxygen (aCMRO2) were derived from this and used as markers for cerebral oxygen metabolism. Monitoring occurred from prior to induction until one hour postoperatively.

Seventeen (46%) of the 37 neonates and infants had regional cerebral oxygen desaturation of below 20% of their baseline – this group was defined as the event group. cFTOE and aCMRO2 were significantly higher and cerebral regional oxygen saturation was significantly lower post-operatively in the event group as compared with the non-event group.

Commentary:

We already know cerebral oxygen desaturation occurs in neonatal and infant anaesthesia. An international multicentre observational study used near-infrared spectroscopy (NIRS) to measure regional cerebral oxygenation and reported incidences of mild (11-20% below baseline), moderate (21-30% below baseline), and severe (greater than 30% below baseline) intraoperative cerebral deoxygenation of 43%, 11%, and 2% respectively in infants aged less than 6 months.2 Jock et al’s article is the first to describe the effect of intraoperative cerebral oxygen desaturations on postoperative cerebral oxygen metabolism in noncardiac paediatric surgical patients, although similar studies have been performed in paediatric cardiac surgery.

Jock et al suggest that an increased aCMRO2 could indicate an increased cerebral oxidative energy metabolism due to repair processes. They found even short moderate cerebral desaturations were associated with higher postoperative cFTOE and aCMRO2 values. Although this study purports cFTOE and aCMRO2 as possible indicators for poor neurological outcome, the more tangible outcome of post-operative neurological function was not measured. The authors did not measure cerebral oxygenation beyond one hour postoperatively so could not comment at which point cerebral oxygenation returns to baseline, although studies in paediatric cardiac surgery have shown a normalisation after 24-48 hours. (3,4)

All patients were ASA 3 and 4, which is likely why there was a higher proportion of patients with intraoperative cerebral deoxygenation below 20% of baseline than Olbrecht et al (2). It is unclear if these results should be extrapolated to our ASA 1 and 2 neonates and infants. The event group had patients who were younger, had lower body weight, and had a higher proportion of thoracic surgery, and although these differences were not statistically significant they may be considered clinically significant by paediatric anaesthetists.

The authors did not postulate what caused cerebral oxygen desaturation, although they did measure some potential contributors including arterial oxygen saturation, arterial partial pressure of carbon dioxide (PaCO2), blood pressure, and temperature. Haemoglobin, anaesthetic medications, and depth of anaesthesia were not documented in this study. Cerebral desaturations were associated with lower arterial pressures, suggesting that adequate blood pressure should be maintained intraoperatively. There remains however a lack of a consensus definition for intraoperative hypotension in paediatric anaesthesia. NIRS and O2C may become useful in determining target blood pressures in neonates and infants in future. The study did not analyse the effect of hyperventilation on cerebral desaturation.

In summary, Jock et al have concluded that cerebral oxygen desaturation during major surgery in ASA 3 and 4 neonates and infants is associated with early postoperative increased cerebral oxygen extraction and possibly increased cerebral oxygen metabolism, which could indicate an elevated oxidative energy metabolism in the “stressed” brain.

References:

1. Jock A, Neunhoeffer F, Rorden A, et al. The effect of intraoperative cerebral oxygen desaturations on postoperative cerebral oxygen metabolism in neonates and infants a pilot study. Pediatr Anesth. 2024;34:138-144.
2. Olbrecht VA, Skowno J, Marchesini V, et al. An international, multicenter, observational study of cerebral oxygenation during infant and neonatal anesthesia. Anesthesiol. 2018;128(1):85-96.
3. Neunhoeffer F, Michel J, Nehls W, et al. Perioperative Assessment of cerebral oxygen metabolism in infants with functionally univentricular hearts undergoing the bidirectional cavopulmonary connection. Pediatr Crit Care Med. 2019;20(10):923-930.
4. Neunhoeffer F, Hofbeck M, Schlensak C, Schuhmann MU, Michel J. Perioperative cerebral oxygenation metabolism in neonates with hypoplastic left heart syndrome or transposition of the great arteries. Pediatr Cardiol. 2018;39(8):1681-1687.

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A randomized controlled trial

Pediatric Anesthesia

Submitted June 2024 by Dr Jon Stacey

Read by 422 Journal Watch subscribers

Augmented Outcomes or Virtual Benefits?

Prior to a more thorough discussion, and for those with limited time, it must first be noted that the text of the abstract and that of the manuscript’s main body are in direct contradiction (see Letter to the Editor: https://doi.org/10.1111/pan.14853)

Recognising the frequency and deleterious effects of perioperative anxiety and distress, Chamberland et al sought to investigate the possible benefits of augmented reality (AR) in the preoperative setting.

Their introduction provides a helpful oversight as to the key differences between augmented and virtual reality (VR).

In a single-centre prospective randomised controlled trial, the authors randomised healthy children over five years of age undergoing elective day case surgery, with a sample size based on pre-existing studies of the use of virtual reality in preoperative anxiety.

‘Standard care’ in the control group involved the child and parents being admitted first to a day surgery waiting room, and then the operating room (OR) waiting room, from whence the child (not parents) was taken to the OR by the anaesthetist. Music, video games and tablets were not allowed in the OR.

Children in the intervention arm followed the same trajectory, but were provided with augmented reality through Microsoft HoloLens2 glasses in the day surgery waiting room. Two virtual ‘avatars’ then guided the children through a variety of breathing, relaxation and motivational exercises. The longest was of 16 minutes, in the day surgery waiting room, followed by shorter exercises in both the OR waiting room and immediately prior to induction. The minimum time required to complete the intervention prior to entry to the OR was 20 minutes.

Pre-medication was used in neither group.

Pre-operative anxiety, as measured by the short form of the modified Yale Preoperative Scale (mYPAS-SF) was measured by a blinded research assistant at the time of admission (T0) and by the unblinded anaesthetist at the time of induction (T1). Patient satisfaction was also crudely measured. Analysis was per protocol, rather than by intention-to-treat.

The 37 patients who completed the augmented reality protocol had significantly lower anxiety scores at the time of induction (median difference [95%CI]: 6.3 [0-10.4], p = 0.01) than the 64 patients of the control arm.

Although the median in both groups was less than the accepted threshold (mYPAS-SF > 30), more children in the control group manifested significant anxiety at induction than in the AR group (risk ratio [95% CI]: 2.7 [1.2-5.9], p = 0.01).

Reported satisfaction in the AR group was high, with no complaints of cybersickness, despite an average wear time of 51 minutes (much longer than VR headsets have been tolerated in previous studies).

In their discussion, the authors accept that they were not able to dissociate the relative contributions of the relaxation techniques themselves and the AR technology through which these were delivered, and resource limitations around the use of headsets.

So what to make of this?
1. The control group represents standard Antipodean practice neither in terms of parental presence nor the acceptance of devices in the OR.
2. Of 64 patients randomised, 23 failed to complete the AR intervention, whether due to hardware malfunction (4), headset removal (9), or change in OR scheduling (10). Analysis by intention-to-treat would have been more revealing, without which it is hard to share the authors’ enthusiastic conclusions.
3. A number of children in both groups demonstrated significant preoperative anxiety as manifest by a mYPAS-SF score of >30. It remains incumbent on all those looking after children to consider how best to mitigate anxiety and distress at each stage of the perioperative journey. On this note, would recommend the work of the EPIC (Effective Peri-procedural Communication) group (epickids.org.au).

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Pediatric Anesthesia

Submitted June 2024 by Dr Andrew Chazan

Read by 266 Journal Watch subscribers

This short ‘perspectives essay’ is aimed at getting anaesthetists to reconsider the routine use of nitrous oxide in mask induction of anaesthesia. The points raised in the article include:

1. Greater time until desaturation in the event of laryngospasm if 100% oxygen is used rather than high concentration N20.
2. Turning the nitrous oxide off as soon as the child is asleep does not guarantee that you will achieve full preoxygenation before a potential laryngospasm event (as washout may take one or two minutes and laryngospasm may occur at any point)
3. Potential impacts of chronic N20 exposure on staff and also definite impacts on the environment, which could be significantly reduced by not routinely using N20 at induction
4. Nitrous oxide use does not guarantee a pleasant/ non traumatic induction in a child and there are many other techniques that can be used to increase the likelihood of a pleasant experience.
5. There is no accepted guidelines on how long one should use high concentration N20 before introducing volatile and some anaesthetists potentially add sevoflurane before euphoria has occurred, negating the potential benefit.
6. The notion that N20 will help speed up induction due to second gas effect is potentially flawed. The main studies looking at this phenomenon reportedly involved using halothane +/- N2O in adult patients. Anaesthesia of small children with sevoflurane is a different pharmacological and physiological scenario.

The article concludes with: “why should we continue a practice which is less safe for children, potentially harmful to ourselves and assuredly more harmful to the atmosphere- without any evidence of benefit to our patients?”

Take home messages/commentary:
I found this to be a very interesting and topical read and it has made me reconsider my practice. I feel that a better title to the article might be “It is time to reconsider the need for N20 in pediatric mask induction” as I suspect there are some occasions where it may still have a role to play. There can be no denying that N20 is harmful for the environment, it is also logical that desaturation will be more rapid if high concentration N20 has been used rather than 100% oxygen in the case of a lost airway (though the degree and relevance will be patient and scenario specific). What will continue to be debated is how much more or less likely the induction is to be peaceful if N20 is used vs if it is not used. A study specifically looking at this would be very useful to add weight to the argument made in this article. There are many other strategies that we can employ to increase the likelihood of peaceful induction other than the routine use of N20.

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A prospective randomized controlled trial

Anaesthesia Critical Care & Pain Medicine

Submitted February 2024 by Dr Priya Sreedharan

Read by 139 Journal Watch subscribers

This prospective, randomised, double-blinded study was conducted at the University hospital of Ostrava in the Czech Republic. The study hypothesized that optimizing the depth of general anaesthesia using BIS as a guide (BIGA) could reduce the incidence of Emergence Delirium (ED) in the high-risk paediatric population (pre-school children, sevoflurane anaesthesia, otolaryngology procedure) compared with the traditional assessment of anaesthetic depth using MAC value.

165 children with ASA I- II undergoing endoscopic adenoidectomy under general anaesthesia were included in the study over a period of 1 year and were randomised into the BIGA or the non- BIGA group. Preoperative anxiolysis was provided with 0.5 mg/kg of midazolam, and preoperative anxiety was assessed by the modified Yale Preoperative anxiety scale (mYPAS).

All children received volatile induction with sevoflurane 8% in oxygen and air (1:1) mixture. Depth of anaesthesia was monitored with ET sevoflurane and BIS applied in the intervention group as soon as possible. Sufentanil 0.2 ug/kg and paracetamol 15 mg/kg was provided and LMA placed after the intravenous cannula was secured.
The intervention group had the BIS targeted at 40-60 by titrating the sevoflurane whilst the control group had sevoflurane maintained at MAC value 1-1.2. The airway was removed awake in theatre prior to PACU transfer.

The PAED score was used to assess ED in PACU, with scores more than 10 used to quantify significant ED. Only in cases of severe ED, as judged by the PACU physician, pharmacological treatment was provided with propofol 1 mg/kg or dexmedetomedine 0.5 ug/kg.

This study observed an incidence of ED of 35.1% in the control (non BIGA) group and 12.8% in the intervention (BIGA) group, which was statistically significant. Overall, children in the intervention group had lower PAED scores throughout the PACU stay. However, no significant differences between the groups were found in the incidence of pharmacological intervention in the treatment of severe ED or indeed the duration of the PACU stay.

They concluded that BIS guided anaesthesia depth maintenance during volatile anaesthetic in children reduces the incidence of ED and that they had a better overall recovery profile.

Take home message:
Incidence of postoperative ED can vary from 10-80% depending on multiple surgical, anaesthetic and patient factors in children. Multiple studies have shown that intravenous anaesthetic techniques using propofol reduce ED in children. This study joins some of the others to try to answer the question as to whether any intervention is helpful to reduce the incidence of ED with volatile anaesthetic technique. Whilst previous studies have not shown a reduction in volatile consumption in children with BIS guided anaesthesia, Han et al also showed a reduction in ED incidence with EEG-parameter-guided volatile anaesthetic depth.

It has been postulated that reduced ET sevoflurane concentrations both at maintenance and emergence contribute to reduced ED, although the exact mechanism is unclear.

However, the value is of this study is arguable, considering that the need for pharmacological intervention in both groups was the same, i.e. the incidence of severe ED was not different between the two groups. PAED score is a subjective assessment of ED and this can lead to variability in the scoring of individual patients. Furthermore, hypoactive ED, recently described by Lee-Archer et al, cannot be assessed by standard ED scales.

Non- pharmacological interventions remain the mainstay of both prevention and treatment of ED in high-risk children with pharmacological therapy reserved for the severe cases only. Monitoring anaesthetic depth using BIS guided parameters may assist in reducing incidence of ED.

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Pediatric Anesthesia

Submitted January 2024 by Dr Sorcha Evans

Read by 128 Journal Watch subscribers

This single centre prospective randomised study in Egypt looked at the use of USS measurements of the transverse cricoid distance (TCD) and the epiphyseal diameter of the distal radius to predict the best fit size endotracheal tubes (ETT) in paediatric patients. This was compared to traditional methods of aged-based formulas.

The incentive for this study was the frequency of paediatric ETT exchanges in children based on aged-based formulas and the concern regarding morbidity associated with it.

The study included 100 children aged 1 – 6 years, ASA I-II for elective surgery, that did not have previous upper airway surgery or malformations, respiratory infections or anticipated difficult airway. The groups were allocated to cuff vs uncuffed ETT. Several steps occurred following this;

1. Preoperative ETT size estimated based on aged-based formulae.
2. A standardised induction protocol was followed including muscle paralysis.
3. TCD measurement was then performed during apnoea.
4. USS measurement of the epiphyseal diameter of the distal radius.
5. ETT was selected for insertion in accordance with TCD measurement and corresponding outer diameter (OD) of ETT.
6. The ETT was assessed whether it was best fit ETT, defined as an uncuffed or deflated cuffed ETT that had a leak detected at inflation pressures of 10-20 cmH20. The ETT was changed accordingly if it was not best fit.

The primary end point was the agreement between the TCD based ETT size and best fit ETT. The agreement rate was 88% and 90% for cuffed and uncuffed ETT. This was associated with ETT exchanges in 12% and 10% for cuffed and uncuffed group and was deemed non-significant.

Additionally, correlation was assessed between best fit ETT and the ETT chosen based on the two USS methods and that based on the aged-based formulas. A higher degree of positive correlation was reported using USS techniques versus traditional methods.

Points for consideration
1. TCD predicts outer diameter rather than inner diameter. Thus, meaning choosing an ETT would be dependent on the brand ETT used and less standardised. If only one brand of ETT is being utilised in an institution this would be preferable, but with recurrent issues in receiving consistent stock, this may be a challenge.
2. Delay in intubating to measure TCD may not be appropriate depending on the child and the emerging situation during induction. TCD can be over or under-estimated depending on the angle, thus it is recommended to use the mean of 3 measurements, which could contribute to further delays. Adding to this would be the initial learning curve associated with this technique and the availability of USS dependent on the institution.
3. The radial epiphyseal measurement is reported in the study as difficult and time consuming. However, this could be performed on an awake child allowing pre-planning. This also may be a better technique than TCD in paediatric patients that are obese or have short necks.
4. The methodology of not inflating the cuff on the cuffed ETT, does not coincide with what I would believe would be most anaesthetists practice. The reason for the cuff is to reduce potential leaks and thus ETT exchanges and concerns associated with this.
5. USS measurements of TCD and the epiphyseal diameter of the distal radius measurement may be useful in the planning of complex airway management. For example, to calculate the maximum ETT size feasible for single lung isolation using a foley catheter.

Take home message
This is an interesting paper, describing USS techniques to size ETTs in paediatric patients. This demonstrates potential and may have a role in preoperative planning for select patients. However, this will not influence my current routine practice in utilising aged based formulaes and microcuff ETTs.

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Journal Watch is a community of SPANZA members who work to identify and review articles of interest in the paediatric anaesthesia literature.


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