COVID and RSV HEADER

COVID and RSV

Cite this article as:
Laura Riddick, Damian Roland and Andrew Tagg. COVID and RSV, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.33694

There was a time, perhaps a century ago, when the only virus we really worried about was RSV. Children, snot dripping from their noses, would come in coughing, and struggling to breath and, as days grew shorter and nights grew longer we knew that bronchiolitis season was upon us once more.

But things have changed. We worry about a different virus now and there is plenty of evidence to show that the usual seasonal variations in RSV have flattened. It was heartening to see the data showing that the mid-winter peak was no more as we kept ourselves to ourselves. Non-pharmacological interventions – physical distancing, respiratory hygiene and restricted movements – meant that the scourge of the paediatric emergemcy department was held at bay. Until…

Half a world away…

Bronchiolitis presentations peaks in June – July in Australia (remember it is our winter in the Southern hemisphere). Last season there was a 98% reduction in RSV (and a 99.4% reduction in cases of influenza (Yeoh et al., 2020). But let’s take a look at the surveillance data from Western Australia to see what has been going on of late.

Western Australia RSV incidence- Based on Foley et al. 2021

McNab et al. (2021) looked to see what had been going on in Victoria, a state that had much stricter lockdown measures than WA. Whilst there was clear suppression of the winter cases of bronchiolitis, these began to increase by the beginning of the year, coinciding with the return to school after the long Christmas break Normally, in February, the Royal Children’s Hospital would return 5.6% positive RSV swabs. In 2021, they returned 32.8%. More worryingly, this peak is higher than the pre-COVID winter peak (30.4%)

RSV incidence in Victoria
Victorian Australia RSV incidence- Based on McNab et al. 2021

But this snapshot doesn’t give you the whole picture. Let’s just slide the data along a few short weeks…

Victorian Australia RSV incidence- Based on McNab et al. 2021

These data have been echoed all over Australia and New Zealand with a ramping up of out of season RSV positive cases. What is most concerning is that numbers appear to be higher than the usual peak and the patients older (mean 18.2 months compared to 7.3 – 12.5 months). Why could this be? It could be, as Foley et al. (2021) suggests due to an increase in RSV-naïve babies born during that first wave coupled with waning herd immunity.

What does this mean for paediatricians in the Northern hemisphere who are about to face this surge in cases?

Getting started?

Paediatricians at the frontline need to be able to see what is going on and so PERUKI will shortly be launching BronchSTART. The aim of this prospective observational study is to both track the potential surge so that health policy is informed as much as possible but also to describe its epidemiology. As highlighted above the data suggests a potentially wider age range and steeper spike but these are from retrospective studies By reporting potential cases (in children under two years of age) presenting to over 50 Emergency Department across the UK, in real-time, clinicians and researchers will be able to really understand the impact and outcomes of this respiratory disease.

Given the challenges of identifying and managing children who may have RSV, COVID-19, or both, some guidelines have been produced by the RCPCH.

What do the guidelines say?

The RCPCH guidelines focus on THREE key areas:-

  • Reducing hospital attendances with mild cases
  • Pathways and guidance for testing and cohorting
  • Minimising patient time on High flow and reducing the exposures to AGPs

The guidelines are designed to reduce potential unnecessary referrals from primary care to the emergency department. Hopefully, reducing the number of children presenting (and then mixing with each other in the waiting room) will lessen the burden on paediatric emergency departments. It offers a traffic light system for reviewing patients, with suggestions of how to manage some borderline cases in the community with secondary care input.

NHS bronchiolitis pathway

When it comes to testing, the aim is to be able to minimise the spread of COVID-19 and protect clinically vulnerable children.  As with what is happening in most hospitals, the recommendation is to only test patients being admitted to the hospital. Any further testing is then influenced by the patient’s condition and the prevalence of COVID in the hospital, as well as cubicle availability.  

Using Point-of-Care-Testing (POCT)/rapid testing for patients going to PICU and HDU may limit cubicle occupancy, and improve cohorting of patients. Additional COVID testing then should be considered in cases where respiratory panels are negative (or suggest low-risk causative organisms such as bocavirus or rhinovirus). Additional testing should also be considered if aerosol-generating procedures (AGPs) are required or parents are displaying symptoms. 

Given that AGPs provide a high risk for transmission, the recommendation is for rapid but weaning of high-flow with guidance provided by north and south Thames retrieval service protocol used.

For those of us in clinical practice, the guidelines remain largely unchanged. Non-pharmacological measures- physical distancing, good respiratory hygiene and use of appropriate PPE are key. Cohorting patients into red and blue, hot and cold or low/high-risk zones may add some value unless physical distancing can be maintained.

As case numbers rise, and cubicle capacity becomes an issue then departments need to come up with a risk mitigation strategy to protect the vulnerable.

  • Weekly testing for all prolonged stays 
  • Test if there are new symptoms 
  • More emphasis on risk assessment for use of RPEs (respiratory protective equipment) 
  • If single room capacity is exceeded, patient may be risk assessed for cohorting 
  • If respiratory virus +ve and COVID –ve patients can be cohorted even if requiring an AGP  
  • We still need to advise those DC’d from CAT/ED with respiratory symptoms of the need for COVID testing via track and trace
  • Parents should not be in hospital if symptomatic. Do not test asymptomatic parents
COVID and RSV flow chart

Bottom line

  • Support community services to reduce strain on hospital services
  • Use testing to help cohort and plan patient care
  • Wean or reduce AGPs where safe to do so
Infographic depicting RSV and COVID guidelines

Selected references

Foley, D.A., Yeoh, D.K., Minney-Smith, C.A., Martin, A.C., Mace, A.O., Sikazwe, C.T., Le, H., Levy, A., Moore, H.C. and Blyth, C.C., 2021. The Interseasonal Resurgence of Respiratory Syncytial Virus in Australian Children Following the Reduction of Coronavirus Disease 2019–Related Public Health Measures. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America.

Huang QS, Wood T, Jelley L, et al. Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand. Nat Commun. 2021;12:1001. https://doi.org/10.1038/s41467-021-21157-9

McNab, S., Do, L.A.H., Clifford, V., Crawford, N.W., Daley, A., Mulholland, K., Cheng, D., South, M., Waller, G., Barr, I. and Wurzel, D., 2021. Changing Epidemiology of Respiratory Syncytial Virus in Australia-delayed re-emergence in Victoria compared to WA/NSW after prolonged lock-down for COVID-19. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America.

Oh, D.Y., Buda, S., Biere, B., Reiche, J., Schlosser, F., Duwe, S., Wedde, M., von Kleist, M., Mielke, M., Wolff, T. and Dürrwald, R., 2021. Trends in respiratory virus circulation following COVID-19-targeted nonpharmaceutical interventions in Germany, January-September 2020: Analysis of national surveillance data. The Lancet Regional Health-Europe6, p.100112.

Public Health England. Weekly national Influenza and COVID19 surveillance report: Week 49 report (up to week 48 data) 3 December 2020. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/940878/Weekly_Flu_and_COVID-19_report_w49.pdf. Accessed July 20, 2021.

Tang, J.W., Bialasiewicz, S., Dwyer, D.E., Dilcher, M., Tellier, R., Taylor, J., Hua, H., Jennings, L., Kok, J., Levy, A. and Smith, D., 2021. Where have all the viruses gone? Disappearance of seasonal respiratory viruses during the COVID-19 pandemic. _Journal of Medical Virology

Waterlow, N.R., Flasche, S., Minter, A. and Eggo, R.M., 2021. Competition between RSV and influenza: Limits of modelling inference from surveillance data. Epidemics35, p.100460.

Williams, T.C., Lyttle, M.D., Cunningham, S., Sinha, I., Swann, O.V., Maxwell-Hodkinson, A. and Roland, D., 2021. Study Pre-protocol for “BronchStart-The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study”. Wellcome Open Research, 6(120), p.120.

Yeoh DK, Foley DA, Minney-Smith CA, et al. The impact of COVID-19 public health measures on detections of influenza and respiratory syncytial virus in children during the 2020 Australian winter. Clin Infect Dis 2020.

Peripheral IV cannulation

miniMAGICal thinking

Cite this article as:
Amanda Ullman, Tricia Kleidon and Elizabeth Andresen. miniMAGICal thinking, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.33480

18-month-old Byron presents to ED with septic arthritis. You know you need to take cultures, so you think you might pop a peripheral intravenous cannula in his antecubital while you’re there – he’ll need intravenous (IV) antibiotics for sure, maybe some fluids. He’s toddler-level chubby, and not exactly compliant.

Time for a deep breath.

Inserting peripheral intravenous catheters (PIVCs) is a core skill in paediatric acute care. We often make a quick decision to insert a PIVC in order to ensure accurate diagnosis and commence important treatments. We often worry about our capacity to insert the PIVC, especially in children like Byron. The vessels can be hard to visualise and palpate, and putting a young child going through a painful procedure can be stressful for all concerned.

But quick decisions have consequences

We know that PIVCs can result in harm. Multiple insertion attempts, extravasations, and infections are all a risk. They often stop working prior to the completion of treatment. PIVCs last only 48 hours, on average, in children and young people. When they fail, we not only pause treatment, but we frequently have to start the process all over again. According to children (and their families) cannulation is the most stressful part of their healthcare experience.

Think carefully about the IV, before it is inserted.

We have an array of IV devices and a variety of places to insert them. In 2020, the Michigan Appropriateness Guide for Intravenous Catheters (miniMAGIC) was published. Its aim was to improve the safe selection of IVs in children across a range of indications. You can read them (open access) here; or download the app for Google or Apple.

In Queensland (Australia) we have developed our first practice targets to improve IV selection, insertion, and securement based on miniMAGIC, and thus reduce IV associated harm. We are currently rolling them out at Queensland Children’s Hospital (Australia). These are:

Paediatric IVC and miniMAGIC

Improving device selection

Peripheral devices (like PIVC or midline catheters) should only be used for peripherally compatible therapies, outside of an emergency or crisis

To ensure safe administration of ‘at risk’ infusates, we consider:

  • Is this PIVC working? Check for good flow prior to administration
  • Is this PIVC optimally placed? Ideally, it should be away from a joint?
  • Are we giving this medication slowly and with enough dilution? Check the Paediatric Injectable Guidelines (PIG)
  • Is this PIVC site visible? It shouldn’t be coverfed up with crepe bandages

We are proactive in our device planning:  

  • If the child needs >2 days of IV therapy, make sure the PIVC is optimally positioned (e.g., in forearm)
  • If the child needs >5 days of IV therapy, consider a midline catheter

STOP and THINK, Make a plan! If this PIVC stops working, do we need to replace it immediately or are there other options? If this child is going to theatre, can we have the device ‘upgraded’?

Peripherally Inserted Central Catheters (PICCs) should not be inserted for antibiotic administration without discussion with the Infectious Diseases team. We use the minimal lumens necessary for treatment (NO just in case PICC/additional lumens).

Improving device insertion

Inserted them away from joints, where possible, looking for visible AND palpable vessels in the forearm. If there is nothing obvious it is time to turn to the trusty ultrasound machine if you have the skills. Even when we place topical anaesthetics, we pop some on the mid-forearm rather than antecubital fossa.

When faced with a child without palpable or visible vessels, don’t have multiple IV insertion attempts. Instead, refer early to an experienced clinician (+/- USG).

Improving device securement

keep the cannula visible, clean and secure
  • Keep it visible: Do not use crepe bandages; use tubular bandages.
  • Keep it clean: Use sterile products
  • Keep it secure: Use two points of securement

Take a look at Henry’s Twelve tips to placing a well secured PIVC.

For Byron, this means we consider the planned duration of intravenous antibiotics, assess his vessels, and our skills. If practical, Byron would have a PIVC inserted in the forearm (most likely via USG) where we can simultaneously take blood cultures. We would also consider an upgrade to midline or PICC, once the cultures and sensitivities are known, providing a better understanding of the actual duration of therapy and targeted antibiotic therapy.

We are evaluating the project, to see its impact on PIVC related morbidity. Based on the impact of MAGIC on adults, this is likely to be considerable (read here).

Another way to make sticking children with sharp needles less painful for everyone.

Want some top tips on paediatric cannulation? Watch our paediatric cannulation video on the DFTB YouTube channel here.

Neonate resus update 2021

2021 Resuscitation Council UK Guidance: What’s new in neonates?

Cite this article as:
Anandi Singh, Jilly Boden and Vicki Currie. 2021 Resuscitation Council UK Guidance: What’s new in neonates?, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.33461

We’ve looked at the changes in the paediatric resuscitation guidelines, here we take a closer look at neonatal guidelines.

Supporting transition at birth

There are no major changes for the newborns (just yet), but there is clarification on certain practices since the last 2015 update.

The umbilical cord: Leave it hanging?

We should delay clamping the cord for sixty seconds after the first cry. Researchers are looking at the benefit of beginning resuscitation whilst the cord still remains intact. Immediate cord clamping (ICC) has been shown to significantly reduce ventricular pre-load while simultaneously adding to left ventricular afterload.

If delayed cord clamping (DCC) is not possible, ‘milking of the cord’ can result in some transient benefits. There may be less need for inotropic support and fewer transfusions but no overall reduction in morbidity or mortality in the premature. There is insufficient data to suggest any benefit in babies 34 weeks to term. Milking of the cord is not recommended below 28 weeks as one large study was terminated early after babies were found to have higher risk of intraventricular haemorrhage.

Inflation and ventilation breaths: Increased pressure

When delivering inflation breaths, the resuscitation guidelines recommend slightly increased pressures than before

<32 weeks gestation, 25cm H2O for peak inspiratory pressure
>32 weeks, we should be using 30cm H2O initially slowly titrating up to achieve good chest wall movement.

Set the PEEP at at 5cm H2O for all babies that need assisted ventilation.

Laryngeal Mask Airways

LMAs are better than (in systematic review of 7 studies, N=794) bag-mask ventilation. Using them reduces the need for intubation and the duration of ventilation, though the evidence was low/moderate quality. The updated guidelines suggest more proactive use of an LMA in babies >34weeks and >2kgs.

Oxygen: Start low

  • For babies >32/40, the guidelines remains unchanged, start in air, monitor SpO2 and increase as needed. It can take several minutes to reach normal saturation levels.
  • For babies born between 28-32 weeks gestation, a small amount of supplemental oxygen (21-30% FiO2) may help with the effort of breathing and reduce mask ventilation time.
  • Start babies born before 28 weeks gestation on 30% FiO2.
  • Turn the FiO2 immediately up to 100% if you have to start chest compressions.

Thick Meconium: Don’t rush to suction

In the past, if a ‘non-vigorous’ baby (i.e. hasn’t cried yet), was delivered through thick meconium, you were supposed to visualise the cords with a laryngoscope and suction before providing inflation breaths. There wasn’t great evidence for this and the thought was that it simply delayed ventilation in an otherwise apnoeic baby.

What about adrenaline dosing?

There are still a few studies looking at the dosing of adrenaline in neonates but now the recommended dose is 20 micrograms/kg (0.2 mL/kg of 1:10,000 adrenaline (1000 micrograms in 10 mL)).  This should be repeated every 3-5 minutes as needed.

Focus on temperature: Aim for 36.5-37.5°C

The admission temperature of all (non-asphyxiated) babies across all settings and gestational ages, is a strong predictive factor for morbidity and mortality.

  • Use heated and humidified gases from the outset if you can, for babies born <32 weeks. A meta-analysis of 2 RCTs (N=476) suggested that this reduced the rate of hypothermia on admission by 36%.
  • Skin-to-skin care may be enough to keep >32 week babies warm, though a study focusing on 28-32+6 gestation babes suggested that this may be sub-optimal compared to conventional means of warming (a mix of radiant heaters, plastic bags, heated mattresses etc).

For each 1 degree Celsius decrease in admission temperature below the recommended range, an increase in the baseline mortality by 28% has been reported.

Emergency access: You know the drill

Umbilical catheterisation remains the prime means of vascular access.   If this is not an option, then use intraosseous access to give emergency drugs and volume.  Simulation studies suggest that the IO route may be quicker, though not without risk. Adverse events such as osteomyelitis, compartment syndrome and fractures have occurred.

Neonatal resuscitation updates

Stopping resuscitation should be considered by the team if there is no response after 20 minutes and reversible (e.g. tension pneumothorax, hypovolaemia, equipment failure) have been discounted.

Selected references

Resuscitation Council UK Guidelines 2021 https://www.resus.org.uk/library/2021-resuscitation-guidelines

Madar J et al European Resuscitation Council Guidelines 2021: Newborn resuscitation and support of transition of infants at birth (2021). https://doi.org/10.1016/j.resuscitation.2021.02.014

ERC Guidelines 2021: https://cprguidelines.eu/

Wyckoff MH, ET AL. Neonatal Life Support Collaborators. Neonatal Life Support 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Resuscitation. 2020 Nov;156:A156-A187.  https://doi.org/10.1016/j.resuscitation.2020.09.015 Epub 2020 Oct 21. PMID: 3309891

Paediatric resus update 2021

2021 Resuscitation Council UK Guidance: What’s new in paediatrics?

Cite this article as:
Anandi Singh, Jilly Boden and Vicki Currie. 2021 Resuscitation Council UK Guidance: What’s new in paediatrics?, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.33450

You are working in Paeds ED. The alert phone rings for a 2-year-old boy coming in a cardiac arrest. You hear some colleagues talking about Plasmalyte, capnography, and reduced respiration rates. Don’t panic! You had heard somebody mention that there were new resuscitation guidelines out though you’ve not read them yet. How much could have really changed?

Let’s take a step back. Where do these resus guidelines come from?

The Resuscitation Council UK recently issued their 2021 guidelines. They are tailored to UK clinical practice and derived from the European Resuscitation Council (ERC) 2021 Guidelines. The International Liaison Committee on Resuscitation (ILCOR) is responsible for the International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations (CoSTR). This consensus document is then used by international member organisations to develop guidelines. They are updated roughly every five years. CoSTR 2020 formed the ERC 2021 guidance.

The guideline development process utilised systematic reviews, scoping reviews, evidence updates and engagement from worldwide stakeholders (including members of the public and cardiac arrest survivors).

The 2021 Resuscitation Council UK Guidance covers both adult and paediatric basic and advanced life support. We have reviewed the corpus of generic guidance, some key additions and the main changes to both paediatric and neonatal life support algorithms.

The new guidelines do not specifically include the management of arrest secondary to COVID-19. You can be find them at https://www.resus.org.uk/covid-19-resources.

Epidemiology of Paediatric Cardiac Arrest

Epidemiology of paediatric cardiac arrest

Changes in paediatric resuscitation

Paediatric Basic Life Support

There are a few minor changes in 2021 to the paediatric BLS guidelines. They all apply to children up to 18 years of age (except for newborns).

Initial Assessment

Assess for signs of life simultaneously with the delivery of rescue breaths. If there are no signs of life, start chest compressions immediately after initial rescue breaths (you do not need to pause here).

Deliver five rescue breaths followed by ventilation breaths with compressions at a ratio of 15:2.

Emphasis on achieving high quality CPR

We should use mobile phones on loudspeaker for dispatcher guidance on how to deliver CPR or to summon emergency medical services (EMS) without leaving the victim.

Whilst the majority of paediatric cardiac arrests are respiratory in nature, effective chest compressions still play their part. Do these on a firm surface( so not a bed) and to a depth of at least one third the anterior-posterior diameter of the chest (or by 4cm in an infant and 5cm in a child). The rate remains at a rate of 100-120/min. The chest needs to fully recoil after each compression and around 80% of the CPR cycle should be composed of compressions.

Airway

The Resus Council recommend cuffed endotracheal tubes in children, if intubation is needed, and uncuffed tubes in neonates (Ed. note-we’ll look at this another day). Monitor this cuff pressures and try to keep it below 20mmHg.

Breathing

Target oxygen saturations (SpO2) of 94-98% with as little supplemental oxygen as possible. Avoid giving pre-emptive oxygen therapy without signs of hypoxemia or shock and try to avoid readings of up to 100% – unless in situations such as carbon monoxide poisoning. Hyperoxia appears to be almost as harmful as hypoxia.

High-flow nasal cannula oxygen (HFNC) or continuous positive airway pressure (CPAP)/non-invasive ventilation (NIV) support should be considered in children that have adeqaute respiratory drive but are not responding to low-flow oxygen. Bag-mask ventilation (BMV) is recommended in children with inadequate respiratory drive. If oxygenation/ventilation doesn’t improve, or ventilation may be ongoing, it is time for more advanced airway techniques – supraglottic airway devices (SGA) or endotracheal intubation.

Changes to paediatric resuscitation guidelines

Monitor capnography

End-Tidal CO2 monitoring is the gold standard, whether using an SGA or bag-valve-mask ventilation. Waveform capnography can reliably confirm tracheal tube placement when has a perfusing rhythm, as long as they are over two kilos in weight. There is a reasonable correlation between ETCO2 and PaCO2 but the guidelines do not go so far as suggesting a threshold ETCO2 or PaCO2 for stopping the resuscitation attempt.

What can the ETCO2 waveform tell us in resuscitation?

Use of end-tidal in paediatric resus

Circulation

No single finding can reliably identify the severity of circulatory failure. We still need to reassess frequently and after every intervention. This can be done by monitoring mean arterial blood pressure, trends in lactate, urine output and, if competent, ultrasound findings.

Vascular Access

Peripheral intravenous (IV) lines are the first choice for vascular access but it’s just two attempts and you are out. Then it is time to move on.

Intraosseous (IO) access is the primary rescue alternative. Remember it can be painful so give proper intraosseous analgesia before giving the first fluid bolus in every (awake) child.

A balanced approach to fluids

In children with shock, use a 10 mL/kg fluid bolus repeated up to 40-60 mls/kg.

How much should we give? There is an emphasis on smaller volumes with careful reassessment after each bolus to enable early identification of signs and symptoms of fluid overload. These include hepatomegaly, bilateral basal lung crackles, and jugular venous distention. Current evidence shows that a restrictive approach to fluid therapy is at least as effective as larger volumes.

In children with shock secondary to haemorrhage, we need to keep crystalloid boluses to a minimum (max 20mls/kg). Early use of blood products is the way to go in children who present with severe trauma.

Having decided to give fluid, what should we give? Balanced isotonic crystalloids (e.g. Plasmalyte) are the first choice with 0.9% sodium chloride being an acceptable alternative. Saline can induce hyperchloremic acidosis and may be associated with a worse outcome. The evidence for Hartmanns/Ringer’s lactate is still limited and shows ‘no more than a trend’ (?) towards a better outcome – so this is still left a bit unclear… Don’t use dextrose-based solutions for volume replacement – these will be redistributed rapidly away from the intravascular space and will cause hyponatremia and hyperglycaemia which may worsen neurological outcome.

Consider using permissive hypotension (mean arterial blood pressure (MAP) at 5th percentile for age) in traumatic injury. Be mindful that It is contraindicated in children with traumatic brain injury. You need to maintain a reasonable cerebral perfusion pressure. The Resus Council UK guidelines recommend giving tranexamic acid (TXA) to all children requiring transfusion after severe trauma and/or significant haemorrhage, as long as it is within three hours of injury

Vasoactive drugs need to be started early In children with persistent decompensated circulatory failure. Noradrenaline or adrenaline are recommended as first-line agents. Vasoactive drug choice may be directed by individual patient circumstances once more detailed information about the pathophysiology is available..

Dopamine is no longer recommended but can be used if adrenaline and noradrenaline are not available.

Cardiac Arrest in Special Circumstances

Specific approach to CPR needed during specific conditions such as cardiac surgery, neurosurgery, trauma, drowning, sepsis, and pulmonary hypertension. However, there are no major changes to any of these guidelines.

When managing traumatic cardiac arrest we need to fix the reversible causes.

Traumatic cardiac arrest guidelines

We need to start simultaneous chest compressions whilst treating these causes. This trumps adrenaline use. Though exceedingly rare we should think about thoracotomy in paediatric TCA patients with penetrating trauma with or without signs of life on ED arrival.

Extracorporeal Life Support (ECLS)

Extracorporeal cardiopulmonary resuscitation (E-CPR) is the implementation of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in a patient with refractory cardiac arrest. E-CPR should only be considered if it is readily available and there is a (presumed) reversible cause.

For specific subgroups of children with decompensated cardiorespiratory failure (e.g. severe refractory septic shock or cardiomyopathy or myocarditis and refractory low cardiac output), the pre-arrest use of ECLS can be lifesaving and provide end-organ support, preventing cardiac arrest.

Post-cardiac arrest care

Avoid hypoxia, hypotension and fever in children and infants who have a return of spontaneous circulation (ROSC) following cardiac arrest. Targeted temperature management of children post-ROSC should comprise active treatment with either normothermia or mild hypothermia and continuous invasive temperature monitoring.

Changes in adult resuscitation guidance

Are you curious about the big people?

For the adults, there are no major changes in ADULT BLS/ ALS 2021 guidelines. The guide states that a child is any person up to 18 years – in terms of when we switch from paediatric to adult algorithm. If the child looks like a child, we use the paediatric algorithm. If it turns out that your patient looks more youthful than they actually are then little harm will ensue. They also recommend a stepwise approach to airway management. The expert consensus is that: providers with a high first-pass success rate should perform tracheal intubation.

The use of adrenaline is controversial. We don’t have great evidence for either the dosing or the timing of doses. A large trial in the UK (PARAMEDIC 3, expected Autumn 2021) will look in more detail at the timing of adrenaline and the potential benefits of an IO first approach.

There is a greater emphasis on POCUS and ECMO. This reflects the increasing evidence as a rescue therapy in certain adult patients in cardiac arrest. There is an increasing role of point-of-care ultrasound (POCUS) in peri-arrest care for diagnosis, but it requires a skilled operator, and the need to minimise interruptions during chest compression.

As with the paediatric population: there is a greater recognition that patients with both in- and out-of-hospital cardiac arrest have premonitory signs, and that many of these arrests may be preventable.

What else is in the guidance?

Health inequality (HI) and it’s impact on cardiac arrest outcome

There is vast inequality in the incidence of cardiac arrest, use of bystander CPR and the distribution of public access defibrillators. Deprived areas, and areas with a greater proportion of residents from minority ethnic backgrounds, have a higher incidence of cardiac arrest, lower incidence of bystander CPR and lower access to public access defibrillators. This needs further discussion and research. Teaching CPR to children in all schools would be a way of improving some of these inequalities.

Improving education and systems can save (more) lives

50% of out-of-hospital cardiac arrests (OHCAs) are witnessed. Bystanders perform CPR in 70% of these. Public education is crucial in saving lives. In 2018, 59% of members of the public in the UK reported having received training in CPR and 19% in how to use an automated external defibrillator (AED).

In 2019, over 291,000 people in the UK were trained in CPR as part of World Restart a Heart Day. Teaching the essential core skills in resuscitation will improve patient survival.

How to get better at paediatric resus

Technology-enhanced education, as well as simulation, can be used to improve teaching and engage learners. Social media and smartphone apps can be used to engage the community. A new section has been added to the guidance named ’Systems Saving Lives’ with the intended audience being governments, managers in health and education systems, health care professionals, teachers, students and members of the public. By emphasising the importance of the connections along the Chain of Survival, we can improve the performance of resuscitation systems.

4 Key areas that have been highlighted are:

What's new in paediatric resus guidelines

Ethics

Another key area in the new guidelines is around integrating decisions about CPR in advanced treatment plans (e.g. Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) process). The guideline highlights the need for communication strategies and interventions to support discussions with patients and their family around resuscitation.

What might we see in the next revision…

  • Could IO become the first choice route of adrenaline?
  • Will we still be using adrenaline in all arrest situations?
  • Will (ab)normal saline be removed entirely?
  • Will we have more concrete evidence on using Hartmann’s/ Ringer’s Lactate in resuscitation fluids?
  • Will we have more information on the barriers and motivators to bystander CPR and AED use in respect of ethnic, socio-economic, cultural and educational background?

Selected references for the updated Resuscitation Council UK guidelines

Resuscitation Council UK Guidelines 2021 https://www.resus.org.uk/library/2021-resuscitation-guidelines

Madar Jet al European Resuscitation Council Guidelines 2021: Newborn resuscitation and support of transition of infants at birth (2021). https://doi.org/10.1016/j.resuscitation.2021.02.014 ERC Guidelines 2021: https://cprguidelines.eu/

Wyckoff MH, ET AL. Neonatal Life Support Collaborators. Neonatal Life Support 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Resuscitation. 2020 Nov;156:A156-A187.  https://doi.org/10.1016/j.resuscitation.2020.09.015 Epub 2020 Oct 21. PMID: 3309891

Bubble Wrap PLUS – June

Cite this article as:
Anke Raaijmakers. Bubble Wrap PLUS – June, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.33425

Can’t get enough of Bubble Wrap? The Bubble Wrap Plus is a monthly paediatric journal club reading list  from Anke Raaijmakers working with Professor Jaan Toelen & his team of the University Hospitals in Leuven. This comprehensive list is developed from 34 journals, including major and subspecialty paediatric journals. We suggest this list can help you discover relevant or interesting articles for your local journal club or simply help you to keep an finger on the pulse of paediatric research.

This month’s list features answers to intriguing questions such as: ‘Do vaccine-hesitant parents think that toxins in vaccines caused their children’s developmental delays?’, ‘What is the community use of paracetamol and ibuprofen in children with fever?’, ‘Is it safe to abandon prefeed gastric aspiration in preterms?’, ‘Is dissatisfaction with school toilets associated with bladder dysfunction?’ and ‘Why has the use of ICU in bronchiolitis doubled between 2010-2019?’.

You will find the list is broken down into four sections:

1.Reviews and opinion articles

Sickle cell nephropathy: insights into the pediatric population.

Adebayo OC, et al. Pediatr Nephrol. 2021 May 29. 

Use of Probiotics to Prevent Necrotizing Enterocolitis: Evidence to Clinical Practice.

Razak A, et al. JAMA Pediatr. 2021 May 28. 

Use of Probiotics in Preterm Infants.

Poindexter B, et al. Pediatrics. 2021 May 24:e2021051485. 

Cat Scratch Disease and Bartonellaceae: The Known, the Unknown and the Curious.

Zangwill KM. Pediatr Infect Dis J. 2021 May 1;40(5S):S11-S15. 

Evidence suggests dexamethasone is a better choice than prednisolone for acute asthma attacks in children.

Sinha IP. Arch Dis Child. 2021 May 24:archdischild-2020-321499

What Will it Take to Achieve Routine Screening for Abuse?

Lindberg DM. J Pediatr. 2021 May 19:S0022-3476(21)00461-3. 

Ambient Air Pollution: Health Hazards to Children.

Brumberg HL, et al. Pediatrics. 2021 May 17:e2021051484. 

Origins and Early Management of Medical Child Abuse in Routine Pediatric Care.

Hamilton JC, et al. JAMA Pediatr. 2021 May 17. 

Paediatric facial paralysis: An overview and insights into management.

Malik M, et al. J Paediatr Child Health. 2021 May 13. 

Drugs in Focus: Proton Pump Inhibitors.

Orel R, Benninga MA, et al. J Pediatr Gastroenterol Nutr. 2021 May 1;72(5):645-653. 

Factors That Influence Infant Immunity and Vaccine Responses.

Zimmermann P, et al. Pediatr Infect Dis J. 2021 May 1;40(5S):S40-S46. 

2.Original clinical studies

Efficacy and Safety of IV Sildenafil in the Treatment of Newborn Infants With, or at Risk of Persistent Pulmonary Hypertension of the Newborn (PPHN): A Multicenter, Randomized, Placebo-Controlled Trial.

Pierce CM, et al. J Pediatr. 2021 May 27:S0022-3476(21)00502-3. 

Birth prevalence of congenital heart defects in Western Australia, 1990-2016.

Hansen M, et al. J Paediatr Child Health. 2021 May 29. 

Long-term follow-up of premature infants with urinary tract infection.

Goldberg L, et al. Eur J Pediatr. 2021 May 28. 

New Daily Persistent Headache in a Pediatric Population.

Strong E, et al. J Child Neurol. 2021 May 28:8830738211004514. 

Understanding Vaccine Hesitancy Among Parents of Children With Autism Spectrum Disorder and Parents of Children With Non-Autism Developmental Delays.

Mensah-Bonsu NE, et al. J Child Neurol. 2021 May 28:8830738211000505. 

Association of Very Preterm Birth or Very Low Birth Weight With Intelligence in Adulthood: An Individual Participant Data Meta-analysis.

Eves R, et al. JAMA Pediatr. 2021 May 28. 

Outcomes of neonatal hypoxic-ischaemic encephalopathy in centres with and without active therapeutic hypothermia: a nationwide propensity score-matched analysis.

Shipley L, et al. Arch Dis Child Fetal Neonatal Ed. 2021 May 27:fetalneonatal-2020-320966. 

Effects of N95 Mask Use on Pulmonary Function in Children.

Lubrano R, et al. J Pediatr. 2021 May 24:S0022-3476(21)00501-1. 

Is There a Molecular Basis to Accelerated Aging?

Factor-Litvak P. Pediatrics. 2021 May 17:e2020038158. 

Extremely Low Birth Weight and Accelerated Biological Aging.

Van Lieshout RJ, et al. Pediatrics. 2021 May 17:e2020001230

Socioeconomic Disadvantage and the Pace of Biological Aging in Children.

Raffington L, et al. Pediatrics. 2021 May 17:e2020024406. 

Too far to fall: Exploring the relationship between playground equipment and paediatric upper limb fractures.

Curnow H, et al. J Paediatr Child Health. 2021 May 25. 

Monoclonal Antibodies for Prevention of Respiratory Syncytial Virus Infection.

Rodriguez-Fernandez R, et al. Pediatr Infect Dis J. 2021 May 1;40(5S):S35-S39. 

Community use of paracetamol and ibuprofen in children with fever.

Kloeden B, et al. J Paediatr Child Health. 2021 May 26. 

Biomarkers of acute kidney injury in pediatric cardiac surgery.

Cavalcante CTMB, et al. Pediatr Nephrol. 2021 May 25. 

Piercing issue: a 10-year single-centre experience of magnet ingestion in children.

John M, et al. Arch Dis Child. 2021 May 25:archdischild-2021-321848. 

Oral steroids for reducing kidney scarring in young children with febrile urinary tract infections: the contribution of Bayesian analysis to a randomized trial not reaching its intended sample size.

Da Dalt L, et al. Pediatr Nephrol. 2021 May 25. 

Longitudinal Associations Between Screen Use and Reading in Preschool-Aged Children.

McArthur BA, et al. Pediatrics. 2021 May 24:e2020011429. 

Delivery Room Interventions for Hypothermia in Preterm Neonates: A Systematic Review and Network Meta-analysis.

Abiramalatha T, et al. JAMA Pediatr. 2021 May 24:e210775. 

Study of Acute Liver Failure in Children Using Next Generation Sequencing Technology.

Hegarty R, et al. J Pediatr. 2021 May 20:S0022-3476(21)00491-1. 

Outcomes of Very Preterm Infants Conceived with Assisted Reproductive Technologies.

Fineman DC, et al. J Pediatr. 2021 May 20:S0022-3476(21)00495-9. 

Randomized Placebo-Controlled Trial of Topical Mupirocin to Reduce Staphylococcus aureus Colonization in Infants in the Neonatal Intensive Care Unit.

Nelson MU, et al. J Pediatr. 2021 May 20:S0022-3476(21)00492-3. 

Minimally invasive surfactant therapy for moderate to late premature neonates with respiratory distress syndrome born in a non-tertiary unit.

Tinoco Mendoza G, et al. J Paediatr Child Health. 2021 May 22. 

Trajectories of Systolic Blood Pressure in Children: Risk Factors and Cardiometabolic Correlates.

Yuan WL, et al. J Pediatr. 2021 May 18:S0022-3476(21)00450-9. 

Routine prefeed gastric aspiration in preterm infants: a systematic review and meta-analysis.

Kumar J, et al. Eur J Pediatr. 2021 May 20. 

Attention deficit and hyperactivity disorder and nocturnal enuresis co-occurrence in the pediatric population: a systematic review and meta-analysis.

de Sena Oliveira AC, et al. Pediatr Nephrol. 2021 May 19. 

Dissatisfaction with school toilets is associated with bladder and bowel dysfunction.

Jørgensen CS, et al. Eur J Pediatr. 2021 May 17

Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy: International Clinical Practice Guideline Based on Systematic Reviews.

Morgan C, et al. JAMA Pediatr. 2021 May 17. 

Duration of mechanical ventilation is more critical for brain growth than postnatal hydrocortisone in extremely preterm infants.

Rousseau C, et al. Eur J Pediatr. 2021 May 16

Altered White Matter Connectivity in Young Acutely Underweight Patients With Anorexia Nervosa.

Geisler D, et al. J Am Acad Child Adolesc Psychiatry. 2021. 

Improving Delayed Antibiotic Prescribing for Acute Otitis Media.

Frost HM, et al. Pediatrics. 2021 May 12:e2020026062. 

Foreign body ingestion in children: a magnet epidemic within a pandemic.

Thakkar H, et al. Arch Dis Child. 2021 May 11:archdischild-2021-322106

ICU Use in Bronchiolitis: Why Has It Doubled?

Alverson B, et al. Pediatrics. 2021 May 10:e2020046276

Trends in Bronchiolitis ICU Admissions and Ventilation Practices: 2010-2019.

Pelletier JH, et al. Pediatrics. 2021 May 10:e2020039115. 

Predictive Intelligent Control of Oxygenation (PRICO) in preterm infants on high flow nasal cannula support: a randomised cross-over study.

Dijkman KP, et al. Arch Dis Child Fetal Neonatal Ed. 2021. 

Road accidents in children involving light electric vehicles cause more severe injuries than other similar vehicles.

Botton IN, et al. Eur J Pediatr. 2021 May 8. 

Prospective comparison of thermometers used in very preterm infants.

Dunne EA, et al. Arch Dis Child Fetal Neonatal Ed. 2021. 

Intrapartum group B Streptococcal prophylaxis and childhood weight gain.

Mukhopadhyay S, et al. Arch Dis Child Fetal Neonatal Ed. 

Premedication with ketamine or propofol for less invasive surfactant administration (LISA): observational study in the delivery room.

Brotelande C, et al. Eur J Pediatr. 2021 May 6. 

Assessing Child Abuse Hotline Inquiries in the Wake of COVID-19: Answering the Call.

Ortiz R, et al. JAMA Pediatr. 2021 May 3:e210525. 

Incidence of gynaecomastia in Klinefelter syndrome adolescents and outcome of testosterone treatment.

Butler G. Eur J Pediatr. 2021 May 2

Health Outcomes in Young Children Following Pertussis Vaccination During Pregnancy.

Laverty M, et al. Pediatrics. 2021 May;147(5):e2020042507. 

Tympanostomy Tubes or Medical Management for Recurrent Acute Otitis Media.

Hoberman A, et al. N Engl J Med. 2021 May 13;384(19):1789-1799. 

Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma.

Menzies-Gow A, et al. N Engl J Med. 2021 May 13;384(19):1800-1809. 

3.Guidelines and best evidence

Pharmacologic Treatment in Functional Abdominal Pain Disorders in Children: A Systematic Review.

Rexwinkel R, et al. Pediatrics. 2021 May 27:e2020042101. 

Systematic review of high-flow nasal cannula versus continuous positive airway pressure for primary support in preterm infants.

Bruet S, et al. Arch Dis Child Fetal Neonatal Ed. 2021 May 20:fetalneonatal-2020-321094. 

Risk Factors for Pediatric Asthma Readmissions: A Systematic Review.

Hogan AH, et al. J Pediatr. 2021 May 12:S0022-3476(21)00438-8. 

Isolated neutropenia appears unlikely to require intervention.

Kirk SE, et al. J Pediatr. 2021 May;232:307-310. 

Association Between Celiac Disease and Autism Spectrum Disorder: A Systematic Review.

Quan J, et al. J Pediatr Gastroenterol Nutr. 2021 May 1;72(5):704-711. 

4.Case reports

Peculiar case of misdiagnosed epistaxis.

Roy S. J Paediatr Child Health. 2021 May 28. 

Lower Limb Bruising Associated with Montelukast in an Asthmatic Child.

Trayer J, et al. J Paediatr Child Health. 2021 May 19. 

Scabies in a 4-week-old baby boy, a diagnostic challenge.

Pérez de Diego E, et al. Arch Dis Child. 2021 May 5:archdischild-2021-321944. 

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments!

Much ado about Meckel’s

Cite this article as:
Peter Tormey. Much ado about Meckel’s, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.33008

Robert is a 14-year-old boy who re-presents to ED with a history of rectal bleeding. He has had four or five episodes of passing bright, red blood PR over the last three days, having been a previously well child. He has also had four or five episodes of non-bilious vomiting.

Mum has noticed that he has now become pale and lethargic.

On his first presentation to ED, two days prior, the working diagnosis was bacterial gastroenteritis. His haemoglobin at that time was 99g/L. It has fallen to 45g/L on this presentation.

On examination, he is very pale, his heart rate is 120, and his blood pressure 95/65.

What are your differentials at this point?

Infectious

  • Bacterial: Campylobacter, Salmonella, Shigella, E. coli, Yersinia, C. difficile
  • Viral: rotavirus, COVID-19

Inflammatory

  • Inflammatory bowel disease

Vascular

Bowel obstruction

  • Intussuception
  • Malignancy

Others

  • Meckel’s diverticulum
  • Anal fissure
  • Haemorrhoids
  • Trauma/NAI

What investigations would you perform?

  • Bloods: FBC, U+E, LFTs, CRP, ESR, VBG, blood culture, coagulation screen
  • Stool culture, stool for C.difficile
  • Covid swab
  • Abdominal ultrasound
  • CT abdomen/pelvis
  • Colonoscopy
  • Meckel’s scan

What is Meckel’s Diverticulum?

You may remember “The Rule of Two’s” from medical school.

MD is a congenital abnormality of the small intestine that is present in 2% of the population. 2% of these people will become symptomatic. It is 2 inches long and 2 feet from the ileocoecal valve. There can be 2 types of ectopic tissue: gastric or pancreatic. There is a 2:1 male preponderance.1,2,3

MD comprises the three layers of the intestinal wall and is, therefore, a true diverticulum.3 It results from the incomplete obliteration of the omphalomesenteric duct. The omphalomesenteric duct connects the yolk sac to the intestinal tract during early foetal life and is usually obliterated by the seventh week of gestation. Failure to regress can result in a spectrum of abnormalities, including: MD, patent vitelline duct, fibrous band, sinus tract, umbilical polyp and umbilical cyst.3

Comparison between vitelline fistula and meckel's

What happens to the symptomatic 2%?

The presentation of MD is highly variable. It is best to consider the different presentations based on the underlying anatomical or pathological processes the diverticulum can undergo.

1. It gets in the way

The abnormal anatomy in MD can lead to intestinal obstruction. In children, this usually presents as intussusception or volvulus.3

The diverticulum acts as the lead point in intussusception. These patients present with abdominal pain. The symptoms can be non-specific, particularly in pre-verbal children. They are “off form”, or parents complain about poor feeding, constipation, abdominal distension. As you can see from Robert’s case, intussusception can also lead to massive GI haemorrhage.

Volvulus of the intestine may occur around the fibrous cord that connects the Meckel’s to the umbilicus.4

2. The ectopic gastric tissue can cause an ulcer

The ectopic gastric mucosa in the diverticulum can secrete acid which results in ulceration of the small bowel. This usually presents as painless bleeding, which can be massive in nature.3 It may also present due to anaemia from chronic bleeding. The bleeding is usually dark red or maroon in colour.3 Robert’s Technitium-99m scan (or Meckel’s scan) was positive, suggesting the presence of gastric mucosa, so he may have intussusception plus ulceration, both leading to his massive GI haemorrhage.

3. It gets angry

As the Meckel’s is a blind ending diverticulum, it can undergo a process of inflammation, similar to appendicitis. Obstruction at the base of the diverticulum leads to bacterial overgrowth and inflammation. This can present with fever, vomiting and abdominal pain, which is often indistinguishable from acute appendicitis. The MD may also perforate, leading to diffuse peritonitis and  a very unwell patient.

As these symptoms are all non-specific, it is important to think of MD as a diagnosis in children presenting with any of the symptoms above.

How is it diagnosed?

MD requires a high index of clinical suspicion to aid diagnosis. Most imaging modalities are non-specific but can still be helpful. X-ray or ultrasound may show a small bowel obstruction and intussusception.5 Finding a normal appendix on ultrasound, may lead to careful consideration of MD as an alternate cause.

A Meckel’s scan may be performed. This is a nuclear medicine scan using Technitium-99m, which accumulates in the ectopic gastric mucosa (see Image 2).5 The test is reliant on the presence of gastric mucosa, which is only present in 4.6-71% of symptomatic MD.5 Premedication with H2 antagonists may increase the accuracy of the scan.5

Radionuclide Meckel scan
Case courtesy of Radswiki, Radiopaedia.org. From the case rID: 11598

MD is often only confirmed on exploratory laparoscopy or laparotomy.

How is it treated?

Definitive treatment is surgical resection of the diverticulum, either laparoscopically or by laparotomy. Simple diverticulectomy and closure of the ileum is acceptable except in cases of GI bleeding where the ulcer may extend to the adjacent ileum, in which case segmental resection with re-anastomosis of the small bowel should be carried out.4

Robert’s haemoglobin is 45. He requires multiple transfusions with packed red cells, FFP and fibrinogen. He is stabilized and transferred to PICU.

He has an emergency OGD and colonoscopy. They do not reveal the source of bleeding. His abdominal ultrasound shows a small bowel intussusception, suspicious for Meckel’s diverticulum (MD). He has a Meckel’s scan which confirms MD. He undergoes surgical resection of the diverticulum and recovers well.

Who was Meckel?

Johann Friedrich Meckel (the younger) was a German anatomist whose principle interest was the study of congenital malformation and the developmental aspects of the lungs and bloods vessels.6

Interestingly, MD was first described by Wilhelm Fabricius Hildanus, a German Surgeon, in 1598.7 It wasn’t named, however, until Meckel reported his research on the diverticulum’s anatomy and embryology in 1809.

He is also responsible for the medical eponyms Meckel cartilage and Meckel syndrome.

He is called Johann Friedrich Meckel The Younger because his grandfather was called by the same name and was also an anatomist, as were his father, younger brother and son.

You can find out more about him and the Meckel anatomist dynast on LITFL.

References for Much Ado about Meckel’s

1. Meckel’s Diverticulum [Internet]. [cited 2021 Apr 1]. Available from: https://pedemmorsels.com/meckels-diverticulum/

2. Rule of 2s in Meckel diverticulum | Radiology Reference Article | Radiopaedia.org [Internet]. [cited 2021 Apr 1]. Available from: https://radiopaedia.org/articles/rule-of-2s-in-meckel-diverticulum-1

3. Keese D, Rolle U, Gfroerer S, Fiegel H. Symptomatic Meckel’s Diverticulum in Pediatric Patients—Case Reports and Systematic Review of the Literature. Front Pediatr [Internet]. 2019 Jun 26 [cited 2021 Apr 12];7(JUN):267. Available from: https://www.frontiersin.org/article/10.3389/fped.2019.00267/full

4. Ivatury RR. Meckel’s diverticulum and the eponymous legend. Vol. 87, Journal of Trauma and Acute Care Surgery. Lippincott Williams and Wilkins; 2019. p. 451–5.

5. Hansen C-C, Søreide K. Systematic review of epidemiology, presentation, and management of Meckel’s diverticulum in the 21st century. Medicine (Baltimore) [Internet]. 2018 Aug 1 [cited 2021 Apr 12];97(35):e12154. Available from: https://journals.lww.com/00005792-201808310-00091

6. Johann Friedrich Meckel The Younger • LITFL • Medical Eponym Library [Internet]. [cited 2021 Apr 12]. Available from: https://litfl.com/johann-friedrich-meckel-the-younger/