Picture of house

Hospital in the Home

Cite this article as:
Jo Lawrence. Hospital in the Home, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28959

Elise is about to have her 8th birthday and has planned a small party at home with her family and two best friends.  Elise also has acute lymphoblastic leukaemia and is in the middle of chemotherapy treatment.  Her next dose of methotrexate is due the day after her birthday but requires pre-hydration the day before….

Thomas is in year 3 and loves playing foursquare at lunch with his friends. He also has CF and requires regular tune-ups of 2 weeks IV antibiotics and physiotherapy…..

MaryKate is an 8 month old and the youngest of 5 children.  She has poor oral feeding due to a complex medical background and requires nasogastric top-ups. Her parents have been told that she could wean from the tube if she participated in an intensive multidisciplinary program but are reluctant to attend hospital due to the significant disruption on family routine…..  

Is there a way Elise could enjoy her birthday at home, Thomas stay active at school and MaryKate receive the treatment she needs without significant family disruption?

What is Hospital in the Home?

Hospital in the Home (HITH) refers to hospital level care provided in the home environment. 

As we look at managing our growing population with a fixed number of hospital beds this is one area of healthcare that is set to boom!  

When admitted to HITH, clinicians visit the home and provide the acute care interventions required in 1-2 visits per day.  The advantages of this model of care on hospital flow and access are readily apparent.  Less obvious, although equally critical, are the substantial benefits for the family and patient.  Being treated in a safe place surrounded by familiar faces eases the stress and anxiety experienced by the child. Cost-savings for families obviously include not having to fork out for travel and hospital parking, but the real cost-savings occur for families because both parents no longer have to take carers leave – one for the hospitalized child, the other for the siblings. On average, HITH ends up being one-third of the cost of hospitalization for families1. In addition, HITH avoids disruption to family routines and unwanted separation.

So what can Hospital in the Home do?

Pretty much anything!  As long as the patient is clinically stable (not heading for ICU) and can have their care needs delivered in up to 2 visits per day, then it can be done.  

Traditionally Hospital in the Home models have centred around IV antibiotics and little else, but that has dramatically changed over the past few years. 

Here are some of the common things that paediatric HITHs are currently doing2:

  • Diabetes education
  • Eczema dressings
  • Subcutaneous infusions
  • Chemotherapy
  • Pre and post-hydration for chemotherapy
  • TPN hook ons and hook offs
  • Wound dressings
  • NG feed support
  • Cardiac monitoring
  • CF tunes ups
  • Physiotherapy 
  • IV antibiotics 

Baseline criteria regarding distance from hospital and safety of home environment exist but solutions exist for almost situations.

Although most centres service a certain distance from hospital, care can often be outsourced for children who live more rurally.  The care continues to be managed by the tertiary hospital but provided by local care teams – a superb option.

In cases where a barrier exists for staff to enter the home, creative solutions can be found by meeting children at school, in parks or family member’s homes.  

What has changed with Covid-19?

Whilst paediatric hospitals in general saw a fall in patient presentations, HITH referrals have sky-rocketed.  Doctors and families have experienced renewed interest in moving vulnerable patients out of hospital walls and away from the potential of cross-infection.  Stricter visitor restrictions meant hospitalisation had an even greater impact on family life and the driver to manage care at home wherever possible has grown.

Most of this growth has been through increasing the proportion of eligible children referred rather than creating new pathways.  A couple of children have been admitted for observation of Covid-19 infection, but these cases have been few and far between.

However, as with every area of healthcare delivery, the biggest changes for HITH have been moving with the technology.  Education visits, medical and nursing reviews and physiotherapy have all been converted to telehealth where safe to do so.

Vaccination for influenza was offered to all patients admitted to HITH and was accepted by 70% of eligible patients.  65% of these were being vaccinated for the first time against flu3.  In an environment where routine vaccinations have been falling4, this is a powerful demonstration of the opportunities that exist within HITH.

Infants with bronchiolitis have been managed through HITH before5 but the care pathway has never stuck due to barriers accessing cylinders on the same day and clinician confidence.  A new model has been rolled out overcoming these barriers through utilising oxygen concentrators and remote monitoring.

With time, our use of remote monitoring and ability to feed vital signs directly into the Electronic Medical Record, will allow massive expansion of HITH services.   Predictive modelling from large EMR datasets will allow more accurate prediction of which children are likely to be safely transferred to the home environment.  Realtime data and predictive modelling will enhance clinician and family confidence and enable us to fully realise the benefits of HITH to hospitals and families.  

So what about our friends Elise, Thomas and MaryKate….

Elise is able to receive her pre-hydration at home on her birthday.  She celebrates her birthday in her parent’s bed with her sister beside her, both building her new lego sets.  Her best friends visit and her mother prepares a special meal and bakes a special cake.  She is able to go to bed that night, knowing the HITH nurses will visit every day over the following week to administer her chemotherapy and post-hydration and she has avoided another week in hospital.

The HITH nurses visit Thomas daily before school to connect his longline to a Baxter antibiotic infusion. Before and after school he performs physiotherapy via telehealth.  At school, he wears his antibiotic in a backpack and can continue to play 4 square at lunch.

MaryKate is visited by the HITH dietitian and speech therapy who provide feeding advice and a regime that fits around the family routine. They can see where MaryKate sits for meals and how her meals are prepared first hand and are able to offer some helpful suggestions. The team are also able to visit MaryKate at her daycare and ensure her routine is consistent. In between visits, MaryKate is reviewed via telehealth by the allied health team.  She makes significant oral progress and by the end of 2 weeks, her tube is no longer required.

Prehospital analgesia: part 2

Cite this article as:
Joe Mooney + Dani Hall. Prehospital analgesia: part 2, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27501

You’re in the rapid response vehicle, having just handed over a 2 year old with a femoral fracture. As you clear the hospital, a call comes in: 8 year old, fall from slide, deformed left arm, conscious and breathing. When you arrive in the house you find him lying on the sofa, with bruising and deformity of his left elbow. The paracetamol and ibuprofen given by his mother has not controlled his pain*, so you take out a methoxyflurane inhaler and explain to him to suck in and blow out through ‘the whistle’. After a few breaths he begins to relax.

Methoxyflurane is a fluorinated hydrocarbon, used as an inhaled anaesthetic in the ’60s and early ’70s, until it fell out of favour after case reports describing renal failure at anaesthetic doses. But, when given in small doses, methoxyflurane has excellent analgesic properties, with no nephrotoxic side effects. It has been used extensively in Australia and New Zealand by prehospital clinicians as a self-administered analgesic for short-term pain relief in adults and children. After being licenced in 2015 in the UK and Ireland for the emergency relief of moderate to severe pain in conscious adults with trauma, methoxyflurane was included in the Irish prehospital CPG for EMTs, paramedics and advanced paramedics with permission under the seventh amendment to allow its use in children.

Added as a liquid to a Penthrox® inhaler, methoxyflurane vaporises, to be inhaled on demand. It has revolutionised prehospital pain control due to its quick onset and easy, pain free administration and, because of its light weight, crews can carry it over rough ground easily. Known as ‘the green whistle‘, each 3ml dose is quoted to last between 20 and 30 minutes, but in practice can sometimes last up to 45 minutes or an hour, depending on a child’s respiratory rate and depth and the way in which they self-administer. The Irish prehospital CPGs allow two inhalers to be administered in 24 hours to a patient, so when there’s an extended journey time, methoxyflurane inhalers used back-to-back can provide up to two hours of analgesia, which can be supplemented by the simple analgesics, paracetamol and ibuprofen, or morphine, fentanyl and ketamine, as needed.

But what’s the evidence for methoxyflurane in children?

Pop methoxyflurane in the PubMed search bar, and a lot comes up. It’s safe, it works, but there are surprisingly few randomised controlled trials (RCTs) that include children. A couple of observational studies are noteworthy. An Australian study in the prehospital setting, published in 2006 by Franz Babl and colleagues, describes an observational case series of 105 children, ranging in age from 15 months to 17 years, who received methoxyflurane while by being conveyed to hospital by ambulance. The children’s pain scores dropped from 7.9 to 4.5, with few side effects, although there was a tendency towards deep sedation in the under 5s. The following year Babl’s team published an ED-based observational case series of 14 children aged 6 to 13 years with extremity injuries who received methoxyflurane for painful procedures in the hospital setting. Although methoxyflurane was a useful analgesic agent, Babl’s team found it did not work as well as a procedural analgesic for fracture reduction.

The first double-blind RCT of methoxyflurane in children was published almost two decades ago by Chin et al in 2002. Forty-one children over the age of 5 with upper limb fractures were randomised to receive either methoxyflurane or placebo. Unsurprisingly, methoxyflurane resulted in a lower pain score at 10 minutes than placebo. Adverse events weren’t reported, but the apparent safety and efficacy of methoxyflurane demonstrated in this study paved the way the some bigger and better RCTs.

A better known, and more recent, RCT involving children was the STOP! trial, published in the EMJ in 2014. This randomised, double-blind placebo-controlled trial was conducted at six EDs in the UK. Three hundred patients, 90 between the ages of 12 and 17, with minor trauma (such as burns, fractures, dislocations and lacerations), were randomised to receive either methoxyflurane or saline via an inhaler. In a nifty way to keep the patients, doctors and nurses blinded to which drug was being administered, a drop of methoxyflurane was added to the outside of every inhaler so both drug devices smelled the same. Pain scores dropped significantly lower in the methoxyflurane group, with a median onset of action of 4 minutes. But what about those adolescents? Although 45 12 to 17 year olds were included in each group, their data wasn’t analysed separately, and children under the age of 12 were excluded from the study, so although we can probably assume methoxyflurane works well and is safe in adolescents, more trials would be helpful.

Segue to the Magpie trial, which is currently recruiting in the UK and Ireland via the PERUKI network. This international multi-centre randomised, double-blind placebo-controlled trial is specifically investigating the efficacy and safety of methoxyflurane in children and young people so that its UK license can be extended to include children. Like STOP!, participants are being randomised to either methoxyflurane or placebo (again saline) via an inhaler. To ensure younger children are well represented in the study data, the study team are aiming to recruit higher numbers of 6 to 11 year olds than adolescents, with a recruitment target of 220 children and adolescents in total. We’re awaiting the results eagerly…


*A top tip on top up dosing

This child had been given 500mg of paracetamol and 280mg of ibuprofen by his mother before the crew arrived. He was 8 years old, with an estimated weight of 31kg. Based on Irish CPGs allowing a paracetamol dose of 20mg/kg (620mg) and ibuprofen dose of 10mg/kg (310mg) he was underdosed. It’s important to top-up simple analgesics as part of your approach to pain relief in children.


But what happened to the 8 year old?

You check CSMs (circulation, sensation and movement) before and after applying a splint and transfer him to the ambulance on a stretcher. His pain is very well controlled, and he asks his mother to take a photo for his friends. This sentence is hard for him to say and he gets the giggles. You transfer him uneventfully to hospital where he’s diagnosed with a supracondylar fracture.

Read more about assessing pain, prehospital analgesia in children and the evidence behind intranasal fentanyl in part 1 of the DFTB prehospital analgesia series.

References

Hartshorn, S., & Middleton, P. M. (2019). Efficacy and safety of inhaled low-dose methoxyflurane for acute paediatric pain: A systematic review. Trauma21(2), 94–102. https://doi.org/10.1177/1460408618798391

Babl FE, Jamison SR, Spicer M, Bernard S. Inhaled methoxyflurane as a prehospital analgesic in children. Emerg Med Australas. 2006;18(4):404-410. doi:10.1111/j.1742-6723.2006.00874.x

Babl FE, Barnett P, Palmer G, Oakley E and Davidson A. A pilot study of inhaled methoxyflurane for procedural analgesia in children. Pediatric Anesthesia. 2007;17:148-153. doi:10.1111/j.1460-9592.2006.02037.x

Chin, R, McCaskill, M, Browne, G A randomized controlled trial of inhaled methoxyflurance pain relief in children with upper limb fracture. J Paediatr Child Health 2002; 38: A13–A13.

Coffey F, Wright J, Hartshorn S, et al. STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain. EMJ 2014;31:613-618

Hartshorn, S., Barrett, M.J., Lyttle, M.D. et al. Inhaled methoxyflurane (Penthrox®) versus placebo for injury-associated analgesia in children—the MAGPIE trial (MEOF-002): study protocol for a randomised controlled trial. Trials 20, 393 (2019). https://doi.org/10.1186/s13063-019-3511-4

It’s Only Wheeze – Treatment Is Simple, Isn’t It?: Meredith Borland at DFTB19

Cite this article as:
Team DFTB. It’s Only Wheeze – Treatment Is Simple, Isn’t It?: Meredith Borland at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.20828

Meredith Borland is a paediatric emergency physician and the Director of Emergency Medicine at Perth Children’s Hospital in Perth, Western Australia. She was a founding member of the PREDICT Executive and is the current chair of PREDICT.

Last year at DFTB18, Meredith continued an ongoing discussion about the use of steroids in wheeze. This year, she took us on a journey through an emergency department visit for a number of children who may or may not receive various interventions. This was a fun, interactive and thought-provoking talk that highlighted some common differences in practice.

#doodlemed on this talk by @char_durand below

This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

Atomoxetine

Cite this article as:
Mary Hardimon. Atomoxetine, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.25536

James is a 7-year-old boy who was diagnosed with ADHD 2 years ago and was started on short-acting Ritalin 10mg in the morning and 10mg at lunch. Since you saw him 6 months ago, you notice that he has lost 3kg. This is in addition to the 2kg he lost when first starting stimulant medication. His mother has been supplementing his diet with high energy foods such as avocado, butter and nut but she is concerned about his weight loss despite these efforts and would like to discuss other medication options (as he has had a good effect reported by school with treatment). You have heard great things about atomoxetine (Strattera) but aren’t comfortable using it yet…

 

How does it work?

Strattera is thought to be a selective noradrenaline reuptake inhibitor (SNRI).

 

Indications for usage

Atomoxetine is indicated for ADHD (diagnosed according to DSM-V criteria) with any of the following:

  • Contraindication to dexamfetamine, methylphenidate or lisdexamfetamine as specified in TGA-approved product information
  • Co-morbid mood disorder that has developed or worsened as a result of dexamfetamine, methylphenidate or lisdexamfetamine treatment and is of a severity necessitating treatment withdrawal
  • Unacceptable medical risk of a severity necessitating permanent stimulant treatment withdrawal if given a stimulant treatment with another agent
  • Experienced adverse reactions of a severity necessitating permanent treatment withdrawal following treatment with dexamfetamine, methylphenidate, and lisdexamfetamine (not simultaneously)

 

TGA contraindications

  • Symptomatic cardiovascular disease – moderate/severe hypertension, atrial fibrillation/flutter, ventricular tachycardia, ventricular fibrillation, advanced atherosclerosis
  • Severe cardiovascular disorders – those whose condition would be expected to deteriorate if they experienced increases in blood pressure or in heart rate (for example, 15 to 20 mmHg in blood pressure or 20 beats per minute in heart rate)
  • Uncontrolled hyperthyroidism
  • Phaeochromocytoma – active or history of
  • MAO inhibitors
  • Narrow-angle glaucoma

 

Dosage and Administration

Initiated at 0.5mg/kg and increased after a minimum of 3 days to a target total daily dose of approximately 1.2mg/kg (may be given as a single daily dose or as evenly divided doses twice daily)

 

Adverse effects

Most common (>10%):

  • Headache
  • Insomnia or drowsiness
  • Hyperhidrosis
  • Xerostomia
  • Nausea/vomiting
  • Anorexia
  • Abdominal pain
  • Constipation

 

WARNING – There is an increased risk of suicidal ideation in children and adolescents

 

Connecting Advanced Care Practitioners

Cite this article as:
Team DFTB. Connecting Advanced Care Practitioners, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.26520

Our last ACP teaching session was on Thursday 8th October 2020. It covered case-based discussion, head injuries that may not be head injuries, and neonatal emergencies. See the recording below.

Our ACP webinar series is an opportunity for Advanced Practitioners who see children to connect with each other and to share knowledge.The webinars are delivered by and aimed at ACPs from any background who would like to share and improve their knowledge about caring for children in acute settings. The sessions are free, and anyone is welcome to join. Each session will comprise three short talks followed by a panel discussion and time for questions. We will be covering clinical and non-clinical topics, from a range of presenters. We will hear from some experienced speakers, as well as giving less seasoned speakers the opportunity to have their voice heard. If you have an idea for a topic you’d like to present, or if there’s something you have a burning desire to find out more about, please get in touch.

October 2020 – case-based discussion, head injuries that may not be head injuries, and neonatal emergencies

July 2020 – antibiotics, lymph nodes, and team leading

Performing the newborn check

Cite this article as:
Taryn Miller. Performing the newborn check, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.25986

There are two situations in which you would examine a newborn:

  • As part of the newborn screening examination as a “baby check”
  • In the emergency department

Both situations are slightly different, but the same structured approach can be applied

Before you begin…gather what you might need

  • Examine the baby in a warm, well-lit environment- get a blanket if needs be, or examine in the neonatal resuscitaire if available
  • Preferably with parent/ guardian present (if newborn screening exam, if not call parent)
  • Tongue depressor
  • Ophthalmoscope that works!
  • Stethoscope – In NICU/SCBU usually each baby will have their own special stethoscope. If you are using your own, make sure to give it a good wipe before and after use
  • Measuring tape for head circumference and a set of weighing scales to examine the baby without the nappy!
  • Keep the baby warm by wrapping them in a blanket or rocking the baby
  • Auscultate the lungs and heart in mum’s arms or when the baby is settled
  • If a newborn is unsettled or crying, consider whether the examination needs to be done at that exact moment. Perhaps suggest that the baby has a feed or a cuddle with mum or dad.

Before you begin

  1. Introduce yourself with “Hello, my name is…
  2. Check the name and DOB on the name band
  3. Explain to parent/guardian why it is important and what the examination will involve
  4. Gain consent
  5. Wash your hands and don gloves!

PS – don’t forget to congratulate mum, it is a really nice touch and makes the parent or guardian feel at ease.

Before the baby cries – Perform these things first!

Assessment of breathing (0:17) – Respiratory rate, look for respiratory distress – intercostal and subcostal recession, tracheal tugging, nasal flaring

Assessment of circulation (0:36) – Auscultate the heart rate (all four areas), auscultate the lungs, feel the femoral pulses on both sides

Abdomen (0:48)- Palpate the abdomen for organomegaly, specifically the liver and the spleen. And look for any hernias

Structured assessment – Top to toe (1:14)

Head (1:14)

General inspection – Look for facial asymmetry and dysmorphic features.
Fontanelle –Palpate the anterior and posterior fontanelles
Ears- Look for skin tags or pits
Mouth – Assess the hard and soft palate. Ideally, you should use a tongue depressor and look directly with a light. Use a gloved finger in the mouth to look at the sucking reflex

*Chest and abdomen as before*

Extremities (1:50)

Hands – count the fingers, and look at the creases, assess the grasp reflex
Feet – count the toes, and look at the grasp reflex
Genitalia – Check for hypospadias and feel both testes
Bottom – make sure the anus is patent

STOP – warn parents- what you are going to do and not “I’m going to drop your baby”!!

Reflexes (2:24)

Head lag (2:30)
Moro reflex (2:42)
Stepping reflex (2:45)
Tone and ventral suspension (2:49)

Spine (2:30) – Look at the sacrum for birthmarks, hairy patches, or for any sacral dimples 

Hips (3:04) – Perform Barlow’s and Ortolani’s test to assess for developmental dysplasia of the hip

And finally

Pre-and post-ductal saturations (3:12)  – right hand for pre-ductal saturations and post-ductal saturations can be either foot

Eyes – Check for the red reflex

TOP TIP! Wrap the baby in a blanket and sit them upwards, the baby should open their eyes and let you get a good look with the ophthalmoscope.

Look at the baby book and plot previous weight measurements and today’s weight on an age-specific growth chart along with the head circumference

This video was created by Bec Packton, Aarani Somaskanthan, Alice Munro, and Izolda Biro with special thanks to Lisa Crouch and baby James. Check out our YouTube channel for more great teaching.

Selected references

American Academy of Pediatrics. Ear Pits, Skin Tags, and Hearing Loss. AAP Grand Rounds. 2009 Jan 1;21(1):2-.DOI: 10.1542/gr.21-1-2

Assessing for a patent anus in a neonate – Turowski, C., Dingemann, J. & Gillick, J. Delayed diagnosis of imperforate anus: an unacceptable morbidity. Pediatr Surg Int 26, 1083–1086 (2010). https://doi.org/10.1007/s00383-010-2691-5

Pre and post ductal saturations – Rüegger, C., Bucher, H.U. & Mieth, R.A. Pulse oximetry in the newborn: Is the left hand pre- or post-ductal?. BMC Pediatr 10, 35 (2010). https://doi.org/10.1186/1471-2431-10-35

Plotting growth chart UK – https://www.rcpch.ac.uk/resources/uk-who-growth-charts-guidance-health-professionals & Plotting growth charts Australia https://www.rch.org.au/childgrowth/Growth_Charts/

Immunisations –  DFTB – Immunisation Quick reference

Bibliography and some other approaches

Queensland Maternity and Neonatal Clinical Guidelines Program – Neonatal Examination

Davies, Cartwright & Inglis, Pocket Notes on Neonatology, 2nd Ed. 2008. Elsevier: Australia

Examination Adapted from; Examination of the Newborn: A Practical Guide. Helen Baston, Heather Durward Pg 3

Oral or IV antibiotics?

Cite this article as:
Alison Boast. Oral or IV antibiotics?, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24974

There are many self-perpetuating myths when it comes to antibiotic use in children. A few that seem intuitive, and come up almost daily, include the idea that intravenous antibiotics are ‘better’, that children require lower doses than adults, and ‘longer is better’ when it comes to treatment duration.

A few key concepts can be helpful to understand why certain routes and doses of antibiotics are required:

  • Pharmacokinetics: the effect of the body on the drug – how the body absorbs, distributes, metabolizes and excretes the antibiotic
  • Pharmacodynamics: the effect of the drug on the body – how the antibiotic effects bacteria in the body 
  • Bioavailability: the amount of the antibiotic which is effectively absorbed when given orally and reaches the bloodstream

Here are some points to consider next time you need to chart antibiotics for a child.

 

When are intravenous antibiotics absolutely required?

  1. Speed – if there is a life (think sepsis, meningitis) or limb-threatening (eg. necrotising fasciitis) intravenous antibiotics are required as they reach peak plasma levels in seconds/minutes, rather than hours
  2. Absorption – for children with poor or unreliable oral absorption (eg. inflammatory bowel disease, short gut) intravenous antibiotics will likely be required
  3. Neonates – in general neonates are considered to have poor oral absorption, therefore antibiotics are usually given intravenously
  4. No oral options – in some cases there may be no oral option available; this is particularly relevant for highly resistant organisms such as extended-spectrum beta-lactamase producing organisms
  5. High dose – if a very high dose of an antibiotic is required the volume of liquid required for a child to consume may be excessive, in these cases intravenous antibiotics may be required
  6. Nil per os – in children who are not able to take any oral medications (eg. bowel obstruction) intravenous antibiotics may be required; remember insertion of a nasogastric tube and NG medications may be an option particularly for younger children
  7. Worsening infection on oral antibiotics – this one can be a little tricky as factors such as wrong dose (antibiotics are commonly under-dosed in the community), wrong antibiotic, and poor compliance need to be considered, but sometimes children may require admission for intravenous antibiotics

 

When can you change to oral antibiotics?

There are four general principles guiding the change from intravenous to oral antibiotics (McMullen et al.)

  • Clinical condition – note that fever alone does not need to prevent switch
  • Ability to absorb oral antibiotics
  • Availability of an appropriate oral antibiotic
  • Practical issues

The above reference gives a thorough discussion on the evidence of when to switch to oral antibiotics for a range of common paediatric infections (skin and soft tissue, urinary tract infections etc).

 

What are other factors need to be taken into account?

Bioavailability – some drugs have excellent oral absorption, therefore there it is almost criminal to give them IV if the child can swallow them! Think metronidazole, rifampicin, doxycycline, ciprofloxacin and clindamycin (which all have good tissue penetration)

“Help – my child refuses to take oral antibiotics!” – this is a tricky one and the use of an experienced paediatric pharmacist is invaluable as there are many aids that can be used to help resilient toddlers take their medications

 

Why is this important?

The implications of shortening the course of intravenous antibiotics and antibiotics overall are numerous…

  • Shorter courses of antibiotics may affect antimicrobial resistance
  • Shorter inpatient stays (required unless outpatient antimicrobial therapy available through a hospital in the home service) associated with improved quality of life in children and their families, and money-saving for the hospital system
  • Intravenous antibiotics may be associated with line complications, pain and traumatic experiences for children

 

Selected references

McMullan BJ, Andresen D, Blyth CC, Avent ML, Bowen AC, Britton PN, Clark JE, Cooper CM, Curtis N, Goeman E, Hazelton B. Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines. The Lancet Infectious Diseases. 2016 Aug 1;16(8):e139-52.

Different halves of the same page: Gayle Hann and Amani Simpson at DFTB19

Cite this article as:
Team DFTB. Different halves of the same page: Gayle Hann and Amani Simpson at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22374

Gayle Hann is a paediatrician that hit the headlines for her tireless work in helping the sufferers of gang violence. She has made it her mission to engage and involve youth gang members in their own care and rehabilitation in an effort to prevent them needing to come to the hospital in the future.

Amani Simpson is now an entrepreneur and founder of Aviard Inspires but at the age of 21, he was stabbed seven times in the course of a robbery. Since then he has dedicated his life to transform the lives (and perceptions of) youths across the country.

Never have such an unlikely couple come together to make a difference. This talk, from #DFTB19, had laughs, tears, and fist-bumps aplenty. It is the feel-good story of the conference that will reaffirm the idea that people are not all bad.

 

©Ian Summers

 

 
DoodleMedicine sketch by @char_durand 
 

 

 

This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal. DFTB20 will be held in Brisbane, Australia.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

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Guillain-Barre Syndrome

Cite this article as:
Aoife Fox. Guillain-Barre Syndrome, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.25051

A 2-year-old girl, Amy, attends the emergency department. Her father says that for the last 24 hours she has been refusing to walk. Prior to this, she was running amuck without difficulty. In the ED, you notice that she is now having difficulty crawling. She has no significant medical history but did have fever along with a runny nose and cough 2 weeks prior to her attendance which her parents managed with paracetamol at home.

 

What is Guillain-Barré Syndrome?

Guillain-Barré Syndrome (GBS) is a group of acute immune-mediated polyneuropathies.  It most commonly presents as an acute monophasic, paralyzing illness provoked by a preceding infection.

It is the most common cause of acute flaccid paralysis in children. The annual incidence is 0.34 to 1.34 cases per 100,000 in under the 18s, which makes it less common in children than in adults. It rarely occurs in children younger than 2 years, but when it does affect younger children because GBS is way off our radars, this can make it really tricky to diagnose. Boys are affected more often than girls.

 

What causes it?

It’s thought that an immune response cross-reacts with the myelin or axon of peripheral nerves due to molecular mimicry. Similar peptide sequences between the body’s own peptides and foreign peptides sometimes cause the immune system to get confused and attack its own tissues.  You probably knew that myasthenia gravis is due to auto-antibodies against the acetylcholine receptor but did you know that the receptor shares a 7 amino acid sequence with HSV, the herpes simplex virus? It’s thought that exposure to HSV may be the precipitant for myasthenia gravis.

Approximate 2/3 of patients give a history of an antecedent respiratory tract or GI infection. Campylobacter infection is the most commonly identified precipitant and can be demonstrated in as many as 30% of cases. Other infectious precipitants include CMV, EBV, Mycoplasma pneumoniae, and influenza-like illnesses.

Other suggested triggers include immunization, although there is no clear causal relationship several cases suggest an association, as well as one with trauma and surgery.

What about Guillain Barre and COVID?

There have been several case studies reporting GBS associated with SARS-CoV-2 during the COVID-19 pandemic. Given the small number of cases, it is unclear whether severe neurological deficits are typical features of COVID-19 associated GBS. An answer to the diagnostic conundrum of whether the respiratory compromise in COVID19-associated-GBS is due to coronavirus or muscle weakness is yet to be answered.

 

How can I recognize it?

GBS classically begins with paraesthesia in the extremities – fingers and toes –  followed by lower extremity symmetric, or modestly asymmetric, weakness that ascends up the body. In severe cases, the muscles of respiration are affected, in about 10-20% of children.

Cranial neuropathy can also occur, most commonly affecting facial nerves, causing bilateral facial weakness.

Autonomic dysfunction occurs in approximately half of children with GBS: cardiac dysrhythmias, orthostatic hypotension, hypertension, paralytic ileus, bladder dysfunction, sweating.

Physical exam typically reveals:

  • Symmetric weakness
  • Diminished or absent reflexes
  • Gait abnormalities
  • Sensory symptoms include pain, paraesthesia (reflecting nerve irritability)

Generally, children have shorter clinical courses and more complete recoveries in comparison to adults. A child’s function typically deteriorates for 2-4 weeks followed by a slow return of function over the coming weeks to months.

 

On examination, you find a quiet child who is otherwise acting appropriately. She is afebrile and the rest of her vitals are within normal limits. No bruises or rashes are observed on her skin and there is no evidence of trauma. Cardiovascular, respiratory, abdominal and ENT exams are unremarkable. Her extremities are warm and well perfused with normal pulses. There is no bony tenderness or deformities on palpation of her limbs. On neurological examination, she is moving all 4 limbs spontaneously. However, she will not bear weight or stand. Both her lower limbs are weak on exam. Her grip strength is reduced and when given a toy, it falls. Both upper and lower extremity reflexes are absent.

 

Subtypes

GBS most commonly presents in the classical way above: a mixed motor and sensory polyneuropathy with lower limb pain and ascending weakness. This is the classic Acute Inflammatory Demyelinating  Polyradiculopathy (AIDP), which accounts for 85 to 90% of cases in the developed world. But, there are a few other subtypes of GBS you should be aware of.

Acute Motor Axonal Neuropathy (AMAN), is a purely motor from of GBS, occurring mainly in Asia, Central and South America and associated with a preceding Campylobacter infection. Its clinical features are similar to AIDP, but respiratory failure is more common.

Acute Motor-Sensory Axonal Neuropathy (AMSAN) is similar to AMAN but with more sensory symptoms. The course tends to be prolonged and severe but is pretty uncommon in children.

Miller-Fisher syndrome is characterized by an external ophthalmoplegia, ataxia and muscle weakness with areflexia. It affects adults more commonly than children but should definitely be on your radar in a child presenting with cranial nerve and lower limb neurology.

 

How can it be diagnosed?

The initial diagnosis of GBS is based on the history and clinical exam – be suspicious of a child with lower limb weakness, weak reflexes and a preceding illness. Use investigations to confirm your suspicion.

CSF

CSF protein above 45mg/dL with a normal WCC count is present in 50-66% of patients in the first week after symptoms onset and ≥75% of patients in the third week. This disconnect between protein and white cells is called albuminocytologic dissociation.

Gadolinium-enhanced MRI of Spine

MRI will show contrast enhancement of the spinal nerve roots, cauda equina or cranial nerve roots. These changes aren’t specific to the GBS, but can be helpful in the correct clinical setting.

Nerve conduction studies

This is the most specific and sensitive test available for GBS, abnormal in up to 90% of cases. The test can be technically difficult in small children.

Antibodies

Antibodies against GQ1b (the ganglioside component of a nerve) are present in the vast majority of patients with Miller-Fisher syndrome.

 

In the emergency department, you send baseline bloods (FBC, U&E, LFTs and CRP) which are all normal and organize a CT head under sedation which is unremarkable. After getting consent from her parents you perform a lumbar puncture. The CSF appears clear. It has no red blood cells, 2 white blood cells and CSF glucose is within the normal limits but her protein is mildly elevated. No organisms were seen on gram stain and cultures had no growth after 5-days. You refer her to the neurology team for further investigation.

 

What else could it be?

The differential diagnosis of GBS is long.

 

Brain

  • Bilateral strokes
  • Acute disseminated encephalomyelitis
  • Acute cerebellar ataxia syndrome
  • Psychogenic symptoms

Spine

  • Anterior spinal artery syndrome
  • Compressive myelopathy
  • Transverse myelitis
  • Poliomyelitis
  • Infectious causes of acute myelitis

Peripheral nervous system

  • Chronic inflammatory demyelinating polyneuropathy
  • Critical illness polyneuropathy
  • Infection-related radiculitis (e.g. HIV, CMV, Lyme disease)
  • Thiamine deficiency
  • Toxins: biologic toxins (diphtheria), heavy metals (arsenic)
  • Vasculitis
  • Metabolic and electrolyte disorders (e.g. hypoglycaemia, hypophosphatemia)

Neuromuscular junction

  • Botulism
  • Myasthenia gravis
  • Neuromuscular blocking agents

Muscle

  • Acute inflammatory myopathies (e.g. dermatomyositis, polymyositis)
  • Acute viral myositis
  • Acute rhabdomyolysis
  • Critical illness myopathy
  • Metabolic myopathies (e.g. hypokalaemia, hyperkalaemia)
  • Mitochondrial myopathies

 

What is the treatment?

The mainstay of treatment is supportive management including close monitoring of motor, autonomic and respiratory function as well as pain management and prevention of immobility complications, such as pressure ulcers. ICU admission for mechanical ventilation will be required in 10-20% of kids. This is more likely to be needed in children with:

  • rapidly increasing weakness,
  • bulbar dysfunction,
  • bilateral facial weakness or

In addition IV immunoglobulin (IVIG) and plasmapheresis (plasma exchange) can be used in children with severe, progressive GBS (i.e. worsening respiratory status or need for mechanical ventilation, rapidly progressing weakness, inability to walk unaided or significant bulbar weakness).

IVIG  is typically preferred to plasmapheresis in children due to its better safety record and ease of administration

Plasmapheresis can be useful in bigger children where technically it is more feasible to perform. However, there are no reliable studies to suggest one has better efficacy than the other in children.

 

During her admission, Amy has a Gadolinium-enhanced MRI of the spine and nerve conduction studies which are consistent with the acute inflammatory demyelinating polyradiculopathy (ADIP) subtype of GBS. She is given IVIG. She does not develop any respiratory complications. On discharge after three weeks, her weakness is greatly improved and completely resolves over the next two months.

 

Bottom line

  • Clinical examination is key – do not forget to examine reflexes!
  • Always ask about recent viral illnesses.
  • GBS is the most common cause of acute flaccid paralysis in children and 10-20% will require mechanical ventilation.

 

Selected references

Bloch SA, Akhavan M, Avarello J. Weakness and the Inability to Ambulate in a 14-Month-Old Female: A Case Report and Concise Review of Guillain-Barre Syndrome. Case Rep Emerg Med [Internet]. 2013 [cited 2020 Apr 11];2013. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572648/

 Yuki N, Hartung H-P. Guillain–Barré Syndrome. New England Journal of Medicine [Internet]. 2012 Jun 14 [cited 2020 Apr 5];366(24):2294–304. Available from: https://doi.org/10.1056/NEJMra1114525

Rudant J, Dupont A, Mikaeloff Y, Bolgert F, Coste J, Weill A. Surgery and risk of Guillain-Barré syndrome: A French nationwide epidemiologic study. Neurology. 2018 25;91(13):e1220–7.

Hicks CW, Kay B, Worley SE, Moodley M. A clinical picture of Guillain-Barré syndrome in children in the United States. J Child Neurol. 2010 Dec;25(12):1504–10.

Dimachkie MM, Barohn RJ. Guillain-Barré Syndrome and Variants. Neurol Clin [Internet]. 2013 May [cited 2020 Apr 5];31(2):491–510. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939842/

Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. The Lancet [Internet]. 2016 Aug 13 [cited 2020 Apr 5];388(10045):717–27. Available from: https://www.sciencedirect.com/science/article/pii/S0140673616003391

Ryan MM. Pediatric Guillain-Barré syndrome. Curr Opin Pediatr. 2013 Dec;25(6):689–93.

Hughes RAC, Wijdicks EFM, Barohn R, Benson E, Cornblath DR, Hahn AF, et al. Practice parameter: Immunotherapy for Guillain–Barré syndrome. Neurology. 2003 Sep 23;61(6):736.

Understanding care arrangements in Australia

Cite this article as:
Mary Hardimon. Understanding care arrangements in Australia, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.23701

When seeing young people, it is important to recognize that their support person/s may vary from that of the typical ‘nuclear family’ which we are accustomed to thinking of. Having an understanding of the types of care arrangements is important to help develop our relationship with the young person and implement realistic management plans (both in the short and long term).

Out of home care is the care of children 0 – 17 years who are unable to live with their primary caregivers. This placement of care may be short or long term and may have been arranged formally or informally. It may be voluntary or involuntary.

Regardless of the care arrangement, the goal is to provide the index child/children with stability, safety and a sense of security

 

Important definitions

  • Residential care – placement in a building where the purpose is to provide placements for children and there are paid staff eg. Mercy Community
  • Family group homes – placement in a provided home with live-in carers who are reimbursed/subsidized for provision of care
  • Home-based care – placement is in the home of the carer who is reimbursed for the care of the child; subcategories include:
    • Relative/kinship
    • Foster care
    • Third-party parental care arrangements
    • Other home-based out of home care
  • Independent living

 

Relative/kinship: placement with relatives or persons well known to the child. This is particularly common within the Indigenous communities as an informal arrangement.

Foster care: A form of out-of-home care where the caregiver is authorized and reimbursed (or was offered but declined reimbursement) by the state/territory for the care of the child

Third-party parental care: transfer of all duties, powers, responsibilities, and authority to which parents are entitled by law to a nominated person(s) whom the court considers appropriate. The nominated person may be an individual such as a relative or an officer of the state or territory department.

Other: boarding schools, hospitals, hotel/motel, defense forces

 

What does out of home care look like in Australia?

In Australia, there are ~48 000 children in out of home care, with children 1 – 4-year old being the most heavily represented age group. These numbers are rising. The majority of children are in home-based care arrangements (93%) with kinship/relative care being the most common.

 

Out of home care arrangements

 

The majority of children have been in care for >12 months.

Up to 40% of individuals will have experienced 2 to 5 different care arrangements.

1/3 of children reported having 5 or more caseworkers during their time in out of home care

Although out of home care is not the preferred arrangement, for a number of young persons in Australia, this is currently their safest and most secure option. Having a good understanding of these arrangements and the difficulties experienced by these young people will allow optimization and coordination of care to better support them.

 

Selected resources

https://aifs.gov.au/cfca/publications/children-care

https://www.betterhealth.vic.gov.au/health/ServicesAndSupport/temporary-and-permanent-care-for-children

https://www.aihw.gov.au/reports-data/health-welfare-services/child-protection/glossary#parental-resp-order

 

 

 

 

Acute COVID management in children – evidence summary

Cite this article as:
Michaela Waak + Cameron Graydon. Acute COVID management in children – evidence summary, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.25071

This post is a rapid review of pertinent paediatric literature regarding the management of COVID-19 disease. The papers have been reviewed by Michaela Waak and Cameron Graydon as part of the Don’t Forget the Bubbles team. This is not a systematic review, but includes relevant published online content available in the English language as of April 24th 2020. Please note some references are pre-prints, editorials or draft society documents and have not undergone peer review. This has been highlighted in the review of the article.

The review is divided into paediatric acute management, critical care management, and emerging therapies.

We will aim to add more papers as more literature becomes available. If you have suggestions for literature to add please email hello@dontforgetthebubbles.com 

Executive Summary (Updated 2nd May)

Currently, there is a paucity of data in children on optimal management because of the lower prevalence of serious cases. There are small case series’ and anecdotal reports that younger infants, medically complex and obese teenagers are at higher risk of severe disease with a possibility of genetic susceptibility. As a result of the lack of trials, only protocols for COVID-19 respiratory management and resuscitation have been published for children. The overarching principles are that best practice care should not be altered by pandemic-related concerns, other aetiologies should be looked for and broad consideration must be given to reduction in health care worker exposure.

 

Acute management

The acute management for mild and moderate respiratory illness should include home or hospital-based monitoring for clinical deterioration and for the prevention of transmission. Symptomatic and supportive care for respiratory symptoms should follow local protocols with the early consideration of a trial of prone positioning of the patient. Minimal data exists either to confirm or refute, indications or safety concerns for non-invasive respiratory support. It should be considered on an individual basis in the context of disease severity, trajectory and local resources available for protection of healthcare workers (such as negative pressure rooms, PPE) titrating to the lowest possible flow to maintain a target saturation.

Management of cutaneous, cardiac and neurological disease/complications could follow published adult evidence until paediatric published and peer-reviewed experience evolves.

There are increasing reports of cutaneous and neurological manifestations that have been hypothesised to be related to endothelial dysfunction and a hyper-coagulable state.

Additionally, reports are emerging of a constellation of findings giving a picture similar to the cardiovascular, cutaneous and gastrointestinal presentation of Kawasaki’s disease but with shock, some requiring mechanical support.  It seems to be occurring in a geographically and ethnically non-uniform distribution perhaps suggesting a genetic susceptibility. Laboratory features of raised BNP, troponin, IL-6, ferritin, d-dimers and lymphopaenia should be looked for early and consideration given to immuno-modulatory medications.  The timing of the onset of symptoms relative to positive rt-PCR and serology tests suggests an immune mediated pathophysiology – it is unsure at the moment of the exact pathophysiology but hypotheses involve direct viral effects, cytokine storm, immune complexes, abnormal T-cell or immunoglobulin responses.  The different presentations may represent a number of different immune-mediated syndromes. Treatment strategy is supportive, with consideration of immuno-modulators – some centres are treating as they would for Kawasaki’s with aspirin and IVIG.

 

Critical care management

The critical care considerations including patient and staff safety, infrastructure, patient flow, planning for PPE, and intra-and inter-hospital transfer should follow published hospital, national and international guidelines, and recommendations. Best practice care considerations for ventilated patients are of utmost importance, now more than ever, and Pediatric Acute Lung Injury Consensus Conference (PALICC) recommendations should be followed for paediatric ARDS (PARDS). This includes regular re-evaluation of the lung dynamics – which have been noted to have unexpected compliance characteristics in adults. Similar considerations apply for the neonatal critical care units where guideline summaries suggest no deviation from best-practice care especially where shared decision-making with parents is possible.

In the face of the current controversy regarding acute interventions including best practice and safety considerations surrounding resuscitation and ECLS support, national guidelines that consider international guidance statements should be followed with local best practice care support.

In the absence of sufficient data on paediatric resuscitation in positive or possible COVID-19 patients, rapid response recommendations have been formulated by the Resuscitation Council United Kingdom, American Heart Association, Advanced Paediatric Life Support, and ILCOR. ILCOR has recently published, in draft, a review of the evidence to assess which aspects of resuscitation are aerosol-generating procedures. Chest compressions, assisted ventilation, and advanced airway manoeuvres are all considered potentially aerosol-generating procedures requiring appropriate PPE, whereas defibrillation can be performed wearing droplet precautions, and most organisations suggest  covering the patient’s mouth and nose.

Paediatric extracorporeal membrane oxygenation (ECMO) for patients with COVID-19 has not been reported in the literature yet, at least two patients have been successfully weaned in Europe and form part of the ELSO registry data and increasing use in the US. It seems likely, as the pandemic progresses, that patients with indications for ECMO may also have COVID-19 infection. It is not known how this might impact upon ECMO outcomes. ELSO recommends standardisation of indications, management, data collection, and containment and consideration of ECMO support for refractory ARDS or sepsis on a case-by-case basis with consideration for capacity and resource availability.

 

Emerging Therapies

Emerging therapies include convalescent plasma, IVIG, antivirals (eg remdesivir), chloroquines, and selective cytokine blockade (eg Tocilizumab), and are currently undergoing rapid review. The pace of change and the paucity of data may mean that potential treatments and management strategies could outpace current paradigms for research and development. Novel management and data collection should be conducted in the setting of best practice trials. If relevant clinical trials are available nationally or internationally, strong consideration should be given to enrolling patients rather than prescribing off-label use.

References

PICU COVID data

First authorLast authorJournalDate of PublicationPaper link
S Balasubramanian A V RamananINDIAN PEDIATRICS 7 May 2020https://indianpediatrics.net/CONVID29.03.2020/SA-00159.pdf
Ye, Y Guyatt, G H CMAJ4 May 2020https://www.cmaj.ca/content/cmaj/early/2020/05/04/cmaj.200648.full.pdf
Al GiwaProbst, M AEB medicine3 May 2020https://www.ebmedicine.net/topics/infectious-disease/COVID-19
Health Policy TeamRCPCHRCPCH website1 May 2020https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf
van den Berg, JTerheggen, UESPNIC online28 Apr 2020https://espnic-online.org/Media/Files/ESPNIC-ESPR-COVID19-Transport-Consensus-recommendations-040420202
Lynch, JSultan, SIDSA guidelines website27 Apr 2020https://www.idsociety.org/practice-guideline/covid-19-guideline-infection-prevention/
Joseph, T Moslehi, M AInternational pulmonologist’s consensus group on COVID26 Apr 2020https://www.unah.edu.hn/dmsdocument/9674-consenso-internacional-de-neumologos-sobre-covid-19-version-ingles
Marini, J JGattinoni, LJAMA24 Apr 2020https://jamanetwork.com/journals/jama/fullarticle/2765302
Shen, K-LWang, X-FWorld Journal of Pediatrics24 Apr 2020https://link.springer.com/article/10.1007/s12519-020-00362-4
Cstagnoli, RLicari, AJAMA Pediatrics22 Apr 2020https://jamanetwork.com/journals/jamapediatrics/fullarticle/2765169
K ChiotisMM NakamuraJ Pediatric Infect Dis Soc22 Apr 2020https://academic.oup.com/jpids/advance-article/doi/10.1093/jpids/piaa045/5823622
Yuki, KKoutsogiannaki, SClin Immunol20 Apr 2020https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169933/
Chiotos, K.Nakamura, MJ Pediatric Infect Dis Soc18 Apr 2020https://academic.oup.com/jpids/article-pdf/doi/10.1093/jpids/piaa045/33112599/piaa045.pdf
APLS AustraliaRetrieved from the APLS Australia website14 Apr 2020https://apls.org.au/sites/default/files/uploadedfiles/APLS%20Australia%20Statement%20on%20Paediatric%20Resuscitation%20during%20the%20COVID-19%20pandemic%20v1.0.pdf
Matava, CTFiadjoe, JEAnesthesia & Analgesia13 Apr 2020https://journals.lww.com/anesthesia-analgesia/Abstract/publishahead/Pediatric_Airway_Management_in_COVID_19_patients__.95683.aspx
Matthai, J Sobhan, PIndian Pediatr. 12 Apr 2020https://indianpediatrics.net/CONVID29.03.2020/SA-00162.pdf
MatthaiSobhanInd Pediatrics12 Apr 2020https://www.ncbi.nlm.nih.gov/pubmed/32279064
Mimouni, FMendlovic, JJournal of Perinatology10 Apr 2020https://www.nature.com/articles/s41372-020-0665-6
Morray, B. H.Sathanandam, S. K.J Invasive Cardiol9 Apr 2020https://www.invasivecardiology.com/sites/invasivecardiology.com/files/articles/images/Morray%202020%20Apr%209%20AOP%20wm.pdf
MorraySathanandam J Invasive Cardiol9 Apr 2020https://www.invasivecardiology.com/articles/resource-allocation-and-decision-making-pediatric-and-congenital-cardiac-catheterization-during-novel-coronavirus-sars-cov-2-covid-19-pandemic-us-multi-institutional-perspective
BalasubramanianRamananInd Pediatrics9 Apr 2020https://www.ncbi.nlm.nih.gov/pubmed/32273490
Edelson, DTopjian, ACirculation9 Apr 2020https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.047463
Thampi, SOng, JPaediatr Anaesth8 Apr 2020https://onlinelibrary.wiley.com/doi/epdf/10.1111/pan.13863
Phua, JDu, BLancet Resp Med6 Apr 2020https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(20)30161-2.pdf
Ashokka, BChoolani, MAmerican Journal of Obstetrics and Gynecology3 Apr 2020https://www.ajog.org/article/S0002-9378(20)30430-0/fulltext
AshokkaChoolaniAm J Obs & Gyn3 Apr 2020https://www.ajog.org/action/showPdf?pii=S0002-9378%2820%2930430-0
Wilson, KRello, J American Thoracic Society3 Apr 2020https://www.thoracic.org/professionals/clinical-resources/disease-related-resources/covid-19-guidance.pdf
Misra, D. PZimba, O.Clin Rheumatol 202031 Mar 2020https://link.springer.com/article/10.1007/s10067-020-05073-9
DP MisraO ZimbaClin Rheum31 Mar 2020https://link.springer.com/article/10.1007%2Fs10067-020-05073-9#author-information
Hasan, AFergie, JCureus31 Mar 2020https://www.cureus.com/articles/29784-coronavirus-disease-covid-19-and-pediatric-patients-a-review-of-epidemiology-symptomatology-laboratory-and-imaging-results-to-guide-the-development-of-a-management-algorithm
Cooper, KPerkins, GD International Liaison Committee on Resuscitation (ILCOR)30 Mar 2020https://costr.ilcor.org/document/covid-19-infection-risk-to-rescuers-from-patients-in-cardiac-arrest
Chandrasekharan, PLakshminrusimha, SAmerican Journal of Perinatology30 Mar 2020https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0040-1709688.pdf
Cook, T MHiggs, AAnaesthesia27 Mar 2020https://onlinelibrary.wiley.com/doi/full/10.1111/anae.15054
Ford, NDoherty, MJIAS26 Mar 2020https://onlinelibrary.wiley.com/doi/epdf/10.1002/jia2.25489
Mimouni Mendlovic J Perinatology25 Mar 2020https://www.nature.com/articles/s41372-020-0665-6.pdf
Al Giwa, LLBDuca, AEmerg Med Pract24 Mar 2020https://www.ebmedicine.net/topics/infectious-disease/COVID-19
Kneyber, MRimsensberger, PEuropean Society for Paediatric and Neonatal Intensive Care23 Mar 2020https://scp.com.co/wp-content/uploads/2020/04/2020-ESPNIC-PEMVECC-COVID-19-practice-recommendations.pdf.pdf
Molloy, EBearer, CFPediatric Research23 Mar 2020https://www.nature.com/articles/s41390-020-0881-y_reference.pdf
Wang, YZhu, L-QWorld Journal of Pediatrics 12 Mar 2020https://link.springer.com/content/pdf/10.1007/s12519-020-00353-5.pdf
Shen, K-LYang, K-LWorld Journal of Pediatrics5 Feb 2020https://link.springer.com/content/pdf/10.1007/s12519-020-00344-6.pdf

Critical care management

Ziehr DR, Alladina J, Petri CR, et al. Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study [published online ahead of print, 2020 Apr 29]. Am J Respir Crit Care Med. 2020;10.1164/rccm.202004-1163LE. doi:10.1164/rccm.202004-1163LE

Boston group peer reviewed publication of a retrospective case series (66 patients intubated during March 11-30). Description of the hospital recommendations included not to use high-flow nasal cannula or non-invasive ventilation, favouring volume-cycled ventilation with a target tidal volume below 6 cc/kg ideal body weight. Early prone ventilation was promoted for patients with a P/F ratio <200 and PEEP was titrated as per ARDSnet table, titration by best compliance, or oesophageal manometry. 85% of patients met the Berlin definition of ARDS. They conclude that their findings differ from earlier series describing near-normal respiratory system compliance and lack of recruitability in early presentations of COVID-19 respiratory failure. Their cohort was managed with established ARDS therapies including low tidal volume ventilation, conservative fluid administration, and prone ventilation. Minimum follow-up was 30 days, overall mortality was 16.7% and most patients were successfully extubated and discharged from the ICU.

 

Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA. Published online April 24, 2020. doi:10.1001/jama.2

Expert opinion paper on ARDS by two Italian authors. The concept of two phenotypes, the traditional “baby lung” classic ARDS pathophysiology versus CARDS with “type L” and high compliance and “type H” with low compliance is described. The table contains suggestions for respiratory management at different time periods (before intubation, during mechanical ventilation, after intubation and weaning phase). These hypotheses have been debated in the literature – based on findings by the Boston group, published as a cohort study by the American Thoracic Society – suggests that management should follow published ARDS management strategies and diagnostic criteria.  Discussion around the Boston cohort has included that they may be patients presenting later in their disease process.

 

Chandrasekharan P et al (April 8, 2020), Neonatal Resuscitation and Postresuscitation Care of Infants Born to Mothers with Suspected or Confirmed SARS-CoV-2 Infection., American Journal of Perinatology, https://doi.org/ 10.1055/s-0040-1709688. ISSN 0735-1631.

This peer-reviewed and published guideline summary article has been authored by international neonatologists (US and Europe).

It outlines the precautions and steps to be taken before, during, and after resuscitation of a newborn born to a COVID-19 mother. Three optional variations of current standards are proposed and involve shared decision making with parents for perinatal management, resuscitation of the newborn, disposition, nutrition, and post-discharge care. The authors highlight that availability of resources may also drive the application of these guidelines.

Key points involve:

  • Unclear risk of vertical transmission (transmission from family members/providers to neonates is possible).
  • Importance of appropriate PPE (airborne vs. droplet/contact precautions for providers to prevent transmission)
  • Parent engagement (shared decision-making: options for rooming-in, skin-to-skin contact, and breastfeeding)

This summary article highlights the key features of current recommendations including options when shared decision making is possible, the tables and diagrams add to the practical scenarios.

 

Edelson et al. Interim Guidance for Life Support for COVID-19. From the Emergency Cardiovascular Care Committee and Get With the Guidelines®-Resuscitation Adult and Pediatric Task Forces of the American Heart Association in Collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, The Society of Critical Care Anesthesiologists, and American Society of Anesthesiologists: Supporting Organizations: American Association of Critical Care Nurses and National EMS Physicians, Originally published 9 Apr 2020 https://doi.org/10.1161/CIRCULATIONAHA.120.047463

This publication contains interim guidance on resuscitation for COVID19 suspected or positive patients including in the paediatric and neonatal setting. It is produced by the AHA in collaboration with several other American societies. General principles include the provision of best practice care balanced with reduction in provider exposure. The main considerations include donning of appropriate PPE before entering the scene and limiting personnel, prioritization of oxygenation and ventilation strategies with lower aerosolization risk (including the application of viral filters) and person-centered consideration of the appropriateness of starting and continuing resuscitation (goals of care for the individual patient).

Specific considerations are given for children and neonates. In cases of out of hospital cardiac arrest – lay rescuers of children should perform chest compressions and consider mouth to mouth ventilation if willing and able, especially if the household members have been exposed to the victim at home. If a face mask is available, it can be placed on the victim or the rescuer if bystanders are unable or unwilling to perform mouth-to-mouth. 

Neonatal resuscitations – Routine initial care, avoid suctioning of the airway. Endotracheal medications such as surfactant and epinephrine (adrenaline) are considered aerosol-generating procedures. Intravenous delivery of epinephrine via a low-lying umbilical venous catheter is the preferred route of administration during neonatal resuscitation.

The provided figures and tables complement this concise guidance statement and are well worth the read for any acute care provider.

 

Couper K et al, COVID-19 infection risk to rescuers from patients in cardiac arrest; on behalf of the International Liaison Committee on Resuscitation. International Liaison Committee on Resuscitation. 2020. “COVID-19 Infection Risk to Rescuers from Patients in Cardiac Arrest.” https://costr.ilcor.org/document/covid-19-infection-risk-to-rescuers-from-patients-in-cardiac-arrest. Draft version accessed 12th April 2020

This document contains the ILCOR Draft Treatment Recommendations in the pre-published form.

The main suggestions read:

  • We suggest that chest compressions and cardiopulmonary resuscitation have the potential to generate aerosols (weak recommendation, very low certainty evidence)
  • We suggest that in the current COVID-19 pandemic lay rescuers consider chest compressions and public access defibrillation (good practice statement).
  • We suggest that in the current COVID-19 pandemic, lay rescuers who are willing, trained and able to do so, consider providing rescue breaths to infants and children in addition to chest compressions (good practice statement).
  • We suggest that in the current COVID-19 pandemic, healthcare professionals should use personal protective equipment for aerosol-generating procedures during resuscitation (weak recommendation, very low certainty evidence).
  • We suggest it may be reasonable for healthcare providers to consider defibrillation before donning personal protective equipment for aerosol-generating procedures in situations where the provider assesses the benefits may exceed the risks (good practice statement).

 

APLS Australia,   Statement    on    Paediatric    Resuscitation    during    the    COVID-19    Pandemic, retrieved from the APLS Australia website on 14th April 2020

APLS Australia has released recommendations that are consistent with ANZCOR and ILCOR guidelines. 

While recognising the concerns of health care providers regarding the risk of transmission of coronavirus they stress the importance any delays have to outcomes. Risk to rescuers is increased (chest compressions and positive pressure ventilation have the potential to generate aerosols) but the underlying principles for CPR remain unchanged. They stress that efforts to anticipate deterioration will allow opportunity for early PPE donning in order to minimise delays.

They also recognise that healthcare systems will need to consider: availability and distribution of appropriate PPE; education of the workforce in appropriate PPE donning and disposal techniques; appropriate resources and personnel to provide on-going care for children resuscitated after cardiac arrest; paediatric resus simulation in the local environments; and for staff to become familiar with and adhere to local guidelines which describe the PPE that should be worn for aerosol generating procedures. 

 Treatment recommendations are given for three situations: 

Out-of-hospital recommendations: 

  • Health care professionals and lay rescuers who are willing, trained and able to do so, should continue to deliver rescue breaths to children in addition to chest compressions.  
  • If rescuers are untrained or unwilling to perform rescue breaths, chest compression only CPR is preferable to no CPR. 

ALS in hospital recommendations:

  • Healthcare professionals should use PPE for aerosol-generating procedures during resuscitation in children with confirmed or suspected COVID 19 infection.  
  • People in the room should be minimised consistent with appropriate care.  
  • Risk associated with aerosol-generating procedures (AGPs) should (where practical) be minimised by:  
    1. Addition of viral filters on all airway devices (BVM, SGA, ETT) where available 
    2. Preferentially allocating the most experienced clinician to manage the airway 
    3. Recognising that a cuffed endotracheal tube (ETT) is preferable to a supraglottic airway (LMA or I-Gel), which is preferable to bag-valve-mask (BVM) ventilation (optimally using a two-person technique, with an oropharyngeal airway, to minimise leak) to minimise aerosol production 
    4. Healthcare professionals should anticipate potential clinical deterioration in high risk patients and don appropriate PPE in preparation for resuscitation 

 Pre-hospital and Rapid Response Teams recommendations: 

  • Use PPE for aerosol-generating procedures during resuscitation in children with confirmed or suspected COVID 19 infection. 
  • To don appropriate PPE prior to arrival at the scene in anticipation of the need to perform aerosol generating procedures during resuscitation.  
  • For early communication with the teams to where they are transferring the patients to allow them to prepare and use appropriate PPE. 

 

Kevin C. Wilson, Sanjay H. Chotirmall, Chunxue Bai, and Jordi Rello on behalf of the International Task Force on COVID‐19.  COVID‐19: Interim Guidance on Management Pending Empirical Evidence, From an American Thoracic Society‐led International Task Force.

The American Thoracic Society convened an international group of experts to develop Consensus on Science with Treatment Recommendations (CoSTR) in the absence of high-grade evidence as of 3rd April.  These recommendations are published as an open-access document on the ATS website.

The main suggestions refer to ARDS rescue management interventions:

  • prone positioning in patients with refractory hypoxemia and COVID-19 pneumonia (i.e. acute respiratory distress syndrome [ARDS])
  • consideration for extracorporeal membrane oxygenation (ECMO) in patients who have refractory hypoxemia, COVID-19 pneumonia (i.e. ARDS), and have failed prone ventilation, and
  • to prescribe hydroxychloroquine (or chloroquine) to hospitalized patients with COVID-19 pneumonia if all of the following apply: a) shared decision-making is possible, b) data can be collected for interim comparisons of patients who received hydroxychloroquine (or chloroquine) versus those who did not, c) the illness is sufficiently severe to warrant investigational therapy, and d) the drug is not in short supply

While referencing adult patients, consideration should be given to the broader applicability of adult recommendations, particularly to our young adult patients.

 

Practice recommendations for the management of children with suspected or proven COVID-19 infections; Paediatric Mechanical Ventilation Consensus Conference (PEMVECC) Section Respiratory Failure – European Society for Paediatric and Neonatal Intensive Care

This consensus statement issued by the European Society for Paediatric and Neonatal Intensive Care in March 2020 is published through the ESPNIC COVID-19 resource webpage.

This is a pragmatic and very useful guide for clinicians caring for COVID-19 positive children with respiratory symptoms.

Main recommendations include:

  • Monitoring respiratory failure severity by the SpO2/FiO2 ratio for noninvasive ventilation; oxygenation index for invasive ventilation.
  • The definition of paediatric ARDS remains unchanged, recommendations for non-invasive and invasive ventilation initiation and settings and PARDS management recommendations including for neuromuscular blockade, prone positioning, escalation of therapies for refractory hypoxemia and caring for the invasively ventilated child are highlighted.

Of note: These recommendations do not suggest deviation from best-practice care as per previously published PALICC guidelines. In fact, critically appraising the data coming from adult practice, before making use of these in paediatric practice is strongly recommended.

 

Jason Phua et al (April 6,2020), Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations, Lancet Respir Med 2020, https://doi.org/10.1016/S2213-2600(20)30161-2

This is a summary article published for the Asian Critical Care Clinical Trials Group. It highlights the epidemiological and clinical features of critically ill COVID-19 patients as of April 2nd, 2020 and emphasizes the evolving case fatality rate in adults of 5.2% compared to 9.6% for SARS and 34.4% for MERS.

Key recommendations include that clinicians should have a high index of suspicion, and a low threshold for diagnostic testing, for COVID-19 as clinical features are non-specific. They should cautiously evaluate unanswered clinical management questions, including the role of non-invasive ventilation, high-flow nasal cannula, corticosteroids, and various repurposed and experimental therapies.

Surge options and preparations are highlighted as important. These include optimizing infrastructure, supplies, staff protection from nosocomial transmission and the promotion of mental wellbeing. Table 3 focuses on evolving therapies and highlights the general lack of peer-reviewed published safety data.

Even though it is mainly based on adult data and authored by the Asian trials group, this article highlights important management and safety considerations for the paediatric setting.

 

Acute management

Shen KL, Yang YH, Jiang RM, et al. Updated diagnosis, treatment and prevention of COVID-19 in children: experts’ consensus statement (condensed version of the second edition) [published online ahead of print, 2020 Apr 24]. World J Pediatr. 2020;1‐8. doi:10.1007/s12519-020-00362-4

Peer reviewed and published paper summarising the chinese guidelines for management of children with COVID-19 disease authored by 30 Chinese experts from 11 national medical academic institutions. Epidemiology is summarised and case definitions clarified. Early warning signs of more severe cases are specified (increased respiratory rate, persistent high fever, lethargy, decreased blood lymphozytes, increased liver enzymes, metabolic acidosis, increased D-dimers, desaturation, extrapulmonary complications, co-infection with other viruses/bacteria). Glucocorticosteroids are recommended for 5 days for severe ARDS. Other treatments including antivirals and convalescent plasma are recommended only as part of clinical trials.

 

Lynch J, Sultan S. Infectious Diseases Society of America Guidelines on Infection Prevention in Patients with Suspected or Known COVID-19; Published by IDSA, 4/27/2020, posted online at www.idsociety.org/COVID19guidelines/ip

This guideline by an American MDT expert panel will be updated online. It contains an executive summary, background, definitions and recommendations based on a literature review and expert consensus on the use of PPE for HCP providing care for patients with suspected or known COVID-19. Recommendations on use of N95 masks and respirators, shoe covers, double vs single glove, face shields and surgical masks. The algorithm provided shows a clear process of what PPE to use in which settings and use either a surgical mask or N95 (or N99 or PAPR) respirator as part of appropriate PPE depending on the procedure related risks.

 

Cook TM, El-Boghdadly K, McGuire B, McNarry AF, Patel A, Higgs A. Consensus guidelines for managing the airway in patients with COVID-19: Guidelines from the Difficult Airway Society, the Association of Anaesthetists the Intensive Care Society, the Faculty of Intensive Care Medicine and the Royal College of Anaesthetists. Anaesthesia. 2020;75(6):785‐799. doi:10.1111/anae.15054
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This peer reviewed published article by a UK anaesthetic expert group aims to provide clinicians with figures and text to be adapted locally for safe provision of airway management in patients with COVID-19 disease drawing on published literature and immediately available information from clinicians and experts. Topics covered include the prevention of contamination of healthcare workers, the choice of staff involved in airway management, the training required, and the selection of equipment namely for emergency tracheal intubation; predicted or unexpected difficult tracheal intubation; cardiac arrest, anaesthetic care; and tracheal extubation. The overarching principle suggested is SAS – safe (for staff and patient), accurate (avoid unreliable, unfamiliar or repeated technique) and swift (timely, without rush or delay). The flowcharts, figures, photos and diagrams provided summarise and highlight the crucial principles and practical suggestions. The panel agreed on eight recommendations and provided narrative summaries of other interventions undergoing evaluations.

 

Castagnoli R, Votto M, Licari A, et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review. JAMA Pediatr. Published online April 22, 2020. doi:10.1001/jamapediatrics.2020.1467

This published and peer reviewed paper from a respected Italian group is a systematic review that assesses and summarises clinical features and management of children with SARS-CoV-2 infection. They included eighteen studies with 1065 participants that reflected research performed in China, except for 1 clinical case in Singapore. Mild respiratory symptoms (fever, dry cough, and fatigue) or asymptomatic children were most commonly described. CXR or CT showed bronchial thickening and ground-glass opacities, and these findings were also reported in asymptomatic patients. No deaths were reported in children aged 0 to 9 years. Available data about therapies were limited. Antibiotics and supportive care were most commonly described, most patients did not require oxygen therapy. They conclude that many therapeutic questions in children with COVID-19 remain unanswered, so in the interim, paediatric knowledge stems from the management of other respiratory infectious diseases.

 

van den Berg J, Terheggen U. European consensus recommendations for neonatal and paediatric retrievals of positive or suspected COVID-19 infants and children, European Society of Paediatric and Neonatal Intensive Care (ESPNIC)

This expert statement published on the ESPNIC website and endorsed by the European society of paediatric research (ESPR) describes procedures and precautions for safe retrievals of infants and children with confirmed or suspected COVID-19. Keypoints include case definitions, PPE suggestions, Airway management, respiratory support recommendations, special considerations for neonates and parents and decontamination recommendations for the transport vehicle.

The summary recommendations regarding respiratory support read:

  • “Use high-efficiency particulate air (HEPA) filters on expiratory and inspiratory hose of ventilator
  • NIV including CPAP and HFNC increases risk of aerosol spread of viral particles
  • Use any form of NIV with caution, if so, best provided by a ventilator with filters / closed circuits systems and under full PPE
  • Consider early intubation

 

The Royal College of Paedaitrics and Child Health publish guidelines on management of ” Paediatric Multisystem Inflammatory Syndrome Temporally Associated with COVID-19 (PMISTAC)

This guidance document published on the Royal College of Paediatrics and Child Health website provides the first case definition and recommendation document raising awareness to clinicians and has been developed after expert review of the cases. In rare instances children that test positive for COVID-19 can present with a multisystem inflammatory syndrome that shows features of Kawasaki disease, staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis and macrophage activation syndromes. Early recognition by paediatricians and specialist referral including to critical care is essential. A clinical management summary is provided and includes health care worker protection, early management, monitoring, and general treatment principles. An MDT approach involving PICU and paediatric infectious diseases, immunology, rheumatology is suggested. Candidate antiviral therapies should only be given in the context of a clinical trial if available (e.g. RECOVERY trial) and all children should be considered for recruitment in research studies such as DIAMONDS and ISARIC-CCP. Any child being considered for antiviral therapy should be discussed at an MDT, Immunomodulatory therapy should be discussed with paediatric ID and/or clinicians with appropriate experience in their use (e.g. rheumatology, immunology, haematology) on a case by case basis and used in the context of a trial if eligible and available.

 

Ye, G Guyatt . Treatment of patients with non severe and severe coronavirus disease 2019: an evidence based guideline. CMAJ 2020.doi: 10.1503/cmaj.200648; early-released April 29, 2020

Published and peer reviewed paper from an international expert panel that included two consumers concludes:

“Given the largely very low-quality evidence regarding benefits of the treatments that the panel considered, and given the panel’s inferences regarding patient values and preferences, the panel made almost exclusively weak recommendations against use of the interventions included in this guideline. The research community should interpret the weak recommendations that this guideline offers as a call to urgently undertake rigorous RCTs of the candidate interventions.” It is designed as a “living guideline” that is updated as evidence evolves.”

In summary current recommendations read:

  • Available evidence is either indirect (from studies of influenza, severe acute respiratory syndrome and Middle East Respiratory Syndrome), from observational studies, or RCTs limited in sample size and rigour, permitting only weak recommendations and very large uncertainty.
  • The panel made only 1 weak recommendation in favour of treatment: use of corticosteroids in patients with acute respiratory distress syndrome (ARDS), based on indirect evidence.
  • The panel made weak recommendations against use of corticosteroids in patients without ARDS, against use of convalescent plasma and against several antiviral drugs that have been suggested as potential treatments for COVID-19.
  • Rigorous randomised trials are urgently needed to establish the benefits and risk of candidate interventions.

 

Giwa AL, Desai A, Duca A. Novel 2019 coronavirus SARS-CoV-2 (COVID-19): An updated overview for emergency clinicians. Emerg Med Pract. 2020;22(5):1‐28.

This is a second updated paper from Giwa et al. – authors in Italy and New York.  While some of the information is already out of date it gives an excellent and comprehensive summary of pathology, infection control management, evaluation, imaging and treatment options.

 

Balasubramanian et al. Coronavirus Disease (COVID-19) in Children – What We Know So Far and What We Do Not? INDIAN PEDIATRICS; APRIL 09, 2020 [E-PUB AHEAD OF PRINT]

Literature Review published in the Indian Journal of Pediatrics

Summary findings:

Pediatric COVID-19 infection usually mild or asymptomatic and with better prognosis (mortality rare)

Hypotheses of reasons for milder disease: differences in immune system function, differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) – Angiotensin converting enzyme 2 (ACE2)

COVID-19 in immunosuppressed children

No severe cases reported (may be protected by their weaker immune response), no data available on severity of COVID-19 infection in children with malnutrition, rheumatic heart disease or HIV

Children with COVID-19

Early management: supportive therapy (adequate nutrition, fluid /electrolyte management O2 supplementation, communication with parents, alleviating anxiety

Severely affected children: Respiratory management as per Pediatric Lung Injury Consensus Conference Group (PARD)

Decision to start antiviral or immunomodulatory treatment should be made carefully in consultation with experts in pediatric infectious disease and immunology and ideally as part of a trial (Hydrochloroquine only without Azitromycin, Lopinavir/Ritonavir, Tolizizumab, Anakinra)

Neonatal management (newborns of COVID-19 infected mothers):

  • Only essential personnel attending with full PPE, follow standard neonatal resuscitation measures, self-inflating mask to be used if positive pressure ventilation required,
  • newborn tested at 24 and 48 hours of life, until 2 consecutive negative tests
  • Antivirals/hydroxychloroquine/steroids or intravenous immunoglobulin (IVIG) should not be administered
  • Breastfeeding encouraged with the mother wearing a mask
  • vaccinations prior to discharge from the hospital

 

Matthai et al. for The Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition.    Coronavirus Disease (COVID-19) and the Gastrointestinal System in Children. Accessed 12 April 2020 (This is a preprint version of an article submitted for publication in Indian Pediatrics)

This is a review article pertaining to COVID and the GI system in paediatrics.

Similar to the respiratory mucosa, angiotensin converting enzyme-2 (ACE-2) receptor and transmembrane serine protease 2 (TMPRSS2) co-express in the gastrointestinal tract, which facilitates viral entry into the tissue. Less than 10% of children with infection develop diarrhea and vomiting. Prolonged rt-PCR positivity in the stool has raised the possibility of feco-oral transmission though they note that there has only been one case of active virus cultured from a stool specimen. It is unclear whether prolonged persistence of RNA in the stool is secondary to its continued positivity in bronchoalveolar sputum, even when nasopharyngeal mucosa swabs are negative.

They suggest upper GI endoscopy carries a higher risk of aerosols then lower GI endoscopy and acute upper or lower GI bleeding, esophageal obstruction, foreign body ingestion etc. may require endoscopy without delay, but should be done with full personal protection equipment including the N95 mask.

A mild rise in bilirubin and transaminases is seen in approximately 25% and more common, approximately 50% with severe disease. Consideration should be given to hypoxic and drug related liver injury (Remdesivir, Tocilizumab) aetiologies.

Available evidence is that IBD and liver transplant patients do not have an increased risk of developing Covid-19 and should stay on their immunomodulating medications. They recommend in an established COVID-19 infection, to continue calcineurin inhibitors targeting a lower trough levels and lower the dose of mycophenolate or azathioprine. Patients on high dose steroids, should have it reduced to a minimum dose based on body weight to prevent adrenal insufficiency.

Children on treatment for chronic liver diseases like Wilson disease, autoimmune hepatitis, Hepatitis B and C should continue their treatment protocols.

 

Morray BH et al. Resource Allocation and Decision Making for Pediatric and Congenital Cardiac Catheterization During the Novel Coronavirus SARS-CoV-2 (COVID-19) Pandemic: A U.S. Multi-Institutional Perspective. J Invasive Cardiol. 2020 Apr 9. pii: JIC20200409-2. [Epub ahead of print] PMID: 32269177

This article is a review of congenital cardiac catheterization practices in 56 US pediatric cardiac centers and highlighted the differences between institutions in high prevalence areas and low prevalence areas.

Noting a large decrease in activity across all centers they discuss the general approach and urgency of cases.

They classified cases in Table 3, but briefly:

1A (urgent/emergent) – haemodynamic instability

  • Pericardiocentesis; atrial septostomy for TGA; atrial septal decompression for HLHS; atrial septal decompression on ECMO; Impella (Abiomed) placement; thrombectomy for symptomatic PE with significant RV strain; coiling of AP collaterals/bronchial arteries due to hemoptysis. 1B (urgent/emergent) – to enable evaluation or discharge
  • PDA/RVOT stenting for decreased pulmonary blood flow; balloon valvuloplasty of critical or severe AS/PS; perforation of PV for PA/IVS; PDA closure in premature infants; biopsy in OHT for acute rejection; surveillance after recent OHT.

2 (semi-elective) – a delay in procedure (>30 days) could be detrimental

  • Pulmonary vein stenosis and significant RV dysfunction; heart failure and a large PDA or muscular VSD/s; increasing aortic valve/pulmonary valve gradients that already meet the threshold for intervention; venous interventions to treat occlusions/ stenoses to alleviate symptoms.

3 (elective) – can be delayed >30d

  • Secundum ASD; PDA without significant heart failure; moderate pulmonary aortic valve stenosis; pulmonary valve dysfunction awaiting pulmonary valve replacement; presurgical catheterization (pre-Fontan catheterization); routine surveillance biopsy post OHT.

There was broad consensus for delaying certain cases, and with the understanding that some cases through delay could change their relative urgency.

They recommend a local action plan should be developed for the neonate born to a positive or possible COVID mother.

They further discuss in detail the concerns in the current pandemic relating to medical resource preservation, minimizing exposure risk and resource reallocation/repurposing.

 

Thampi S et al, Special considerations for the management of COVID-19 pediatric patients in the operating room and pediatric intensive care unit in a tertiary hospital in Singapore. Paediatr Anaesth. 2020 Apr 8. doi: 10.1111/pan.13863

This article is based on a single centre experience at the National University Hospital in Singapore, a mixed adult and paediatric tertiary hospital.

General measures, as well as specific strategies in the operating rooms and paediatric intensive care unit (PICU), are presented.

PPE-related measures discussed included mask fitting and doffing/donning exercises and simulation medicine as well as powered air-purifying respirator PARP training, especially for staff who failed N95 mask fitting. With these PPE measures in place no nosocomial infections were observed. Anaesthesia considerations included a limitation on the number of accompanying adults, PPE considerations, having the most senior available operator manage the airway, the use of closed breathing systems, in-line suction and minimization of circuit disconnections as well as strict disinfection guidelines. These measures were similar in the PICU setting but also included recommendations on the use of negative pressure rooms and simulation training for emergency situations and airway management.

Limitations of this article include that it reflects accepted care in a single centre only and does not refer to the more widely accepted principle that best practice care should be provided to children during the pandemic including safe bag-mask ventilation in the event of clnical deterioration or arrest.

 

Ashokka, et al.  Care of the Pregnant Woman with COVID-19 in Labor and Delivery: Anesthesia, Emergency cesarean delivery, Differential diagnosis in the acutely ill parturient, Care of the newborn, and Protection of the healthcare personnel. 3 April 2020 (Journal Pre-proof American Journal of Obstetrics and Gynaecology) https://doi.org/10.1016/j.ajog.2020.04.005 

This is a review article with a summary of recommendations based on evidence to date.  The main recommendations:

Pertaining to staff are:

  • all healthcare staff attending to women in active labor need to don full personal protective equipment (PPE)

Pertaining care of the newborn:

  • no proven vertical transmission during pregnancy
  • possibility of acquiring the infection post-delivery

Advised against:

  • delayed cord clamping
  • skin to skin bonding between mothers and newborns

Can be considered:

  • breast feeding

Care of the unwell newborn

  • Designated NICU room with full infectious precautions

 

Mimouni et al. Mendlovic Perinatal aspects on the covid-19 pandemic: a practical resource for perinatal–neonatal specialists. Journal of Perinatology 25th Mar 2020 https://doi.org/10.1038/s41372-020-0665-6

They summarise

  • Vertical transmission from maternal infection during the third trimester probably does not occur or likely it occurs very rarely.
  • Consequences of COVID-19 infection among women during early pregnancy remain unknown.
  • We cannot conclude if pregnancy is a risk factor for more severe disease in women with COVID-19.
  • Little is known about disease severity in neonates, and from very few samples, the presence of SARS-CoV-2 has not been documented in human milk.
  • Links to websites of organizations with updated COVID-19 information are provided.
  • Infographics summarize an approach to the pregnant woman or neonate with suspected or confirmed COVID-19.

 

Al Giwa, LLB et al, Novel 2019 Coronavirus SARS-CoV-2 (COVID-19): An Updated Overview for Emergency Clinicians Publication Date March 23, 2020. Pub Med ID: 32207910

This is a peer-reviewed article dated 23rd March summarising COVID-19 data and experience from United States and Italian physicians. They provide a comprehensive review of the epidemiology, virology, pathophysiology, and management with an adult emergency department perspective.

The Italian experience in the emergency department is described – the first wave of upper airway symptoms, then patients with persistent fever and finally patients with interstitial pneumonia. Lung ultrasound was more sensitive than CXR and a useful screening tool and is discussed in some detail. Some patients presented with only gastro-intestinal symptoms and in small cohorts in California where 22% of adults and in Wuhan 40%  of children had co-infection with another virus.

Reference is made to the immunopathogenesis of COVID-19 (cytokine storm) and its implication in the rapid clinical deterioration seen. The release of inflammatory cytokines/chemokines initiates a positive feedback loop that leads to ARDS, multi-organ failure and death with histopathological features of virus-induced hemophagocytic lymphohistiocytosis. Elevated ferritin and IL-6 were associated with severe disease in adults in China.

They note the joint statement from multiple cardiology bodies highlighting there is “no clinical or scientific evidence to suggest that treatment with ACEI’s and ARB’s should be discontinued because of the COVID-19 infection.”

Even though mainly based on adult data some consideration should be given to the broader applicability in the young adult/paediatric context.

 

Hasan A, Mehmood N, Fergie J (March 31, 2020) Coronavirus Disease (COVID-19) and Pediatric Patients: A Review of Epidemiology, Symptomatology, Laboratory and Imaging Results to Guide the Development of a Management Algorithm. Cureus 12(3): e7485. doi:10.7759/cureus.7485

This is a review article from authors in the United States and has undergone peer-review.  Standard sections include epidemiology, symptomatology, imaging, labs, transmission, and a proposed management algorithm.

The algorithm recommends consideration for use of Remdesivir (which has no published in vivo data in paediatrics currently and is the subject of ongoing clinical trials) and use of procalcitonin to assess for superimposed bacterial infection (a recent systematic review by Kamat et al. did not support its use for differentiation of viral and bacterial, while a meta-analysis by Lippi suggested the higher PCT in severe COVID-19 patients might suggest bacterial infection). Serial PCTs may add to the clinical picture.

Given the limited evidence the suggestions should be taken with caution, especially in settings where clinical trials are available.

 

Matava, Clyde T, et al. On behalf of the PeDI-Collaborative Pediatric Airway Management in COVID-19 patients – Consensus Guidelines from the Society for Pediatric Anesthesia’s Pediatric Difficult Intubation Collaborative and the Canadian Pediatric Anesthesia Society, Anesthesia & Analgesia: April 13, 2020 – Volume Publish Ahead of Print – Issue – doi: 10.1213/ANE.0000000000004872  

Given challenges to medical systems and clinicians globally due to COVID-19’s rapid spread – namely clinicians required to care for patients with a highly contagious disease without evidence-based guidelines, this consensus guideline was created. The well-established and accepted nominal group technique, a structured, multistep, facilitated, group meeting technique used to generate and prioritise responses to a specific question was virtually adapted by the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from six countries, to arrive at this published and peer reviewed guideline based on expert opinion and early data about the disease. 

They are endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society 

Overarching goals during care: 

  • minimizing aerosolized respiratory secretions  
  • minimizing the number of clinicians in contact with a patient recognizing that undiagnosed asymptomatic patients may shed the virus and infect healthcare workers 

 The main recommendations are summarised here: 

  • administering anxiolytic premedications 
  • intravenous anaesthetic inductions preferred over gas inductions, but child temperament needs to be considered 
  • tracheal intubation using video laryngoscopes and cuffed endotracheal tubes
  • use of in-line suction catheters 
  • modifying workflow to recover patients from anesthesia in the operating room 
  • Anesthesiologists should consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19 
  • Airway procedures should be done in negative pressure rooms when available 
  • Adequate time should be allowed for operating room cleaning and air filtration between surgical cases 

 Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic 

 

Emerging therapies

Immune modulation (contributed by Dr Alberto Pinzon)

ANTI-CYTOKINES 

SARS-CoV-2 induced pneumonia is characterised by hyperactivation of effector T-cells and excessive production of inflammatory cytokines, particularly IL-6 (Cheng C, Zhang XR, et al. Advances in the Research of Cytokine Storm Mechanism Induced by Coronavirus Disease 2019 and the Corresponding Immunotherapies. Zhonghua Shao Shang Za Zhi:36:e005. In Chinese). Other pro-inflammatory cytokines (i.e., IL-1, TNF and IFN-g) are likely to contribute to this cytokine storm leading to progressive immunopathology, cytopaenias, plasma leakage, increased vascular permeability and disseminated intravascular coagulation. Consequently, anti-cytokine therapy has been postulated to confer protection against severe SARS-CoV-2 disease by reversing this hyperinflammatory response (Monteleone, G, Sarzi-Puttini P.C et al. Preventing COVID-19-induced pneumonia with anti-cytokine therapy. The Lancet Rheumatology.doi:10.1016/s2665-9913(20)300092-8.)

Preliminary evidence suggest that IL-6 inhibition with Tocilizumab (anti IL-6R) can reverse the detrimental inflammatory response in severe cases of SARS-CoV-2-pneumonia. An unpublished report from China including 21 patients, 17 with severe and 4 with critical illness showed that most patients had a marked improvement in oxygen requirement and CT changes within the first week of treatment.  Interestingly, all patients survived despite the severity of their disease (Xu X et al. Effective Treatment of Severe COVID-19 Patients with Tocilizumab. Unpublished study. 2020 [https://chinaxiv.org]). Another unpublished study in 21 Italian patients with severe SARS-CoV-2-pneumonia showed that Siltuximab (anti IL-6) was able to afford improvement in 33 % of patients while also stabilising a further 43% of patients. Nonetheless, 24% of the patients worsened, suggesting that cytokine blockade appears more effective if used earlier in the disease course (Gritti G, Raimondi F et al. Use of Siltuximab in patients with COVID-19 Pneumonia Requiring Ventilatory Support. Unpublished study. 2020 [https://www.medrxiv.org])

Multiple trials evaluating anti-cytokines and immune modulators are currently underway in Europe, the US and Asia including Tocilizumab and Sarilumab (anti-IL6R), Siltuximab (anti IL-6),Anakinra (anti-IL-1), interferon beta-1, Sirolimus as well JAK/STAT inhibitors (Baricitinib/Ruxolitinib/Tofacitinib). The use of anti-cytokines should be in the context of a randomised controlled trial and thus if a clinical trial is available, consider enrolling patients rather than prescribing off-label use.

The REMAP-CAP trial (Randomised, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia) driven by the Australian and New Zealand Intensive Care Society has implemented the Pandemic Appendix to the Core protocol to respond to COVID-19. Specific domains including: no immune-modulation, interferon beta-1, and Anakinra (anti IL-1) arms have already been approved. An amendment is also planned to add Tocilizumab (anti IL-6R) and Sarilumab (anti IL-6R) as interventions.

CONVALESCENT SERUM

The successful use of convalescent serum against coronavirus infection had been previously demonstrated in patients infected by SARS-CoV (Cheng Y, Wong R, et al. Use of Convalescent Plasma Therapy in SARS Patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005) as well as MERS-CoV. The anticipated mechanism of protection would be viral neutralisation although other mechanisms such as antibody-dependent cellular cytotoxicity and phagocytosis may be possible. In the case of COVID-19, a small study of 5 Chinese patients with severe disease in showed that convalescent serum containing neutralising antibodies improved the clinical status of all patients (Shen C, Wang Z, et al. Treatment of 5 Critically Ill Patients With COVID-19 with Convalescent Plasma. JAMA, 2020). Interestingly, a recent study of 222 Chinese patients identified risk factors for severe SARS-CoV-2-pneumonia a high neutrophil count, a low lymphocyte count and a high SARS-Cov-2-specific IgG level (Zhang B, Zhou X, et al. Immune phenotyping based on neutrophil to lymphocyte ratio and IgG levels predicts disease severity and outcome for patients with COVID-19). While these data highlight the detrimental effect of hyperinflammation with dysregulated cell counts, it also brings into focus the potential role for high non-neutralising antibody titres and thus antibody dependent enhancement (ADE) of viral entry as a contributor to disease severity. As such, convalescent serum is likely useful only in the subset of patients with poor neutralising antibody responses.

Further clinical trials of convalescent plasma are currently registered and some are underway for patients with severe or life-threatening COVID-19 disease in Europe, Latin America and the US. The FDA has in fact, approved its use under the Emergency Investigational New Drug whereby requestors must procure the convalescent serum from individual blood banks. Considerations including risk of pathogen transmission as well as adverse reactions (allergic, transfusion-associated circulatory overload (TACO), and transfusion-related acute lung injury (TRALI)) should be discussed prior to consenting patients for this treatment.  If a clinical trial is available please consider enrolling patients rather than prescribing off-label use.

INTRAVENOUS IMMUNOGLOBULIN

High dose intravenous immunoglobulin (IVIg) has long been utilised as an immune modulator in autoimmune and inflammatory diseases given its ability to modulate Fc receptors and antigen-presenting cells, inhibit the complement cascade as well as neutralise cytokines and regulate activated lymphocytes. High dose IVIg has been shown to be beneficial in SARS-CoV, MERS-CoV and influenza infections. Therefore, high dose IVIg has been proposed to modulate the severe hyperinflammatory responses associated with SARS-Cov-2. A preliminary report of three Chinese patients treated with IVIg at the early stage of clinical deterioration suggested a beneficial role despite the concomitant use of antivirals and steroids. (Cao, W, Liu X, et al. High-dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients with Coronavirus Disease 2019. Open Forum Infectious Disease. 2020).

Further trials are currently registered and underway in Europe and Asia. At present no clinical trials assessing the role of IVIg are available in Australia. If a clinical trial becomes available please consider enrolling patients rather than prescribing off-label use.

 

Yuki, K., Fujiogi, M., & Koutsogiannaki, S. (2020). COVID-19 pathophysiology: A review. Clinical immunology (Orlando, Fla.), 215, 108427. Advance online publication. 20 Apr 2020 https://doi.org/10.1016/j.clim.2020.108427

This is a recent review of the current knowledge about COVID-19 and consideration of the potential explanation of the different symptomatology between children and adults.

It has an excellent summary of the pathophysiology going into detail regarding the spike protein and subsequent activation of a fusion peptide through protease cleavage. A furin cleavage site, which has been associated with pathogenicity of viruses, is present on COVID-19. They discuss the immuno-pathogenesis especially with respect to the cellular response.

They discuss hypotheses regarding the differing clinical findings between adults and children:

  • Expression of ACE2 may differ
  • Qualitatively different response – ?immunosenescence or differing inflammatory response.

 

Ford N, Vitoria M, Rangaraj A, Norris SL, Calmy A, Doherty M. Systematic review of the efficacy and safety of antiretroviral drugs against SARS, MERS or COVID-19: initial assessment. J Int AIDS Soc. 26 March 2020. 2020;23(4):e25489. doi:10.1002/jia2.25489

This is a systematic review of the clinical outcomes of using antiretroviral drugs for the prevention and treatment of the related coronaviruses – SARS, MERS and COVID-19. Studies regarding Lopinivir/ritonavir predominated. The certainty of the evidence for the randomised trials was low. In the observational studies 3 out of 361 patients who received LPV/r died; the certainty of evidence was very low. Three studies reported a possible protective effect of LPV/r as post-exposure prophylaxis. Again, the certainty of the evidence was very low due to uncertainty due to limited sample size.

They concluded on the basis of the available evidence it is uncertain whether LPV/r and other antiretrovirals improve clinical outcomes or prevent infection among patients at high risk of acquiring COVID-19.

 

INTERNATIONAL PULMONOLOGIST’S CONSENSUS ON COVID-19; first edition Book; Editors: T Joseph and M Ashkan

This consensus statement by international authors from the US, Europe and Asia and edited by the chair of the paediatric section in World Association for Bronchology and Interventional pulmonology summarises recommendations regarding the mode of mode of transmission, epidemiology, clinical features, diagnosis, initial management, treatment options, prognostic features and prevention of patients presenting with COVID-19 disease. A summary of currently available drug treatments is summarised in table format. Critical care management is divided into respiratory management and supportive therapies. They conclude that there is presently no standardised treatment or vaccination available therefore a need for containment and prevention.

 

K Chiotis et al. Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2. J Pediatric Infect Dis Soc. 2020 Apr 22. pii: piaa045. doi: 10.1093/jpids/piaa045. [Epub ahead of print] PMID: 32318706

A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions convened to develop a set of guidance statements, recognizing the lack of clinical trials and generally low quality evidence.

Their key points are supportive care is sufficient for nearly all pediatric patients with COVID-19 given the overwhelming tendency toward mild illness in children. No agent has been identified with proven efficacy against SARS-CoV-2. They suggest a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, they suggest remdesivir as the preferred agent. Hydroxychloroquine can be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available.

They addressed 4 questions:

  1. Are antiviral agents indicated in children with COVID-19?
  • Supportive care is the mainstay – if they are to be considered enroll in study and with ID support
  1. What criteria define the pediatric population in whom antiviral use may be considered?
  • They suggest antiviral agents be considered only in children with positive virologic COVID-19 testing (or with very high suspicion and no prompt testing available), and that clinical criteria, specifically respiratory support requirements, be used to define scenarios in which use of antiviral agents are considered. If patients have mild or moderate disease they should be managed without antivirals. Patients with severe disease consideration should be given to disease trajectory and comorbidities that may confer increased risk. For critical disease (new or increased need for noninvasive or invasive mechanical ventilation, or there is sepsis or multi-organ failure) can be considered on a case by case basis.
  1. Does presence of any underlying medical condition or characteristic warrant different criteria for antiviral use based on increased risk of COVID-19-related morbidity or mortality?
  • There are no definitive data to support any specific risk factor for severe COVID19 in children but they suggest consideration of immunosuppression – particularly T-cell deficiency or dysfunction, obesity, chronic cardiac or respiratory disease and diabetes.
  1. What agents are preferred if antiviral therapy is offered to children with COVID-19?
  • If an antiviral is used, the panel suggests use of remdesivir as the preferred agent.
  • If used, they stress compliance with local institutional and regulatory policies for experimental therapies, with appropriate monitoring for toxicity and the input of a pediatric ID consultant.

 

DP Misra et al. Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets Clinical Rheumatology.  doi.org/10.1007/s10067-020-05073-9   31 Mar 2020

In the absence of high-quality evidence in this emerging disease, understanding of pathogenesis may help postulate potential therapies. Angiotensin converting enzyme 2(ACE2) appears important for viral entry into pneumocytes; dysbalance in ACE2 as caused by ACE inhibitors or ibuprofen may predispose to severe disease. Preliminary evidence suggests potential benefit with chloroquine or hydroxychloroquine. Antiviral drugs like lopinavir/ritonavir, favipiravir and remdesivir are also being explored.

Cytokine storm and secondary HLH might require heightened immunosuppressive regimens. Current international society recommendations suggest that patients with rheumatic diseases on immunosuppressive therapy should not stop glucocorticoids during COVID-19 infection, although minimum possible doses may be used. Disease-modifying drugs should be continued; cessation maybe considered during infection episodes as per standard practices. Development of a vaccine maybe the only effective long-term protection against this disease.

 

Eleanor J. Molloy et al, COVID-19 in Children and Altered Inflammatory Responses, Pediatric Research doi:10.1038/s41390-020-0881-y

This summary article highlights that severe COVID-19 infection is characterized by a massive pro-inflammatory response (cytokine storm) that can result in ARDS and multi-organ dysfunction (MODS). It suggests that patients with severe COVID-19 should be screened for HLH (increasing ferritin, decreasing platelet counts, rising ESR) to identify the subgroup of patients where anti-inflammatory treatment could improve mortality.
Therapeutic options discussed include steroids, IVIG, selective cytokine blockade (anakinra or tocilizumab), Remdesivir, hydroxychloroquine, and Janus kinase (JAK) inhibitors.

The sepsis model describes two different phases, first the cytokine storm which is followed by a period of potentially prolonged immunosuppression. The second phase is quoted as the major cause of sepsis-related fatalities.

It is suggested that anti-inflammatory therapies administered in the second phase might be deleterious and that the individualized immune response would be useful to guide therapy.

Further understanding of the differences in immune responses in different age groups is also referred to as the basis for future targeted immunotherapies.

This article provides a useful summary of the pathophysiological basis and practical implications of immunomodulatory therapies in children.

 

Kun‑Ling Shenet al, Diagnosis and treatment of 2019 novel coronavirus infection in children: a pressing issue. World Journal of Pediatrics, https://doi.org/10.1007/s12519-020-00344-6

This is an editorial from the 1st Feb discussing Interferon therapy.

Interferons are a group of low-molecular weight glycoproteins that modulate the responses of the immune system and form one of the first-line innate immune defences against viruses. There are three groups – alpha, beta, and gamma – that affect different immune responses, primarily through inducing antiviral effector proteins and activating cellular immunity to clear the virus.  There is some evidence from two Chinese studies looking at respiratory viruses showing inhibition with atomized interferon. They also reference evidence of SARS-CoV infection being inhibited by an alpha-interferon in a simian model.

 

Yan Wang, Li‑Qin Zhu Pharmaceutical care recommendations for antiviral treatments in children with coronavirus disease 2019. 2 March 2020, World Journal of Pediatrics https://doi.org/10.1007/s12519-020-00353-5

This is a viewpoint paper from two authors in China. They discuss interferon-alpha, Lopinavir/ritonavir (LPVr), ribavirin, umifenovir, and chloroquine. Suggested dosing regimens are provided in a table.

Chinese expert statements recommend IFN-alpha for children in high-risk populations who have a close history of contact with suspected infected patients or those with only upper respiratory tract symptoms in the early phase. They describe contraindications to the regime as being liver function test abnormalities, CrCl reduced below 50ml/min, mental illness, severe or unstable heart disease, aplastic anaemia, and suggest caution in infants less than 2-months of age.

Ribavarin, chloroquine, and umifenovir are discussed but no recommendations are given for use.

Umifenovir is currently only available in Russia and China.