Post ROSC care

Cite this article as:
Costas Kanaris. Post ROSC care, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.29109

Or some pointers on clinical management following the successful return of spontaneous circulation in children. 

It’s 5:40 am at Bubblesville ED. The red phone rings. The paramedic crew informs you that they are five minutes away with a 7 kg, 6-month-old, previously thriving, baby boy called Tarquin. He has had a witnessed out of hospital cardiac arrest at home and there was no prodromal illness according to the family. He choked during a breastfeed, turned blue, and stopped breathing. He had 5 minutes of CPR by the parents by the time the ambulance arrived and had ROSC by the paramedic team after a further 8 minutes. The rhythm strip was consistent with a PEA arrest. They are hand-ventilating him through an LMA.

This is his capillary gas on arrival in the ED
  1. What are your clinical priorities?
  2. What clinical problems do you anticipate in the immediate post-arrest phase?
  3. Who do you call for help?
  4. What do you do with the family whilst you’re managing the patient?
  5. What investigations do you need?

A systematic, collaborative, well-led approach to advanced paediatric life support can maximize the chances of the clinical team achieving a return of spontaneous circulation in a child that has arrested. We’ve seen the drill be before. We can go through our algorithms expertly and the 5-H’s and 5-T’s roll off the tongue, even under duress. The return of a pulse is heralded as the “hallelujah moment”, almost as if the patient is now healthy and safe and all we have to do is wait for the paediatric critical care retrieval team to arrive.

Whilst traditional APLS teachings are vital for the dissemination of knowledge and it’s application in everyday clinical life, their main focus is on the initial phase of achieving a pulse with very little attention placed on the all-important post-resuscitation phase.  This part of care is crucial, not only if we are to minimize secondary brain injury to the child but also to improve the chances of permanent returns of spontaneous circulation. Good short and long term outcomes rely heavily on how well we manage the post-resuscitation stage. 

There are four phases of cardiac arrest:-

Phase one: Prevention. This is the pre-arrest phase. Child safety and injury prevention strategies are in place to recognize deterioration. Adequate monitoring by using early warning systems and a pro-active approach to management is likely to contribute to avoiding an arrest.

Phase two: No flow arrest. This is a period of cardiac arrest prior to us commencing CPR. Our aim here is to minimize the time it takes to start life support. It is key that we involve the cardiac arrest team quickly, we start chest compressions early, and that we do not delay defibrillation if this is needed. 

Phase three: Low flow resuscitation. This phase describes when CPR is in progress. The aim is to achieve high-quality CPR in order to allow adequate coronary and cerebellar perfusion. Maintaining good ventilation and oxygenation whilst avoiding aggressive over-ventilation is paramount. It is during this phase that we systematically approach and threaten the reversible causes of cardiac arrest. 

Phase four: This is the post-resuscitation phase after ROSC has been achieved. Our aim here is to optimize coronary and cerebral perfusion. Neuroprotection and treatment of arrhythmias as well as treatment of post-cardiac arrest syndrome come under this phase. 

Adult v paediatric arrest: What’s the difference?

Out of hospital cardiac arrests in children >16 years of age are relatively rare – reported at 8-20/100000/ year. The incidence is only comparable to that of the adult population, estimated at 70/100000/year. The incidence of in-hospital paediatric arrests is much higher, with a nearly one-hundred-fold increase, compared to the out-of-hospital incidence for the <16’s. 

Survival, and especially a “good” survival from a neurological perspective still remain poor. Out of hospital survival rates are estimated to be 5 – 12%. Only 0.3 to 4% of those that survive have no long-term neurological insult.

Children have cardiac arrests due to severe respiratory insult or circulatory collapse, in the main. Either can lead to a respiratory arrest coupled with hypoxia, which then results in a cardiac arrest. The overwhelming majority of cardiac arrests present with a non-shockable rhythm.  It is also worth noting that almost half of the paediatric population that have a cardiac arrest have other chronic comorbidities such as respiratory conditions e.g. asthma, congenital cardiac disorders, or neurodisability. 

In the adult population, cardiac arrest is more likely due to long-term comorbidities such as ischaemic heart disease. This contributes to the development of an acute myocardial insult and (usually) a shockable rhythm. Understanding the difference in pathology leading to a cardiac arrest between adults and children is vital. Reversing the cause of the respiratory compromise can make the impalpable pulse palpable, allowing us to perfuse our patient once again. 

The recommended CPR ratio of 15:2 for children aims to provide adequate ventilation for oxygenation as well as satisfactory cardiac compressions to maintain sufficient perfusion of the coronary and cerebral circulation. Adult studies looking at compression-only CPR in patients with VF arrest have shown that success in achieving ROSC is due to pre-existing pre-arrest aortic blood oxygen and pulmonary oxygen stores.  As a mere 14% of cardiac arrests are due to a shockable rhythm, combining ventilation and compressions is vital. 

What is the Post Cardiac Arrest Syndrome (PCAS)? 

PCAS describes the period in which our patients are at the highest risk of developing ventricular arrhythmias and reperfusion injuries after ROSC. This is secondary to prolonged ischaemia then reperfusion of vital organs, primarily the myocardium and central nervous system. Its systemic effects are not dissimilar to those encountered in severe sepsis. There are four stages to PCAS:

  • Immediate post-arrest – First 20 minutes. 
  • Early post-arrest – 20 minutes to 6-12 hours. 
  • Intermediate phase – 6-12 hours up to 72 hours.
  • Recovery phase – From 72h onwards. 

Neuroprotection

Even high-quality closed-chest CPR can only achieve 50% of normal cerebral blood flow at best. It is not a secret that the brain does not tolerate hypoxia or ischaemia, the effects on both of these processes are exponential during a cardiac arrest, the longer the downtime, the worse the neurological hit

The pathophysiological cascade for neurodegeneration following cardiac arrest is complex and multi-factorial. Following a hypoxic or ischaemic period the brain develops cerebral oedema and cerebral hyperaemia. There is impaired cerebral vascular reactivity and like any other organ trying to reperfuse, the post-ischaemic biochemical cascade is activated. All these factors contribute to a secondary brain injury. Of course, the duration of hypoxia will in large part dictate how severe the primary brain injury is and whether the patient is likely to survive or not. Brain injury can manifest as myoclonus, stroke, seizures, coma, or brain death. 

We can minimize the extent of secondary brain injury with simple proactive, neuroprotective measures:

  • Strict normothermia
  • Aggressive seizure prophylaxis
  • Avoiding hypoxia and hyperoxia
  • Tight circulatory monitoring and support
  • Patient position
  • Eucapnia and normoventilation
  • Vigilant glucose monitoring
  • Frequent neurological assessment, especially before the administration of anaesthetic agents and paralysis

Strict normothermia

Therapeutic hypothermia following a cardiac arrest during the intermediate phase (after VF in adults), as well as newborns with birth asphyxia, has shown some correlation with better neurological outcomes and reduced neurodisability.  Similarly, there is strong evidence linking core temperature above 38° with worse neurological outcomes in patients following cardiac arrest. There is a wide variation in practice in relation to therapeutic hypothermia.  Mild hypothermia after paediatric cardiac arrest is in the policy of some PICU’s. Patients are cooled to 33-34°C for 1 – 2 days and are then gradually rewarmed. Paralysis can be used as an adjunct to stop shivering. Temperatures below 32°C should be avoided as they are associated with worse survival, immunosuppression, arrhythmias, coagulopathies, and infections.  The decision to “cool” must be made early and in conjunction with your critical care transport team. You have many tools at your disposal to achieve this such as cold IV fluids, cooling blankets, and catheters. 

What is, and should be, more aggressively targeted is strict normothermia (temperatures between 36-37°C), and depending on local practice hypothermia can be targeted to 33-36°C. Avoidance of pyrexia is crucial. Fever can result in an increased metabolic demand of the brain. This contributes to more ischemic injury and more infarcts as the threshold for ischemia in the injured brain is lower than that of the normal brain. The brain can no longer auto-regulate the mismatch between cerebral blood flow and metabolic demand.

Aggressive seizure prophylaxis

Seizures after paediatric cardiac arrest can occur in up to 47% of cases. 35% of these can lead to refractory status epilepticus.  Whilst CFAM/EEG monitoring is unlikely to be available in your local PED, it is important to have a low threshold to administer a long-acting anti-epileptic or a continuous infusion of a short-acting medicine to prevent/avoid this from happening. Ideally, a continuous infusion of midazolam +/- levetiracetam (less arrhythmogenic than phenytoin but both will work) and standard national guidelines should be followed. 

Clues as to whether a patient is still fitting include:

  • Unexpected changes in the pupillary size (beware of the child that had atropine on induction with the “fixed dilated pupils”).
  • Sudden changes in BP or heart rate.  

If you have given a paralytic for intubation, do not fall into the trap of thinking that the patient is not seizing, only an EEG or CFAM can tell you that. It is better to err on the side of caution.

Avoiding hypoxia and hyperoxia

Avoiding hypoxia and hyperoxia are also key components in minimizing secondary brain injury.  Whilst hypoxia will further exacerbate secondary brain injury, hyperoxia  (PaO2 > 40 kPa) is also be associated with worse survival due to oxygen free-radical formation that can inactivate intracellular enzymes, damage DNA, and destroy lipid membranes. It is reasonable to have high concentration oxygen therapy during the low-flow resuscitation and early post-resuscitation phases (as the commonest causes are respiratory). In the subsequent phases, we should target oxygen saturations between 94 and 96% and be proactive in how we reduce the FiO2 whilst avoiding hypoxia. There is a caveat in cases of severe anaemia or carbon monoxide poisoning. Then it is clinically appropriate for the highest concentration of oxygen to be administered.

Tight circulatory monitoring and support

Inotropic support may also be needed early. A degree of myocardial dysfunction/stunning is expected following CPR. To ensure adequate cerebral perfusion we need to target an age-specific, physiologically normal blood pressure. Both hypo and hypertension can exacerbate secondary brain injury. Because of this, monitoring the blood pressure through an arterial line is preferred. If the local set-up or skillset does not allow for arterial line placement, especially in smaller children, having non invasive blood pressure on 1-2 minute cycles can be a useful proxy.  

The paediatric myocardium is much more resilient than its adult counterpart.  If the arrest is not secondary to congenital heart disease the paediatric heart can regain normal function within 12-24 hours.  During the first 20 minutes following ROSC poor cardiac function is due to profound systemic vasoconstriction and cellular acidosis. We can support the myocardium by supplying adequate fluid resuscitation, targeting normal (age-appropriate) blood pressure and inotropic support. Point of care ultrasound, CVP monitoring, or assessing for hepatomegaly/rales if there is no access to the former, can help us prevent fluid overload

Inotrope choice is usually made with the help of the critical care team and depends on the balance between the need for inotropy and vasoconstriction.  Adrenaline is preferred for inotropy, noradrenaline for vasoconstriction.  Be aware that severe acidosis can cause catecholamine resistance, so giving some bicarbonate if the pH <7 may help your inotropes work better. Routine administration of bicarbonate has not been shown to improve clinical outcomes. There are some special circumstances in which we should consider its use such as cases of hyperkalaemia or hypermagnesaemia and arrests due to tricyclic antidepressant overdose. 

Patient position

The patient position that can achieve optimum cerebral perfusion is with the patient semi-sat up at a 30-45 degree angle.

Eucapnia and normoventilation

Avoidance of hypercapnia or hypocapnia is important in preventing secondary brain injury. It is, therefore, recommended that eucapnia is achieved by targeting a PaCO2 between 4.5 and 5.5 kPa. Hyperventilation can cause hypoxia and increase intracranial pressure due to hyperaemia, it can also cause further cerebral ischemia. As the intrathoracic pressures increase, cardiac venous return is impaired. Since the myocardium is already injured this can have catastrophic effects causing the BP to plummet and subsequently impair cerebral perfusion.

Vigilant glucose monitoring 

Following ROSC, children are also at risk of developing hypoglycemia (glucose <3 mmol/L). There is good evidence to suggest that hypoglycaemia negatively impacts neurological outcome and cause hypoglycaemic seizures, especially in the younger ages. Vigilant glucose monitoring and correction as per APLS guidelines is important. If regular dextrose boluses are needed, consider a continuous glucose infusion. If the patient mounts an adequate stress response, they may become hyperglycaemic.  There is no evidence to suggest that aggressive glucose control with insulin in the non-diabetic patient is beneficial; wait with watchful deliberation and the glucose will usually return to normal levels with no intervention.

Frequent neurological assessment

It is important to frequently assess neurological status frequently after ROSC as this can help us prognosticate. Take the time to do a very quick assessment ideally before the administration of anaesthetic agents and paralysis. Document clearly pupillary size/reactivity, GCS (and its break down) and any respiratory effort or gasping. 

Adjunctive investigations

Following ROSC a number of investigations will be needed to guide diagnosis and therapy. Routine bloods such as renal function, electrolytes, liver function tests, full blood count, and clotting are a basic standard. In cases of lactaemia and/or severe metabolic acidosis ammonia and toxicology is useful. Arterial blood sampling is invaluable to allow quick correction of any electrolyte abnormalities and help titrate ventilation settings and (in part) guide inotropic support. Arterial samples will also help uncover any exposure to carbon monoxide, especially in burns cases. 

From an imaging perspective, a chest X-ray is vital in ascertaining tube positioning and lung pathology as well as cardiac contours in case a congenital or acquired heart disease is suspected. Head CT is obviously useful in cases in keeping with traumatic arrest and NAI but timing of the CT and whether it should take place pre-departure to PICU or after depends largely on local trauma network protocols so should ideally be discussed with the regional trauma team lead and paediatric critical care transport team. 

Children that die or arrest unexpectedly in the UK are subject to a sudden unexpected death in infancy investigation (SUDI) so the appropriate referrals need to be made to the child protection team, police and social care. It is important to clarify that even near-miss cases merit triggering the same SUDI process to ensure that any NAI cases don’t slip through the net. 

Transport pearls

After ROSC the patients will need stabilisation and transfer to PICU for on-going management. Depending on the geographical location of your hospital and the availability of a critical care retrieval service you may have to transfer the patient yourselves or look after them until he/she is retrieved by transport team. A good transport and adequate neuroprotection can be achieved by applying these simple pearls: 

  1. Aggressive temperature monitoring and control between 33°C and 37°C.
  2. Monitor for seizures and pre-empt with long-acting antiepileptic accordingly.
  3. Correct electrolytes and hypoglycaemia and monitor frequently.
  4. Nurse the patient a 45° degree angle.
  5. Aim for a higher end of normal BP and use inotropes to achieve this. If you can’t insert an arterial line, have the NIVBP cycle every couple of minutes. 
  6. In cases of trauma, blood products should be used for volume. In an atraumatic arrest, balanced solution boluses are less harmful than 0.9% saline; don’t forget that you are still likely to need blood products. 
  7. Aim for a pCO2 of 4.5-5.5 kPa; use your continuous EtCO2 monitor to titrate ventilation. 
  8. Vigilant and through history/examination to rule out NAI. Free up a member of the team to do a thorough history from the family, always suspect NAI until proven otherwise especially in children under 6 months. 
  9. Know your anaesthetic drug side-effects (atropine dilates pupils for example so impairs our ability to monitor for seizures). Primum non nocere. 
  10. Intraosseous access can be used instead of a central line, have a low threshold to insert one and do it early.
  11. Have a member of the team check-in with the family every 10-15 minutes to explain what is happening, this is a bad day at work for you but probably the worst day of their lives. 

Conclusion

Achieving ROSC is an important step to give our patients a shot at survival. In some cases, achieving ROSC can only give us enough time to prognosticate and understand that survival is not possible. In some other cases ROSC can be the stepping-stone for a good, meaningful survival with a good quality of life. To achieve that, we must be able to apply good quality post–ROSC care and aggressive, pre-emptive neuroprotection. Learn the PCAS disease process to beat the PCAS disease process.  The APLS algorithm has become the bread and butter of anyone that is involved in paediatric care. Understanding and applying the principles of post-cardiac arrest syndrome is equally vital in improving survival outcomes for our patients. Learn the pearls, use them, teach them and I guarantee that it will make a difference.

Haemolytic Uraemic Syndrome

Cite this article as:
Jennifer Watt. Haemolytic Uraemic Syndrome, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.26233

What is HUS?

Haemolytic Uraemic Syndrome is a combination of findings which involves the triad of:

  • Microangiopathic haemolytic anaemia with red blood cell fragmentation on blood film
  • Acute renal failure
  • Thrombocytopenia

 What causes HUS?

About 90% of cases follow an infection, most commonly with entero-haemorrhagic E. Coli (EHEC). Other infective causes to be considered include Shigella and Streptococcus pneumoniae.

These infections are commonly contracted by the ingestion of contaminated food or water sources. In the US and UK, E. Coli 0.157 forms part of the natural intestinal microflora of cattle and sheep, therefore infection can be caused by direct contact with animal faeces. This can take place at farms or petting zoos, or via undercooked contaminated meat or dairy products.

The other 10-15% of cases represent atypical HUS and are due to a variety of causes, which will not be discussed here.

How do children present?

In children infected with EHEC about 10-15% of them will go on to develop HUS.

The common presentation includes bloody diarrhoea +/- cramping abdominal pain, fever and/or vomiting. The average onset of HUS after development of diarrhoea is about 7-10 days, with children under the age of 5 at highest risk.

Dependent on the extent of HUS progression, children may present with pallor, oedema, lethargy, or reduced urine output.

How to approach the examination

As with any unwell child, an A to E assessment is critical to rule out any immediate, life threatening complications.

Specific attention should be paid to assessing their fluid status, especially for evidence of dehydration.

*Although they may be oedematous, it is important to assess if they are intra-vascularly dry.

Things to examine for:

  • Prolonged capillary refill time
  • Observations: Tachycardia; hypotension or hypertension
  • Are they are cool peripherally?
  • Assess fontanelle tension (if applicable)
  • Dry mucus membranes/reduced skin turgor
  • Oedema (common locations in children include lower limbs, sacral and peri-orbital)

Is there evidence of neurological sequelae?

  • Irritable/restlessness
  • Confusion
  • Reduced GCS

Key investigations to perform

A. Initial blood samples:

  • Full blood count with blood film to assess for RBC fragmentation
  • Coagulation
  • Group and Save +/- cross match if haemoglobin low
  • Biochemistry: U&Es, calcium, phosphate, magnesium, bicarbonate
  • Glucose
  • CRP
  • Liver function including albumin
  • Amylase/Lipase (hospital dependent)
  • LDH
  • Blood gas
  • Blood cultures

B. Stool MC&S + E. Coli PCR

C. Urinalysis + MC&S

How to approach the management of HUS

Management should always be discussed with your local paediatric nephrologist in order to individualise/optimise management.

This is a generalised framework for the approach to management. Treatment involves supportive therapy to allow time for the infection to clear and the HUS process to cease.

1. Fluid Management:

  • IV access
  • Assess fluid status
  • Monitor for electrolyte disturbances and correct as per local guidelines
  • Daily weight, In/Out fluid balance, close monitoring of patient observations

*Fluid rehydration should be administered cautiously and in the setting of oliguria/anuria and oedema, fluids given should not exceed insensible loss + urine output.

*Evidence has shown that children presenting to hospital with dehydration in the prodromal phase of EHEC-induced HUS have a higher risk of developing an oliguric AKI and the requirement for dialysis. The administration of isotonic fluid in this phase has shown to be nephroprotective. 

2. Hypertension:

  • Can be secondary to fluid overload or as a result of the HUS process
  • Trial of diuretics or if receiving dialysis, fluid can be offloaded
  • If unresponsive to diuretics, consider a vasodilator (For example, amlodipine/ nifedipine *hospital dependent)

3. Anaemia:

  • Target Haemoglobin: 70-100g/L
  • Avoid excessive transfusion due to the associated risk of development of hyperkalaemia or fluid overload

4. Thrombocytopenia:

  • Consideration for platelet transfusion if platelets <10 x109
  • If undergoing surgery may require platelets > 50 x 109

5. Abdominal pain/vomiting:

  • Secondary to colitis
  • Regular paracetamol for pain relief
  • Avoid opiates if possible due to constipating side effects

*NSAIDS like Ibuprofen should not be prescribed*

6. Nutrition:

  • All patients should be reviewed by a dietician
  • NG tube and feeding regime

7. Dialysis (Peritoneal Dialysis or Haemodialysis) Indications:

  • Intractable acidosis
  • Diuretic resistant fluid overload
  • Electrolyte abnormalities Hyperkalaemia
  • Symptoms of uraemia

In children with HUS, peritoneal dialysis is the preferred treatment option as it is a gentler form of dialysis.

Haemodialysis is indicated for children with severe colitis, severe electrolyte abnormalities and those with neurological complications.

 HUS Complications

  • AKI:  Oliguria/anuria; hyperkalaemia; hypertension
  • Neurological: Irritable, confusion, seizures
  • Bleeding Risk
  • Cardiac: Hypertensive cardiomyopathy/myocarditis
  • Gastrointestinal: Severe colitis with bleeding/perforation
  • Pancreatitis
  • Pulmonary oedema

Selected references

Mayer CL, Leibowitz CS, Kurosawa S and Stearns-Kurosawa DJ. Shiga Toxins and the Pathophysiology of Hemolytic Uremic Syndrome in Humans and Animals. Toxins (Basel). Nov 2012. [Cited June 2020]; 4 (11): 1261-1287. doi: 10.3390/toxins4111261

Kausman. J 517 Haemolytic uraemia syndrome. Royal Hospital for Children- Nephrology. Dec 2013. [Cited June 2020]; Available from:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509707/

Hughes D. Management and investigation of bloody diarrhoea and haemolytic uraemic syndrome [draft].  GG&C Paediatric Guidelines- Kidney Diseases. Oct 30 2019. [Cited June 2020]; Available from: https://www.clinicalguidelines.scot.nhs.uk/ggc-paediatric-guidelines/ggc-guidelines/kidney-diseases/management-and-investigation-of-bloody-diarrhoea-and-haemolytic-uraemic-syndrome-draft/

Balestracci A et al. Dehydration at admission increased the need for dialysis in hemolytic uremic syndrome children. Pediatr Nephrol. 2012. [ Cited June 2020];27: 1407-1410. Doi: 10.1007/s00467-012-2158-0

Scheiring J. Andreoli SP. Zimmerhackl LB. Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Ped Neprhrol. 2008. [Cited June 2020]; 23: 1749-1760. Doi: 10.1007/s00467-008-0935-6

Grisaru Silviu. Management of hemolytic-uremic syndrome in children. Int J Nephrol Renovasc Dis. 2014 [Cited June 2020]; 7: 231-239. Doi: 10.2147/IJNRD.S41837.

Metabolic presentations part 1: neonates

Cite this article as:
Taciane Alegra. Metabolic presentations part 1: neonates, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.28423

You are working in the Paediatric Emergency Department and are called in to see a neonate with a history of irritability and seizures. You enter the room and are told the following: “Emma is a 3 day old, term baby who has been refusing feeds and crying excessively. Her mother says she has been irritable since birth. There has been no history of fever or cough. At home she had seizure-like activity with tonic posturing”. When you examine her, you find an awake, extremely irritable baby with flexed upper limbs flexed, extended lower limbs and global hyperreflexia. She is not dysmorphic and has no cardiac murmurs, respiratory distress or abdominal organomegaly.

Babies cry (a lot!) and we all know that, however Emma is presenting some red flags: she’s irritable and has an acute onset of seizures, without any obvious trigger.

The basics

In this post we will discuss some acute metabolic presentations in the neonatal period, how to identify potential problems and emergency treatment in the ED. You don’t need to make a diagnosis (bonus points if you do) but do need to remember that spotting the zebra will lead to more favourable outcomes. Metabolic diseases / disorders are also called inborn errors of metabolism (IEM).

How common are metabolic conditions?

Individually, metabolic conditions are rare, most having an incidence of less than 1 per 100,000 births. However, when considered collectively, the incidence may reach 1 in 800 to 1 in 2500 births (Applegarth et. al, 2000; Sanderson et.al, 2006). 

Remember: some symptoms can be unspecific and can mimic sepsis; or a child with an undiagnosed metabolic condition can decompensate with an intercurrent infection. 

An easy-to-understand classification by Saudubray divides the IEM in three groups of disorders, depending on how they present. 

Intoxication disorders

An acute or progressive intoxication from the accumulation of toxic compounds, usually small molecules. 

These usually present with a symptom-free interval and clinical signs of ‘intoxication’, which may be acute, although can be intermittent.

  • disorders of amino acid catabolism: e.g. phenylketonuria, maple syrup urine disease, homocystinuria, tyrosinemia 
  • most organic acidurias: e.g. methylmalonic, propionic, isovaleric acidaemia
  • urea cycle defects: e.g. Ornithine transcarbamylase deficiency (OTC deficiency), Citrullinemia type I (ASS1 deficiency).
  • sugar intolerances: galactosemia
  • metals: Wilson’s, Menkes, hemochromatosis
  • porphyrias

Disorders involving energy metabolism

A deficiency in energy production or utilization, within the liver, myocardium, muscle, brain or other tissues. 

Common symptoms include hypoglycemia, hyperlactatemia, hepatomegaly, failure to thrive and cardiac failure. 

  • Mitochondrial defects: congenital lactic acidemias (defects of pyruvate transporter, pyruvate carboxylase, pyruvate dehydrogenase, and the Krebs cycle), mitochondrial respiratory chain disorders and the fatty acid oxidation defects (MCAD deficiency).
  • Cytoplasmic energy defects: disorders of glycogen metabolism (collectively known as glycogen storage diseases), hyperinsulinism.  

Complex molecules disorders

Problems in the synthesis or catabolism of complex molecules, leading to storage of big molecules. 

Symptoms are chronic, progressive and independent of intercurrent events or food intake. 

  • Mucopolysaccharidosis (I-IV, VI and VII). The eponymous names are used less frequently now, particularly in the literature, but you might come across them in clinical practice (MPS I, Hurler’s Syndrome; MPS II, Hunter’s Syndrome; MPS VI, Maroteaux- Lamy) 
  • Gaucher disease
  • Peroxisomal disorders: e.g. X-linked adrenoleukodystrophy (X-ALD) and Zellweger’s Syndrome.

Treatment strategies

Remember your biochemistry: a substrate is transformed by an enzyme into a product .

If there is a problem with the enzyme, the substrate will accumulate. If this substrate accumulation is a problem, we eliminate it, like avoiding protein in the diet or removing toxins with treatments such as ammonia scavengers.  If a lack of the product is the problem, we can supplement it (for example the administration of carbohydrate in glycogen storage disease). And for some diseases the  enzyme can be “corrected” with organ transplantation or enzyme replacement therapy.

A bonus on smells

Due to accumulation of “unusual” products in their body fluids, people with certain metabolic conditions have distinctive odours (better observed in urine, for practical reasons):

  • Maple syrup, burnt sugar, curry: Maple syrup urine disease
  • Sweaty feet: glutaric aciduria type II, isovaleric acidaemia
  • Cabbage: tyrosinemia
  • Mousy, musty: phenylketonuria
  • Rotting fish: trimethylaminuria
  • Swimming pool: Hawkinsinuria 

Back to Emma. You explain to Emma’s mother that there are lots of things that could be making her unwell so you’re going to send some tests to help work out what the problem is. You put in a cannula, take a gas, send some bloods to the lab and set her and her mother up to collect a urine.

Seeing that Emma has a metabolic acidosis on her gas you send a metabolic screen: plasma amino acids, urine organic acids, acylcarnitine profile. Her urine dip has some ketones but is otherwise unremarkable, except for a strange smell of sweaty feet…

Remembering a fabulous infographic about the importance of calculating the anion gap in children with a metabolic acidosis (and how to interpret them!), you get out your pen and paper and do the following calculations: 

Just as you’re pondering the causes of a raised anion gap, the lab phones with Emma’s blood results… Her ammonia is 184!

Emma has an acute neurological presentation, with metabolic acidosis, increased anion gap and mildly elevated ammonia, suggestive of an organic acidaemiaIn the context of a sick neonate with a raised anion gap, a normal lactate and normal ketones, think organic acids.

Are you familiar with ammonia?

A normal ammonia level is <50 mol/l but mildly raised values are common, up to 80 mol/l.

In neonates, any illness may be responsible for values up to 180 mol/l.

Artifactually high values can be caused by muscle activity, haemolysis or delay in separating the sample. Capillary samples are often haemolysed or contaminated and therefore should not be used.

There’s debate as to whether a level of >100 or 200 should be discussed with a metabolic specialist, but if in doubt, follow the RCPCH DeCon guideline and seek advice for any patient presenting with a level >100 mmol/l.

Urine organic acids and blood acylcarnitines will also be sent as part of this baby’s metabolic work-up. Although the results won’t be available in ED, the urine organic acid profile will confirm a diagnosis of an organic acidaemia, while the blood acylcarnitine profile will support the diagnosis as the organic acids conjugate with carnitines creating compounds such as isovalerylcarnitine.

The emergency treatment of suspected organic acidaemias

It’s important to think about your differentials. Sepsis is the most common – these conditions can mimic sepsis, or decompensation can be triggered by an infection, always cover with broad spectrum antibiotics. But don’t forget non-accidental injury and other differentials – the baby is likely to need a CT head if presenting encephalopathic or with seizures. If she continues to seize, load with an anticonvulsant.

 Specific emergency treatment of her metabolic presentation requires:

  • stopping sources of protein (milk)
  • avoiding catabolism (by giving glucose IV – 2mL/kg 10% glucose) 
  • rehydration (IV fluids resuscitation and maintenance)

What about that urine?

The “sweaty feet” smell of the urine points towards the diagnosis of Isovaleric Acidaemia. Remember that this condition can be part of the Newborn Screening in some countries (Ireland, UK, Australia, New Zealand).

Isovaleric acidaemia is a type of organic acidemia, inherited in an autosomal recessive way. It is caused by a problem with the enzyme that usually breaks down the amino acid leucine. This amino acid accumulates and is toxic at high levels, causing an ‘intoxication’ encephalopathy. The sweaty feet smell is stronger without treatment or  during acute exacerbations.

Maple Syrup Urine Disease (MSUD) is another organic acidaemia, associated with sweet smelling urine during decompensation. These children cannot break down leucine, valine and isoleucine. They may not have hypoglycaemia, hyperammonemia or acidosis and, if not picked up on newborn screening, can be diagnosed late, resulting in neurological sequelae.

Organic acidaemias: the take homes

  • Always measure the anion gap and send an ammonia sample in any sick neonate.
  • Sick neonates with metabolic acidosis, increased anion gap and mildly elevated ammonia may have an organic acidemia.
  • Treatment is to stop feeds, prevent catabolism with 10% dextrose (and standard electrolytes for IV maintenance) and cover for sepsis with IV antibiotics, whilst considering other differentials.

The next case feels like déjà vu…

The next baby you see is remarkably like Emma but with a subtle difference. Lucy is a 3 day old baby, presenting with poor feeding, irritability and seizures at home. There has been no fever, cough, coryza, or sick contacts. On examination she’s awake, extremely irritable, with upper limbs, extended lower limbs extended and global hyperreflexia. She has no dysmorphic features, cardiac murmur or abdominal organomegaly. You notice that she seems tachypnoeic at 70, although her lungs are clear. The rest of her observations are normal. 

The key differences between Emma and Lucy’s presentations is that Lucy is tachypnoeic and has a respiratory alkalosis; this should make you suspicious of hyperventilation. Always check an ammonia level in sick babies, but particularly in this case as hyperammonemia stimulates the brain stem respiratory centre, causing hyperventilation and, as consequence, respiratory alkalosis. 

The lab phones you with Lucy’s ammonia result…

Acute neurological presentations, with respiratory alkalosis and extremely elevated ammonia point towards a urea cycle disorder. Respiratory alkalosis is a common early finding caused by hyperventilation secondary to the effect of hyperammonemia on the brain stem, although later the respiratory rate slows as cerebral oedema develops and an acidosis is seen. Lucy also has a low urea and mildly deranged liver enzymes and INR, all of which support the diagnosis of a urea cycle disorder.

The emergency treatment of suspected urea cycle disorders

Overall the acute treatment is similar to the first case: cover for sepsis, manage seizures and consider differentials.

And as in the first suspected metabolic case:

  • stop sources of protein – stop feeds 
  • avoid catabolism – giving glucose IV – 2mL/kg 10% glucose 
  • rehydrate – IV fluids resuscitation and maintenance

In urea cycle disorders, the toxic metabolite is ammonia, so ammonia scavengers are used, all given intravenously:

  • sodium benzoate
  • phenylbutyrate 
  • arginine

A nice guideline on the management of hyperammonemia secondary to an undiagnosed cause can be found on the British Inherited and Metabolic Disease Group website.

Urea cycle disorders are autosomal recessive inborn errors of metabolism. A defect in one of the enzymes of the urea cycle, which is responsible for the metabolism of nitrogen waste from the breakdown of proteins, leads to an accumulation of ammonia as it cannot be metabolised to urea. The urea cycle is also the only endogenous source of the amino acids arginine, ornithine and citrulline.   The most common urea cycle disorder is Ornithine Transcarbamylase (OTC) deficiency. Unlike the other urea cycle disorders (which are autosomal recessive), OTC deficiency is x-linked recessive, meaning most cases occur in male infants. Female carriers tend to be asymptomatic.

CPSI: Carbomoyl Phosphate Synthetase; OTC: Ornithine Transcarbamylase; ASS: Arginosuccinate Acid Synthase; ASL: Arginosuccinate; ARG: Arginase

Classically, urea cycle disorders present in the neonatal period with vomiting, anorexia and lethargy that rapidly progresses to encephalopathy, coma and death if untreated. In these circumstances, ammonia accumulates leading to a very high plasma ammonia. 

Children presenting in infancy generally have less acute and more variable symptoms than in the neonatal period and include anorexia, lethargy, vomiting and failure to thrive, with poor developmental progress. Irritability and behavioural problems are also common. The liver is often enlarged but, as the symptoms are rarely specific, the illness is initially attributed to many different causes that include gastrointestinal disorders. The correct diagnosis is often only established when the patient develops a more obvious encephalopathy with changes in consciousness level and neurological signs. 

Adolescents and adults can present with encephalopathy and or chronic neurological signs. 

What are ammonia scavengers?

In urea cycle defects, ammonia cannot be converted to urea so instead is converted to glutamine and glycine. 

Ammonia scavengers phenylbutyrate and sodium benzoate offer alternative pathways for ammonia excretion through urinary pathways.

Phenylglutamine and hippurate are produced and are excreted in urine.

Urea cycle disorders: the take homes

  • Always measure the anion gap and send an ammonia sample in any sick neonate.
  • Sick neonates with respiratory alkalosis, normal anion gap and very elevated ammonia may have a urea cycle defect. 
  • Emergency treatment of urea cycle disorders is the same as for an organic acidaemia (stopping feeds, starting dextrose and rehydrating) PLUS intravenous ammonia scavengers.

Thank you to Dr Roshni Vara, Consultant in Paediatric Inherited Metabolic Disease at the Evelina London Children’s Hospital for her help with this post.

References

Adam , HH. Ardinger, RA. Pagon, S. E. Wallis, L. J. H. Bean, K. Stephens, & A. Amemiya (Eds.), GeneReviews® [online book].

Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics. 2000 Jan;105(1):e10.

Sanderson S, Green A, Preece MA, Burton H. The incidence of inherited metabolic disorders in the West Midlands, UK.Arch Dis Child. 2006 Nov;91(11):896-9. 

Saudubray J-M, Baumgartner MR, Walter JH. (editors) Inborn Metabolic Diseases. Diagnosis and treatment. 6th Edition. Springer 2016. 

Neonatal ventilation basics

Cite this article as:
Jasmine Antoine. Neonatal ventilation basics, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.19875

A term infant is admitted to the intensive care nursery with severe respiratory distress. They are currently on CPAP 8cm H2O and FiO2 0.50  with no signs of improvement. You begin preparing for intubation. The nurse looking after the baby is setting up the ventilator. “What ventilator setting would you like, doctor”?

 

Before listing off some ventilator settings, there are several decisions that we need to make. What type of ventilation should we be using for this baby? What settings will we start them on? What do we need to do post ventilation? This post will begin to answer some of these questions, but as always, it is advisable to be guided by your unit policies and senior staff members.

 

Ventilation modes

This post will discuss the basics of conventional ventilation. High-frequency oscillatory ventilation (HFOV) is also commonly used in the nursery, particularly for extremely preterm infants or those with persistent pulmonary hypertension. Stay tuned for an upcoming post on HFOV.

Synchronized intermittent mandatory ventilation (SIMV)

This type of ventilation administers a set amount of mechanical breaths that are synchronized with the patient’s own inspiration. When the infant breaths above the set ventilator respiratory rate, these additional breaths do not receive a ventilator breath. This mode can be useful when weaning ventilation.

Synchronized intermittent positive pressure ventilation (SIPPV) or patient triggered ventilation (PTV) or Assist Control (AC)

This form of ventilation confusingly has many different names. It supports every breath the infant makes. The set ventilator respiratory rate is the backup number of breaths that will be mechanically administered if the infant makes no spontaneous breaths. Each mechanical breath is synchronized with the patient’s own inspiration.

Pressure support ventilation (PSV)

Similar to SIPPV in that every breath is supported with mechanical ventilation. However, the inspiratory time is limited depending on the infant’s own inflation. The infant sets their own mechanical breath rate and inspiratory time.

Volume controlled (VC) or volume guarantee

This mode of ventilation can be used with SIMV or SIPPV. The ventilator aims to deliver tidal volumes (VT) set by the clinician. A maximum peak inspiratory pressure (PIP) is set, the ventilator’s PIP will vary to reach the target volume.

 

So, which is better for our infant?

There have been no large prospective trials that have determined if SIMV or SIPPV is the superior format of ventilation. The choice of ventilation will largely depend on unit preference. Studies have illustrated that volume-controlled ventilation reduces the duration of ventilation, risk of pneumothorax, grade 3/4 intraventricular haemorrhage, and chronic neonatal lung disease.

 

So what’s on your ventilator screen?

Peak end expiratory pressure (PEEP):

The maximum pressure that provides continuous distension of the lungs. Usually between 6-8cmH20

Peak inspiratory pressure (PIP):

Maximum pressure used during inspiration. Consider the tidal volumes achieved to determine a suitable PIP. VT are usually around 4-5ml/kg.

Respiratory rate (RR):

Set number of mechanical breaths administered in a minute. Usually between 40-60. In SIMV the set RR is both the maximum and minimum rate while in SIPPV the RR is the minimum but not the maximum rate.

Inspiratory time (Ti):

Set time for inspiration during a breath. Usually between 0.3-0.5s

Patient Circuit Flow Rate or Rise Time or Rise Slope:

Depending on the manufacturer or the unit policy, one of these options will be available. If only the patient circuit flow rate is available then this is set 6 – 10 L/min. If rise time or slope is available then this is set to 30 – 50% of the Ti.

Pmax:

In the volume-controlled mode this is the maximum peak inspiratory pressure you wish the ventilator to administer to reach target tidal volumes. Usually set 5 cmH2O higher than the average PIP used to achieve the set tidal volume.

FiO2:

The amount of supplementary oxygen. Target saturations will depend on the gestational age and the underlying condition affecting the infant. Your unit’s policy on SpO2 targets should guide the FiO2 setting.

Many other ventilators exist

 

What are the ventilator measurements we should be aware of?

Minute volume (MV):

Amount of gaseous exchange in one minute. MV= VT x RR

Tidal volume (VT):

The amount of gas in an expiration. Usually around 4-5ml/kg.

Leak:

Traditionally in neonates, uncuffed tubes are used for intubation due to concerns regarding subglottic stenosis and pressure necrosis. As a result, most infants will have a percentage of leak. It will change during an infant’s respiratory cycle, it is usually greater in inspiration.

 

What do we need to do next?

After attaching our infant to the ventilator, clinical checks should once again be undertaken to ensure adequate ventilation. Review the infant, is there misting of ETT, equal air entry by auscultation, symmetrical chest rise, stable observations and adequate tidal volumes being achieved.

A post-intubation chest x-ray should be taken as early as possible to check the placement of the endotracheal tube. The ideal placement is between T1-3,  just above the carina.

An arterial gas should be undertaken post-intubation to check adequate ventilation, within an hour. The timing of the next gas will depend on the results, clinical condition and how old the patient is. Your boss will be able to give you some guidance.

 

Take-home messages

  • Avoiding mechanical ventilation using early continuous positive airway pressure (CPAP) with, or without, surfactant administration is the most effective way to reduce the risk of lung injury.
  • Using volume-controlled ventilation reduces the risk of chronic neonatal lung disease.
  • If you’re not sure where to start or how to alter ventilation, ask for your boss’ help.

 

Resources

Keszler M. State of the art in conventional mechanical ventilation. Journal of Perinatology. 2009 Apr;29(4):262.

Mechanical ventilation of the premature neonate. Respir Care. 2011 Sep;56(9):1298-311; discussion 1311-3. doi: 10.4187/respcare.01429

Aerosol Generating Procedures

Cite this article as:
Tagg, A. Aerosol Generating Procedures, Don't Forget the Bubbles, 2020. Available at:
https://dontforgetthebubbles.com/aerosol-generating-procedures/

As more cases of Covid19 present to health care facilities across the world, there seems to be some confusion as to what is an aerosol-generating procedure. Turning up to work is not without risk with a large number of healthcare workers in Italy and Ireland. diagnosed with COVID19. There is a case report of asymptomatic carriage lasting up to 16 days so we need to be careful whether the child in front of us has been diagnosed with COVID19 or not.

A lot of the data we have comes from the 2003 SARS epidemic and the H5N1 influenza outbreaks. There are always going to be a number of confounding variables when looking at these reports – whether the HCW was wearing appropriate PPE (or had access to it), how good their hand-washing was, how close together patients are – but nosocomial infections do occur.

First off,  we are going to take a look at what an aerosol is, then how aerosols and droplets relate to some common, and uncommon, things we do in paediatrics.

 

Aerosol or droplet?

Let’s define some terms before we get started – not as easy as it sounds, it turns out.

A  respiratory droplet is a fluid bundle of infectious particles that travels from the respiratory tract of the infected individual onto the mucosal surface of another, rather than floating down the respiratory tract. Small droplets are between 5-20μm and tend to hang up around the glottis. Large droplets are > 20μm and are probably too big to follow airflow. They tend to obey the laws of gravity and so settle on nearby surfaces when you sneeze. If you inadvertently touch the same surface then touch your face you can potentially transmit the infection. This is why we wash our hands. In healthcare, droplet precautions include a surgical mask, eyewear, disposable gown, and gloves. The surgical mask acts as a physical barrier to droplets that are too large to be inhaled.

A droplet nucleus is what is left once the liquid rapidly evaporates from a droplet. They are in the order of 10μm in diameter and are in the respirable range. This is generally defined as any particle less than 10μm. The inspirable range is defined as anything between 10 – 100μm in size.

An aerosol is a liquid (or solid) suspended in the air – think mist and fog. These small particles are less than 5μm and so are in the respirable range (rather than the inspirable range like droplets) and can enter the lower respiratory tract. They are affected by diffusion rather than gravity so tend to hang around for a while.  Measles is one such airborne disease. A recent letter in the NEJM suggests that SARS-CoV-2 can remain viable in aerosols for at least 3 hours, though the WHO’s guidance is clear that it should be managed with droplet and contact precautions UNLESS you are performing an aerosolising procedure.

Consider them on the continuum of aerosol -> small droplets -> large droplets -> puddles. Aerosols and small droplets have the ability to travel fair distances, especially if powered by a blast of oxygen or expired air. Larger droplets tend to obey the laws of gravity and settle on surfaces.

 

Just breathing, coughing and sneezing

But even putting an oxygen mask on the patient may not protect you. Hui et al. (2006) used fancy laser beams and smoke to detect just how far a single breath might travel.  With a standard oxygen mask on the patient and a flow rate of 4l/min, a tidal volume of 500mls, and 12 breaths a minute the smoke plume traveled approximately 0.45m. In most experiments, scientists use smoke as a stand-in for the more nebulous breath of air. Non-biological aerosols will behave differently depending on the airflow and ventilation in the room and have a constant density. Mathematical modelling would suggest that the further from the source a sample is taken then the lower the potential infectivity until a state of equilibrium is reached. Fortunately, the air is exchanged in most hospital rooms on a regular basis.

A patient that is coughing and sneezing can produce large, short-range droplets and small, long-range aerosols. The aerosols produced by coughing are heavier than the smoke used in experiments so hopefully, they may not be able to travel as far. Experimental data will tend to over-estimate the spread of droplets.

Thompson et al (2013) took 99 air samples around presumptive AGPs. 26.1% of them contained viral RNA. But the baseline level of contamination, when no AGPs (as defined by WHO 2009) were performed was 10.5%. Just because a procedure might generate an aerosol, it does not hold true that the aerosol can cause an infection.

Most of the data we have comes from the fast SARS-CoV epidemic in 2002-2003. Tran et al. tried to find all of the papers related to HCW infection and aerosol-generating procedures. They found 10 – 5 non-randomized cohort studies and 5 retrospective cohort studies. They then created pooled estimates of odds ratios.

Judson and Munster usefully categorized AGPs into those that mechanically create and disperse aerosols and those that make the patient wriggle and cough. Or you could think of them, as suggested by Brewster et al. (2020) as those procedures that require gas flow and those that require no extrinsic gas flow.

 

 

Bag-valve-mask ventilation and CPR

High risk 

A paediatric cardiac arrest is uncommon. When it occurs your first move* should be to open the airway and provide rescue breaths. In this time of COVID19, I doubt anyone is going to be doing mouth-to-mouth/nose ventilation. They are going to reach for an appropriately sized bag-valve-mask. Just like when placing a standard oxygen mask, there is a transverse movement of droplets even with a reasonable seal. The addition of an HME filter does appear to attenuate some of this, as demonstrated by Chan et al.(2018).

Adapted from Chan MT, Chow BK, Lo T, Ko FW, Ng SS, Gin T, Hui DS. Exhaled air dispersion during bag-mask ventilation and sputum suctioning-Implications for infection control. Scientific reports. 2018 Jan 9;8(1):1-8.

 

Adult CPR guidelines are advocating for chest compression-only CPR in the community and rapid intubation pre-compressions if circumstances allow. There has been little guidance on paediatric CPR from the ALSG but a number of enterprising teams are looking at it.

Possible cases of SARS transmission by CPR have been reported (Christian et al. 2004) but BVM ventilation took place during the cases and this may be the most important factor for possible viral transmission.

 

Intubation

High risk 

Anything, where the clinician is inches away from the respiratory tract of the patient, is going to be a high-risk procedure. There have been huge collaborative efforts worldwide creating COVID intubation algorithms. They share a lot of commonalities.

  • The most experienced operator performs the procedure – this is not a time for learning
  • No bag-valve-mask ventilation prior to intubation
  • Use of videolaryngoscopy to maximize the distance between intubator and patient
  • Minimum number of staff present

This is my favourite paediatric intubation resource from Queensland Children’s Hospital.

 

Nebulizing a medication

High risk / Unclear evidence

There are few indications for nebulizing medication. Bronchodilators are best delivered by MDI and spacer when possible but in cases of severe asthma or perhaps, more commonly, in croup, a nebulizer chamber may be the way to go. The UK guidelines do not consider the delivery of nebulized medications as an AGP. The rationale behind this is that the aerosol is derived from a non-patient source. Even if they do have the disease the medication sticks to the mucus membranes and so will not get released into the general environs. There seems to be a lack of global consensus on this.

Nebulizers generate small particles, between 1-5microns in diameter, in order to get down into the bronchioles and not just be deposited in the oropharynx. Viable COVID19 viral RNA has been detected in aerosol form 3 hours after delivery by nebulizer in experimental conditions but this does not prove infectivity, just infectious potential.

In 2009 O’Neill et al. performed air sampling studies for common patient activities, including making the bed and providing nebulized therapy, as well as some more invasive treatments (bronchoscopy and suctioning). Although small numbers they found an increase in influenza particle numbers (from baseline) of up to 70,000/cm³.

 

High Flow Nasal Cannula

High risk 

In adult practice, high flow oxygen delivery is anything over 6l/min. In paediatrics, it is 2l/kg/min up to the adult maximum of 60l/min. In one of my favourite studies to date (and certainly in keeping with the DFTB ethos) five anaesthetists gargled 10mls of red food dye, inhaled to their vital capacity and then coughed. They then repeated the experiment using blue food dye and HFNC at 60l/min and compared the distance traveled. They showed a baseline cough distance of 2.48m increasing up to 2.91m with high flow. Of course, children have a much smaller vital capacity.

This is in contradiction to the data from Hui et al. (2019). They used a human-patient-simulator (as opposed to humans in the above study), smoke and lasers. With a properly fitted mask flow forward flow was increased to ~26 cm with 5cm of CPAP and to around 33cm with 20cm of CPAP. With HFNC the exhalation distance increased from 6.5cm (10l/min) to ~17cm (60l/min). When the mask became loose or disconnected smoke was detected up to ~62cm laterally.  So why the big difference in the studies? It is the cough that causes the problem.

This video from Sick Kids in Toronto says more than any words ever could.

Whether you believe in the benefits of high-flow or not, pushing oxygen through the nose at 2l/kg/min and out through the mouth can create an aerosol spread of snot and virus. We would advise that it is only be used in cases where low flow oxygen therapy has failed. It also makes sense then, that it should only be started in the place where the patient is going to end up. It would not be wise to start a patient on HFNCO2 then wheel them through the hospital leaving a cloud of viral particles in their wake like some overactive Bisto Kid. And if you are going to do it with a coughing patient then it would be sensible to put a standard face mask on first.

 

Non-invasive ventilation (CPAP or BiPAP)

High risk 

High flow nasal cannula seems to have superseded non-invasive ventilation in many cases, though CPAP is regularly used in neonatal practice. There is very little evidence for maternal transmission of COVID19 and one might suppose that full PPE is then not warranted. However, you need to consider where the baby has come from.

Open suctioning and chest physiotherapy

High risk 

Removal of nasal foreign body

Medium to high risk

There are lots of ways to remove a nasal foreign body but all of them will generate snot. The old standby – the mother’s kiss – is, realistically, no more dangerous for the parent than living in close proximity. If your pre-encounter probability of infection with SARS-CoV-2 is low, i.e. there is little community transmission, then the risk to the provider is probably low.

Nitrous oxide

Medium to high risk 

Respiratory illness is a contra-indication to nitrous sedation but given that there is a degree of asymptomatic carriage it is not impossible that we might need to use it. With children not going to school and being told to stay away from their friends, there is going to be a spike in trampoline and bunk-bed related injuries. Again consideration should be made as to the possibility of community transmission. Logically holding a continuous flow mask on an uncooperative toddler would expose a HCW to higher risk than being a room Sith a cooperative patient using a demand system with appropriately attached to suction.

Examining the throat

Medium to high risk 

In normal times, no paediatric examination is complete without looking in the ears, nose, and throat, no matter how hard it might be. You can argue that looking at tonsils might not be overly helpful, given that the inter-rate variability is pretty high but there are other things to look for too – emerging teeth, Koplik spots, ulcers. But does a look in the throat put us at risk?

The Royal College of Paediatric and Child Health concurs, and in a statement put out on the 24th of March suggest that we only look in the throat if it is essential. If we have to do it we should be wearing appropriate protection (glove, gown, surgical face mask). If a child is at particularly high risk then they recommend empiric antibiotics.

Even ENT experts, like Eric Levi, recognize the unique risks that fiddling around near the upper respiratory tract hold.

Inserting a nasogastric tube

Medium to high risk

The combined Colleges of Surgeons of Great Britain and Ireland suggest that insertion of a nasogastric tube in an adult is an AGP, probably as it may induce coughing.

Taking a nasopharyngeal swab

Low to moderate risk 

The CDC state that collecting a nasopharyngeal swab doesn’t need to take place in an isolation room but should at least be performed in a single room with a closed door. The health care practitioner should wear an N95 mask or equivalent, coupled with eye protection, gloves, and gown. Given how far the swab has to travel up the nasopharynx nobody should be surprised that it might make someone sneeze.

The current Australian guidance contains slightly different advice.

 

We can also add things like IV access, suprapubic aspiration and performance of a lumbar puncture to this list of LOW-risk procedures.

And let’s not forget our surgical and dental colleagues

Surgical procedures

Clearly, some surgical procedures are more dangerous than others. Eric Levi. advocates for a risk assessment before any procedure takes place, starting with ‘Does it need to be done now?” Take a look at his post on how he is modifying his operative technique in order to reduce risk to himself and his colleagues.

On the 25th of March, the combined Colleges of Surgeons of Great Britain and Ireland recommended against laparoscopic surgery due to the potential for aerosol formation. Endoscopy, at either end, also has the potential for the creation of fomites and aerosolizing droplets and so should be carried out with extreme caution.

Dental procedures

There are very few dental procedures that need to be performed as an emergency but given that high-speed drills can lead to aerosolization have a care for our dental colleagues that may also be exposed in the course of duty.

The guidance for these procedures is common sense. Don’t perform them if you don’t have to. This is not the time for some minor dental procedures. If they have to be carried out then it should happen in the appropriate space with the appropriate staff. This means in a single room (ideally) with the minimum number of staff wearing appropriate PPE.

 

These are our thoughts, based on the current evidence, and we’d love you to persuade us otherwise in the comments below.

*Clearly the first step of the algorithm is D for Danger. That means putting on your PPE.

Selected references

Bourouiba L. Turbulent Gas Clouds and Respiratory Pathogen Emissions: Potential Implications for Reducing Transmission of COVID-19. JAMA. 2020 Mar 26.

Brewster DJ, Chrimes NC, Do TB, Fraser K, Groombridge CJ, Higgs A, Humar MJ, Leeuwenburg TJ, McGloughlin S, Newman FG, Nickson CP. Consensus statement: Safe Airway Society principles of airway management and tracheal intubation specific to the COVID-19 adult patient group.

Brown JS, Gordon T, Price O, Asgharian B. Thoracic and respirable particle definitions for human health risk assessment. Particle and fibre toxicology. 2013 Dec 1;10(1):12.

Davies A, Thompson G, Walker J, Bennett A. A review of the risks and disease transmission associated with aerosol generating medical procedures. J Infect Prev 2009; 10:122–6.

van Doremalen N, Bushmaker T, Morris D, Holbrook M, Gamble A, Williamson B, Tamin A, Harcourt J, Thornburg N, Gerber S, Lloyd-Smith J. Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1. medRxiv. 2020 Jan 1.

Hui DS, Ng SS. Recommended hospital preparations for future cases and outbreaks of novel influenza viruses. Expert Review of Respiratory Medicine. 2020 Jan 2;14(1):41-50.

Hui DS, Ip M, Tang JW, Wong AL, Chan MT, Hall SD, Chan PK, Sung JJ. Airflows around oxygen masks: A potential source of infection. Chest. 2006 Sep 1;130(3):822-6.

Judson SD, Munster VJ. Nosocomial Transmission of Emerging Viruses via Aerosol-Generating Medical Procedures. Viruses. 2019 Oct;11(10):940.

Kam KQ, Yung CF, Cui L, Lin Tzer Pin R, Mak TM, Maiwald M, Li J, Chong CY, Nadua K, Tan NW, Thoon KC. A well infant with coronavirus disease 2019 (COVID-19) with high viral load. Clinical Infectious Diseases. 2020 Feb 28.

Liu Y, Ning Z, Chen Y, Guo M, Liu Y, Gali NK, Sun L, Duan Y, Cai J, Westerdahl D, Liu X. Aerodynamic Characteristics and RNA Concentration of SARS-CoV-2 Aerosol in Wuhan Hospitals during COVID-19 Outbreak. bioRxiv. 2020 Jan 1

Macintyre CR, Seale H, Yang P, Zhang Y, Shi W, Almatroudi A, Moa A, Wang X, Li X, Pang X, Wang Q. Quantifying the risk of respiratory infection in healthcare workers performing high-risk procedures. Epidemiology & Infection. 2014 Sep;142(9):1802-8.

Noti JD, Lindsley WG, Blachere FM, Cao G, Kashon ML, Thewlis RE, McMillen CM, King WP, Szalajda JV, Beezhold DH. Detection of infectious influenza virus in cough aerosols generated in a simulated patient examination room. Clinical Infectious Diseases. 2012 Jun 1;54(11):1569-77.

Seto WH. Airborne transmission and precautions: facts and myths. Journal of Hospital Infection. 2015 Apr 1;89(4):225-8.

Shiu EY, Leung NH, Cowling BJ. Controversy around airborne versus droplet transmission of respiratory viruses: implication for infection prevention. Current opinion in infectious diseases. 2019 Aug 1;32(4):372-9.

Somogyi R, Vesely AE, Azami T, Preiss D, Fisher J, Correia J, Fowler RA. Dispersal of respiratory droplets with open vs closed oxygen delivery masks: implications for the transmission of severe acute respiratory syndrome. Chest. 2004 Mar 1;125(3):1155-7.

Tang JW, Li Y, Eames I, Chan PKS, Ridgway GL. Factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises. J Hosp Infect 2006;64:100-14.

Tellier, R., Li, Y., Cowling, B.J. et al. Recognition of aerosol transmission of infectious agents: a commentary. BMC Infect Dis 19, 101 (2019). https://doi.org/10.1186/s12879-019-3707-y

Thompson KAPappachan JVBennett AM, et al. EASE study consortium. Influenza aerosols in UK hospitals during the H1N1 (2009) pandemic–the risk of aerosol generation during medical procedures. PLoS One. 2013;8:e56278.

Tran K, Cimon K, Severn M, Pessoa-Silva CL, Conly J. Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review. PloS one. 2012;7(4).

World Health Organization. Infection prevention and control during health care when novel coronavirus (‎‎‎ nCoV)‎‎‎ infection is suspected: interim guidance, January 2020. World Health Organization; 2020

Intubation

Cheung JC, Ho LT, Cheng JV, Cham EY, Lam KN. Staff safety during emergency airway management for COVID-19 in Hong Kong. The Lancet Respiratory Medicine. 2020 Feb 24.

Nebulizing a medication

O’Neil CA, Li J, Leavey A, Wang Y, Hink M, Wallace M, Biswas P, Burnham CA, Babcock HM. Characterization of aerosols generated during patient care activities. Clinical Infectious Diseases. 2017 Oct 1.

Amirav I, Newhouse MT. RE: Transmission of Corona Virus by Nebulizer-a serious, underappreciated risk!.

High Flow Nasal Cannula

Hui DS, Chow BK, Lo T, Tsang OT, Ko FW, Ng SS, Gin T, Chan MT. Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks. European Respiratory Journal. 2019 Apr 1;53(4):1802339.

Leung CCJoynt GMGomersall CD, et al. Comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial. J Hosp Infect. 2019;101(1):8487.

Loh NH, Tan Y, Taculod J, Gorospe B, Teope AS, Somani J, Tan AY. The impact of high-flow nasal cannula (HFNC) on coughing distance: implications on its use during the novel coronavirus disease outbreak. Canadian Journal of Anesthesia/Journal canadien d’anesthésie. 2020 Mar 18:1-2.

Non-invasive ventilation

Singh A, Sterk PJ. Noninvasive ventilation and the potential risk of transmission of infection. European Respiratory Journal. 2008 Sep 1;32(3):816-.

Bag-Valve-Mask Ventilation

Chan MT, Chow BK, Lo T, Ko FW, Ng SS, Gin T, Hui DS. Exhaled air dispersion during bag-mask ventilation and sputum suctioning-Implications for infection control. Scientific reports. 2018 Jan 9;8(1):1-8.

Christian MD, Loutfy M, McDonald LC, Martinez KF, Ofner M, Wong T, Wallington T, Gold WL, Mederski B, Green K, Low DE. Possible SARS coronavirus transmission during cardiopulmonary resuscitation. Emerging infectious diseases. 2004 Feb;10(2):287.

Suctioning

Inserting a nasogastric tube

Nitrous oxide

Taking a naso-pharyngeal swab

Examining the throat

Lu D, Wang H, Yu R, Zhao Y. Integrated infection control strategy to minimize nosocomial infection of corona virus disease 2019 among ENT healthcare workers. Journal of Hospital Infection. 2020 Feb 27.

Tang JW, Nicolle AD, Klettner CA, Pantelic J, Wang L, Suhaimi AB, Tan AY, Ong GW, Su R, Sekhar C, Cheong DD. Airflow dynamics of human jets: sneezing and breathing-potential sources of infectious aerosols. PLoS One. 2013;8(4).

Removal of foreign bodies

Surgical spread

Ong J, Cross GB, Dan YY. The prevention of nosocomial SARS-CoV2 transmission in endoscopy: a systematic review of recommendations within gastroenterology to identify best practice. medRxiv. 2020 Jan 1.

Dental spread

Divya R, Senthilnathan KP, Kumar MP, Murugan PS. Evaluation of aerosol and splatter contamination during minor oral surgical procedures. Drug Invention Today. 2019 Sep 1;12(9).

Sabino-Silva R, Jardim AC, Siqueira WL. Coronavirus COVID-19 impacts to dentistry and potential salivary diagnosis. Clinical Oral Investigations. 2020 Feb 20:1-3.

Prepare for transport: Costas Kanaris at DFTB19

Cite this article as:
Team DFTB. Prepare for transport: Costas Kanaris at DFTB19, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22605

Costas Kanaris is a paediatric intensivist working in Manchester. He is also internet-famous for his challenging #fridayquiz in which he presents a case, drip-feeding information, as the Twitter audience figure out the diagnosis and the best way to treat the patient in front of them.

This time he tries it in front of a live studio audience. Here is a teaser to tickle your brain.

 

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.

iTunes Button
 

 

Surviving Sepsis Campaign International Guidelines

Cite this article as:
Damian Roland. Surviving Sepsis Campaign International Guidelines, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.23460

The lens with which you view sepsis is dependent on the environment and emotion in which you associate the term. For a parent, this may be the spectrum from having never heard the term before “Your child is well enough to go home, we’ve ruled out sepsis and other serious conditions” to the anguish of being told, “I’m afraid your child died of sepsis“. This spectrum remains equally wide for health care professionals. A family doctor or general practitioner may never see a case of confirmed sepsis, and an emergency clinician can potentially go years between seeing a truly shocked child. An intensivist, however, may deal with the consequences on a weekly basis. Even in the last month, we have seen two papers from the same publishing group; one highlighting the global burden of sepsis and the other challenging the current hype surrounding its recognition and management.

Regardless of your viewpoint, the publication of the Surviving Sepsis campaign’s international guidance will have been of interest.

 

Weiss, S.L., Peters, M.J., Alhazzani, W. et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Intensive Care Med 46, 10–67 (2020). https://doi.org/10.1007/s00134-019-05878-6

 

It is important to recognize two features of this publication which should carry an important health warning in its interpretation.

The first is that the authors are clear that they are focusing on severe sepsis or septic shock. While in adult practice definitions have changed, these have not been formalized or ratified for children:

 

“For the purposes of these guidelines, we define septic shock in children as severe infection leading to cardiovascular dysfunction (including hypotension, need for treatment with a vasoactive medication, or impaired perfusion) and “sepsis-associated organ dysfunction” in children as severe infection leading to cardiovascular and/or non-cardiovascular organ dysfunction.”

 

The authors clearly recognize that the absence of a clear definition of paediatric sepsis is challenging health care providers and organizations. The group has steered away from suggesting management options in the ‘pre-sepsis’ group i.e. those children with potential infections that may result in sepsis and have physiological instability but without organ dysfunction. They suggest that management practices for this group aren’t radically different, however:

 

Even though these guidelines are not intended to address the management of infection with or without SIRS when there is not associated acute organ dysfunction, we recognize that sepsis exists as a spectrum and some children without known acute organ dysfunction may still benefit from similar therapies as those with known organ dysfunction

 

The second is that this is a consensus document. It is neither a systematic review nor a clinical practice guideline (in a local hospital sense). It comprises the opinions of an expert group of clinicians (49 in fact) from a variety of international settings using the best available evidence. The publication is essentially a list of recommendations. This approach is valid in situations where evidence may be heterogeneous and that randomized controlled trials can not be performed for all possible permutations of clinical practice. As with all things in science, however robust the data is, it still needs interpreting and that interpretation is subject to all manner of explicit and implicit bias.

 

The panel supports that these guidelines should constitute a general scheme of “best practice,” but that translation to treatment algorithms or bundles and standards of care will need to account for variation in the availability of local healthcare resources.

 

Without becoming meta it’s important that this blog itself needs a health warning. It’s an interpretation of an interpretation of evidence.

So the big-ticket items

1. A child was defined as beyond 37 weeks gestation and up to 18 years old.

2. They apply to children with severe sepsis or septic shock as defined by the 2005 International Pediatric Sepsis Consensus Conference or inclusive of severe infection leading to life-threatening organ dysfunction.

2005 definition:

  • greater than or equal to two age-based systemic inflammatory response syndrome (SIRS) criteria
  • confirmed or suspected invasive infection, and cardiovascular dysfunction
  • acute respiratory distress syndrome (ARDS), or greater than or equal to two non-cardiovascular organ system dysfunctions

Septic shock was defined as the subset with cardiovascular dysfunction, which included hypotension, treatment with a vasoactive medication, or impaired perfusion.

3. Panel members were selected through recommendations from chairs and vice-chairs of the 12 worldwide member organizations. Each panel member was required to be a practicing healthcare professional with a focus on the acute and/or emergent care of critically ill children with septic shock or other sepsis-associated acute organ dysfunction. There was lay representation and the final membership was felt to be demographically diverse with regard to sex, race, and geography.

4. The panel was assisted by various methodological experts and split into six groups

  • recognition and management of infection
  • hemodynamics and resuscitation
  • ventilation
  • endocrine and metabolic therapies
  • adjunctive therapies
  • review research priorities in pediatric sepsis

5. A list of critical questions was developed in the PICO format (Population, Intervention, Control, and Outcome) which was then rigorously searched for by a specialist medical librarian and the resulting literature assessed according to GRADE criteria a well-recognized methodology for systemically presenting summaries of evidence.

6. Following discussion and debate recommendations would be made:

 

We classified recommendations as strong or weak using the language “We recommend…” or “We suggest…” respectively. We judged a strong recommendation in favor of an intervention to have desirable effects of adherence that will clearly outweigh the undesirable effects. We judged a weak recommendation in favor of an intervention to have desirable consequences of adherence that will probably outweigh the undesirable consequences, but confidence is diminished either because the quality of evidence was low or the benefits and risks were closely balanced.

 

The paper goes into considerable detail (which is why it is 55 pages long) into the rationale behind the recommendations. They are all summarised in the appendix (commencing page e102). It is beyond the scope of this blog to explore all the recommendations in detail, and it is important that health care providers read the paper itself. The following highlights some of the areas which may prompt debate or query.

 

‘Screening’ remains in

For those in emergency and acute care, this recommendation may have come as a surprise given a large amount of anecdotal feedback and experience suggesting that current screening mechanisms for the un-differentiated child are neither specific nor sensitive. It is worth nothing again the panel was looking at severe sepsis or shock and the evidence for ‘bundles’ of care i.e. targeted or mandated treatments once recognized is relatively robust. There is a further section on protocols/guidelines for treatment but it may have been useful to separate the afferent limb (recognition) from the efferent limb (response) in relation to collated evidence. This is important as the evidence for ‘bundles’ is cited under screening, with minimal evidence of screening approaches alone put forward (or to be fair to the panel perhaps of insufficient quality to make a judgment on).

Although subtle I think the panel recognized how important local buy-in is in relation to quality improvement. Of note, there is nothing on national guidance for recognizing sepsis. They also highlight how blindly integrating screening with any other scoring system may not be as beneficial as believed.

Ultimately no one particular screening system is recommended.

 

There is no target lactate

There appears to be a palpable sense of regret that the evidence didn’t support any particular threshold for lactate. Despite evidence of rising mortality with increasing lactate, the panel was not able to determine a specific level.

However, no RCTs have tested whether initial or serial measurement of blood lactate directly informs evaluation and/or management in children. Lactate levels should, therefore, be interpreted as a part of a more comprehensive assessment of clinical status and perfusion.

 

Take blood cultures but don’t delay treatment to obtain them

Appreciating this isn’t a particularly scientific response, but well, duh.

 

One hour time to treatment for those in shock but up to three hours without it. 

This is the potential game-changer from this body of work. While the evidence shows a temporal relationship between the administration of antibiotics and outcome in severe sepsis some pooled data demonstrated that it was unlikely the hour alone made the difference. Given the numerous papers showing a linear relationship between time to administration and outcome the ‘golden hour” was maintained. In the absence of shock, the panel felt, based on data showing a three-hour threshold effect, this would be a reasonable time point. This will be a welcome relief for those working in areas where there are associated penalties for not reaching the hour window and hopefully will remove some of the gaming associated with this target.

 

Broad spectrums antibiotics, but narrow when pathogens available

Little controversy here. The panel highlight that 48 hours should be the maximum time that is allowed to pass before re-evaluation in the absence of culture growth rather than a standard time to elapse.

If no pathogen is identified, we recommend narrowing or stopping empiric antimicrobial therapy according to clinical presentation, site of infection, host risk factors, and adequacy of clinical improvement in discussion with infectious disease and/or microbiological expert advice.

There are a number of recommendations on immunocompromised children and source control which appear pragmatic.

 

Bolus if intensive care available, if not then don’t unless documented hypotension

In units with access to intensive care, 40-60ml/kg bolus fluid (10-20ml/kg per bolus) over the first hour is recommended. With no intensive care, and in the absence of hypotension, then avoiding bolus and just commencing maintenance is recommended. It is not clear how long access to intensive care has to be to switch from fluid liberal to restrictive.

**Post-publication note (13/02/20): A more correct description of no intensive care would be “in health systems with no access to intensive care”. The guidance states, “For children with septic shock without signs of fluid overload in low-resource settings where advanced supportive and intensive care is not available, the panel recommends against bolus fluid administration,”. This question is raised in the comments section below as for units in without intensive care on site but it will resourced health systems then ‘access’ to intensive care should be assumed**

For purposes of this weak recommendation, hypotension can be defined as:

 

The panel suggests crystalloids, rather than albumin, and balanced/buffered crystalloids rather than 0.9% saline. They recommend against using starches or gelatin.

 

Use advanced haemodynamic variables, not bedside clinical signs in isolation

The evidence didn’t support a target mean arterial blood pressure but suggested avoiding using clinical signs to differentiate into cold and warm shock. No one monitoring approach was advised but included cardiac output, cardiac index, systemic vascular resistance, and central venous oxygen saturation.

 

Intensive care vasoactive and ventilation management is given but acknowledged as weak recommendations 

There is a list of suggestions regarding vasoactive infusion and ventilatory strategies that are very specific to intensive care management. While a number of recommendations are given (epinephrine rather than dopamine for septic shock for example) these are generally based on the panels summation of weak evidence.

There are further suggestions on corticosteroid management, nutrition, and blood products which will be of interest to those in intensive care and anaesthetic settings.

 

Summary

This is a very rich piece of work that is well structured and easy to read (even if you are not an expert on a particular field of practice). For most paediatricians there is unlikely to be an immediate change in practice but the softening of antibiotic time to delivery in the non-shocked child and emphasis of local review of sepsis incidence and performance will be welcome. How these filter into national guidance will be determined country by country but it is unlikely that radically different views can be drawn from the available evidence. What is still sorely needed is a working definition for the non-hypotensive child with sepsis (or an acknowledgment that perhaps this isn’t really a clinical entity…)

 

Diabetic Ketoacidosis

Cite this article as:
Dani Hall. Diabetic Ketoacidosis, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.22689

Maisie is 2 years old. Apart from a few coughs and colds, she is usually a very well, happy little girl. She’s been a bit poorly for the last 48 hours – a bit off colour, off her food, lethargic and just not her usual cheeky self.

She’s been drinking though and has had good wet nappies. In triage she has a runny nose and slight cough. She is pretty tachycardic and tachypnoeic and doesn’t look well and so she’s moved to majors.

Maisie is put on a monitor and immediately you can see that her respiratory rate is elevated at 40 breaths per minute with saturations of 97% in air. Her heart rate is also elevated at 150 beats per minute with a normal blood pressure of 105/65. Her capillary refill time is 3 seconds peripherally and she is afebrile.

Her heart sounds are normal, her chest is clear and her abdomen is soft although mildly tender throughout.

The only objective thing you have is the tachypnoea with a bit of a runny nose. You wonder if she has viral induced wheeze and is just too tight for the wheeze to be audible so you prescribe salbutamol and review after 10 minutes. But that’s made no difference to her respiratory rate, and her chest is still completely clear.

Things just don’t add up. She’s holding her tummy – perhaps her tachypnoea and tachycardia are secondary to pain. Her abdomen remains soft with no guarding, but she doesn’t like you palpating it. Could this be appendicitis? Or even worse an intussusception? You speak to the paediatric surgeon who asks you to cannulate Maisie and send some blood. They’ll be down to review her shortly.

You cannulate Maisie and take a venous gas. The results seem to take an age. And your heart sinks when you see them…

She’s acidotic at 7.15 and it looks metabolic with a bicarbonate of 13.9 and base deficit of minus 8.7. Her lactate is 2.9 and her glucose is very high at 29.5. You run a drop of Maisie’s blood through the bedside ketone monitor. Her blood beta-hydroxybutyrate is. 5.1.

This is diabetic ketoacidosis.

DKA can be really difficult to diagnose in toddlers

Classically children with DKA present with polyuria and polydipsia with abdominal pain, nausea, and vomiting. This can progress to dehydration, weakness, and in severe cases, they may be lethargic. Blood tests show a raised white cell count as a physiological response to the raised stress hormones, cortisol and catecholamines, and so are not a reliable indicator of infection. But, and this is a big but, an infection can precipitate DKA so it is important it is considered.

Although ketoacidosis may result in a classic ‘pear drop/acetone’ smell to the breath, not everyone has the chemoreceptors to detect it.

Common misdiagnoses include dehydration secondary to infection or respiratory presentations. Ketoacids stimulate the respiratory centre resulting in rapid fast breathing – Kussmaul breathing – blowing off carbon dioxide to compensate for the metabolic acidosis. It may also present as an acute abdomen as abdominal pain and ileus can result from hypokalaemia, acidosis, and poor gut perfusion. If opioids are given for pain this can suppress the Kussmaul breathing leading to worsening acidosis

 

The BSPED (2020), and ISPAD definitions of DKA are:

acidotic with a bicarbonate of <15 mmol/l or a pH <7.3 and ketones of >3.0 mmol per litre

 

However… just when you starting thinking it was easy… children with known diabetes may develop DKA with normal glucose and so you must keep a high index of suspicion and check pH and ketones in an unwell child with diabetes.

Lack of insulin leads to rising blood glucose levels in the bloodstream. However, this glucose is not transported into the cells and so the body needs to produce an alternative energy source for cellular activity. Three processes occur:

  • muscle is broken down to mobilise amino acids which are then used to create glucose (catabolism)
  • fat is broken down to produce glycol and ketones (lipolysis)
  • the liver uses lactate, glycol and amino acids to create more glucose (gluconeogenesis)

High ketone levels lead to metabolic acidosis.

Hyperglycaemia leads to glucose spilling into the urine (glycosuria). These glucose molecules exert an osmotic pull, dragging water, cations, and anions such as phosphate, potassium, and sodium into the urine (osmotic diuresis). The child becomes dehydrated with physiologically low levels of potassium and phosphate. Ketones also spill into the urine (ketonuria) in preference to chloride, which is retained in the plasma, leading to a worsening chloride-driven acidosis.

Maisie is dehydrated because of the osmotic diuresis exerted by the glucose in her urine. And she’s acidotic because of the ketones circulating in her bloodstream. The question is, what are we going to do about this?

The complications of DKA have incredibly high mortality and morbidity, so we’re going to start here.

 

Cerebral oedema

Cerebral oedema occurs in approximately 1% of children with DKA. While relatively rare, it can have devastating consequences with mortality of approximately 25%. In fact, more than half of all diabetes-related deaths in children are caused by cerebral injury.

Cerebral oedema usually occurs within the first four to 12 hours of starting treatment for DKA, suggesting that it’s the treatment itself that precipitates cerebral oedema.

Risk factors for cerebral oedema in DKA can be split into two groups.

The first group is characterised by children who have a longer duration of symptoms and are therefore more severely dehydrated at presentation. Younger children, particularly toddlers, and children who present in DKA without a previous diagnosis of diabetes mellitus, fall into this group, most likely because they have been in DKA for a long period of time before the diagnosis is made.

The second group is children who develop cerebral oedema because of the treatment they have received. Giving insulin within the first hour of treatment increases the risk of cerebral oedema – the theory is that the usually inactive sodium-hydrogen ion exchange pump is activated by the double hit of high intracellular hydrogen ions early in treatment while children are more acidotic plus insulin crossing the leaky blood-brain-barrier. The exchange pump transports sodium into the intracellular fluid, which then drags water with it due to its osmotic effect, leading to cerebral oedema.

Giving bicarbonate also increases the risk of cerebral oedema. The physiological mechanism of this is unclear but there is some thought that giving bicarbonate to correct acidosis can worsen tissue hypoxia due to effects on 2,3-DPG in erythrocytes (remember acidosis shifts the oxygen dissociation curve to the right, increasing the affinity of haemoglobin and oxygen) or that giving bicarbonate may lead to preferential movement of carbon dioxide across the blood-brain barrier, both of which will promote acidosis and poor oxygen offload in the CSF. However, whatever the cause, it is clear from a systematic review published in 2011 by Chua et al that giving bicarbonate to children with DKA is linked with increased rates of cerebral oedema. The guidance, therefore, mandates that bicarbonate should not be used routinely to correct acidosis. Fluids and insulin will do that by improving skin perfusion and reducing ketosis. Only give bicarbonate if the acidosis is resulting in reduced cardiac function, and then give very carefully…

So, with that in mind, how are we going to treat Maisie?

 

ABC resuscitation

The initial management of a child with DKA follows the principles laid out in APLS: ABC resuscitation.

If a child is obtunded and not protecting their own airway then they should be intubated because of the risk of airway obstruction. However, intubation in DKA is risky… both sedation and the resultant hypercarbia can cause cerebral herniation. Central lines are also risky in these children because of the increased risk of thrombosis. Only use them if absolutely necessary and remove them as soon as possible.

Luckily, Maisie is maintaining her own airway, her GCS is 15 and she is not obtunded. The airway is not a problem for her.

After managing the airway and breathing we move onto circulation. So the question is: should we give Maisie a fluid bolus?

This is a big question.  We are taught that children with cardiovascular compromise should receive fluid boluses to support their circulation.  But assessing cardiovascular compromise in children with DKA can be very challenging. Clinical evaluation of hydration and shock is very difficult in children with DKA. Acidosis drives tachycardia and reduces peripheral skin perfusion.

Koves et al set out to look at this by studying a group of 37 children under 18 presenting with DKA.

Emergency Department doctors recorded heart rate, respiratory rate, blood pressure, cool peripheries, capillary refill time, skin turgor, the presence or absence of sunken eyes and dry mucous membranes to provide a clinical estimate of dehydration. A second emergency department doctor, blinded to the clinical interpretations of the primary doctor, was asked to review the patient before treatment and record their assessment of the same clinical variables. There was a good clinical correlation between the two assessments. Following admission, the children’s weights were measured daily until discharge and percentage dehydration was calculated from the weight gain from admission to discharge.

There was no agreement between assessed and measured dehydration. There was a tendency to overestimate dehydration in children with <6% measured dehydration and underestimate in children >6% dehydrated.

It’s a tricky business and these same parameters clearly won’t be of use in estimating shock in these children.

A true assessment of shock in DKA should rely on assessment on blood pressure measurements and peripheral pulse volume. So that doesn’t really help us. Maisie’s blood pressure and pulse volumes are normal so she’s not shocked. But she clearly is dehydrated. 

BSPED (2020) uses pH and bicarbonate to classify the severity of DKA:

  • pH 7.2–7.29 or bicarbonate <15 mmol/l is mild DKA with 5% dehydration
  • pH 7.1–7.19 or bicarbonate <10 mmol/l is moderate DKA with 7% dehydration
  • pH < 7.1 or bicarbonate <5 mmol/l is severe DKA with 10% dehydration

 

So, are we going to give her a fluid bolus?  Let’s turn to the guidelines…

 

BSPED 2020 states:

Any child in DKA presenting with shock (as per the APLS definition of tachycardia and prolonged capillary refill time) should receive a 20 ml/kg bolus of 0.9% saline over 15 minutes. Let’s call this a ‘resuscitation bolus’.

Further 10 ml/kg boluses may be given if required up to a total of 40 ml/kg. Then add inotropes if the child remains shocked.

Boluses given to treat shock should NOT be subtracted from the calculated fluid deficit.

All children with DKA, whether mild, moderate or severe, who require IV fluids should receive an initial 10 ml/kg bolus over 60 minutes. Let’s call this a ‘rehydration bolus’. This bolus SHOULD be subtracted from the calculated fluid deficit.

 

The American Academy of Pediatrics, agrees that all children with DKA should have a bolus of 10ml/kg over 30 minutes to an hour. If a child is critically unwell with hypovolaemic shock, then additional boluses of 20ml/kg of 0.9% saline should be given.

Australian guidelines vary depending on region – from no routine fluid boluses to 10-20 ml/kg 0.9% saline for the sickest. Some say subtract fluid boluses from rehydration calculations, others don’t. There is no clear consensus.

So why is there so much international variation?

Traditionally, we have been warned about the danger of causing cerebral oedema in children with DKA by giving them too much fluid, reducing serum osmolality and literally flooding the brain. This is based, on the most part, by an old paper that showed an association between large volume fluid resuscitation in DKA and cerebral oedema. Note the word association, not causation.

 

Fluid management in DKA

Dogma has been to restrict fluids in paediatric DKA. It is widely thought that the rapid administration of intravenous fluids reduces serum osmolality, resulting in cerebral oedema. Guidelines traditionally have, therefore, advised slow fluid replacement using isotonic fluids as using hypotonic fluids was thought to cause further drops in osmolality. 

And the evidence seemed to support this.  Retrospective reviews showed better outcomes in children with DKA who received less fluid.

But…

  • only an association had been demonstrated, not causality.
  • and it is reasonable to suspect a confounder in that those with more severe DKA could be expected to be both at higher risk of cerebral oedema and more likely to receive large volumes of fluid resuscitation based on their clinical presentation.

And then along came this paper by Kupperman et al published in the New England Journal of Medicine in 2018, which has shifted thinking a bit, as well as causing some controversy…

Lead authors Nate Kupperman and Nicole Glaser suggested the causal effect of fluid resuscitation and cerebral oedema was a myth in Glaser’s 2001 retrospective case-control study that gave us the list of risk factors for cerebral oedema in DKA.

Kupperman’s team wanted to look specifically at the relationship between fluids and cerebral oedema (defined in the study as a drop in GCS, or longer-term evidence of neurological injury defined as a drop in IQ or short-term memory difficulties 2-6 months later) in DKA in children. They looked at 1255 children with DKA presenting to 13 hospitals in the States over a 9 year period, which, because 101 children presented twice, equated to 1389 episodes of DKA. Children were excluded if their GCS was less than 12, or if they had already received significant DKA management prior to assessment. 289 were withdrawn by the treating physician. The mean age was 11. It’s important to think about all of this as these exclusion criteria mean that the very sick and the very young, two groups who are at significantly increased risk of cerebral oedema, were probably lost in this cohort.

Children were randomized into 4 groups. All patients in both groups received IV insulin at 0.1u/kg/hr. Dextrose was added to the saline solution when blood glucose dropped to 11.1 to 16.7 mmol/l.

 

Children were randomized into 4 groups:

  • FAST rehydration with 0.45% sodium chloride
  • FAST rehydration with 0.9% sodium chloride
  • SLOW rehydration with 0.45% sodium chloride
  • SLOW rehydration with 0.9% sodium chloride

In short, Kupperman’s team found no difference between the groups. There was no significant difference in GCS, or longer-term evidence of neurological injury. The endpoint that many of us are most concerned about, clinically apparent brain injury (deterioration in neurological status requiring hyperosmolar therapy or endotracheal intubation or resulting in death) was a secondary outcome, presumably due to its rarity and hence difficulty in showing statistically significant differences between groups. But again, there was no significant difference between groups.

There was a 0.9% rate of brain injury overall and it didn’t matter which type of fluids or how fast. Patients were more likely to get hyperchloraemic acidosis in the 0.9% NaCl group but this is of debatable clinical significance.

The evidence does not seem to support our traditionally cautious approach to DKA. The speed of IV fluids does not seem to be the cause of brain injury in DKA. But… and this is a big but… don’t forget the youngest and sickest patients weren’t included. All we can probably really conclude is that children who are not in the at-risk group for cerebral oedema are probably more resilient to higher volumes of fluids delivered at faster rates.

Ok… back to Maisie. How are we going to manage her fluids

 

Well, again it depends where in the world Maisie presents. 

 

BSPED 2020 advises to calculate maintenance fluids the same way as they’re normally calculated for children in the UK:

  • 100 ml/kg/day for the first 10kg
  • plus 50ml/kg/day for each kg between 10 and 20kg
  • plus 20ml/kg/day for each kg above 20kg

(A maximum weight of 80kg should be used for fluid calculations)

 

The International Society for Pediatric and Adolescent Diabetes guidance is as follows:

ISPAD says

  • Shock is rare in DKA but if present should be treated with 20ml/kg fluid boluses, repeated as necessary to achieve tissue perfusion.
  • Give all children a 10ml/kg bolus over an hour to rehydrate them.
  • Calculate maintenance fluids in the normal way using the simplified Holliday-Segar formula.
  • Replace rehydration fluids over 24-48 hours, using clinical signs of dehydration to estimate the degree of dehydration. 2 or 3 signs would constitute to 5% dehydration, more signs would equate to 7% dehydration and weak pulses, hypotension or oliguria would indicate the child is 10% dehydrated.

Managing electrolytes

Once you’ve navigated the quagmire of fluid management in DKA, you need to think about adding electrolytes. Remember, glucose molecules in the urine exert an osmotic pull, dragging water, cations, and anions such as phosphate, potassium, and sodium into the urine: the child becomes dehydrated with physiologically low levels of the electrolytes potassium and phosphate.

Always assume whole body potassium depletion in DKA. This is compounded by the treatment you give which causes potassium to move intracellularly. Replace potassium as soon as the patient has urine outpatient and labs confirm the child is not hyperkalaemic.

An ECG will give you clues about clinically significant hypokalaemia:

  • Prominent U waves (an extra positive deflection at the end of the T wave)
  • Flat or biphasic T waves
  • ST-segment depression
  • Prolonged PR interval

Although phosphate is lost in the urine as part of the osmotic diuresis in DKA, prospective studies involving relatively small numbers of subjects and with limited statistical power have not shown clinical benefit from phosphate replacement. Administrating phosphate can be dangerous, by causing calcium levels to drop. However, symptomatic severe hypophosphataemia, when serum phosphate levels drop below 1 mg/dL with an ensuing metabolic encephalopathy or depressed cardiorespiratory function, can be dangerous, albeit very rare. A sensible approach is to monitor phosphate levels alongside regular potassium level checks and, if a child is hypophosphataemic and symptomatic, replace phosphate whilst carefully monitoring serum calcium levels.

Back to Maisie. We’ve managed her fluids according to our local guidelines. But how can we tell if we’ve got the balance right?

We can’t monitor urine output as Maisie is going to be polyuric anyway because of the osmotic effect of glycosuria. Her capillary refill time will be prolonged because she’s acidotic and therefore skin perfusion will be reduced.

And her serum sodium and osmolality won’t be reliable indicators of fluid balance because of the effect of plasma glucose on her electrolytes. On top of this, her kidneys will preferentially excrete chloride from any saline and potassium chloride over ketones so there’s limited value to monitoring the anion gap because it doesn’t differentiate between hyperchloraemia or ketones. Instead, we should measure Maisie’s corrected sodium.

Because of its osmotic effect, glucose drags water with it into the intravascular compartment diluting the other osmols – 1mmol rise in glucose will drop sodium and chloride by 1mmol/L.  If Maisie’s glucose goes up by 1 the other osmols will go down by 1.  If glucose goes down by 1 the other osmols will go up by 1.

The corrected sodium must rise with therapy at a rate of 0.5-1 mmol/h

  • Falling corrected sodium means too much water gain: we’ve been overzealous the fluids.
  • A rapidly rising corrected sodium means too much water loss: we’ve been too fluid restrictive.

The Evelina London South Thames Retrieval Service has a great corrected sodium calculator on their website. You plug in her numbers – her initial sodium was 148 with glucose of 29.5, giving her a corrected sodium of 157.6. A couple of hours have passed and her latest gas shows that her glucose has come down to 24.5 – great – and her sodium has improved slightly to 144. You press calculate…

… and your heart sinks as you see her second corrected sodium has fallen by 6 points to 151.6 as you know that the corrected sodium must rise with treatment.

You go back to Maisie’s bedside to review her.

Maisie has dropped her GCS to 12 (E3, V4, M5).  This is incredibly worrying – her GCS was 15 when you last checked on her.  You move her round to resus and ask your nurse to grab some hypertonic saline.

 

Clinical features of cerebral oedema

  • Headache
  • Slowing heart rate
  • Rising blood pressure
  • Focal neurology such as cranial nerve palsies
  • Falling oxygen saturations
  • Change in neurological status including restlessness, irritability, drowsiness, confusion, incontinence

Treat cerebral oedema with either hypertonic saline or mannitol.

Calculate your dose of hypertonic saline or mannitol before you need it and know where it’s kept. If a child has an acute deterioration, treat it.

Mannitol is an osmotic diuretic and can be given at 0.5 – 1 g/kg over 10-15 minutes. The effects should be apparent after 15 minutes. Mannitol lasts about 2 hours and can be repeated at this point if needed.

Hypertonic saline is a good alternative to mannitol or can be used after mannitol if a second agent is needed.

Don’t forget other neuroprotective measures like elevating the head of the bed to 30 degrees and intubation if concern regarding airway protection.

If there’s no improvement in GCS, do a CT, but not until the child is stable. CT is used to identify any potential lesion that would warrant neurosurgery – intracranial haemorrhage, or a lesion that would warrant anticoagulation such as thrombosis.

Hypertonic saline or mannitol?

DeCourcey et al (2013) conducted a retrospective cohort study over a 10 year period to see whether the increase in the use of hypertonic saline had had any effect on mortality in DKA. They looked at over 43,000 children under the age of 19 with DKA presenting to 41 children’s hospitals in America and found that the use of hypertonic saline replaced mannitol as the most commonly used agent in many of the participating hospitals. Controversially, their data suggested that hypertonic saline may not have benefits over mannitol and may be associated with a higher mortality rate.

However, this does remain controversial, with a counter-argument published as a letter to the editor a few months later arguing that (1) the fact that mortality from cerebral oedema in DKA had decreased by 83% over the same time period that use of hypertonic saline had increased, along with (2) the fact that DeCourcey’s paper only found a statistically significant difference in mortality between hypertonic saline and mannitol once age and race were removed from analyses (two factors that, themselves, have a significant influence on mortality in DKA-related cerebral oedema), meant that we shouldn’t be rushing to conclude that hypertonic saline is less safe than mannitol in the treatment of cerebral oedema.

No guidelines are yet to recommend mannitol over hypertonic saline. This seems to be one of those situations where a prospective study is needed to really answer the question of whether mannitol is superior, or at least non-inferior to hypertonic saline.

 

Back to Maisie. You give Maisie 3ml / kg 3% saline over 15 minutes and are relieved to see her wake up.  You decrease her fluid prescription and thankfully from that point on her corrected sodium starts to slowly rise.

 

Insulin

Finally, you’re ready to give Maisie some insulin. Insulin will control Maisie’s glucose and switch off ketosis, therefore improving her acidosis.  Some departments use 0.1 units/kg/hr and some use 0.05 units/kg/hr.  The question is, what is the optimal dose? 

Nasllasamy’s team set out to compare the efficacy and safety of low-dose and standard-dose insulin infusions. They randomized 50 children under the age of 13 with DKA presenting over a 12 month period to receive insulin infused at either 0.05 units/kg/hr or 0.1 units/kg/h. They found that the rate of decrease in blood glucose and time to resolution of acidosis were similar in each group. There was no statistical difference in complication rates of hypokalaemia, hypoglycaemia or cerebral oedema.

This study suggests that low dose insulin is non-inferior to standard-dose insulin in managing children with DKA.  It’s important to note that this was a non-inferiority trial and a larger study, powered to show superiority would be helpful. However, many units have been using lower doses of insulin at 0.05 units/kg/hr safely for some time and this study supports the use of lower dose insulin.

BSPED 2020 states:

Insulin can be given at 0.05units/kg/hr or 0.1 units/kg/hr, although ‘0.05 units/kg/hr would probably be sufficient in most cases except perhaps severe DKA’.

Children under 5 years should be given 0.05 units/kg/hr.

And so, as Maisie is young and therefore in the higher risk group of children with DKA, you opt to start her on insulin at 0.05 units/kg/hr.

In children who are already on long-acting insulin, BSPED 2020 states that it should be continued, or if they are newly diagnosed, they advise to consider starting long-acting subcutaneous insulin alongside intravenous insulin.<

Manage high-risk children in PICU

  • pH <7.1
  • young (under 2s or under 5s depending which guideline you read)
  • cardiovascular shock
  • corrected sodium >150 or <130
  • hyper or hypokalaemia
  • altered conscious state
  • glucose >50

Maisie has multiple risk factors: she’s young and she developed clinically apparent cerebral oedema.  You admit her to PICU where she makes stable progress and is discharged home 4 days later on a subcutaneous insulin regime.

Selected references

Take a read of Chris Gray’s take for St Emlyns here

Lawrence SE, Cummings EA, Gaboury I, Daneman D. Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J Pediatr 2005; 146:688

Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med 2001; 344:264

Edge JA, Jakes RW, Roy Y, et al. The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia 2006; 49:2002

Marcin JP, Glaser N, Barnett P, et al. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. J Pediatr 2002; 141:793

Scibilia J, Finegold D, Dorman J, et al. Why do children with diabetes die? Acta Endocrinol Suppl (Copenh) 1986; 279:326

Edge JA, Hawkins MM, Winter DL, Dunger DB. The risk and outcome of cerebral oedema developing during diabetic ketoacidosis. Arch Dis Child 2001; 85:16

Chua HR, Schneider A and Bellomo R. Bicarbonate in diabetic ketoacidosis – a systematic review. Ann Intensive Care. 2011; 1:23

Koves IH et al. The Accuracy of Clinical Assessment of Dehydration During Diabetic Ketoacidosis in Childhood. Diabetes Care 2004:27(10);2485-2487

Kuppermann N et al. Clinical Trial of Fluid Infusion Rates  for Pediatric Diabetic Ketoacidosis. N Engl J Med. 2018;378:2275-87

DeCourcey et al. Increasing use of hypertonic saline over mannitol in the treatment of symptomatic cerebral edema in pediatric diabetic ketoacidosis: an 11-year retrospective analysis of mortality. Pediatr Crit Care Med. 2013; 14(7):694-700

Tasker RC, Burns J. Hypertonic saline therapy for cerebral edema in diabetic ketoacidosis: no change yet, please. Pediatr Crit Care Med. 2014;15(3):284-285

Nallasamy K et al. Low-Dose vs Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis. A Randomized Clinical Trial. JAMA Pediatr. 2014; 168(11): 999 – 1005

ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidodis and the hyperglycaemic hyperosmlar state. Pediatric Diabetes 2018; 19 (Suppl. 27): 155–177

The curious incident of the wheeze in the night time

Cite this article as:
Costas Kanaris. The curious incident of the wheeze in the night time, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.22330

The first rule of the DFTBquiz is that the approach to each particular case and patient is not dogma, nor is it the only way in which the case can be safely managed in our virtual ED. There are numerous ways to approach critical illness. As long as the applied clinical treatment passes both the evidenced based medicine and family litmus then we have nothing to fear apart from the disease process itself.

So how would the DFTB team at Bubbles Central Hospital approach the child with life threatening bronchospasm, altered sensorium that has a pneumothorax and an SVT?

If you missed the original question – check it out here

This has been the second most successful #pedsicu f#ridayquiz to date with >30k impressions and answers from 29 different countries! It was a complex case of common pathologies amalgamated in one patient – status asthmaticus with a pneumothorax and SVT.

We outline the DFTB team’s take on the case and how we would approach it if we had this patient in our own resus bay. Please note this is not the only way to approach the patient but rather what our consensus is as to how to prioritize clinical issues and minimize risk in this patient by using a rational, evidence-based and pharmacologically prudent approach.  There were numerous excellent answers from across the globe. Here are a few highlights…

Things to consider are:

  • What is immediately the most life-threatening pathology? The pneumothorax? The SVT? The severe bronchospasm?
  • Why does the child have lactic acidosis?
  • Is it really an SVT or is it a tachycardia, exacerbated by nebulized beta-agonists? What risks are posed by any intervention we undertake?
  • How do we minimize the risks identified above?
  • What drugs should we use for intubation and what how do we maintain anaesthesia thereafter?

1. What is immediately the most life-threatening pathology? 

It is clear that this child is at high risk of cardiorespiratory arrest if we do nothing.

Clues to that are hypoxia, hypercarbia (especially in the context of altered sensorium)[1]; air trapping to the extent where a pneumothorax has developed (a known complication of asthma)[2] and the lactic acidosis, which in this case is likely to be secondary to a combination SVT leading to myocardial hypoperfusion and the respiratory muscles tiring (more on that later).

On the ABCDEFG approach (Airway, Breathing, Circulation, Disability, Exposure, Fluids, Glucose) we are taught to approach airway first. This failsafe approach may work well in most clinical emergencies but in this case, intubating before achieving cardiorespiratory stability is likely to put the patient in an even stickier situation.  Breathing (i.e. adequate oxygenation) is likely to be the first pathology to lead to cardiorespiratory arrest. That needs to be addressed first. The SVT is likely to cause considerable instability during intubation; this is superimposed to the pre-existing high risk of adverse events that accompany life-threatening asthma[3]. So the SVT needs to be cardioverted prior to intubation if possible.

Furthermore, the risk of converting a pneumothorax to a full-blown tension pneumothorax by attempting to intubate first is significant. Most modified RSI methods include a bag and mask ventilation technique. The application of positive pressure ventilation either before or after the ETT is in place –once the patient is established on a ventilator- risks changing the nature of the pneumothorax from a simple one to a life-threatening tension-type one[4].

In this case, therefore, airway stabilization – although high on the list of priorities – should come after we have optimized breathing and circulation (unless the patient arrests beforehand).


2. Why does the child have lactic acidosis?

The latter is important to understand and differentiate in someone who has been receiving a beta-agonist.

In the context of asthma lactic acidosis may be due to overproduction and/or inadequate clearance of lactic acid. Therefore, lactic acidosis in a child with severe bronchospasm could result:-

      • if patients were in occult shock
      • if produced by tiring respiratory muscles (i.e., respiratory muscle oxygen demand outstripping oxygen supply)
      • if produced by the lung parenchyma
      • if changes in glycolysis were caused by beta-agonist administration.
      • lactic acid could also be under metabolized by the liver

In our case the patient did not receive any IV salbutamol and only a couple of nebulizers; pharmacogenic lactic acidosis is therefore unlikely.

Much more likely is a lactic acidosis as a result of tiring respiratory and cardiac muscles. The latter is especially important to recognize in the context of an SVT. The myocardium perfuses during diastole[6]. If the HR is 300, the diastolic time is minimal, so there isn’t much time for the myocardium to be adequately perfused.

Tired respiratory and cardiac muscles make for a very high-risk intubation process.


3. Is it really an SVT or is it a tachycardia, exacerbated by nebulized beta-agonists?

It is tempting to think that such a significant tachycardia has been caused by a combination of factors: the patient is hypovolaemic, the patient is stressed, we gave him a couple of salbutamol nebs – and so on.

How can we differentiate a sinus tachycardia from an SVT?

Most textbooks will empirically state if the HR is >210-220 then the rhythm’s is more likely to be SVT, if it is <200-210 then it is likely to be sinus tachycardia.

This is loosely true but not always, especially in the context of paediatrics where we have different HR norms for each age.

Beat-to-beat variability is important in differentiating SVT from sinus tachycardia. Whilst in SVT each (P) QRST complex looks the same as the one after it, in sinus tachycardia each PQRST complex is different. A 12 lead ECG will help you ascertain this more accurately.

The presence of P waves is another determining factor.  A true SVT oughtn’t to have P waves preceding the QRS complex, whereas in a sinus tachycardia a P wave is usually present.  This is often tricky to differentiate in practice, especially if the ECG or cardiac monitors are tuned onto real-time speed. The best trick to apply is to slow the monitors down enough. This will slow down the speed of the PQRST complexes, allowing us to better visualize the P wave.

Vagal manoeuvers and pharmacological therapy if there is uncertainty about the cardiac rhythm is poor practice and should be avoided.  Cardiac output equals stroke volume times heart rate (CO= SVxHR). If we try to slow down the heart in the context of very fast sinus tachycardia with drugs or by stimulating the vagus nerve we will drop the cardiac output and put the patient at risk of a cardiac arrest.  We always need to be sure of the rhythm before any intervention.

If you are still uncertain, a reasonably safe bedside test would be to give 10ml/kg fluid bolus (ideally balanced solution) and keep an eye on the monitor whilst it’s infusing. If it is an SVT the HR will not budge. If it is sinus tachycardia, you are much more likely to see some slowing down of the rate.


4. What risks are posed by any intervention we undertake?

The risks of intubating someone with pneumothorax have been outlined above.

PPV can change a stable, small pneumothorax into a life-threatening tension pneumothorax. This dictates that we should ideally put a temporary chest drain in to decompress the thorax prior to intubation.

The other risk in optimizing breathing in this scenario is an exacerbation of the SVT by giving IV bronchodilating agents that are known to have a potent chronotropic effect. Both aminophylline [7] and salbutamol [8] are known to be chronotropic, but evidence would suggest that aminophylline causes less of a chronotropic effect than salbutamol[9]. With that in mind, loading with IV aminophylline in order to break the bronchospasm spiral would be the best (or least bad) option.

Also worth noting that MgSO4 is a potent vasodilator, so if we intend to use it in this setting to optimize bronchodilation it needs to be done as a low infusion (over 25-30 minutes)

The risks we may encounter whilst in improving circulation prior to intubation are twofold.

Firstly, in addressing cardioversion, adenosine is the most commonly used agent in treating SVT pharmacologically. A known side effect of adenosine, however, is bronchospasm[10].  There is little high-quality evidence to assess the effects of adenosine on asthmatic airways. What little evidence there is (and the evidence is nearly all from adult subjects) would suggest that adenosine is safe to use in patients with reactive airways[11],[12].

Secondly, this patient is likely to have a degree of dehydration. This degree of tachypnoea and work of breathing increases fluid loss through the respiratory tract. The degree of tachycardia also suggests a hyper-metabolic demand, again suggesting increased fluid consumption. It would, therefore, be prudent to give this patient some volume prior to intubation.  As the patient already has metabolic acidosis,  (ab)normal saline would be a poor choice. The chloride content is likely to increase chloride levels leading to a worsening metabolic acidosis [13], which in turn would worsen myocardial contractility [14],[15]. Balanced solutions (Plasmalyte 148 or Hartmann’s) are by far more physiologically appropriate and unlikely to exacerbate the metabolic acidosis [16],[17] and therefore preferred in this instance.


5. How do we minimize the risks identified above?

We have alluded to a lot of the steps in the analysis above. The main objective is to optimize oxygenation and primum non-nocere.

Bronchodilation prior to intubation is key. In this case, it is reasonable to go “all-out” and load with IV aminophylline, IV Hydrocortisone, IV Magnesium and a triple agent nebulizer (repeat if needed) consisting of salbutamol, ipratropium, and adrenaline (croup dose) to try and minimize air trapping by opening up the airways.

A temporary chest drain is important. This will help with pre-intubation oxygenation and reduce the risk of a peri-intubation tension pneumothorax from developing.

Cardiovascular stabilization is also important prior to intubation. Volume resuscitation prior to intubation is best done with a balanced solution (as outlined above) and –if anaemic- possibly blood as that would help with the overall oxygen-carrying capacity and give the patient more reserve. It is important to remember that this should be done in 10ml/kg aliquots because a high proportion of children with SVT will have concomitant congenital anatomical abnormalities. Give the fluid, assess response, check for rhonchi and hepatomegaly, and repeat as necessary. It is possible that the patient may still need cardiovascular support after intubation.

Which inotrope is best will be dictated by whether or not we have managed to successfully cardiovert (by vagal maneuvers first, by incremental doses of adenosine second and by DC cardioversion third). The inotropes need to be pre-drawn, prior to intubation so that we can start them quickly. This is not a scenario where we should be playing catch-up and preparation is key.

IV adrenaline would be a strong favorite in the usual asthmatic, not least because it has potent bronchodilatory effects and is reasonably safe to use in asthmatics[18]. If we have managed to stop the SVT then there would be a strong argument to favour this.  Adrenaline, of course, is also a potent chronotrope, so we should; on balance avoid it in someone with SVT. Noradrenaline is the least chronotropic out of our inotrope choices, so if we are still in SVT or we think that the patient is at high risk of reverting back into SVT then it would, on balance, be our best choice. Have a low threshold for inserting an IO if you don’t have enough large-bore access.


6. What drugs should we use for intubation and what how do we maintain anaesthesia thereafter?

 There is a long-standing truism in the art of rapid sequence intubation that says, “there is no such thing as a cardiostable induction”. This is especially true in the intubation process of critically ill children. All induction agents tend to vasodilate and cause a blood pressure drop. Couple that with the vagal stimulation caused by the laryngoscope and you can see why RSI is tricky business.

Arguably the least cardio-unstable combination of drugs in this setting would be ketamine  (1-2mg/kg),fentanyl (1mcg/kg), and rocuronium (1-2mg/kg). Ketamine has the added benefit of being a bronchodilator so it would definitely help in reducing the bronchospasm[19].

Intubating using sevoflurane may also be attractive for experienced anesthetists, not least because of the potent bronchodilatory effect that it can offer us[20]. This would still be my second choice however, because of how much vasodilation and blood pressure drop it may cause.

Always be prepared for adverse events during intubation. In this case, our chest drain needs to be in first, we need some inotropes pre-drawn as well as some volume in case the BP drops. A favorite trick of mine is using dilute adrenaline as a bolus to improve BP or HR or both should they drop during intubation.

The dilution is essentially tenfold of the resuscitation dose. Take the resus dose, dilute it with 10 ml of saline and you can bolus the eventual solution in 1ml aliquots. This is a superior drug when compared to commonly used atropine as it addresses also the BP drop and not just the HR drop.

Maintenance of anaesthesia is often with continuous infusion of morphine and midazolam. In this case, those agents would not be the best choice. Morphine is known to increase histamine release and is therefore likely to exacerbate bronchospasm and peripheral vasodilatation.  Fentanyl, as a continuous infusion, is proven to cause less histamine release and is, therefore, a superior choice in this case[21].

Coupling the fentanyl with a ketamine infusion (instead of midazolam) would also be preferable, mainly because of ketamine’s bronchodilatory effects. For doses /rates and dilutions of these pharmacological agents fill in and print the drug chart on crashcall.net or the one provided by your regional paediatric critical care transport team.

 

So what plan would go up on the PED resus board?

  1. Optimize B and C first. Prepare Airway trolley  (including 4, 4.5 and 5 cuffed ETT) and draw up 10ml aliquots of Plasmalyte dilute adrenaline. Draw up noradrenaline and adrenaline for infusions if needed.
  2. Break the bronchospasm cycle. IV aminophylline, slow IV MgSO4, triple neb (adrenaline, salbutamol, ipratropium). Temporary chest drain –and prepare for a more robust one after intubation.
  3. Confirm rhythm. 10ml/kg fluid volume, vagal maneuvers, incrementally increasing doses of adenosine until Cardioversion 100mcg/kgè200mcg/kgè 300mcg/kgè500mcg/kg. If adenosine fails for DC Cardioversion. Ideally prior to intubation.
  4. 1-2mg/kg ketamine, 1mcg/kg fentanyl, 1-2mg/kg Rocuronium; maintain anaesthesia with ketamine and fentanyl infusions (crashcall.net doses/rates)
  5. Empirical cover, include cover for atypical infections: Ceftriaxone + Clarithromycin. If flu possible consider Oseltamivir.
  6. Avoid 0.9%Saline, 10ml/kg aliquot of Plasmalyte or Hartman’s, if anaemic consider blood. Reassess after every bolus (liver size and rales).
  7. Keep an eye, likely to rise (stress response, steroids, salbutamol) unlikely to need treatment even if high.

Remember, this is just the DFTB team’s approach. There are numerous ways to skin a cat; if you have an alternative way we are keen to hear it!

References

[1] Holley, Anthony D., and Robert J. Boots. “management of acute severe and near‐fatal asthma.” Emergency Medicine Australasia 21.4 (2009): 259-268.

[2] Porpodis, Konstantinos, et al. “Pneumothorax and asthma.” Journal of thoracic disease 6.Suppl 1 (2014): S152.

[3] Zimmerman, JANICE L., et al. “Endotracheal intubation and mechanical ventilation in severe asthma.” Critical care medicine 21.11 (1993): 1727-1730.

[4] Bacon, A. K., et al. “Crisis management during anaesthesia: pneumothorax.” BMJ Quality & Safety 14.3 (2005): e18-e18.

[5] Forsythe, Sean M., and Gregory A. Schmidt. “Sodium bicarbonate for the treatment of lactic acidosis.” Chest 117.1 (2000): 260-267.

[6] Heusch, G. “Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents.” British journal of pharmacology 153.8 (2008): 1589-1601.

[7] Urthaler, Ferdinand, and Thomas N. James. “Both direct and neurally mediated components of the chronotropic actions of aminophylline.” Chest 70.1 (1976): 24-32.

[8] Crane, J. et al “Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline.” Thorax 44.2 (1989): 136-140.

[9] Morice, A. H., et al. “A comparison of the ventilatory, cardiovascular and metabolic effects of salbutamol, aminophylline and vasoactive intestinal peptide in normal subjects.” British journal of clinical pharmacology 22.2 (1986): 149-153.

[10] Bennett-Guerrero, Elliott, and Christopher C. Young. “Bronchospasm after intravenous adenosine administration.” Anesthesia & Analgesia 79.2 (1994): 386-388.

[11] Burki, Nausherwan K., Mahmud Alam, and Lu-Yuan Lee. “The pulmonary effects of intravenous adenosine in asthmatic subjects.” Respiratory research 7.1 (2006): 139.

[12] Terry, Polly, and Gail Lumsden. “Using intravenous adenosine in asthmatics.” Emergency Medicine Journal 18.1 (2001): 61-61.

[13] Kellum, John A. “Saline-induced hyperchloremic metabolic acidosis.” Critical care medicine 30.1 (2002): 259-261.

[14] Cingolani, Horacio E., et al. “Depression of human myocardial contractility with “respiratory” and “metabolic” acidosis.” Surgery 77.3 (1975): 427-432.

[15] Williamson, John R., et al. “Effects of acidosis on myocardial contractility and metabolism.” Acta medica scandinavica199.S587 (1976): 95-112.

[16] Bellomo, Rinaldo, et al. “Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.” Jama 308.15 (2012): 1566-1572.

[17] Chowdhury, Abeed H., et al. “A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte® 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers.” Annals of surgery 256.1 (2012): 18-24.

[18] Putland, Mark, Debra Kerr, and Anne-Maree Kelly. “Adverse events associated with the use of intravenous epinephrine in emergency department patients presenting with severe asthma.” Annals of emergency medicine 47.6 (2006): 559-563.

[19] Allen, Joseph Y., and Charles G. Macias. “The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma.” Annals of emergency medicine 46.1 (2005): 43-50.

[20] Schutte, D., et al. “Sevoflurane therapy for life-threatening asthma in children.” British journal of anaesthesia 111.6 (2013): 967-970.

[21] Rosow, Carl E., et al. “Histamine release during morphine and fentanyl anesthesia.” Anesthesiology 56.2 (1982): 93-96.

 

Practice made perfect?

Cite this article as:
Sonia Twigg. Practice made perfect?, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20694

Okay, perhaps  not perfect but we think these bite sized chunks of simulation from Children’s Health Queensland are pretty good! They are free to download and play with. You can find access to all current OPTIMUS resources here. Enjoy!

 

Introducing BONUS – A Bank of Independently Useful Sims

 

 

 

What are they?

OPTIMUS BONUS is an ongoing project driven by Children’s Health Queensland involving the creation of simulation education packages on topics in paediatric resuscitation.  Each package contains;

  • An introduction by an expert explaining why the topic is important.
  • A simulation with clear learning objectives, instructions and hints for debriefing.
  • Pre-reading resources for participants. These are fun and easy to read resources including podcasts, videos, guidelines and apps.
  • An infographic summarising the topic. QR codes on the posters link to Just In Time Training resources including videos and guidelines.  Just point the camera on your smart phone at the poster and a link will appear to the website to see the video.

 

Who writes them?

The STORK team (Simulation Training Optimising Resuscitation in Kids) from Children’s Health Queensland provides simulation based education throughout Queensland.  We provide two courses as part of our OPTIMUS curriculum; Optimus CORE (for first responders) and Optimus PRIME (for mid phase care while awaiting retrieval).

 

 Why did we make them?

 

What we love about them

  • They’re free to download, expert reviewed, repeatedly tested and assessed by a statewide advisory group to ensure we’re providing a quality product.
  • Our infographics look awesome, summarise the key messages, are easy to share on social media and easy to store on your phone.
  • Some packages contain Just in Time Training JITT resources and videos via QR codes to give you the info you need when you need it :
    • Just scan the QR codes on your phone to see refresher videos before you go and perform that skill
  • We’ve curated great open access #FOAMed resources on paediatric topics for each Simulation, so you can deep dive into more learning before or after the Sim!

 

Love the simulations and want to help out?

Thanks!  We need your help to share these simulations and infographics online any way you can. Shout out to @childhealthqld @LankyTwig @Caroelearning @paedsem and @symon_ben on twitter if you’re using them!

The other thing that REALLY helps is getting good feedback.  So, if you have thoughts on them to share fill out the surveys via the QR codes in the package so we can keep making better simulations to share with the world.

If you’d like to know more, email us at stork@health.qld.gov.au

Other than that, retweet them, share them widely, and help us improve paediatric care everywhere in the world.

 

Enjoy!

Sonia and the BONUS team

Dr Sonia Twigg (@LankyTwig), Dr Benjamin Symon (@symon_ben), Dr Carolina Ardino Sarmiento (@caroelearning), Dr Ben Lawton (@paedsem) Ms Louise Dodson and Mrs Tricia Pilotto.

 

Selected references

Case, Nicky, “How to remember anything forever-ish.:  Oct 2018.  Available at: https://ncase.me/remember/

Cheng et al, “Resuscitation Education Science: Educational Strategies to Improve Outcomes from Cardiac Arrest; A Scientific Statement from the American Heart Association.”Circulation 2018; 138: e82-e122. Available at: https://www.ahajournals.org/doi/10.1161/CIR.0000000000000583

Cheng et al, “Highlights from the 2018 AHA Statement on Resuscitation.” June 2018.  Available at: https://canadiem.org/aha-scientific-statement-on-resuscitation-education/

Dubner S.“Freakonomics Radio.  How to become great at just about anything (Ep 244).” Apr 2016.  Available at: https://freakonomics.com/podcast/peak/

Ericsson A,“Peak” Vintage 2017.

What is the evidence for high flow in bronchiolitis?

Cite this article as:
Tessa Davis. What is the evidence for high flow in bronchiolitis?, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20191

Over recent years, the use of high flow nasal cannula in the treatment of bronchiolitis in infants has increased. Whilst it used to be mainly used in PICU, it is now widely used in EDs and on the wards. The recent PARIS trial examined whether delaying starting high flow in infants with bronchiolitis led to a worse outcome (it didn’t). See Alasdair Munro’s excellent analysis here.

But is high flow actually useful in these patients, and if so when? Should we be using it in our Emergency Departments at all?

The PREDICT research group published an updated systematic review this month in the Journal of Paediatrics and Child Health.

Anticoagulation in children : Fiona Newall at DFTB18

Cite this article as:
Team DFTB. Anticoagulation in children : Fiona Newall at DFTB18, Don't Forget the Bubbles, 2019. Available at:
https://doi.org/10.31440/DFTB.20144

Professor Fiona Newall is Director of Nursing Research at the Royal Children’s Hospital in Melbourne and has a special interest in anticoagulation in children. If you think that the only patients in a hospital that need anticoagulation are old people then you should watch this talk from DFTB18.