Challenges in cannulation

Cite this article as:
Vicki Currie. Challenges in cannulation, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.33103

A look at paediatric cannulation. The good, the bad and the seemingly impossible.

We have all been there – coming onto a busy shift and a child who is well known for having ‘difficult’ vascular access needs a cannula.

It can be a heart sink moment when you realise that the team from the previous shift have already tried and failed. You feel your palms begin to sweat as the nursing staff tell you that access was a huge problem on the last admission. The father of the child tells you that you can have ‘just one go’.

But what really affects the chances of success of getting that tricky cannula in? Are there any modifiable factors that make it easier or harder? And how can we feel more confident in paediatric cannulation?

What is the evidence?

There are several factors that have been shown in the literature to negatively impact the success rates of paediatric cannulation:

  • Use of previous central venous access
  • Obesity
  • Attempts in the hand and lower legs
  • Non-black / non-white race
  • Poor cooperation of the child
  • Lack of confidence prior to the procedure

A recent study by Maduemem et al looked at the ‘Challenges Faced by Non- Consultant Hospital Doctors (NCHDs) in Paediatric Peripheral Intravenous Cannulation in Ireland.’ It aimed to evaluate the level of confidence of NCHD’s and looked to identify the factors that positively or negatively impacted confidence. This is a unique piece of research that is one of the first qualitative studies looking at the level of confidence in doctors in peripheral intravenous cannulation (PIVC).

Maduemem, K., Umana, E., Adedokun, C. et al. Challenges Faced by Non-consultant Hospital Doctors in Paediatric Peripheral Intravenous Cannulation in Ireland. SN Compr. Clin. Med. 2021

The team performed a cross-sectional national survey in 12 hospitals in Ireland using paper-based questionnaires. The survey captured data on the respondents’ clinical demographics (primary speciality, number of years postgraduate experience), clinical experience with PIVC (any paediatric clinical experience, number of children cannulated in preceding three months etc), the level of confidence in paediatric PIVC and potential factors influencing confidence in PIVC.

The primary outcome was the level of confidence in cannulation, measured by a five-point Likert scale assessing the overall level of confidence with ‘agree and strongly agree’ determined as a good level of confidence. Secondary outcomes were self-rated success in PIVC, previous experience and the effect of parental presence during the procedure.

The study had 202 respondents (45% response rate). The median number of years postgraduate experience for SHO level was three years (IQR 2-4) and at registrar level seven years (IQR 5-10.5). Interestingly ALL respondents had carried out paediatric cannulation in the preceding three months with 76% performing the procedure at least 10 times during the three-month time frame.  Despite 89% of respondents rating their performance as at least average, less than half (48%) of respondents reported themselves as feeling confident with the procedure.

Only 29% of respondents were reported as feeling confident in attempting PIVC that had been unsuccessful by a colleague. 37% of the cohort felt anxious when asked to perform PIVC in children, unsurprisingly with NCHD’s below registrar level feeling more anxious than their registrar counterparts.

What was driving this anxiety? More than half of the respondents (56%) stated that nursing staff and parental presence were sources of anxiety with 52% preferring to carry out this procedure without parents present.

Specific phrases that were noted by participants to have an adverse effect on confidence before the procedure were phrases which I’m sure the majority of us have heard before:

So what can we do?

Practice, practice and more practice

The study found that levels of confidence increased with seniority so encouraging junior colleagues and supporting them to perform cannulation is key. Including sessions on simulated patient arms to practice venepuncture may be a useful adjunct for clinicians with limited previous exposure.

Think before we speak

The phrases we use prior to performing a procedure can be powerful – not just the ones we say to ourselves but those we utter to colleagues. Feeding back to colleagues that phrases were unhelpful or signposting to the above study, in a polite way, might be a good way to raise awareness of the impact such phrases can have.

We all have seen the effect a ‘fresh set of eyes’ can have on that difficult cannula. So, if you are the person attempting after a colleague has already had a go, then be confident and try to start from fresh.

What about ultrasound?

Ultrasound guidance as an adjunct to PIVC has been shown to increase the success of the first attempt with good training in the use of ultrasound a big factor in first attempt success.

This is not a mandatory or even optional skill in general paediatric training in the UK. Experience is often gained from placements in PICU, ED or time with anaesthetic colleagues. Courses are becoming more frequent . If you have the opportunity or access to learn this skill from a colleague (paediatric or adult trained) it can be extremely useful.

Vein finders (infra-red lights that magically show veins through the skin) and the cold light that can often be found on the neonatal unit (used to look for evidence of pneumothorax) can be useful adjuncts too.

Are there any scores that can predict if a child’s access is going to be difficult?

The Difficult Intravenous Access (DIVA) prediction score is based upon four variables that are proportionally weighted. The variables are: vein palpability, vein visibility, age (infants score higher) and a history of prematurity. A score > 4 equates to a 50% increase in the likelihood of failure rate with first attempt.

But if a child has a high score, what next? Some difficult access pathways have been proposed with the utilisation of ultrasound, early contact with anaesthetic colleagues to help with access and consideration of midline/ PICC/ CVC in children who are particularly difficult. In practice, highlighting children early who have factors that put them at higher risk of being difficult and early escalation to senior colleagues, limiting attempts and utilisation of some of the steps mentioned can be helpful.

Keep things calm and pain free…

Optimisation of the position of the child and parents can help to not just keep the environment a calmer place but can reduce anxieties all round. The classic ‘bear hug’ position with a parent on a chair and the child chest to chest can provide not only comfort but easy access to limbs.

The use of freeze spray or anaesthetic creams on the area you are going to attempt cannulation can help to reduce pain as well as child and parental anxiety.

The use of distraction techniques can also reduce the child’s perception of pain. Singing, a YouTube video, home video on a smartphone or even bubbles can be easily done whilst attempting cannulation.

And if despite all of this you are still unsuccessful then limit yourself to a maximum number of attempts – usual practice is two to three (two attempts usually for more junior colleagues) before you ask for additional help. This ensures that there are still some veins left for that fresh set of eyes to have a look at. It also gives the child, parent and other staff helping a break from the procedure and means you don’t become super task-focused. In a situation where the child is unwell and access just needs to be attained, this is a different matter, and you will hopefully have multiple people around with lots of sets of eyes.

PIVC in children is tough, it is a skill that takes years to get right and still people who have been doing it for years can have a bad day where they just cannot get that cannula in. Keep practising, keep smiling, think about the words you use in relation to the procedure and how they can affect others and don’t forget the bubbles!

References

Bauman M, Braude D, Crandall C. Ultrasound-guidance vs. standard technique in difficult vascular access patients by ED technicians. Am J Emerg Med. 2009;27(2):135–40.

de Negri DC, Avelar AFM, Andreoni S, et al. Predisposing factors for peripheral intravenous puncture failure in children. Rev Latam Enfermagem. 2012;20(6):1072–80.

Larsen P, Eldridge D, Brinkley J, Newton D, Goff D, Hartzog T, et al. Pediatric peripheral intravenous access: does nursing experience and competence really make a difference? J Infus Nurs. 2010;33(4):226–35.

Maduemem, K., Umana, E., Adedokun, C. et al. Challenges Faced by Non-consultant Hospital Doctors in Paediatric Peripheral Intravenous Cannulation in Ireland. SN Compr. Clin. Med. 2021. https://doi.org/10.1007/s42399-021-00881-9

Nafiu OO, Burke C, Cowan A, et al. Comparing peripheral venous access between obese and normal weight children. Pediatr Anaesthesia. 2010;20:172–6.

Petroski A, Frisch A, Joseph N, Carlson JN. Predictors of difficult pediatric intravenous access in a community emergency department. J Vasc Access. 2015;16(6):521–6.

Sou V, McManus C, Mifflin N, Frost SA, Ale J, Alexandrou E. A clinical pathway for the management of difficult venous access. BMC Nurs. 2017 Nov 17;16:64. doi: 10.1186/s12912-017-0261-z.

Vinograd AM, Chen AE, Woodford AL, Fesnak S, Gaines S, Elci OU, et al. Ultrasonographic guidance to improve first-attempt success in children with predicted difficult intravenous access in the emergency department: a randomized controlled trial. Ann Emerg Med. 2019;74(1):19–27.

Yen K, Riegert A, Gorelick MH. Derivation of the DIVA score: a clinical prediction rule for the identification of children with difficult intravenous access. Pediatr Emerg Care. 2008 Mar;24(3):143-7. doi: 10.1097/PEC.0b013e3181666f32.

Adolescent trauma – destination unknown

Cite this article as:
Rie Yoshida. Adolescent trauma – destination unknown, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.33178

Amit is a 16-year-old male who lives in a city in England. He is the front seat passenger in a serious road traffic accident and has sustained multiple severe injuries. The ambulance arrives. There is a child, mixed and adult major trauma centre within a similar distance. Which one should Amit be taken to? Will it affect the outcome?  

A recent EMJ publication by Evans et al. aimed to answer this question by comparing adolescent mortality rates in England between children’s, mixed and adult major trauma centres (MTCs). The results suggest mortality rates are lower in children’s major trauma centres and is worth exploring further. 

Evans J, Murch H, Begley R, et al.  Mortality in adolescent trauma: a comparison of children’s, mixed and adult major trauma centres. Emergency Medicine Journal Published Online First: 30 March 2021. http://dx.doi.org/10.1136/emermed-2020-210384

Firstly, how common is adolescent trauma and how do trauma networks work in England? 

Among children and young people, adolescence is the stage of life that carries the second-highest risk of death after infancy. There were approx. 1,330 deaths for young people aged 10 to 19 years across the UK in 2018 and this has increased since 2014 (ONS, 2018).  The leading cause of adolescent mortality is trauma.  

In a previous EMJ publication, Roberts et al. provided an overview of adolescent trauma epidemiology in England from 2008-2017 using the TARN (Trauma Audit Research Network) database. This paper, along with the Evans et al. study, extends the age definition of adolescents to 10-24 years as endorsed by the RCPCH. Over a 10 year period, they found that there were 40680 trauma cases. 80.5% of these cases were aged 16–24 years and 77.3% were male. The main mechanism of injury was road traffic collisions accounting for 50.3% of cases.

NB: The TARN database includes patients of any age who sustain injury resulting in hospital admission for three days or greater, critical care admission, transfer to a tertiary/specialist centre or in-hospital death within 30 days. 

Mechanism of injury in adolescent trauma in England 2008 – 2017

Trauma networks were established in England in 2012 with the designation of major trauma centres (MTCs) and linked trauma units (TUs). The 27 MTCs are divided into 11 adult, 5 paediatric and 11 mixed major trauma centres (MTCs).  Where you are treated depends on age and location. As a general rule,  trauma patients under 16 years will be triaged to children’s MTCs whilst those 16 years and above are triaged to adult MTCs. Mixed MTCs are able to treat both adult and paediatric trauma patients. Major trauma is defined as having an Injury Severity Score (ISS) of over 15.

Why was this study needed and what did it find?

Since the establishment of trauma networks, there have been no studies comparing the outcomes for adolescent trauma between MTC types. Adolescents are a unique and often neglected cohort, especially those at the age when services transition between children and adult services.  

In their cross-sectional study, Evans et al present data from TARN comparing the outcomes of adolescent trauma patients who had a primary transfer to an MTC from 2012 to 2018. Using this data, they compare mortality rates for severely injured adolescents in the different MTC types. Note the study does not include trauma units (TUs) or transfers from a TU to an MTC. 

The study population included 30321 patients aged 10–24.99 years in the 6 year period.  The majority were treated in mixed MTCs (54%) with the fewest being treated in children’s MTC (8%). Even accounting for the variation in numbers seen, the study found that children’s MTCs had a lower 30-day mortality rate for adolescent trauma than adult or mixed MTC.  

Percentage patients seen and mortality by MTC

So does this mean Amit should be taken to a children’s MTC after his road traffic collision? 

We need to take a look at this further under two themes: patients and setting.   

Patients

As you might imagine, the study found that mixed and adult MTCs were more likely to see patients with more severe injuries. Stabbings and shootings were more frequent in adult and mixed MTCs. Patients in children’s MTCs had a lower median Injury Severity Score and fewer comorbidities. All of these trends could reasonably contribute to the higher mortality rate in mixed and adult MTCs. However, the study accounted for all of these potential confounding factors and found that the lower mortality associated with children’s MTC remained statistically significant (Table 1).  

You could argue that comparing the treatment of 10-year-olds to 24-year-olds is unrealistic and that the extremes of age are not where the interest lies. Recognising this, the study analysed those aged 14-17.99 years given the potential of this age group to be treated in any MTC. In this subgroup, the adjusted odds ratio for mortality was significantly higher in adult MTCs in comparison to children’s MTCs. There was no significant difference between mixed and children’s MTCs.  

Adjusted odds ratio for mortality by MTC type – variables include mechanism, the severity of trauma, comorbidities, baseline physiological parameters and GCS

Setting

Could the difference in mortality rate be explained by differences in staff experience and specialism at each MTC type? Do the MTCs use different management strategies or guidelines that could account for the difference in outcomes? These questions were not within the scope of this study although it did look at the most senior clinician present at the initial resuscitation and time to CT as secondary outcomes. It found that consultants were the most senior clinician likely to be present at all MTC types. With regards to imaging, trauma cases were less likely to have a CT if they presented to a children’s MTC reflecting one of the differences in managing adult and childhood trauma cases. It also took longer to perform a CT at children’s MCTs when compared with other MTC types but this does not seem to have affected the outcome.  

Number of patients receiving CT scan by MTC and average time taken to perform

In their editorial, Leech et al (2021)  suggest further reasons for the outcomes found in this study. They highlight that the majority of trauma patients present to non-children’s MTCs with the inherent danger of ‘trauma alert fatigue’. The rarer incidence of these alerts in paediatric centres may, however, give a more focused response. Other influences may be different approaches to education and training and also the nature of parents often being present for children and young people. What impact this has will probably need to be the subject of further research and evaluation.

Back to Amit, our 16-year-old patient post-RTC.  He is being transferred to the nearest adult MTC as per current protocol. 

Has this study changed your opinion on where he should be seen? Should the cut-off age for triage for adolescents be changed based on this study? More research is required but this study does show us that children’s MTCs can manage adolescent trauma with good outcomes despite seeing a lower volume of cases.  

Some thoughts from Jordan Evans

Adolescent healthcare crosses paediatric and adult services with transition predominantly based on age (16 in the UK). The same applies for trauma provision, with an adolescent trauma patient potentially treated in a children’s, adult or mixed MTC. What I wanted to know was does the centre type (children’s, adult or mixed) that an adolescent trauma patient attends affect the outcome?

We used one of the largest trauma databases in Europe (TARN) to help answer this question, defining adolescence as 10-24, in keeping with our previous research and international consensus. Appreciating that some would find this definition too broad, we performed sub-group analysis narrowing the age to 14-17.99 and for those defined as severe trauma (ISS>15). The primary outcome was mortality at 30 days and secondary outcomes included grade running resus, CT and length of stay. Both crude and adjust statistical analysis were performed (adjusting for mechanism, ISS, physiology amongst others).

Our total population for the study was 30 321 patients of which 54% presented to a mixed MTC, 38% to an adult MTC and 8% to a children’s MTC. Mortality within 30 days of injury was higher in mixed (4.4%) and adult MTCs (4.9%) compared with children’s MTCs (2.5%, p<0.0001). The same trend was noted in the adjusted analysis. For those aged 14–17.99 the crude OR of mortality was 1.73 (p=0.032) and adjusted 2.77 (p=0.030) in adolescents treated at the adult MTC. The trend for improved outcomes in children’s MTC was also noted in those with severe trauma.  For secondary outcomes, there was no difference in median total or ICU length of stay although less CT’s were performed in the children’s MTCs compared to the others. A slightly higher proportion of cases were managed by juniors in adult MTCs.

I think this is a timely paper and I feel greater attention is being paid to the adolescent cohort who are often appropriately labelled as the ‘forgotten tribe. The divided approach to adolescent healthcare is certainly a hindrance, with neither adult or paediatric services fully embracing the challenge to help drive down the high mortality and morbidity rates. A sister paper to this, reported an increase in adolescent trauma cases within the UK and a marked rise in stabbings, placing the onus on us to formulate a cross speciality approach to address the needs of this cohort.

I would thoroughly recommend reading the commentary in EMJ by Caroline Leech and Rachel Jenner who give a balanced discussion on the results with the authors hailing from adult and paediatric EM backgrounds. Personally, I would not suggest changing current trauma provision based solely on this data but that it acts as a conduit for further research and discussion. 

Selected references

  1. Office for National Statistics. Deaths registered in England and Wales – 21st-century mortality: November 2018.
  2. Roberts Z, Collins J, James D. On behalf of PERUKI, et al. Epidemiology of adolescent trauma in England: a review of TARN data 2008–2017Emergency Medicine Journal 2020;37:25-30.
  3. Evans J, Murch H, Begley R, et al.  Mortality in adolescent trauma: a comparison of children’s, mixed and adult major trauma centres. Emergency Medicine Journal Published Online First: 30 March 2021. doi: 10.1136/emermed-2020-210384
  4. Leech C, Jenner R Injured adolescents—should they be treated as big kids or little adults?Emergency Medicine Journal Published Online First: 30 March 2021. doi: 10.1136/emermed-2020-211105

Notes

Given the age cut-off of 16 years of age, there is limited overlap in the patients treated at children’s and adult MTCs making the comparison difficult.  However, there are times when triaging by age is not possible.  Indeed, the study found that there were 430 patients in the study under 16 years old who were treated in adult MTCs (9.9% of all aged <16 years) and 17 patients over 16 years attended a children’s MTC (0.1% of all aged 16–24.99 years). 

Urine dipsticks

Cite this article as:
Laura Riddick. Urine dipsticks, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.32596

This post will cover what’s what on a urine dipstick and clarify what it means when “it lights up like a Christmas tree

It’s 3 am and the 4-year-old with fever has finally produced a urine sample. You dip it and it lights up “positive for everything”. You’re sure it’s positive for infection, but what if the pH is 5.5? What does it mean that there is blood and protein in it?

Leukocytes

Surely white blood cells must mean an infection is present? If you have read the NICE UTI guidelines, so you know that is not necessarily the case.

The dipstick tests for leukocyte esterase. This is an enzyme produced by neutrophils and can be a sign of a urinary tract infection (white cells in urine = pyuria). These neutrophils, however, and the enzyme they produce can also be a sign of infection outside of the body such as vulvovaginitis. They may also be found in the presence of haematuria.

The overall sensitivity for leukocyte esterase is 49 – 79% with a specificity of 79 – 87%. As a result, it can be considered to be suggestive of “possible UTI”, and “probable UTI” if found with a positive nitrite sample (specificity increased to 99%).

What does this mean/bottom line: If positive and history suggestive (i.e. dysuria or fever) consider UTI and send for culture. If negative, then it is quite unlikely that there is an infection.

Nitrites

Nitrites are the breakdown product by gram-negative organisms such as E.coli. They are a more specific test (93-98%) than leukocytes but their sensitivity is lower (47-49%). The sensitivity is particularly poor as the urine needs to sit in the bladder for a while (at least 4 hours) for it to be positive.

What does this mean/bottom line: If it is positive, it is highly suggestive of infection. If it is negative, then does not necessarily rule out infection and needs correlation with leukocytes and presentation

Blood

Blood (haematuria) can be present for many reasons, so it is important to determine if there is microscopic (dipstick only) or macroscopic (visibly bloody). If blood is seen seen with leukocytes and/or nitrites then you should consider the child to have a UTI. If blood is seen with protein, then glomerulonephritis needs to be considered as a cause.

Causes of haematuria

  • Infection
  • Fever
  • Kidney stones
  • Glomerulonephritis
  • Renal tumour
  • Exercise
  • Trauma
  • Menstruation (doesn’t cause haematuria but will show up on dipstick so don’t forget to ask)

Isolated microscopic haematuria is common and only needs investigation if persistent, but make sure a blood pressure is checked as this is an often missed test. If haematuria is persistent it may need further investigation.

Reasons for further investigation

  • Macroscopic haematuria
  • Proteinuria
  • High blood pressure
  • Clinical oedema or features of fluid overload
  • Persisting microscopic haematuria (>2 occasions over 2-4 weeks apart)

Bottom line: If just microscopic haematuria on dipstick without explanation, then request a repeat sample with GP in 2-4 weeks. Don’t forget to check a blood pressure!

Protein

The body excretes a small amount which is usually not enough to pick up on dipstick.

If the body is “stressed” in illness or infection, it can cause proteinuria, however it is also a sign of inflammation or damage within the kidney and so further history and examination is required.

When there is proteinuria of 2+ or more occurs during illness or a UTI, it can be repeated in a couple of weeks to ensure that it does not persist when the patient is well.

If there is no illness or infection, you would need to consider other causes such as glomerulonephritis and nephrotic syndrome, examine for oedema, and send off a protein:creatinine ratio sample.

Bottom line: small amounts can be seen in illness, but large amounts needs review depending on how the patient is.

Glucose

This is not usually found in the urine, but small amounts can be detected if the patient is unwell, or is on steroids. If there is a large amount of glucose, consider checking a blood glucose to rule out diabetes, and see if there is any other evidence of kidney problems.

Ketones

A by-product from the breakdown of fat when sugar stores cannot be used. These can be seen in patients who have not been eating, vomiting and in DKA. It is always worth checking the blood glucose in these patients, as its absence in hypoglycaemic patients should alert you to a potential metabolic disorder.

Bottom line: Seen during periods of vomiting or not eating. Always check a blood glucose.

Bilirubin

Excessive bilirubin that is not dealt with in the liver is excreted in urine. Thus the presence of bilirubin in the urine can be seen in conjugated hyperbilirubinaemia, and therefore a feature of liver disease. If the urine dipstick measures urobilirubin then this can be seen normally on a dipstick (normal to 1+). A high urobilirubin could suggest haemolytic disease, as it reflects unconjugated bilirubin.

Bottom line: Bilirubin – not normal. Urobilinogen – normal (in small amounts)

Specific Gravity

This measures how dilute your urine is by comparing the solubility if the urine to water. If <1.005 then the urine is very dilute – do they drink a lot of water? If not the kidney may be unable to concentrate the urine, there it would be wise to consider checking a serum sodium and assess the patient for features of diabetes insipidus.

A high specific gravity means the urine is concentrated, and suggests that the patient may be dehydrated. If they do not appear hydrated, then does the patient appear oedematous? This could suggest systemic disease

A list of causes of high specific gravity

Bottom line: compare to the patient’s hydration status

pH

The urine pH varies and is usually slightly acidic. It can be influenced by diet and medication. Usually, alkaline urine is a product of vegetarian diets and medication. It can also be present in UTIs caused by urea splitting organisms, such as Proteus and Pseudomonas. It is seen in renal tubule anomalies or if the patient has metabolic alkalosis. Urinary acidosis is seen with high protein diets and can reflect systemic acidosis (for example, DKA, diarrhoea and vomiting)

Bottom line: Not very useful on its own.

Urine dipticks infographics

Selected references

https://litfl.com/dipstick-urinalysis/

https://patient.info/treatment-medication/urine-dipstick-test

Yates A. Urinalysis: how to interpret results. Nursing Times. 2016 Jun 8;112(2):1-3.

https://geekymedics.com/urinalysis-osce-guide/

https://www.mayoclinic.org/tests-procedures/urinalysis/about/pac-20384907

https://www.nice.org.uk/guidance/cg54/chapter/Recommendations#diagnosis

https://www.clinicalguidelines.scot.nhs.uk/nhsggc-paediatric-clinical-guidelines/nhsggc-guidelines/emergency-medicine/haematuria-management-and-investigation-in-paediatrics/

Fernandes DJ, Jaidev M, Castelino DN. Utility of dipstick test (nitrite and leukocyte esterase) and microscopic analysis of urine when compared to culture in the diagnosis of urinary tract infection in children. Int J Contemp Pediatr 2017;5:156-60

Jeng-Daw Tsai, Chun-Chen Lin, Stephan S. Yang, Diagnosis of pediatric urinary tract infections, Urological Science, Volume 27, Issue 3, 2016, Pages 131-134

Tsai JD, Lin CC, Yang SS. Diagnosis of pediatric urinary tract infections. Urological Science. 2016 Sep 1;27(3):131-4.

Sepsis 2020

Cite this article as:
Emma Lim. Sepsis 2020, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.32392

Where do we start?

Fever and suspected sepsis is our bread and butter. This post will take you through a whirlwind 2020 sepsis update. We’ll cover what sepsis is, how to recognize deterioration and the recent management updates in light of the new 2020 International Surviving Sepsis Campaign Guidelines1.

For me, it is all about “What keeps me up at night?” and there are two things I worry about. The first is missing cases of suspected sepsis.  Think back to all those hot, miserable children you sent home over your career and the heart sink you feel when someone says, “Remember that child you sent home yesterday?”.  My second worry is making bad choices; making mistakes about how much fluid to give or which antibiotics to choose or when to start inotropes.

What is sepsis?

Let’s start at the beginning. How do you get sepsis? A bacterial or viral infection causes a systemic, inflammatory response syndrome (SIRS). We are used to seeing children who have a fever and a fast heart rate or respiratory rate and a raised white cell count, for example with bronchiolitis. A certain proportion of those children will go on to get sepsis but not a lot.

Spotting sepsis in the paediatric ED is like a game of Where’s Wally: there are a whole lot of hot febrile children with accompanying hot cross parents. Fever is common but sepsis is rare – at a quick glance they all look like Wally, but, of course, there is actually only one real one and it takes a bit of time and patience to find him. It is the same with all those children with fever: around 55% have self-limiting viral infections, only 7-13% have serious bacterial infection (SBI)2-4 and only 1% have sepsis. The picture’s different in PICU; 10% of PICU admissions are for sepsis. The 2015 SPROUT study5 looked at 569 children in PICU with sepsis (8.2% point prevalence). 40% were caused by respiratory infections and 19% percent by bloodstream infections. A quarter (25%) of them died.

That quote “7-13% of febrile children have a serious bacterial infection” seems high. There are predefined criteria (such as pneumonia, urinary tract infection, meningitis, osteomyelitis, septic arthritis), but in a reductionist sense, sepsis is any infection that makes a child so unwell that they are admitted to hospital for more than 72 hours and need IV antibiotics. But, the need for admission is very subjective and dependent on the experience of the doctor and the parents’ level of concern.  The goal posts are constantly shifting.  Ten years ago, we would admit children with osteoarticular infections for 6 weeks of IV antibiotics. Now they can be in and out within 72 hours (with most of their course given orally). That doesn’t mean the infections have got less severe, it’s just that our treatments have changed.  And is a urinary tract infection over a year of age really a serious infection?  Most will get treated with a short course of oral antibiotics, as will children with pneumonia.  Because that’s a whole other controversy; reporting focal consolidation on a X ray is art not science and has been shown to be famously unreliable in double blind studies.  So if we remove children who have simple pneumonia, urinary tract infections in older children,  skin and soft tissue infections that do not have positive cultures, the number of true SBI is quite a lot less than the quoted 1 in 10.

Unbelievably, there is no good definition of ‘sepsis’ in paediatrics6, so we tend to use the adult Sepsis 3 definition7 which states:

“Sepsis is life threatening organ dysfunction caused by a dysregulated host immune response to infection including renal, respiratory, hepatic dysfunction or metabolic acidosis”. A small proportion of children or young people with sepsis will go into septic shock, where shock is defined as hypotension, or impaired perfusion requiring inotropes with a higher risk of death than sepsis.”

This doesn’t really help us spot sepsis early enough to prevent these children going into shock.  So far, there is no reliable way of pinpointing who these children are. However, there is some exciting news. 2020 has brought us new international evidence-based guidelines for the management of septic shock and sepsis associated organ dysfunction in children; the Surviving Sepsis Campaign.

This has been a huge piece of work by an incredible transatlantic consortium, including Mark Peters (for the horse’s mouth listen to our latest RCPCH Paediatric Sepsis Podcasts). I am going to take you through some of these recommendations, but I think everybody should read it themselves.  The consortium took 3 years and reviewed over 500 papers, but you only have to read this one paper, so go on, make your life easy!  

Spotting sepsis

Recommendation number one. In children who present acutely well, “we suggest implementing systematic screening for timely recognition.”

Take note of the word suggest. This means there is some, but not definitive, evidence. We all recognise systematic screening for sepsis is a huge problem for paediatricians. Most children with a fever have a self-limiting viral infection, and many of these children will have fever, tachycardia and tachypnoea. But most do not have sepsis.  However, if we use the UK-based NICE high-risk ‘Red Flag’ criteria, these children are all flagged as potentially having sepsis. They over-trigger, shown by a 2020 paper by Ruud Nijman which showed that 41% of all febrile children in PED present with warning signs of sepsis3. If you look at this paper in some detail, 50% of children aged 1-2 years triggered the NICE red high-risk category for tachycardia alone. This mirrors data from a local audit from the Great North Children’s Hospital Emergency Department, conducted between April and June of 2017. Of 868 patients, 5% had serious bacterial infections, but 50% triggered NICE high-risk criteria. Sam Romaine from Alderhey Children’s Hospital, and part of Enitan Carrol’s group, looked at 12,241 patients and again, 55% triggered NICE high risk criteria8. For a full critical review of Ruud’s paper, take a look at our Searching for Sepsis post.

The NICE high risk criteria have a very high sensitivity but limited specificity, which means although they ‘over-trigger’, if a child doesn’t have any red flags then they are potentially ‘good to go’, helping inform safe discharge.

Is there a better score?

For a long time, adults have used the Q-SOFA score, a quick sepsis related organ failure assessment. Typically, this adult score has performed poorly in children. Enitan Carroll’s group have looked at a modified Q-SOFA score called the LQ-SOFA score (L for Liverpool), modified to predict critical care admission rather than sepsis. Critical care admission is a more common outcome than sepsis, particularly relevant because this helps us understand which children are at risk of deterioration. The modified score, is made up of four simple, straightforward criteria, including capillary refill, AVPU (that’s Alert, Verbal, only to Pain or Unresponsive), heart rate and respiratory rate, purposefully not including blood pressure, making this quick and easy to use as a screening tool. But what did they find? Carroll’s group compared five different scores that could help us predict sepsis or deterioration: lactate, CRP, adult Q-SOFA, NICE and LQ-SOFA. Lactate performed the least well, CRP and Q-SOFA a little bit better, NICE high-risk criteria better again, but best of all was the LQ-SOFA score. 

This work suggests that there are more sensitive tools out there, but these need to be combined with some way of de-escalating children who trigger because most of these children have a SIRS response from a self-limiting viral infection and not sepsis. De-escalation is usually done by ‘a senior review,’ with the intention of differentiating the hot and bothered child who has a viral infection from early sepsis.

Listen to parents

There are many examples of systematic screening protocols, the best being electronic scores. But they are not perfect.  Most importantly, the good ones listen to parents. Parental concern or health professional concern is particularly important for children with complex medical conditions: neurodisability, recurrent chest infections, those with indwelling lines or fed by gastrostomy. These children often don’t have typical signs and symptoms that health care professionals associate with infections or sepsis, often presenting with nothing more than their parents saying that they’re not well or not quite themselves. These children can be hypothermic (due to hypothalamic dysfunction) and run ‘cold’ so when they get an infection, their temperature may goes up to ‘normal’ (37 degrees), not triggering at all. The presenting signs can be very, very subtle like not tolerating their feed, or vomiting, or they may just be miserable and unhappy. This is why any escalation tool or score must in some way include parental concern. The NICE sepsis guidelines from 2017 tells us to pay particular attention to ‘concerns expressed by parents, families or carers’, for example, changes from usual behaviour.’  We must not underestimate the expertise of parents and we should incorporate them into the team of people caring for their children.

Doctors can be wary of parental concern but if we look at a systematic review of family-initiated escalation of care for the deteriorating patients in hospital, we can see that this wariness is unfounded.  Gill et al 20169 looked at a systematic review of ten articles (all descriptive studies) over ten years evaluating response systems for patients and families; five described a triaged response; five reported systems for families to directly activate the rapid response team. There were a total of 426 family-initiated calls, range 0.17 to 11 per month, with no deaths reported. All calls were deemed to be appropriate and three calls resulted in intensive care unit admissions.”

I believe there is evidence that parents only escalate when they need to.  As one of our parents of a child with a complex medical condition said;

Please listen to us when we say something is not right, we can see subtle changes in children, in our children, in their health and behaviour. That may not be apparent to the casual observer or even health professionals like yourselves and children like them cannot speak for themselves. Therefore, as parents, we have to ensure that we advocate for them in the strongest possible terms. We do not think we are better than the team, nor are we full of our own importance. But we are simply trying to give a voice to our children as they don’t have one of their own.”

What do you do next?

The Surviving Sepsis campaign developed a management algorithm for children, and while it is useful, there’s a lot of information, for many different teams in a small space. Firstly, when you look closely, the lower half (in black) is actually all about management in a Paediatric Intensive Care (PICU) setting -treatment of refractory shock and advanced haemodynamic monitoring. For paediatric emergency physicians, there is a lot that has to happen first! Let’s break it down.

The first thing that the international guidelines asks us to do is get intravenous or intraosseous access. Please only have three tries at getting intravenous access and if this isn’t successful, go straight to intraosseous access. It’s a great safe route and can be much easier to get than intravenous especially in children with complex medical conditions whom may be difficult to cannulate. Although it may feel like using an IO in an awake child will be traumatic , flushing with 0.5mg/kg of 2% lignocaine before you infuse fluids, antibiotics and other drugs, will reduce the pain.

Test, tests, tests

Recommendation number two. Get a blood culture.

This should always be your next priority, as long as it does not delay treatment. Let’s just think for a moment about blood cultures. Blood cultures are old technology. They were developed in the 1950s and have not really changed since. Traditionally, blood cultures are read at 48 hours but often don’t give any definitive answer. The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS)10 was a prospective, multi-centre, cohort study of 2844 children under 18  with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 hospitals across Europe and incredibly in 50% of patients the causative organism remained unidentified! Alasdair Munroe explains more in his blood culture post.

What we really want is a point of care test, a test that takes less than 60 minutes, that can quickly differentiate between viral and bacterial infections at the child’s bedside11. Andreola et al12 (and more recent studies by Ruud Nijman again) looked at febrile children and infants in Emergency Departments and this is what they found:

White cell counts, we know, are not helpful. A raised white cell count has poor sensitivity and specificity, so while CRP is better and PCT better still there is room for improvement.  All these tests have problems with sensitivity which means there is still going to be a worrying number of falsely negative tests.  We know this, for example, in children with diseases that progress quickly like meningococcaemia or sepsis who can have normal inflammatory markers early on.

However, new tests are on the horizon. The PERFORM/IRIS group published a diagnostic test using a two-transcript host RNA signature that can discriminate between bacterial and viral infections in febrile children (Herberg, JAMA 2016), using gene arrays to demonstrate up or down regulation of protein expression. Sensitivity in the validation group was 100% and specificity 96.4%13.  

But we don’t just want to know if a child has a bacterial or viral infection, we really want a clinical predictor of severity that could tell us which children are going to get very ill.  We have a few tests, but they’re not very specific. We often look at blood gases, looking for a metabolic acidosis. But that is very broad. What about a lactate >2mmol/l? The international guidelines did not recommend the use of lactate as the evidence is lacking, although it can give an idea of the trend and whether a child is getting better or worse and is generally considered to be best practice and is already standard in adult sepsis. But this is in direct contrast to a study by Elliot Long and team published earlier this year14 looking at predictors of organ dysfunction in over 6000 children presenting to the ED with fever. A lactate of 4 or higher was one of the best performing ED predictor of new organ dysfunction, the need for inotropic support and the need for mechanical ventilation. Take a look at Deirdre Philbin’s DFTB review of the study.

More new tests are coming.  For example, interleukin 6 and 10 may be able to predict which children with febrile neutropenia have serious infections and mid regional pro-adrenoedullin (MR pro-ADM) may be a promising biomarker to predict sepsis and septic shock15. So, watch this space!

Antibiotics

Recommendation number three. Start broad-spectrum antibiotics.

Moving on from tests to treatment, we now want to look at recommendation number three, when to start broad-spectrum antibiotics. There is a change in timing here.

In children with septic shock, antimicrobial therapy should be started as soon as possible and within one hour of recognition of sepsis.”  But, in children with suspected sepsis (i.e. organ dysfunction, but not shock), most of the children we see, guidelines suggest starting antimicrobial treatment as soon as possible after evaluation – you have 3 hours not 1 hour16.

This is important, because it gives you a chance to do tests and decide whether the child in front of you has sepsis or just a SIRS response due to a viral infection. This has bigger implications than just saving hospital beds, because we know timely initial empirical antibiotics will save lives, but unnecessary antibiotic use for all children with fevers increases antibiotic side effects, antibiotic resistance and cost.

Antibiotic choice

There are other recommendations around antibiotics. Importantly, the new consensus recommends a broad-spectrum antibiotic therapy with one single drug in normal children, such as  cefotaxime or ceftriaxone or, if they are allergic, meropenem.

As a quick aside, let’s think about penicillin allergy.

It’s important to get a history and to understand what a ‘real’ penicillin allergy is. We see a lot of children who present with a vague story of having been given a couple of doses of penicillin many years ago, who developed a rash and have been labelled as ‘penicillin allergic’.  But doing that in the heat of the moment can be tricky.

Zagursky believes “Avoidance of cephalosporins, when they are the drug of choice in a penicillin-allergic individual, results in significant morbidity that outweighs the low risk of anaphylaxis. We conclude that there is ample evidence to allow the safe use of cephalosporins in patients with isolated confirmed penicillin or amoxicillin allergy”17

Studies have found the risk of crossover between penicillin/cephalosporin reactions is <1%, so using cephalosporins as a first line is safe.  If the child also has cephalosporin sensitivity, they may need a carbapenem like meropenem.  Later, please think about referring these children to your local allergy service for penicillin or cephalosporin de-labelling, which entails having an antibiotic challenge under controlled, safe circumstances.

Moving on… antibiotics in immunocompromised children

The guidelines suggest using empiric multi-drug therapy in children with immunocompromise and those at high risk for multi-drug resistant pathogens. In this case, you might choose piperacillin-tazobactam and, if shock is present, amikacin. You can add teicoplanin if you suspect a line infection, with rigors when flushing the line, or a line site infection, with redness around their exit site, or signs of any soft tissue cellulitis.

The recommendations also cover antimicrobial stewardship. Once the pathogen and sensitivities are available, the guidelines recommend narrowing antimicrobial therapy coverage. This means narrowing down the antibiotic to something specific to the clinical presentation, site of infection, or risk factors.  Ask yourself these questions:

  • Is the child is showing clinical improvement?
  • Can they have their antibiotics at home? (via a paediatric out-patient antibiotic service)
  • Can they switch to oral antibiotics?
  • Can they stop their antibiotics?  If you don’t find any bugs, and the child is well, then the guidelines recommend stopping antimicrobial therapy.

Remember to phone a friend

Infectious disease teams or microbiologists; you never need to make decisions alone. The guidelines recommended daily assessment with clinical laboratory assessment for de-escalation of antimicrobial therapy. Assessment includes a review of the ongoing indication for antibiotics after the first 48 hours and should be guided by results from microbiology, signs of clinical improvement and evidence of reducing inflammatory markers, such as a halving of CRP, or if the child’s fever has settled for more than 24 hours.

Fluids

Moving on from antibiotics to fluids. The Surviving Sepsis Campaign has another paediatric management algorithm for fluid and vasoactive drugs. It’s also quite busy, incorporating the results of the FEAST study18.  It’s split into two, a green side and a blue side. The green side is for children who live in healthcare systems without intensive care, while the blue side is healthcare systems with paediatric intensive care. The change boils down to being more cautious with fluids.  The guidelines recommend 10-20 ml/kg boluses. I suggest giving 10 ml/kg and then reassessing for signs of fluid overload with hepatomegaly and listening for basal crackles suggesting pulmonary oedema, repeating a second or third bolus as needed.  I use 10 ml/kg because it’s the same in sepsis, in neonates and in trauma.

If the child needs more volume, give them more volume; you can repeat 10ml/kg boluses up to 40 ml/kg or more as needed just use smaller aliquots.  Remember there may still be children who need big volumes of fluid early on, and we have PICU readily available and the technology to support children’s circulation and ventilation and ‘dry them out’ later.  There isn’t enough evidence to fluid restrict children with sepsis in the ‘resource rich’ world just yet but trials are ongoing. The Squeeze Canadian Critical Care Group19 has started a study, so watch this space for results.

Which fluids should you choose?

Please use crystalloids not colloids. And although historically we have used 0.9% saline, it is better to choose balanced or buffered solutions such as Ringer’s lactate or Plasmalyte. Too much saline can cause hyperchloremic acidosis.   

Inotropes

There has been a real sea change in our approach with inotropes. As we’re being more cautious with fluid resuscitation, we need to start giving inotropes earlier. After giving 40 to 60 ml/kg have your inotrope lined up ready to go.  There is good evidence that the drug of choice should be adrenaline20.  You can give adrenaline via a peripheral intravenous cannula or an intra osseous cannula safely if you don’t have central access. There have also been studies in adults that showed that peripheral adrenaline is also safe, especially when given for less than four hours or in a diluted dose.

Safety netting

Most of the febrile children we see will be discharged; safe discharge is a big priority because that’s what the majority of hot bothered children need: good advice and home care.  Winters (2017)21 looked at 33,000 children who were discharged from Emergency Departments with abnormal vital signs. 27,000 (80%) of them were discharged with normal vital signs, with only one case of potentially preventable permanent disability (a child who presented with tummy pains and came back with torsion of the testes, unlucky). 5,500 children (16%) were discharged with abnormal vital signs; there were no permanent disability or deaths from this group. So, you can send children home with fevers safely. But, the proviso to this is they need good safety netting on discharge, including both verbal and written information. This is one of the NICE recommendations. Our discharge safety netting leaflet22, which (gives some straightforward, practical information about giving anti-pyretic medication like paracetamol and ibuprofen), works like a ‘parent’s PEWS’ chart. It allows parents to see if their child is OK to stay at home or if they’re at some risk and should contact the GP, go to a walk in centre or call 111-advice line if they haven’t got better in 48 hours.  If the child is on the ‘high risk’ side, we want to see them back in the Paediatric Emergency Department.

In summary…

So, in summary, please screen for sepsis, we should all be doing it. I don’t know the best systems to help you but, ideally, you should have electronic observations, protocols and local guidelines.  Be aware that in the ED the incidence of sepsis is rare and that recent surviving sepsis campaign guidance suggests you can safely observe while you make a decision on treatment. Give antibiotics within 60 minutes in septic shock, but in sepsis with no shock you have three hours. If you are treating use fluid cautiously, with 10-20 ml/kg boluses and frequent reassessments.  Start adrenaline early if appropriate, and this can be given safely, peripherally.  Finally, safety netting is essential.

Thank you very much for reading this right through to the end! If you want to hear more, please have a listen to our Paediatric Sepsis podcast, hosted by the RCPCH.

Selected references

  1. Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. Weiss SL et al. Pediatr Crit Care Med. 2020 Feb;21(2):e52-e106. doi: 10.1097/PCC.0000000000002198.PMID: 32032273
  2. Craig JC et al. The accuracy of clinical symptoms and signs for the diagnosis of serious bacterial infection in young febrile children: prospective cohort study of 15 781 febrile illnesses. BMJ. 2010;340:c1594 10.1136/bmj.c1594
  3. Nijman RG et al. Clinical prediction model to aid emergency doctors managing febrile children at risk of serious bacterial infections: diagnostic study. BMJ. 2013;346:f1706 10.1136/bmj.f1706
  4. van de Maat J et al. Antibiotic prescription for febrile children in European emergency departments: a cross-sectional, observational study. Lancet Infect Dis. 2019;19:382–91. 10.1016/S1473-3099(18)30672-8
  5. Weiss SL et al. Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015 May 15;191(10):1147-57. doi: 10.1164/rccm.201412-2323OC. Erratum in: Am J Respir Crit Care Med. 2016 Jan 15;193(2):223-4. PMID: 25734408; PMCID: PMC4451622.
  6. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis.Pediatr Crit Care Med. 2005 Jan;6(1):2-8. doi: 10.1097/01.PCC.0000149131.72248.E6. PMID: 15636651 Review
  7. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Shankar-Hari M et al. Sepsis Definitions Task Force. JAMA. 2016 Feb 23;315(8):775-87. doi: 10.1001/jama.2016.0289. PMID: 26903336
  8. Romaine ST et al. Accuracy of a Modified qSOFA Score for Predicting Critical Care Admission in Febrile Children. Pediatrics. 2020 Oct;146(4):e20200782. doi: 10.1542/peds.2020-0782. PMID: 32978294; PMCID: PMC7786830.
  9. Gill FJ et al. The Impact of Implementation of Family-Initiated Escalation of Care for the Deteriorating Patient in Hospital: A Systematic Review. Worldviews Evid Based Nurs. 2016 Aug;13(4):303-13. doi: 10.1111/wvn.12168. Epub 2016 Jun 3. PMID: 27258792.
  10. Martinón-Torres F et al. EUCLIDS Consortium. Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study. Lancet Child Adolesc Health. 2018 Jun;2(6):404-414. doi: 10.1016/S2352-4642(18)30113-5. Epub 2018 Apr 28. PMID: 30169282.
  11. Herberg JA et al. IRIS Consortium. Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children. JAMA. 2016 Aug 23-30;316(8):835-45. doi: 10.1001/jama.2016.11236. Erratum in: JAMA. 2017 Feb 7;317(5):538. PMID: 27552617; PMCID: PMC5997174.
  12. Andreola, B et al. Procalcitonin and C-Reactive Protein as Diagnostic Markers of Severe Bacterial Infections in Febrile Infants and Children in the Emergency Department, The Pediatric Infectious Disease Journal: August 2007 – Volume 26 – Issue 8 – p 672-677. doi: 10.1097/INF.0b013e31806215e3
  13. Herberg JA et al. Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children. JAMA. 2016 Aug 23-30;316(8):835-45. doi: 10.1001/jama.2016.11236. Erratum in: JAMA. 2017 Feb 7;317(5):538. PMID: 27552617; PMCID: PMC5997174.
  14. Long E, Solan T, Stephens DJ, et al. Febrile children in the Emergency Department: Frequency and predictors of poor outcome. Acta Paediatr. 2020; 00: 1– 10 
  15. Xia T, Xu X, Zhao N, Luo Z, Tang Y. Comparison of the diagnostic power of cytokine patterns and procalcitonin for predicting infection among paediatric haematology/oncology patients. Clin Microbiol Infect. 2016 Dec;22(12):996-1001. doi: 10.1016/j.cmi.2016.09.013. Epub 2016 Sep 22. PMID: 27665705.
  16. Elke G et al. SepNet Critical Care Trials Group. The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis – a secondary analysis of a large randomised controlled trial. Crit Care. 2018 Mar 21;22(1):79. doi: 10.1186/s13054-018-2001-5. PMID: 29562917; PMCID: PMC5863464.
  17. Zagursky RJ, Pichichero ME. Cross-reactivity in β-Lactam Allergy. J Allergy Clin Immunol Pract. 2018 Jan-Feb;6(1):72-81.e1. doi: 10.1016/j.jaip.2017.08.027. Epub 2017 Oct 7. PMID: 29017833.
  18. Maitland K et al. FEAST Trial Group. Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011 Jun 30;364(26):2483-95. doi: 10.1056/NEJMoa1101549. Epub 2011 May 26. PMID: 21615299.
  19. Parker, M.J., Thabane, L., Fox-Robichaud, A. et al. A trial to determine whether septic shock-reversal is quicker in pediatric patients randomized to an early goal-directed fluid-sparing strategy versus usual care (SQUEEZE): study protocol for a pilot randomized controlled trial. Trials 17, 556 (2016). https://doi.org/10.1186/s13063-016-1689-2
  20. Ramaswamy KN, Singhi S, Jayashree M, Bansal A, Nallasamy K. Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock. Pediatr Crit Care Med. 2016 Nov;17(11):e502-e512. doi: 10.1097/PCC.0000000000000954. PMID: 27673385.
  21. Winter J, Waxman MJ, Waterman G, Ata A, Frisch A, Collins KP, King C. Pediatric Patients Discharged from the Emergency Department with Abnormal Vital Signs. West J Emerg Med. 2017 Aug;18(5):878-883. doi: 10.5811/westjem.2017.5.33000. Epub 2017 Jul 19. PMID: 28874940; PMCID: PMC5576624.
  22. Lim E, Mistry RD, Battersby A, Dockerty K, Koshy A, Chopra MN, Carey MC, Latour JM. “How to Recognize if Your Child Is Seriously Ill” During COVID-19 Lockdown: An Evaluation of Parents’ Confidence and Health-Seeking Behaviors. Front Pediatr. 2020 Nov 17;8:580323. doi: 10.3389/fped.2020.580323. PMID: 33313025; PMCID: PMC7707121.

Febrile Infection-Related Epilepsy Syndrome (FIRES)

Cite this article as:
Jessica Archibald and Catherine Murphy. Febrile Infection-Related Epilepsy Syndrome (FIRES), Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.32716

An 8-year-old presents to the emergency department following a first seizure episode. They had a witnessed generalised tonic-clonic seizure that morning lasting approximately 60 seconds and remain post-ictal. They have a history of being non-specifically unwell yesterday with subjective fever, lethargy and a mild headache. They have no significant past medical history and no family history of seizures. The examination is unremarkable. Whilst in the emergency department they have a further two self-terminating generalised tonic-clonic seizures.

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a rare epileptic encephalopathy that results in prolonged refractory status epilepticus in previously well patients.

Presenting Features

FIRES typically presents in children between the age of 3 to 15 years, with intractable status epilepticus, 2 to 10 days post a febrile illness. The preceding illness is most commonly an upper respiratory tract infection or gastroenteritis. Fevers may have resolved prior to the onset of the acute phase of the condition.

The acute phase of the illness is characterised by frequent seizures, rapidly progressing to status epilepticus. Although the seizures are initially focal in nature, they may evolve into secondary generalised seizures. The acute phase can be prolonged, lasting from weeks to months. An association with rash, liver derangement and arrhythmia has been noted in the literature. There is no latency period.

The chronic phase is denoted by refractory epilepsy, resulting in seizures that may cluster every 2 to 4 weeks. This is often associated with severe neurological impairment and cognitive decline.

FIRES had previously been thought to only occur in children, and New-Onset Refractory Status Epilepticus (NORSE) only in adults, however this theory has been disproven. Although FIRES is more prevalent in children, it has been known to also occur in adults. As such, FIRES is now considered a subtype of NORSE, characterised by a preceding febrile illness. It has previously been known as Acute Encephalitis with Refractory, Bepetitive Partial Seizures (AERRPS) and Devastating Epilepsy in School-age Children (DESC).

Aetiology

The aetiology of FIRES in unknown and as such the pathophysiology remains unclear.

One theory is that FIRES is a form of severe infectious encephalitis, but as yet no infectious agent has been identified, and the refractory nature of the seizures is atypical of encephalitis. Another hypothesis suggests FIRES is the result of an immune response, however, there is not enough evidence to support this theory.

A case identifying anti-GABA A receptor antibodies in the CSF of a patient who presented with severe refractory status epilepticus associated with a fever led to speculation that the condition may be autoimmune-mediated. Again this has not been proven and the case may have been an exception rather than a rule.

Other theories include genetic associations and potential links with metabolic disease, but as yet a cause has not been identified.

Diagnosis and Differentials

The diagnosis of FIRES is essentially clinical, as FIRES is a cryptogenic illness. The work up is initially general, and focused on the exclusion of other treatable causes, such as infectious or autoimmune encephalitis.

A detailed history will identify the preceding febrile illness, and would be focussed on the identification of risk factors for other causes for the presentation, including exposure to animals, drugs and toxins, recent foreign travel and immunosuppression.

Blood sampling will be used to identify an infectious cause for the presentation, through full blood count, blood cultures and a screen for atypical infective agents. Lumbar puncture should be performed for CSF sampling in order to investigate bacterial, viral, fungal or autoimmune causes. CSF may show a mildly elevated white cell count in those with FIRES.

EEGs may show a generalised slowing, in keeping with an encephalopathic picture, but do little in the way of distinguishing between other causes of seizures. However, they are useful in guiding treatment and identifying non-convulsive seizures.

Initial MRI imaging is often normal, however, follow up imaging has been associated with devastating changes. Early MRI, in the first weeks of the acute illness, has shown swelling of the mesial temporal structures and increased T2 weighted signal. Follow up MRI, greater than 6 months after onset, may be associated with bilateral mesial temporal atrophy and increased T2 weighted signal. It should be noted that MRI may be normal in 50% of cases.

Differentials to consider are Dravet Syndrome, which presents with a febrile illness associated with status epilepticus, though this tends to present within the first year of life. Also Alper’s Disease, which presents with refractory seizures in previously well children, and is often associated with liver disease.

The patient is loaded with levetiracetam (40mg/kg) as per hospital guidelines, and admitted under paediatrics locally. A CT head is unremarkable and bloods show mild LFT derangement with normal inflammatory markers. They are treated empirically with intravenous cefotaxime and aciclovir. Later that afternoon they develop a fever of 38.3.

The GCS fluctuates between 11 to 13 with no full recovery to baseline until later that evening. Following two focal seizures the next afternoon, they are transferred to the local tertiary centre for further investigation and management.

Initial Management

Initial management involves treating the seizure, and more often status epilepticus. Local hospitals have their own guideline for managing status epilepticus but the first line is typically benzodiazepines (lorazepam, diazepam, midazolam, clonazepam). Second-line treatment is standard anti-convulsants (levetiracetam, phenytoin, phenobarbitone, sodium valproate), however, FIRES does not typically respond to these medications even in high doses.


The seizure pattern in FIRES is often resistant to multiple anti-epileptics. Alternative treatment options have to be sought although there is limited evidence as to the optimal treatment.

Long-term Management

There is limited data on the treatment of FIRES, however, they all conclude the seizures are very difficult to manage and often require polytherapy. Some of the alternative treatment options include drug-induced burst-suppression comas, immunotherapy, a ketogenic diet, vagus nerve stimulation, therapeutic hypothermia and intravenous magnesium sulfate. The most commonly used and researched options are discussed below.

Burst suppression coma

Burst suppression coma induction is viewed as standard care for refractory status epilepticus. If first and second-line treatments fail the next option involves high doses of anti-convulsants along with anaesthetic agents, for example, an infusion of midazolam, barbiturates or propofol. Unfortunately when the anti-convulsants are weaned the seizures tend to reoccur. Prolonged burst suppression coma has been associated with a significantly worse cognitive outcome and poorer prognosis.

Immunotherapy

Immunotherapy has been trialled due to the suspected role of inflammation in the pathogenesis of FIRES. High dose steroids, intravenous immunoglobulin and plasmapheresis have all been used. There is limited evidence to suggest a beneficial role in the management of refractory epilepsy. A large-scale Japanese study described 2 out of 12 patients responding to steroids, although there is not enough evidence to support this as a treatment option. Treatment with immunotherapy is often associated with significant side effects

Anakinra is a recombinant and modified human interleukin-1 receptor antagonist protein. Recent evidence has shown it to be an effective and promising treatment option in patients with FIRES, though relapse has been reported after withdrawal. It has been shown to decrease the duration of mechanical ventilation and hospital length of stay, and possibly seizure reduction. Future studies are required to understand the optimum dosing regime and safety of anakinra.

Ketogenic diet

A ketogenic diet is a high fat, adequate protein and low carbohydrate diet aimed at imitating the body’s fasting state. The body, therefore, metabolises fat for energy. The early introduction of the ketogenic diet has shown to be beneficial in the management of FIRES in uncontrolled trials. It has been suggested that the ketogenic diet may have an anti-inflammatory, as well as an anti-convulsant effect. Some reports suggest it may also have a positive effect on long term cognition. Currently, it is one of the only management options shown to be effective. Future controlled studies are needed to prove this efficacy.

Vagus nerve stimulation

Vagus nerve stimulation (VNS) involves the implantation of an electrode that produces intermittent electrical stimulation into the left cervical vagus nerve. Case reports have found benefit from VNS in the cessation of seizures in patients with refractory status epilepticus and NORSE. There is limited evidence of its use in FIRES.

Long term effects

The prognosis of FIRES is poor. The outcome varies with the length of the acute phase with mortality rates up to 30%. Of those patients who survive there is 66-100% chance that they will have long term cognitive impairment due to damage of the frontal and temporal lobe functions. Survivors with a normal cognitive function will present with a spectrum of learning disabilities, behavioural disorders, memory issues and sensory changes. There is a high risk of recurrent status epilepticus. Unfortunately, only a small proportion of survivors will have no neurologic sequelae.

The patient required a lengthy PICU admission where they were managed with a burst suppression coma, ketogenic diet, high dose steroids and intravenous immunoglobulin.

They were later diagnosed with Febrile-Infection Related Epilepsy Syndrome after extensive investigations, including a normal brain MRI and a lumbar puncture which showed a mildly elevated white cell count but was otherwise unremarkable.

They are currently seizure free on a combination of oral phenobarbitone, perampanel and levetiracetam but have some cognitive sequelae.

References

  1. Fox K, Wells ME, Tennison M, Vaughn B. Febrile Infection-Related Epilepsy Syndrome (FIRES): A literature Review and Case Study. Neurodiagn J. 2017;57(3):224-233. doi: 10.1080/21646821.2017.1355181. PMID: 28898171
  2. Lee H, Chi C. Febrile infection-related epilepsy syndrome (FIRES): therapeutic complications, long-term neurological and Neuro imaging follow-up. Seizure. 2018;56:53-59.
  3. Serino D, Santarone M, Caputo D, Fusco L. Febrile infection-related epilepsy syndrome (FIRES): prevalence, impact and management strategies. Neuropsychiatric Disease and Treatment. 2019;Volume 15:1897-1903.
  4. NORSE (New Onset Refractory Status Epilepticus) and FIRES (Febrile Infection-Related Epilepsy Syndrome) – NORD (National Organization for Rare Disorders) [Internet]. NORD (National Organization for Rare Disorders). 2021 [cited 20 January 2021]. Available from: https://rarediseases.org/rare-diseases/new-onset-refractory-status-epilepticus-norse
  5. Orphanet: Febrile infection related epilepsy syndrome [Internet]. Orpha.net. 2021 [cited 20 January 2021]. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=163703
  6. Caputo D, Iorio R, Vigevano F, Fusco L. Febrile infection-related epilepsy syndrome (FIRES) with super-refractory status epilepticus revealing autoimmune encephalitis due to GABA A R antibodies. European Journal of Paediatric Neurology. 2018;22(1):182-185.
  7. Diagnostic Evaluation — NORSE INSTITUTE [Internet]. NORSE INSTITUTE. 2021 [cited 20 January 2021]. Available from: http://www.norseinstitute.org/definitions
  8. Dravet Syndrome – NORD (National Organization for Rare Disorders) [Internet]. NORD (National Organization for Rare Disorders). 2021 [cited 20 January 2021]. Available from: https://rarediseases.org/rare-diseases/dravet-syndrome-spectrum
  9. Alpers Disease – NORD (National Organization for Rare Disorders) [Internet]. NORD (National Organization for Rare Disorders). 2021 [cited 20 January 2021]. Available from: https://rarediseases.org/rare-diseases/alpers-disease
  10. Wheless. J. Treatment of refractory convulsive status epilepticus in children: other therapies. Seminars in Paediatric Neurology (2010) 17 (3) 190-194.
  11. Kramur U et al. Febrile infection-related epilepsy syndrome (FIRES): Pathogenesis, treatment and outcome. Epilepsia (2011) 52: 1956-65.
  12. Gaspard et al. New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES): State of the art and perspectives. Epilepsia (2018). 59 (4) 745-752.
  13. Sakuma et al. 2010. Acute encephalitis with refractory, repetitive partial seizures (AERRPS): a peculiar form of childhood encephalitis. Acta Neurol Scand 121:251–256.
  14. Hon et al. Febrile Infection-Related Epilepsy Syndrome (FIRES): An overview of treatment and recent patents. Recent Patents on Inflammation & Allergy Drug Discovery (2018). 12 (2): 128-135
  15. Maniscalco et al. The off-label use of anakinra in pediatric systemic autoinflammatory diseases. The Advance Musculoskeletal Disease (2020)
  16. Shukla N et al. Anakinra (IL-1 blockade) use in children with suspected FIRES: a single institution experience. Neurol 2018; 90: 346
  17. Lai et al. Anakinra usage in febrile infection related epilepsy syndrome: an international cohort. Annals of Clinical and Translational Neurology (2020). 7(12): 2467 – 2474
  18. Dibue-Adjei et al. 2019. Vagus nerve stimulation in refractory and super-refractory status epilepticus – A systematic review. Brain Stimuatlion. 12 (4) 1101-1110.
  19. Kurukumbi et al. 2019. Vagus nerve stimulation (VNS) in super refractory new onset refractory status epilepticus (NORSE). Case Reports in Neu

The 49th Bubble Wrap

Cite this article as:
Currie, V. The 49th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:
https://dontforgetthebubbles.com/the-49th-bubble-wrap/

With millions upon millions of journal articles being published every year it is impossible to keep up.  Every month we ask some of our friends from PERUKI (Paediatric Emergency Research in UK and Ireland) to point out something that has caught their eye.

Article 1: The associations between initial serum pH value and outcomes of paediatric out-of-hospital cardiac arrest

Okada A, Okada Y, Kandori K, Nakajima S, Okada N, Matsuyama T, Kitamura T, Hiromichi N, Iiduka R. Associations between initial serum pH value and outcomes of pediatric out-of-hospital cardiac arrest. Am J Emerg Med. 2021 Feb;40:89-95. doi: 10.1016/j.ajem.2020.12.032. Epub 2020 Dec 17. PMID: 33360395.

What’s it about? 

This paper reviewed the association between initial pH, obtained via intra-arrest VBG, and patient outcomes to evaluate if pH can be used to prognosticate in paediatric out of hospital cardiac arrest.

The authors reviewed a large, multicentre, prospective register of out-of-hospital cardiac arrests in 87 hospitals in Japan. They included paediatric out-of-hospital cardiac arrest patients younger than 16 between June 2014- December 2017 (458 patients included in the analysis – however over 35,000 listed in the registry). The primary outcome was 1-month survival. They divided the patients into four groups (based on initial pH on blood gas) and compared this to the patient’s ultimate outcome.

Interestingly, the median age of the patients was one year of age. Just over 6 in 10 of the patients were male. In 7 out of 10 patients, the first monitored rhythm was asystole. Cardiogenic arrest occurred in 4 out of 10 patients.

Mortality, and survival with good neurologic function, were lookd for. The overall survival rate at one month was just over 1 in 10 patients. In the group with pH > 6.82 survival rate was around 4 in 10 patients. However, with a pH< 6.47, thesurvival rate was 1 in 100 patients.

Of particular interest, in the entire study population of 458 patients, there were no patients who survived with good neurological function with a pH <6.8.

Why does it matter? 

Deciding when to stop resuscitation in a paediatric cardiac arrest can be difficult. Guidance is sparse and there are no universally recommended measures to help providers decide when to stop resuscitative measures. This is a stark contrast to adult cardiac arrest management where there are many validated termination of resuscitation rules based on measurements such as end-tidal CO2 s.

This is the first study to assess the association between pH and prognosis in paediatric out-of-hospital cardiac arrest. It presents robust evidence to support an objective, easily obtained measure that can be used to assist decision making around the termination of resuscitation. Important exclusions in this study were patients where resus was not attempted at a hospital, unknown age, traumatic or arrest secondary to hanging and those with no pre-hospital data.

This is an exciting paper providing guidance in an area sorely lacking any previous data. It gives providers a valuable tool that can substantially assist when making a difficult decision.

Clinically Relevant Bottom Line:

In out of hospital paediatric cardiac arrest, according to this study, no patients with a pH <6.8 survived with a neurologically favourable outcome. Survival in general was significantly lower in patients with an initial pH <6.8.

Reviewed by: Sean Croughan

Article 2: Should we be using focused cardiac ultrasound to guide therapy in children with sepsis?

Arnoldi s, Glau CL et al. integrating focused cardiac ultrasound into Pediatric septic shock assessment. Pediatr Crit Care Med. 2021 mar 1;22(3):262-274

What’s it about? 

This paper looks at whether the integration of FCU (focused cardiac ultrasound) in clinical assessment of children with sepsis would alter clinician’s evaluation of their haemodynamic characteristics.

The authors conducted a retrospective, observational study from January 2014 – December 2016 in a large PICU in America. They reviewed 74 PICU patients who received FCU within 72 hours of sepsis pathway initiation. Assessment by clinicians prior to FCU was compared to assessment after FCU in 46 patients, to determine if there was a difference in the haemodynamic characterisation of patients.

They demonstrated that incorporation of FCU changed the clinician characterisation of haemodynamic assessment made prior to FCU in more than 2 out of 3 of cases. The most common new finding identified post-FCU was myocardial dysfunction in (7 out of 22) cases. The most commonly ruled-out physiologies by clinician after FCU performance were obstructive physiology (5 in 8 cases), fluid responsiveness (13 in 26 cases).

Why does it matter? 

Sepsis in children continues to be one of the leading causes of mortality and morbidity worldwide.  Most children who die of sepsis suffer from refractory shock and/or multiple organ dysfunction within the initial 48 -72 hours of treatment, thus demonstrating the need for early and targeted interventions.

The previous method of classifying patients as having either ‘warm shock’ or ‘cold shock’ to guide therapy has been demonstrated to have poor correlation with cardiac function and systemic vascular resistance, and has not led to improved outcomes. It is now recommended that more advanced techniques such as focused cardiac ultrasound (FCU) be used alongside clinical assessment to identify haemodynamic status and direct therapy.  This is already widely the case in adult practice and algorithms have been created for its integration into patient management. 

Although this is a small study, it makes us think about the use of cardiac ultrasound alongside clinical assessment of children with sepsis in order to understand the haemodynamic characterisation of these patients.

This may be particularly useful in relation to fluid responsiveness, as half of the children who were thought to be fluid responsive pre-FCU, were found not to be after a FCU was performed. We know that children with sepsis often receive significantly more fluid per kilogram than adults which is associated with worse outcomes.

Clinically Relevant Bottom Line:

FCU, when incorporated into shock assessment, has the potential to identify myocardial dysfunction earlier and could result in reduced fluid administration as well as more targeted therapy based on haemodynamic status. However, further work is needed to determine how this can be used within paediatric practice.

Reviewed by: Laura Duthie

Article 3: Don’t forget the planet

Di Cicco, M.E., Ferrante, G., Amato, D., Capizzi, A., De Pieri, C., Ferraro, V.A., Furno, M., Tranchino, V., La Grutta, S. (2020) Climate Change and Childhood Respiratory Health: A Call to Action for Paediatricians. Int J Environ Res Public Health, Vol 24;17(15):5344

What’s it all about?

The authors conducted a systematic review looking at papers which examined the connection between respiratory illnesses in children aged 0 – 18 years. Keywords used separately and in combination were (allergic rhinitis, rhinitis, asthma, bronchitis, pneumonia, infections) and key environmental phrases (climate change, pollution, particulate matter, ozone, nitrogen dioxide, allergen, pollen). There was no limitation on the date of paper or country of origin.

Whilst much of the research at this stage is not completely conclusive key points from the review include:

  • Several studies from different countries found a connection between the increased prevalence of rhinitis and asthma, as well as the frequency of symptoms with increased global temperatures, which has changed many plant species’ lifecycles and led to longer pollen seasons
  • Positive correlations between the incidence of pneumonia and other acute respiratory tract infections in the context of increased extreme weather events such as heatwaves, fires and floods
  • Positive associations between the increased relative humidity and increased activity of respiratory viruses such as respiratory syncytial virus

Why does it matter?

Climate change is the long-term shift in weather conditions (temperature, humidity, winds and extreme weather events) and is often talked about in regards to protecting our wildlife or preventing further damage to our oceans and forests. It is less talked about when considering the impact on our own health. A child born in 2020 will live in a world that is more than 4 degrees warmer than the pre-industrial average, and subsequently will be at greater risk of a variety of acute illnesses as well as long term health consequences.

The Bottom Line:

More research needs to be done to accurately define the burden of climate change on our health. In the interim, we can all be environmental champions, from making changes in our own lives to reduce our carbon footprint as well as educating and influencing our colleagues and patients to do the same.

 …And for those with spare time; conducting research into the direct effects of climate change on specific health conditions along with contributing to government policies to create change at a higher level and reducing the carbon footprint of our healthcare systems are excellent places to start! 

Reviewed by: Tina Abi Abdallah

Article 4: Domo arigato, Mr Roboto

Littler BKM, Alessa T, Dimitri P, et al Reducing negative emotions in children using social robots: systematic reviewArchives of Disease in Childhood  Published Online First: 08 March 2021. doi: 10.1136/archdischild-2020-320721

What’s it about?

The paper looks at a number of studies that have used social robots in paediatric outpatient settings to interact and provide multi-sensory experiences to patients. The author postulates that using social robots provides better interaction and distraction for children, thus reducing anxiety and distress during the visit.

This systematic review managed to find ten studies that used social robots ranging from humanoid-based robots to ones simulating toy bears, dinosaurs and seals. The robots interact verbally and physically, and can respond to patient cues and tactile stimulation. They were used before or during the intervention. The studies included randomised controlled trials, exploratory trials, pilot and an observational study, with patient numbers varying from 2 to 73 (320 in total).

Why does it matter?

For lots of children a visit to the hospital can be a stressful and anxiety inducing event. There has been research to suggest that social robots have a positive impact on supporting adults with dementia and in children with autism they have been a useful tool in conducting therapy. The outcomes of this study were measured by observation, and by recording levels of distress, anxiety, pain and emotion using a variety of behavioural questionnaires. Overall, the feedback from the studies showed positive engagement from patients with their robots, reducing negative emotions, distress and pain.

The bottom line

There is promising data to suggest that robots may improve the experience of children in the healthcare environment. However, the evidence is weak due to the nature of the studies, lack of uniformity in the measurements, and low patient numbers. More research is needed on this topic to be able to really change practice but this sci-fi intervention may well become a reality in the not so distant future.

Reviewed by: Laura Riddick

Article 5: Children visiting the Paediatric emergency department during Ramadan

Sawaya,R., Wakil, C., et al (2021) Pediatric emergency department utilisation during Ramadan: a retrospective cross- sectional study. Archives of Disease in Childhood 2021;106:272-275.

What’s it about?

 This study looks to investigate the impact of Ramadan on patient characteristics, diagnoses and metrics in the paediatric emergency department (PED). There is limited data on how Ramadan impacts paediatric ED’s.

Why does it matter?

The authors looked at patient and illness characteristics as well as PED metrics including peak patient load, presentation timings, length of stay, time taken to order tests, receive samples and reporting of results to see how these were affected during the months of Ramadan and those before and after. 

This is a retrospective cross-sectional study on paediatric patients from 0 – 18 years presenting to a PED tertiary centre in Lebanon. Data was collected from all PED visits with any complaint at any time during Ramadan and the months (30days) before and after in 2016 and 2017. A bivariate analysis was performed between the Ramadan and non-Ramadan groups. The main outcomes were illness severity, chief complaints, final diagnoses, PED metrics including peak patient load, presentation timings, length of stay, and PED efficiency metrics such as time to order tests, times to samples being received and reported. 5711 patients were included and 1672 of these presented during Ramadan. There was no significant difference between age, gender or illness severity between the Ramadan or non-Ramadan group. This study found a significant difference in the number of GI complaints during Ramadan (39%) compared with the non-Ramadan group (35%). 

Trauma related complaints increased during Ramadan (3 in 100) vs (2 in 100) in non-Ramadan periods. Especially during the non-fasted periods of Ramadan (4 in 100) vs (2 in 100) during the fasted period of Ramadan. The number of daily visits during Ramadan (28.3) was reduced compared with non-Ramadan attendances (31.5). The Ramadan group did not have to wait longer for tests to be ordered or to have samples collected. 

This study was a single centre- and the charts that were reviewed did not have information on the patients individual fasting status. This would be interesting to see if the patient’s individual status affected diagnosis. The team used months immediately before and after Ramadan to reduce the confounding effects of seasonal bias.

Clinically Relevant Bottom Line:

This study revealed that there were some changes in GI and trauma presentations during the Ramadan period. There was also a reduction in cases presenting in this centre- this could help to influence staffing during this time if the patient population reflected that of the population in this study.

Reviewed by: Vicki Currie

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

That’s it for this month. Many thanks to all of our reviewers who have taken the time to scour the literature so you don’t have to.

All articles reviewed and edited by Vicki Currie