Fighting fires

One question I am asked almost every day at work is whether to give paracetamol (acetaminophen) or ibuprofen to reduce a childs’ fever. Today’s paper takes a look at just that question.

Before we take a closer look at the paper though, please bear in mind that I am not advocating that we should give anti-pyretic agents to all children with a raised temperature. It’s hard enough working out if their temperature is up in the first place without considering if reducing the temperature is of any benefit. Here’s the article from this months Journal of Paediatrics and Child Health…

Narayan K, Cooper S, Morphet J, Innes K. Effectiveness of paracetamol versus ibuprofen administration in febrile children: A systematic literature review. J Paediatr Child Health. 2017 Apr 24. doi: 10.1111/jpc.13507. [Epub ahead of print] PubMed PMID: 28437025.

Before jumping straight to the conclusions we need to check out the rigour of the literature review. I was taught, and use, the AMSTAR checklist. This is Assessing the Methodological quality of SysTematic Reviews.

What are the items on this checklist?

Was an ‘a priori’ design provided?

Not stated

Was there duplicate study selection and data extraction?

Once the initial screening had taken place two authors assessed the full-text articles for relevance. If there was any disagreement a third reviewer dived in and gave their opinion.

Was a comprehensive literature search performed?

At least two electronic sources were searched – CINAHL Plus, Cochrane Library, Web of Science, EBM Reviews, OVID Medline, SCOPUS, The Joanna Briggs Institute and my personal favourite, Google Scholar. The search was limited to papers from 1994 to 2014 (when the data search took place). The initial search managed to identify 3023 papers. After all the duplicates were taken out there were 2914 papers for perusal. The investigator then took the time to weed out 2842 papers just by looking at the titles. All in all 8 papers were identified that met the study criteria.

Search terms were stated in Table 2 of the article but did not appear to include the American spelling of paediatric (though this might be a typographical error). Studies were limited to those published in English.

Was the status of publication (e.g. grey literature) used as an inclusion criteria?

No mention was mentioned of searching the grey literature, consulting with topic experts or searching for conference abstracts though the authors did go through the references from previous papers.

Was a list of studies (included and excluded) provided?

It would be completely impractical to provide a list of the 3023 papers examined but they do provide a list of the included papers as well as those excluded after full text review.

Were the characteristics of the included studies provided?

Yes. Table 4 provides the basic details of the papers and Table 8 provides the more important data regarding sample size, drug dosage, means of temperature measurement as well as degree of fever reduction.

If you look at these single dose studies you should immediately notice the heterogeneity not just in dosage but how temperature is measured.

Was the scientific quality of the included studies assessed and documented?

Only RCTs were included in the search and a quality appraisal using a pre-determined strategy was undertaken.

Was the quality of the included studies used appropriately in formulating conclusions?

The heterogeneity of the studies was mentioned in the conclusions though the individual quality (very low,low, medium, high) was not mentioned.

Were the methods used to combine the findings of the studies appropriate?

There was no pooling of data. Looking at the data it is easy to see why. There were different doses, different means of recording temperatures and different outcome measures. The authors, therefore, provided a more narrative based conclusion.

Was the likelihood of publication bias assessed?


Was the conflict of interest included?

None were mentioned, in relation to the individual papers, or those performing the search. I doubt Big Pharma are overly interested in either of these agents.

So, for the bottom line, what were the results?

There was very little difference between either paracetamol or ibuprofen to reduce fever in the studies included. The authors conclusion that either agent is equally effective but, inevitably, recommends further rese3arch with a larger study population.

Given this clinical equipoise there is a place for a group such as PECARN, PREDICT or PERUKI to finally answer the question.

What does this mean for me in practice?

If you have to suggest something then you can be happy recommending either agent to parents perhaps guided by something more important, such a taste.

What about alternating between the paracetamol (acetaminophen) and ibuprofen?

A 2013 Cochrane review looked at this very subject. At that time they found 6 studies that took a look at this treatment regime. It is important to remember that the outcomes of any meta-analysis are only as good as the trials that are entered – the ‘garbage in, garbage out’ principle. All of trials were of very low, low or moderate quality. Giving both agents together seemed to result in a lower temperature at one hour than a single agent alone. The mean difference was only 0.27°C with pretty broad confidence intervals (0.45 to 0.08 degrees).

If they were given alternating treatments – paracetamol then ibuprofen, for example – then the mean difference at one hour was 0.6°C (with 95% confidence intervals of -0.94 to -0.26 degrees. More important than the potential drop in temperature though was the potential effect on child discomfort (what I like to call ‘grumpiness’, a core measurement that parents care about). Alternating therapy was associated with lower mean pain scores over a 72 hour period.

Is there any difference in the safety profiles of the two drugs?

If either drug is administered, in the therapeutic dosage range, then there is no statistically significant difference in adverse events between either agent. Kanabar provides a good review of the literature in a recent edition of my favourite beside reading – Inflammopharmacology.


I’ve spent a bit of time looking at the primary literature and I think it is important to point out the heterogeneity in dosing regimes.  I’ve seen paracetamol doses range from 10 to 20mg/kg and ibuprofen range from 7.5mg to 10mg per kilo. If you are comparing efficacy of the two agents then a clinically appropriate dosing strategy should be used.



Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, Porter AC, Tugwell P, Moher D, Bouter LM. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC medical research methodology. 2007 Feb 15;7(1):10.
Narayan K, Cooper S, Morphet J, Innes K. Effectiveness of paracetamol versus ibuprofen administration in febrile children: A systematic literature review. J Paediatr Child Health. 2017 Apr 24. doi: 10.1111/jpc.13507. [Epub ahead of print] PubMed PMID: 28437025.
Wong T, Stang AS, Ganshorn H, Hartling L, Maconochie IK, Thomsen AM, Johnson DW. Combined and alternating paracetamol and ibuprofen therapy for febrile children. Evidence‐Based Child Health: A Cochrane Review Journal. 2014 Sep 1;9(3):675-729

Temple AR, Zimmerman B, Gelotte C, Kuffner EK. Comparison of the Efficacy and Safety of 2 Acetaminophen Dosing Regimens in Febrile Infants and Children: A Report on 3 Legacy Studies. The Journal of Pediatric Pharmacology and Therapeutics. 2017 Jan;22(1):22-32.

Vyas FI, Rana DA, Patel PM, Patel VJ, Bhavsar RH. Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Perspectives in clinical research. 2014 Jan;5(1):25.

Jayawardena S, Kellstein D. Antipyretic Efficacy and Safety of Ibuprofen Versus Acetaminophen Suspension in Febrile Children Results of 2 Randomized, Double-Blind, Single-Dose Studies. Clinical Pediatrics. 2016 Nov 20:0009922816678818.

Langhendries JP, Allegaert K, Van Den Anker JN, Veyckemans F, Smets F. Possible effects of repeated exposure to ibuprofen and acetaminophen on the intestinal immune response in young infants. Medical hypotheses. 2016 Feb 29;87:90-6.

Kanabar DJ. A clinical and safety review of paracetamol and ibuprofen in children. Inflammopharmacology. 2017 Jan 6:1-9.

Alarm fatigue

It is easy to be bamboozled by the amazing technology we have at our fingertips – portable monitors, ultrasound machines, tricorders – but you only really need to know one button. It’s that one we all instinctively reach for before have even assessed the patient. It’s the big button marked “Silence“.

Emergency departments, operating theatres and intensive care units are noisy places. Our ears are assaulted by the auditory artillery so often it is a wonder that we don’t all get alarm fatigue.

What is alarm fatigue?

With the majority of physiological alarms completely irrelevant to the patient, it is no wonder that we quickly learn to ignore them. The high number of false alarms leads to a degree of alarm fatigue. Some of the alarms you might hear are relatively unimportant and may be viewed as a nuisance – the ECG lead has fallen off – and some – the patient has gone into VT – are critical.  And unfortunately most of them sound the same. A systematic review by Paine et al. found that whilst up to 26% of alarms in an adult ICU might be considered actionable, only around 1% are actionable in a paediatric ward setting. It is no wonder that alarm fatigue has been linked with a number of sentinel events if 99% of them require no action. Such sentinel events have led to ‘alarm hazards’ being ranked in the top three causes of technology related death and have rightfully become a target of The Joint Commission’s National Patietn Safety Goal.

Let’s take a look at this paper from JAMA.

Bonafide CP, Localio AR, Holmes JH, Nadkarni VM, Stemler S, MacMurchy M, Zander M, Roberts KE, Lin R, Keren R. Video Analysis of Factors Associated With Response Time to Physiologic Monitor Alarms in a Children’s Hospital. JAMA pediatrics. 2017 Apr 10.

This single-centre prospective cohort study attempted to look at what factors might be associated with alarm response time. The authors analysed 551 hours of video related to the care of 100 children and involving 38 nurses. Whilst the study tries to extrapolate which factors might be related to delays in response time, I think it is worth starting with some of the raw data.

In the 551 recorded hours the nursing staff were subjected to 11,745 alarms – or one every 168 seconds!! Only 50 of the 11,745 actually required any action. Actionable alerts or alarms were defined as those which identified physiological condition that required either an intervention or consultation with a health care provider.


So what factors were associated with a faster response time?

  • A potentially lethal arrhythmia
  • A one to one nurse to patient ratio
  • Previous interventions required
  • Less experienced nursing staff
  • No family members present

The reason for the faster response time seems intuitive in the first three cases. Perhaps less experienced nursing staff respond faster because they do not know which alarms to ignore.


What about a slower response time?

I think the most telling reason for delay in response was how far into the shift the staff were. As each hour into the shift passed, a 15% delay in response time was noted. Perhaps the constant tintinabullation of tachycardic tones leads to cognitive overload or perhaps it leads to a degree of desensitisation. It is more likely that there is a complex interplay of the two.


What were the limitations of this study?

This was a single centre study involving just a small number of nursing staff. The nurses were aware that they were being videotaped and this may have affected their response times. However, one would suppose that it would globally reduce the time it took to hit the big silence button.


How can we reduce alarm fatigue in the workplace?

Dealing with the problem requires both clever engineering solutions as well as some human ingenuity. Both software and hardware engineers are hard at work, behind the scenes, working out how to use multiple physiological parameters combined to come up with a more accurate alarm. I’ve often wondered where the standardised charts of physiological data for children come from. Most of the data is based on small studies that are 50 years old. Using real-time data from hospital patients analysts are able to calculate the new normal. They can then use this data to alter alarm parameters.


Is there anything I can do on my next shift?

Karnik and Bonafide came up with a great framework to reduce alarm fatigue that you can read here.

Set some limits. Most monitoring devices allow you to set alarm parameters. Use them. If your monitors do not recognise age related limits then you’ll need to set them yourself. Whilst a pulse rate of 160 might be normal for a 6 month old it is not for a 6 year old. If you are lucky then your monitoring device has a (small) built in delay. If the sats dip below 90% for just a couple of seconds before rebounding back, do you need to hear an alarm?

Stick to it. Some of the invalid non-actionable alarms are due to sticky electrodes coming  off, so take the time to attach them securely.

Take it off. Does the patient actually need to be monitored? This is not so much a problem in the paediatric world, thank goodness, where careful observation often outweighs technology. Do you need to use continual sats monitoring in a child with normal oxygen saturations or not requiring oxygen therapy?

Switch off. If monitors, ventilators, syringe drivers and infusion pumps all bleeping and pinging may lead to cognitive overload and sensory desensitisation please switch off your phone. Unless you need it for work how can you complain about alarms going off if you reach for your pocket every time you get a Facebook notification?


I think Edgar Allen Poe got it right…

Hear the loud alarum bells-
Brazen bells!
What a tale of terror, now, their turbulency tells!
In the startled ear of night
How they scream out their affright!
Too much horrified to speak,
They can only shriek, shriek,
Out of tune,
In a clamorous appealing to the mercy of the fire,
In a mad expostulation with the deaf and frantic fire,
Leaping higher, higher, higher,
With a desperate desire,
And a resolute endeavor,
Now- now to sit or never,
By the side of the pale-faced moon.
Oh, the bells, bells, bells!
What a tale their terror tells
Of Despair!

How they clang, and clash, and roar!
What a horror they outpour
On the bosom of the palpitating air!
Yet the ear it fully knows,
By the twanging,
And the clanging,
How the danger ebbs and flows:
Yet the ear distinctly tells,
In the jangling,
And the wrangling,
How the danger sinks and swells,
By the sinking or the swelling in the anger of the bells-
Of the bells-
Of the bells, bells, bells,bells,
Bells, bells, bells-
In the clamor and the clangor of the bells!

From The Bells by Edgar Allen Poe c. 1848


Bonafide CP, Localio AR, Holmes JH, Nadkarni VM, Stemler S, MacMurchy M, Zander M, Roberts KE, Lin R, Keren R. Video Analysis of Factors Associated With Response Time to Physiologic Monitor Alarms in a Children’s Hospital. JAMA pediatrics. 2017 Apr 10.

Bonafide CP, Lin R, Zander M, Graham CS, Paine CW, Rock W, Rich A, Roberts KE, Fortino M, Nadkarni VM, Localio AR. Association between exposure to nonactionable physiologic monitor alarms and response time in a children’s hospital. Journal of hospital medicine. 2015 Jun 1;10(6):345-51.

Korniewicz DM, Clark T, David Y. A national online survey on the effectiveness of clinical alarms. American Journal of Critical Care. 2008 Jan 1;17(1):36-41.

Goel VV, Poole SF, Longhurst CA, et al. Safety analysis of proposed data-driven physiologic alarm parameters for hospitalized children. J Hosp Med. 2016;11(12):817-823.

Karnik A, Bonafide CP. A framework for reducing alarm fatigue on pediatric inpatient units. Hospital pediatrics. 2015 Mar;5(3):160.

Lawless ST. Crying wolf: false alarms in a pediatric intensive care unit. Critical care medicine. 1994 Jun 1;22(6):981-5.

Sowan AK, Reed CC. A Complex Phenomenon in Complex Adaptive Health Care Systems—Alarm Fatigue. JAMA pediatrics. 2017 Apr 10.

Paine CW, Goel VV, Ely E, Stave CD, Stemler S, Zander M, Bonafide CP. Systematic review of physiologic monitor alarm characteristics and pragmatic interventions to reduce alarm frequency. Journal of hospital medicine. 2016 Feb 1;11(2):136-44

Ancker JS, Edwards A, Nosal S, Hauser D, Mauer E, Kaushal R. Effects of workload, work complexity, and repeated alerts on alert fatigue in a clinical decision support system. BMC Medical Informatics and Decision Making. 2017 Apr 10;17(1):36.

Speakers Corner – Henry Goldstein

As it gets closer to our inaugural Don’t Forget The Bubbles conference in Brisbane later this year we thought it about time we showcased some of the amazing and inspiring speakers we have lined up for you.  Coming from a wide range of backgrounds and life experiences we hope that they will help us all become better at looking after unwell children and better at looking after each other.


Henry Goldstein is a paediatric registrar and one of the key players behind the DFTB conference and it was a treat to interview him and get to know more about the man behind the posts.

1) Who inspires you in your clinical practice and why?

I am inspired by people who exude energy and enthusiasm with an equal measure of calm, compassion and knowledge. Folk who are curious and unafraid to question (even if for the sake of it!). Obviously, Captain Jean-Luc Picard comes to mind. In this universe, Dr Tom Hurley from the Sunshine Coast has stoked the fire of many juniors keen on paediatrics. He was my first supervisor and mentor; I actually first met Dr Hurley at a hospital talent show! He was dressed as AC/DC’s Angus Young having just performed “It’s a long way to the top”; sage advice from the start, really.

Outside Paediatric medicine, a handful of other clinicians I’ve worked with fit the above description. They include; Dr Steven Hamwood, a model of physicianly qualities, one of the most compassionate clinicians and astute diagnosticians I’ve worked with. Dr Jannie Geertsema, a Child and Adolescent Psychiatrist, opened the world of child & adolescent psychiatry, not just in a way that allowed me to function clinically, but also to see interpersonal interaction and the mind’s growth and development through a profound new viewpoint.  Another figure I have tremendous respect for is Dr Terry Nash; he’s considered by his peers a master for trauma and resus, which is unsurprising given that has also run a NATO trauma hospital. As well as running a resus with Zen-like calm, Terry is also one of the humblest medics I’ve come across any sphere.

2) What is a “career defining” moment that you can recall?

I would hope that my career is yet to be defined; however, my most memorable moment thus far certainly influenced the way I practice medicine. During one of my interviews to be a paediatric registrar, I was asked by the consultant what I would do if I was working nights and a child I was looking after died, and correctly or incorrectly, I felt that I was to blame. At the time I was caught slightly off guard by the question and managed an answer along the lines of having an extremely supportive medical fiancé (now wife) and friends and family. Unfortunately, events transpired that I encountered this scenario during a run night shifts only a few months later. The Birthsuite had called several times for an “Early discharge check”, and having done my best to defer things until the baby was now eight hours of life, I could find no medical indication for the baby to stay. I even discussed the case with the consultant on call; retrospectively, and despite all evidence to the contrary, I had this odd feeling that something wasn’t quite right. The mother took her baby home. Almost exactly 24hours later, just after dawn, a Cat 1 was called in ED. I was so Paediatrically-minded, I actually thought to myself “That’s an odd place for a C/section”. Instead, it was the same baby, CPR in progress. Time in the resus just flew past and was withdrawn once it was clearly futile. This experience has made me very cautious about early neonate discharges. If this child’s life can contribute anything to the wider clinical world, it is in the telling; most midwives wanting an early discharge check will hear it before I send one of their newborns home early!

3) How did you get involved with DFTB?

As a medical student, I wrote an anonymous blog which reached it’s natural end at graduation. In the interceding years, I’d become more active on twitter and had attended several Archives of Disease in Childhood  (#ADC_JC) journal clubs. In early 2013, I had begun to miss blogging and sought an outlet for study; I started pumping out a weekly “top five” list of #FOAMped, which was pretty clearly unsustainable. Tessa sent me a message along the lines of “I like what you are trying to do. Want to do this properly?”  Earlier in the year I’d also met Ben at (the now decommissioned) RCH Brisbane orientation. We caught up for a coffee and chatted about doing the project together; Tessa brought Andy on board, and the four of us began work on the site, launching DFTB on 1st September 2013.

4)  What is a little-known fact about you?

I once won a “Where’s Wally?” look-alike competition.

5)  What does DFTB mean to you?

Don’t Forget the Bubbles is about education; actively breaking down silos (both specialist and geographic), fostering a spirit of curiosity and asking, as well as answering, all kinds of questions. There is such a beautifully held tension between established knowledge & experience, knowledge translation and patient-specific or local information.

I also feel that DFTB provides a platform where we can consolidate primary evidence; that is, looking at, understanding and appreciating historical papers which explain the evolution of many of the therapies that fall into the “because we’ve always done it this way” box.  Don’t Forget the Bubbles is also a way to rapidly increase interest in published literature. People often refer to textbooks for medical knowledge and, particularly when you are relatively junior, it can be difficult and overwhelming to figure out where to look once your knowledge or the fidelity of your clinical question eclipses the fundamental texts. At DFTB we can provide an independent cultivation of things to read that seek to go to the next level.


If you haven’t yet checked it out, you can find the programme for DFTB17 here.