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Transcript: Twitter Journal Club Eighth Meeting 8pm, Sunday 7th August 2011

Maitland et al. (2011) Mortality after Fluid Bolus in African Children with Severe Infection (FEAST), NEJM Available at Hosted by Natalie Silvey

twitjournalclub Good evening and welcome to this week's discussion of FEAST - a summary post can be found at #twitjc -8:01 PM twitjournalclub A list of the discussion points for tonight can be found at #twitjc -8:01 PM twitjournalclub I am Natalie (tweet as @silv24) and I will be running tonight's discussion of this fascinating paper #twitjc -8:02 PM twitjournalclub First of all a huge thank you to Professor Kathryn Maitland from the FEAST study group for taking the time to replying to my email #twitjc -8:03 PM PaedsSHO David, paeds SHO in the Midlands. Really looking forward to tonight. #twitjc -8:03 PM twitjournalclub To start proceedings as always we begin with introductions... #twitjc -8:03 PM fidouglas Fi, medical student, also very much looking forward to this evening's discussion. #TwitJC -8:04 PM AnnabelleSouth Annabelle, working with FEAST team to communicate the results. Look forward to the discussions. #TwitJC -8:05 PM Victoria_W_S Tori, medical student, haven't taken part before so may just be observing, but excited nonetheless #twitjc -8:07 PM Puffles2010 Puffles asks any medics to follow #TwitJC tonight on medical & medical-public sector issues -8:07 PM welsh_gas_doc DJ - Anaesthetics Registrar. #TwitJC -8:08 PM thefourthcraw @twitjournalclub Mike, SpR Paeds in the Midlands. More spectating than participating tonight though. #twitjc -8:08 PM BenCosway Ben. Medical student. Really interested to see where discussion of this paper goes #twitjc -8:09 PM SuzetteWoodward for some reason #TwitJC and #twitjc show different tweets! So moving between the two -8:10 PM twitjournalclub @AnnabelleSouth thank you for joining in, very much appreciate it #twitjc -8:10 PM MedicScott Scott, medical student. Just observing as I'm also trying to get some work done tonight. #twitjc -8:11 PM Laeeq FEAST NEJM paper should make for interesting discussion points #twitjc -8:11 PM twitjournalclub @SuzetteWoodward That's odd. Shouldn't be happening. At least, it's never happened before... #TwitJC -8:11 PM

rodedun Rebecca, f1 (!) hopin to do Paeds. Haven't read paper as no internet so only popping in #Twitjc -8:12 PM twitjournalclub 1. Was the inclusion group in this trial too wide, especially in regards to ages (from a 60 day old baby to a 12 year old child)? #twitjc -8:13 PM fidouglas Hi @SuzetteWoodward, I can see the same tweets here regardless of capitalisation. That's using to follow. #twitjc -8:14 PM Buzzmf87 Matt, final year from Sheffield, bt only really listening as I have a prior engagement that kinda has to happen #twitjc -8:14 PM keirshiels Keir Paeds trainee and #juniordoctors monkey #twitjc -8:14 PM SuzetteWoodward @fidouglas may be cos I am using Echofon. #TwitJC works for both but the lower case doesnt (probably just me)... -8:15 PM silv24 My paeds knowledge is sorely limited but isn't there a huge difference in physiology in this age spectrum #twitjc -8:16 PM rodedun @twitjournalclub i think physiologically a baby and a 12 year old are too different for it #Twitjc -8:16 PM SuzetteWoodward @twitjournalclub #TwitJC love to know whether a neonatologist would think differently to a paediatrician about the age range -8:16 PM welsh_gas_doc I would say Yes. Big difference in physiology of 60 days to 12 years. Fixed cardiac output, underdeveloped RAS etc. #twitjc -8:16 PM fidouglas @SuzetteWoodward Haven't used Echofon before. Are you on a phone? I use TweetDeck if I'm following on my mobile. Seems to work. #twitjc -8:17 PM silv24 Yes the fluid boluses are tailored to weight but still physiologically there are lots of changes #twitjc -8:17 PM PaedsSHO For me, the inclusion criteria are very wide. Would be interesting to see results split e.g. infants, 1-5, 5-12. #twitjc -8:17 PM Buzzmf87 I was always told to almost think of babies as a whole different species almost as things can be so different. #twitjc -8:17 PM Buzzmf87 Where there any other results that showed outcomes in different age brackets? 60d-1yr, 1yr-3rd and 3 ye above or similar? #twitjc -8:18 PM SuzetteWoodward Exactly RT @Buzzmf87: I was always told to almost think of babies as a whole different species almost as things can be so different. #twitjc -8:18 PM twitjournalclub @Buzzmf87 correct me if I am wrong but that data isn't reported in the paper, would be interesting to see if age did have an effect #twitjc -8:19 PM BenCosway I agree with @PaedsSHO . Given number of participants, would be useful to have stratified ages #twitjc -8:20 PM SuzetteWoodward #TwitJC RT @BenCosway: I agree with @PaedsSHO. Given number of participants, would be useful to have stratified ages. -8:20 PM twitjournalclub Does the wide age inclusion make the study results less valid? #twitjc -8:20 PM fidouglas Is it possible that results were actually opposite for infants vs older children, but the study only considered the average? #twitjc -8:21 PM rodedun @twitjournalclub #Twitjc it just can't be a valid comparison when even simple things like cvs are diff eg resting hr -8:22 PM

silv24 I think ultimately a subgroup analysis by age would be very interesting but possibly too small numbers? #twitjc -8:23 PM SuzetteWoodward Poss makes it hard to convince people to change practice RT Does the wide age inclusion make the study results less valid? #TwitJC -8:24 PM Buzzmf87 @fidouglas I was wondering about this. What if there were more infants and they skewed it, while older kids responded as expected? #twitjc -8:25 PM alasdairforrest @twitjournalclub Difficult to see alternative: CIs would be very wide if subgroups were added, unless study much bigger. #twitjc -8:25 PM silv24 MT @trufflethebendy: presentation of the results that makes them less valid. Results split according to age would have been better #twitjc -8:25 PM fidouglas I wonder if the question that the study asked was too general. Surely best research asks (& hopefully answers) a specific question. #twitjc -8:25 PM SuzetteWoodward Agree MT @HF_IHI_Fellow #twitjc Large RCT tries to answer "a big simple question" -8:26 PM AnnabelleSouth Median age & interquartile range were similar for the 3 groups #twitjc -8:26 PM fidouglas ...and the different responses expected (presumably) of the different age groups in the study made it too general. #twitjc -8:26 PM fidouglas @Buzzmf87 Exactly. I've not had time to look into the results section in enough detail tho. #twitjc -8:27 PM anaestheticdoc sorry for a late arrival! as you were #twitjc -8:27 PM fidouglas @alasdairforrest Although the study had to be terminated - was deemed unethical to continue. #twitjc -8:27 PM twitjournalclub This leads us on to the second discussion point... #twitjc -8:27 PM BenCosway #twitjc there were more than 3000 participants. Still would be pretty large even with sub groups. -8:28 PM twitjournalclub Criticism has been made about the reliance on one non-specific clinical feature for the diagnosis of hypovolaemic shock... #twitjc -8:29 PM twitjournalclub Does this make the study invalid for evaluating fluid boluses in children with hypovolaemic shock? #twitjc -8:29 PM fidouglas @BenCosway Surely that depends a lot on the size of difference you are trying to measure. All to do with power analyses I assume. #twitjc -8:30 PM silv24 The editorial in Archives stated that this study was "not specifically treating shock as currently defined by WHO" #twitjc -8:31 PM welsh_gas_doc Would be dubious about using this paper in pure hypovolaemics; mechanism of shock is somewhat different to that in sepsis. #twitjc -8:31 PM PaedsSHO Hypovolaemic shock defined as "children with clinical signs of severe illness and impaired perfusion plus severe hypotension" #twitjc -8:32 PM AnnabelleSouth FEAST team have done further analysis using ACCM-PALS, Surviving Sepsis Campaign & WHO definitions of shock - same result. #twitjc -8:32 PM silv24 The concern they raised was that these signs have poor specificity for hypovolaemic shock & that it was inappropriately designed #twitjc -8:32 PM

BenCosway #twitjc from what I see, pyrexia, tachycardia, resp distress, cap refill, bp. It is what I would use to diagnose shock... -8:33 PM silv24 Quote "reliance was placed on including children with clinical signs that individually have poor specificity for shock" #twitjc -8:33 PM PaedsSHO Impaired perf.: "1 of: capillary refill >2 seconds; lower limb temperature gradient; weak radial pulse volume; severe tachycardia" #twitjc -8:34 PM SuzetteWoodward the hard part of knowing whether to change practice or not MT @welsh_gas_doc dubious about using this paper in pure hypovolaemics #twitjc -8:35 PM rodedun @PaedsSHO ...Which is a vague def. I did audit on under 5s with suspected gastroenteritis, found dehydration poorly defined #Twitjc -8:35 PM twitjournalclub @rodedun children with gastroenteritis were excluded from this trial, as were severe malnutrition, & non-infective causes shock #twitjc -8:37 PM silv24 Would it have been better if to diagnose hypovolaemic shock they had needed to all three of the criteria? #twitjc -8:37 PM SuzetteWoodward Interesting MT @AnnabelleSouth FEAST analysis c ACCM-PALS, Surviving Sepsis Campaign & WHO definitions of shock, same result. #twitjc -8:37 PM PaedsSHO You wonder as to the pathogenesis of poor perfusion: large proportion of kids likely to be P. falciparum... #twitjc -8:38 PM PaedsSHO Sequestration of infected cells into microcirculation may cause mechanical "poor perfusion" rather than hypovolaemia. #twitjc -8:39 PM silv24 @AnnabelleSouth that is very interesting - have those results been published or are being published #twitjc -8:39 PM welsh_gas_doc It's hard distinguishing septic shock from hypovolaemic shock in ITU with SVO2 and lactate, doing it from end of bed impossible. #twitjc -8:39 PM yazman89 I missed #TwitJC ... again! *SHOCK/HORROR* ... no pun intended -8:39 PM anaestheticdoc does make you wonder whether the large proportion with anaemia secondary to malaria, dilution reduced oxygen carrying capacity #twitjc -8:40 PM silv24 Impaired perfusion wasn't the only inclusion criteria, these were pretty poorly children #twitjc -8:41 PM SuzetteWoodward Not sure this discussed enough RT @silv24: Impaired perfusion wasn't the only inclusion criteria, these were pretty poorly children #twitjc -8:41 PM AnnabelleSouth @silv24 They're currently under review. Biggest increase in mortality was for WHO definition, but few kids in this category. #twitjc -8:42 PM anaestheticdoc was heamatocrit noted. maybe these kids were being haemodiluted down to very low Hbs #twitjc -8:43 PM PaedsSHO @anaestheticdoc Hb was noted. Transfused below 5g/dl #twitjc -8:43 PM silv24 Interesting results for the children with confirmed malaria parasitemia (see table 1 for the details). All but 4 had falciparum #TwitJC -8:44 PM SuzetteWoodward #TwitJC challenging subject tonight! Still good fun. -8:46 PM twitjournalclub Third discussion point - How applicable are these results to the use of fluid boluses in febrile children in the developed world? #twitjc -8:47 PM

welsh_gas_doc Findings probably aren't applicable to 'West'. We (thankfully) get our septic kids into ED a lot earlier in disease than they did. #twitJC -8:49 PM anaestheticdoc Developed world or Caucasian world? #twitjc -8:49 PM PaedsSHO I'm not convinced the results are directly applicable; different pathophysiology, different comorbidities... #twitjc -8:50 PM twitjournalclub @anaestheticdoc what would be your answer to both of those points? #twitjc -8:50 PM anaestheticdoc we know that there is genetic differences for angiotensin receptors #twitjc -8:50 PM PaedsSHO Very interesting question! @anaestheticdoc: Developed world or Caucasian world? #twitjc -8:50 PM JonesTheGas #twitJC Does anyone know the mortality of healthy young kids from malarial sepsis in this country. Is it of the same order as 10%? -8:50 PM welsh_gas_doc So we can get Abx in much earlier, and the merest suggestion of them becoming wet gets them a ride on the blower (ventilator) #TwitJC -8:50 PM tobyhillman @welsh_gas_doc Could still be applicable in certain cases, often v late presentations from marginalised groups #twitjc #twitjc -8:51 PM twitjournalclub @anaestheticdoc so there could be completely different fluid physiology then? #twitjc -8:51 PM silv24 Different causes of a febrile illness and can imagine they presented later & been sicker (having worked in Tanzania for a bit) #twitjc -8:51 PM SuzetteWoodward Not convinced MT @twitjournalclub How applicable are results to the use of fluid boluses in febrile children in the developed world #twitjc -8:51 PM PaedsSHO Plus, likely to transfuse sooner in UK #twitjc -8:52 PM anaestheticdoc @twitjournalclub @anaestheticdoc possibly, maybe a higher incidence of non responders. but also agree it maybe later presentation #twitjc -8:53 PM welsh_gas_doc Was it the education of staff and actual recognition of sepsis that made the difference, rather than altering the fluid regimens? #TwitJC -8:53 PM tobyhillman MT @welsh_gas_doc: Was it education of staff and actual recognition of sepsis that made difference, rather than the fluid regimens? #twitjc -8:54 PM twitjournalclub MT @welsh_gas_doc: Was it education of staff & actual recognition of sepsis that made the difference rather than altering the fluid? #twitjc -8:54 PM twitjournalclub This leads on perfectly to the final discussion point.... #twitjc -8:56 PM twitjournalclub Does there need to be a similar study in developed countries? If so, would such a study ever get ethical approval? #twitjc -8:56 PM welsh_gas_doc We need to always question current practice, but I doubt we would have a suitably powered study if FEAST was attempted in 'West' #twitjc -8:58 PM anaestheticdoc there was the wet v dry study of sorts wasn't there? someone help me out? in meningicoccal sepis? wet did better? #twitjc -8:58 PM silv24 Although differences as we have highlighted think that this study might force us to look at fluid boluses in a wider context #twitjc -8:58 PM

SuzetteWoodward Keep agreeing with MT @welsh_gas_doc We need to always question current practice, but ..... #twitjc -8:59 PM keirshiels @twitjournalclub #TwitJC it would be incredibly difficult to randomise children in resus to one of two treatments ethically or practically -8:59 PM silv24 But I doubt if anyone would dare even suggesting running an RCT such as this & doubt would get ethical approval #twitjc -9:00 PM SuzetteWoodward Agree RT @silv24: But I doubt if anyone would dare even suggesting running an RCT such as this & doubt would get ethical approval #twitjc -9:00 PM silv24 But could it be possible that a study carried out in Africa could end up forcing us to look at current practices? Very interesting #twitjc -9:01 PM PaedsSHO Highly unlikely to be approved I think. #twitjc -9:01 PM fidouglas Double standards for research in 1st vs 3rd world? #twitjc -9:01 PM anaestheticdoc well the question is not should it be done, but IS it ethical to do it. #twitjc -9:02 PM anaestheticdoc NO #twitjc -9:02 PM silv24 Is there enough clinical uncertainty now to allow such a trial to take place and for it to be ethical? #twitjc -9:02 PM twitjournalclub @anaestheticdoc what do you think? #twitjc -9:02 PM maria101 '@anaestheticdoc Forgot the #TwitJC -9:03 PM twitjournalclub Why do you think this would be the case? RT @PaedsSHO: Highly unlikely to be approved I think. #twitjc -9:03 PM SuzetteWoodward That must be something the WHO have written about? RT @fidouglas: Double standards for research in 1st vs 3rd world? #twitjc -9:03 PM mjryandaly @keirshiels @twitjournalclub Ethically and legally we'd probably allow it. There's a few similar studies out there. #twitjc -9:03 PM welsh_gas_doc The aim of FEAST was to rationalise fluids, not to restrict their use. Findings were a surprise to the study designers. #TwitJC -9:03 PM BenCosway If we dont think its ethical to do the trial here are we missing a point...was it ethical do this trial at all? #twitjc -9:03 PM welsh_gas_doc And don't forget, all children had the same volume of fluids, just whether it was BOLUSED was the difference. #TwitJC -9:04 PM twitjournalclub @BenCosway the points made by Prof Maitland were very interesting (can see them on the blog) - they really didn't expect the results #twitjc -9:05 PM SuzetteWoodward Is it the results, rather than the study that questions our ethics? #twitjc -9:06 PM twitjournalclub Prof Maitland 1/2 - "...all surprised by the result. There was no signal from the SAEs and the clinicians involved in the trial" #twitjc -9:07 PM twitjournalclub 2/2 " said they all saw children improve on boluses and believed that boluses were good. This is why trials are important." #twitjc -9:07 PM christiplady #twitjc Chris. Haematologist. Watching discussion wrt anaemia too. Lots of potentially confounding issues I think -9:08 PM

silv24 @SuzetteWoodward they really didn't know and no-one expected these results, there was genuine clinical uncertainty #twitjc -9:08 PM welsh_gas_doc The other wonderful thing about FEAST was that simply being in the trial improved mortality (no matter what group). #twitJC -9:08 PM maria101 RT @SuzetteWoodward: Is it the results, rather than the study that questions our ethics? #twitjc Quite possibly, yes! -9:09 PM fidouglas @welsh_gas_doc Did it improve access to otherwise unavailable treatment? #twitjc -9:09 PM twitjournalclub Seems like everyone thought these children would improve by being given boluses, this result was a complete shock #twitjc -9:09 PM PaedsSHO @fidouglas May have improved access to monitoring etc, ensured hospital admission #twitjc -9:10 PM twitjournalclub Prof Maitland "Overall, mortality was lower than they had previously experienced... probably due to training of all staff involved" #twitjc -9:10 PM AnnabelleSouth Is the evidence that practice in the West is based on strong enough to ignore the results of RCT that suggest it's harmful in Africa?#twitjc -9:11 PM silv24 I have read this study several times for this week and still think it is an amazing study and shows why we need to do trials #twitjc -9:11 PM BenCosway Training + Hawthorne....not that surprising #twitjc -9:11 PM silv24 @trufflethebendy the Hawthorne effect #twitjc -9:12 PM AnnabelleSouth Triage was a new thing for many of the hosptials involved, so that probably helped lower mortality. #twitjc -9:13 PM welsh_gas_doc Hawthorne Effect shows why clinical research is important in improving patient safety. It is under threat from cutbacks #NHSReforms #TwitJC -9:14 PM twitjournalclub @AnnabelleSouth have to say, it is a fascinating trial and I have really enjoyed reading widely about it for this week #twitjc -9:15 PM PaedsSHO @trufflethebendy We'd do it in A+E or on PAU. #twitjc -9:16 PM twitjournalclub Thank you all for joining in this week's discussion of a very interesting paper and thank you to @AnnabelleSouth for her thoughts #twitjc -9:16 PM twitjournalclub As always please feel free to continue the discussion using the hashtag or comment on the blog, summary post will be published ASAP #twitjc -9:17 PM anaestheticdoc very well done again guys #twitjc -9:17 PM AnnabelleSouth @twitjournalclub Thanks for facilitating a fascinating discussion. Some v. good points raised. #twitjc -9:17 PM anaestheticdoc well done again guys #twitjc -9:18 PM PaedsSHO Really found it interesting this week. Thanks everyone. #twitjc -9:18 PM welsh_gas_doc Very good paper, very well moderated and led by @silv24. The #twitJC really is a very, very good hashtag. Nice one everybody. -9:19 PM BenCosway First #twitjc this week. Great discussion and great learning opportunity re shock and fluid balance. -9:21 PM

christiplady #twitjc sorry I was late. Nutritional status, sickle, malaria all very different incidence. Do these confound response to fluid challenges? -9:22 PM Mrskelseysalter Just logged on. Missed #twitjc (again! surely not deliberate?) Looks an interesting discussion. Added a surreal quality to my timeline too! -9:26 PM