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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 http://bit.ly/nG6pLv Hosted by Natalie Silvey

twitjournalclub Good evening and welcome to this week's discussion of FEAST - a summary post can be found at http://bit.ly/pg2Xj0 #twitjc -8:01 PM twitjournalclub A list of the discussion points for tonight can be found at http://bit.ly/pXBHZg #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 TweetChat.com 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