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Understanding fluid administration approaches in children with co-morbidities and septic shock Kissoon, Niranjan Aug 2, 2017

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EDITORIAL Open AccessUnderstanding fluid administrationapproaches in children withco-morbidities and septic shockNiranjan Kissoon1,2,3See related research by Obonyo et al., https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1679-0.Keywords: Severe malnutrition, Children, Hypovolemic shock, Septic shock, Mortality, Myocardial function,Echocardiography, Fluid resuscitation, Low and middle income countriesFluid infusions are given to children to treat cardiovas-cular compromise from shock in locations across theglobe, where resources vary widely. The most commoncause of cardiovascular compromise is septic shock. Inlow and middle income countries severe malnutritioncomplicates sepsis largely from malaria, pneumonia, anddiarrheal diseases, leading to interesting treatmentconundrums. The high mortality rate of about 40% inchildren with severe malnutrition and shock fromdiarrheal diseases results from the confluence of clinicalfactors, inequity, socio-economic and cultural contextresulting in late presentation, increased vulnerability,and sub-optimal care [1]. Fluid resuscitation in thiscontext is risky with little margin for error, where smalldeficits or excesses can lead to cardiovascular collapse orrespiratory failure. Thus, the WHO recommends acautious approach with frequent clinical monitoring.This recommendation is supported by weak evidenceand accompanied by a suggestion that research isneeded to determine optimal fluid management inchildren with severe malnutrition and shock [2].In response to these uncertainties, Obonyo andcolleagues investigated the cardiovascular response totwo fluid infusion regimes (bolus and continuous infu-sion over 5 h) in severely malnourished children withhypovolemic shock due to diarrheal diseases with dehy-dration [3]. The authors concluded that the concern ofcompromised cardiac function and vulnerability to fluidoverload in children with severe malnutrition anddiarrheal diseases with dehydration is not supported bytheir findings. However, there was a high mortality rateat 48 h (36–44%) and 28 days (56–82%) [3]. The ration-ale for this study is partly based on the FEAST trial inwhich bolus fluid in febrile children in Africa resulted inworse outcomes [4]. However, the FEAST trial excludedchildren with dehydration from diarrheal diseases, fewenrolled had septic shock, and almost 60% of thechildren suffered from malaria. The findings of theFEAST trial signals a cautious approach to fluid bolusesin low resource settings, but the final chapter on fluidapproaches in children with septic shock in any settingis not yet written.Septic shock is a complex pathophysiological derange-ment; its expression depends on microbial agent virulence,systemic inflammation, endothelial and microcirculationdisruption, primary and secondary immune derangements,and coagulation and parenchymal tissue insults [5, 6].Endothelial barrier dysfunction occurs early in septic shockand whether it is amplified in SM is unclear [7]. Mortalityin children with diarrheal disease and septic shock is higher(67%) than in controls with dehydration (14%). Those withseptic shock are also more likely to receive a bloodtransfusion and mechanical ventilation, therapieswhich may not be available in low and middle incomecountries [8]. Thus, the distinction between hypovol-emic and septic shock has tremendous implicationsregarding treatment and outcomes because those inseptic shock are more likely to need mechanical ven-tilation which may not be available [9].Correspondence: nkissoon@cw.bc.ca1Department of Pediatrics, BC Children’s Hospital, University of BritishColumbia, B245, 4480 Oak Street, Vancouver, BC V6H 3V4, Canada2Child & Family Research Institute (CFRI), Vancouver, British Columbia, CanadaFull list of author information is available at the end of the article© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Kissoon Critical Care  (2017) 21:204 DOI 10.1186/s13054-017-1741-yPoor outcomes in children with septic shock inresource-poor settings are likely due to multi-organ dys-function of late sepsis and insults to the myocardiumwhere intensive care support is limited. Robust cardiaccontractility relies on the myocardial milieu where sub-strates such as magnesium, calcium, acid base balance,hemoglobin, temperature, and energy stores are normal.Levels of these substrates are commonly abnormal incritically ill children. Thus, the inability to monitor ortreat electrolyte disturbances and acid base may resultin higher mortality rates due to cardiovascular collapse[3, 10]. Where intensive care support is available,mortality has decreased such that experts have pro-posed a composite outcome measure which includesboth mortality and long-term morbidity.The optimal approach to fluid administration in bothhigh and low income countries is not yet settled, withno rigorous study conducted in high income countries.The FEAST trial, the largest and most rigorous attemptto address approaches to fluid administration was donein low and middle income settings in Africa. Validatedapproaches to administration of fluid in septic shock aresorely needed in view of the myriad etiologies andpathophysiologic perturbations and the recent body ofevidence pointing to positive fluid balance as a predictorof poor outcomes in critically ill children even whenintensive care is available.Fluid resuscitation in sepsis has endured a long historyof success, starting with initial experiences with cholera.What is still unclear is how much fluid should beinfused and how fast to replenish intravascular volumedeficits in children with shock and complex co-morbidities. We need to challenge our present dogmaregarding approaches to fluid resuscitation. For instance,we need to further explore the role of increased lactatein septic shock because direct tissue oximetry has failedto show hypoxia and tissue partial pressure of oxygenmay be elevated [11]. Oliguria, which is widely used as aguide to fluid resuscitation on the presumption of renalhypoperfusion, has been challenged [12]. Understandingthe potency of fluids to increase vascular volume andremain in the vascular compartment [13] may possiblylead to revision of the Starling equation. Whether moremodest fluid volumes and earlier introduction ofinotropes will decrease overload and improve outcomesare also being explored [14].While impractical in most low and middle income set-tings, an in-depth understanding of the pathophysiologyand response to fluid in shock will be best obtainedusing multimodal monitoring including clinical examin-ation and invasive central venous pressure and echocar-diographic monitoring [15]. Ideally, organ function andmicrovascular tissue perfusion and oxygenation shouldalso be monitored to understand the evolution of multi-organ dysfunction, such as in malaria where both micro-and macrovascular dysfunction may be contributoryfactors.Scientific evidence thrives by unearthing facts andburying opinions. Thus, we need randomized clinicaltrials if we are to further our understanding of fluidtherapies. Each child with sepsis is unique and factorssuch as their genetic predisposition, the social economiccontext, the inciting agent, and the trajectory of theseptic episode must be considered in enrolment tounderstand and transition from generic to personalizedand ultimately precision therapies. Challenging thestatus quo is never easy, but it may be time to rewritehistory.AbbreviationsFEAST Trial: Fluid Expansion As Supportive Therapy Trial; WHO: World HealthOrganisationAcknowledgementsNone.FundingNone.Availability of data and materialsNot applicable.Competing interestsThe author declares that he has no competing interests.Consent for publicationNot applicable.Ethics approval and consent to participateNot applicable.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.Author details1Department of Pediatrics, BC Children’s Hospital, University of BritishColumbia, B245, 4480 Oak Street, Vancouver, BC V6H 3V4, Canada. 2Child &Family Research Institute (CFRI), Vancouver, British Columbia, Canada.3Division of Critical Care, BC Children’s Hospital, University of BritishColumbia, Vancouver, British Columbia, Canada.References1. Akombi BJ, Agho KE, Hall J, et al. Stunting and severe stunting amongchildren under-5 years in Nigeria: a multilevel analysis. BMC Pediatr.2017;17(1):15.2. WHO. WHO updated guideline: pediatric emergency triage, assessment andtreatment: care of critically ill children. 2016. http://apps.who.int/iris/bitstream/10665/204463/1/9789241510219_eng.pdf.3. Obonyo N, Brent B, Oluput-Oluput P, et al. Myocardialand haemodynamicresponses to two fluid regimens in African children with severe malnutritionand hypovolaemic shock. Crit Care. 2017;21:103.4. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in Africanchildren with severe infection. N Engl J Med. 2011;364(26):2483–95.5. Deutschman CS, Tracey KJ. Sepsis: current dogma and new perspectives.Immunity. 2014;40(4):463–75.6. Levi M, Schultz M, van der Poll T. Sepsis and thrombosis. Semin ThrombHemost. 2013;39(5):559–66.Kissoon Critical Care  (2017) 21:204 Page 2 of 37. White LE, Hassoun HT, Bihorac A, et al. Acute kidney injury is surprisinglycommon and a powerful predictor of mortality in surgical sepsis. J TraumaAcute Care Surg. 2013;75(3):432–8.8. Sarmin M, Ahmed T, Bardhan PK, Chisti MJ. Specialist hospital study showsthat septic shock and drowsiness predict mortality in children under fivewith diarrhoea. Acta Paediatr. 2014;103(7):e306–11.9. Chisti MJ, Shahunja KM, Afroze F, et al. Hypoxaemia and septic shock wereindependent risk factors for mechanical ventilation in Bangladeshi childrenhospitalised for diarrhoea. Acta Paediatr. 2017. doi:10.1111/apa.13836[Epub ahead of print].10. Shahrin L, Chisti MJ, Huq S, et al. Clinical manifestations of hyponatremiaand hypernatremia in under-five diarrheal children in a diarrhea hospital.J Trop Pediatr. 2016;62(3):206–12.11. Boekstegers P, Weidenhöfer S, Kapsner T, Werdan K. Skeletal muscle partialpressure of oxygen in patients with sepsis. Crit Care Med. 1994;22(4):640–50.12. Langenberg C, Wan L, Egi M, May CN, et al. Renal blood flow inexperimental septic acute renal failure. Kidney Int. 2006;69(11):1996–2002.13. Nunes TS, Ladeira RT, Bafi AT, et al. Duration of hemodynamic effects ofcrystalloids in patients with circulatory shock after initial resuscitation. AnnIntensive Care. 2014;4:25.14. Parker MJ, Thabane L, Fox-Robichaud A, et al. A trial to determine whetherseptic shock-reversal is quicker in pediatric patients randomized to an earlygoal-directed fluid-sparing strategy versus usual care (SQUEEZE): studyprotocol for a pilot randomized controlled trial. Trials. 2016;17(1):556.15. Ranjit S, Aram G, Kissoon N, et al. Multimodal monitoring for hemodynamiccategorization and management of pediatric septic shock: a pilotobservational study. Pediatr Crit Care Med. 2014;15(1):e17–26.Kissoon Critical Care  (2017) 21:204 Page 3 of 3

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