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John Myburgh: Fluid Resuscitation: Which, When and How Much?


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The erudite John Myburgh condenses fluid resuscitation data down to a palatable brew.

The erudite John Myburgh condenses fluid resuscitation data down to a palatable brew.

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  • 1. Resuscitation fluids:which, when, how much?UNSWJohn MyburghMBBCh PhD FCICM FAICDThe George Institute for Global HealthSt George Clinical School, University of New South Wales
  • 2. Leith Infirmary 1831Thomas Aitchinson Lattac1790-1833
  • 3. “The most wonderful andsatisfactory effect is theimmediate consequenceof the injection.”“The quantity necessaryto be injected willprobably be found todepend upon the quantityof serum lost..”Lewins: London Medical Gazette 1832
  • 4. Sydney Ringer1834-1910Alexis Hartmann1898-1964
  • 5. “I don’t care if you use dog’s piss, as long as you useit carefully.”Malcolm Fisher AO
  • 6. Roberts: BMJ 1998RRD 1.68 (1.25 – 2.23)Overall excess mortalityof 6%(95% C.I. 3 - 9%)24/30 studiesn=1104/1419FavoursalbuminFavourscontrolHypovolaemiaHypoalbuminaemiaBurnsTOTAL
  • 7. SAFE Study Investigators: NEJM 2004
  • 8. “Professor Myburgh, I can’t find SAFE fluidin MIMS.Is it a crystalloid or a colloid?”ICU Registrar: St George Hospital 2003
  • 9. SAFE Study Investigators: NEJM 2004
  • 10. Should you change practice?
  • 11. SAFE Study Investigators: NEJM 2007Mortality at 28 days Mortality at 2 years
  • 12. P=0.059(Test for common relative risk)SepsisSAFE Study Investigators: Int Care Med 2011MVLR adjusting for baseline covariates in patients with complete data:919/1218 (75.5%)0.71 (0.52 – 0.97) p=0.03.
  • 13. Maitland: New Eng J Med 2011
  • 14. Mortality at 4 hours Mortality at 4 weeksMaitland: New Eng J Med 2011Multicentred open-label RCTAlbumin vs saline bolus vs no bolus in febrile hypotensivechildrenn=3141/3600Primary outcome: Mortality at 48h2009-2011
  • 15. T H Huxley1825 - 1895m“That the great tragedy ofScience is the slaying of abeautiful hypothesis withan ugly fact”
  • 16. Summary: albuminEquivalence to saline in terms of safety and haemodynamic effectCost effectiveness not establishedIncreased mortality in traumatic brain injuryRelated to the development of intracranial hypertensionPotential hypotonicityPotential beneficial effects for fluid resuscitation in sepsis unproven
  • 17. What about synthetic colloids?
  • 18. Capital cost500mL Cost(AUD)Normal Saline 0.61Hartmann’s Solution 0.61Plasmalyte® 1.54Hypertonic Saline 2.54Gelatins 14.99Dextrans 38.34Hetastarch 53.00Albumin 42.75Albumin (Australia) 0.00*
  • 19. Colloid Trials n RR 95%CIAlbumin 23 7754 1.01 0.92 to 1.10HES 16 637 1.05 0.63 to 1.75Gelatin 11 506 0.91 0.49 to 1.72Dextran 9 834 1.24 0.94 to 1.65Perel: Cochrane Collaboration 2007Colloids vs crystalloids
  • 20. SAFE TRIPS Investigators: Crit Care 2010Fluid volumes delivered
  • 21. Choice of Colloid: Severe sepsis050100150200250300350400450OCEANIA AMERICAS ASIA NORTHERNEUROPESOUTHERNEUROPEWESTERNEUROPEAllmLperpersonAlbumin Starch Gelatin DextranChoice of Colloid: Severe sepsisSAFE TRIPS Investigators: Crit Care 2010
  • 22. Renal replacement therapy: 31.0 v 18.8% p=0.001Brunkhorst: New Engl J Med 2008
  • 23. Outcome Trials n RR 95%CIRenal replacement therapy 34 1236 1.38 0.89 to 2.16RRT : sepsis 3 702 1.59 1.2 to 2.1Author-defined ARF 34 1199 1.50 1.12 to 1.87Author-defined ARF: sepsis 4 832 1.55 1.22 to 1.96Dart: Cochrane Collaboration 2010HES: effects on renal function
  • 24. Perner: New Engl J Med 2012
  • 25. 6S 2012P=0.48 P=0.09SepNet (VISEP) 2008P=0.07
  • 26. ANZICSClinical Trials GroupMyburgh: New Engl J Med 2012
  • 27. Myburgh: New Engl J Med 2012
  • 28. Systematic reviews 2013SystematicreviewHESpreparationComparator PatientpopulationMortalityRR (95% CI)RRTRR (95%CI)Gattas 6% HES(130/0.4-042)Isotonic salineHypertonic salineLactated Ringer’sAcetated Ringer’sAlbumin 4%, 5%,20%Gelatin 4%Polygeline 3.4%Dextran 70HES (200/0.5)HES (670/0.75)Acutely ill patients inintensive care,perioperative andoperative setting1.08 (1.00 to 1.17) 1.25 (1.08-1.44)Haase 6% HES(130/0.4-0.42)Isotonic salineLactated Ringer’sAcetated Ringer’sAlbumin 20%Sepsis/septic shock 1.04 (0.89 to 1.22) 1.36 (1.08 to 1.72)Zarychanski 6-10% HES(130/0.4-0.42)6-10% HES(200/0.43-0.66)Isotonic salineHypertonic salineLactated Ringer’sAcetated Ringer’sAlbumin 4%, 5%,20%Gelatin 3%, 4%PlasmaCritically ill patientsin emergency orintensive care setting1.06 (1.00 to 1.13) 1.32 (1.15 to 1.50)Patel 6% HES(130/0.4-0.42)Isotonic salineAcetated Ringer’sAlbumin 20%Severe sepsis 1.13 (1.02 to 1.25) 1.42 (1.09 to 1.85)Myburgh: Int Care Med (in press)
  • 29. Study fluid volume and doseStudy HES Control PatientpopulationHES DoseMed (IQR)RRTRR (95%CI)MortalityRR (95%CI)VISEP 10% HES(200/0.5)LactatedRinger’sSevere sepsis 70 mL/kg(33 to 144.2)1.62(1.19 to 2.21)1.17(0.94 to 1.47)6S 6% HES(130/0.4-0.42)AcetatedRinger’sSevere sepsis 44 mL/kg(24 to 75)1.35(1.01 to 1.80)1.17(1.01 to 1.36)CHEST 6% HES(130/0.4)0.9%salineAdult ICUpatients5 mL/kg(3 to 9)1.21(1.00 to 1.45)1.06(0.96 to 1.18)
  • 30. Summary: hydroxyethyl starchMost commonly prescribed colloid globally.Cost effectiveness not establishedEvidence for dose-dependent nephrotoxcity with all HES preparationsEvidence for adverse effects related to accumulation in RESNo demonstrable clinical benefit and increased risk of harm overcrystalloids
  • 31. Bayer: Critical Care Medicine 2011
  • 32. Colloids vs crystalloidsPere: Cochrane Library; Yesterday
  • 33. What about crystalloids?“Abnormal” saline vs “Balanced” salt solutions
  • 34. Hartog Jacob Hamburger1859-1924Determination of osmotic pressurevery small amounts of liquid in avolumetric way, using blood cells.0.9% concentration of salt in humanblood = “Normal“ salineCrystalloids: normal saline
  • 35. Crystalloids: normal salineThe most commonly used resuscitation fluid globally.Normal saline is the most extensively studied crystalloid in high-quality randomised-controlled trials.Established, although unproven, role in trauma resuscitation,particularly traumatic brain injuryThere is increasing evidence of potential iatrogenic harm:Hyperchloraemic acidosisOedemaMicrocirculatory effects
  • 36. Yunos: JAMA 2012Grade 2 or Grade 3 AKI Use of RRT in ICULog rank p=0.001Log rank p=0.004
  • 37. Crystalloids: balanced salt solutionsPhysicochemical properties of balanced salt solutions render none as“ideal”Ringer’s lactate: hypotonicityRingers acetate: cardiotoxicityPlasmalyte 148: alternative non-physiological anionsNew, non-propietary solutions not establishedNo major emerging trials at present
  • 38. Emerging issues in fluid resuscitationUbiquitous intervention in acute medicineSelection and use is entirely dependent on geographyAdministered by relatively junior medical staff in random fashionInconsistent haemodynamic and physiological endpointsConsistent data on haemodynamic equivalence between colloids andcrystalloidsNet association of fluid retention with consequent adverse clinical effectsThe place and rationale for “maintenance” fluids is questionable
  • 39. Emerging issues in fluid resuscitationOverall, there is little evidence to support the use of in acutely illpatients.In particular, semi-synthetic colloids are essentially non-biologicaland non-physiological solutionsRestricted volumes of balanced salt solutions appear to be logical,albeit unproven fluids of choice in the majority of patients
  • 40. Emerging issues in fluid resuscitationParadigm shift to regard fluid resuscitation as same as a drug:The type of fluid will affect patient outcomeSpecific contraindicationsThe volume (dose) will affect patient outcomeToxicity presents in the post resuscitation period.
  • 41. “The dose makes the poison”Paracelus1495