Which fluid and when aagbi wsm

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Powerpoint slides for Association of Anaesthetists Winter Scientific Meeting, London, Jan 2011.
"Which fluids and when?"
Speaker Dr Craig Morris, Derby, UK

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Which fluid and when aagbi wsm

  1. 1. Which fluid and when?<br />Craig Morris<br />Derby<br />Consultant Intensivist and Anaesthetist<br />Honorary Lecturer Universities Derby and Teesside<br />
  2. 2. Housekeeping<br />Non-promotional<br />Corporate educational material<br />No conflicts<br />Retraction Boldt<br /> A&A 2009;109:1752-62<br /> >200 publications… <br />http://www.bmj.com/content/341/bmj.c7026.full<br />
  3. 3. www.derbyintensivecareecho.co.uk<br />(DICE)<br />
  4. 4.
  5. 5. Content: which fluid and when?<br />Resuscitation not maintenance<br />Colloid<br /> Starch<br />Crystalloid<br /> “Balanced” solutions<br />Recommendations?<br />
  6. 6. To debate hot issues in fluid management, including<br /><ul><li>Does the third space exist?
  7. 7. Blood transfusion triggers?
  8. 8. Are old RBCs ok?
  9. 9. Do colloids cause renal failure?
  10. 10. Acidosis – good or bad?
  11. 11. Do I have to use 1:1 FFP:RBCs in massive haemorrhage?
  12. 12. What is the haemodynamic monitor of choice?
  13. 13. Does saline really harm patients?</li></ul>http://www.ebpom.org/<br />
  14. 14. Sizes<br />RBC<br />7 μ<br />Capillary width 5 μ<br />Endothelial cell thickness<br />0.2 μ<br />Large pore 40 nm<br />Small pore 5 nm<br />The “size” of colloid is not what keeps it put!!! <br />K+ 0.15nm<br />Na+ 0.10 nm<br />Starch fragments 4.5nm<br />Albumin 3.5nm<br />
  15. 15. Relative sizes…<br />RBC 7μ<br />Large pore 40nm<br />Small pore 5nm<br />Colloid 5nm (1/10 pore) <br />1mm muscle<br />32 endothelial cells<br />10 000 small pores<br />2 large pores<br />Pore area <0.05% surface area<br />
  16. 16. Molecular weights<br />Older HES >500 kDa<br />Modern <br />HES 140 kDa<br />Biological HES<br />70kDa<br />HES amylase fragments<br />50 kDa<br />Albumin 70 kDa<br />Renal threshold<br />Gelatines<br />MW 30kDa<br />Crystalloid<br />< 1 kDa<br />Dextran<br />40 (10%)- <br />70 (6%) kDa<br />
  17. 17. Colloid kinetics<br />Pores 5- 40 nm<br />Albumin < 5 nm<br />Basement membrane negative charge stops leak NOT size<br />Albumin net negative charge -15<br />
  18. 18. Brief colloid/ HES<br /><ul><li>Big and not leaky
  19. 19. Inert (glycogen)
  20. 20. Osmolality 6%
  21. 21. Renal clearance
  22. 22. No “surprises” eg coagulation</li></li></ul><li>Wax Corn Starch amylopectin<br />Extraction and Hydrolysis of desired MW<br />Hydroxy<br />ethylation<br />Amylopectin<br />Hydroxyethyl Starch (HES)<br />Analogue molecule to the human glycogen<br />
  23. 23. Molecular weight<br />MW (weight average MW)= viscosity<br />MN (number average MW or median)= oncotic effect<br />Monodisperse (eg albumin)<br />Polydisperse (MW/MN= index)<br />Voluven 130 +- 20kDa in vitro <br />
  24. 24. HES substitution<br />Water bindingcapacity20 ml g-1HES<br />Increases water binding<br />Resists amylase<br />“Chose”<br /><ul><li> MW
  25. 25. Proportion glucose HE
  26. 26. Position</li></li></ul><li>OHCH2<br />CH2OH<br />CH2OH<br />CH2OH<br />6<br />O<br />O<br />O<br />O<br />O<br />OH<br />OH<br />OH<br />OH<br />OH<br />O<br />2<br />O<br />O<br />O<br />O<br />O<br />HO<br />HO<br />OH<br />HO<br />CH2OH<br />6<br />O<br />OHCH2<br />CH2OH<br />OHCH2<br />CH2OH<br />CH2OH<br />CH2OH<br />OH<br />O<br />6<br />O<br />CH2--O-CH2-CH2-OH<br />OHCH2<br />OHCH2<br />OHCH2<br />CH2--O-CH2-CH2-OH<br />OHCH2<br />OHCH2<br />6<br />O<br />O<br />O<br />O<br />O<br />O<br />OH<br />OH<br />OH<br />OH<br />OH<br />OH<br />6<br />6<br />2<br />OH<br />O<br />2<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />HO<br />O<br />O<br />O<br />OH<br />OH<br />OH<br />OH<br />OH<br />OH<br />OH<br />HO<br />HO<br />HO<br />HO<br />OH<br />2<br />OH<br />2<br />2<br />2<br />2<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />HO<br />HO<br />-O-CH2-CH2-OH<br />-O-CH2-CH2-OH<br />-O-CH2-CH2-OH<br />-O-CH2-CH2-OH<br />-O-CH2-CH2-OH<br />The higher the degree of substitution <br />the longer duration in blood<br />Degree of substitution of 0.5=5 of 10 HE groups<br />0.4=4 of 10 HE groups<br />
  27. 27. Position HES groups<br /><ul><li>Hydroxyethylgroups C2 and C6
  28. 28. C2 resistant amylase
  29. 29. ↑ C2/C6 ratio ↑intravascular space</li></li></ul><li>OHCH2<br />CH2OH<br />OHCH2<br />OHCH2<br />CH2OH<br />CH2OH<br />CH2OH<br />OHCH2<br />CH2OH<br />6<br />6<br />O<br />6<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />OH<br />OH<br />OH<br />2<br />OH<br />OH<br />OH<br />OH<br />OH<br />OH<br />2<br />OH<br />2<br />O<br />2<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />OH<br />OHCH2<br />CH2OH<br />OHCH2<br />OHCH2<br />CH2OH<br />CH2OH<br />CH2OH<br />OHCH2<br />CH2OH<br />6<br />6<br />O<br />6<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />OH<br />OH<br />OH<br />2<br />OH<br />OH<br />OH<br />OH<br />OH<br />OH<br />2<br />OH<br />2<br />O<br />2<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />O<br />OH<br />OH<br />OH<br />OH<br />Substitution Pattern 9:1=9 hydroxyethylC2 and 1 C6<br />Substitution Pattern 5:1= 5 hydroxyethylC2 and 1 C6<br />OH<br />
  30. 30. The life of HES<br />Starting macromolecule<br />In vitro MW <br />EgHemohes200 kDa<br />Voluven 130 kDa<br />In vivo MW <br />EgElohes 145 kDa<br />Voluven 65 kDa<br />Amylase smaller <br />molecules <br />Aim to have in vivo<br />MW above renal threshold<br />Lysis increases osmotic effect!!!<br />50kDa renal threshold<br />Renally eliminated<br />
  31. 31. In vivo lysis<br />HES 6%, 450/0.65 <br />3:1<br />Br J ClinPharm `1979;7:505- 9<br />
  32. 32.
  33. 33. HES: a few numbers<br /><ul><li>Concentration (%)
  34. 34. MW (kDa)
  35. 35. Substitution (coagulation)
  36. 36. C2/C6 (coagulation)
  37. 37. Suspending solution</li></li></ul><li>*in vitro, kDa<br />+ 2464 mOsmolkg-1<br />
  38. 38. Potato vs maize?<br />Potato ↑amylose, esters, P and 20% amylase<br />“= pentastarch + HES 130/0.4/9 : 1 colloid osmotic.. + haemodilution”<br />HES 130/0.42/6 : 1 fastest clearance<br />↑ Viscosity<br />No head to head<br />Tetraspanvs albumin CRF<br />http://clinicaltrials.gov/ct2/show/NCT00936247<br />http://www.bbraun.com/cps/rde/xchg/bbraun-com/hs.xsl/plasma-volume-replacement.html<br />http://adisonline.com/drugsrd/Abstract/2007/08040/Bioequivalence_<br />Comparison_between_Hydroxyethyl.3.aspx <br />
  39. 39. Contained 2 studies<br />10% Pentastarch 200/ 0.5 in 0.9% saline (Hemohes) vs lactated Ringer’s <br />Stopped early<br />Ringer’s Lactate (Sterofundin, B. Braun). 1000 ml Na+<br />140, K+ 4.0, Ca++ 2.5 Mg++ 1.0, Cl- 106 lactate- 45.0<br />(mmol)<br />VISEP group NEJM 2008;358:125- 39 <br />
  40. 40. VISEP- a problem?<br />
  41. 41. Whatever HES 200/0.5 does,<br /> it is not improved haemodynamics!<br />
  42. 42. Dose dependent<br />250mlkg-1<br />18litres<br />The whole point is<br />You are meant to give<br /> less!!<br />
  43. 43. Hyperoncotic colloids<br />AKI assoc hyperoncotic starch, <br />albumin,dextran… mannitol<br />But not saline!<br />Shortgen. Intensive Care Med 2008;34:2157- 68<br />Ragaller et al, J.Am.Soc.Nephrol. 2001<br />
  44. 44. VISEP- should I worry?<br />YES!<br />X2 rates CRRT<br />No benefit<br />Alternatives exist<br />Consistent previous work<br />Would you use it as a “drug”?<br />NO!<br />Complex design<br />Lactated solution vs chloride<br />Hyperoncotic colloid<br />Not representative “current” HES<br />Perhaps AKI is only with higher doses 10% 200/0.5...<br />It doesn’t improve heamodynamics, costs more and assoc death<br />
  45. 45. I don’t do ICU...<br />Sick laparotomy<br />Pressors<br />AKI<br />Elderly, gent, CT...<br />Avoid 10% 200/ 0.5<br />Await further studies?...<br />
  46. 46. HES 130/ 0.4<br />N= 363<br />Retrospective<br />2 organ failures<br />HES 130/ 0.4<br />France, non-protocolised<br />763 ml HES 48 hrs, 1.4l 21 days<br />Both identical >6l crystalloid<br />PRC 2.8 vs 3.9<br />Boussekey et al., Critical Care, 2010<br />
  47. 47. Starches: max “dose”<br />Even with modern LMW tetrastarches 50 mlkg-1<br />
  48. 48. Albumin<br />SAFE overall =<br />Cochrane= SAFE<br />Crystalloid 1.4:1 colloid not 3:1<br />Possible benefit sepsis?<br /> RR 0.77 controlled<br />Possible harm trauma?<br />Finfer S. NEJM 2004;350:2247- 56<br />Vincent JL. CCM 2004;32:2029- 38 <br />
  49. 49. HyperCl-<br />Associatedn+v<br />Cells sepsis<br />Splanchnic perfusion<br />Pyloric dysfunction<br />Renal effects<br />Coagulation<br />Handy JM. BJA 2008;101:141- 50<br />
  50. 50. Keyser Soze<br />I don’t believe in the devil, <br />but that doesn’t mean I’m not scared of him…<br />
  51. 51. Alternatives<br />Morris CG et al. Anaesthesia 2009;64:703- 5 <br />
  52. 52. The irony!<br />Gelofusine® is a 4% solution of modified fluid gelatine. It contains 154 mmol/l sodium but only 120 mmol/l chloride because of the substantial negative charge of the gelatine molecules… <br />http://www.iv-partner.com/index.cfm?2A450D1AB7B24C098978DB9F6D6602DB<br />
  53. 53. Safer than Cl- ?<br />Acetate-> hypotension<br />Lactate assoc hypotension<br />Osmotic effects<br />Direct toxicity<br />Glucose and protein metabolism<br />Chloride effects?<br />Morris CG et al. Anaesthesia 2009;64:703- 5<br />Handy JM. BJA 2008;101:141- 50<br />
  54. 54. Demand more!<br />“Ringer’s” few flavours!<br />Manufacturer: cheap + stable in solution…<br /> (Acetate, malate, gluconate, lactate)<br />Clinician: try again…<br />http://www.ncbi.nlm.nih.gov/pubmed/16163918?dopt=Abstract&holding=f1000,f1000m,isrctn<br />http://www.ajinomoto.com/about/rd/pharmaceutical.html<br />
  55. 55. CRRT solution<br />HCO3- separate pouch<br />Mix administration<br />
  56. 56. Bicarbonated Ringer’s<br /> HCO3- rapid-> CO2 + CaCO3ppt<br />Add citrate 5mEql chelate Ca<br />1 mEql Mg<br />Add CO2pH 7.0<br />
  57. 57. What fluids and when?<br />I (and no one else) can make a<br /> level 1 recommendation for practice…<br />
  58. 58. GIFTASUP: periop<br />http://journal.ics.ac.uk/pdf/1001013.pdf <br />
  59. 59.
  60. 60. What about Shortgen, VISEP, Cochrane, <br />sepsis, renal impairment, <br />and lack of improved outcomes?...<br />
  61. 61. Compared with Gelofusine, the perioperative pulmonary function<br /> of patients treated with HES (Elohaes) after AAA was better.<br />Ortho HES 200 0.5 vs 3% gelatine<br />Comparable COP, clinical expansion<br />the haemodynamics in the two colloid groups appeared to be similar, <br />but superior to the Ringer’s acetate group (alb 4% vs 6% 130/0.4) <br />3.5% urea-linked gelatin is as effective as 6% HES 200/0.5 <br />for volume management in cardiac surgery patients…<br />HES could result in a higher need for allogeneic blood transfusion. <br />Rittoo. BJA 2004<br />Beyer BJA 1997<br />Shramko. Perfusion 2010<br />Linden CJA 2004 <br />
  62. 62. Periop confused?... You will be!<br /><ul><li>N= small, equivocal or contradictory
  63. 63. Surrogates or basic science
  64. 64. Non-inferiority healthy volunteers
  65. 65. Gelatine vs HES very close
  66. 66. Lap chole 1l Gelo vs Voluven (4 hrs!)</li></ul>http://clinicaltrials.gov/ct2/show/NCT00868062?term=gelatin+and+hydroxyethyl+starch&rank=1<br />
  67. 67.
  68. 68. Mortality end point?<br />Major non-cardiac (n= 90)<br />LR vs 6% HES vs 6% balanced<br />Thio + sux<br />OR 7mlkg-1 loading and<br /> 5mlkg-1 hr-1 RL intraop<br />Morretti. A+A 2003;96:611- 7<br />
  69. 69. Outcomes<br />CRF exclusion!<br />6% Hetastarch: Hextend 650/0.7/4:1<br />10% difference mortality n= 5 700 <br />
  70. 70. Costs<br />>£200 000 annually!!!<br />
  71. 71. 4Sinclair S. BMJ 1997<br />5McKendry M. BMJ 2004 <br />1Venn R et al. BJA 2002<br />2Wakeling HG et al. BJA 2005<br />3Noblett SE. BJS 2006<br />
  72. 72. Gelatine<br />Noblett BJS 2006<br />Succinylated 4% gelatine (Volplex)<br />Wakeling HG. BJA 2005 <br />
  73. 73. HES<br />Sinclair S. BMJ 1997<br /># NOF<br />HES 3mlkg-1<br />McKendry M. BMJ 2004<br />Mixture colloids: Hespan 450/0.7<br />
  74. 74. FRACTALE<br />#NOF<br />ODM guided<br />30% ↓ death + complications<br />N= 800, >70<br />HES 130/0.4<br />Cholley B et al http://www.clinicaltrials.gov/ct2/show/NCT00444262?term<br />=trauma+and+hydroxyethyl+starch&rank=11<br />
  75. 75. Critical Care<br />*CIST http://www.clinicaltrials.gov/ct2/show/NCT00890383?term=trauma+and+hydroxyethyl+starch&rank=3<br />
  76. 76. Surviving Sepsis Campaign<br />CCM 2008, SAFE 2004<br />http://www.survivingsepsis.org/About_the_Campaign/Documents/Final%2008%20SSC%20Guidelines.pdf<br />
  77. 77. Gelatine vs HES sepsis (2001)<br />HES 200/ 0.6 (Elohes) vs 3% gelatin (Plasmagel)<br />ARF, creatinine and oliguria all higher HES <br />HES independent risk factor ARF X 2.57<br />http://wwdaa.com/adqi/web_users/akin4/references%20AKIN%20wg%204/<br />Shortgen. Lancet 2001<br />
  78. 78. ARDS: Replacement albumin with HES<br />Red= RR ARF/ ARDS <br />Black albumin<br />Green HES (200 to 2002<br />-> 130<br />N= 44 <br />http://www.springerlink.com/content/h765t1llj424518m/<br />http://www.pptaglobal.org/<br />
  79. 79. Burns<br />Crystalloid<br />Vs colloid<br />Which type colloid<br />Unresolved…<br />N= 30<br />HemoHaes 10% 200/0/5 <br />vscrystallloid (LR)<br />11.2 vs 7.1 (1.6:1)<br />RR death 7.12 <br />CRRT 25% vs 7% <br />ARDS identical<br />Ventilators 7 vs 12 (HES)<br />Bechir M. Crit Care 2010;14:R123<br />
  80. 80. Management of Major Trauma<br />Crystalloids initially (1B)<br />Consider hypertonic solutions (2B)<br />Suggest addition of colloids in unstable (2C)<br /> “modern HES or gelatin”<br /> Avoid dextran or albumin <br />Retrospective aggressive resuscitation-> compartment syd<br />Pre-hospital assoc coagulopathy (>40% 2l, >70% 4l)<br />Rossaint et al: Trauma and bleeding a European Guideline. Crit Care 2010;14:R52<br />Maegele et al. Injury 2007;38:298- 304 <br />
  81. 81. EAST: Pre-hospital<br />Level 2<br />...vascular access at the scene of injury...delays<br />patient transport to definitive care and... benefit is lacking <br />Iv fluids... Withheld... pre-hospital... patients with penetrating torso injuries<br />Level 3:<br /> (a) Iv fluid resuscitation... withheld until active bleeding/hemorrhage addressed<br /> (b) Iv fluid... titrated for palpable radial pulse using (250ml) boluses of fluid rather than fixed volumes or continuous administration<br />http://www.east.org/tpg/FluidResus.pdf<br />
  82. 82. NICE 2004: Hypovolaemic shock<br />Ie absent radial or central pulse<br />Boluses crystalloid to return pulse<br />Shouldn’t delay transport (ieen route)<br />“...only healthcare professionals who have been appropriately trained in advanced life-support techniques and pre-hospital care should administer intravenous fluid therapy in the pre-hospital setting” <br />https://www.nice.org.uk/niceMedia/pdf/2004_006_prehospfluidtherapy.pdf<br />
  83. 83. If fluid is given which type?<br />Level 1:<br /> (a) There is insufficient data to recommend one solution or type of fluid...<br /> (b) Boluses (250 mL) of 3% and 7.5% hypertonic saline (HTS) are<br /> equivalent (...vascular expansion and hemodynamic changes) to large<br /> volume boluses (one liter) of standard solutions such as lactated Ringer’s (LR) or 0.9% normal saline (NS)<br />
  84. 84. EAST resuscitation trauma<br />Level 1<br />There is insufficient data to formulate a level 1 recommendation.<br />Level 2<br />1. During resuscitation, attempts should be made to increase O2 delivery to normalize base deficit, lactate, or pHi during the first 24 hours. The optimal algorithms for fluid<br /> resuscitation, blood product replacement, and the use of inotropes and/or vasopressors<br /> have not been determined.<br />http://www.east.org/tpg/endpoints.pdf<br />
  85. 85. Ongoing studies<br />58 studies HES<br />CEASE: 6% Hetastarchvs 5% albumin ARDS<br />6S Tetraspan HES vsRingerfundin acetate septic shock <br />http://clinicaltrials.gov/ct2/results?term=hydroxyethyl+starch<br />http://clinicaltrials.gov/ct2/show/NCT00796419?term=hydroxyethyl+starch&rank=14<br />http://clinicaltrials.gov/ct2/show/NCT00962156?term=hydroxyethyl+starch&rank=13<br />
  86. 86. CHEST<br /><ul><li>Saline vs 130/0.4 HES
  87. 87. All comers
  88. 88. N= 7000
  89. 89. Mortality, AKI and organ failures
  90. 90. SAFE with starch!</li></ul>http://clinicaltrials.gov/ct2/show/NCT00935168?term=hydroxyethyl+starch+CHEST&rank=1<br />
  91. 91. <ul><li>Potential for increased risk of AKI should be considered when weighing the risks and benefits of HES for volume resuscitation, particularly in septic patients. Large studies with adequate follow-up are required to evaluate the renal safety of HES products in non-septic patient populations. RIFLE criteria should be applied to evaluate kidney function in future studies of HES and, where data is available, to re-analyse those studies already published. There is inadequate clinical data to address the claim that safety differences exist between different HES products
  92. 92. ...34 studies (2607 patients)... RR of kidney failure 1.50 (95% CI 1.20 to 1.87; n = 1199) and 1.38 for requiring RRT (95% CI 0.89 to 2.16; n = 1236) in HES treated individuals compared with other fluid therapies. Subgroup analyses suggested increased risk in septic patients compared to non-septic (surgical/trauma) patients</li></ul>http://www.ncbi.nlm.nih.gov/pubmed/20091640?ordinalpos=1&itool=<br />PPMCLayout.PPMCAppController.PPMCArticlePage.PPMCPubmedRA&linkpos=3<br />http://www2.cochrane.org/reviews/en/ab007594.html<br />
  93. 93. Recommendations for practice…<br />No level 1<br />Fit volunteers tolerate anything<br />All fluids leak and come with baggage<br />Colloids expensive<br />SAFE colloid (4% albumin) vs crystalloid (0.9% saline)=<br /> Ratio 1: 1.4<br /> No evidence superiority colloid<br />Albumin ↓morbidity and mortality sepsis<br />Albumin ↑mortality trauma/ TBI<br />
  94. 94. Recommendations for practice<br />“Routine” perioperativefluid-> Hartmann’s<br />Gelatine vs HES... Still going!<br />SV/ optimisation both-> gelatine cheaper, no AKI<br />AKI HES MW, substitution, osmolality/ lack crystalloid<br /> (+ Sepsis, renal impairment)<br />VISEP 50% ↑CRRT, ↑mortality<br />CHEST ongoing (HES 130/0.4 vs saline)<br />Sepsis or kidney impairment avoid HES<br />
  95. 95. Recommendations for practice<br />ARDS pathogenesis + fluid-> controversial<br />ARDS established-> -ve balance<br />Little evidence colloid preventing ARDS<br />Impact hyperCl- unclear<br />Benefit “balanced” alternatives unclear<br />Demand better “balanced”<br />
  96. 96. Summary<br />HES fascinating-> evolving drugs<br />Lots volunteer, non-inferiority studies!<br />HES: origin, MW, substitution, C2:C6<br />Few level 1 recommendations <br />SAFE only robust crystalloid vs colloid (saline/alb)<br />CHEST recruiting (HES/ saline)<br />
  97. 97. Thank you<br />So, where does this leave us in the big fluid debate?<br />The present results are interesting and add another little piece to the big puzzle, but much more work is needed before we will be able to see the full picture and to better determine where each fluid fits. Although<br />we use these fluids every day, we still know<br />surprisingly little about them.<br />http://www.anesthesia-analgesia.org/content/104/3/484.full.pdf+html<br />
  98. 98. www.derbyintensivecareecho.co.uk<br />(DICE)<br />

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