What Fluid? Tim Harris Prof emergency Medicine

Transcription

1 What Fluid? Tim Harris Prof emergency Medicine

2 Why We prescribe fluids to prevent dehydra>on Oral or IV Post op care what do you use? fluids for resuscita>on Which and how much? 39 year old pyelonephri>s BP 90/64 aker 1500 ml Hartmanns

3 You are called to see 68 year old man Phx BPH and IHD with stent in situ but no CCF medn aspirin, ramipril, metoprolol, tamsulosin Now in ED with BP of 88/46, temp 40, P=118, GCS 15 with urosepsis Which fluid? How much No change aker 2000 ml crystalloid What would you do now? Which fluid? How much? His is now Hb 8.9 Which fluid how much? Blood transfusion?

4 Background - why we give fluids Maintenance preserve normovolaemia prevent intravascular dehydra>on Prevent unpleasant sensa>on of dehydra>on Therapeu>c intravascular & cellular dehydra>on Replace losses & restore circula>ng volume Resuscita>on cellular hypoxia and organ failure Restore oxygen delivery to match needs

5 Fluids available The pros and cons of fluid chooses

6 Dextrose Dextrose - expands all spaces, useful for longer term hydra>on aimed at ICS Is diure>c 60ml per 1000lm delivered remain IVS (poor resus fluid) Distribu>on to ICS causes cellular hydra>on (avoid any cerebral pathology) Not a resus fluid

7 Fluids for resuscita>on Predominantly distributed in IVS Crystalloids and colloids and blood products

8 NaCl 0.9% Crystalloid Balanced solu>ons refers to composi>on being similar to plasma Hartmann's (278, Na 131 mmoll, K 5 mmoll, Ca 2 mmoll, lactate 29 mmoll, Cl 111 mmoll) Ringer s (312, Na 147mmolL, K mmoll, Ca 2.2 mmoll, Cl 156 mmoll) Plasmolyte A & B Advantages Cheap, no anaphylaxis, replace lost fluids, target to ECF, IVS Disadvantages Oedema & fluid overload

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11 Why do we have Synthe>c colloids? Australia has free access to albumen, elsewhere expensive Colloids are manufactured to use in place of albumen Expensive Use driven by shareholders as expensive compared to crystalloid No evidence of benefit for colloids Huge varia>on between volume and type of fluids between clinicans, special>es and countries Most are delivered in saline

12 Albumen Remains circn 8-12 hrs, 50% IVS (5L) 50% ECS (12L), freely exchanged, half life 21 days Advantages: An>oxidant, Natural, Sugges>on of improved outcome in sepsis Buffer (half the anion gap) Transport pn - drugs, hormones, ions Disadvantages Blood product, expensive, may increase ICP(vs HES) Increased mortality in TBI -? as hypotonic Congenital absence confers no harm Nephro>cs do not go into APO - need change in hydrosta>c pressure too

13 Starches 3 genera>ons, very different effects (elo- Haes, Haes- steril, hemohes, voluven - in 0.9% NaCl) Expensive - ( per 500ml) Large group, remain circ 2-12 hrs, KD Most widely used colloid in world, usu anaesthesia Accumulates in re>cular system renal impairment and pruri5s Coagulopathy - reduce vwf, 3rd genera>on do not effect

14 Gela>ns Anaphylaxis 0.03% In NS No evidence to support use, very few trials, emerging evidence of renal toxicity Gelofusion ml IVS 2-4 hours, 30 KD but - ve charge gives greater osmo>c effect Minimal metabolism, renal excre>on, cleared 3/7 plasma Minimal coagula>on effects un>l high mix (305 dilu>on), vwf/plt Haemaccel IVS 2 hours Renal excre>on, minimal metabolism Very high Ca++ load at 6.25 & cl at 145 (30ml Ca gluconate per 500ml)

15 Dextrans Developed WWII Remain circ 4-6 hrs Dextran 40 Improves rheology High allergy rate Marked an>coagulant - binds vwf and pnc Interferes with X match Dextran 70 Drama>c coagula>on effects equivalent heparin Prevents thromboembolism Improves microcircula>on

16 The great Fluid Debate: Colloid vs. crystalloid

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18 RCT ICU Australia 6997 pts albumen in NS vs. NS End points death ICU, organ failure, ven>lated days, RRT no difference between two agents Important addi>onal findings: Colloid : crystalloid ra>o 1:1.4 not 1:3 s previously taught TBI mortality trend increased if used albumen as opposed to saline, fist study to show fluids alter mortality highly significant mortality 33 vs 20% P=0.003 Sep>c shock, non significant trend to increase survival with albumen resus as opposed to saline; need trial

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21 FEAST NEJM 2011;354: RCT, Children sepsis & impaired perfusion, central Africa Excluded non- sep>c shock, gastroenteri>s, severe malnutri>on Interven>on groups: Albumen in saline 20-40ml/Kg vs 0.9% saline 20-40ml/Kg vs no bolus Fluids over one hour Primary end point Death at 48 hours, Mortality lower if no bolus fluid 10.6% vs. 10.5% vs. 7.3% RR 1.44 CI P=0.01 fro saline vs no bolus Startum B mortality 69% vs. 56% P=0.45 This study ques>ons the role of bolus therapy in fluids

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23 7000 pts, ICU, 6% HES in NS (130/0.4 voluven) vs. NS powered to find 3.5% increase in mortality at 90 days Findings: HES vs. NS Mortality 18.0% vs. 17.0% P=0.26 RRT 7% vs. 5.8% RR 1.21 CI P=0.04 AKI 34.6% vs. 38.0% P=0.005 Adverse events 5.3 vs. 2.8% P<0.001

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27 6S trial NEJM RCT 6% starch (HES 130/0.4) vs. Ringers acetate 26 Scandinavian ICU s, 798 pts, severe sepsis 1ry end point = death or RRT at day 90 primary end point, HES vs. Ringers 51% vs. 43% P=0.03 8% increase in mortality assoc starch use no difference at day 28 sugges>ng accumula>on of starch is the significant factor

28 Cochrane review 78 trials, 70 had mortality data Albumen 24 trials, 9220 pts, RR1.01 CI Starches, HES, 25 trials, 9147 pts, RR 1.10 CI Gela>ns, 11 trials, 506 pts, RR 0.91 CI (no change if Boldt s trials removed) Dextrans, 9 trials, 843 pts, RR Feb 2013

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30 The great Fluid Debate: Which Crystalloid?

31 0.9% saline Not normal 200 million L annual consump>on! Osmolarity 308 (plasma , Na 154, Cl 154) Hyperchloraemic Commonest hospital cause acidosis is hyperchloraemia?significance of this Cause of acidosis rather than ph is what maters Chloride decreases renal blood flow, worsens renal func>on Pro- inflammatory Ques>on of worse outcomes in sepsis Useful where hypertonicity may be of benefit TBI, stroke, neurological illness

32 Hartmanns / Ringers Hyponatraemia 131, hypo osmolar 278, 281 Concern re cellular swelling, compartment syndrome, oedema, hyponatraemic encephalopathy Avoid post surgery, hyponatraemia May elevate lactate Advantages of low choride No adverse effects renal func>on, acid base

33 So why cant we just make fluid like plasma? The problem is bicarbonate is not stable in plas>c, needs to be stored glass So fluids need inorganic ions that body coverts to bicarbonate Hartmanns - lactate Plasmolyte - acetate & gluconate Answer is not simply to give HCO 3 as converts to CO 2 & this will require increased RR

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35 Associa>on between chloride liberal vs chloride restrici>ve IV fluid administra>on and kidney injury in cri>cally ill adults. Bellomo et al JAMA ; Prospec>ve open label sequen>al period pilot trial 760 pts consequ>vely admited to ICU in control period vs. 773 pts admited during interven>on period Interven>on all chloride rich fluids (0.9% saline, 4% gela>ns, 4% albumen) restricted to specialist approval Std fluids were Hartmann solu>on, Plasmolyte 148 & salt poor albumen Results Mortality no difference AKI by RIFLE 14% vs. 8.4% (P<0.001) RRT 10% vs. 6.3% (P=0.005) Chloride restric-ve regieme assoc less AKI and RRT

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37 60734 pa>ents, 360 ICU USA NS mortality 20.2% vs. NS & balanced soln 17.7% (P<0.001) Vs. NS + colloid 24.2% (P<0.001) Vs. NS + bal + colloid 19.2% (P=0.401)

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44 NICE 2013

45 Fluids and Cloxng Need ica > 0.5 for coagula>on, Mg also impt for coagula>on an>coagulants are in lower concentra>on than procoagulants in blood so at lower levels dilu>on alone is procoagulant Arterial clot is mainly plt dependent (plt <1% HCT) Venous clot/capillary ooze thrombin dependent and more effected by fluids Many colloids are an5coagulant and as such may increase bleeding

46 Transfusion in haemorrhage

47 Hypotensive resuscitation Fluid increases BP, dilutional anaemia/coag proteins, acidosis and crystalloid load assoc impaired tissue perfusion Pop the clot Clot reaches 80% ultimate tensile strength in first hour

48 Trauma - haemosta>c resuscita>on For the very few who are dying of blood loss Resus strategy targe>ng early coagulopathy to improve outcome via haemorrhage control Coagulopathy accompanies trauma TIC occurs minutes of injury and assoc 4 fold mortality increase

49 Haemosta>c resuscita>on Resus strategy targe>ng early coagulopathy to improve outcome via haemorrhage control Blood and blood product based fluid resus Whole blood or RBCs/FFP then +platelets/cryoppt Avoid crystalloids and catecholamines No RCT, retrospec>ve data Is bennefit from blood products or avoiding crystalloid?

50 Trauma Transfusion 9% require transfusion 0.5% (UK) 3% (US) require massive transfusion (50% blood use) Massive transfusion carries mortality 30-60%

51 TIC and blood products MT data - FFP:RBC 1:1 vs. 1:8 reduced mortality by 60% 1:8 = 65%; 1:4 = 34%; 1:2.5 = 19% (p=o.oo1) (Borgman J Trauma 2007) Further military & civilian data Rajasekhar Crit care med 2011;39: PRBCs > 14 days doubled mortality Weinberg J trauma 2008

52 Mul>center RCT, major trauma, median ISS 26 Plasma:platelets:PRBC 1:1:1 (338 pa>ents) vs. 1:1:2 (342 pa>ents) 24 hour mortality 12.7% vs. 17.0%, P=0.12 (CI / 1.1); 30/7 mortality 22.4 vs 26.1% (CI - 10/2.7)? Effect of TBI?? Underpowered as power cal to 10% mortality difference Significant difference in exanguina>on at 24 hours in 1:1:1 group, mortality 9.2 vs. 14.6%, (CI - 5.4/- 10.4) Beter haemostsis in 1:1:1 group, 86% vs. 78%, p<0.001 JAMA Feb 2015

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54 Liberal vs. restric>ve transfusion strategy GI bleed Non blinded single centre RCT, Acute upper GI bleed, target Hb 7 vs 10, 900 pts Exclude lower/ac>ve cardiovasular syndromes/extanguishing Did include liver diseases Endoscopy within 6 hours key to risk stra>fica>on Results: Restric>ve group had less blood, more pts had no transfusion Mortality at 6 weeks 9% 10 Hb vs 5% 7 Hb (less re- bleeding, lower adverse events) Why? Lower portal pressure, beter coagula>on similar trauma

55 Summary Oral fluids unless C/I Fluids are toxic drugs and colloids are more toxic than crystalloids and have no place outside clinical trials No ideal crytsalloid Blood product based resuscita>on paradyne in severe trauma

56 Summary Haemosta>c resuscita>on hypotension & 1:1:1 severe blood loss in severe trauma Tolerate anaemia in most illness (Hb >7, > 10 IHD,? Neurological disease) including GI bleed Top up transfusion very rarely needed

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59 Anemia and blood transfusion in cri>cally ill pa>ents JAMA 2002;288: pts, ICU, 146 ICU s in W Europe, prospec>ve observa>onal study ICU (18.5 vs. 10.1% P<0.001) & overall (19 vs. 14.9% P<0.001) mortality higher in pts who had vs. had not had blood transfusion Matched pts 28/7 mortality 22.7 vs % P=0.02 Associa>on but may not be cause and effect

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61 The Evidence around Blood Transfusion Neutral SOAP pts - ICU, europe - showed no harm from transfusion?leucoreduc>on accounts for difference fro other trials Favours not transfusing ACS pts, post hoc analysis from GUSTO Iib, PURSUIT, PARAGON; transfusion assoc increased mortality, esp if hct > 25% (retrospec>ve analysis, (JAMA 2004;292: ) Post op: 8787 pts post NOF, observa>onal trial, 42% transfused, data avilable only for hb > 80 g/l, transfusion did not alter 30/7 or 90/7 mortality (JAMA 1998;279: ) CRIT study USA, 4892 pts, 213 hospitals, ICU study, 44% ICU pts received >= 1 unit PRBC s, number transfusions independently assoc mortality but does not necessarily imply cause & effect (crit care 2004;32:39-52)

62 The Evidence around blood Transfusion Favor's higher Hb TRICC inves>gators crit care pts, anaemia (Hb<100) assoc increased risk death in pts with heart disease (Am J Resp crit Care Med 1997;155: ) ACS - Retrospec>ve study 78974pts > 65yrs with AMI, lower Hct assoc increased mortality, tranfusion trigger of 110gL (HCT<33%) assoc lower 30/7 mortality (NEJM 2001;345: ) CCF NY 3/4, increase Hb 103 to 129 assoc improved LF EF and lower mortality (J Am Coll Card 2001;29: ) Common factor is IHD/cardiac disease

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64 Top up transfusion

65 Blood Transfusion Severe anaemia kills, blood harms Anaemia effects - DO2, pulse, infec>on, APO Hb 40-50gL well tolerated in normovolaemic young fit pts if reached slowly as adequate DO2 In young fit adult at rest adequate DO2 can be met with Hb 3 (increases in CO and extrac>on) (JAMA 1998; 279:217-21) Jehovas witness do badly Hb 6 mort 16x Don't confuse minimal tolerated Hb with clinically acceptable Hb in elderly diseased ac>vely bleeding pt - they can not increase CO and selec>vely dilate organ perfusion to compensate

66 Dangers of Blood Transfusion Mechanical Air embolism, microembolism, fluid overload Anaphylac>c/oid reac>ons Infec>on HIV HABCV prion malaria (s>ll 1: HIV, 1: HCV) Incompa>bility and haemolysis ABO resus duffy kell TRIM (transfusion related immunomodula>on) Increased renal allograk survival, enhanced metasts>c spread cancer, increased post op infec>on TRALI (transfusion related lung injury)

67 838 pts, euvolaemic, ini>al Hb<9 within 72 hours admission Randomised to Restric>ve group transfused if Hb < 7 & maintained 7-9 Liberal group transfused if Hb < 10 and Hb maintained g/ dl 1ry end point 30/7 mortality 18.7% vs. 23.3% P=0.11 If less sick, APACHE <=20 then 8.7 vs. 16.1% P=0.03, in favour of restric>ve group If < 55 yrs old 5.7% vs. 13.0%, P=0.02 But not if cardiac disease, 20.5% vs. 22.2%, P=0.69 Mortality rate during hospitaliza>on lower in restric>ve group, 22.2% vs. 28.1% P=0.05

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69 So when to Transfuse Target Hb 70 in young, 100 in elderly/cvs disease Weigh up risks and benefits using Phase of illness (acute, high VO2, ongoing losses) Co morbidity - IHD, CVD Age Predicted cause Probably wise to use leuco- reduced RBCs