"colloids: what did we learn last year and what happened in the meantime?" 2nd fluid...

"Colloids: What did we learn last year and what happened in the meantime?"

2nd Fluid Academy DayAntwerpen 2012

Rainer GatzICU physician

Herlev HospitalCopenhagen,

Denmark

Rainer Gatz, Herlev, Denmark -november 2012

2nd Fluid Academy Day Antwerpen 2012"Colloids: What did we learn last year and what happened in the

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Sweden

Denmark

Ringer's

“normal” saline


Bleck Scale of Evidence (BMJ 2000)

Class 0: Things I believeClass 0a: Things I believe despite the available dataClass 1: Randomised controlled clinical trials that agree with what I believeClass 2: Other prospectively collected dataClass 3: Expert opinionClass 4: Randomised controlled clinical trials that don't agree with what I believeClass 5: What you believe that I don't.

Thomas P BleckProfessor of Neurology, Neurosurgery, and Medicine,Northwestern University Feinberg School of Medicine


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my topics are:


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- the types of colloids

- what we learnt last year

- the state of the colloid-crystalloid debate

- last year's trials on this subject

- ongoing trials- recommendations for future use of

starches- all within 15 minutes ......

- what we learnt last year

- last year's trials on this subject



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What did we learn last year?

in the eyes of the coagulation specialist“6% isooncotic hetastarch is better than gelatin”


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“colloids in general are not better than crystalloids in ICU patients “

“but seem to be better in severe sepsis, cardiac surgery and liver cirrhosis “


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“albumin is better for patients with liver disease““and seems to be beneficial in sepsis“


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“the last generation starches are perfectly acceptable and safe “


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“looking forward to small volume, hypertonic solutions with a colloid that is charged “


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an acknowledgement!this work has been done with much

inspirationand information from

the critical care mailing listccm-l

http://www.ccm-l.orglistowner David Crippen, Pittsburgh, USA


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starches and their substitution degrees

0.7 Hetastarch0.6 Hexastarch0.5 Pentastarch0.4 Tetrastarch Voluven® 0.42 Tetraspan®

derived from: maizepotato

gelatins - urea-linked gelatin Haemaccel® - succinylated gelatin Gelofusin®

albumin

colloid types


colloid types


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source: Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill AdultsYunos et alii, JAMA 2012;308(15):1566-1572

SID (mEq/l) 0 29 34 50 12 81 (without metabolisable anions)



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colloid types

albumin

just a reminder: this is not a completely pure product, completely identical to the

natural thing- produced by ethanol fractionation and

chromatography

- undergoes a virus inactivation process- contains impurities:

protein aggregates and prekallikrein activator- contains additives: octanoate

ff



meantime?"albumin - a 1953 tracer study

Tracer Experiments With I181 Labeled Human Serum Albumin: Distribution And Degradation StudiesSolomon A. Berson et alii, J Clin Invest., 1953, 746-768

plasma

vessel rich

vessel poor

60%



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albumin - a 1953 tracer study

Tracer Experiments With I181 Labeled Human Serum Albumin: Distribution And Degradation StudiesSolomon A. Berson et alii, J Clin Invest., 1953, 746-768

"The apparent space of distribution in non-ascitic subjects averaged about 2.5 times the plasma volume.

Two apparent rates of transfer between plasma and extravascular spaces

with half times of approximately 3 and 24 hours, were observed."



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albumin - transmembrane transportalbondin

Albondin-mediated capillary permeability to albuminSchnitzer JE, Oh PJ Biol Chem 1994 Feb 25;269(8):6072-82

"About 50% of albumin transport is dependent on binding to the endothelial cell surface glycoprotein, albondin.

The remaining, binding- and concentration-independent transport could occur through intercellular junctions and/or

fluidphase transport via vesicular transcytosis and/or transendothelial channels."

albumin - transmembrane transportalbondin



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albumingenetically determined analbuminaemia

Analbuminemia: Three cases resulting from different point mutations in the albumin geneProc. Nati. Acad. Sci. USA Vol. 91, pp. 9417-9421, September 1994Scott Watkins, Jeanne Madison, Monica Galliano, Lorenzo Minchiotti, and Frank W. Putnam

"Analbuminemia was reported in a 39-yr-old Italian man .... Analysis by rocket electrophoresis gave a serum albumin

value of 5 mg/dl. The subject did not exhibit edema and was essentially asymptomatic."

"Analbuminemia was reported in a 39-yr-old Italian man .... Analysis by rocket electrophoresis gave a serum albumin

value of 5 mg/dl. The subject did not exhibit edema and was essentially asymptomatic."

october 2011 EARSS, first results at ESICMjanuary 2012 Simon et alii, two hit model of renal damagejanuary 2012 Saw et alii, gelatin metaanalysisfebruary 2012 Muller et alii, HES and renal dysfunctionmarch 2012 Thomas-Rueddel et alii, gelatin metaanalysismay 2012 CRYSTMAS trial *june 2012 6S trialjune 2012 BaSES trial, first results at ESAjuly 2012 PAL pilot study *august 2012 Bayer, colloids or crystalloids in shock reversaloctober 2012 CHEST trialoctober 2012 Albios study, first results at ESICMoctober 2012 Yunos et alii, chloride effect

* results already communicated at last year's fluid academy day




last year's developments - a timeline


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what DOES a clinician want to know?

mortality

morbidity

renal injury and failure

amount of bleeding

amount of fluid needed for primary resuscitation

cumulative fluid balance

The EARSS study



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results as communciated at ESICM in Berlin, october 2011

NCT00327704Early Albumin Resuscitation during Septic ShockJulien Charpentier, Jean Paul Mira, Hôpital Cochin, Paris

The EARSS study



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- type of trial: prospective, multicentre, randomised, open clinical trial- eligible patients: septic shock of up to 6 hours duration- type of intervention: albumin versus 0.9% NaCl control group: 0.9% NaCl 100 ml /8h for 3 days albumin group: albumin 20% 20 g/8h for 3 days- primary outcome measure: 28 and 90 days mortality- secondary outcome measures: SOFA scores ICU and hospital length of stay incidence of renal failure and pulmonary oedema

- type of trial: prospective, multicentre, randomised, open clinical trial- eligible patients: septic shock of up to 6 hours duration- type of intervention: albumin versus 0.9% NaCl control group: 0.9% NaCl 100 ml /8h for 3 days albumin group: albumin 20% 20 g/8h for 3 days- primary outcome measure: 28 and 90 days mortality- secondary outcome measures: SOFA scores ICU and hospital length of stay incidence of renal failure and pulmonary oedema

The EARSS study



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- number of patients included: 399 albumin group 393 control group- primary outcome results: 28 days mortality: albumin group: 24.1% control group: 26.3%

P=0.43 subgroups: community acquired infection difference albumin versus control group P=0.29 nosocomial infection difference albumin versus control group P=0.85 90 days mortality albumin group: 34.7% control group: 35.1%

P=0.94

The EARSS study



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- secondary outcome results: ICU length of stay

P=0.61 hospital length of stay

P=0.45 incidence of renal failure oedema number with renal replacement therapy and creatinin levels virtually identical between both groups free of mechanical ventilation within 28 days:P=0.24

The EARSS study



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quote from the presentation at ESICM Berlin

"3 days hyperoncotic albumin administration is well tolerated"

Simon et alii, two hit model of renal damage



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- type of trial: prospective randomised animal experiment- eligible patients: none, study done in 23 pigs- type of intervention: sham-treated group versus group with two-hit model combining haemorrhagic and septic shock- outcome measure: renal function and inflammatory response

creatinine clearance, ml/min, 12 hours after sepsis: Ringer's acetate: 76 ± 23 6% HES 130/0.42 in acetate: 97 ± 15 10% HES 200/0.5: 13 ± 14(significant) 4% gelatin in acetate: 38 ± 8

(significant) sham treated: 98 ± 48




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fluid balance, ml/kg BW, 12 hours after sepsis: 335 ± 94 in the Ringer's treated group versus 70 to 150 in the other groups (P< 0.05)

creatinine clearance, ml/min, 12 hours after sepsis: Ringer's acetate: 76 ± 23 6% HES 130/0.42 in acetate: 97 ± 15 10% HES 200/0.5: 13 ± 14(significant) 4% gelatin in acetate: 38 ± 8

(significant) sham treated: 98 ± 48 histology, acute tubular necrosis score: Ringer's acetate: 0.8 ± 0.3 6% HES 130/0.42 in acetate: 1.8 ± 1.1 10% HES 200/0.5: 2.2 ± 0.4(significant) 4% gelatin in acetate: 2.6 ± 0.5(significant) sham treated: 0.3 ± 0.6

histology, acute tubular necrosis score: Ringer's acetate: 0.8 ± 0.3 6% HES 130/0.42 in acetate: 1.8 ± 1.1 10% HES 200/0.5: 2.2 ± 0.4(significant) 4% gelatin in acetate: 2.6 ± 0.5(significant) sham treated: 0.3 ± 0.6

Saw et alii, gelatin metaanalysis



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- type of trial: meta-analysis (studies using randomisation, no cross-over, with comparison of gelatin use to that of crystalloids or other colloids including isotonic albumin, but not other blood products)

- eligible patients: patients in perioperative and critical care settings 30 randomised controlled trials involving 2709 patients, primary endpoint available in 14 studies with 1788 patients- primary outcome measure: hospital mortality, alternatively 28-day mortality- secondary outcome measures: incidence of acute renal failure total blood loss during study periods volume of blood transfused incidence of allergic reactions hospital length of stay

- type of trial: meta-analysis (studies using randomisation, no cross-over, with comparison of gelatin use to that of crystalloids or other colloids including isotonic albumin, but not other blood products)

- eligible patients: patients in perioperative and critical care settings 30 randomised controlled trials involving 2709 patients, primary endpoint available in 14 studies with 1788 patients- primary outcome measure: hospital mortality, alternatively 28-day mortality- secondary outcome measures: incidence of acute renal failure total blood loss during study periods volume of blood transfused incidence of allergic reactions hospital length of stay




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- primary outcome result: - risk of mortality:

gelatin versus all other types of fluids:(odds ratio 1.03, 95% confidence interval 0.80 to 1.32)not significantly different




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- secondary outcome results: - amount of blood lossed: 19 studies with 1252 patients report this no significant differences - amount of blood transfused: 11 studies with 796 patients report this - gelatin versus all other types of fluids no significant differences - gelatin versus crystalloids weighted-mean-difference 180 ml

95% CI 8 to 354 ml - significant - incidence of acute renal failure: 5 studies with 431 patients report this no significant differences in the subgroup of gelatin versus HES treatment there were fewer cases of acute renal failure in the gelatin group, but the comparison was mainly with HES 200




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- concerns / comments: "The quality of the published studies on gelatin solutions was also unsatisfactory, with no study having both adequate allocation concealment and double-blinding."

Thomas-Rueddel et alii, gelatin metaanalysis



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40 RCTs published between 1976 and 2010

patients receiving gelatin for resuscitation in comparison to albumin or crystalloids

3275 patients included




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"No study was adequately powered to investigate the frequency of patient-important outcomes."

"Despite over 60 years of clinical practice, the safety and efficacy of gelatin cannot be reliably assessed in at least some settings in which it is currently used."



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Muller et alii, Fluid management and risk factors for renal dysfunction




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- type of trial: observational multicenter study in 15 Southern French ICUs, two periods- eligible patients: patients without a history of renal failure and treated for severe sepsis and septic shock surviving after 24 hours- type of intervention: intervention based on the Surviving Sepsis Campaign in the second period- primary outcome measure: factors associated with renal dysfunction and renal replacement therapy- number of patients included: 388




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- primary outcome results: factors independently associated with renal dysfunction:

- male gender- increase in SAPS II scores- being a surgical patient- no decrease in SOFA scores during the first 24

hours- being treated during the interventional period of

the study factors independently associated with renal replacement therapy:

- need for vasopressors- baseline value of plasma creatinine

- secondary outcome results: mortality rate in patients with renal dysfunction versus in those without renal dysfunction (48% versus 24%, P < 0.01) mortality rate in patients requiring RRT 52% versus 26% in those not requiring RRT (P < 0.01)




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Use of colloids

315 of 388 patients received colloids

association with renal dysfunction (no versus yes):185 (78%) versus 101 (86%) P=0.07

association with renal replacement therapy (no versus yes):241 (81%) versus 74 (82%) P=0.82

“Despite being used in more than 80% of patients with severe sepsis and/or septic shock, the administration of HES 130/0.4 in the first 24 hours of management was not associated with the occurrence of renal dysfunction.”

The CRYSTMAS study



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The CRYSTMAS study



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- type of trial: randomised, prospective, multicenter, active-controlled, double-blind- eligible patients: patients with severe sepsis requiring fluid resuscitation in several French and German ICUs- type of intervention: HES 6% (130/0.4) (Voluven®) versus NaCl 0.9% to haemodynamic stability- primary outcome measure: amount of fluid to achieve haemodynamic stability

- type of trial: randomised, prospective, multicenter, active-controlled, double-blind- eligible patients: patients with severe sepsis requiring fluid resuscitation in several French and German ICUs- type of intervention: HES 6% (130/0.4) (Voluven®) versus NaCl 0.9% to haemodynamic stability- primary outcome measure: amount of fluid to achieve haemodynamic stability

The CRYSTMAS study



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- secondary outcome measures: time to achieve haemodynamic stability ICU and hospital length of stay mortality total quantity of study drug infused over four consecutive days area under the curve of SOFA score acute renal failure

- number of patients included: 196 randomised, 174 (88 / 86) with complete datasets

- secondary outcome measures: time to achieve haemodynamic stability ICU and hospital length of stay mortality total quantity of study drug infused over four consecutive days area under the curve of SOFA score acute renal failure

- number of patients included: 196 randomised, 174 (88 / 86) with complete datasets

The CRYSTMAS study



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- primary outcome results: amount of fluid to achieve haemodynamic stability - HES 1400 ± 890ml - NaCl 0.9% 1700 ±1200ml (mean difference = 331 ±1033ml, 95% CI 21 to 640ml, P = 0.02)

==> ratio crystalloid to colloid needed to achieve the same haemodynamic goals:

1.21SAFE trial:1.4, VISEP 1.6 (day 1), FIRST trial 1.4

- primary outcome results: amount of fluid to achieve haemodynamic stability - HES 1400 ± 890ml - NaCl 0.9% 1700 ±1200ml (mean difference = 331 ±1033ml, 95% CI 21 to 640ml, P = 0.02)

The CRYSTMAS study



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- secondary outcome results: time to achieve haemodynamic stability: - HES 11.8 ±10.1 hours - NaCl 0.9% 14.3 ±11.1 hours (difference not significant) acute renal failure 24 (25%) and 19 (20%) patients for HES and NaCl, respectively (P = 0.454) no difference between AKIN and RIFLE criteria no significant difference in ICU and hospital length of stay, total quantity of study drug infused over four consecutive days or area under the curve of SOFA score no difference in mortality, coagulation, transfusion requirement, incidence of infections or pruritus up to 90 days after treatment initiation

The 6S study



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Scandinavian Starch for Severe Sepsis / Septic Shock

NEnglJMed 2012; 367:124-134

130/0.42



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- type of trial: investigator-initiated, multicenter, parallel-group, blinded trial, randomised, in Denmark, Norway, Finland, and Iceland

- eligible patients: patients with severe sepsis

- type of intervention: fluid resuscitation in the ICU with either 6% HES 130/0.42 or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day

- primary outcome measure: was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization

The 6S study- type of trial: investigator-initiated, multicenter, parallel-group, blinded trial, randomised, in Denmark, Norway, Finland, and Iceland

- eligible patients: patients with severe sepsis

- type of intervention: fluid resuscitation in the ICU with either 6% HES 130/0.42 or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day

- primary outcome measure: was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization

The 6S study



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- secondary outcome measures: death at 28 days death at the time of the latest follow-up assessment severe bleeding while the patient was in the ICU severe allergic reactions SOFA score at day 5 after randomization the development of acute kidney injury doubling of the plasma creatinine level in the ICU acidosis (arterial pH <7.35) in the ICU percentage of days alive without renal-replacement therapy days alive without mechanical ventilation days alive out of the hospital in the 90 days after randomization

The 6S study



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- planned subgroup analyses: patients with shock at the time of randomisation patients with acute kidney injury at the time of randomisation- type of analysis: modified intention-to-treat- statistical power: 800 patients needed for the study to have 80% power to show an absolute between-group difference of 10 percentage points in the primary outcome measure and a 5% rate of dependence on dialysis at 90 days- number of patients included: 804 patients underwent randomisation, 798 were included

- planned subgroup analyses: patients with shock at the time of randomisation patients with acute kidney injury at the time of randomisation- type of analysis: modified intention-to-treat- statistical power: 800 patients needed for the study to have 80% power to show an absolute between-group difference of 10 percentage points in the primary outcome measure and a 5% rate of dependence on dialysis at 90 days- number of patients included: 804 patients underwent randomisation, 798 were included

The 6S study



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“Trial fluid (6% HES 130/0.42 in Ringer's acetate (Tetraspan 6%®, B. Braun) or Ringer's acetate (Sterofundin ISO®, B. Braun)”

SID (without metabolisable anions) 29 mEq/l

The 6S study



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- primary outcome result: - death at 90 days: - HES 130/0.4: 201 of 398 patients (51%) - Ringer's acetate: 172 of 400 patients (43%) relative risk, 1.17 95% confidence interval (CI), 1.01 to 1.36; P = 0.03

The 6S study



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The 6S study



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- secondary outcome results

- renal-replacement therapy: - HES 130/0.4: 87 patients (22%) - Ringer's acetate: 65 patients (16%) (relative risk, 1.35; 95% CI, 1.01 to 1.80; P = 0.04)

- severe bleeding: - HES 130/0.4: 38 patients (10%) - Ringer's acetate: 25 patients (6%) (relative risk, 1.52; 95% CI, 0.94 to 2.48; P = 0.09)

- secondary outcome results

- renal-replacement therapy: - HES 130/0.4: 87 patients (22%) - Ringer's acetate: 65 patients (16%) (relative risk, 1.35; 95% CI, 1.01 to 1.80; P = 0.04)

- severe bleeding: - HES 130/0.4: 38 patients (10%) - Ringer's acetate: 25 patients (6%) (relative risk, 1.52; 95% CI, 0.94 to 2.48; P = 0.09)

The 6S study



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relative risks with 95% confidence intervals (CIs) for the primary outcome of death or dependence on dialysis at day 90, among all patients and in the two predefined subgroups

Fluid Therapy before and after Randomisation

The 6S study



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The 6S study

source: http://www.nejm.org/doi/full/10.1056/NEJMoa1204242

The 6S study



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source: http://uk.finance.yahoo.com/

Fresenius share prices

The 6S study



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The 6S study



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source: http://uk.finance.yahoo.com/

Basel Starch Evaluation in Sepsis



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- type of trial: double-blind, randomised, controlled monocentric study- eligible patients: 240 consecutive patients with sepsis, severe sepsis and septic shock- type of intervention: volume therapy with Ringer's lactate and saline or HES 130/0.4 in the first five days of intensive care treatment




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- primary outcome measure: intensive care length of stay hospital length of stay mortality kidney function




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Bayer et alii, colloids or crystalloids in shock reversal



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- type of trial: single centre, prospective before and after study comparing three different treatment periods (not randomised, sequential groups)

- eligible patients: consecutive patients with severe sepsis

- type of intervention: fluid therapy directed at preset haemodynamic goals with - HES (predominantly 6% hydroxyethyl starch 130/0.4) in the first period - 4% gelatin in the second period - only crystalloids in the third period




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- primary outcome measures: time to shock reversal (serum lactate <2.2 mmol/l and discontinuation of vasopressor use) required fluid volumes in patients with septic shock

- secondary outcome measures: acute kidney injury (defined by RIFLE criteria) new need for renal replacement therapy ICU length of stay

- number of patients included: hydroxyethyl starch: 360 gelatin: 352 only crystalloids: 334




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- primary outcome results:

all groups showed similar time to shock reversal more fluid was needed over the first 4 days in the crystalloid group: fluid ratio 1.4:1 crystalloids to HES

1.1:1 crystalloids to gelatin




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- primary outcome results:

Total fluids day 1 to 4, in ml/kg: - HES 205 (156 - 267) (versus crystalloid P<0.01) - gelatin 224 (176 - 305) - crystalloid 239 (171 - 314)

after day 5, fluid balance was more negative in the crystalloid group

Total fluids day during ICU stay, in ml/kg: - HES 790 (355 - 1512) (versus crystalloid P<0.001) - gelatin 631 (276 - 1091) (versus crystalloid P<0.001) - crystalloid 406 (205 - 918)




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- secondary outcome results:

intensive care unit length of stay (in days): - HES 18 (8 - 30) (versus crystalloid P<0.001) - gelatin 13 (6 - 24) (versus crystalloid P<0.001) - crystalloid 10 (4 - 18)

Acute kidney injury by RIFLE (number and %): - HES 254 (71) (versus crystalloid P<0.001) - gelatin 238 (68) (versus crystalloid P=0.014) - crystalloid 195 (58)




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- secondary outcome results:

no significant differences for: - ICU or hospital mortality - mean and maximum SOFA scores - hospital length of stay




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concerns / comments:

24,326 surgical ICU patients were screened, 23,280 patients met exclusion criteria, including a total of 1,046 patients with severe sepsis or septic shock

exclusion criteria- < 18 years- solid organ transplantation- renal failure requiring haemodialysis before ICU- extracorporeal membrane oxygenation- serum creatinine values missing at admission- admission during the 1 month wash-out period between changes in resuscitative fluid regimens


The CHEST study

N Engl J Med, October 2012 DOI: 10.1056/NEJMoa1209759


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Stephen Streat on ccm-l, 20120321:(intensivist, Auckland, New Zealand)

The protocol was published in ICM in January 2011.This was a 7000-patient trial which finished recruitment on 23rd

January 2012 - on schedule.It was done in 18 months, at an average recruitment rate of 75

patients per week.There was only a 2.9% loss to follow-up, mainly due to withdrawal of

consent, and an 11% protocol violation rate.The study involved the administration of 4 million mls of fluids in

47720 bags of fluid!Tertiary outcomes (health economics etc.) will be analysed in 2013.

Then they plan to follow-up practice with 'CHEST-TRIPS' in 2014.


Stephen Streat on ccm-l, 20120321:(intensivist, Auckland, New Zealand)

The protocol was published in ICM in January 2011.This was a 7000-patient trial which finished recruitment on 23rd

January 2012 - on schedule.It was done in 18 months, at an average recruitment rate of 75

patients per week.There was only a 2.9% loss to follow-up, mainly due to withdrawal of

consent, and an 11% protocol violation rate.The study involved the administration of 4 million mls of fluids in

47720 bags of fluid!Tertiary outcomes (health economics etc.) will be analysed in 2013.

Then they plan to follow-up practice with 'CHEST-TRIPS' in 2014.

The CHEST study


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The CHEST study


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- type of trial: prospective, multicentre, concealed, randomised controlled trial

- eligible patients: 7000 patients planned to be recruited from 32 intensive care unit throughout Australia and New Zealand all pts admitted to the ICU and needing fluids, according to the treating physician, no strict treatment protocol

- type of intervention: 6% HES (130/0.4) versus 0.9% sodium chloride for intravascular volume resuscitation in the Intensive Care Unit

- type of trial: prospective, multicentre, concealed, randomised controlled trial

- eligible patients: 7000 patients planned to be recruited from 32 intensive care unit throughout Australia and New Zealand all pts admitted to the ICU and needing fluids, according to the treating physician, no strict treatment protocol

- type of intervention: 6% HES (130/0.4) versus 0.9% sodium chloride for intravascular volume resuscitation in the Intensive Care Unit


The CHEST study


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- primary outcome measure: 90-day all-cause mortality

- secondary outcome measures: mortality in predefined subgroups incident renal failure (RIFLE criteria) Sequential Organ Failure Assessment (SOFA) score use of renal replacement therapy other organ failures (measured using SOFA) ICU mortality hospital mortality length of ICU stay quality of life assessment measured using EQ5D score in patients with traumatic brain injury, functional outcome measured using the Glasgow Outcome Score

- primary outcome measure: 90-day all-cause mortality

- secondary outcome measures: mortality in predefined subgroups incident renal failure (RIFLE criteria) Sequential Organ Failure Assessment (SOFA) score use of renal replacement therapy other organ failures (measured using SOFA) ICU mortality hospital mortality length of ICU stay quality of life assessment measured using EQ5D score in patients with traumatic brain injury, functional outcome measured using the Glasgow Outcome Score


The CHEST study


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- planned subgroup analyses: patients admitted for trauma with traumatic brain injury patients admitted for trauma without traumatic brain injury patients with severe sepsis patients with pre-existing chronic renal failure in the absence of oliguria or anuria

- type of analysis: intention-to-treat

- statistical power: 90% power to detect an absolute difference of ≥3.5% in mortality 90% power to detect a relative risk increase of renal failure by 1.5

- number of patients included: 7000



meantime?"The CHEST study




primary outcome result

90-day all-cause mortality: - HES group: 597 of 3315 (18.0%) - saline group: 566 of 3336 (17.0%)(relative risk in the HES group, 1.06

95% confidence interval, 0.96 to 1.18; P=0.26




primary outcome results




secondary outcome results



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The CHEST study

source: supplement at http://www.nejm.org


The CHEST study


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controversy on ccm-l!

Ho-hum - elderly patients in first world ICUs don't differ whether treated with crystalloid or colloid. Still want to know

how to apply this to a 25 year old with a 3 day old perf appendix or in a 25 year old who blows up like a

Michelin Man on Ringer's but maintains normal body weight (and most other parameters) on starch (or gelatin back in the

day).

Ericintensivist, Durban, South Africa

De: Eric HodgsonPara: International Critical Care Medicine

Group<[email protected]>


The CHEST study


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controversy on ccm-l!

I see such patients and don't use HES and they don't bloat.You are overtreating with crystalloids in that case. 1 liter of HES

cannot miraculously make a patient less bloaty.

Prasannathoracic surgeon, Bangalore, India

answer by Prasanna, ccm-l, 20121017:

De: Prasanna SimhaPara: International Critical Care Medicine Group

<[email protected]>

The Albios study



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Efficacy of Albumin Administration for Volume Replacement in Patients With Severe Sepsis or Septic

Shockthe ALBumin Italian Outcome Sepsis (ALBIOS) Study

The Albios study



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- type of trial: interventional, randomised, open label

- eligible patients: severely septic and septic shock patients admitted to ICU

- type of intervention: albumin to plasma level of >=30g/l versus crystalloid infusion, to predefined haemodynamic goals according to the early-goal directed therapy (infusion of other colloids was not allowed)

- type of trial: interventional, randomised, open label

- eligible patients: severely septic and septic shock patients admitted to ICU

- type of intervention: albumin to plasma level of >=30g/l versus crystalloid infusion, to predefined haemodynamic goals according to the early-goal directed therapy (infusion of other colloids was not allowed)

The Albios study



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- primary outcome measures: 28-day, 90-day survival

- secondary outcome measures: number and severity of organ dysfunction (as recorded by the SOFA score) hospital and intensive care unit (ICU) length of stay

- number of patients included: 1815 patients, interim analysis of DSMB advised to continue after 1300 patients 908 in the albumin, 907 in the crystalloid group

- primary outcome measures: 28-day, 90-day survival

- secondary outcome measures: number and severity of organ dysfunction (as recorded by the SOFA score) hospital and intensive care unit (ICU) length of stay

- number of patients included: 1815 patients, interim analysis of DSMB advised to continue after 1300 patients 908 in the albumin, 907 in the crystalloid group

The Albios study



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- primary outcome results: (no final results yet; only results till hospital discharge) mortality at hospital discharge: - 36% for the albumin group, 37% for the crystalloid group (no significant difference)

- secondary outcome measures: not available yet

The Albios study



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comment on ccm-l, 20121017

Septic shock has a trend to low mortality with albumin (p=0.056). We will have to wait for final results.

Murillo Santucci Cesar de AssunçãoSão Paulo, Brasil



meantime?"

JAMA 2012;308(15):1566-1572



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“Conclusion:The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT.”

0.7 l of gelatin per patient in the control period, no artificial colloids administered during the intervention period 154 / 120

possible confounders:

succinylated gelatin (as used in this study) contains Na / Cl 154 / 120 mmol/l, is thus naturally "balanced"


open studies


meantime?"

CRISTAL studyEfficacy and Safety of Colloids Versus Crystalloids for Fluid Resuscitation in Critically Ill PatientsNCT00318942

BaSES trialBasel Starch Evaluation in SepsisNCT00273728

RASP trialLactated Ringer Versus Albumin in Early Sepsis TherapyNCT01337934

Efficacy and Safety of Colloids Versus Crystalloids for Fluid Resuscitation in Critically Ill PatientsNCT00318942

and many, many more ....http://www.clinicaltrials.gov


meantime?"


Consensus statement of the ESICM task force on colloid volume therapy in critically ill patients

Konrad Reinhart, Anders Perner, Charles L. Sprung, Roman Jaeschke, Frederique Schortgen, A. B. Johan Groeneveld, Richard Beale and Christiane S. HartogIntensive Care Medicine Volume 38, Number 3 (2012), 368-383

We recommend not to use HES with molecular weight >=200 kDa and/or degree of substitution >0.4 in patients with severe sepsis or risk of acute kidney injury

and suggest not to use 6% HES 130/0.4 or gelatin in these populations. We recommend not to use colloids in patients with head injury and not to administer gelatins and HES in organ donors.We suggest not to use hyperoncotic solutions for fluid resuscitation. We conclude and recommend that any new colloid should be introduced into clinical practice only after its patient-important safety parameters are established.



meantime?"

my two conflicts of interest

http://www.acidbase.org/fluidacademy/

"colloids: what did we learn last year and what happened in the meantime?" 2nd fluid...

Documents

denmark slide

nd fluid academy day

subject slide

sepsis slide

safe slide

gelatin slide

types of colloids

liver cirrhosis slide