Current issues in Volume therapy

Transcription

1 CCM Inter-Hospital Grand Round Hong Kong, May 22, 2012 Current issues in Volume therapy Dr. Hrishikesh Kulkarni Medical Director Fresenius Kabi Asia Pacific, Hong Kong

2 Controversies in Intravenous fluids Crystalloids versus colloids Colloids versus colloids Recent events Crystalloids versus Crystalloids Restrictive versus Liberal fluids

3 Acta Anaesthesiol Scand 2009; 53:

4 How much fluid in surgical patients? Brandstrup et al, Ann Surg 2003;238: Restrictive versus liberal: Restrictive better! Restrictive = 2700 ml/d, Liberal = 5500 ml/d Restrictive = 900 ml/d, Liberal = 2800 ml/d Holte et al, Ann Surg 2004;240: Restrictive versus liberal: Liberal better!

5 Volume overload: bad outcome Secondary analysis of a cohort study of the NIH NHLBI ARDS Network ~ 900 patients on mechanical ventilation and low tidal volume Rosenberg et al J Intensive Care Med 2009;24:35-46 Negative fluid balance on day 4 associated lower hospital mortality (OR, 0.50; 95% CI, ; P <.001) more ventilator and ICU-free days Recently in a prospective study each 100 ml/24h positive fluid balance was found associated with 3% increased risk of mortality in the ICU. -Almeida et al, ISICEM 2010 Poster A659

6 Resuscitation fluid & Fluid balance Sheep model of smoke lung injury + MRSA instillation via bronchoscope Resuscitation by either normal saline or Voluven Ringer lactate 4 ml/kg/h as basic fluid to all groups 80% Voluven group and 40% saline group animals survived 150 Voluven Saline 5000 Voluven Saline Sham Voluven Saline Sham h MAP (mm Hg) Net fluid Balance (ml) Increase in lung vascular permeability index (ml/h) Asmussen et al, SHOCK 2011;35:31

7 Fluid Expansion As Supportive Therapy (FEAST) Study Maitland et al, NEJM 2011, May 26 (Epub) Crit Care 2011, June 10 (Epub)

8 3141 children (median age 2) severe febrile illness (Malaria 59%) + impaired consciousness + respiratory distress + impaired perfusion Baseline infusion of 2.5 to 4 ml/kh/h fluids PLUS Randomized to Control (no bolus) 20 (to 40) ml/kg 0.9% saline bolus 20 (to 40) ml/kg 5% albumin bolus Control group significantly less mortality than bolus groups at 48h (p=0.003) and 4 wk (p=0.004).. To question the role of fluids in severe sepsis can no longer be considered taboo. Hilton & Bellomo, Crit Care 2011, June h 4 wk Fluid in 8h ml/kg Mortality % Control Saline bolus Albumin bolus Maitland et al, NEJM 2011, May 26 (Epub)

9 Is more fluid not beneficial? Prospective study of 164 unselected septic shock patients from 6 Scandinavian ICUs over 3 months, 95 still had shock on d 3 (Colloids used HES 130/0.4 (n=52), 5% albumin (n=22), 20% albumin (n=23), n=10 got dextran) Patients who received higher (>7.5 L) of total fluids over 3 d had higher fluid balance (9.2 vs. 2.9 L, p<0.0001) but lower mortality (40 vs. 62%, p=0.03) Self-reported potential biases and weaknesses Confounding by indication, time-dependency, repeated exposure of the intervention and competing risks Unadjusted statistical analyses Systematic exclusion of most sick and least sick patients Descriptive design No record of co-morbidities, pre-icu interventions, post-shock-resolution interventions, timings, rates or targets of fluid infusion. Smith & Perner, Critical Care epub 8 May 2012

10 Targeted volume therapy in high-risk surgery Pilot study on high risk surgical patients Both groups given crystalloids + HES 130/0.4 Control group : standard practice Intervention group: 200 ml bolus every 10 in until top of Starling Curve Intervention group (n=26) Control group (n=26) Significant differences Intra-op colloids (ml) SVV changes Reduction No reduction Post-op infections 0 7 Trends Patients with complications 46% 62% Complications/patient Max. SOFA score Cumulative TISS score Scheeren et al, Anästh Intensivmed 2011;52:S278

11 Overall, HES most commonly used colloid 24 h Cross sectional study :25 countries, 391 ICUs, 5274 patients, 1234 colloid infusions Finfer et al. Critical Care 2010, 14:R185

12 Crystalloid-colloid debate: Cochrane metaanalysis It s about critical care, conclusion based on mortality The Cochrane Library, 2011 Conclusion: As colloids are not associated with an improvement in survival and they are expensive it s hard to see how their continued use.can be justified. Major problems: Sufficient patients only to look at albumin (n = 7754, 6997 from SAFE) In case of HES: Different HES, different indications, not all critically ill patients

13 6% Heta & Pentastarch, CABG 6% Penta & tetrastarch, major abd. surgery 10% Pentastarch, ICU 6% Pentastarch, Children-Dengue 6% Heta, hexa & pentastarch, middle ear surgery 6% Pentastarch, Knee replacement 6% Unspecified HES, Ovarian ca surgery Withdrawn study Withdrawn study 6% Hetastarch, elective non-cardiac surg? % Pentastarch, Trauma 10% Pentastarch, Whipple s operation 6% Hetastarch, Hypovolemic/septic shock 6% Pentastarch, Mitral valve repair Unspecified HES, post-cardiovasc surg 10% Pentastarch, Hypoalbuminemia, conf. abstract 10% Pentastarch, Trauma

14 All Colloids are not the same Efficacy: Volume expansion in volunteers after 500 ml infusion of gelatin, dextan, HES and RL (Kröll et al, 1993) end infus. 30Min 60Min 120Min GEL 3,5% DX40 10% HES 200/0,5 6% Safety: The French prospective multicentre study of ~ 20,000 patients showed different incidences of anaphylactoid reactions for gelatin, albumin, dextran and HES (Laxenaire et al, 1994) Gelatine Dextran Albumin HES

15 Q: Why so many hydroxyethyl starches? 1 670/0.7 3 Recent focus 4 130/0.4 in saline 130/0.4 in balanced solution Effects on capillary leak/ microcirculation/ healing * Safety Coagulation Renal Niemi, Miyashita & Yamakage, J Anesth Epub 17 Oct 2010

16 HES 200 vs HES 130 in surgery 7 studies (mixed) 449 patients Pooled data analysis Parameter Change by HES 130 P value Blood loss ml Drainage loss ml RBC loss ml RBC transfusions ml Kozek-Langenecker et al, Anesth Analg 2008;107(2):382-90

17 Coagulation effects HES 130/0.4 < Hetastarch 2 x 27 patients of spine surgery Randomized to hetastarch or HES 130/ ml/kg intraoperative use of colloid Less TEG abnormalities And Less transfusion requirements With HES 130/0.4 Choi et al, Spine 2010;35:

18 Coagulation effects of HES 130/0.4 = of albumin 18 x 2 patients Randomized to 6% HES 130/0.4 or 5% albumin in prime of CPB prior to valvular surgery Similar blood loss, HCT, platelets, PT, aptt, TEG changes Choi et al, Minerva Anestesiol (2010 Aug) 76(8):584-91

19 Coagulation effects of HES 130/0.4 = of gelatin 25 x 2 healthy full term parturients randomized to 500 ml pre-load of 6% HES 130/0.4 or 4% succ. gelatin prior to Caesarian section Similar TEG changes in both groups Turker et al, J Int Med Res 2011;39 (1):

20 HES and nephrotoxicity (All HES not same) The VISEP study. Brunkhorst et al, New Engl J Med 2008 Conclusion: As used in this study, HES was harmful, and its toxicity increased with accumulating doses Hyper-oncotic High molecular weight Higher than recommended doses.

21 Sheep with endotoxemia randomized to 10% HES 200/0.5, 6% HES 130/0.4 or Crystalloid Creatinine Urea Electron microscopy: Renal injury by HES 130/0.4 < crystalloid < HES 200/0.5 Ertmer et al, Anesthesiology 2010; 112(4):936-47

22 Retrospective observation All ICU patients admitted >72 h during were given HES 130/0.4 (HES+) and 195 were not (HES-) HES + patients were sicker Similar mortality as HES- patients AKI incidence followed by evolution of Urine output RIFLE classification SOFA score No difference between HES+ and HES - Authors conclusion: Volume expansion with low volume HES 130 kda/0.4 was not associated with AKI.

23 Retrospective analysis of 3591 surgical ICU patients (tetrastarch receivers 3152). Overall AKI rate 20.4% Risk factors for acute renal failure SOFA score Male gender Creatinine on admission Age SAPS II score Body weight APACHE II score Daily colloid amount Tetrastarch infusion Pentastarch infusion 0,9 0,95 1 1,025 1,125 1,25 1,5 2 OR (95% CI) Ertmer et al, ISICEM (Brussels) 2010 Poster A303

24 Fluid management and risk factors for renal dysfunction in patients with severe sepsis and/or septic shock Muller et al Crit Care 2012 Epub 1 March 2012 Follow up on the earlier Sepsis d Oc study in France Surviving sepsis guidelines rolled out in 15 ICUs in south France 6 mo observational vs. 6 mo intervention period During intervention mortality decreased from 40% to 27% (p=0.02) Muller et al explored renal dysfunction and RRT during Sepsi d Oc Renal dysfunction defined as S. creatinine increase by > 50% of baseline Of 388 eligible patients (combined from both periods) 117 had renal dysfunction 98% were given i.v. fluids in 1 st 24h HES 130/0.4 only (n=39), Crystalloids only (n=63) or both HES + Crystalloids (n=276) Mortality was higher with renal dysfunction (48 vs, 24%, p<0.01) Independent risk factors were (multivariate analysis) Male gender SAPS II score Surgical patient Lack of decrease in SOFA score in 24h Despite use in >80% patients, HES 130/0.4 was NOT a risk factor.

25 115 Trauma patients (65 penetrating) resuscitated with either Voluven or normal saline Double blind randomized study, start in emergency room follow up 30 days Voluven group required less volume for stabilization (5.1 vs. 7.4 L, p<0.001) In penetrating trauma: better S. lactate and better renal function & Better max SOFA score (2.4 vs. 4.5, p=0.012) than saline group P=0.029 Renal outcomes, penetrating trauma P<0.05 British Journal of Anaesthesia Advance access published 19 Aug 2011

26 HES 130/0.4 and inflammation Rat model of sepsis, treated with saline or 3 doses of HES 130/0.4 (7.5, 15 or 30 ml/kg) Xie JR et al, J Surg Res 160, (2010)

27 HES, EGDT & microcirculation in sepsis 20 patients with severe sepsis Randomized to 6% HES 130/0.4 Or Normal saline HES NaCl HES NaCl EGDT protocol Similar to Rivers et al, 2001 Sublingual Microcirculation Evaluated by Sidestream dark field imaging After 24 h of EGDT HES NaCl HES NaCl Dubin et al, J Crit Care Aug 31. [Epub ahead of print]

28 2 groups of pigs, hemorrhaged, resuscitated with RL or HES 130/0.4 to same MAP LR p<0.001 HES Lactate LR HES LR Microvascular permeability score P=0.017 LR Lung histology HES Acute lung injury score P=0.044 HES Balkamou et al, Anesthesiology 2010; 113:1092 8

29 HES and ALI in sepsis Rabbit sepsis model, resuscitated by Saline or NS + pentastarch or NS + tetrastarch Pulm. Capillary perfusion improved by both starches Thickening of alveolocapillary septum prevented only by HES 130/0.4 Alveolo-arterial oxygen difference reduced only by HES 130/0.4 Electron microscopy Alveolocapillary membrane A: Control B: Saline C: HES 130/0.4 D: HES 200/0.5 Heckel et al, Crit Care Med 2012; 40:

30 Observational study 32 Adults >40% burns (mean 45%) Fluid by Parkland Formula Control (10): Only RL Voluven (22): RL + Voluven Target urine output 1ml/kg/h 48h observation Estimated Control NS Actual Voluven p< h fluid rqmt. (L) p= Control Voluven 48 h wt. gain (kg) A similar study reported from Tunisia 72 h wt gain 8 vs kg (p=0.002) ALI incidence 35 vs. 65% (p=0.01) -Mokline et al, ISICEM 2012 (P 252) Transfusion Alternatives in Transfusion Medicine 2008;10:43 50

31 Pig model of colon anastomosis, mechanically ventilated. RL vs. RL + RL vs. RL + HES 130/0.4 The last 2 groups were goal directed : Bolus when SCVO2 below 60% small differences in hemodynamic parameters, i.e., HR, MAP, CVP, CI, PCWP, and arterial lactate among the 3 groups. But microcircilation in colon significantly better in the HES 130/0.4 group

32 Rats: Colostomy + CLP, treated with NS or HES 130/0.4, healing checked up to day5 Strength of Anastomosis Protein synthesis in Anastomosis Oxidative stress in Anastomosis Anti-oxodants in Anastomosis Anastomotic tissue Endoplasmic Reticulum Viable Non-viable NS group HES group Wang et al, The American Journal of Surgery (2010) 199,

33 Acid base balance Hyperchloremic Acidosis Hemostasis

34 No definitive recommendations yet about colloids in a balanced solution But clinicians are increasingly favouring balanced solution approach To see a difference in a clinical trial, sometimes artificial settings needed

35 HCMA in practice

36 Newer HES 130 solutions: Less Chloride Sodium Brand 1 Brand 2 Volulyte mmol/l Carrier solutions have some differences Potassium Calcium 5, mmol/l 0 The common thread is less chloride Magnesium Chloride 1 112, ,5 mmol/l 110 mmol/l Voluven/Volulyte are made from waxy corn starch Acetate mmol/l Other starches: Potato Malate 5.0

37 HES HES Amylopectin Amylose Maize starch 98% 2% Potato starch 75% 25% Westphal et al, Anesthesiology 2009; 111:

38 Transf Alt Transf Med 2006;2: identical brands of HES Identical mol. wt & degree of substitution brand A (FK), brand B in vivo mol wt Plasma conc over 10 d Significantly different plasma levels, in-vivo mol. wt and coagulation profiles.

39 Waxy maize-derived HES and potato-based HES are not bioequivalent, since there is clear difference in AUC and plasma clearance. Lehmann G, et al. Drugs R&D 2007, 8:

40 HES HES Maize starch (130/0.4) Potato Starch (130/0.42) Molar Substitution C2/C6 ratio Free Phosphate ppm Total Phosphate 15 ppm ppm Amylopectin 98% 75% Amylose 2% 25% Westphal et al, Anesthesiology 2009; 111: Publications to date (January, 2012) ~160 ~40

41 The CHEST study 7000 patients double blind PRCT in ICU patients Voluven vs. Saline with Mortality end point Intensive Care Medicine 2011 (Epub ahead of print) Support fully disclosed : samples + logistics Recently Australian government gave a grant to the CHEST study -thus confirming its high quality -and non-interference from industry (Fresenius Kabi)

42 RaFTinG : A European multi-centre observational database on i.v. fluids in ICU > 4000 patients enrolled Analysis ongoing Registry also being rolled out to Asia (RaFTA)

43 Crystalloids Colloids Colloids colloids HES HES (different Mw) HES HES (same Mw) Research continues Thank you!