Bapen Conference 2009 13 th October 2009 Cardiff International Arena Salt of the earth or a drop in the ocean An overview of the properties of iv fluids Peter Gosling BSc MSc PhD FRCPath Consultant Clinical Scientist Honorary Senior Clinical Lecturer University Hospital Birmingham UK Potential conflicts of interest declaration: In receipt of two grants from Bayer Diagnostics to study microalbuminuria in critical illness and surgery, and two grants from Fresenius- Kabi to study the effects of hydroxyethyl starch in vascular surgery
Crystalloids and Colloids: is there really a debate? Crystalloids Definition: crystalloids are salt solutions containing electrolytes or easily metabolised small molecules such as glucose Properties: Crystalloid solutions are isotonic with plasma at the time of intravenous administration, but in the case of glucose solutions, they become hypotonic in vivo as the glucose is metabolised. Primary Uses: 1. To provide free water (dextrose) 2. To replace lost electrolytes (salt solutions) 3. To provide a vehicle for i.v. delivery of drugs
Crystalloids and Colloids: is there really a debate? Crystalloids Definition: crystalloids are salt solutions containing electrolytes or easily metabolised small molecules such as glucose Ad hoc uses for salt solutions: Properties: Crystalloid solutions are isotonic with plasma at the Poor time man s of intravenous volume expander administration, (10-20% but stays in the in vasc. case space) of glucose solutions, they become hypotonic in vivo as the glucose is metabolised. An i.v. fluid for the unthinking e.g. normal saline must be safe Primary Uses: 1. To provide free water (dextrose) 2. To replace lost electrolytes (salt solutions) 3. To provide a vehicle for i.v. delivery of drugs
Crystalloids and Colloids: is there really a debate? Colloids Definition: A colloid solution contains molecules which are large enough to be retained by the vascular endothelium Properties: A colloid has the property of trapping water: e.g. 1 gram of albumin binds18 grams of water. The ability of a colloid solution to remain in the vascular space depends upon: 1. Molecular size (30kD up to >500kD) 2. Rate of degradation 3. Permeability of the endothelium Primary use: To fill the depleted vascular compartment
Capillary permeability of different tissues Tissue Pore sizes for capillary walls in various tissues Large pore diameter nm Small pore diameter nm Subcutaneous 20.0 5.0 1:3000 Skeletal muscle 22.0 6.0 1:3600 Brain.. 0.4 Intestine 20.0 4.6 1:6400 Liver 33.0 9.5 1:50 Lung 20.0 8.0 1:200 Ratio large to small pores Adapted from Aubrey Taylor
Scanning EM: normal endothelial cell junction McDonald DM, Thurston G, Baluk P.Endothelial gaps as sites for plasma leakage in inflammation. Microcirculation 1999; 6:7-22 X 40,000
Scanning EM: 1 minute after substance P
Capillary inflammation (microalbuminuria) during burns/surgery/trauma SIRS - Organ Failures Vascular permeability (Microalbuminuria) Normal Pre op Induct injury 2h 6h 12h 24h
Distribution of Infused Solutions Plasma Interstitial fluid Intracellular fluid Colloids 0.9% NaCl 5% Dextrose 0% 20% 40% 60% 80% 100% Courtesy of Dileep Lobo
Distribution of Infused Solutions Plasma Interstitial fluid Intracellular fluid Colloids Remember: The ability of colloids to remain in the vascular space depends upon: 1. Molecular size (30kD up to >500kD) 2. Rate of degradation 3. Permeability of the endothelium 0.9% NaCl 0% 20% 40% 60% 80% 100% 5% Dextrose Courtesy of Dileep Lobo
Fluid Chemical and Physical Properties of Crystalloids Sodium mmol/l Chloride mmol/l Potassium mmol/l Normal 140 95 4 295 plasma 0.9% 154 154 0 308 saline Ringers 130 109 4 273 lactate Hartmanns 131 111 5 275 Osmolarity mosm/l Plasmalyte 140 98 5 294 7.5% saline 1283 1283 0 2566
Effects of 2000 ml acute fluid loading in 10 volunteers. Blind cross over trial (Lobo et al Br J Surg 2001) 10 volunteers 5 given 2L 0.9% saline 5 given 2L 5% dextrose 2 week interval 5 given 2L 5% dextrose 5 given 2L 0.9% saline
Effects of Saline Loading Hyperchloraemic metabolic acidosis Hyperosmolar states Stimulation of ADH - fluid retention Chloride causes renal vasoconstriction fluid retention Nausea, vomiting, abdo pain, hyperventilation, headaches, thirst Hartmann AF, Senn MJE 1932 J Clin Invest 11:337-44 Waters JH et al Anesthesiology 2000:93:1184-7 Williams EL et al Anesthesia & Analgesia 1999;88:999-1003 Skellett S et al. Arch Dis Child 2000;;83:514-6 Healey MA et al J Trauma;45:894-9 (Ab)normal saline Na 154 mmol/l Cl 154 mmol/l
Hypertonic Saline Solutions Fluid Composition mmol/l mmol/250ml Hypertonic saline 7.5% NaCl 1283 321 Hypertonic saline 6% Dextran 70 kda 1283 321 with dextran in 7.5% saline RescueFlow (Vitaline) Hypertonic HES 6% HES 200 kda 1232 308 HyperHES in 7.2% saline (Fresenius-Kabi) Normal sodium intake only 70 mmol/24h
Hypertonic Saline - Mechanisms of Action 1. Bio Physical Effects (clinical and animal studies) Osmotic mobilization of cellular water into the circulation Reduction of haematocrit and viscosity In brain reduces ICP and draws fluid from cerebral oedema (HSD gives 10 times volume expansion of Ringer's) Increased preload for about 30 minutes Hyperosmotic vasodilation - reduces afterload BETTER PERFUSION!
Hypertonic Saline - Mechanisms of Action 2. Anti inflammatory effects (animal studies) Decreases neutrophil endothelial cell interaction Reduces capillary leak Less interstitial oedema Better organ function Early administration is essential for benefit
Chemical and Physical Properties of Colloids Fluid Sodium mmol/l Chloride mmol/l Mean Mol. weight Duration of vol. expan. Normal plasma 140 95 - - 25 COP mmhg Gelofusine 145 120 30,000 2h 27 Albumin 5% Pentastarch 10% Tetrastarch 6% 154 154 68,000 3-4h 13 154 154 200,000 12-24h 50 140 118 130,000 6h 38
Half glucose molecules substituted with HES, substitution =0.5
Characteristics of different hydroxyethyl starch preparations Adapted from Anesthesiology: 2005; 103:654-660 Tetra Penta Heta Heta Hepta Hepta
Structure of hydroxyethyl starches HES substituted glucose molecules can be 40 to 70%
Structure of hydroxyethyl starches Amylase C2 to C6 substitution ratio
Characteristics of different hydroxyethyl starch preparations Adapted from Anesthesiology: 2005; 103:654-660 Tetra Penta Heta Heta Hepta Hepta
Fluids for volume expansion Saline 58 D 5 times more needed than HES colloids Large sodium, chloride and water load Hyperchoraemic acidosis Fluid retention Interstitial oedema
Properties of resuscitation fluids Ringers lactate 5 times more needed than HES colloids Less sodium, less chloride, better excreted than saline Interstitial oedema still a risk if given in large volumes
Properties of resuscitation fluids Gelatine 30,000 Da Volume expansion lasts 1-2 hours Larger volume required than for HES Sodium, chloride and water load
Properties of resuscitation fluids Pentastarch 200 kd 0.5 substitution Volume expansion lasts 6-18 h Compared with crystalloid- only or gelatine less Na + Cl - and H 2 O Anti-inflammatory, less capillary leak Repeated infusions risk of accumulation
Properties of resuscitation fluids Tetrastarch 130 kda 0.4 substitution Volume expansion lasts 6-8 h Smaller volumes needed than cryst. gelatine Now in balanced electrolyte solution Gone after 12 h Anti-inflammatory, less capillary leak No accumulation claimed
Advantages of HES for fluid resuscitation Better vascular retention than gelatins, albumin or crystalloid alone Less extravascular Na + & water - less oedema Better kidney, gut and lung function Reduction of cytokine inflammation
Side effects of HES administration Osmotic like nephrosis after high dose Retention in reticuloendothelial system Pruritis after chronic administration Coagulopathy
Normal oncotic pressure (22 mmhg) Filtration (Blood) pressure Normal oncotic pressure Effects of oncotic pressure on glomerular filtration NORMAL ONCOTIC PRESSURE Normal renal function Normal urine output
High oncotic pressure (e.g. 40 mmhg) Filtration (Blood) pressure High oncotic pressure Effects of oncotic pressure on glomerular filtration HIGH ONCOTIC PRESSURE e.g. starch load with insufficient water Oliguria - renal impairment Low urine output
Stopped after 537 patients recruited due to high incidence of renal dysfunction and hypoglycaemia
VISEP Study Design Conventional insulin therapy Blood glucose is adjusted by using human insulin (Actrapid ) in the range between 180-200 mg/dl (10,0-11,1 mmol/l) Intensified insulin therapy Blood glucose is adjusted by using human insulin (Actrapid ) in the range between 80-110 mg/dl (4,4 6,1 mmol/l) CrysConv Crystalloid-based volume replacement Volume replacement is performed by exclusively using crystalloids (Sterofundin ). CollConv Colloid-based volume replacement Volume replacement is performed by using 10% HES (Hemohes 10%) until reaching the maximum daily dose of 20 ml/kg BW. CrysInt Crystalloid-based volume replacement Volume replacement is performed by exclusively using crystalloids (Sterofundin ). CollInt Colloid-based volume replacement Volume replacement is performed by using 10% HES (Hemohes 10%) until reaching the maximum daily dose of 20 ml/kg BW. Ringer s lactate 10% 200/0.5 HES in 0.9% Saline
VISEP Study: Amount of crystalloids Amount of crystalloids infused: Crystalloids (n = 275) HES (n = 262) min max median min max median 0 24 h 500 33,507 3,787 146 13,000 2,400 0 48 h 500 40,568 5,960 100 20,024 3,400 HES 10% 200 kd Not enough crystalloid in some patients Major risk of hyperoncotic state
VISEP Study: Amount of HES infusions 60 ml Hemohes / kg /BW/day 40 20 22 ml/kg BW HES (n = 262) Overdose % n At least at one day 38.2 100 Within first 24 h 28.2 74 0-24h 24-24h 38% Patients overdosed HES 10% 200 kd: high risk of hyperoncotic acute renal failure
VISEP Study: Reasons for renal impairment Study design: Ringers versus HES in 0.9% saline choride nephrotoxicity Volume therapy with HES 10% (HES 200/0.5) with insufficient free water in some patients HES 200/0.5 administered in some patients with contraindication renal impairment HES 200/0.5 has been overdosed in 38% patients
Eur J Anaesthesiol. 2008 May 20:1-9. Safety of HES 130/0.4 (Voluven(R)) in patients with preoperative renal dysfunction undergoing abdominal aortic surgery: a prospective, randomized, controlled, parallel-group multicentre trial. Godet G et al. Paris, France. 6% 130 0.4 hydroxyethyl starch; n = 32 3% gelatin; n = 33. Crit Care Med. 2007;35:2740-6. Influence of volume therapy with a modern hydroxyethylstarch preparation on kidney function in cardiac surgery patients with compromised renal function: a comparison with human albumin. Boldt J et al, Ludwigshafen, Germany. 6% 130kD 0.4 hydroxyethyl starch (130 kd 0.4); n = 25 5% human albumin; n = 25
Minerva Anestesiol. 2006;72:655-64. The effects of hydroxyethyl starch solution in critically ill patients. Palumbo D et al, Naples, Italy. PATIENTS Critically ill with sepsis INTERVENTION Hydroxyethyl starch 6% ( 130/0.4) n=10 Albumin 20% n = 10 To maintain PCWP 15-18 mmhg RESULTS: Compared with 20% albumin group, HES treated patients showed increased cardiac index (CI), right ventricular ejection fraction (RVEF), oxygen consumption index (VO(2)I), oxygen delivery index (DO(2)I), PaO2/FiO2 ratio (P<0.05). APACHE II score decreased significantly only in HAES treated group (P<0.05),
HES versus Gelatine: Renal function in Aortic Surgery Serum creatinine lower in Voluven group 140 Voluven Gelofusine elohes 120 Median serum creatinine umol/l 100 80 60 40 20 0.0009 0.0384 0.0074 0.0414 0.0123 n = 20 0 1 2 3 4 5 6 Days Mahmood A, Gosling P, Vohra RK. Br J Surg 2007;94:427-33. Rittoo D, Gosling P, et al Cardiovasc Surg. 2002;10:128-33.
Lung function during AAA Rittoo D, Gosling P, et al Br J Anaesth. 2004;92:61-6
Effect of Ringers Lactate, Saline and HES 130 on inflammation and endothelial activation in elderly major abdominal surgery Boldt, Intens Care Med 2004 Saline Ringers Lactate
Anti inflammatory effects of hydroxyethyl starch Clinical studies show reduced expression of pro inflammatory cytokines and adhesion molecules In vitro and animal studies suggest attenuation of endothelial cell response to activated neutrophils
To correct serious hypovolaemia Effective colloid to fill vascular space. One part starch to two parts balanced crystalloid. Avoid overdose! Red blood cells And finally. Give fluid for a reason! Clotting factors/platelets for haemostasis
Give fluid for a reason! To replace electrolyte losses For small scale resuscitation or replacement use balanced electrolyte solution (Hartmann s or Ringers) Avoid 0.9% saline except for extreme Na + Cl - deficits To provide free water Give enough water as 5% dextrose iv or enterally. This is to excrete urea and sodium and replace insensible losses. In critical illness measure urine electrolytes to ensure natriuresis and urine volume is adequate for solute load STOP! when resuscitation or replacement completed
Thank you for listening Peter.Gosling@uhb.nhs.uk Before a patient can recover they have to excrete all the fluid and electrolytes we give them