The story of colloids By Dr /Ahmed Mohamed Abdelazim Salem Lecturer of anesthesia & surgical I.C.U Benha University Hospital Senior registrar ( SAUC)

Total Body fluid

Total Body fluid

introduction Trauma , surgery & critical illness alter the volumes & composition of IC & EC spaces. Therapeutic fluid infusion further alter the volumes , composition , kinetics of fluid redistribution & excretion.

Introduction

Introduction Fluid replacement therapy is used millions of times a day around the world. For this reason, even small differences between the risks, benefits, and costs of the various volume replacement fluids can have major effects overall.

Crystalloids Aqueous solution of low MW < 30000 Dalton & distribute to all compartment.

Crystalloids Ringer lactate Ringer acetate Most physiological solution. Lactate bicarbonate. In circulatory shock & hepatic insufficiency lactate not converted to bicarbonate hyperlactatemia. * Do not take blood sample for lactate from same line. * Ca content in both can bind to Ampiciline ,thiopental & citrate of blood products Recently introduce , not FDA. Acetate bicarbonate. Used safely in hypovolemic shock & hepatic insufficiency Recommended in lactic acidosis. Muscle Liver

Colloids Definition Solution of high MW > 30000 Dalton . Colloids is Greek word means glue. Substance microscopically dispersed through another substances . Types : 1- Natural : albumin 5% & 25% -MW 66-69000. 2- Synthetics: Plant derived polymers of glucose that chemically modified to resist degradation

Colloids History The development of synthetic colloids markedly driven during times of war. Gum Arabic on polysaccharides was the 1st one 1906 & clinically used during world war I but ceased in 1937. 1st commercially synthetic colloids ( periston) 1939& clinically used during world war II but ceased in 1960.

First generation colloids 1st dextran was introduced to market 1944. Not used nowadays due to allergic reaction , R.F. & interfere blood grouping.

Seconde generation colloids From bovine collagen. May produce allergic reaction.

Third generation colloids 1st clinical use during Vietnam war 1959-1975. 1st synthetic colloids with globular configuration similar to albumin. Derived from Maize & potato starch. HES much lower viscosity than others but not reach to albumin. Types : 1- Heta-starch: MW 450000 - Hestril. 2- Penta-starch : MW 200000. 3- Tetra-starch : MW 130000- Voluven.

HES REASSESSMENT HES REASSESSMENT

The use of older HES solutions of a higher * In the past, the occurrence of a higher incidence of renal failure or bleeding complications in patients treated with HES fluids was believed to be associate with: The use of older HES solutions of a higher Molecular weight (450 or 200 kD) Higher degree of molar substitution 0.5 to 0.7. Exceeding the recommended daily dose limit. * Modern HES solutions of the so-called third generation with a mean molecular weight of only 130 kD and a molar substitution degree of 0.4 were regarded as safer * Westphal M, James MF, Kozek-Langenecker S, et al.:Hydroxyethyl starches: different products—different effects. Anesthesiology 2009; 111: 187–202.

2011 the debate was marked by controversy because of the absence of sufficient clinical data on HES. 2013 several high-quality studies on the modern 6% HES 130 solutions used in intensive care (Myburg etal: 2012) and in patients with sepsis (perner etal: 2012) have triggered an international debate on the safety of HES. FDA & EMA have reassessed the risk–benefit of HES. EMA conclude that that the benefits no longer outweigh the risks.

There is two large study (CHEST) 7000 ,( 6S )800 patients. Method: Retrospective randomized controlled trials (RCTs) that ● Carried out in patients with sepsis, trauma & ICU. ● Compared HES 130/0.4 or HES 130/0.42 with crystalloid fluids or human albumin. ● Fluid replacement for more than 24 hours. Results: 7 RCTs with a total of 7838 trauma ,sepsis, ICU patients and 8 meta-analyses. There is two large study (CHEST) 7000 ,( 6S )800 patients.

* Prospective RCT , multicenter in 32 hospital in Australia & New Zeland. * Published after FDA workshop 2012.

6S- study Compare HES 6% with Ringer acetate in sepsis . HES P-value Death at 90 days 201/398 172/400 0.03 Dialysis dependance 87/398 65/400 0.04

FDA safety communication: boxed warning on increased mortality and severe renal injury, and additional warning on risk of bleeding, for use of hydroxyethyl starch solutions in some settings November 25, 2013 * On September 6-7, 2012, FDA Public Workshop1 discuss the risks and benefits of HES solutions. * Presented data from randomized controlled trials (RCTs), meta-analyses and observational studies that showed increased mortality and/or renal replacement therapy when HES was used in critically ill adult patients, including patients with sepsis.

FDA Recommendations for Health Professionals 1) Do not use HES solutions in critically ill adult patients, including those with sepsis. 2) Avoid use in patients with pre-existing renal dysfunction. 3) Discontinue use of HES at the first sign of renal injury. 4) Need for renal replacement therapy has been reported up to 90 days after HES administration. Continue to monitor renal function for at least 90 days in all hospitalized patients.

5) Monitor the coagulation status of patients undergoing open heart surgery in association with cardiopulmonary bypass as excess bleeding has been reported with HES solutions in this population.a  Discontinue use of HES at the first sign of coagulopathy. 6) Do not use HES products in patients with severe liver disease. 7) Monitor liver function in patients receiving HES products

* HES is a chemically altered plant-derived substance recognized by the body as foreign, phagocytic cells of the immune system ingest it. * HES has been identified not only in the circulating plasma macrophages and monocytes, but also in the tissue-resident macrophages, such as histiocytes in the skin, muscle, and bone marrow and Kupffer cells in the liver.

In the plasma, HES can be metabolized by a amylase * In the plasma, HES can be metabolized by a amylase. This enzyme is not present in cellular lysosomes. Acid a-glucosidase is the lysosomal enzyme that primarily breaks down starch and disaccharides to glucose. There have been no reports of acid glucosidase’s ability to metabolize HES.

# HES localization in skin was shown by 17 studies, in kidney by 12, in liver by 8, and in bone marrow by 5. Additional sites of HES deposition were lymph nodes, spleen, lung, pancreas, intestine, muscle and placental stroma. # Storage was cumulative, increasing in proportion to dose, although in 15 % of patients storage and associated symptoms were demonstrated at the lowest cumulative doses (0.4 g kg-1). Some HES deposits were extremely longlasting, persisting for 8 years or more in skin and 10 years in kidney.

This review underscores that HES cellular uptake has been much less investigated and reported than the plasma presence of HES. However, tissue accumulation may be an important determinant of HES safety and needs to be further elucidated. By its very nature, tissue uptake is much harder to investigate than the plasma volume expanding effects of HES. The need for invasive multiple biopsies limits the type, size, and scope of studies that can realistically be conducted.

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