1. Crystalloids v/s colloids
Dr. YASSER SULTAN

2. CRYSTALLOID V/S COLLOID
Colloids are mainly distributed to the IVS. Even with increased capillary leakage, a greater proportion of a colloid solution will remain in the IVS compared to a crystalloid solution. On the other hand crystalloid solutions are mainly distributed to the ISS. Approximately two-thirds of all infused crystalloid is distributed to the ISS, without any inherent COP,

3. CRYSTALLOID V/S COLLOID
As well as expansion of the ISS in the lungs, peripheral oedema also occurs.  Peripheral oedema can markedly decrease oxygen consumption. This may be related to increased distance between the cells and capillary or be as a result of occlusion of the thin walled capillaries by an increase in the surrounding ISS pressure. This may explain why colloids have been demonstrated to improve tissue oxygenation compared to crystalloids.

4. CRYSTALLOID V/S COLLOID
Peripheral oedema also results in delayed wound healing. Doubling the volume of the ISS decreases oxygen delivery to such an extent that capillary blood flow needs to be increased by 20-fold in order to maintain the same oxygen tension.

5. CRYSTALLOID V/S COLLOID
Fluid resuscitation for hypovolaemia is a mainstay of the medical management of critically ill patients--trauma, burns, major surgery or sepsis.
At one level the choice is between a colloid or crystalloid solution.
Colloids were widely used, having been recommended in a number of resuscitation guidelines and intensive care management algorithms
(Armstrong 1994; Vermeulen 1995)

6. ‘SAFE’ study
It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival.
A multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU was carried out.
N Engl J Med 2004; 350: May 27, 2004

7. HYPOTHESIS
‘We tested the hypothesis that when 4 percent albumin is compared with 0.9 percent sodium chloride (normal saline) for intravascular-fluid resuscitation in patients in the ICU, there is no difference in the 28-day rate of death from any cause’.

8. METHODS
Eligible patients were randomly assigned to receive either 4 percent albumin or normal saline,
Study fluids were supplied in identical 500-ml bottles, and blinding was ensured through the use of specially designed masking cartons and specially designed and manufactured administration sets.
The treating clinicians determined the amount and rate of fluid administration according to each patient's clinical status and response to treatment.
The allocated study treatment was to be used for all fluid resuscitation in the ICU until death or discharge or until 28 days after randomization.
The administration of intravenous fluids outside the ICU was not controlled.

9. METHODS
After randomization, the heart rate, central venous pressure, mean arterial blood pressure, volume of study fluid administered, volume of non study fluid and blood products administered, net fluid balance (calculated as the total fluid input minus the total fluid output), use of mechanical ventilation, and use of renal-replacement therapy (intermittent or continuous hemodialysis) were recorded daily until discharge from the ICU or death or until day 28

10. METHODS
Patients 18 years of age or older who had been admitted to the closed, multidisciplinary ICUs of 16 academic tertiary hospitals in Australia and New Zealand between November 2001 and June 2003 were assessed for eligibility for the study.
Eligible patients were those whom the treating clinician judged to require fluid administration to maintain or increase intravascular volume
Patients admitted to the ICU after cardiac surgery, after liver transplantation, or for the treatment of burns were excluded.

11. METHODS
They randomly assigned patients who had been admitted to the ICU were to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days.

12. OUTCOME MEASURES
The primary outcome measure--death from any cause within 28 days after randomization.
Secondary outcome measures—
the survival time during the first 28 days,
the proportion of patients who had one, two, three, four, or five new organ failures (defined as a documented change in the cardiovascular, respiratory, renal, hematologic, or hepatic component during the ICU stay
the duration of mechanical ventilation,
the duration of renal-replacement therapy,
the duration of the ICU and hospital stay.

13. RESULTS
The study population comprised 6997 patients, 3497 of whom were assigned to receive albumin and 3500 of whom were assigned to receive saline. 
At baseline, the only statistically significant difference between the two groups was a higher mean (±SD) central venous pressure in the albumin group (9.0±4.7 mm Hg, vs. 8.6±4.6 mm Hg in the saline group; P=0.03). 

14. RESULTS
On each of the first three study days, the patients who had been randomly assigned to receive albumin received significantly less study fluid than did those assigned to saline, resulting in a significantly greater net positive fluid balance in the saline group on each of those days The ratios of the volume of albumin to the volume of saline administered during the first four days were as follows: 1:1.3 on day 1, 1:1.6 on day 2, 1:1.3 on day 3, and 1:1.2 on day 4. 

15. RESULTS
There were no significant differences between the groups in the MAP measured at the end of each of the first four days of the study.
The patients assigned to receive albumin had a lower heart rate at the end of the first day than those assigned to receive saline.
Central venous pressure was significantly higher in the albumin group than in the saline group at all time points during the first four days, and the serum albumin concentration was higher in the albumin group throughout the study period .

16. RESULTS
There were 726 deaths in the albumin group, as compared with 729 deaths in the saline group.

17. RESULTS
The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups.
There were no significant differences between the groups in the mean (±2SD) numbers of days spent in the ICU (6.5±6.6 in the albumin group and 6.2±6.2 in the saline group.

18. RESULTS
Days spent in the hospital (15.3±9.6 and 15.6±9.6, respectively;),
Days of mechanical ventilation (4.5±6.1 and 4.3±5.7, respectively;),
Days of renal-replacement therapy (0.5±2.3 and 0.4±2.0, respectively; P=0.41).

19. CONCLUSIONS
In patients in the ICU, use of either albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days.

20. LIMITATION
Study– higher death rates in trauma patients receiving colloids due to RCT– head injury patients received the colloids.

21. LIMITATION
Patients who were assigned to albumin received a significantly greater volume of packed red cells during the first two days of the study. The reasons for this difference remain speculative but may include greater hemodilution with albumin than with saline or increased blood loss with albumin due to transient alterations in coagulation. 

22. LIMITATION
In a subgroup analysis of patients with the acute respiratory distress syndrome, the relative risk of death among those assigned to receive albumin as opposed to saline was 0.93; the corresponding relative risk among patients without this syndrome was 1.00 (P=0.74 by the test for a common relative risk).

23. Evidence-based Colloid Use in the Critically Ill American Thoracic Society Consensus Statement Am. J. Respir. Crit. Care Med.December 1, 2004 vol. 170 no. 11 
Sepsis is the leading cause of death in the ICU and the most common cause of ALI and ARDS, occurring in 30–40% of patients .

24. Evidence-based Colloid Use in the Critically Ill American Thoracic Society Consensus Statement Am. J. Respir. Crit. Care Med.December 1, 2004 vol. 170 no. 11 
The pulmonary edema that develops in ALI/ARDS results from alveolocapillary barrier dysfunction, although reduced COP may contribute to the generation and persistence of pulmonary edema .
Both intravascular hydrostatic pressure and plasma COP may be manipulated by colloid or crystalloid administration, and the preponderance of data supports exaggerated edema formation in states of reduced COP, particularly if hydrostatic pressures rise above normal .

25. Evidence-based Colloid Use in the Critically Ill
As in sepsis, varying recommendations have emerged over the past 25 years regarding appropriate fluid management in patients with ALI/ARDS, although no definitive evidence supports a given fluid to improve relevant clinical outcomes. Early studies of critically ill patients with acute hypoxemic respiratory failure reported inconsistent physiologic improvements. In patients with established pulmonary insufficiency, intrapulmonary shunt was significantly improved with albumin administration.

26. Evidence-based Colloid Use in the Critically Ill
Hypoproteinemic patients with established ALI treated with a combination of albumin and furosemide achieved significant diuresis and weight loss with concomitant 40% improvements in oxygenation and sustained improvements in hemodynamic stability.
Independent of colloid administration, management of patients with ALI/ARDS by means of a fluid restrictive strategy may benefit both hydrostatic and oncotic pressures and has been shown to reduce the extravascular lung water content while shortening the duration of mechanical ventilation (9 versus 28 days) and producing trends toward reduced ICU length of stay and mortality.

27. Conclusion
Colloids have rarely been studied in trials designed to determine clinical outcome benefits. The SAFE trial is a notable exception, supporting a neutral mortality influence of colloids in a general ICU population. From the data reviewed by this group, colloids are superior resuscitative agents and are important adjuncts in the therapy of dialysis-related hypotension and in the management of ascites requiring paracenteses. Their role in certain forms of brain injury and in spontaneous bacterial peritonitis requires further study and confirmation. Given the inadequate clinical trial data and wide confidence intervals in the meta-analyses, further investigation is needed in many areas of intensive care colloid use. In particular, outcome-centered trials are needed in septic shock, renal failure, ALI/ARDS, and certain forms of brain injury.

28. The COCHRANE review
Colloids versus crystalloids for fluid resuscitation in critically ill patients (Review)
Perel P, Roberts I, Pearson M
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2009, Issue 3
Copyright © 2009 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd.

29. BACKGROUND
Colloid solutions are widely used in fluid resuscitation of critically ill patients. There are several choices of colloid and there is ongoing debate about the relative effectiveness of colloids compared to crystalloid fluids.

30. OBJECTIVE
To assess the effects of colloids compared to crystalloids for fluid resuscitation in critically ill patients.

31. Albumin or plasma protein fraction - 23 trials reported data on mortality, including a total of 7754 patients.
Hydroxyethyl starch - 17 trials compared hydroxyethyl starch with crystalloids, n = 1172 patients.
Modified gelatin - 11 trials compared modified gelatin with crystalloid, n = 506 patients..
Dextran - nine trials compared dextran with a crystalloid, n = 834 patients.

32. AUTHOR’S CONCLUSION
There is no evidence that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery.
As colloids are not associated with an improvement in survival, and as they are more expensive than crystalloids, it is hard to see how their continued use in these patients can be justified outside the context of RCTs.

33. S U M M A R Y
No evidence that colloids are more effective than crystalloids in reducing mortality in people who are critically ill or injured

34. SUMMARY POINTS
Colloids have various nononcotic properties that may influence vascular integrity, inflammation, and pharmacokinetics, although the clinical relevance of these properties has not been elucidated .
All colloids affect the coagulation system, with dextran and starch solutions having the most potent antithrombotic effects .

35. HES may be deposited in the reticuloendothelial tissues for prolonged periods; the clinical significance of this is unknown .
Colloids restore intravascular volume and tissue perfusion more rapidly than crystalloids in all shock states, regardless of vascular permeability .
There is conflicting evidence that HES increases the risk of bleeding after cardiopulmonary bypass surgery .

36. Although hydrostatic pressure is more important than COP for accumulation of pulmonary edema, colloid administration reduces tissue edema and may ameliorate pulmonary edema as a consequence of shock resuscitation .
There is no evidence of a benefit of colloids in treating ischemic brain injury or subarachnoid hemorrhage . Colloids may adversely impact survival in traumatic brain injury.

37. HES administration may increase the risk of acute renal failure in patients with sepsis .
Treatment of dialysis-related hypotension with colloids is superior to crystalloids for chronic dialysis patients; presumably, colloids are similarly superior for acutely ill patients (II-A).
Colloids are superior to crystalloids in intravascular volume replacement with large-volume paracentesis and as adjunctive therapy to antibiotics in treating spontaneous bacterial peritonitis .

38. Meta-analyses of critical care colloid use are conflicting because of entry trial heterogeneity and varied analytic techniques, and a large prospective trial suggests a neutral influence of colloids on clinical outcomes.

39. Therapeutic Implications
Crystalloids should be administered first in nonhemorrhagic shock resuscitation .
Hydroxyethyl starch solutions should be used with caution in cardiopulmonary bypass and in patients with sepsis .
Colloids should be avoided or used with caution in patients with traumatic brain injury.

40. Fluid restriction is appropriate for patients with hemodynamically stable ALI/ARDS ; the combination of colloids and diuretics may be considered in patients with hypo-oncotic ALI/ARDS.
Colloids are preferred for treating dialysis-associated hypotension and in maintaining hemodynamics to achieve dialysis goals .

41. Hyperoncotic albumin should be administered in conjunction with large-volume paracentesis for diuretic-refractory ascites .
Albumin may be administered in conjunction with antimicrobial therapy to patients with spontaneous bacterial peritonitis .

42. Thank you