Colloids versus crystalloids for fluid resuscitation in critically ill patients

  • Review
  • Intervention

Authors


Abstract

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.

Objectives

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

Search methods

We searched the Cochrane Injuries Group Specialised Register (searched 16 March 2012), the Cochrane Central Register of Controlled Trials 2011, issue 3 (The Cochrane Library), MEDLINE (Ovid) 1946 to March 2012, EMBASE (Ovid) 1980 to March 2012, ISI Web of Science: Science Citation Index Expanded (1970 to March 2012), ISI Web of Science: Conference Proceedings Citation Index-Science (1990 to March 2012), PubMed (searched 16 March 2012), www.clinical trials.gov and www.controlled-trials.com. We also searched the bibliographies of relevant studies and review articles.

Selection criteria

Randomised controlled trials (RCTs) of colloids compared to crystalloids, in patients requiring volume replacement. We excluded cross-over trials and trials in pregnant women and neonates.

Data collection and analysis

Two review authors independently extracted data and rated quality of allocation concealment. We analysed trials with a 'double-intervention', such as those comparing colloid in hypertonic crystalloid to isotonic crystalloid, separately. We stratified the analysis according to colloid type and quality of allocation concealment.

Main results

We identified 74 eligible trials; 66 of these presented mortality data.

Colloids compared to crystalloids

Albumin or plasma protein fraction - 24 trials reported data on mortality, including a total of 9920 patients. The pooled risk ratio (RR) from these trials was 1.01 (95% confidence interval (CI) 0.93 to 1.10). When we excluded the trial with poor-quality allocation concealment, pooled RR was 1.00 (95% CI 0.92 to 1.09). Hydroxyethyl starch - 21 trials compared hydroxyethyl starch with crystalloids and included 1385 patients. The pooled RR was 1.10 (95% CI 0.91 to 1.32). Modified gelatin - 11 trials compared modified gelatin with crystalloid and included 506 patients. The pooled RR was 0.91 (95% CI 0.49 to 1.72). (When the trials by Boldt et al were removed from the three preceding analyses, the results were unchanged.) Dextran - nine trials compared dextran with a crystalloid and included 834 patients. The pooled RR was 1.24 (95% CI 0.94 to 1.65).

Colloids in hypertonic crystalloid compared to isotonic crystalloid

Nine trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1985 randomised participants. Pooled RR was 0.91 (95% CI 0.71 to 1.06).

Authors' conclusions

There is no evidence from RCTs 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.

Plain language summary

Are colloids more effective than crystalloids in reducing mortality in people who are critically ill or injured?

Trauma, burns or surgery can cause people to lose large amounts of blood. Fluid replacement, giving fluids intravenously (into a vein) to replace lost blood, is used to try to maintain blood pressure and reduce the risk of dying. Blood products, non-blood products or combinations are used, including colloid or crystalloid solutions. Colloids are increasingly used but they are more expensive than crystalloids. This review of trials found no evidence that colloids reduce the risk of dying compared with crystalloids.

Background

Fluid resuscitation for hypovolaemia is a mainstay of the medical management of critically ill patients, whether as a result of trauma, burns, major surgery or sepsis. Although some studies (Bickell 1994) have suggested that the timing of volume replacement deserves careful consideration, when it comes to selecting the resuscitation fluid, clinicians are faced with a range of options. At one level the choice is between a colloid or crystalloid solution. Colloids are widely used, having been recommended in a number of resuscitation guidelines and intensive care management algorithms (Armstrong 1994; Vermeulen 1995).

The US Hospital Consortium Guidelines recommend that colloids are used in haemorrhagic shock prior to the availability of blood products, and in non-haemorrhagic shock following an initial crystalloid infusion. However, a 1995 survey of US academic health centres found that the use of colloids far exceeded even the Hospital Consortium recommendations (Yim 1995). Surveys of burn care in the US (Fakhry 1995) and in Australia (Victorian DUAC 1991) found that the use of colloids for resuscitation varied without a set pattern.

The choice of fluid has considerable cost implications. Volume replacement with colloids is considerably more expensive than with crystalloids. Clinical studies have shown that colloids and crystalloids have different effects on a range of important physiological parameters. Because of these differences, all-cause mortality is arguably the most clinically relevant outcome measure in randomised trials comparing the two fluid types.

Why it is important to do this review

Although there have been previous meta-analyses of mortality in randomised trials comparing colloids and crystalloids (Bisonni 1991; Velanovich 1989), neither of these satisfy the criteria that have been proposed for scientific overviews (Oxman 1994), and they predate most of the trials that have been conducted using synthetic colloids, and hypertonic crystalloid solutions. The purpose of this systematic review is to identify and synthesise all available unconfounded evidence of the effect on mortality in critically ill patients of colloids compared to crystalloids for volume replacement.

Objectives

To assess the effects on mortality of using colloids compared to crystalloids, during fluid resuscitation in critically ill patients.

Methods

Criteria for considering studies for this review

Types of studies

Controlled trials in which participants were randomised to treatment groups (colloid or control) on the basis of random allocation. As the comparison between fluid type was in terms of effects on mortality, we excluded randomised cross-over trials.

Types of participants

Critically ill patients (excluding neonates and pregnant women) who required volume replacement. We included patients who were critically ill as a result of trauma, burns, undergoing surgery, or had other critical conditions such as complications of sepsis.

We excluded preoperative elective surgical patients.

Types of interventions

We considered the following colloids: dextran 70, hydroxyethyl starches, modified gelatins, albumin or plasma protein fraction.

There is overlap between albumin given for volume replacement and albumin given as a nutritional supplement, and many patients with a critical illness have low serum albumin. Where the trial was of total parenteral nutrition with or without albumin, we excluded it. We included trials where the albumin was given as part of volume replacement guided by colloid osmotic pressure or albumin levels.

The control group received crystalloid (isotonic or hypertonic) for fluid replacement. We included trials in which both groups received blood.

We excluded trials of fluids used for other purposes. For example, we excluded trials of pre-loading in preparation for elective surgery, and trials in patients undergoing fluid loading before cardiopulmonary bypass.

Types of outcome measures

The principal outcome measure was mortality from all causes, assessed at the end of the follow-up period scheduled for each trial.

Search methods for identification of studies

We did not restrict the search for trials by date, language or publication status.

Electronic searches

We searched the following electronic databases:

  • Cochrane Injuries Group Specialised Register (searched 16 March 2012);

  • the Cochrane Central Register of Controlled Trials 2011, issue 3 (The Cochrane Library);

  • MEDLINE (Ovid) 1946 to March, Week 1, 2012;

  • EMBASE (Ovid) 1980 to March 2012;

  • ISI Web of Science: Science Citation Index Expanded (1970 to March 2012);

  • ISI Web of Science: Conference Proceedings Citation Index-Science (1990 to March 2012);

  • PubMed (searched 16 March 2012);

  • National Research Register (2006, Issue 4).

All search strategies are listed in full in Appendix 1.

Searching other resources

We searched the reference lists of all relevant papers and published review articles. We also contacted known trialists to identify any further studies that we may have missed. We searched the online trials registers www.clinical trials.gov and www.controlled-trials.com for published and unpublished studies.

Data collection and analysis

The Injuries Group Trials Search Coordinator ran the electronic database searches, collated the results and removed duplicates before passing the list of citations to the lead review author (PP) for screening.

Selection of studies

Two review authors independently examined the list of citations for eligibility. We obtained full-text copies of all relevant records and independently assessed whether each met the pre-defined inclusion criteria. We resolved disagreement by discussion.

Assessment of risk of bias in included studies

We scored allocation concealment as described by Higgins 2011, assigning 'high risk of bias' to poorest quality and 'low risk of bias' to best quality (the presence of solutions in identical containers was only taken to mean adequate concealment if the fluid containers were used sequentially).

  • Low risk of bias = trials deemed to have taken adequate measures to conceal allocation (i.e. central randomisation; serially numbered, opaque, sealed envelopes; or other description that contained elements convincing of concealment).

  • Unclear = trials in which the authors either did not report an allocation concealment approach at all or reported an approach that did not fall into one of the other categories.

  • High risk of bias = trials in which concealment was inadequate (such as alternation or reference to case record numbers or to dates of birth).

We collected but did not score information on blinding and loss to follow-up.

Data synthesis

As a result of comments on the previous version of this review, we have stratified trials by type of fluid rather than type of original injury.

We calculated risk ratios (RRs) and 95% confidence intervals (CI) for each study using a fixed-effect model. We then inspected each comparison visually for evidence of heterogeneity and performed a Chi2 test. If there was no evidence of heterogeneity (visually or with a P value < 0.1) the trials were pooled within each type of fluid, but not combined between type of fluid.

Sensitivity analysis

We then excluded trials with allocation concealment judged as inadequate and repeated the calculations.

The editorial group is aware that a clinical trial by Professor Joachim Boldt has been found to have been fabricated (Boldt 2009). As the editors who revealed this fabrication point out (Reinhart 2011; Shafer 2011), this casts some doubt on the veracity of other studies by the same author. All Cochrane Injuries Group reviews that include studies by this author have therefore been edited to show the results with this author's trials included and excluded. Readers can now judge the potential impact of trials by this author on the conclusions of the review.

Results

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of ongoing studies.

We identified 74 trials meeting the inclusion criteria for study design, participants and interventions. We were able to obtain mortality data for 66 of these. We have reported details of the included trials in the 'Characteristics of included studies' table.

Reasons for exclusion of trials were: the use of a cross-over design, testing a resuscitation algorithm, giving the control group oral fluids, the intervention being directed to the maintenance of serum albumin levels, for haemodilution, for fluid loading and for the reduction of intracranial pressure (see 'Characteristics of excluded studies' table).

Of the 66 trials with data on deaths, the quality of allocation concealment was adequate in 13 trials and unclear in most of the others.

There were 65 comparisons of colloids and crystalloids (add-on colloid), 12 comparisons of colloid in hypertonic crystalloid with isotonic crystalloid and three comparisons of colloid with hypertonic crystalloid.

Risk of bias in included studies

In general, the design of studies was not well reported. This is reflected in the number of unclear scores given for allocation concealment. We also collected information on blinding and loss to follow-up. Blinding was not well reported and loss to follow-up was generally small. The characteristics for each trial are listed in the 'Characteristics of included studies' table.

Effects of interventions

Colloids compared to crystalloids

Albumin or plasma protein fraction

Twenty-four trials reported data on mortality, including a total of 9920 patients. The pooled RR was 1.01 (95% CI 0.93 to 1.10). When trials by Boldt were removed, the results were unchanged (RR 1.01; 95% CI 0.93 to 1.10). When we excluded the trial with poor-quality allocation concealment (Lucas 1978), pooled RR was 1.00 (95% CI 0.92 to 1.09).

Hydroxyethyl starch

Twenty-one trials compared hydroxyethyl starch with crystalloids, including a total of 1385 randomised patients. The pooled RR was 1.10 (95% CI 0.91 to 1.32). When trials by Boldt were removed, the results were unchanged.

Modified gelatin

Eleven trials compared modified gelatin with crystalloid, including a total of 506 randomised patients. The pooled RR was 0.91 (95% CI 0.49 to 1.72). When trials by Boldt were removed, the results were unchanged.

Dextran

Nine trials compared dextran with a crystalloid, including a total of 834 randomised patients. The pooled RR was 1.24 (95% CI 0.94 to 1.65).

Colloids in hypertonic crystalloid compared to isotonic crystalloid

One trial compared albumin and hypertonic saline with isotonic crystalloid. The RR of death was 0.50 (95% CI 0.06 to 4.33). One trial compared 6% hydroxyethyl starch 130/0.4 and hypertonic saline with Ringer's lactate. The RR of death was 0.25 (95% CI 0.03 to 2.15).

Nine trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1879 randomised patients. The pooled RR was 0.91 (95% CI 0.79 to 1.06).

Colloids in isotonic crystalloid compared to hypertonic crystalloid

Three trials compared colloids in isotonic crystalloid with hypertonic crystalloid. In two of these, where the colloid was either gelatin or starch, there were no deaths in either group. In the remaining trial, with 38 patients, there was a RR of death of 7.00 (95% CI 0.39 to 126.93) for use of colloid, based on three deaths in the treatment group and none in the control group.

Sensitivity analysis

When all trials authored by Professor Boldt (Boldt 1986; Boldt 1993; Boldt 2001; Lang 2001; Lang 2003) were excluded conclusions remain unchanged.

Discussion

This systematic review synthesises the evidence from RCTs comparing colloid and crystalloid fluid resuscitation across a wide variety of clinical conditions. The review has been updated and extensively revised to take into account the comments made since it was first published. In particular, several commentators pointed out that it is inappropriate to combine effect estimates from studies of different colloids. For example, it was argued that large molecular weight colloids such as hydroxyethyl starch may be better retained in the vascular compartment than albumin and gelatins, and would therefore be more likely to show a favourable effect on mortality (Gosling 1998). In response to these concerns, the review has been stratified by type of colloid. However, the pooled RRs fail to show a mortality benefit for resuscitation with any type of colloid.

There was a trend towards a favourable effect on mortality for colloids in hypertonic crystalloid, compared to isotonic crystalloids. Nevertheless, the results are compatible with the play of chance.

Common to all meta-analyses, this systematic review may have included studies whose interventions and patient characteristics are sufficiently incomparable that the calculation of a summary effect measure may be questioned. The resuscitation regimen differed between trials. Some trials randomised participants to an initial quantity of colloid or crystalloid, and then proceeded with some form of standard resuscitation for all participants. Other trials resuscitated with the allocated fluid to pre-determined end points, either resuscitation end points, or in the case of trauma, until corrective surgery. In addition, the type of colloid or crystalloid, the concentration, and the protocol to determine the quantity of fluid varied. Despite these differences, all participants were in need of volume replacement, and we believe that this variation in the intervention would have an impact on the size of the effect, rather than on its direction.

As regards the effects of albumin versus crystalloid, most of the information (as indicated by the weighting in the meta-analysis) was provided by the SAFE (Saline versus Albumin Fluid Evaluation) trial (SAFE 2004). The SAFE trial used central randomisation with a minimisation algorithm to ensure balance on known potential confounders. Blinding was assured through the use of specially designed masking cartons and specially designed and manufactured administration sets. The trial authors report that the effectiveness of the blinding was confirmed in a formal study before the trial was initiated. In brief, this was a well-conducted, high-quality trial. There were 726 deaths (20.9%) in the albumin-treated group and 729 deaths (21.1%) in the saline-treated group (RR of death 0.99; 95% CI 0.91 to 1.09). Although even this large trial was unable to confirm or refute the possibility of a modest benefit or harm from albumin, it has provided some reassurance that any hazard from albumin, if indeed there is any, is unlikely to be as extreme as was suggested by the results from the previously published (now here updated) meta-analysis of much smaller trials. The pooled RR for death with albumin in this updated meta-analysis is now 1.02 (95% CI 0.93 to 1.11). It is important to note that the effect estimate from the SAFE trial is entirely consistent with the results of previous trials of albumin in hypovolaemia and there is no significant heterogeneity (I2 = 0%, P = 0.46).

The results of this updated meta-analysis have important policy implications. There is still no evidence that colloids are superior to crystalloids as a treatment for intravascular volume resuscitation in critically ill patients. Importantly, the SAFE trial also provided no evidence of any other clinical advantages from using albumin. It also debunked the belief, from pathophysiological inference, that very large volumes of crystalloid must be administered to reach the same resuscitation end points as can be achieved using much smaller volumes of colloid. In the SAFE trial, the ratio of albumin administered to saline administered was approximately 1:1.4. Colloids, in particular albumin, are considerably more expensive than crystalloids, and albumin is a blood product and so carries at least a theoretical infectious disease risk. The economic opportunity cost of ongoing colloid use, particularly albumin use, is likely to be considerable and for this reason its ongoing use in this context is unjustified.

Authors' conclusions

Implications for practice

There is no evidence from RCTs that resuscitation with colloids, instead of crystalloids, reduces the risk of death in patients with trauma, burns or following surgery. As colloids are not associated with an improvement in survival, and further, colloids are considerably more expensive than crystalloids, it is hard to see how their continued use outside the context of RCTs in subsets of patients of particular concern, can be justified.

Implications for research

Future trials may need to concentrate on specific subgroups of patients to identify people who may benefit from colloids rather than crystalloids.

Acknowledgements

We acknowledge the contribution of Phil Alderson, Frances Bunn, Paul Chinnock, Gillian Schierhout and Mia Pearson who were authors of earlier versions of this review.

We would like to acknowledge the Intensive Care National Audit and Research Network in London (UK), for assistance with identification of trials for this review.

We thank Dr. Frank M. Brunkhorst for providing the Supplementary Appendix to the paper Brunkhorst 2008.

Data and analyses

Download statistical data

Comparison 1. Colloid versus crystalloid (add-on colloid)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Deaths52 Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
1.1 Albumin or plasma protein fraction249920Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.93, 1.10]
1.2 Hydroxyethyl starch211385Risk Ratio (M-H, Fixed, 95% CI)1.10 [0.91, 1.32]
1.3 Modified gelatin11506Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.49, 1.72]
1.4 Dextran9834Risk Ratio (M-H, Fixed, 95% CI)1.24 [0.94, 1.65]
Analysis 1.1.

Comparison 1 Colloid versus crystalloid (add-on colloid), Outcome 1 Deaths.

Comparison 2. Colloid and hypertonic crystalloid versus isotonic crystalloid
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Deaths11 Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
1.1 Albumin or plasma protein fraction114Risk Ratio (M-H, Fixed, 95% CI)0.5 [0.06, 4.33]
1.2 Hydroxyethyl starch190Risk Ratio (M-H, Fixed, 95% CI)0.25 [0.03, 2.15]
1.3 Modified gelatin00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
1.4 Dextran91879Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.79, 1.06]
Analysis 2.1.

Comparison 2 Colloid and hypertonic crystalloid versus isotonic crystalloid, Outcome 1 Deaths.

Comparison 3. Colloid versus hypertonic crystalloid
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Deaths3 Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
1.1 Albumin or plasma protein fraction138Risk Ratio (M-H, Fixed, 95% CI)7.0 [0.39, 126.92]
1.2 Hydroxyethyl starch116Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
1.3 Modified gelatin120Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
1.4 Dextran00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 3.1.

Comparison 3 Colloid versus hypertonic crystalloid, Outcome 1 Deaths.

Appendices

Appendix 1. Search strategy

Cochrane Injuries Group Specialised Register (searched 16 March 2012)
colloid* or hydrocolloid* or crystalloid*

Cochrane Central Register of Controlled Trials 2011, issue 3 (The Cochrane Library)
#1 MeSH descriptor Plasma Volume explode all trees
#2 MeSH descriptor Fluid Therapy explode all trees
#3 MeSH descriptor Resuscitation explode all trees
#4 (fluid* OR volume OR plasma OR rehydrat* OR blood OR oral) next (replac* OR therapy OR substitut* OR restor* OR resuscitat* OR rehydrat*):ti,ab,kw
#5 (#1 OR #2 OR #3 or #4)
#6 MeSH descriptor Colloids explode all trees
#7 MeSH descriptor Hetastarch explode all trees
#8 MeSH descriptor Rehydration Solutions explode all trees
#9 MeSH descriptor Isotonic Solutions explode all trees
#10 MeSH descriptor Serum explode all trees
#11 MeSH descriptor Plasma explode all trees
#12 MeSH descriptor Plasma Substitutes explode all trees
#13 MeSH descriptor Albumins explode all trees
#14 MeSH descriptor Serum Albumin explode all trees
#15 (colloid* OR hydrocolloid* or crystalloid* OR albumin* OR albumen* OR plasma OR starch* OR dextran* OR gelofus* OR hemaccel* OR haemaccel* OR serum OR hetastarch OR isotonic OR ringer* OR gelatin* OR gentran* OR pentastarch* OR pentaspan* OR hartman OR sodium OR potassium OR saline):ti
#16 (Isotonic next saline next solution*) OR (Blood next substitut*) OR (blood next expan*) OR (plasma next volume next expan*) OR (volume next expan*)
#17 (#6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16)
#18 (#5 AND #17)

MEDLINE (Ovid) 1946 to March Week 1 2012
1. exp Plasma Volume/
2. exp Fluid Therapy/
3. exp Resuscitation/
4. ((fluid* or volume or plasma or rehydrat* or blood or oral) adj1 (replac* or therapy or substitut* or restor* or resuscitat* or rehydrat*)).ab,ti.
5. 1 or 2 or 3 or 4
6. exp Colloids/
7. exp Hetastarch/
8. exp Rehydration Solutions/
9. exp Isotonic Solutions/
10. exp Serum/
11. exp Plasma/
12. exp Plasma Substitutes/
13. exp Albumins/
14. exp Serum Albumin/
15. (colloid* or hydrocolloid* or crystalloid* or albumin* or albumen* or plasma or starch* or dextran* or gelofus* or hemaccel* or haemaccel* or serum or hetastarch or isotonic or ringer* or gelatin* or gentran* or pentastarch* or pentaspan* or hartman or sodium or potassium or saline).ti.
16. ((Isotonic adj1 saline adj1 solution*) or (Blood adj1 substitut*) or (blood adj1 expan*) or (plasma adj1 volume adj1 expan*) or (volume adj1 expan*)).ab,ti.
17. or/6-16
18. 5 and 17
19. randomi?ed.ab,ti.
20. randomized controlled trial.pt.
21. controlled clinical trial.pt.
22. placebo.ab.
23. clinical trials as topic.sh.
24. randomly.ab.
25. trial.ti.
26. 19 or 20 or 21 or 22 or 23 or 24 or 25
27. (animals not (humans and animals)).sh.
28. 26 not 27
29. 18 and 28
30. (2008* or 2009* or 2010* or 2011*).ed.
31. 29 and 30

EMBASE (Ovid) 1980 to 2012
1. exp plasma volume/
2. exp fluid therapy/
3. exp fluid resuscitation/
4. ((fluid* or volume or plasma or rehydrat* or blood or oral) adj1 (replac* or therapy or substitut* or restor* or resuscitat* or rehydrat*)).ab,ti.
5. 1 or 2 or 3 or 4
6. exp colloid/
7. exp hetastarch/
8. exp "solution and solubility"/
9. exp isotonic solution/
10. exp serum/
11. exp serum albumin/
12. exp crystalloid/
13. exp hetastarch/
14. exp plasma/
15. exp plasma substitute/
16. exp albumin/
17. exp serum albumin/
18. or/6-17
19. (th or ad or iv).fs.
20. 18 and 19
21. (colloid* or hydrocolloid* or crystalloid* or albumin* or albumen* or plasma or starch* or dextran* or gelofus* or hemaccel* or haemaccel* or serum or hetastarch or isotonic or ringer* or gelatin* or gentran* or pentastarch* or pentaspan* or hartman or sodium or potassium or saline).ti.
22. ((Isotonic adj1 saline adj1 solution*) or (Blood adj1 substitut*) or (blood adj1 expan*) or (plasma adj1 volume adj1 expan*) or (volume adj1 expan*)).ab,ti.
23. 20 or 21 or 22
24. exp Randomized Controlled Trial/
25. exp controlled clinical trial/
26. randomi?ed.ab,ti.
27. placebo.ab.
28. *Clinical Trial/
29. randomly.ab.
30. trial.ti.
31. 24 or 25 or 26 or 27 or 28 or 29 or 30
32. exp animal/ not (exp human/ and exp animal/)
33. 31 not 32
34. 5 and 23 and 33
35. (2008* or 2009* or 2010* or 2011*).em.
36. 34 and 35

ISI Web of Science: Science Citation Index Expanded (1970 to March 2012), ISI Web of Science: Conference Proceedings Citation Index-Science (1990 to March 2012)
#1 colloid* OR hydrocolloid* or crystalloid*)
#2 (Isotonic NEAR/1 saline NEAR/1 solution*) OR (Blood NEAR/1 substitut*) OR (blood NEAR/1 expan*) OR (plasma NEAR/1 volume NEAR/1 expan*) OR (volume NEAR/1 expan*))
#3 #1 OR #2
#4 (fluid* OR volume OR plasma OR rehydrat* OR blood OR oral) NEAR/2 (replac* OR therapy OR substitut* OR restor* OR resuscitat* OR rehydrat*))
#5 (random*) NEAR/3 (study or trial)
#6 (singl* OR doubl* OR trebl* OR tripl*) NEAR/3 (blind* OR mask*) NEAR/3 (study or trial)

PubMed (searched 16 March 2012)
#1 (((plasma volume[MeSH Terms]) ) OR fluid therapy[MeSH Terms]) OR resuscitation[MeSH Terms]
#2 (fluid* OR volume OR plasma OR rehydrat* OR blood OR oral) AND (replac* OR therapy OR substitut* OR restor* OR resuscitat* OR rehydrat*)
#3 #1 or #2
#4 colloids[MeSH Terms]
#5 (colloid* OR hydrocolloid* or crystalloid* OR albumin* OR albumen* OR plasma OR starch* OR dextran* OR gelofus* OR hemaccel* OR haemaccel* OR serum OR hetastarch OR isotonic OR ringer* OR gelatin* OR gentran* OR pentastarch* OR pentaspan* OR hartman OR sodium OR potassium OR saline)[title]
#6 #4 or #5
#7 #3 and #6
#8 (randomised OR randomized OR randomly OR random order OR random sequence OR random allocation OR randomly allocated OR at random OR randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized controlled trials [mh]) NOT ((models, animal[mh] OR Animals[mh] OR Animal Experimentation[mh] OR Disease Models, Animal[mh] OR Animals, Laboratory[mh]) NOT (Humans[mh]))
#9 #7 and #8

What's new

Last assessed as up-to-date: 16 March 2012.

DateEventDescription
17 October 2012AmendedCopy edits made to graph labels.

History

Protocol first published: Issue 4, 1997
Review first published: Issue 4, 1997

DateEventDescription
8 June 2012AmendedCopy edits made and citation corrected.
14 May 2012New citation required but conclusions have not changedAn updated search was conducted in March 2012. Nine new trials have been included (Bulger 2011; Cooper 2006; Du 2011; Dubin 2010; James 2011; Lu 2012; Maitland 2011; McIntyre 2008; Zhu 2011) The analysis and results sections have been revised accordingly. The conclusions remain unchanged. 3 ongoing studies were identified (CHEST Trial; RASP trial; The 6S trial). We plan to update this review once the CHEST Trial (a large phase 3 trial comparing 6% hydroxyethyl starch and saline) is published.
16 March 2012New search has been performedAn updated search was conducted in March 2012.
10 February 2011New citation required but conclusions have not changed

The editorial group is aware that a clinical trial by Prof. Joachim Boldt has been found to have been fabricated (Boldt 2009). As the editors who revealed this fabrication point out (Reinhart 2011; Shafer 2011), this casts some doubt on the veracity of other studies by the same author. All Cochrane Injuries Group reviews which include studies by this author have therefore been edited to show the results with this author's trials included and excluded. Readers can now judge the potential impact of trials by this author (Boldt 1986, Boldt 1993, Boldt 2001, Lang 2001, Lang 2003) on the conclusions of the review.

The authors of the review have changed.

17 April 2009New search has been performed

April 2009

An updated search for new trials was conducted in October 2008. One new study was included (Brunkhorst 2008). The analysis, results and discussion sections have been revised accordingly.

16 July 2008AmendedConverted to new review format.
1 July 2007New search has been performedAugust 2007
An updated search for new trials was conducted in December 2006. Ten new studies were included (Evans 2003, Cifra 2003, Fries 2004, Guo 2003, Lang 2003, Maitland 2005, Moretti 2003, Upadhyay 2004, Verheij 2006, Wills 2005). The analysis, results and discussion sections have been revised accordingly.

Contributions of authors

July 2007: PP and IR examined trials for inclusion or exclusion, reaching agreement by discussion. PP and IR extracted data from the new studies. PP amended the text of the review.

April 2009: IR and MP examined trials for inclusion or exclusion, reaching agreement by discussion. IR and MP extracted data from the new study. MP amended the text of the review. PP edited the final version.

February 2011: The Cochrane Injuries Group amended the text (Emma Sydenham, Managing Editor). Both authors agreed with the changes to the manuscript.

Declarations of interest

None known.

Sources of support

Internal sources

  • Institute of Child Health, University of London, UK.

  • UK Cochrane Centre, NHS R&D Programme, UK.

External sources

  • NHS R&D Programme: Mother and Child Health, UK.

  • Cochrane Review Incentive Scheme, Department of Health, UK.

Notes

The editorial group is aware that a clinical trial by Professor Joachim Boldt has been found to have been fabricated (Boldt 2009). As the editors who revealed this fabrication point out (Reinhart 2011; Shafer 2011), this casts some doubt on the veracity of other studies by the same author. All Cochrane Injuries Group reviews that include studies by this author have therefore been edited to show the results with this author's trials included and excluded. Readers can now judge the potential impact of trials by this author (Boldt 1986; Boldt 1993; Boldt 2001; Lang 2001; Lang 2003) on the conclusions of the review.

Emma Sydenham, Managing Editor, performed the sensitivity analysis.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Boldt 1986

MethodsRCT, using sealed opaque envelopes
Information on allocation concealment was obtained on contact with the authors
Blinding and loss to follow-up not mentioned
Participants55 patients undergoing elective aorta-coronary bypass surgery
Exclusion criteria: ejection fraction < 50% and LVEDP > 15 mmHg
Interventions
  1. 300 mL 20% Human albumin solution (n = 15)

  2. 500 mL 3% HES (n = 13)

  3. 500 mL 3.5% Gelatin (n = 14)

  4. No colloid (n = 13)

OutcomesHaemodynamic variables were measured
Deaths not reported
NotesFollow-up until discharge from ICU
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Boldt 1993

MethodsRCT, allocation concealment by sealed opaque envelopes (information from author)
Blinding and loss to follow-up not mentioned
Participants75 males undergoing elective aortocoronary bypass grafting, who had a pulmonary capillary WP < 5 mmHg after induction of anaesthesia
Interventions
  1. 5% Albumin (n = 15)

  2. 6% HES, mean molecular weight 450,000 (n = 15)

  3. 6% HES, mean molecular weight 200,000 (n = 15)

  4. 3.5% Gelatin (n = 15)

  5. No colloid (n = 15)

Fluid used through operation and on intensive care postoperatively

OutcomesDeaths not reported, author confirmed there were no deaths
NotesFollow-up to 1 day
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Boldt 2001

MethodsRCT, using a closed-envelope system
Participants100 patients undergoing major abdominal surgery
Interventions
  1. Ringer's lactate (n = 25)

  2. 6% HES, mean molecular weight 200 kDa, degree of substitution 0.5 (n = 25)

  3. 6% HES, mean molecular weight 130 kDa, degree of substitution 0.4 (n = 25)

  4. 4% Modified fluid gelatin, molecular weight 35 kDa (n = 25)

OutcomesDeaths
Orthostatic problems
Haemodynamics and laboratory data
Fluid input and output
Costs
NotesFollow-up period unclear
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Boutros 1979

MethodsRCT ("randomly divided"), method of allocation concealment not described
Blinding not mentioned
No loss to follow-up
Participants24 people undergoing major operative procedures on the abdominal aorta
Interventions
  1. Albumin in 5% dextrose (n = 7)

  2. 5% Dextrose and Ringer's lactate (n = 8)

  3. 5% Dextrose in 0.45% saline (n = 9)

Allocated fluids were used on admission to ICU, following surgery, guided by PAWP. Whole blood also given if clinically needed

OutcomesDeaths reported
NotesFollow-up to discharge from hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Bowser-Wallace 1986

MethodsQuasi-RCT, allocation by alternation
Blinding not mentioned
No loss to follow-up
ParticipantsAdmitted for burns of 30% or more
Age range 5 months to 21 years
Excluded if already given more than half calculated daily requirement before reaching hospital
Interventions
  1. 2 mL/kg/%burn Ringer's lactate over 24 hours, then 0.5 mL plasmanate/kg/%burn over 24 hours plus 5% dextrose (n = 19)

  2. 2 mL/kg/%burn hypertonic lactated saline over 24 hours, then 0.6 mL/kg/%burn hypertonic lactated saline over 24 hours plus oral Haldane's solution (n = 19)

IV fluids stopped at 48 hours (n = 19)

OutcomesDeaths reported
Fluid and electrolytes given, weight, haematocrit
NotesFollow-up to 5 days
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)High riskInadequate

Brunkhorst 2008

Methods

Multicentre, RCT

Blinding not mentioned

Use of a 2 x 2 factorial, open label study design

ParticipantsCritically ill patients with severe sepsis or septic shock of at least 18 years of age. Excluded if onset of symptoms commenced > 24 hours before admission to the ICU, if the symptoms commenced > 12 hours after onset in the ICU or if patient had received more than 1000 mL of HES in the 24 hours before randomisation
Interventions 
OutcomesDeaths reported at 28 and 90 days. 90-day mortality rate was cited as it marked the end of the follow-up period
Notes-
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Bulger 2011

MethodsDouble-blind RCT
Participants15 years or older with hypovolaemic shock (< 70 mmHg SBP or SBP 71 mmHg to < 90 mmHg and HR < 108 bpm
Interventions
  1. 7.5% saline per 6% dextran (n = 220)

  2. 0.9% saline (n = 376)

Outcomes

Primary outcome: 28-day survival

Secondary outcomes: fluid and blood requirements, ARDS, MODS and nosocomial infections

Notes-
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskAll care providers, investigators and patients remained blinded to the treatment assignment

Chavez-Negrete 1991

MethodsRCT, allocation by "random numbers"
Blinding not mentioned
No loss to follow-up
ParticipantsAdults admitted to an emergency department with acute GI haemorrhage, SBP ≤ 90 mmHg for up to 1 hour and normal ECG
Excluded if pregnant or had renal, cardiac or neurological disease
Interventions
  1. Initial infusion of 250 mL 7.5% saline/6% dextran 60 given IV (16 patients) or intraosseous (n = 10)

  2. Initial IV infusion of 250 mL Ringer's lactate (n = 23)

Resuscitation continued with red cells, 0.9% saline and dextran 40 according to clinical judgement

OutcomesDeath
Haemodynamic variables
NotesFollow-up to 24 hours
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Cifra 2003

MethodsQuasi-RCT (allocation by alternation), allocation concealment not reported
Blinding not reported
No loss to follow-up
Participants27 children with dengue shock syndrome
Exclusion criteria included: other severe infection, protein-deficient abnormalities, bleeding diathesis, patients who have been given multiple plasma substitutes
Interventions
  1. 6% Haes-Steril (n = 11)

  2. Ringer's lactate (n = 16)

1 patient from group 1 and 3 patients from group 2 were excluded because they needed inotropic support and multiple plasma substitute

OutcomesDuration of control of shock
Recurrence of shock
Length of ICU stay
Death not reported as an outcome but they reported that 4 patients died
NotesLength of follow-up not reported but all outcomes were in hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskNot used

Cooper 2006

MethodsMulticentre unblinded controlled trial with stratified block randomisation by centre and mortality prediction at enrolment
ParticipantsPatients with cutaneous thermal burns of at least 20% TBSA within 12 hours of injury
Interventions
  1. Ringer lactate and 5% albumin (n = 19)

  2. Ringer lactate (n = 23)

Outcomes

Primary outcome was MODS

Mortality was reported

NotesThe trial was suspended due to slow enrolment
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskPatients were allocated to study groups with stratified randomisation with a computer-generated randomisation list and sequentially numbered sealed, opaque envelopes

Dawidson 1991

MethodsRCT, allocation by drawing a card from a deck
Blinding not mentioned
No loss to follow-up
ParticipantsAdults undergoing elective abdominal aortic surgery
No exclusions mentioned
Interventions
  1. 3% Dextran 70 in Ringer's lactate (n = 10)

  2. IV Ringer's lactate (n = 10)

Fluid used during and for 24 hours after operation, guided by haemodynamic variables

OutcomesDeath
Volume transfused, weight change, haemodynamic variables
NotesFollow-up to discharge from hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)High riskInadequate

Dehne 2001

MethodsRCT, allocation by sealed envelope assignment
Participants60 male patients (of ASA physical status 1 or 2) scheduled for middle ear surgery
Interventions
  1. Ringer's lactate solution (n = 15)

  2. 6% HES: molecular weight 200 kDa, degree of substitution 0.5 (n = 15)

  3. 6% HES: molecular weight 200 kDa, degree of substitution 0.60 to 0.66 (n = 15)

  4. 6% HES: molecular weight 450 kDa, degree of substitution 0.7 (n = 15)

OutcomesDeaths not stated but 'all' patients discharged 10 to 14 days after surgery; therefore no deaths
Central venous pressure
Urine output
Blood osmolality
Urine osmolality
NotesFollow-up 2 days
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Du 2011

MethodsRandomised controlled study
ParticipantsParticipants had confirmed diagnosis of severe acute pancreatitis. Patients were included within 72 hours after the onset of symptoms
Interventions
  1. 6% HES 130/0.4 (n = 20)

  2. Ringer's lactate (n = 21)

OutcomesPrimary outcome was intra-abdominal pressure. They also reported in-hospital mortality, organ complications, inflammatory markers and fluid requirement
NotesPatients were excluded if they died within 72 hours after admission
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Dubin 2010

MethodsRCT
ParticipantsPatients with severe sepsis
Interventions
  1. 6% HES 130/0.4 (n = 12)

  2. Normal saline (n = 13)

OutcomesSublingual microcirculation
NotesData on mortality are not clear from the report
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear risksealed enveloped were used

Eleftheriadis 1995

MethodsPatients "randomizedly distributed"
Blinding not mentioned
Unable to assess loss to follow-up
ParticipantsParticipants were undergoing coronary artery bypass surgery
Interventions
  1. 6% HES

  2. 3.5% Gelatin

  3. Ringer's lactate

Allocated fluid was used in the postoperative period only guided by mean arterial pressure

OutcomesDeaths were not reported
Haemodynamic variables
NotesFollow-up period unspecified
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Ernest 1999

MethodsRCT, allocation concealment not described
No blinding
No loss to follow-up mentioned
ParticipantsPatients with a clinical diagnosis of sepsis
Interventions
  1. 5% Albumin (n = 9)

  2. 0.9% Saline (n = 9)

Volume of infusion guided by PAWP

OutcomesHaemodynamic variables and volume measurements
Deaths not reported
NotesFollow-up to immediately after infusion
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Evans 1996

MethodsQuasi-randomised trial, allocation by day of the week
Blinding not mentioned
No loss to follow-up
ParticipantsAged ≥ 16 years, admitted with trauma to an emergency centre within 2 hours after injury, only crystalloid as a pre-hospital infusion
Excluded if had underlying illness likely to affect clotting
Interventions
  1. IV Haemaccel (n = 11)

  2. IV Ringer's lactate (n = 14)

Fluid was used until vital signs were stable

OutcomesDeaths from author
Clotting variables
NotesFollow-up period unspecified
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)High riskInadequate

Evans 2003

MethodsRCT, allocation concealment not reported
Blinding methods not reported
Loss to follow-up not reported
Participants55 patients undergoing primary unilateral total hip replacement
Exclusion criteria: pre-existing defect in platelet function or on aspirin that could not be stopped for 2 weeks prior to the operation
Interventions
  1. 4.5% Albumin (n = 13)

  2. Gelofusine (n = 14)

  3. Haemaccel (n = 14)

  4. 0.9% Saline (n = 14)

OutcomesHaemostatic parameters
Death not reported
NotesLength of follow-up not reported but all outcomes were in-hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Fries 2004

MethodsRCT, patients "randomly" received crystalloid or colloids
Method of allocation concealment not reported
Blinding not reported
Loss to follow-up not reported
Participants60 patients undergoing knee replacement surgery
Exclusion criteria: contraindication for regional anaesthesia, known allergies or haemostatic disorders
Interventions
  1. HES (n = 20)

  2. Modified gelatin (n = 20)

  3. Ringer's solution (n = 20)

Groups 1 and 2 also received a basis of Ringer's solution infusion

OutcomesCoagulation parameters
Death not reported
NotesLength of follow-up not reported but all outcomes were in-hospital measures
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Gallagher 1985

MethodsRCT, method of allocation concealment not described. Author contacted - allocation concealment by computerised system - patient details were entered before treatment assignment was revealed
Blinding not mentioned
No loss to follow-up
ParticipantsPatients after coronary artery bypass graft surgery
Exclusion criteria: patients with significant left main coronary artery stenosis, poor left ventricular function or poor pulmonary function
Interventions
  1. IV 5% albumin (n = 5)

  2. IV 6% HES (n = 5)

  3. IV Ringer's lactate (n = 5)

Fluid used from admission to ICU post operation, guided by PAWP. RBC given if needed

OutcomesDeaths were not reported. Author contacted and confirmed that there were no deaths in any group
Haemodynamic data
NotesFollow-up to 1 day
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskAdequate

Goodwin 1983

MethodsRCT, assigned by "random numbers table", method of allocation concealment unclear
Blinding not mentioned
No loss to follow-up
Participants79 previously healthy young adults admitted with burns
No exclusion criteria reported
Interventions
  1. 2.5% Albumin in Ringer's lactate (n = 40)

  2. Ringer's lactate (n = 39)

Fluids on day 1 guided by haemodynamic variable. On day 2, given at 0.3 to 0.5 mL/kg/%burn, then 5% dextrose

Outcomes

Deaths reported
Pulmonary oedema

Infections

NotesFollow-up to discharge from hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Grundmann 1982

MethodsRCT, method of allocation concealment unclear
Blinding not mentioned
No loss to follow-up
Participants20 people undergoing partial gastrectomy
The average age was 50 years (range 19 to 84 years)
No exclusion criteria reported
Interventions
  1. Colloid group received human albumin solution (n = 14)

  2. Details of crystalloid were not reported (n = 6)

Allocated fluid was continued for 4 days after operation

OutcomesDeaths reported
Volumes of fluid given
Haemodynamic variables
NotesFollow-up to discharge from hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Guo 2003

MethodsRCT, allocation concealment not reported
Blinding not reported
No loss to follow-up reported
Participants42 patients undergoing elective cytoreductive surgery for ovarian cancer
Exclusion criteria: preoperative anaemia, allergic response to HES or perioperative administration of cardiovascular agents
2 patients randomised but excluded because of use of cardiovascular agents
Interventions
  1. Ringer's lactate (n = 20)

  2. 6% HES (n = 20)

OutcomesSplanchnic perfusion
Death not reported but in results authors mentioned that "all patients were discharged"
NotesFollow-up to discharge from hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Hall 1978

MethodsQuasi-RCT (participants were stratified by age, extent of burn and aetiology, and then allocated by alternation)
Blinding not mentioned
No loss to follow-up
ParticipantsBurns covering > 10% of the body surface (for children), and > 15% of the body surface (for adults)
No exclusions mentioned
Interventions
  1. 120 mL/%burn IV 6% dextran 70 in 0.9% saline over 48 hours plus oral water or IV 5% dextrose for 'metabolic requirements' (n = 86)

  2. 4 mL/kg/%burn IV Ringer's lactate over 24 hours, then 10% of initial body weight of fluid over 24 hours plus oral water (n = 86)

OutcomesDeath
Fluid given, haemodynamic variables
NotesFollow-up to discharge from hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)High riskInadequate

Hartmann 1993

MethodsRCT, method of allocation unclear
Blinding not mentioned
No loss to follow-up
ParticipantsAdults undergoing major abdominal surgery
Exclusion criteria: cardiorespiratory dysfunction, uraemia, diabetes, taking steroids, anticoagulants or diuretics
Interventions
  1. IV Dextran 70 in saline (concentration not given) with 2.5% dextrose (n = 15)

  2. IV Saline (concentration not given) with 2.5% dextrose (n = 14)

Both groups given red cells, plasma, dextran 70 and crystalloids during the operation as decided by the clinician. Postoperative fluids according to the trial group guided by tissue oxygen tension to the end of resuscitation

OutcomesDeath not reported
Fluid given, haemodynamic variables
NotesFollow-up to 7 days
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

James 2011

Methods

RCT

Double-blind

ParticipantsPatients with blunt or penetrating trauma requiring more than 3 L volume resuscitation (blunt and penetrating trauma patients were randomised separately)
Interventions
  1. HES 130/0.4, penetrating trauma (n = 36)

  2. 0.9% Saline, penetrating trauma (n = 34)

  3. HES 130/0.4, blunt trauma (n = 22)

  4. 0.9% Saline, blunt trauma (n = 23)

OutcomesPrimary outcomes were the volumes of first fluid needed in the first 24 hours, and normal GI function by day 5
NotesAlthough mortality at 30 days was a safety measure, the authors did not report data on mortality for each group
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskPlastic bags with concealed label were randomly selected and placed sequentially in a warming cabinet

Jelenko 1978

MethodsRCT, method of allocation concealment unclear
Blinding not mentioned
No loss to follow-up
Participants19 people with burns covering more than 20% of body surface
Interventions
  1. 12.5% Albumin in hypertonic saline (240 mEq/L sodium, 120 mEq/L chloride, 120 mEq/L lactate) (n = 7)

  2. Hypertonic saline (240 mEq/L sodium, 120 mEq/L chloride, 120 mEq/L lactate) (n = 5)

  3. Ringer's lactate (n = 7)

Allocated fluid was used, guided by haemodynamic variables, to the end of resuscitation

OutcomesDeaths reported
Haemodynamic variables
NotesFollow-up to end of resuscitation
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Karanko 1987

MethodsRCT, description of allocation procedure unclear
Blinding not mentioned
No loss to follow-up
Participants32 adult men scheduled for coronary artery bypass surgery
Exclusion criteria: LVEF < 40%, abnormal lung function
Interventions
  1. 6% Dextran 70 (n = 14)

  2. Ringer's lactate (n = 18)

Allocated fluid was used to the end of resuscitation

OutcomesDeaths reported
Haemodynamic variables
Pulmonary oedema
NotesFollow-up 2 weeks
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Lang 2001

MethodsRCT, using a closed-envelope system
Participants42 patients scheduled for elective major abdominal surgery
Interventions
  1. Ringer's lactate (n = 21)

  2. 6% HES, molecular weight 139 kDa, degree of substitution 0.4 (n = 21)

OutcomesDeaths
Haemodynamics and laboratory data
Tissue oxygenation
Volume input and output
NotesFollow-up period unclear
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskAdequate

Lang 2003

MethodsRCT, allocation concealment not clearly reported ("closed envelope system")
Blinding method not reported ("...treatment in the ICU was performed by physicians who were blinded to the study")
Participants36 patients undergoing elective major abdominal surgery
Exclusion criteria: myocardial failure, renal insufficiency, severe pulmonary disease, liver dysfunction, diabetes mellitus, steroid therapy, pre-existing viral or bacterial infection and known allergic reactions to starch preparations
Interventions
  1. 6% HES (n = 18)

  2. Ringer's lactate (n = 18)

Additional crystalloid solutions were supplied to equalise insensible fluid loss or as a solvent for drugs in group 1

OutcomesPro- and anti-inflammatory cytokines
All patients survived
NotesLength of follow-up not reported but all outcomes were in-hospital measures
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Ley 1990

MethodsRCT, method of allocation concealment unclear
Assessment of chest x-ray blinded
No loss to follow-up
Participants21 people undergoing coronary artery bypass grafting or valve surgery
Interventions
  1. 6% Hetastarch up to 1.5 L then 5% plasma protein fraction (n = 11)

  2. 0.9% Saline (n = 10)

Allocated fluid was used for postoperative fluid resuscitation

OutcomesDeaths were not reported
Pulmonary and peripheral oedema
Haemodynamic variables
NotesFollow-up to discharge
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Lowe 1977

MethodsRCT, allocation by sealed envelopes
Blinding not mentioned
No loss to follow-up
ParticipantsParticipants with serious trauma
Interventions
  1. 25% Albumin in Ringer's lactate (n = 77)

  2. Ringer's lactate (n = 94)

Allocated fluid was used throughout the pre- and intraoperative period

OutcomesDeaths reported
NotesFollow-up to 5 days postoperatively. Data on the 30 participants with chest injuries who were left out of the Lowe 1977 report, but included in Moss 1981, have been included in the meta-analysis
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Lu 2012

MethodsRandomised controlled study
Participants42 patients with septic shock
Interventions
  1. Ringer's lactate (n = 20)

  2. HES 130/0.4 (n = 22)

OutcomesMortality, fluid replacement, use of vasoactive drugs and inflammatory markers
Notes-
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Lucas 1978

MethodsRCT, randomisation was based on the last digit of each patient's case number
Participants52 seriously injured patients
Interventions
  1. Standard resuscitation regimen ('balanced electrolyte', blood, fresh frozen plasma) plus salt-poor albumin, maximum 150 g during surgery and 150 g/day for the next 5 days (n = 27)

  2. Standard resuscitation regimen as above (n = 25)

OutcomesDeaths reported in some patients
NotesIn the final report of 94 randomised patients deaths were not reported. However, in this preliminary report of 52 injured patients deaths were reported
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)High riskInadequate

Maitland 2005

MethodsRCT, open label, random allocation was assigned by the use of sealed cards
No loss to follow-up
Participants159 children with severe malaria and metabolic acidosis
Exclusion criteria: pulmonary oedema, oedematous malnutrition or papilloedema
Interventions

Severe acidosis

  1. 4.5% Albumin (n = 23)

  2. 0.9% Saline (n = 26)

Moderate acidosis

  1. 4.5% Albumin (n = 33)

  2. 0.9% Saline (n = 35)

  3. Control (n = 33)

OutcomesReduction in base deficit
Neurological sequelae
Death reported
NotesLength of follow-up not reported but all outcomes were in-hospital measures
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Maitland 2011

Methods2 stratum multicentre open, RCT
ParticipantsChildren aged between 60 days and 12 years, with severe febrile illness, randomly assigned within 2 strata (stratum A was children with severe febrile illness and impaired perfusion but without severe hypotension; stratum B was children with severe hypotension)
Interventions

Children were randomly allocated to rapid volume replacement over the course of 1 hour with either:

  1. 20 mL 5% Human albumin solution per kg body weight (n = 1063)

  2. 20 mL 0.9% Saline solution per kg body weight (n = 1063)

OutcomesMortality at 4 weeks after randomisation
NotesChildren (n = 1044) assigned to no treatment were not included in the analysis
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskTrial numbers kept inside opaque, sealed envelopes. Opened in numerical order by clinician

Mattox 1991

MethodsQuasi-randomised, allocation by alternation
Double-blind
2 patients excluded from the analysis as code of fluid lost
ParticipantsParticipants were pre-hospital trauma victims attended to by emergency personnel within 1 hour of injury, with SBP ≤ 90 mmHg, ≥ 16 years. 72% of participants had sustained penetrating trauma
Interventions
  1. 250 mL Dextran 70 in 7.5% saline (n = 211)

  2. 250 mL Ringer's lactate, saline or plasmalyte (n = 211)

Allocated fluid was for initial pre-hospital resuscitation only

OutcomesDeaths reported
NotesFollow-up to hospital discharge or transfer
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)High riskInadequate

Mazher 1998

MethodsPatients "randomized"
Blinding of carers by use of pharmacy-prepared solutions
No loss to follow-up
ParticipantsPatients undergoing elective coronary artery surgery
Exclusion criteria: age > 75 years, ejection fraction < 35%, creatinine > 135 μmol/L, ACE inhibitors
Interventions
  1. 5 mL/kg Polygeline (n = 10)

  2. 5 mL/kg 7.2% Saline (n = 10)

Allocated fluid given postoperatively over 1 hour. All patients subsequently receive polygeline and RBCs

OutcomesHaemodynamic variables
Death
NotesFollow-up to discharge from ICU
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

McIntyre 2008

MethodsA feasibility RCT
ParticipantsPatients with early septic shock defined with at least 2 systemic inflammatory response syndrome criteria, infectious source and persistent hypotension after > 1 L of crystalloid fluid
Interventions
  1. Normal saline (n = 19)

  2. Pentastarch (n = 21)

OutcomesPrimary outcomes were feasibility measures for the pilot RCT. ICU and 28-day mortality were also reported
Notes-
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskOnly the designated research pharmacist at each institution was aware of the treatment allocation for individual patients. Study fluids were prepared and blinded ahead of time by the site research pharmacist

McNulty 1993

MethodsRCT, method of allocation concealment not described
Blinding not mentioned
No loss to follow-up
ParticipantsPatients following elective cardiopulmonary bypass
Interventions
  1. 5% Albumin and cell-saved blood (n = 14)

  2. Plasmalyte and cell-saved blood (n = 14)

Allocated fluid used as part of fluid volume replacement

OutcomesDeaths not reported
Study was designed to look at the effect of protein infusion on the accuracy of a haematocrit measuring device
NotesLength of follow-up unspecified
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Metildi 1984

MethodsRCT
Blinding not mentioned
No loss to follow-up
ParticipantsParticipants were admissions to an ICU and a trauma unit with ARDS and established pulmonary failure. Included both trauma and non-trauma patients
Interventions
  1. 5% Salt-poor albumin (n = 20)

  2. Ringer's lactate (n = 26)

Allocated fluid was used throughout resuscitation, and if an operation was required the allocated fluid was used for volume replacement before and during the operation

OutcomesDeaths reported
Haemodynamic variables
NotesFollow-up to discharge
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Modig 1983

MethodsQuasi-RCT, allocation by admission date
Blinding not mentioned
No loss to follow-up
ParticipantsParticipants were trauma admissions to an emergency department with SBP < 70 mmHg. Age range 20 to 58 years
Interventions
  1. Dextran 70 in Ringer's lactate (n = 12)

  2. Ringer's lactate (n = 11)

Allocated fluids were given as the initial resuscitation fluid on admission to the emergency department, and continued as needed until after the 6th day when major reconstructive surgery was undertaken

OutcomesDeaths reported
Development of ARDS
NotesFollow-up to definitive reconstructive surgery
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)High riskInadequate

Moretti 2003

MethodsRCT, allocation concealment method not clearly reported ("Patients randomized...by using a closed-envelope technique")
Blinding method not clearly reported ("Researchers were unaware of the patient's randomization")
No loss to follow-up
Participants90 adult patients undergoing major elective general, gynaecological, orthopaedic or urological surgery with an anticipated blood loss > 500 mL
Exclusion criteria: age < 16 years, coagulopathy, renal or hepatic dysfunction and congestive heart failure
Interventions
  1. Hetastarch-normal saline (n = 30)

  2. Hetastarch-balanced salt (n = 30)

  3. Ringer's lactate (n = 30)

OutcomesPostoperative nausea and vomiting
Death not reported
NotesFollow-up to discharge
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Nagy 1993

MethodsRCT, contact with author showed it was an open-label study
Blinding not mentioned
No loss to follow-up
ParticipantsParticipants were adult admissions to a trauma unit, with measurable SBP < 90 mmHg
Interventions
  1. Pentastarch in 0.9% saline (n = 21)

  2. Ringer's lactate (n = 20)

Allocated fluid was used throughout resuscitation with the exception that colloid patients received a maximum 4 L of pentastarch, after which Ringer's lactate was given

OutcomesDeaths were not reported
Haemodynamic variables
NotesFollow-up to discharge
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)High riskInadequate

Ngo 2001

MethodsRCT, opaque envelopes containing only treatment pack number
Participants230 children with dengue shock syndrome
Interventions
  1. Dextran 70 (n = 55)

  2. 3% Gelatin (n = 56)

  3. Ringer's lactate (n = 55)

  4. 'Normal' saline (n = 56)

OutcomesInitial pulse recovery time
Occurrence of timing and subsequent episodes of shock
Decrease in haematocrit
Volume of fluid administered until recovery
Complications
No deaths in any group
NotesFollow-up period unclear
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskAdequate

Nielsen 1985

MethodsRCT, method of allocation concealment not described
Blinding not mentioned
No loss to follow-up
Participants26 patients admitted for reconstructive surgery of the abdominal aorta
Interventions
  1. Whole blood, crystalloid plus 80 g albumin on the day of the operation, and 20 g/day for the next 3 days. Albumin given as 100 mL 20% human albumin solution (n = 13)

  2. Whole blood and crystalloid, type not specified (n = 13)

OutcomesDeaths not reported
Author when contacted confirmed that there were no deaths in either group
NotesLength of follow-up 4 days
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Pockaj 1994

MethodsRCT, allocation concealment unclear
Blinding not mentioned
Loss to follow-up: 18/54 in colloid group, 13/53 in saline group
ParticipantsParticipants required fluid resuscitation as a result of vascular leak syndrome associated with interleukin-2 therapy for metastatic cancer
Interventions
  1. 250 mL Bolus of 5% albumin in saline (n = 36 reported)

  2. 250 mL Bolus of 0.9% normal saline (n = 40 reported)

Boluses guided by haemodynamic variables. Both groups also received 0.45% saline with 10 mmol/L KCl

OutcomesDeaths
Toxic effects of chemotherapy
Haemodynamic variables
Notes-
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Prien 1990

MethodsRCT
Blinding not mentioned
No loss to follow-up
ParticipantsParticipants were undergoing modified Whipple's operation
Interventions
  1. 10% HES in 0.9% saline plus plasma protein fraction if requirements > 20 mL/kg (n = 6)

  2. 20% human albumin solution (n = 6)

  3. Ringer's lactate (n = 6)

Allocated fluid was administered intraoperatively only

OutcomesDeaths
Intestinal oedema formation
NotesFollow-up period was unspecified
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Rackow 1983

MethodsRCT, allocation concealment unclear
Blinding not mentioned
No loss to follow-up
ParticipantsParticipants were aged 54 to 97 years, and had any 1 of the following pre-determined indicators of shock: SBP ≤ 90 mmHg, cardiac index < 2.2 L/minute/m2, serum arterial lactate > 18 mg/dL and WP < 15 mmHg
Interventions
  1. 6% HES (n = 9)

  2. 5% Albumin (n = 9)

  3. 0.9% Saline (n = 8)

Allocated fluid was given as needed until the end of resuscitation

OutcomesDeaths reported
Fluid balance
NotesFollow-up to discharge from hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Rocha e Silva 1994

MethodsRCT
ParticipantsParticipants were admissions to the emergency department, with SBP ≤ 90 mmHg and ≥ 16 years of age
Interventions
  1. 6% Dextran 70 in 7.5% saline

  2. Ringer's lactate

Allocated fluid was used for the first IV infusion only

OutcomesDeath was the main outcome measure, but the data are unpublished
NotesFollow-up to 30 days. By April 1994, 125 patients had been entered into the study
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

SAFE 2004

MethodsRCT. Randomisation by minimisation algorithm accessed through secure website
ParticipantsPatients aged ≥ 18 years admitted to closed multidisciplinary ICUs in 16 tertiary hospitals in Australia over 19-month period
Interventions
  1. 4% Albumin (Albumex, CSL) (n = 3499)

  2. Normal saline (n = 3501)

OutcomesDeath
Patients with new single- or multiple-organ failure
Mean number of days: in ICU, in hospital, on mechanical ventilation, on renal replacement therapy
NotesFollow-up to 28 days
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskAdequate

Shah 1977

MethodsRCT, allocation by sealed envelope
Blinding not mentioned
No loss to follow-up
ParticipantsPatients with severe, multiple trauma and SBP < 90 mmHg. All patients were adults and both sexes were included
Interventions
  1. 5% Salt-poor albumin in Ringer's lactate (n = 9)

  2. Ringer's lactate (n = 11)

Volume infused guided by physiological parameters

OutcomesDeath reported
Haemodynamic variables
NotesLength of follow-up not stated
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Shires 1983

MethodsPatients 'assigned randomly'
Blinding not mentioned
No loss to follow-up
ParticipantsPeople undergoing aortic reconstruction surgery
No exclusion criteria mentioned
Interventions
  1. Plasmanate (n = 9)

  2. Ringer's lactate (n = 9)

Allocated fluid used guided by haemodynamic variables until the first postoperative morning. All patients then received 0.45% saline

OutcomesPulmonary oedema
Haemodynamic variables
Death
NotesFollow-up to 2 days postoperative
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Sirieix 1999

Methods

Patients "randomly assigned"

Blinding not described
2 patients excluded after randomisation due to arrhythmias on giving the fluid (both in hypertonic saline group)

ParticipantsPatients undergoing mitral valve repair
Exclusion criteria: LVEF < 0.4, systolic PAP > 50 mmHg, coagulation disorders, creatinine > 150 mmoL/L, electrolyte imbalance, diabetes, previous atrial fibrillation lasting > 1 year
Interventions
  1. 250 mL 7.2% Hypertonic saline, 6% HES (n = 8)

  2. 250 mL 7.2% Hypertonic saline (n = 10)

  3. 250 mL 6% HES (n = 8)

Fluid given over 15 minutes, 1 hour after admission to postoperative ICU

OutcomesHaemodynamic variables
Deaths reported
Side effects (severe hypotension: 1 patient in group 1 and 2 patients in group 2; arrhythmias: 1 patient in group 1, 3 patients in group 2 and 1 patient in group 3)
NotesFollow-up to discharge from hospital (all within 10 days)
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Skillman 1975

MethodsRCT, allocation concealment unclear
Blinding not mentioned
No loss to follow-up
ParticipantsParticipants were undergoing elective abdominal reconstructive surgery
Interventions
  1. 25% Salt-poor albumin 1 g/kg and 5% albumin 1 L (n = 7)

  2. Ringer's lactate

Allocated fluid was given intraoperatively. All patients received crystalloids only for pre-loading before surgery

OutcomesDeaths were not reported
Notes-
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Tollofsrud 1995

MethodsRCT, allocation by sealed envelopes
Blinding not mentioned
No loss to follow-up
ParticipantsParticipants were adults in need of volume replacement during and after coronary artery bypass surgery
Interventions
  1. Haemaccel (n = 10)

  2. Dextran 70 (n = 10)

  3. Albumin 40 (n = 10)

  4. Ringer's lactate (n = 10)

Allocated fluid was used throughout resuscitation

OutcomesDeaths reported
Fluid balance
NotesFollow-up to 48 hours
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Tollofsrud 1998

Methods

RCT, allocation by sealed envelope

Described as double blind

No loss to follow-up mentioned

Participants

Patients with 3 vessel coronary artery disease undergoing elective coronary artery surgery

Exclusion criteria: LVEF < 0.4, ventricular aneurysm, significant arrhythmia, diabetes, renal failure, lung disease

Interventions
  1. 4 mL/kg of 75 mg/mL hypertonic saline in dextran 70 60 mg/mL over 30 minutes (n = 10)

  2. Same volume and rate of isotonic saline (n = 10)

Fluid given just after surgery while still in operating theatre. Ringer's lactate for additional fluid

OutcomesFluid balance
Haemodynamic variables
Deaths not reported
NotesFollow-up to 48 hours
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Upadhyay 2004

MethodsOpen-label randomised trial, allocation by sealed envelope
No loss to follow-up mentioned
Participants60 patients with septic shock aged 1 month to 12 years
Exclusion criteria: age < 1 month, multiorgan failure and immunodeficiency states
Interventions
  1. Normal saline (n = 31)

  2. Polymer from degraded gelatin in saline (n = 29)

OutcomesHaemodynamic data
Death reported
NotesLength of follow-up not reported but all outcomes were in-hospital measures
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Vassar 1990

MethodsRCT, allocation concealment unclear
Double-blind study (solutions prepared in identical containers)
No loss to follow-up
ParticipantsParticipants were emergency department admissions with trauma and SBP < 80 mmHg and ≥ 18 years of age
Exclusion criteria: pregnant women and people with pre-existing cardiac, hepatic or renal disease
Interventions
  1. 6% Dextran 70 in 7.5% saline (n = 23)

  2. Ringer's lactate (n = 24)

Allocated fluids were given as the initial resuscitation in the emergency department. Additional isotonic crystalloids (Ringer's lactate) were given as needed

OutcomesDeaths reported
Haemodynamic variables
NotesFollow-up to hospital discharge
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Vassar 1991

MethodsRCT, allocation by randomised sequence of coded containers
Double-blind study
No loss to follow-up
ParticipantsParticipants were pre-hospital trauma cases undergoing helicopter transport to an emergency centre, with SBP ≤ 100 mmHg and ≥ 18 years
Exclusion criteria: pre-existing cardiac renal, hepatic or neurological disease; peripheral oedema
Interventions
  1. 4.2% Dextran 70 in 7.5% saline or 6% dextran 70 in 7.5% saline (n = 83)

  2. Ringer's lactate (n = 83)

Fluids were given as the initial resuscitation fluid in the pre-hospital setting. Supplemental isotonic fluids were given at the discretion of the flight nurses

OutcomesDeaths reported
Haemodynamic variables
NotesFollow-up to discharge. Allocation was to 4.2% dextran 70, to 6% dextran 70, or to crystalloid; for the calculation of the summary effect measure, the 2 dextran groups were combined
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskAdequate

Vassar 1993a

MethodsRCT, allocation concealed by random sequence of identical containers
Double-blind study
36 people excluded post randomisation as deemed not to have met eligibility criteria
No loss to follow-up
ParticipantsParticipants, who were undergoing ambulance transport to an emergency centre, SBP ≤ 90 mmHg, ≥ 18 years
Exclusion criteria: asystolic; undergoing CPR; lack sinus complex on ECG; > 2 hours after trauma; pregnant; pre-existing seizures; bleeding disorder; hepatic, cardiac or renal disease
Interventions
  1. 6% Dextran 70 in 7.5% saline (n = 89)

  2. 7.5% Saline (n = 85)

  3. 0.9% Saline (n = 84)

Participants received 250 mL of the allocated fluid in the pre-hospital setting. Additional isotonic crystalloids were given as needed

OutcomesDeaths reported
Haemodynamic variables
Trauma scores
NotesFollow-up was to discharge from hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskAdequate

Vassar 1993b

MethodsRCT, allocation concealed by sequential use of coded identical containers
Double-blind study
39/233 patients excluded as deemed not to meet eligibility criteria, unclear from which groups
ParticipantsParticipants were pre-hospital trauma cases undergoing helicopter transport to an emergency centre, SBP ≤ 100 mmHg, ≥ 18 years
Exclusion criteria: asystolic; undergoing CPR; lack sinus complex on ECG; > 2 hours after trauma; pregnant; pre-existing seizures; bleeding disorder; hepatic, cardiac or renal disease
Interventions
  1. 12% Dextran 70 in 7.5% saline (n = 49)

  2. 6% Dextran 70 in 7.5% saline (n = 50)

  3. 7.5% Saline (n = 50)

  4. Ringer's lactate (n = 45)

Participants received 250 mL of the allocated fluid in the pre-hospital setting. Additional isotonic crystalloids were given as needed

OutcomesDeaths reported
Haemodynamic variables
Trauma scores and neurological outcome scores
NotesFollow-up to hospital discharge
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskAdequate

Verheij 2006

MethodsRCT, allocation concealment by "the sealed envelope method"
Blinding method not reported
No loss to follow-up
Participants67 patients with presumed hypovolaemia after cardiac and major vascular surgery
Exclusion criteria: age > 79 years and known anaphylactoid reaction to colloids
Interventions
  1. Saline (n = 16)

  2. Gelatin (n = 16)

  3. HES (n = 16)

  4. Albumin (n = 16)

OutcomesHaemodynamic data
Death not reported
NotesLength of follow-up not reported but all outcomes were in-hospital measures
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Virgilio 1979

MethodsAllocation "by random number"
Blinding not mentioned
No loss to follow-up
ParticipantsParticipants were undergoing abdominal aortic surgery
Interventions
  1. 5% Albumin (n = 15)

  2. Ringer's lactate (n = 14)

Allocated fluid was used during operation for maintenance of pre-defined physiological parameters, and the resuscitation was continued with the allocated fluid until the day following the operation. This was followed by 5% dextrose in half-normal saline, with potassium chloride as needed

OutcomesDeaths reported
NotesFollow-up 2.5 weeks
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Wahba 1996

MethodsPatients "randomly allocated"
Blinding not mentioned
2 patients excluded as they required reoperation for bleeding
Participants22 adults in need of volume replacement following coronary artery bypass surgery
Exclusion criteria: abnormal left ventricular function, platelet active medication or heparin
Interventions
  1. Haemaccel (n = 10)

  2. Ringer's lactate (n = 10)

Allocated fluid was used from the time of admission to ICU following operation, to the end of resuscitation

OutcomesDeaths reported
Pulmonary oedema
NotesFollow-up to discharge
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Wills 2005

MethodsRCT, allocation concealed by specially prepared cardboard containers
Method of blinding not mentioned
No loss to follow-up
Participants512 children with dengue shock syndrome aged 2 to 15 years
Interventions

Children with immoderately severe shock were randomised to the 3 interventions

  1. Ringer's lactate (n = 128)

  2. 6% Dextran 70 (n = 126)

  3. 6% HES 200/0.5 (n = 129)

Children with severe shock were randomised only to either of the 2 colloids interventions:

  1. 6% Dextran 70 (n = 67)

  2. 6% HES 200/0.5 (n = 62)

OutcomesRequirement for supplemental intervention with rescue colloid
Time taken to achieve initial cardiovascular stability
Time taken to achieve sustained cardiovascular stability
Volume required
Change in haematocrit
Days in hospital
1 death reported but not specified in which group
NotesLength of follow-up not clear
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Low riskAdequate

Woittiez 1997

MethodsRCT, allocation concealment by sealed opaque envelopes
No information on blinding or loss to follow-up
Participants60 patients who had developed hypoalbuminaemia (< 20 g/L) after major surgery
2 patients died after randomisation and before treatment started. They were excluded from the analysis
Interventions
  1. Saline (500 mL/24 hours) (n = 16)

  2. 20% Albumin (300 mL/24 hours) (n = 15)

  3. 10% HES (500 mL/24 hours) for 3 days (n = 27)

Aim was to restore COP

OutcomesChanges in fluid balance, serum albumin, COP and clinical signs of oedema were followed daily
Death rates supplied by the author
NotesLength of follow-up unspecified
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Wu 2001

MethodsRCT. No details given of randomisation method
Participants41 adolescent or adult patients in emergency department suffering from shock
Interventions
  1. 4% Modified fluid gelatin: succinated gelatin 40 g/L, sodium chloride 7 g/L, sodium hydroxide 1.36 g/L (n = 18)

  2. Ringer's lactate (n = 16)

OutcomesDeath
Haemodynamic variables
NotesNot intention-to-treat: 5 patients who received blood transfusion and 2 who had surgery within the first hour of resuscitation were dropped from the analysis
Length of follow-up not clear
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Younes 1992

MethodsRandomised "in a double blind fashion"
Blinding by use of similar bottles
No loss to follow-up
ParticipantsParticipants were emergency department admissions, SBP < 80 mmHg, ≥ 19 years
Exclusion criteria: pregnant, pre-existing cardiac or metabolic disease
Interventions
  1. 6% Dextran 70 in 7.5% saline (n = 35)

  2. 7.5% Saline (n = 35)

  3. 0.9% Saline (n = 35)

Allocated fluid was for initial bolus of 250 mL, followed by isotonic crystalloids as needed

OutcomesDeaths reported
Fluid balance
NotesFollow-up to discharge from hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Younes 1994

MethodsTrial conducted in a "double blind randomised fashion"
Blinding by use of coded, identical containers
ParticipantsParticipants were trauma admissions to the emergency department requiring treatment for haemorrhagic hypovolaemia; all were over 15 years old
Exclusion criteria: pregnant, cardiac or renal failure, cardiac arrest on arrival
Interventions
  1. 6% Dextran 70 in 7.5% saline (n = 101)

  2. 0.9% Saline (n = 111)

Allocated fluid was for the first IV infusion only

OutcomesDeaths reported
Complications
NotesFollow-up period was 30 days
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Younes 1998

Methods

RCT, allocation by sealed envelope

Blinding not mentioned

No apparent loss to follow-up

ParticipantsTrauma patients SBP < 90 mmHg admitted to the emergency department, with no previous treatment
Interventions
  1. 10% Pentastarch (n = 12)

  2. 0.9% Saline (n = 11)

Fluid given in 250 mL boluses until systolic blood pressure > 100 mmHg

OutcomesDeaths reported
No complications reported in either group
NotesFollow-up to 24 hours
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Zetterstrom 1981a

MethodsThe patients were randomly divided into 2 groups
Allocation concealment was by sealed opaque envelopes (information supplied by study author)
Blinding not mentioned
No loss to follow-up
ParticipantsAdults undergoing elective major abdominal surgery
Interventions
  1. Standard volume replacement regimen (1 L dextran 70 then up to 4 units of RBC with electrolyte, then whole blood or RBC with plasma; postoperative patients were given crystalloids and whole blood) plus 20% human albumin solution 100 mL at end of operation, 200 mL to 300 mL on same day, then 200 mL on first postoperative day, then 100 mL for next 3 days (n = 15)

  2. Standard volume replacement regimen (as above) (n = 15)

OutcomesDeaths reported
Haemodynamic variables
NotesLength of follow-up unspecified
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Zetterstrom 1981b

MethodsPatients were randomly divided into 2 groups
Allocation concealment was by sealed opaque envelopes (information supplied by study author)
Blinding not mentioned
No loss to follow-up
Participants18 patients who had undergone elective abdominal aortic surgery
No exclusions mentioned
Interventions
  1. 5% Human albumin solution (n = 9)

  2. Ringer's lactate solution (n = 9)

Administration guided by pulmonary arterial occlusion pressure

OutcomesDeaths reported
Haemodynamic variables
NotesFollow-up to discharge from hospital
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Zhu 2011

  1. a

    ACE: angiotensin-converting enzyme; ARDS: adult respiratory distress syndrome; ASA: American Society of Anesthesiologists; bpm: beats per minute; COP: colloid osmotic pressure; CPR: cardiopulmonary resuscitation; GI: gastrointestinal; HES: hydroxyethyl starch; HR: heart rate; ICU: intensive care unit; IV: intravenous; LVEDP: left ventricular end diastolic pressure; LVEF: left ventricular ejection fraction; MODS: multiple organ dysfunction score; PAP: pulmonary artery pressure; PAWP: pulmonary artery wedge pressure; RBC: red blood cell; RCT: randomised controlled trial; SBP: systolic blood pressure; TBSA: total body surface area; WP: wedge pressure.

MethodsRCT
Participants135 participants with severe sepsis
Interventions
  1. 7.5% Hypertonic saline plus 6% HES 130/0.4 (n = 45)

  2. Ringer's lactate plus 6% HES 130/0.4 (n = 45)

  3. Ringer's lactate (n = 45)

OutcomesBiomarkers, fluid requirements, and MODS. Mortality was also reported
Notes-
Risk of bias
BiasAuthors' judgementSupport for judgement
Allocation concealment (selection bias)Unclear riskUnclear

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Artru 1989Intervention to control intracranial pressure not directed at fluid resuscitation
Bocanegra 1966Study contained 2 quasi-randomised comparisons of colloid with glucose and plasma/saline with saline. In both studies, the control solution was only given IV if the patient was in coma or shock. It was therefore not a reasonable comparison of colloid and crystalloid
Boldt 1996All groups received some colloid
Boldt 2007Comparison was not between colloids and crystalloids, rather 2 different colloid solutions
Bothner 1998Participants were having minor elective surgery, therefore not considered to be critically ill
Breheme 1993Intervention directed at haemodilution, not at volume replacement
Bueno R 2004The participants had elective surgery
Chin 2006Participants were undergoing elective surgery, therefore not considered to be critically ill
Golub 1994Albumin given solely as a nutritional supplement
Goslinga 1992Intervention directed at haemodilution, not volume replacement
Green 2008Article is a review
Greenhalgh 1995Intervention directed at the maintenance of serum albumin levels, not for volume replacement
Hauser 1980Cross-over trial
Ko 2007Comparison of crystalloids and colloids as pre-loading solutions
Krasheninnikov 2007Not an RCT
Lagonidis 1995Intervention was pre-loading for coronary artery bypass surgery
Lange 2011Article was a review
Lobo 2008Experiment conducted on rabbits
Marhofer 1999Trial of fluid for pre-loading before spinal anaesthesia
Mittermayr 2007Patients were undergoing elective surgery
Mittermayr 2008Outcome was the change in concentration of tissue-type plasminogen activator
Morrison 2011Study evaluated the effect of hypertonic saline in patients with blunt head injury
Niemi 2008Solutions were used for pump priming
Nilsson 1980Albumin given as a nutritional supplement
Oliviera 2002The participants had sepsis
Paton-Gay 2007The outcome was non-relevant to comparing crystalloids and colloids
Paul 2003The participants had elective surgery
Rehm 20012 colloids (albumin and hetastarch) compared
Steinberg 1989Cross-over trial
Tiryakioglu 2008Patients were undergoing elective surgery and not considered critically ill. Also, the solutions were used as priming solutions
Tseng 2008Crystalloid and colloid treatment was not randomised
Valetova 2007Patients were randomised depending upon their treatment not prior to treatment
van der Heijden 2009The report did not provide separate data for the 3 arms that received colloids (gelatin 4%, hydroxyethyl starch 6% and albumin 5%)
Vercueil 2006Article is a review
Wilkes 20011 group received saline plus hetastarch, the other received 'balanced' fluid plus hetastarch. Thus, each group received both a colloid and a crystalloid. This conflicts with the purpose our review, which compares patients who had 1 of these with patients who had the other
Woods 1993This quasi-randomised trial looked at albumin supplementation in postoperative patients, with the aim of maintaining the serum albumin. Since the main aim of giving albumin was not to replace volume, the study was excluded

Characteristics of ongoing studies [ordered by study ID]

CHEST Trial

Trial name or titleCrystalloid Versus Hydroxyethyl Starch Trials (CHEST)
MethodsMulticentre phase 3 RCT of fluid resuscitation
Participants7000 patients in ICU requiring fluid resuscitation
Interventions
  1. 6% HES (130/0.4)

  2. Saline

Outcomes90 days all-cause mortality
Starting dateDecember 2009
Contact informationJohn A Myburgh, The George Institute, Sydney, New South Wales, Australia
NotesNCT00935168

RASP trial

Trial name or titleLactated Ringer Versus Albumin in Early Sepsis Therapy (RASP)
MethodsRCT
Participants360 patients with severe sepsis or septic shock
Interventions
  1. Ringer's lactate

  2. 4% Albumin

Outcomes28 days all-cause mortality
Starting dateMay 2012
Contact informationJuliano P Almeida, Cancer Institute of Sao Paulo, School of Medicine, University of Sao Paulo
NotesNCT01337934

The 6S trial

  1. a

    HES: hydroxyethyl starch; ICU: intensive care unit; RCT: randomised controlled trial.

Trial name or titleScandinavian Starch for Severe Sepsis/Septic Shock Trial (6S)
MethodsMulticentre, randomised, double-blinded trial with concealed allocation
Participants800 patients with severe sepsis in 30 Scandinavian ICUs
Interventions
  1. 6% HES 130/0.4 in Ringer's acetate

  2. Ringer's acetate

OutcomesThe composite end point of 90-day mortality or end-stage kidney failure is the primary outcome measure
Starting dateDecember 2009
Contact informationAnders Perner, ICU, Rigshospitalet, University of Copenhagen
NotesNCT00962156

Ancillary