Colloids versus crystalloids for fluid resuscitation in critically ill people

Sharon R Lewis; Michael W Pritchard; David JW Evans; Andrew R Butler; Phil Alderson; Andrew F Smith; Ian Roberts

doi:10.1002/14651858.CD000567.pub7

. 2018 Aug 3;2018(8):CD000567. doi: 10.1002/14651858.CD000567.pub7

Colloids versus crystalloids for fluid resuscitation in critically ill people

Sharon R Lewis ^1,^✉, Michael W Pritchard ¹, David JW Evans ², Andrew R Butler ³, Phil Alderson ⁴, Andrew F Smith ³, Ian Roberts ⁵

Editor: Cochrane Injuries Group

PMCID: PMC6513027 PMID: 30073665

Abstract

Background

Critically ill people may lose fluid because of serious conditions, infections (e.g. sepsis), trauma, or burns, and need additional fluids urgently to prevent dehydration or kidney failure. Colloid or crystalloid solutions may be used for this purpose. Crystalloids have small molecules, are cheap, easy to use, and provide immediate fluid resuscitation, but may increase oedema. Colloids have larger molecules, cost more, and may provide swifter volume expansion in the intravascular space, but may induce allergic reactions, blood clotting disorders, and kidney failure. This is an update of a Cochrane Review last published in 2013.

Objectives

To assess the effect of using colloids versus crystalloids in critically ill people requiring fluid volume replacement on mortality, need for blood transfusion or renal replacement therapy (RRT), and adverse events (specifically: allergic reactions, itching, rashes).

Search methods

We searched CENTRAL, MEDLINE, Embase and two other databases on 23 February 2018. We also searched clinical trials registers.

Selection criteria

We included randomised controlled trials (RCTs) and quasi‐RCTs of critically ill people who required fluid volume replacement in hospital or emergency out‐of‐hospital settings. Participants had trauma, burns, or medical conditions such as sepsis. We excluded neonates, elective surgery and caesarean section. We compared a colloid (suspended in any crystalloid solution) versus a crystalloid (isotonic or hypertonic).

Data collection and analysis

Independently, two review authors assessed studies for inclusion, extracted data, assessed risk of bias, and synthesised findings. We assessed the certainty of evidence with GRADE.

Main results

We included 69 studies (65 RCTs, 4 quasi‐RCTs) with 30,020 participants. Twenty‐eight studied starch solutions, 20 dextrans, seven gelatins, and 22 albumin or fresh frozen plasma (FFP); each type of colloid was compared to crystalloids.

Participants had a range of conditions typical of critical illness. Ten studies were in out‐of‐hospital settings. We noted risk of selection bias in some studies, and, as most studies were not prospectively registered, risk of selective outcome reporting. Fourteen studies included participants in the crystalloid group who received or may have received colloids, which might have influenced results.

We compared four types of colloid (i.e. starches; dextrans; gelatins; and albumin or FFP) versus crystalloids.

Starches versus crystalloids

We found moderate‐certainty evidence that there is probably little or no difference between using starches or crystalloids in mortality at: end of follow‐up (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.86 to 1.09; 11,177 participants; 24 studies); within 90 days (RR 1.01, 95% CI 0.90 to 1.14; 10,415 participants; 15 studies); or within 30 days (RR 0.99, 95% CI 0.90 to 1.09; 10,135 participants; 11 studies).

We found moderate‐certainty evidence that starches probably slightly increase the need for blood transfusion (RR 1.19, 95% CI 1.02 to 1.39; 1917 participants; 8 studies), and RRT (RR 1.30, 95% CI 1.14 to 1.48; 8527 participants; 9 studies). Very low‐certainty evidence means we are uncertain whether either fluid affected adverse events: we found little or no difference in allergic reactions (RR 2.59, 95% CI 0.27 to 24.91; 7757 participants; 3 studies), fewer incidences of itching with crystalloids (RR 1.38, 95% CI 1.05 to 1.82; 6946 participants; 2 studies), and fewer incidences of rashes with crystalloids (RR 1.61, 95% CI 0.90 to 2.89; 7007 participants; 2 studies).

Dextrans versus crystalloids

We found moderate‐certainty evidence that there is probably little or no difference between using dextrans or crystalloids in mortality at: end of follow‐up (RR 0.99, 95% CI 0.88 to 1.11; 4736 participants; 19 studies); or within 90 days or 30 days (RR 0.99, 95% CI 0.87 to 1.12; 3353 participants; 10 studies). We are uncertain whether dextrans or crystalloids reduce the need for blood transfusion, as we found little or no difference in blood transfusions (RR 0.92, 95% CI 0.77 to 1.10; 1272 participants, 3 studies; very low‐certainty evidence). We found little or no difference in allergic reactions (RR 6.00, 95% CI 0.25 to 144.93; 739 participants; 4 studies; very low‐certainty evidence). No studies measured RRT.

Gelatins versus crystalloids

We found low‐certainty evidence that there may be little or no difference between gelatins or crystalloids in mortality: at end of follow‐up (RR 0.89, 95% CI 0.74 to 1.08; 1698 participants; 6 studies); within 90 days (RR 0.89, 95% CI 0.73 to 1.09; 1388 participants; 1 study); or within 30 days (RR 0.92, 95% CI 0.74 to 1.16; 1388 participants; 1 study). Evidence for blood transfusion was very low certainty (3 studies), with a low event rate or data not reported by intervention. Data for RRT were not reported separately for gelatins (1 study). We found little or no difference between groups in allergic reactions (very low‐certainty evidence).

Albumin or FFP versus crystalloids

We found moderate‐certainty evidence that there is probably little or no difference between using albumin or FFP or using crystalloids in mortality at: end of follow‐up (RR 0.98, 95% CI 0.92 to 1.06; 13,047 participants; 20 studies); within 90 days (RR 0.98, 95% CI 0.92 to 1.04; 12,492 participants; 10 studies); or within 30 days (RR 0.99, 95% CI 0.93 to 1.06; 12,506 participants; 10 studies). We are uncertain whether either fluid type reduces need for blood transfusion (RR 1.31, 95% CI 0.95 to 1.80; 290 participants; 3 studies; very low‐certainty evidence). Using albumin or FFP versus crystalloids may make little or no difference to the need for RRT (RR 1.11, 95% CI 0.96 to 1.27; 3028 participants; 2 studies; very low‐certainty evidence), or in allergic reactions (RR 0.75, 95% CI 0.17 to 3.33; 2097 participants, 1 study; very low‐certainty evidence).

Authors' conclusions

Using starches, dextrans, albumin or FFP (moderate‐certainty evidence), or gelatins (low‐certainty evidence), versus crystalloids probably makes little or no difference to mortality. Starches probably slightly increase the need for blood transfusion and RRT (moderate‐certainty evidence), and albumin or FFP may make little or no difference to the need for renal replacement therapy (low‐certainty evidence). Evidence for blood transfusions for dextrans, and albumin or FFP, is uncertain. Similarly, evidence for adverse events is uncertain. Certainty of evidence may improve with inclusion of three ongoing studies and seven studies awaiting classification, in future updates.

Plain language summary

Colloids or crystalloids for fluid replacement in critically people

Background

Critically ill people may lose large amounts of blood (because of trauma or burns), or have serious conditions or infections (e.g. sepsis); they require additional fluids urgently to prevent dehydration or kidney failure. Colloids and crystalloids are types of fluids that are used for fluid replacement, often intravenously (via a tube straight into the blood).

Crystalloids are low‐cost salt solutions (e.g. saline) with small molecules, which can move around easily when injected into the body.

Colloids can be man‐made (e.g. starches, dextrans, or gelatins), or naturally occurring (e.g. albumin or fresh frozen plasma (FFP)), and have bigger molecules, so stay in the blood for longer before passing to other parts of the body. Colloids are more expensive than crystalloids. We are uncertain whether they are better than crystalloids at reducing death, need for blood transfusion or need for renal replacement therapy (filtering the blood, with or without dialysis machines, if kidneys fail) when given to critically ill people who need fluid replacement.

Study characteristics

The evidence is current to February 2018. We searched the medical literature and identified 69 relevant studies with 30,020 critically ill participants who were given fluid replacement in hospital or in an emergency out‐of‐hospital setting. Studies compared colloids (starches; dextrans; gelatins; or albumin or FFP) with crystalloids.

Key results

We found moderate‐certainty evidence that using colloids (starches; dextrans; or albumin or FFP) compared to crystalloids for fluid replacement probably makes little or no difference to the number of critically ill people who die within 30 or 90 days, or by the end of study follow‐up. We also found low‐certainty evidence that using gelatins or crystalloids may make little or no difference to the number of deaths within each of these time points.

We found moderate‐certainty evidence that using starches probably slightly increases the need for blood transfusion. However, we are uncertain whether using other types of colloids, compared to crystalloids, makes a difference to whether people need a blood transfusion because the certainty of the evidence is very low.

We found moderate‐certainty evidence that using starches for fluid replacement probably slightly increases the need for renal replacement therapy. Using albumin or FFP compared to crystalloids may make little or no difference to the need for renal replacement therapy. One study comparing gelatins did not report results for renal replacement therapy according to the type of fluid given, and no studies comparing dextrans assessed renal replacement therapy.

Few studies reported adverse events (specifically, allergic reactions, itching, or rashes), so we are uncertain whether either fluid type causes fewer adverse events (very low‐certainty evidence). We found little or no difference between starches or crystalloids in allergic reactions, but fewer participants given crystalloids reported itching or rashes. We found little or no difference in allergic reactions for the use of dextrans (four studies), gelatins (one study), and albumin or FFP (one study).

Certainty of the evidence

Some study authors did not report study methods clearly and many did not register their studies before they started, so we could not be certain whether the study outcomes were decided before or after they saw the results. Also, we found that some people who were given crystalloids may also have had colloids, which might have affected the results. For some outcomes, we had very few studies, which reduced our confidence in the evidence.

Conclusions

Using colloids (starches; dextrans; or albumin or FFP) compared to crystalloids for fluid replacement probably makes little or no difference to the number of critically ill people who die. It may make little or no difference to the number of people who die if gelatins or crystalloids are used for fluid replacement.

Starches probably increase the need for blood transfusion and renal replacement therapy slightly. Using albumin or FFP may make little or no difference to the need for renal replacement therapy. We are uncertain whether using dextrans, albumin or FFP, or crystalloids affects the need for blood transfusion. Similarly, we are uncertain if colloids or crystalloids increase the number of adverse events. Results from ongoing studies may increase our confidence in the evidence in future.

Summary of findings

Background

Description of the condition

Critically ill people may experience excessive fluid loss, and hypovolaemia, because of haemorrhage from serious injury or burns, or because of critical illnesses, which lead to dehydration, vomiting, or diarrhoea. Fluid loss may lead to mortality and morbidity, for example, haemorrhage accounts for almost half of deaths in the first 24 hours after traumatic injury (Geeraedts 2009; Kauvar 2006), and, worldwide, traumatic injury is a leading cause of death (Peden 2002). Changes in body fluid balance may also lead to acute kidney injury or failure.

Description of the intervention

Fluid resuscitation is one of the most important strategies for early management of critically ill people (Rhodes 2016; Rossaint 2016). Fluids used for this purpose are crystalloids or colloids.

Crystalloids, such as saline and Ringer's lactate, are solutions of salt, water and minerals, and are commonly used in the clinical setting. They have small molecules, and, when used intravenously, they are effective as volume expanders. They may have an isotonic or hypertonic composition, which could affect the distribution of fluid in the body; for example, because hypertonic crystalloids lower plasma osmolality they cause water movement from the intravascular to the extravascular space, and a lower volume may be required for fluid resuscitation (Coppola 2014). They are cheap and easy to use, with few side effects. However, because they move more easily into the extravascular space, their use may increase oedema (Coppola 2014). The composition of the crystalloid may not affect clinical outcomes; recent reviews have examined the possible effect of hypertonic solutions (Shrum 2016), and compared buffered with non‐buffered fluids (Bampoe 2017), but have not found important clinical differences.

Colloids, which are suspended in crystalloid solutions, are similarly given for the purpose of volume expansion. Different types of colloids may be grouped as synthetic or semi‐synthetic, for example: starches, dextrans, gelatins; or naturally occurring, such as human albumin or fresh frozen plasma (FFP). These colloid solutions have different pharmacokinetic properties that may affect plasma expansion in different ways (Orbegozo 2015). All colloids have a larger molecular weight than crystalloids and do not cross the endothelium into the interstitial fluid easily. This means that they stay in the intervascular space for longer than crystalloids, provide the benefit of rapid plasma expansion, and can correct colloidal osmotic pressure (McClelland 1998). Colloids are a more expensive fluid replacement option, and they may have adverse effects such as allergic reactions, blood clotting disorders, and kidney failure (Bailey 2010).

Why it is important to do this review

This is an update of a Cochrane Review that was first published in 1997 and has been updated several times since. The most recent published version of this Cochrane Review looked at the effect of colloids and crystalloids on mortality at the end of study follow‐up (Perel 2013). Meta‐analysis demonstrated no evidence of a difference in mortality when participants were given dextrans, gelatins, albumin or FFP, versus crystalloids. However, the review found evidence of an increase in mortality with the use of starches. Whilst some advise against using starches as a first line of resuscitation (Reinhart 2012), this is not consistent with findings from large randomised trials (Myburgh 2012; Perner 2012), nor with some other systematic reviews (He 2015; Qureshi 2016).

It is possible that results from Perel 2013 could have been confounded by the inclusion of a wider variety of participants in need of fluid resuscitation. In this review, we have sought to reduce heterogeneity in a critically ill population as much as possible by excluding participants who were scheduled for elective surgery; whilst these participants may require fluid replacement during perioperative management to reduce the risk of hypovolaemia, they are less likely to be critically ill at the point of randomisation ‐ even elderly people undergoing semi‐urgent surgery can seldom be seen as critically ill (Lewis 2016).

Also, our aim was to explore other effects of colloids or crystalloids on resuscitation. In particular we aimed to consider whether colloids or crystalloids affect the number of people who require blood transfusion, and the effect on renal function by assessing whether more or fewer critically ill people are likely to need renal replacement therapy after fluid resuscitation interventions, because evidence suggests that use of some types of fluids may increase these risks (Zarychanski 2013). In addition, we considered the effect of type of fluids on adverse events (allergic reactions, itching or pruritis, and rashes) that have been reported in trials (e.g. in Myburgh 2012).

Objectives

To assess the effect of using colloids versus crystalloids in critically ill people requiring fluid volume replacement on mortality, need for blood transfusion or renal replacement therapy, and adverse events (specifically: allergic reactions, itching, rashes).

Methods

Criteria for considering studies for this review

Types of studies

We included parallel‐design randomised controlled trials (RCTs), and quasi‐randomised studies (e.g. studies in which the method of assignment is based on alternation, date of birth or medical record number). We excluded randomised cross‐over trials. We excluded study reports that had been retracted after publication.

Types of participants

We included participants who required fluid volume replacement in hospital or in an emergency out‐of‐hospital setting. We included participants who were described as critically ill, and participants who required fluid volume replacement as a result of trauma, burns, or medical conditions such as sepsis.

We excluded studies of participants undergoing elective surgical procedures. We excluded neonates, and women undergoing caesarean section.

See Differences between protocol and review.

Types of interventions

We included studies that compared a colloid (suspended in any crystalloid solution) versus a crystalloid. We excluded studies in which a colloid was given in both groups of participants.

We included the following colloids: starches; dextrans; gelatins; albumin or fresh frozen plasma (FFP). We included crystalloids of different electrolyte compositions (isotonic or hypertonic).

We considered each colloid type as a separate comparison group. Therefore, we compared:

starches versus crystalloids;
dextrans versus crystalloids;
gelatins versus crystalloids;
albumin or FFP versus crystalloids.

We excluded studies in which the colloid was given to replace a known nutritional deficiency (for example, given for hypoalbuminaemia), or was given as a preloading solution before surgery. We excluded studies in which fluids were given to people with head injury to control intracranial pressure.

See Differences between protocol and review.

Types of outcome measures

We did not exclude studies that did not measure or report review outcomes.

We collected outcome data for mortality from any cause at end‐of‐study follow‐up; we included data for this outcome for which the time point was not reported, and for which the time point was reported as 'before hospital discharge', 'within the ICU', or within 30 days, 60 days, or 90 days. In addition, we collected mortality data that were clearly reported within 90 days, or within 30 days. Our secondary outcomes assessed the effectiveness of the resuscitation fluids and included need for transfusion of any blood product, and need for renal replacement therapy. In addition, we collected data for outcomes of adverse events, specifically: allergic reactions, itching/pruritis, and rashes.

Primary outcomes

All‐cause mortality (at end of follow‐up)
All‐cause mortality (within 90 days)
All‐cause mortality (within 30 days)

Secondary outcomes

Transfusion of blood products
Renal replacement therapy
Adverse events (allergic reactions, itching, and rashes)

Search methods for identification of studies

Electronic searches

We developed subject‐specific search strategies in consultation with the Cochrane Injuries Group Information Specialist. We identified RCTs through literature searching of the following electronic databases:

Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2) (which contains the Cochrane Injuries Trials Register) in the Cochrane Library (searched 23 February 2018) (Appendix 1);
MEDLINE Ovid (1946 to 23 February 2018) (Appendix 2);
Embase Ovid (1974 to 23 February 2018) (Appendix 3);
PubMed (1948 to 23 February 2018) (Appendix 4);
Web of Science (Core Collection, 1970 to 23 February 2018) (Appendix 5);
US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov; searched 13 April 2018) (Appendix 6);
World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp; searched 13 April 2018) (Appendix 7)
OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu; searched 12 April 2018) (Appendix 8).

This review was an update of a previous Cochrane Review (Perel 2013). However, because we made changes to the inclusion criteria and increased the outcome measures, we ran all the searches from database inception.

Searching other resources

We conducted citation searching of identified included studies published from 2013 onwards in Web of Science (apps.webofknowledge.com) (12 April 2018). We scanned reference lists of relevant systematic reviews (identified during database searches) to search for additional trials.

Data collection and analysis

Two review authors (Sharon Lewis (SL) and either: Michael Pritchard (MP), Andrew Butler (AB), or David Evans (DE)) independently completed all data collection and analyses before comparing results and reaching consensus. We consulted a third review author (Andrew Smith (AS)) to resolve conflicts if necessary.

Selection of studies

We used Endnote reference management software to collate the results of the searches and to remove duplicates. We used Covidence software to screen titles and abstracts and identify potentially relevant studies. We sourced the full texts of all potentially relevant studies and assessed whether the studies met the review inclusion criteria (see Criteria for considering studies for this review). We reviewed abstracts at this stage and included these in the review only if they provided sufficient information to assess eligibility.

We reassessed eligibility of studies included in the last version of the review (Perel 2013), because of changes made to review inclusion criteria.

We recorded the number of papers retrieved at each stage and reported this in a PRISMA flow chart (Liberati 2009; Figure 1). We reported in the review brief details of closely related but excluded papers.

Data extraction and management

We used Covidence software to extract data from individual studies. A basic template for data extraction forms is available at www.covidence.org. We adapted this template to include the following information.

Methods ‐ type of study design; setting; country; dates of study; funding sources
Participants ‐ number of participants randomised to each group, number of lost participants, and number of analysed participants, participant condition or reason for fluid resuscitation. Baseline characteristics to include: age, gender, weight or body mass index, blood pressure, prognostic or illness severity scores (American Society of Anaesthesiologists (ASA), Acute Physiology and Chronic Health Evaluation (APACHE) I or II, Simplified Acute Physiology Score (SAPS), Sequential Organ Failure Assessment (SOFA), Glasgow Coma Scale (GCS))
Interventions ‐ details of colloid and crystalloid (concentration of solution, volume, and rate of administration), additional relevant patient management
Outcomes ‐ all outcomes reported by study authors, relevant outcomes (including time of measurement for mortality)
Outcome data ‐ results of outcome data

Because of changes in reporting expectations in Cochrane Reviews ‐ the Methodological Expectations of Cochrane Intervention Reviews (MECIR) (Higgins 2016) ‐ since the last version of the review (Perel 2013), we also used Covidence to re‐conduct data extraction on studies included in the last version of the review.

We considered the applicability of information from individual studies and the generalisability of data to our intended study population (i.e. the potential for indirectness in the review). If we found associated publications from the same study, we created a composite data set based on all eligible publications.

Assessment of risk of bias in included studies

Two review authors (SL and MP, AB, or DE) independently assessed study quality, study limitations, and the extent of potential bias using the Cochrane 'Risk of bias' tool (Higgins 2017). We completed 'Risk of bias' assessment only for studies that reported the review outcomes.

We assessed the following domains.

Sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of participants, personnel, and outcome assessors (performance bias and detection bias)
Incomplete outcome data (attrition bias)
Selective outcome reporting (reporting bias)
Baseline characteristics
Other bias

We made separate judgements for performance and detection bias for mortality and for blood transfusion/renal replacement therapy/adverse events.

For each domain, we judged whether study authors had made sufficient attempts to minimise bias in their study design. We made judgements using three measures, high, low and unclear risk of bias. We recorded this decision in 'Risk of bias' tables and present a 'Risk of bias' graph and summary figure (Figure 2; Figure 3).

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. We did not make judgements for studies that did not report outcomes of interest in the review, which are indicated by blank spaces

Risk of bias summary: review authors' judgements about each risk of bias item for each included study. We did not make judgements for studies that did not report outcomes of interest in the review, which are indicated by blank spaces

Because of changes in reporting expectations in Cochrane Reviews (MECIR; Higgins 2016) since the last version of the review, we also completed a 'Risk of bias' assessment on all studies included in Perel 2013.

Measures of treatment effect

We collected dichotomous data for each outcome measure (the number of participants who had died, the number of participants who required transfusion of blood products, the number of participants who required renal replacement therapy, and the number of participants who had adverse events).

Unit of analysis issues

We reported data separately according to type of colloid (starches; dextrans; gelatins; albumin or FFP).

For multi‐arm studies that included more than one of the same type of study fluid (e.g. two groups of starches combined with an isotonic or a hypertonic crystalloid), we combined data from study groups in the same analysis only when it was appropriate and when it did not include double‐counting of participants.

In subgroup analysis, in which studies were grouped by different types of crystalloid solution, it was not always appropriate to combine data from multi‐arm study groups. If we had included multi‐arm studies in subgroup analysis, we planned to use the halving method to avoid unit of analysis issues (Deeks 2017).

Dealing with missing data

We assessed whether all measured outcomes had been reported by study authors by comparing, when possible, published reports with protocols or clinical trials register documents that had been prospectively published.

We assessed whether all randomised participants had been included in outcome data. In the absence of an explanation for loss of data, we used the 'Risk of bias' tool to judge whether a study was at high risk of attrition bias.

Assessment of heterogeneity

We assessed whether evidence of inconsistency was apparent in our results by considering heterogeneity. We assessed clinical and methodological heterogeneity by comparing similarities in our included studies between study designs, participants, and interventions, using data collected during data extraction (Data extraction and management). We assessed statistical heterogeneity by calculating the Chi² test and I² statistic (Higgins 2003), and judged any heterogeneity using values of I² greater than 60% and Chi² P value of 0.05 or less to indicate moderate to substantial statistical heterogeneity (Deeks 2017).

As well as looking at statistical results, we considered point estimates and overlap of confidence intervals (CIs). If CIs overlap, then results are more consistent. Combined studies may show a large consistent effect but with significant heterogeneity. Therefore, we planned to interpret heterogeneity with caution (Guyatt 2011a).

Assessment of reporting biases

We attempted to source published protocols for each of our included studies by using clinical trials registers. We compared protocols or clinical trials register documents that had been prospectively published with study results to assess the risk of selective reporting. We generated a funnel plot to assess risk of publication bias in the review, for outcomes in which we identified more than 10 studies (Sterne 2017). An asymmetrical funnel plot may suggest publication of only positive results (Egger 1997). We included funnel plot figures for the primary outcome: all‐cause mortality (at the end of follow‐up) (Figure 4; Figure 5; Figure 6).

Funnel plot of comparison 1. Starches vs crystalloid, outcome: 1.1 mortality at end of follow‐up

Funnel plot of comparison 2. Dextrans vs crystalloid, outcome: 2.1 mortality at end of follow‐up

Funnel plot of comparison 4. Albumin and FFP vs crystalloid, outcome: 4.1 mortality at end of follow‐up

Data synthesis

We completed meta‐analysis of outcomes in which we had comparable effect measures for more than one study, and when measures of clinical and methodological heterogeneity indicated that pooling was appropriate.

We presented results according to type of colloid (starches; dextrans; gelatins; albumin or FFP) as four separate comparisons (see Types of interventions).

We used the statistical calculator in Review Manager 5 (RevMan 5) to calculate risk ratios (RR) using the Mantel‐Haenszel model (Review Manager 2014). We used a random‐effects statistical model that accounted for the variation amongst participant groups in the review. We calculated CIs at 95% and used a P value of 0.05 or less to judge whether a result was statistically significant. We considered imprecision in the results of analyses by assessing the CI around an effect measure; a wide CI would suggest a higher level of imprecision in our results. A small number of identified studies may also reduce precision (Guyatt 2011b).

Subgroup analysis and investigation of heterogeneity

We explored potential differences in the tonicity of crystalloid solutions that had been used with colloids or used as the comparative crystalloid. This was an a priori subgroup analysis included in the previous version of the review (Perel 2013). We used the calculator in RevMan 5 to perform subgroup analysis, comparing the Chi² and P value for the test for subgroup differences; we interpreted a P value of less than 0.05 as being indicative of a difference between subgroups. We conducted subgroup analysis when data were available for more than 10 studies (Deeks 2017). We considered subgroup analysis only for the primary outcome (all‐cause mortality (at end of follow‐up)) for each of our comparisons (starches; dextrans; gelatins; albumin or FFP). Subgroups were as follows.

Tonicity of crystalloid solution:
- colloid + isotonic crystalloid versus isotonic crystalloid;
- colloid + hypertonic crystalloid versus isotonic crystalloid;
- colloid + isotonic crystalloid versus hypertonic crystalloid;
- colloid + hypertonic crystalloid versus hypertonic crystalloid.

Sensitivity analysis

We explored the potential effects of decisions made as part of the review process as follows.

We excluded all studies that we judged to be at high or unclear risk of selection bias.
We excluded studies in which we noted that some participants in the crystalloid group were given, or may have been given, additional colloids.
We conducted meta‐analysis using the alternative meta‐analytical effects model (fixed‐effect).
We used alternative data for individual studies in which we noted discrepancies in reported data.

We conducted sensitivity analysis on the primary outcome: all‐cause mortality (at end of follow‐up).

'Summary of findings' table and GRADE

We used the GRADE system to assess the certainty of the body of evidence associated with the following outcomes (Guyatt 2008).

All‐cause mortality (at end of follow‐up)
All‐cause mortality (within 90 days)
All‐cause mortality (within 30 days)
Transfusion of blood products
Renal replacement therapy
Adverse events (allergic reactions, itching, rashes)

The GRADE approach appraises the certainty of a body of evidence based on the extent to which one can be confident that an estimate of effect or association reflects the item being assessed. Evaluation of the certainty of a body of evidence considers within‐study risk of bias, directness of the evidence, heterogeneity of the data, precision of effect estimates, and risk of publication bias.

We constructed four 'Summary of findings' tables using the GRADEpro GDT software to create 'Summary of findings' tables for the following comparisons in this review (GRADEpro GDT 2015).

Starches versus crystalloids
Dextrans versus crystalloids
Gelatins versus crystalloids
Albumin or FFP versus crystalloids

One review author (SL) completed the table in consultation with a second author (MP).

Results

Description of studies

Results of the search

We screened 7920 titles and abstracts from database searches, forward and backward citation searches, and clinical trials register searches. We assessed 248 full‐text reports for eligibility. See Figure 1.

Included studies

See Characteristics of included studies.

We included 69 studies; 42 of these had been included in the previous version of the review (Perel 2013), and 27 were included for the first time in this update.

These 69 studies comprised a total of 114 publications, and included 30,020 participants (Alpar 2004; Annane 2013; Baker 2009; Bechir 2013; Bentsen 2006; Brunkhorst 2008; Bulger 2008; Bulger 2010; Bulger 2011; Caironi 2014; Chavez‐Negrete 1991; Cifra 2003; Cooper 2006; Du 2011; Dubin 2010; Dung 1999; Ernest 1999; Evans 1996; Finfer 2004; Goodwin 1983; Grba‐Bujevic 2012; Guidet 2012; Hall 1978; Heradstveit 2010; James 2011; Jelenko 1979; Jie 2015; Kumar 2017; Li 2008; Lowe 1977; Lu 2012; Lucas 1978; Mahrous 2013; Maitland 2005; Maitland 2011; Martin 2005; Masoumi 2016; Mattox 1991; McIntyre 2008; McIntyre 2012; Metildi 1984; Modig 1986; Morrison 2011; Myburgh 2012; Nagy 1993; Ngo 2001; O'Mara 2005; Oliveira 2002; Park 2015; Perner 2012; Philips 2015; Pockaj 1994; Quinlan 2004; Rackow 1983; Shah 1977; Upadhyay 2005; Van der Heijden 2009; Vassar 1990; Vassar 1991; Vassar 1993a; Vassar 1993b; Vlachou 2010; Wills 2005; Wu 2001; Younes 1992; Younes 1997; Younes 1998; Zhao 2013; Zhu 2011).

Four studies were quasi‐randomised (Alpar 2004; Cifra 2003; Lucas 1978; Modig 1986), and the remaining studies were RCTs.

We included three studies for which we could only source the abstract (Mahrous 2013; Park 2015; Philips 2015); we sourced the full text of all remaining studies.

Study population

Participants had a wide variety of diagnoses for which fluid volume resuscitation was required, including: trauma, burns, and medical conditions such as sepsis and hypovolaemic shock. We have listed each study with the primary participant conditions in Table 5.

1. Summary of participant conditions.

Participant condition	Study ID
Admission to an ICU with any condition (which included trauma, sepsis, ARDS, head injury)	Finfer 2004; Myburgh 2012
Trauma (includes studies of 'any trauma admissions', and head, chest, and abdominal injuries, and trauma with haemorrhagic or hypovolaemic shock)	Annane 2013*; Alpar 2004; Baker 2009; Bulger 2008; Bulger 2010; Bulger 2011; Evans 1996; Grba‐Bujevic 2012; James 2011; Lowe 1977; Lucas 1978; Masoumi 2016; Mattox 1991; Morrison 2011; Shah 1977; Vassar 1990; Vassar 1991; Vassar 1993a; Vassar 1993b; Wu 2001
Sepsis or septic shock	Annane 2013; Brunkhorst 2008; Caironi 2014; Dubin 2010; Ernest 1999; Guidet 2012; Jie 2015; Li 2008; Lu 2012; Mahrous 2013; McIntyre 2008; McIntyre 2012; Modig 1986; Oliveira 2002; Park 2015 (cancer with sepsis); Perner 2012; Rackow 1983; Upadhyay 2005; Zhu 2011
Hypovolaemia, hypovolaemic shock, haemorrhagic shock	Annane 2013; Chavez‐Negrete 1991; Nagy 1993; Rackow 1983; Van der Heijden 2009; Younes 1992; Younes 1997; Younes 1998
Burns	Bechir 2013; Cooper 2006; Goodwin 1983; Hall 1978; Jelenko 1979; O'Mara 2005; Vlachou 2010
ALI, ARDS	Martin 2005; Quinlan 2004
Spontaneous subarachnoid haemorrhage	Bentsen 2006
Dengue shock syndrome	Cifra 2003; Dung 1999; Wills 2005
Postcardiac arrest	Heradstveit 2010
Perforation peritonitis	Kumar 2017
Severe malaria	Maitland 2005
Severe febrile illness	Maitland 2011
Severe pulmonary insufficiency	Metildi 1984
Vascular leak syndrome (cancer patients)	Pockaj 1994
Cirrhosis and septic induced hypotension	Philips 2015
Severe acute pancreatitis	Du 2011; Zhao 2013

Starches compared to crystalloid for fluid resuscitation in critically ill patients
Participants: critically ill people requiring fluid resuscitation  Setting: in hospital, in Algeria, Argentina, Belgium, Brazil, Canada, China, France, Germany, India, the Netherlands, Phillipines, South Africa, Switzerland, Tunisia, the UK, USA and Vietnam  Intervention: starches to include hydroxyethyl starch, hetastarch, and pentastarch  Comparison: crystalloids to include normal saline, hypertonic saline, Ringer's lactate and Ringer's acetate
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with crystalloids	Risk with starches
All‐cause mortality (at end of follow‐up)	Study population		RR 0.97  (0.86 to 1.09)	11,177  (24 studies)	⊕⊕⊕⊝ Moderate^a	We excluded data from 1 study because we could not be certain whether it accounted for attrition
	233 per 1000	226 per 1000  (201 to 254)
All‐cause mortality (at 90 days)	Study population		RR 1.01  (0.90 to 1.14)	10,415  (15 studies)	⊕⊕⊕⊝ Moderate^b	We excluded data from 1 study because we could not be certain whether it accounted for attrition
	238 per 1000	241 per 1000  (214 to 272)
All‐cause mortality (within 30 days)	Study population		RR 0.99  (0.90 to 1.09)	10,135  (11 studies)	⊕⊕⊕⊝ Moderate^b	We excluded data from 1 study because we could not be certain whether it accounted for attrition
	191 per 1000	189 per 1000  (172 to 208)
Transfusion of blood products	Study population		RR 1.19  (1.02 to 1.39)	1917  (8 studies)	⊕⊕⊕⊝ Moderate^a	1 study included different types of colloids (HES, gelatins, or albumin). We did not include this in analysis because study authors did not report data for only starches; we noted little or no difference between groups in need for transfusion of blood products in this study
	299 per 1000	356 per 1000  (305 to 416)
Renal replacement therapy	Study population		RR 1.30  (1.14 to 1.48)	8527  (9 studies)	⊕⊕⊕⊝ Moderate^b	1 study included different types of colloids (HES, gelatins, or albumin). We did not include this in analysis because study authors did not report data for only starches; we noted little or no difference between groups in need for renal replacement therapy in this study
	82 per 1000	106 per 1000  (93 to 121)
Adverse events	Allergic reaction				⊕⊝⊝⊝ Very low^c
	Study population		RR 2.59 (0.27 to 24.91)	7757 (3 studies)
	0 per 1000	0 per 1000 (0 to 0)
	Itching
	Study population		RR 1.38 (1.05 to 1.82)	6946 (2 studies)
	26 per 1000	35 per 1000 (27 to 46)
	Rashes
	Study population		RR 1.61 (0.90 to 2.89)	7007 (2 studies)
	5 per 1000	9 per 1000 (5 to 15)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; RR: risk ratio
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Dextrans compared to crystalloid for fluid resuscitation in critically ill patients
Participants: critically ill people requiring fluid resuscitation  Setting: in hospital, or out of hospital, in Brazil, Canada, Denmark, Mexico, Sweden, UK, USA and Vietnam  Intervention: dextrans  Comparison: crystalloids to include: normal saline, hypertonic saline, Ringer's lactate, Ringer's acetate, and unspecified types of crystalloids
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with crystalloids	Risk with dextrans
All‐cause mortality (at end of follow‐up)	Study population		RR 0.99  (0.88 to 1.11)	4736  (19 studies)	⊕⊕⊕⊝ Moderate^a
	237 per 1000	235 per 1000  (209 to 263)
All‐cause mortality (within 90 days and within 30 days)	Study population		RR 0.99  (0.87 to 1.12)	3353  (10 studies)	⊕⊕⊕⊝ Moderate^a
	258 per 1000	256 per 1000  (225 to 289)
Transfusion of blood products	Study population		RR 0.92 (0.77 to 1.10)	1272 (3 studies)	⊕⊝⊝⊝ Very low^b
	332 per 1000	305 per 1000 (255 to 365)
Renal replacement therapy	‐	‐	‐	‐	‐	Not measured
Adverse events	Allergic reactions
	Study population		RR 6.00 (0.25 to 144.93)	739 (4 studies)	⊕⊝⊝⊝ Very low^c
	0 per 1000	0 per 1000 (0 to 0)
	Itching
	Study population		Not measured	‐
	‐	‐
	Rashes
	Study population		Not measured	‐
	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: confidence interval; RR: risk ratio
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Gelatins compared to crystalloid for fluid resuscitation in critically ill patients
Participants: critically ill people requiring fluid resuscitation  Setting: in hospital, in Algeria, France, Germany, India, South Africa, Taiwan, Tunisia and Vietnam  Intervention: gelatins  Comparison: crystalloids to include normal saline and Ringer's lactate
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with crystalloids	Risk with gelatins
All‐cause mortality (at end of follow‐up)	Study population		RR 0.89  (0.74 to 1.08)	1698  (6 studies)	⊕⊕⊝⊝ Low^a
	301 per 1000	268 per 1000  (223 to 325)
All‐cause mortality (within 90 days)	Study population		RR 0.89 (0.73 to 1.09)	1388 (1 study)	⊕⊕⊝⊝ Low^b
	334 per 1000	298 per 1000 (244 to 364)
All‐cause mortality (within 30 days)	Study population		RR 0.92 (0.74 to 1.16)	1388 (1 study)	⊕⊕⊝⊝ Low^b
	266 per 1000	244 per 1000 (197 to 308)
Transfusion of blood products	Study population		RR 5.89 (0.24 to 142.41)	167 (1 study)	⊕⊝⊝⊝ Very low^c	We calculated an effect estimate for one small study, with one event in the gelatin group. 1 study reported transfusion of blood products but data were not reported by group. 1 study included different types of colloids (HES, gelatins, or albumin). We did not include this in analysis because study authors did not report data for only gelatins. We noted little or no difference between groups in need for transfusion of blood products
	0 per 1000	0 per 1000 (0 to 0)
Renal replacement therapy	‐	‐	‐	‐	‐	1 study included different types of colloids (HES, gelatins, or albumin). We did not include this in analysis because study authors did not report data for only gelatins. We noted little or no difference between groups in need for renal replacement therapy
Adverse events	Allergic reaction				⊕⊝⊝⊝ Very low^c	We calculated an effect estimate for one small study, with five incidences of allergic reactions in the gelatin group
	0 per 1000	0 per 1000 (0 to 0)	RR 21.61 (1.22 to 384.05)	167 (1 study)
	Itching
	‐	‐	‐
	Rashes
	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Albumin and fresh frozen plasma compared to crystalloid for fluid resuscitation in critically ill patients
Participants: critically ill people requiring fluid resuscitation  Setting: in hospital and out of hospital, in Algeria, Brazil, Canada, France, Germany, Kenya, India, Italy, Tanzania, Tunisia, Uganda and USA  Intervention: albumin and fresh frozen plasma  Comparison: crystalloids to include: normal saline, hypertonic saline, Ringer's lactate, electrolytes, and unspecified types of crystalloids
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect  (95% CI)	Number of participants  (studies)	Certainty of the evidence  (GRADE)	Comments
	Risk with crystalloids	Risk with albumin and FFP
All‐cause mortality (at end of follow‐up)	Study population		RR 0.98  (0.92 to 1.06)	13,047  (20 studies)	⊕⊕⊕⊝ Moderate^a	One study also reported mortality but not by group, and so could not be included in analysis
	254 per 1000	249 per 1000  (234 to 270)
All‐cause mortality (within 90 days)	Study population		RR 0.98  (0.92 to 1.04)	12,492  (10 studies)	⊕⊕⊕⊝ Moderate^a	One study also reported mortality but not by group, and so could not be included in analysis
	259 per 1000	254 per 1000  (239 to 270)
All‐cause mortality (within 30 days)	Study population		RR 0.99  (0.93 to 1.06)	12,506  (10 studies)	⊕⊕⊕⊝ Moderate^a	One study also reported mortality but not by group, and so could not be included in analysis
	234 per 1000	231 per 1000  (217 to 248)
Transfusion of blood products	Study population		RR 1.31  (0.95 to 1.80)	290  (3 studies)	⊕⊝⊝⊝ Very low^b	1 study included different types of colloids (HES, gelatins, or albumin). We did not include this in analysis because study authors did not report data for only albumins or FFP; we noted little or no difference between groups in need for transfusion of blood products
	281 per 1000	368 per 1000  (267 to 506)
Renal replacement therapy	201 per 1000	223 per 1000 (193 to 255)	RR 1.11 (0.96 to 1.27)	3028 (2 studies)	⊕⊕⊝⊝ Low^c	One study stated that renal replacement data were measured but it was not reported in the study report (abstract) 1 study included different types of colloids (HES, gelatins, or albumin). We did not include this in analysis because study authors did not report data for only albumin and FFP. We noted little or no difference between groups in need for renal replacement therapy
Adverse events	Allergic reactions				⊕⊝⊝⊝ Very low^d
	Study population		RR 0.75 (0.17 to 3.33)	2097 (1 study)
	4 per 1000	3 per 1000 (1 to 13)
	Itching
	‐	‐	‐	‐
	Rashes
	‐	‐	‐	‐
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).    CI: Confidence interval; FFP: fresh frozen plasma RR: Risk ratio
GRADE Working Group grades of evidence  High certainty: we are very confident that the true effect lies close to that of the estimate of the effect.  Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.  Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Study ID	Outcome	Events in colloid group: n/N	Events in crystalloid group: n/N	Effect estimate
Colloids (at the discretion of the clinician: HES, gelatins, or albumin) versus crystalloids
Annane 2013	Transfusion of blood products	377/1414	358/1443	RR 1.07, 95% CI 0.95 to 1.22; 2857 participants
Annane 2013	Renal replacement therapy	156/1414	181/1443	RR 0.88, 95% CI 0.72 to 1.08; 2857 participants
Gelatin versus crystalloids
Annane 2013	Mortality (within 90 days)	84/281	346/1035	RR 0.89, 95% CI 0.73 to 1.09; 1388 participants
Annane 2013	Mortality (within 30 days)	69/281	275/1035	RR 0.92, 95% CI 0.74 to 1.16; 1388 participants
Albumin versus crystalloid
Maitland 2011	Adverse events: allergic reactions	3/1050	4/1047	RR 0.75, 95% CI 0.17 to 3.33; 2097 participants

Date	Event	Description
1 May 2018	New citation required and conclusions have changed	We found that there was probably little or no difference in mortality according to whether starches or crystalloids were used for fluid resuscitation. Mortality data for other types of colloids remained the same.
1 May 2018	New search has been performed	New authors added (Sharon Lewis, Michael Pritchard, Andrew Butler, David Evans, Andrew Smith, Phil Alderson). Two review authors removed (Pablo Perel and Katharine Ker). Edits made to the Background and Methods sections. Change to criteria for considering studies in the review (we excluded elective surgery). Added three new outcomes (transfusion of blood products, need for renal replacement therapy; adverse events ‐ allergic reaction, itching, rashes). We reassessed all studies included in the previous version of the review and excluded studies that did not meet the new inclusion criteria. We completed data extraction and risk of bias on all studies, including those from the previous version of the review. We added a 'Summary of findings' table for each of four comparisons by type of colloid (starches; dextrans; gelatins; and albumin or fresh frozen plasma).

Date	Event	Description
25 February 2013	Amended	Minor corrections made to the results section.
31 January 2013	New citation required and conclusions have changed	New study data have been included. The conclusions of the review have changed.
17 January 2013	New search has been performed	Four new studies have been included (Guidet 2012, Lee 2011, Myburgh 2012, and Perner 2012). Mortality data from a reply letter (http://bja.oxfordjournals.org/content/107/5/693/reply) of a previous included study was added (James 2011).
17 October 2012	Amended	Copy edits made to graph labels.
8 June 2012	Amended	Copy edits made and citation corrected.
14 May 2012	New citation required but conclusions have not changed	An 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. Three 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 2012	New search has been performed	An updated search was conducted in March 2012.
10 February 2011	New 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 2009	New 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 2008	Amended	Converted to new review format.
1 July 2007	New search has been performed	August 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.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality at end of follow‐up	24	11177	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.86, 1.09]
2 Mortality within 90 days	15	10415	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.90, 1.14]
3 Mortality within 30 days	11	10135	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.90, 1.09]
4 Transfusion of blood product	8	1917	Risk Ratio (M‐H, Random, 95% CI)	1.19 [1.02, 1.39]
5 Renal replacement therapy	9	8527	Risk Ratio (M‐H, Random, 95% CI)	1.30 [1.14, 1.48]
6 Adverse event: allergic reaction	3	7757	Risk Ratio (M‐H, Random, 95% CI)	2.59 [0.27, 24.91]
7 Adverse event: itching	2	6946	Risk Ratio (M‐H, Random, 95% CI)	1.38 [1.05, 1.82]
8 Adverse event: rash	2	7007	Risk Ratio (M‐H, Random, 95% CI)	1.61 [0.90, 2.89]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality at end of follow‐up	19	4736	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.88, 1.11]
2 Mortality within 90 days and 30 days	10	3353	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.87, 1.12]
3 Transfusion of blood products	3	1272	Risk Ratio (M‐H, Random, 95% CI)	0.92 [0.77, 1.10]
4 Adverse events: allergic reaction	4	738	Risk Ratio (M‐H, Random, 95% CI)	6.0 [0.25, 144.93]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality at end of follow‐up	20	13047	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.92, 1.06]
2 Mortality within 90 days	10	12492	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.92, 1.04]
3 Mortality within 30 days	10	12506	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.93, 1.06]
4 Transfusion of blood product	3	290	Risk Ratio (M‐H, Random, 95% CI)	1.31 [0.95, 1.80]
5 Renal replacement therapy	2	3028	Risk Ratio (M‐H, Random, 95% CI)	1.11 [0.96, 1.27]

Methods	Quasi‐RCT Parallel design Single centre
Participants	Total number of randomised participants: 180 Inclusion criteria: patients admitted to MIU Exclusion criteria: no details Participant condition: head, chest, abdominal injuries Baseline characteristics Colloids group Age, mean (range): 28 (21‐60) years Gender, M:F: 81:9 BP, mean (range): SBP: 95 (35‐130); DBP: 49 (10‐70) mmHg Crystalloids group Age, mean (range): 27 (21‐59) years Gender, M:F: 81:9 BP, mean (SD): SBP: 97 (40‐127); DBP: 51 (12‐75) mmHg Country: UK Setting: MIU
Interventions	Colloids group Participants: n = 90; losses = 0; analysed = 90 Details: 7.5% NaCl in 4.2% dextran 70; 4 mL/kg up to a maximum 250 mL Additional details: further fluid infusions continued with Hartmann's or blood transfusions, if required Crystalloids group Participants: n = 90; losses = 0; analysed = 90 Details: we have assumed that crystalloid solution was RL from other information in the study report Additional details: further fluid infusions continued with Hartmann's (RL) or blood transfusions if required
Outcomes	Outcomes measured/reported: haemodynamic analysis; urine outputs; recovery; LoS Outcomes relevant to the review: mortality (time not reported)
Notes	Funding/declarations of interest: none apparent Study dates: not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Alternate participants added to each group based on odd/even numbers
Allocation concealment (selection bias)	High risk	Alternate allocation used and therefore unlikely to be concealed
Blinding of participants and personnel (performance bias): mortality	Low risk	No details of blinding; unlikely to introduce bias for this outcome
Blinding of outcome assessment (detection bias): mortality	Low risk	No details of blinding; not likely to introduce bias for this outcome
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No apparent losses
Selective reporting (reporting bias)	Unclear risk	No details of clinical trials registration; not feasible to assess risk of selective reporting bias
Baseline characteristics	Unclear risk	The proportion of participants in each arm with chest injuries differed. It is unclear whether this influenced results.
Other bias	Low risk	No other sources of bias identified

Methods	RCT Parallel design Multicentre
Participants	Total number of randomised participants: 2857 Inclusion criteria: no prior fluid resuscitation in ICU; required fluid resuscitation for acute hypovolaemia Exclusion criteria: received fluid resuscitation in ICU; anaesthesia‐related hypotension; advanced chronic liver disease; acute anaphylactic reaction; inherited coagulation disorders; do‐not‐resuscitate order; pregnant; burned > 20% of TBSA; allergy to study drug; refused consent; dehydrated; brain death or organ donor; other (not specified) Participant condition: acute hypovolaemia, sepsis, and trauma Baseline characteristics Colloids group Age, median (IQR): 63 (50‐76) years Gender, M:F: 880:534 Weight, median (IQR): 70 (60‐81) kg BP, median (IQR): SBP: 92 (80‐112) mmHg SAPS II, median (IQR): 48 (35‐64) Crystalloids group Age, median (IQR): 50 (36‐65) years Gender, M:F: 902:541 Weight, median (IQR): 70 (61‐81) kg BP, median (IQR): SBP: 94 (80‐113) mmHg SAPS II, median (IQR): 50 (36‐65) Country: France, Belgium, Canada, Algeria, Tunisia Setting: ICU
Interventions	Colloids group Participants: n = 1414; losses = 0; analysed = 1414 Details: colloids, any type from 4% gelatin, 5% albumin, dextrans, HES, 20% or 25% albumin; at discretion of local investigators; not > 30 mL/kg/d; median in first 7 days 2000 mL (IQR, 1000 mL‐3502 mlL; median 2 d duration Additional details: participants received colloids or crystalloids prior to ICU Crystalloids group Participants: n = 1443; losses = 0; analysed = 1443 Details: crystalloids, any type; at discretion of local investigator; median for first 7 days 3000 mL (IQR, 500 mL‐5200 mL); median 2 d duration Additional details: isotonic saline or HS, any buffered solutions; participants received colloids or crystalloids prior to ICU
Outcomes	Outcomes measured/reported: mortality at 28 days; mortality at 90 days and at ICU and hospital discharge; number of days alive and not receiving renal replacement therapy, mechanical ventilation or vasopressor therapy; days not in ICU or hospital; days without organ failure Outcomes relevant to the review: mortality (at 28 days, 90 days, and at end of follow‐up); renal replacement therapy; requiring blood transfusion
Notes	Funding/declarations of interest: funded by French Ministry of Health. Study sponsors not involved in design and conduct of study Study dates: Febuary 2003‐November 2012 Note: study was stopped early because study authors noted no difference in 28‐day mortality rates.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated sequence
Allocation concealment (selection bias)	Low risk	Sealed envelopes were used at the bedside to allow randomisation of eligible participants without any delay and was done blinded to block size
Blinding of participants and personnel (performance bias): mortality	Low risk	Clinicians were not blinded because of immediate need for resuscitation; unlikely to introduce bias for this outcome
Blinding of participants and personnel (performance bias): transfusion/renal replacement therapy/adverse events	High risk	Clinicians were not blinded because of immediate need for resuscitation; could introduce bias for this outcome
Blinding of outcome assessment (detection bias): mortality	Low risk	Quote: "mortality end‐points were collected and assessed by study members blinded to treatment assignment." Unlikely to introduce bias for this outcome
Blinding of outcome assessment (detection bias): transfusion/renal replacement therapy/adverse events	Unclear risk	No details
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No losses
Selective reporting (reporting bias)	Low risk	Prospective clinical trials registration (NCT00318942); all outcomes listed on registration site were reported
Baseline characteristics	Low risk	Baseline characteristics appear comparable
Other bias	High risk	47.5% of participants in the crystalloid group were given colloids within 12 h before the start of the study and this may have influenced study results

Methods	RCT Parallel design Multicentre (2 x level 1 adult trauma centres)
Participants	Total number of randomised participants: 64 Inclusion criteria: coma, with a loss of consciousness because of isolated blunt head trauma or a GCS score ≤ 8 Exclusion criteria: primary penetrating injury; previous IV therapy ≥ 50 mL; time of arrival at scene to IV access > 4 h; < 16 years of age; burn or amputation; presumed to be pregnant; vital signs absent prior to randomisation Participant condition: blunt trauma head injury Baseline characteristics Colloids group Age, mean (SD): 42.5 (± 20.9) years Gender, M:F: 18:13 APACHE II, mean (SD): 13.2 (± 5.6) Crystalloids group Age, mean (SD): 42.3 (± 20.7) years Gender, M:F: 23:10 APACHE II, mean (SD): 14.4 (± 5.2) Country: Canada Setting: ambulatory prior to adult‐designated level 1 trauma centres
Interventions	Colloids group Participants: n = 31; losses = 0; analysed = 31 Details: 7.5% HS in 6% dextran 70; 250 mL Additional details: emergency medical service personnel administered the study solution prehospital; after administration of study fluid participants were treated according to ATLSG; participants received additional crystalloid for ongoing resuscitation per existing protocols Crystalloids group Participants: n = 33; losses = 0; analysed = 33 Details: 0.9% isotonic NS; 250 mL Additional details: same as colloid group
Outcomes	Outcomes measured/reported: neurological outcomes at hospital discharge (or 30 days) using various scales; mortality; biomarkers Outcomes relevant to the review: mortality (at 28 days)
Notes	Funding/declarations of interest: funded by Defence Research and Development Canada Study dates: September 2004‐January 2006
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated sequence
Allocation concealment (selection bias)	Low risk	Computer randomisation was used to assign sequentially numbered identical IV bags to the ambulance
Blinding of participants and personnel (performance bias): mortality	Low risk	Participants and personnel were blinded to treatment allocation
Blinding of outcome assessment (detection bias): mortality	Low risk	Paramedics, physicians and study co‐ordinators were blinded to treatment allocation
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No apparent losses
Selective reporting (reporting bias)	Unclear risk	No details of clinical trials registration; not feasible to assess risk of selective reporting bias
Baseline characteristics	Low risk	Baseline characteristics appear comparable
Other bias	High risk	Study authors report that participants could receive additional fluid resuscitation during standard care and this could influence outcome results for this study

Methods	RCT Parallel design Single centre
Participants	Total number of randomised participants: 48 Inclusion criteria: ≥ 16 years of age with second‐ or third‐degree acute burn injuries and > 15% of body surface area burned Exclusion criteria: expected to die within 24‐36 h (i.e. burn victims with whole body burn trauma); in situations of palliative care; pregnancy; lack of informed consent; known allergy to HES; contraindications for balanced 6% HES 130/0.04; intracerebral bleeding; acute renal failure; severe hypernatraemia and other severe electrolyte disorders; severe von Willebrand Syndrome; acute liver failure Participant condition: burns; TBSA > 15% Baseline characteristics Colloids group Age, median (IQR): 49 (22‐69) years Gender, M:F: 17:6 Weight, median (IQR): 75 (70‐83) kg BP, median (IQR): SBP: 109 (93‐130); DBP: 60 (55‐65) mmHg TBSA, median burned (IQR): 31% (21‐47) Crystalloids group Age, median (IQR): 47 (26‐61) years Gender, M:F: 17:5 Weight, median (IQR): 80 (70‐80) kg BP, median (IQR): SBP: 123 (104‐150) mmHg; DBP: 68 (59‐76) mmHg TBSA, median burned (IQR): 32% (20%‐50%) Country: Switzerland Setting: tertiary burns unit
Interventions	Colloids group Participants: n = 24; losses = 0; analysed = 24 Details: 6% HES 130/0.4; 500 mL; each participant first received 2 bags of unblinded RL solution (500 mL each bag); after each bag of study solution, all participants again received 2 bags of unblinded RL solution, before a next bag of study solution from the blinded box was infused; maximum to be given as 50 mL/kg/24 h Additional details: fluid was administered until target variables were met; 2 bags of unblinded RL (500 mL each bag); then 1 bag of HES; then 2 bags of unblinded RL Crystalloids group Participants: n = 24; losses = 0; analysed = 24 Details: RL solution; 500 mL; each participant first received 2 bags of unblinded RL solution (500 mL each bag); after each bag of study solution, all participants again received 2 bags of unblinded RL solution, before a next bag of study solution from the blinded box was infused Additional details: as for colloids group but given RL in blinded bags in between unblinded bags
Outcomes	Outcomes measured/reported: group difference in administration of fluid with 72 h; creatinine levels; urine output; ARDS; LoS in ICU; LoS in hospital; in‐hospital mortality and at 28 days; post‐hoc 90‐day mortality; RRT Outcomes relevant to the review: mortality (28 days; and 90 days); RRT (collected as a 90‐day post‐hoc analysis)
Notes	Funding/declarations of interest: funding from manufacturer of HES, which supplied study fluids; 2 of the authors have vocationally been members of advisory board meetings. No competing interests declared. Funders reported as having no input in study design and interpretation of results Study dates: November 2009‐January 2013
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation completed using minimisation technique, conducted by a third party
Allocation concealment (selection bias)	Low risk	A third party not involved in conduction of study, performed the randomisation process
Blinding of participants and personnel (performance bias): mortality	Low risk	All personnel blinded. Fluids prepared externally, and concealed in bags of black plastic
Blinding of participants and personnel (performance bias): transfusion/renal replacement therapy/adverse events	Low risk	All personnel blinded. Fluids prepared externally, and concealed in bags of black plastic
Blinding of outcome assessment (detection bias): mortality	Low risk	No details in study report. However, trial registration report states that outcome assessors were blinded
Blinding of outcome assessment (detection bias): transfusion/renal replacement therapy/adverse events	Low risk	No details in study report. However, trial registration report states that outcome assessors were blinded
Incomplete outcome data (attrition bias)   All outcomes	Low risk	2 participants were retrospectively excluded because of meeting exclusion criteria. Data missing from 1 additional participant because of early discharge. Overall, < 10% dropout/exclusion; data reported for 45/48 randomised participants
Selective reporting (reporting bias)	High risk	Prospective clinical trials registration (NCT01012648). Only primary outcome (fluid volume administered) was listed on the trial registration site
Baseline characteristics	Low risk	Baseline characteristics comparable
Other bias	Low risk	No other sources of bias identified

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 All‐cause mortality at end of follow‐up	16	4247	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.90, 1.13]
1.1 colloid + hypertonic crystalloid vs isotonic crystalloid	8	2845	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.87, 1.13]
1.2 colloid + isotonic crystalloid vs hypertonic crystalloid	2	493	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.62, 2.06]
1.3 colloid + hypertonic crystalloid vs hypertonic crystalloid	6	909	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.74, 1.41]

Methods	RCT Parallel design Single centre (assumed, but not reported by study authors)
Participants	Total number of randomised participants: 47 Inclusion criteria: people attending the emergency department with ≤ SBP 90 mmHg Exclusion criteria: people who appeared to be < 18 years of age; pregnant women; known severe pre‐existing cardiac, hepatic, or renal disease Participant condition: SBP ≤ 80 mmHg Baseline characteristics Colloids group Age, mean (SEM): 35 (± 3) years BP, mean (SEM): 52 (± 8) mmHg Revised trauma score (SEM): 4.0 (± 0.6) Crystalloids group Age, mean (SEM): 33 (± 3) years BP, mean (SEM): 55 (± 8) mmHg Revised trauma score (SEM): 3.4 (± 0.6) Country: USA Setting: emergency department
Interventions	Colloids group Participants: n = 23; losses = 0; analysed = 23 Details: 250 mL 7.5% NaCl in 6% dextran 70 Crystalloids group Participants: n = 24; losses = 0; analysed = 24 Details: RL; 250 mL
Outcomes	Outcomes measured/reported: haemodynamic variables; blood chemistry; mortality; adverse events (allergic reactions) Outcomes relevant to the review: mortality (28 days); adverse events (allergic reactions)
Notes	Funding/declarations of interest: supported in part from the National Institutes of Health Study dates: April 1987‐May 1988
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described as randomised; no additional details
Allocation concealment (selection bias)	Unclear risk	No details
Blinding of participants and personnel (performance bias): mortality	Low risk	Identical bottles used to conceal study fluids from participants and personnel
Blinding of outcome assessment (detection bias): mortality	Low risk	No details of blinding; unlikely to introduce bias for mortality
Incomplete outcome data (attrition bias)   All outcomes	Low risk	No apparent losses
Selective reporting (reporting bias)	Unclear risk	No details of clinical trials registration; not feasible to assess risk of selective reporting bias
Baseline characteristics	Low risk	Baseline characteristics appeared comparable
Other bias	Low risk	No other sources of bias detected

Study	Reason for exclusion
Boutros 1979	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for major abdominal aortic surgery
Bowser‐Wallace 1986	Included in previous version of review (Perel 2013). Excluded because study was not an RCT
Dawidson 1991	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for abdominal aortic surgery
Dehne 2001	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for middle ear surgery
Eleftheriadis 1995	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Evans 2003	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for hip replacement
Fries 2004	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for knee replacement
Gallagher 1985	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Grundmann 1982	Included in previous version of the review (Perel 2013). Does not appear to be an RCT, and associated reference does not include crystalloid group; therefore, we have excluded this study from the review
Guo 2003	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for cytoreductive surgery
Hartmann 1993	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for major abdominal surgery
Hondebrink 1997	Included in previous version of review (Perel 2013); hypoalbuminaemia after major surgery. Study ID was Woittiez 1997 in previous version of the review
Karanko 1987	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Lee 2011	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Ley 1990	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Mazher 1998	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
McNulty 1993	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Moretti 2003	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for general, gynaecological, orthopaedic, or urological procedures
Nielsen 1985	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for abdominal aortic surgery
Prien 1990	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for modified Whipple's operation
Rocha e Silva 1994	Abstract only. Included in previous version of review (Perel 2013). Protocol for a study that has not been published. We have excluded this study because we no longer expect that results for this study will be published
Shires 1983	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for aortic reconstruction surgery
Sirieix 1999	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Skillman 1975	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for abdominal reconstructive surgery
Tollusfrud 1995	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Tollusfrud 1998	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Verheij 2006	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Virgilio 1979	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for abdominal aortic surgery
Wahba 1996	Included in previous version of review (Perel 2013). Excluded because participants were elective cardiac surgical patients
Zetterstorm 1981a	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for abdominal surgery
Zetterstorm 1981b	Included in previous version of review (Perel 2013). Excluded because participants were elective surgical patients scheduled for abdominal aortic surgery

Methods	RCT Parallel design
Participants	Number of randomised participants: no details Inclusion criteria: no details Exclusion criteria: no details Participant condition: no details Country: Russia Setting: no details
Interventions	Colloids group 1 Details: 6% HES 200/0.5 Colloids group 2 Details: 6% HES 130/0.4 Crystalloids group Details: NS
Outcomes	Outcomes measured/reported: no details Outcomes relevant to the review: no details
Notes	Funding/declarations of interest: no details Study dates: no details Study report requires translation from Russian to assess eligibility

Trial name or title	Impact of fluid resuscitation therapy on pulmonary edema as measured by alveolar fluid clearance in patients with acute respiratory distress syndrome (ARDS)
Methods	RCT Parallel design Single centre
Participants	Estimated number of randomised participants: 70 Inclusion criteria: ≥ 18 years of age; ICU patients under mechanical ventilation; within the first 24 h after onset of moderate or severe ARDS; hypovolaemia requiring fluid resuscitation therapy Exclusion criteria: pregnancy; < 18 years of age; refusal of the protocol; contraindications for the use of Voluven or RL; contraindications for femoral artery catheterisation or subclavian venous catheterisation Participant condition: ARDS; hypovolaemia; pulmonary oedema Country: France Setting: university hospital
Interventions	Colloids group Details: 4% albumin Crystalloids group Details: no details
Outcomes	Outcomes measured/reported: rate of alveolar fluid clearance; alveolar oedema fluid resorption; mortality (at 20 days) Outcomes relevant to the review: mortality
Starting date	December 2012
Contact information	Patrick LACARIN; email: placarin@chu‐clermontferrand.fr
Notes	Funding/declarations of interest: sponsored by University Hospital, Clermont‐Ferrand

Trial name or title	Comparison of colloid (20% albumin) versus crystalloid (Plasmalyte) for fluid resuscitation in cirrhotics with sepsis induced hypotension
Methods	RCT Parallel design Single centre
Participants	Estimated number of randomised participants: 90 Inclusion criteria: between 18 and 75 years of age; cirrhosis with suspected or documented sepsis with MAP < 65 mm Hg Exclusion criteria: already received colloid or 2 L of fluid within the first 12 h of presentation; already on vasopressors and/or inotropes; spontaneous bacterial peritonitis and serum albumin less then 1.5 g/dL; structural heart disease; on maintenance haemodialysis; other causes of hypotension; pregnant or lactating women; in need of emergent surgical interventions; chronic obstructive lung disease and congestive heart failure; previous adverse reaction to human albumin solution Participant condition: cirrhosis with sepsis Country: India Setting: medical centre
Interventions	Colloids group Details: 20% albumin Crystalloids group Details: Plasmalyte
Outcomes	Outcomes measured/reported: reversal of hypotension; mortality (at 7 and 28 days); proportion of patients with new organ failures; duration of mechanical ventilation; requirement of RRT; length of ICU stay Outcomes relevant to the review: mortality; requirement of RRT
Starting date	March 31, 2016
Contact information	Dr Abhinav Verma; email: abhinav.3183@gmail.com
Notes	Funding/declarations of interest: sponsored by Institute of Liver and Biliary Sciences, India

Trial name or title	A comparison of crystalloid alone versus crystalloid plus colloid in shock resuscitation
Methods	RCT Parallel design Single centre
Participants	Estimated number of randomised participants: 320 Inclusion criteria: ≥ 18 years of age; new onset of shock within 24 h; MAP < 65 mmHg or SBP < 60% of baseline BP; evidence of poor tissue perfusion including: urine output < 0.5 mL/kg/h, lactate > 2 mmol/L, alteration of consciousness without other explanation; evidence of fluid inadequacy (CVP < 12 mmHg, PCWP < 18 mmHg) or evidence of fluid responsive (IVC diameter variation > 15%, pulse pressure variation > 15%, positive fluid challenge test) Exclusion criteria: prolonged shock > 24 h; received colloid solution > 1000 mL in previous 72 h; do‐not‐resuscitate order; contraindication for fluid therapy including: suspected cardiogenic shock, evidence of pulmonary oedema, history of anaphylaxis after fluid therapy Participant condition: shock Country: Thailand Setting: hospital
Interventions	Colloids group Details: colloid solution resuscitation Crystalloids group Details: isotonic crystalloid solution resuscitation
Outcomes	Outcomes measured/reported: proportion of patients who had shock reversal; mortality (at 28 and 90 days); total fluid resuscitation within 24 h; need of RRT Outcomes relevant to the review: mortality; need of RRT
Starting date	September 2014
Contact information	Surat Tongyoo, MD; email: surat_Ty@yahoo.co.uk; Prapan Laophannarai, MD; email: praphan113@hotmail.com
Notes	Funding/declarations of interest: sponsored by Mahidol University

PERMALINK

Colloids versus crystalloids for fluid resuscitation in critically ill people

Sharon R Lewis

Michael W Pritchard

David JW Evans

Andrew R Butler

Phil Alderson

Andrew F Smith

Ian Roberts

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

1.

Data extraction and management

Assessment of risk of bias in included studies

2.

3.

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

4.

5.

6.

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

'Summary of findings' table and GRADE

Results

Description of studies

Results of the search

Included studies

Study population

1. Summary of participant conditions.

Study setting

Interventions and comparison

Colloids

Crystalloids

Outcomes

Funding sources

Excluded studies

Studies awaiting classification

Ongoing studies

Risk of bias in included studies

Allocation

Blinding

Incomplete outcome data

Selective reporting

Baseline characteristics

Other potential sources of bias

Effects of interventions

Summary of findings for the main comparison. Starches compared to crystalloid for fluid resuscitation in critically ill patients.

Summary of findings 2. Dextrans compared to crystalloid for fluid resuscitation in critically ill patients.

Summary of findings 3. Gelatins compared to crystalloid for fluid resuscitation in critically ill patients.