Intensive Care Medicine

, Volume 38, Issue 7, pp 1134–1142 | Cite as

Safety of gelatin for volume resuscitation—a systematic review and meta-analysis

  • D. O. Thomas-Rueddel
  • V. Vlasakov
  • K. Reinhart
  • R. Jaeschke
  • H. Rueddel
  • R. Hutagalung
  • A. Stacke
  • C. S. Hartog
Original

Abstract

Purpose

Gelatin is frequently used as a volume expander in critical care. Our goal was to investigate its safety.

Methods

Systematic review of randomized controlled trials (RCT) in patients receiving gelatin for resuscitation in comparison to albumin or crystalloids.

Results

We identified 40 RCTs published between 1976 and 2010 with 3,275 patients. Median sample size in the gelatin groups was 15 patients (range 10–249). Median gelatin dose was 17 ml/kg (range 6–57 ml/kg). In 32 RCTs (n = 1,946/3,275, 59 % of all patients), the study period was ≤24.0 h. Twenty-nine RCTs (n = 2,001) investigated elective surgical patients, mostly undergoing cardiac surgery (18 RCTs, n = 819). Three RCTs (n = 723) investigated critically ill adults. Two RCTs (n = 59) were performed in emergency room patients, and six RCTs (n = 492) were performed in neonates or children. No study was adequately powered to investigate the frequency of patient-important outcomes. Risks were not statistically significantly different for mortality (RR 1.12, 95 % confidence interval, 0.87–1.44) and exposure to allogeneic transfusion (RR 1.28, 0.89–1.83). On account of only few included studies and the small number of patients, subgroup analyses (high vs. low dose, >24 h vs. shorter periods, and critically ill patients vs. others) were uninformative. Only three RCTs reported the occurrence of acute renal failure.

Conclusion

Despite over 60 years of clinical practice, the safety and efficacy of gelatin cannot be reliably assessed in at least some settings in which it is currently used. We suggest the need to investigate and establish such safety.

Keywords

Plasma expander Acute renal failure Coagulopathy Colloids Crystalloids 

Introduction

Gelatin, a degradation product of collagen [1], is a plasma expander used in patients in emergency departments, intensive care units, and operating and recovery rooms. Being one of the first synthetic colloids used for fluid resuscitation in humans [2], it came into more widespread use when different modifications of the gelatin molecules became available (oxypolygelatin [3], succinylated or modified fluid gelatin [4], and urea-linked gelatin [5]). These products entered the market long before current regulatory rules requiring proof of efficacy and safety of drugs came into existence [6].

Generally, gelatin solutions are considered to have no dosage-related side effects, specifically not impairing surgical hemostasis [7, 8], and being less harmful to the kidneys than other non-protein colloids [9, 10].

It was therefore surprising that retrospective analyses in observational studies found the use of gelatin to be associated with increased renal impairment and the need for transfusion products in patients with severe sepsis [11] and cardiac surgery [12]. Considering that the use of non-protein colloids is not associated with improved clinical outcomes [13, 14], potentially harmful effects of gelatins should be carefully explored.

Cumulative effects of gelatin on mortality were previously assessed by two Cochrane groups as part of larger meta-analyses that included studies until 2007 or 2008, respectively. Perel et al. [13] compared gelatin to crystalloid fluids in 506 critically ill adult patients, whereas Bunn et al. [15] compared gelatin with albumin or PPF in 636 patients thought to need volume replacement. No review found a significant effect on mortality. However, effects on renal function or blood product use were not systematically explored. In view of the emerging safety concerns, we considered that a systematic overview of the current clinical evidence on the safety of gelatin would be timely.

Methods

Eligibility criteria

Inclusion criteria

Inclusion criteria were: (1) prospective, randomized controlled trials, (2) hospital or pre-hospital setting, (3) patients with acute hypovolemia with need for fluid resuscitation, (4) study fluid was administered for resuscitation, (5) at least one intervention group received gelatin solution, and (6) at least one intervention group received another resuscitation fluid.

Exclusion criteria

Exclusion criteria were: (1) only volunteers or blood donors were recruited, (2) administration of fluid was solely for the purpose of volume preloading before anesthesia including volume loading for neural block, acute normovolemic or hypervolemic hemodilution without subsequent intra- or postoperative use, (3) retracted studies [16], (4) unsuitable control fluids, i.e., other synthetic colloids (as those may have similar risk profile), and (5) study results published in a language other than English, German, French, or Italian.

Search strategy

Three electronic databases were searched: Ovid Medline (1948–May 2011), EMBASE (1947–May 2011), and the Cochrane Central Register of Controlled Trials (CENTRAL) (through May 2011). In addition, reference lists from studies that met the inclusion criteria and from published systematic reviews were hand searched. Authors were contacted for further clarification if necessary.

The search terms used in MEDLINE or EMBASE are provided in the Electronic Supplement. Cochrane CENTRAL was searched using MeSH descriptor Polygeline (exploded).

Study selection, validity appraisal, and data extraction

Two reviewers independently screened the results of the search. Full-text manuscripts of potentially eligible articles were obtained and assessed independently against inclusion and exclusion criteria. Two out of five reviewers read the full-text reports and independently extracted the data into a datasheet. Differences were then compared and resolved by agreement or referral to a third reviewer. If results of one study were included in different publications, all extracted data were collated under one publication, and the others were removed from the datasheet.

Study validity was assessed by a tool developed by the Cochrane Collaboration’s tool for assessing risk of bias based on “low-high-uncertain” responses to the following seven domains: randomization, allocation concealment, blinding of participants, blinding of outcome assessment, incomplete outcome data, selective reporting, and other sources of bias [17].

Extracted data included: type and volume of gelatin, types and volumes of control fluids, fluid regimen, observation period, clinical condition, patient numbers, potential conflict of interest (COI) and type of funding, and reported outcomes. Outcomes of interest were defined as all-cause mortality at a time reported by the investigators, number of patients exposed to allogeneic blood products, acute kidney injury (AKI) by RIFLE criteria [18] or new need for renal replacement therapy (RRT), anaphylaxis, or itching. These outcomes were assessed in studies where gelatin was compared to suitable control fluids (albumin, plasma protein, or crystalloid); synthetic colloids such as hydroxyethyl starch, dextran, or other gelatins were defined as unsuitable control fluids because their comparative safety was not in question for this systematic review. Where possible, subgroup analyses were performed for different patient populations (i.e., critically ill, trauma, surgical patients), and subgroups with higher risk for gelatin effects were analyzed [high-dose gelatin (≥30 ml/kg), study periods >24 h].

Data analysis

The primary analysis of the data was descriptive, determining the proportion of studies meeting each of the criteria. Data were analyzed using SPSS 17.0 for Windows (SPSS Inc, Chicago, IL). Summarized fluid volumes were calculated as median values from all reported mean or median fluid volumes or from median/mean values for cumulative dose and body weight, if available.

For studies with more than one suitable control group, all control comparisons were pooled for the overall meta-analysis.

The relative risk of death and the relative risk of allogeneic blood product transfusion were calculated using a random-effects model (RevMan 5.1, Cochrane Collaboration). We specified subgroup analyses by study duration (>24 h vs. shorter periods), total gelatin dose (≥30 ml/kg versus less), and study population (critically ill patients vs. others). The statistical program used excludes studies with no events from the pooled estimate of relative risk.

Results

Descriptives

The structured search yielded 1,288 reports, of which 210 were read in full. The final sample contained 40 RCTs (full list is provided in Electronic Supplement). Studies were published between 1976 and 2010. The study flow graph is shown in Fig. 1.
Fig. 1

Study flow

Risk of bias is shown in Fig. 2. Three studies had a a low risk of bias in all domains [19, 20, 21], and five studies had a low risk in all domains except blinding [22, 23, 24, 25, 26].
Fig. 2

Risk of bias in included studies

Characteristics of all included studies are shown in Table 1. The total number of 3,275 patients was included in 40 studies, and 1,265 patients overall received gelatin. Median sample size in the gelatin groups was 15 patients (range 10–249). Two trials [27, 28] were multi-centered. In 32 RCTs (80 % of RCTs, n = 1,946 patients, 59 % of all 3,275 patients), the study period was ≤24 h. The total gelatin dose was 17 ml/kg (median, range 6–57). Twenty-nine RCTs (73 % of RCTs, 2,001/3,275, 61 % of all patients) investigated elective surgical patients, mostly undergoing cardiac surgery (18 RCTs, 819 patients). Three RCTs (723 patients) investigated critically ill adults. Two RCTs (59 patients) were in emergency department patients, and six RCTs (492 patients) were in children (Table 1).
Table 1

Characteristics of included studies

First author

Year

Patients

Population

Type of gelatin

Crystalloid or albumin comparator

Additional comparator fluids and comments

Akech

2006

88

Children with severe malaria

MFG 4 %

Albumin 4.5 %

 

Dung

1999

50

Children with Dengue shock syndrome

MFG 3 %

NS, RL

6 % dextran 70

Haas

2007

42

Small infants undergoing elective surgery

MFG 4 %

Albumin 5 %

6 % HES 130/0.4

Ngo

2001

222

Children with Dengue shock syndrome

MFG 3 %

RL, NS

6 % dextran 70

Stoddart

1996

30

Neonates with elective surgery

Polygeline 3.5 %

Albumin 4.5 %

 

Upadhyay

2005

60

Children with septic shock

Polygeline 3.5 %

NS

 

Gondos

2010

200

Critically ill adults

MFG 4 %

RL, Albumin 5 %

6 % HES 130/0.4

Stockwell

1992

475

Critically ill adults

Polygeline 3.5 %

Albumin 4.5 %

Patients received additional albumin

van der Heijden

2009

48

Critically ill adults

MFG 4 %

NS, Albumin 5 %

6 % HES 200/0.5

Boldt

1986

55

Adults with cardiac surgery

Polygeline 3.5 %

Albumin 20 %

3 % HES 200/0.5; additional FFP and albumin in both groups

Boldt

1992

60

Adults with cardiac surgery

Gelatin 3.5 %

RL, Albumin 20 %, 5 %

10 % HES 200/0.5; additional albumin in both groups

Boldt

1993

75

Adults with cardiac surgery

Gelatin 3.5 %

Crystalloid, albumin 5 %

6 % HES 450/0.5, 6 % HES 200/0.5; additional albumin in both groups

Himpe

1991

105

Adults with cardiac surgery

Polygeline 3.5 %, MFG 3 %

Albumin 20 %

 

Liskaser

2000

21

Adults with cardiac surgery

Polygeline 3.5 %

NS

 

Schramko

2010

45

Adults with cardiac surgery

MFG 4 %

R-Ac

6 % HES 130/0.4

Scott

1995

93

Adults with cardiac surgery

Polygeline 3.5 %

NS, albumin 4.6 %

All patients received additional colloids

Soares

2009

40

Adults with cardiac surgery

MFG, percentage unclear

NS

 

Tabuchi

1995

60

Adults with cardiac surgery

Oxypolygelatine

Albumin 20 %

10 % HES 200/0.5

Tigchelaar

1998

33

Adults with cardiac surgery

MFG 3 %

Albumin 4 %

 

Tollofsrud

1995

40

Adults with cardiac surgery

Polygeline 3.5 %

R-Ac, albumin 4 %

6 % dextran 70

Wahba

1996a

20

Adults with cardiac surgery

Polygeline 3.5 %

Albumin 5 %

 

Wahba

1996b

20

Adults with cardiac surgery

Polygeline 3.5 %

Ringers

 

DuGres

1989

30

Adults post cardiac surgery

Polygeline 3.5 %

Albumin 4 %

 

Kuitunen

2007

45

Adults post cardiac surgery

MFG 4 %

Albumin 4 %

6 % HES 200/0.5

Karanko

1987

37

Adults post cardiac surgery

Oxypolygelatine 5.5 %

Plasma protein solution 4 %

6 % dextran 70; patients received unspecified colloids prior to study

Verheij

2006

67

Adults post cardio-thoracic surgery

MFG 4 %

NS, albumin 5 %

6 % HES 200/0.5; all patients received gelatin for cardiac prime

Evans

2003

55

Adults with orthopedic surgery

Polygeline 3.5 %, MFG 4 %

NS, albumin 4.5 %

 

Fries

2004

60

Adults with orthopedic surgery

MFG 4 %

RL

6 % HES 200/0.5

Karoutsos

1999

42

Adults with orthopedic surgery

MFG 3.5 %

Albumin 5 %

6 % HES 200/0.6

Mittermayr

2007

61

Adults with orthopedic surgery

MFG 4 %

RL

6 % HES 130/0.4

Parker

2004

396

Adults with orthopedic surgery

MFG 4 %

NS

 

Evans

1996

25

Adult trauma patients

Polygeline 3.5 %

RL

 

Wu

2001

34

Adults with hypovolemic or neurogenic shock

MFG 4 %

RL

 

Lamke

1976

83

Adults with elective surgery

Polygeline 3.5 %

NS, Albumin 5 %

6 % Dextran 70, 6 % HES (Volex)

Korttila

1983

132

Adults with elective surgery

MFG 4 %

Balanced glucose/salt solution

6 % dextran, 6 % HES 120, 6 % HES 70

Lorenz

1994

231

Adults with elective surgery

Polygeline 3.5 %

RL

 

van Wyk

1998

20

Adults with elective surgery

Polygeline 3.5 %

RL

 

Volta

2007

36

Adults with major abdominal surgery

Polygeline 3.4 %

RL

6 % HES 130/0.4

Vedrinne

1991

30

Adults undergoing surgery with neural block

MFG 3 %

RL

3.5 % Dextran 40

Jin

2010

36

Adults with major abdominal surgery

MFG 4 %

RL

6 % HES 130/0.4

MFG modified or fluid gelatin, NS normal saline, RL Ringer’s lactate, R-Ac Ringer's acetate, HES hydroxyethyl starch

References for Table 1 are given in the Electronic Supplementary Material

Outcomes

Mortality

Mortality rates were provided in 15 RCTs with 1,766 patients. Seven RCTs were in critically ill patients, and 8 RCTs were in trauma, emergency, or elective surgery. Overall mortality was similar in gelatin or control groups (RR 1.12, 95 % confidence interval CI, 0.87–1.44) (Fig. 3a).
Fig. 3

Forest plots of pooled estimates

Exposure to allogeneic blood products

Eight RCTs with 712 patients reported the number of patients with transfusion of allogeneic blood products. Overall RR for exposure to allogeneic blood products was 1.28 (CI 0.89–1.83) (Fig. 3b).

AKI and need for RRT

Only three RCTs (n = 172 patients) reported the occurrence of AKI, ARF, or new need for RRT [25, 29, 30]. In two of these studies, gelatin was used in high dosage; one RCT was in critically ill adults and one in critically ill children. There was no difference in the risk of AKI between groups with a wide confidence interval around the RR estimate (Fig. 3c).

Subgroups

Higher doses of gelatin were used in four RCTs that reported deaths; no difference was seen between fluid groups. Exposure to allogeneic transfusions could be assessed in one RCT with high-dose gelatin; the RR was 7.62 (95 % CI 1.05, 55.55, only 9 transfusion events) [31] (Table 2).
Table 2

Subgroup outcomes

Subgroup

Outcome

Studies

Patients

No. of events/

no. of patients

Effect estimatea

Gelatin

Control

High doseb

Mortality

4

623

66/322

55/301

1.19 (0.66, 2.13)

 

Exposure to allogeneic transfusions

1

41

8/21

1/20

7.62 (1.05, 55.55)

>24 h

Mortality

6

1,213

69/558

55/655

1.27 (0.72, 2.22)

 

Exposure to allogeneic transfusions

2

420

32/210

22/210

1.44 (0.87, 2.38)

aStatistical method: risk ratio (M-H, random, 95 % CI); <1 favors gelatin, >1 favors control

bGelatin dose ≥30 ml/kg

Study periods longer than 24 h were found in six RCTs that reported mortality, and in two RCTs that reported exposure to allogeneic transfusions. No difference was seen between groups (Table 2).

Other outcomes

Ten RCTs reported anaphylactoid reactions, but events occurred only in two RCTs (1/44 and 5/56 in the gelatin group, and 0/44 and 0/111 in the control groups) [21, 32]. No RCTs reported itching.

Discussion

This systematic review included all controlled studies that randomized adult and pediatric patients with acute hypovolemia due to surgery, trauma, severe infection, or critical illness to receive either gelatin or suitable albumin or crystalloid control fluids for resuscitation. We did not consider synthetic colloids as suitable control fluids because they have a similar risk profile and may all be associated with coagulopathy, renal dysfunction, and anaphylaxis [33, 34], whereas albumin and crystalloids are not associated with these side effects. Main outcomes were mortality, need for transfusion of allogeneic blood products, and renal failure reported as AKI according to RIFLE criteria or new need for RRT.

There was no difference in the overall risks of death and of patient exposure to allogeneic transfusions. However, all point estimates were on the one side of the potential range, and their confidence ranges were wide. Considering blood product use, the effect estimate by fixed effect model achieved significance (RR 1.36 [1.02, 1.81]), while the more conservative random effect model did not (RR 1.28 [0.89, 1.83]). RR for exposure to transfusion was increased in the subgroup of high-dose gelatin use (RR 7.62 [1.05, 55.55]), but here only one RCT was included [31], and the result is very imprecise. Almost all studies had considerable risk of bias and small sample sizes. The study period was 24 h or less in three-quarters of studies, and two-thirds investigated elective surgical patients, mostly from cardiac surgery, making inferences regarding the use of those fluids in critically ill patients more difficult.

Except for three studies [25, 29, 30], no RCT assessed renal failure in terms of AKI or RRT in comparison to a suitable control fluid. There are only few reports of renal nephroses associated with gelatin [35, 36] and one case report of acute renal failure after vascular surgery [37]. Recently, retrospective analyses found that AKI occurred more frequently in patients with sepsis as well as cardiac surgical patients who received gelatin compared to patients who had received only crystalloids [11, 12]. In each case we consider the evidence regarding influence of gelatins on renal outcome in critically ill patients as having low quality. Two previous fluid trials with critically ill patients found that the older 6 % starch solution had more deleterious effects on kidney function than a 3 % gelatin solution [9, 10]. Small trials that compared third-generation starches with 4 % gelatin solution in cardiac surgical patients found no difference in renal function [38, 39], whereas a retrospective sequential analysis of 346 patients with severe sepsis found that AKI occurred in 70 % of patients with HES 130/0.4 (adjusted p = 0.002) and in 68 % of patients with 4 % gelatin (adjusted p = 0.025) compared to 47 % of patients receiving only crystalloids [11].

The strength of this review is the comprehensive approach that identified RCTs published over the last 35 years, the systematic focus on potentially harmful effects, and the selection of studies with suitable control fluids. A limitation of its conclusion is the overall poor quality of the evidence coming from analysis of the included studies. This results from the design limitations of numerous studies, bringing their validity into question, imprecision stemming from the small numbers of events, indirectness about to the clinically important use of those drugs in critically ill populations, short observation periods, and relatively low doses used. In our view, the available data do not allow definitive inferences about the safety of gelatins in the populations of interest, especially when gelatins are used in larger doses over longer periods of time.

Conclusion

Gelatins were introduced into clinical practice before legislation in the aftermath of the thalidomide tragedy made clinical proof of safety mandatory [6]. Despite over 60 years of clinical experience with its use, the safety of gelatin in all settings in which it is used cannot be reliably assessed and confirmed. We suggest the need to investigate and establish such safety.

Notes

Acknowledgments

Support was provided solely from institutional and/or departmental sources.

Conflicts of interest

None.

Supplementary material

134_2012_2560_MOESM1_ESM.doc (48 kb)
Supplementary material 1 (DOC 47.5 kb)

References

  1. 1.
    Saddler JM, Horsey PJ (1987) The new generation gelatins. A review of their history, manufacture and properties. Anaesthesia 42:998–1004PubMedCrossRefGoogle Scholar
  2. 2.
    Hogan JJ (1915) The intravenous use of colloidal (gelatin) solutions in shock. JAMA 64:721–726CrossRefGoogle Scholar
  3. 3.
    Campbell DH, Koepfli JB, Pauling L, Abrahamsen N, Dandliker W, Feigen GA, Lanni F, Le RA (1951) The preparation and properties of a modified gelatin (Oxypolygelatin) as an oncotic substitute for serum albumin. Tex Rep Biol Med 9:235–280PubMedGoogle Scholar
  4. 4.
    Parkins WM, Perlmutt JH, Vars HM (1953) Dextran, oxypolygelatin and modified fluid gelatin as replacement fluids in experimental hemorrhage. Am J Physiol 173:403–410PubMedGoogle Scholar
  5. 5.
    Schmidt-Thome J, Mager A, Schoene HH (1962) On the chemistry of a new plasma expander. Arzneimittelforschung 12:378–380PubMedGoogle Scholar
  6. 6.
    Ziporyn T (1985) The Food and Drug Administration: how those regulations came to be. JAMA 254:2037–2039, 2043–2036Google Scholar
  7. 7.
    Lundsgaard-Hansen P, Tschirren B (1980) Clinical experience with 120,000 units of modified fluid gelatin. Dev Biol Stand 48:251–256PubMedGoogle Scholar
  8. 8.
    de Jonge E, Levi M (2001) Effects of different plasma substitutes on blood coagulation: a comparative review. Crit Care Med 29:1261–1267PubMedCrossRefGoogle Scholar
  9. 9.
    Cittanova ML, Leblanc I, Legendre C, Mouquet C, Riou B, Coriat P (1996) Effect of hydroxyethylstarch in brain-dead kidney donors on renal function in kidney-transplant recipients. Lancet 348:1620–1622PubMedCrossRefGoogle Scholar
  10. 10.
    Schortgen F, Lacherade JC, Bruneel F, Cattaneo I, Hemery F, Lemaire F, Brochard L (2001) Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet 357:911–916PubMedCrossRefGoogle Scholar
  11. 11.
    Bayer O, Reinhart K, Sakr Y, Kabisch B, Kohl M, Riedemann NC, Bauer M, Settmacher U, Hekmat K, Hartog CS (2011) Renal effects of synthetic colloids and crystalloids in patients with severe sepsis: a prospective sequential comparison. Crit Care Med 39:1335–1342PubMedCrossRefGoogle Scholar
  12. 12.
    Bayer O, Kohl M, Kabisch B, Sakr Y, Schelenz C, Bauer M, Riedemann N, Badreldin A, Doenst T, Hartog C, Reinhart K (2011) Effects of synthetic colloids on renal function in cardiac surgical patients. Intensive Care Med 37:S202Google Scholar
  13. 13.
    Perel P, Roberts I (2011) Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane database of systematic reviews (Online) 3:CD000567Google Scholar
  14. 14.
    Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, Moerer O, Gruendling M, Oppert M, Grond S, Olthoff D, Jaschinski U, John S, Rossaint R, Welte T, Schaefer M, Kern P, Kuhnt E, Kiehntopf M, Hartog C, Natanson C, Loeffler M, Reinhart K (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. New Eng J Med 358:125–139PubMedCrossRefGoogle Scholar
  15. 15.
    Bunn F, Trivedi D, Ashraf S (2011) Colloid solutions for fluid resuscitation. Cochrane database of systematic reviews (Online) 3:CD001319Google Scholar
  16. 16.
    Editors in-Chief statement regarding published clinical trials conducted without IRB approval by Joachim Boldt,http://journals.lww.com/ejanaesthesiology/Documents/EIC%20Joint%20Statement%20on%20Retractions%2012Mar2011.pdf. Accessed 12 March 2011 DOI
  17. 17.
    Higgins JPT, Green S (eds) (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. http://www.cochrane-handbook.org. Accessed March 2011
  18. 18.
    Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care (London, England) 11:R31Google Scholar
  19. 19.
    Dung NM, Day NP, Tam DT, Loan HT, Chau HT, Minh LN, Diet TV, Bethell DB, Kneen R, Hien TT, White NJ, Farrar JJ (1999) Fluid replacement in dengue shock syndrome: a randomized, double-blind comparison of four intravenous-fluid regimens. Clin Infect Dis 29:787–794PubMedCrossRefGoogle Scholar
  20. 20.
    Lorenz W, Duda D, Dick W, Sitter H, Doenicke A, Black A, Weber D, Menke H, Stinner B, Junginger T et al (1994) Incidence and clinical importance of perioperative histamine release: randomised study of volume loading and antihistamines after induction of anaesthesia. Trial Group Mainz/Marburg. Lancet 343:933–940PubMedCrossRefGoogle Scholar
  21. 21.
    Ngo NT, Cao XT, Kneen R, Wills B, Nguyen VM, Nguyen TQ, Chu VT, Nguyen TT, Simpson JA, Solomon T, White NJ, Farrar J (2001) Acute management of dengue shock syndrome: a randomized double-blind comparison of 4 intravenous fluid regimens in the first hour. Clin Infect Dis 32:204–213PubMedCrossRefGoogle Scholar
  22. 22.
    Evans PA, Heptinstall S, Crowhurst EC, Davies T, Glenn JR, Madira W, Davidson SJ, Burman JF, Hoskinson J, Stray CM (2003) Prospective double-blind randomized study of the effects of four intravenous fluids on platelet function and hemostasis in elective hip surgery. J Thromb Haemost 1:2140–2148PubMedCrossRefGoogle Scholar
  23. 23.
    Jin SL, Yu BW (2010) Effects of acute hypervolemic fluid infusion of hydroxyethyl starch and gelatin on hemostasis and possible mechanisms. Clin Appl Thromb Hemost 16:91–98Google Scholar
  24. 24.
    Schramko AA, Suojaranta-Ylinen RT, Kuitunen AH, Raivio PM, Kukkonen SI, Niemi TT (2010) Comparison of the effect of 6% hydroxyethyl starch and gelatine on cardiac and stroke volume index: a randomized, controlled trial after cardiac surgery. Perfusion 25:283–291Google Scholar
  25. 25.
    Upadhyay M, Singhi S, Murlidharan J, Kaur N, Majumdar S (2005) Randomized evaluation of fluid resuscitation with crystalloid (saline) and colloid (polymer from degraded gelatin in saline) in pediatric septic shock. Indian Pediatr 42:223–231PubMedGoogle Scholar
  26. 26.
    van der Heijden M, Verheij J, van Nieuw Amerongen GP, Groeneveld AB (2009) Crystalloid or colloid fluid loading and pulmonary permeability, edema, and injury in septic and nonseptic critically ill patients with hypovolemia. Crit Care Med 37:1275–1281Google Scholar
  27. 27.
    Gondos T, Marjanek Z, Ulakcsai Z, Szabo Z, Bogar L, Karolyi M, Gartner B, Kiss K, Havas A, Futo J (2010) Short-term effectiveness of different volume replacement therapies in postoperative hypovolaemic patients. Eur J Anaesthesiol 27:794–800Google Scholar
  28. 28.
    Korttila K, Lauritsalo K, Sarmo A, Gordin A, Sundberg S (1983) Suitability of plasma expanders in patients receiving low-dose heparin for prevention of venous thrombosis after surgery. Acta Anaesthesiol Scand 27:104–107PubMedCrossRefGoogle Scholar
  29. 29.
    Stockwell MA, Scott A, Day A, Riley B, Soni N (1992) Colloid solutions in the critically ill. A randomised comparison of albumin and polygeline 2. Serum albumin concentration and incidences of pulmonary oedema and acute renal failure. Anaesthesia 47:7–9PubMedCrossRefGoogle Scholar
  30. 30.
    Soares RR, Ferber L, Lorentz MN, Soldati MT (2009) Intraoperative volume replacement: crystalloids versus colloids in surgical myocardial revascularization without cardiopulmonary bypass. Revista brasileira de anestesiologia 59:439–451PubMedCrossRefGoogle Scholar
  31. 31.
    Mittermayr M, Streif W, Haas T, Fries D, Velik-Salchner C, Klingler A, Oswald E, Bach C, Schnapka-Koepf M, Innerhofer P (2007) Hemostatic changes after crystalloid or colloid fluid administration during major orthopedic surgery: the role of fibrinogen administration. Anesth Analg 105:905–917PubMedCrossRefGoogle Scholar
  32. 32.
    Akech S, Gwer S, Idro R, Fegan G, Eziefula AC, Newton CR, Levin M, Maitland K (2006) Volume expansion with albumin compared to gelofusine in children with severe malaria: results of a controlled trial. PLoS Clin Trials 1:e21PubMedCrossRefGoogle Scholar
  33. 33.
    Barron ME, Wilkes MM, Navickis RJ (2004) A systematic review of the comparative safety of colloids. Arch Surg 139:552–563PubMedCrossRefGoogle Scholar
  34. 34.
    Groeneveld AB, Navickis RJ, Wilkes MM (2011) Update on the comparative safety of colloids: a systematic review of clinical studies. Ann Surg 253:470–483PubMedCrossRefGoogle Scholar
  35. 35.
    Skinses OK (1947) Gelatin nephrosis; renal tissue changes in man resulting from the intravenous administration of gelatin. Surg Gynecol Obstet 85:563–571Google Scholar
  36. 36.
    Kief H, Engelbart K, Arnold G, Baehr H (1968) Vacuolar reabsorption of native and digested gelatin (so-called osmotic nephrosis). Virchows Arch Abb B Zellpathol 1:240–250Google Scholar
  37. 37.
    Hussain SF, Drew PJ (1989) Acute renal failure after infusion of gelatins. BMJ 299:1137–1138Google Scholar
  38. 38.
    Godet G, Lehot JJ, Janvier G, Steib A, De Castro V, Coriat P (2008) Safety of HES 130/0.4 (Voluven(R)) in patients with preoperative renal dysfunction undergoing abdominal aortic surgery: a prospective, randomized, controlled, parallel-group multicentre trial. Eur J Anaesthesiol 25:986–994Google Scholar
  39. 39.
    Ooi JS, Ramzisham AR, Zamrin MD (2009) Is 6% hydroxyethyl starch 130/0.4 safe in coronary artery bypass graft surgery? Asian Cardiovasc Thorac Annals 17:368–372Google Scholar

Copyright information

© Copyright jointly held by Springer and ESICM 2012

Authors and Affiliations

  • D. O. Thomas-Rueddel
    • 1
    • 2
  • V. Vlasakov
    • 1
  • K. Reinhart
    • 1
  • R. Jaeschke
    • 3
  • H. Rueddel
    • 1
    • 2
  • R. Hutagalung
    • 1
  • A. Stacke
    • 1
  • C. S. Hartog
    • 1
    • 2
  1. 1.Department of Anesthesiology and Intensive Care Medicine, Jena University HospitalFriedrich Schiller University JenaJenaGermany
  2. 2.Center for Sepsis Control and Care (CSCC Jena), Integrated Research and Treatment CenterFriedrich Schiller University JenaJenaGermany
  3. 3.Department of Medicine and Department of Clinical Epidemiology and BiostatisticsMcMaster UniversityHamiltonCanada

Personalised recommendations