title: How safe is gelatin? A systematic review and meta-analysis of gelatin-containing plasma expanders vs crystalloids and albumin.
abstract: Gelatin is a widely used synthetic colloid resuscitation fluid. We undertook a systematic review and meta-analysis of adverse effects in randomized and nonrandomized studies comparing gelatin with crystalloid or albumin for treatment of hypovolemia. Multiple databases were searched systematically without language restrictions until August 2015. We assessed risk of bias of individual studies and certainty in evidence assessment by the Grading of Recommendations Assessment, Development, and Evaluation approach. Sixty studies were eligible, including 30 randomized controlled trials, 8 nonrandomized studies, and 22 animal studies. After gelatin administration, the risk ratios were 1.15 (95% confidence interval, 0.96-1.38) for mortality, 1.10 (0.86-1.41) for requiring allogeneic blood transfusion, 1.35 (0.58-3.14) for acute kidney injury, and 3.01 (1.27-7.14) for anaphylaxis. Well-performed nonrandomized trials found increased rates of hospital mortality and acute kidney injury or renal replacement therapy in the gelatin intervention periods. Between 17% and 31% of administered gelatin was taken up extravascularly. The mean crystalloid-to-colloid ratio was 1.4. Gelatin solutions increase the risk of anaphylaxis and may be harmful by increasing mortality, renal failure, and bleeding possibly due to extravascular uptake and coagulation impairment. Until well-designed randomized controlled trials show that gelatin is safe, we caution against the use of gelatins because cheaper and safer fluid alternatives are available.
authors.affiliation: Department for Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Moeller
authors.affiliation: Department for Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany; Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Fleischmann
authors.affiliation: Department for Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany; Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Thomas-Rueddel
authors.affiliation: Department for Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
authors.forename: Vlasislav
authors.initials: V
authors.lastname: Vlasakov
authors.affiliation: Department of Medicine (Division of Critical Care) & Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Bram
authors.initials: B
authors.lastname: Rochwerg
authors.affiliation: Department for Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Theurer
authors.affiliation: Dipartimento di Fisiopatologica Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Gattinoni
authors.affiliation: Department for Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany; Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany. Electronic address: konrad.reinhart@med.uni-jena.de.
authors.forename: Konrad
authors.initials: K
authors.lastname: Reinhart
authors.affiliation: Department for Anesthesiology and Intensive Care, Jena University Hospital, Jena, Germany; Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
authors.forename: Christiane S
authors.initials: CS
authors.lastname: Hartog
mesh_terms: D000077324:Crystalloid Solutions; D005440:Fluid Therapy; D005780:Gelatin / Q000008:administration & dosage* / Q000009:adverse effects; D017052:Hospital Mortality; D006801:Humans; D020896:Hypovolemia / Q000401:mortality / Q000628:therapy*; D007552:Isotonic Solutions / Q000008:administration & dosage* / Q000009:adverse effects; D010952:Plasma Substitutes / Q000009:adverse effects*
chemical_list: D000077324:Crystalloid Solutions; D007552:Isotonic Solutions; D010952:Plasma Substitutes; D005780:Gelatin
keywords: Adverse effects; Anaphylaxis; Bleeding; Colloids; Plasma substitutes; Renal insufficiency