What adverse events have been reported in clinical trials of gelatide?
Executive summary
Clinical trials and systematic reviews of products containing gelatin report a range of adverse events, most commonly mild gastrointestinal or procedure‑related events in topical/enteral uses, but serious concerns—anaphylaxis, bleeding/coagulation problems, and kidney injury—have been repeatedly raised in the literature on intravenous gelatin plasma expanders (e.g., succinylated gelatin) [1] [2] [3] [4] [5]. Large systematic reviews conclude gelatin "may have serious adverse effects" and urge caution until higher‑quality randomized data show safety [6] [3].
1. Intravenous gelatin solutions: signals for anaphylaxis, bleeding and kidney harm
Randomized and nonrandomized trials pooled in systematic reviews show gelatin plasma expanders are associated with safety signals: increased risk of anaphylaxis, coagulation impairment with bleeding risk, and possible renal injury including higher rates of acute kidney injury (AKI) in surgical and critical care contexts [3] [7] [5]. The 2016 systematic review and meta‑analysis concluded "gelatin may have serious adverse effects" and cautioned against routine use when safer fluids exist [3] [6]. Observational and small randomized studies have specifically linked gelatin use to increased biomarkers of renal tubular injury and higher AKI incidence after cardiac surgery [5].
2. How frequent and how severe are the allergic reactions?
Reports estimate severe hypersensitivity (anaphylaxis) to succinylated gelatin products in the low but non‑negligible range (reported 0.0062–0.038% in older analyses), comparable to some radiologic contrast agents; systematic reviewers flag this as a clinically relevant risk that requires the same risk‑management mindset as for contrast media [8] [3]. Drug‑or‑product summaries likewise list anaphylaxis risk and bleeding/renal concerns among important safety items [7] [4].
3. Context matters: route, formulation and indication change the safety profile
Not all "gelatin" uses are the same. Intravaginal gelatin capsules used to deliver probiotics showed no severe adverse events in a phase I randomized safety trial, and were well tolerated overall, illustrating that topical or localized formulations carry very different risk profiles from intravenous colloids [2] [9]. Hemostatic gelatin matrices applied topically during surgery reported most adverse events as mild and attributed to anesthesia or surgery rather than the gelatin product itself [1]. These contrasts show adverse event type and frequency depend on formulation, dose, and route [1] [2].
4. What major reviews recommend — caution and comparative choices
Systematic reviewers and meta‑analysts do not ban gelatin outright but recommend caution: until robust randomized data show acceptable safety, clinicians should prefer cheaper and safer alternatives for volume resuscitation (crystalloids, albumin where indicated) and apply risk‑management strategies when using gelatin [3] [6] [8]. Recent large trials remain limited; one 2025 trial in septic patients found no difference in serious adverse events or mortality for a balanced gelatin solution but was terminated early and thus leaves residual uncertainty [10].
5. Gaps, limitations and what the sources do not say
Available sources do not mention a single, comprehensive incidence rate for all gelatin‑related adverse events across modern formulations and clinical settings; risk estimates vary by product type (succinylated vs other gelatin derivatives), indication, and study quality [3] [4]. Sources also do not provide up‑to‑date regulatory consensus that uniformly restricts all gelatin products worldwide—reviews instead call for cautious use and more high‑quality trials [3] [6].
6. Practical implications for clinicians and patients
Clinicians should recognize that intravenous gelatin colloids carry documented risks of hypersensitivity, coagulation impairment and possible renal harm and should weigh these against alternatives; when gelatin is used, monitor renal function and be prepared to manage allergic reactions [3] [5] [8]. For non‑intravenous gelatin uses (topical hemostats, vaginal capsules, oral supplements), trials report mainly mild, procedure‑related or gastrointestinal adverse events, but safety conclusions must be formulation‑specific [1] [2] [11].
7. Bottom line — measured caution, targeted research
The evidence base shows real safety signals for intravenous gelatin colloids—anaphylaxis, bleeding/coagulation issues and AKI—that have led systematic reviewers to advise caution and to prefer safer alternatives where possible [3] [6] [5]. Other gelatin formulations used topically or enterally report far fewer severe harms in trials, but the diversity of products means each formulation requires its own safety assessment before generalizing findings [1] [2].