What is the clinical safety of using glutaraldehyde in patients undergoing surgery?

What is the clinical safety of using glutaraldehyde in patients undergoing surgery?

Comment by InpharmD Researcher

Several studies in animal models and human cases have shown glutaraldehyde can cause mucosal injury, inflammation, acute colitis, peritonitis and other complications when inadvertently contacted or absorbed during endoscopic, laparoscopic or other procedures. Autologous tissue treated with glutaraldehyde has been used successfully in some cardiac surgeries, but the overall evidence suggests glutaraldehyde exposure carries risks for patients with some literature suggesting minimizing or discontinuing if possible alternatives exist.

Background

Although the risk of glutaraldehyde as an occupational hazard for healthcare workers has been documented and warned against by the CDC and NIOSH, discussions regarding safety for patients undergoing surgery are more limited. Some literature warns increased duration and level of disinfectant exposure may have adverse effects, including upper and lower respiratory tract irritation, inflammation, edema, ulceration, and allergic reactions, although this is not specific to patients. Still, effects of glutaraldehyde in patients undergoing surgery are not well elucidated in the literature, aside from small studies and some case reports that demonstrate its use in a surgical setting. [1]

A 2024 review on the use of glutaraldehyde during laparoscopic and endoscopic procedures looked at potential complications from inadvertent contact or exposure. The review synthesized evidence from 35 studies in animal models and human cases on the harmful effects of glutaraldehyde. While glutaraldehyde has useful disinfectant properties, the review found it can damage tissues depending on concentration and duration of contact. In animal studies, glutaraldehyde injected into the colon or introduced during simulated laparoscopy caused mucosal injury, inflammation, and organ damage. [2]

The review further identified over 160 reported human cases of glutaraldehyde-induced colitis following colonoscopy or endoscopy. Symptoms usually appear within 24 hours and include bleeding, diarrhea, and abdominal pain. Imaging and biopsies revealed features of acute colitis. Residual glutaraldehyde left in endoscope channels or used instead of saline seemed to be the cause. Rare cases of peritonitis and complications like fistulae were reported after glutaraldehyde entered the abdominal cavity during laparoscopy. Overall outcomes were good with conservative management. Given the potential harms, occupational hazards and limited disinfection properties, the authors suggested the use of glutaraldehyde in patient care should be discontinued. Proper rinsing and drying of instruments was emphasized to minimize risk if use was unavoidable. [2]

Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

What is the clinical safety of using glutaraldehyde in patients undergoing surgery?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-4 for your response.

Use of glutaraldehyde-treated autologous pericardial patch in complete atrioventricular septal defect repair
Design	Retrospective study N= 34
Objective	To investigate the impact of glutaraldehyde-treated autologous pericardial patch on postoperative atrioventricular valve function
Study Groups	Autologous pericardial patch (n= 44) Polytetrafluoroethylene (PTFE) patch (n= 15)
Inclusion Criteria	Patients who underwent repair of complete atrioventricular septal defects using the double-path technique
Exclusion Criteria	Patients with ventricular septal defects (VSD) components not closed with a patch, those with Fallot-type AVSD, and those who had previous pulmonary banding
Methods	Patient data were compiled from a pediatric cardiac center in Turkey. Patients were divided into two groups based on type of patch used for the repair of the ventricular component of the atrioventricular septal defect. Patients in group 1 received a glutaraldehyde-treated autologic pericardial patch, while those in group 2 received a polytetrafluroethylene patch.
Duration	Treated between January 1, 2018 and May 15, 2023
Outcome Measures	Mortality, length of stay, postoperative atrioventricular valve insufficiency
Baseline Characteristics		Autologous pericardial patch (n= 44)	PTFE (n= 15)
	Age at repair, months	6 (5 to 18)	7 (5 to 12)
	Female	25	9
	Body weight, kg	5.5	5.4
	Preoperative condition Intensive care unit Mechanical ventilation	4 2	3 1
Results	Endpoint	Autologous pericardial patch (n= 44)	PTFE (n= 15)	p-Value
	Mortality Early (< 30 days) Late	5 0	1 1	NS NS
	Length of stay Hospital ICU	11.5 (6 to 42) 7 (2 to 30)	13 (5 to 64) 9 (4 to 34)	NS NS
	Postoperative left atrioventricular valve regurgitation Trivial/mild Moderate/severe	31 12	11 4	NS NS
	Postoperative right atrioventricular valve regurgitation Trivial/mild Moderate/severe	35 9	14 1	NS NS
	No significant differences were observed between the two groups in terms of cross-clamp time, cardiopulmonary bypass time, postoperative atrioventricular valve insufficiency, ICU stay, and hospital stay.
Adverse Events	Most common postoperative complication included arrhythmia, with postoperative AV block reported in 11 patients (18.6%), as well as sepsis in five patients (8.5%), acute renal failure requiring peritoneal dialysis in four patients (6.8%), low cardiac output syndrome in four patients (6.8%), and pneumonia in two patients (3.4%).
Study Author Conclusions	Glutaraldehyde-treated autologous pericardium is a reliable material for the repair of the ventricular component in complete AVSD. Fixation with glutaraldehyde enhances the usability of the pericardium and reduces the risk of aneurysmal dilation. The use of this patch allows for effective closure of the ventricular septal defect in complete AVSD without significant residual shunting. However, further stu- dies are needed to evaluate its long-term efficacy.
InpharmD Researcher Critique	Although glutaraldehyde-treated patches were considered to be overall safe, limited discussion focused on safety endpoints specific to the use of this particular disinfectant. Rather, overall outcomes and complications appear to be general events associated with the procedure.

References:

Doyurgan O, Balık H. Use of glutaraldehyde-treated autologous pericardial patch in complete atrioventricular septal defect repair. Eur Rev Med Pharmacol Sci. 2023;27(22):11013-11020. doi:10.26355/eurrev_202311_34470

Surgical site infection associated with the use of bovine serum albumine-glutaraldehyde surgical adhesive (BioGlue®) in cranial surgery: a case–control study
Design	Case–control study N= 90
Objective	To assess whether the use of BioGlue® (albumine-glutaraldehyde) surgical adhesive is a risk factor for surgical site infections (SSI) in cranial surgery
Study Groups	Cases (n= 30) Controls (n= 60)
Inclusion Criteria	Patients who underwent craniotomy between January 2006 and June 2007, needed a second operation to wash out the wound, had an intraoperative culture grown, and had an infection noted in the discharge report
Exclusion Criteria	Burr hole operations and shunt procedures
Methods	A retrospective review of medical reports, microbiology data, and surgical details at a single neurosurgical unit was conducted. Univariate and multivariate analyses were performed to identify risk factors of SSI. BioGlue® and Neuropatch® was utilized at the discretion of the surgeon. For dural defects during surgery, if sutures alone were insufficient for water-tight closure, surgeons either applied BioGlue® alone on a Surgicel® patch for small defects, performed duraplasty fixed with sutures potentially enhanced with BioGlue® for larger defects, or used autograft or Neuropatch® for the duraplasty material.
Duration	January 1, 2006 to June 30, 2007
Outcome Measures	Cases and assessment of risk factor for SSI with BioGlue®
Baseline Characteristics		Study patients (N= 90)
	Age, years	52.7 ± 16.8
	Female	51
	Underwent infratentorial surgery	15
Results	Endpoint	Cases (n= 30)	Control (n= 60)	Odds ratio (95% confidence interval [CI])	p-Value
	Univariate comparison of BioGlue®	13 (43.3%)	4 (6.7%)	10.7 (3.08 to 37.17)	< 0.05
	Univerate comparison of BioGlue® + Neuropatch®	12 (40%)	2 (3.3%)	19.3 (4.0 to 94.6)	< 0.05
	Multivariate logistic regression comparison of BioGlue®	--	--	9.39 (1.85 to 47.67)	0.007
Adverse Events	N/A
Study Author Conclusions	BioGlue® seems to increase the risk of SSI for patients who underwent craniotomy, especially when associated with synthetic dural graft. BioGlue® triggers an intense inflammatory response, which causes wound breaches allowing bacteria to spread down in the wound, and then creates an ideal environment for bacterial growth.
InpharmD Researcher Critique	Limitations include a non-matched case-control design, potential confounding factors not fully accounted for, and lack of data on CSF leakage.

References:

Gaberel T, Borgey F, Thibon P, Lesteven C, Lecoutour X, Emery E. Surgical site infection associated with the use of bovine serum albumine-glutaraldehyde surgical adhesive (BioGlue) in cranial surgery: a case-control study. Acta Neurochir (Wien). 2011;153(1):156-163. doi:10.1007/s00701-010-0830-3

Precise reconstruction of the aortic valve using glutaraldehyde-treated autologous pericardium in new formula: a case report
Design	Case report
Case presentation	A 35-year-old male patient with past history of aortic valve disease and endocarditis underwent aortic valve reconstruction surgery. Echocardiography prior to procedure found a degenerative aortic valve with severe regurgitation, reduced left ventricular ejection fraction, and specific aortic root dimensions. The patient underwent a novel technique utilizing glutaraldehyde, which allows for avoidance of anticoagulation requirements and thus improved quality of life. The procedure was performed through a midline sternotomy and pericardiectomy. A large piece of pericardium (10 cm × 10 cm) was harvested and treated with 6.25% glutaraldehyde for 15 min, then rinsed in normal saline for 10 min. Acquired parameters for reconstruction of the new aortic cusp were measured for each aortic valve size.
Study Author Conclusions	The reported surgical technique offers a promising approach for aortic valve reconstruction using autologous pericardium. The detailed preoperative planning and the systematic surgical steps described in this article can potentially improve the outcomes of aortic valve repair procedures, especially in patients with complex aortic valve pathologies. This technique may provide a viable alternative to conventional aortic valve replacement, preserving the patient’s native valve structure and potentially reducing the need for lifelong anticoagulation. Further clinical studies are warranted to evaluate the long-term durability and efficacy of this technique.

References:

Sabzi F, Heydari A, Asadmobini A. Precise reconstruction of the aortic valve using glutaraldehyde-treated autologous pericardium in new formula: a case report. J Med Case Rep. 2024;18(1):314. Published 2024 Jul 9. doi:10.1186/s13256-024-04637-6

Efficacy of Glutaraldehyde-Treated Leaflets for Mitral Valve Repair to Treat Active Infective Endocarditis: A Case Report
Design	Case report
Case presentation	A patient presented to the hospital with complaints of left maxillary and left wrist pain following intermittent fever and arthralgia over the previous 6 months. Laboratory testing found elevated white blood cell levels and C-reactive protein level of 13.8 mg/dL, while echocardiography found severe mitral regurgitation, anterior leaflet prolapse, and a mobile vegetation >10 mm at the A3 scallop of the mitral valve, plus a dilated left atrium. Brain infarction in the left cerebellar hemisphere was also found, and blood cultures were positive for Streptococcus parasanguinis. The patient underwent urgent mitral valve repair surgery. During the course of the operation, glutaraldehyde 0.6% was used to debride and decontaminate following removal of large vegetation from valve and ventricle. Scrubbing with glutaraldehyde was noted to strengthen edges of erosion sites, allowing them to withstand stitch suturing. The surgery was eventually completed, and the patient's postoperative course was uneventful. The patient was extubated after 1 day and discharged from intensive care unit on day 2. The patient was discharged from the hospital on postoperative day 28 without any complications.
Study Author Conclusions	We report intraoperative GA use in a case of valve repair for mitral valve prolapse associated with active infective endocarditis. GA scrubbed at the site of infection resulted in decontamination and reinforcement of infected fragile tissue, prevention of excessive debridement, and strengthening of the edges of valve leaflets to facilitate suturing.

References:

Isoda S, Yamazaki I, Matsuki Y, et al. Efficacy of Glutaraldehyde-Treated Leaflets for Mitral Valve Repair to Treat Active Infective Endocarditis: A Case Report. Ann Thorac Cardiovasc Surg. 2019;25(6):340-343. doi:10.5761/atcs.cr.17-00222