Table 7. Literature Search: Specific Reported Adverse Events, in Alphabetical order by first author.

Author, year	Report type	Adverse event reported and incidence	Comments
Beierlein, 2000 [61]	Case report	48 year old woman developed a liquid fistula after cranial surgery for cerebral metastasis. 29 days postsurgery, 4 ml fibrin sealant (Tissucol) was injected into subgaleal cavity. 40 days postsurgery another 4 ml of fibrin sealant was injected followed by clinical signs of anaphylactic shock. Serology identified aprotinin specific IgE and IgG.	Serology confirmed. Aprotinin is a bovine protein and as such is a potential allergen.
Czepko, 2006 [62]	Single case report	Limited information from abstract in English: 259 consecutive cases performed using a transsphenoidal approach. Intraoperative rhinorrhea occurred in 40 cases where fibrin sealant was used in sella reconstruction. Twenty-six (26) cases (group I) received Surgicel, artificial dura or fascia and fibrin sealant (Tissucol) and 14 cases (group II) received TachoComb + fibrin sealant, fascia or artificial dura. One patient died due to the meningitis (group I). No further information is available and no causality is given.	Very limited information and no causality to fibrin sealant given.
Felema, 2013 [63]	Case report	A 5-month old, Ex-33-week premature, 6.6-kg male scheduled for endoscopic cranial vault remodeling for sagittal craniosynostosis. At the completion of the surgical procedure and prior to skin closure, 4 ml of fibrin sealant (Tisseel) was applied for haemostasis at an approximate distance of 5 cm from the anterior endoscopic entrance site using an aerosolized spray applicator device (Easyspray) with nitrogen as a propellent gas at a pressure of 15 psi. Immediately after fibrin sealant delivery, a sudden drop in blood pressure from 88/42 to 38/21 was noted lasting 5 min. with no perceived change in blood loss. It was hypothesized that air was introduced to the vascular system with the spray device.	Causality to fibrin sealant only a hypothesis. Tisseel fibrin sealant has a special warning and precaution in Summary of Product Characteristics for use with gas and in confined spaces.
Handa, 1989 [64]	Case report	In an observational study fibrin sealant (Beriplast B) was used in 48 places, at 36 neurosurgical operations in 34 patients. In one case where fibrin sealant was applied over the dural surface, obstruction of an epidural drain occurred resulting in an epidural haematoma (no further details in abstract).	Spray directly on drain potential obstruction.
Kanazawa, 2010 [65]	Case report	A 65 year old woman underwent surgical craniotomy where arachnoid plasty with fibrin sealant (Beriplast) was completed. Nine days post-surgery the patient underwent abrupt neurological deterioration. Neuroimaging and clinical findings indicated allergic reaction that was successfully treated with steroids. It was hypothesized that components in the fibrin sealant led to the observed allergic reaction.	Causality to fibrin sealant only a hypothesis.
Schlenker, 1987 [66]	Controlled trial. One case report	This controlled trial evaluated fibrin sealant (Tissucol) for the prevention of post lumbar puncture headache. Following lumbar puncture, patients were treated with fibrin sealant injected through lumbar needle immediately after dural tap. The first 6 patients were treated uneventfully. The 7th patient, a 58 year old female, developed aseptic meningitis treated with antibiotics. Allergy test for fibrin sealant components were negative. No evidence of contamination of trial product. The author suspected chemical irritation caused by component of the fibrin sealant could not be excluded.	Causality to fibrin sealant only a hypothesis.
Wakamoto, 2002 [67]	2 Case reports	Limited information from abstract in English: A 56 year old female undergoing microvascular decompression. Eighteen days after procedure the patient was diagnosed with aseptic meningitis. A 30 year old male experienced the same symptoms 15 days after same surgery. Dacron, Goretex and Lyodula were used together with fibrin sealant, the latter to prevent CSF leak. It was suggested that the human fibrinogen was the cause of the aseptic meningitis that was successfully treated with steroids.	Causality to fibrin sealant only a hypothesis.