MAUDE Adverse Event Report: BONESUPPORT AB CERAMENT BONE VOID FILLER

Model Number A0210-11

Device Problems Adverse Event Without Identified Device or Use Problem (2993); Insufficient Information (3190)

Patient Problems Bradycardia (1751); Asystole (4442)

Event Date 12/08/2021

Event Type  Death  

Event Description

According to the reporter the following occurred: patient undergoing hip revision experienced cardiac collapse with death following injection of cerament bone void filler.Microscopic autopsy examination conclude cause of death as extensive pulmonary micro-emboli of foreign material consistent with cerament bone void filler material.No fat emboli were identified.

Manufacturer Narrative

Manufacturer batch investigation: review of batch records for mlot0742 including quality release results have been performed.All results from release tests were within limits.The first device from the batch was sold in july 2020.As per the 14th of december 2021, (b)(4) devices of the total batch size of (b)(4) devices have been sold and it is highly likely that the majority of the sold devices have been implanted.No other complaints have been received for the batch.Manufacturer medical investigation: as of today, 4th jan 2022, available medical data is very scarce.Information has been requested, but no medical records or other documentation, have been received from reporting hospital.Therefore, the final medical investigation will be performed once the requested documentation has been received.The letter from fda, dated 21st dec 2021, contained a narrative of the autopsy report: "microscopic autopsy examination concluded the cause of death as: extensive pulmonary micro-emboli of foreign material consistent with cerament bone void filler material.Not fat emboli were identified." the cause of death has been identified, however the circumstances how the incident occurred, are unclear.To evaluate the circumstances, the medical records are needed.The "extensive pulmonary micro-emboli of foreign material" point to a syndrome called "bone cement implantation syndrome (bcis)".Background on bone cement implantation syndrome bone cement implantation syndrome (bcis) is an established clinical syndrome which orthopaedic surgeons and anesthetists are aware of, and the importance of various risk stratification and risk mitigating actions in such patients undergoing cemented total hip replacement surgery.Bcis is characterized by a number of clinical features that may include hypoxia, hypotension, cardiac arrhythmias, increased pulmonary vascular resistance (pvr), and cardiac arrest.It is most commonly associated with hip arthroplasty surgery, usually occurring at one of the five stages in the surgical procedure: femoral reaming, acetabular or femoral cement implantation, insertion of the prosthesis or joint reduction.The suggested etiologies of bcis are increase in intramedullary pressure with insertion of bone cement, air embolism, bone marrow embolism or fat embolism, histamine release, complement activation with cement or prosthesis insertion and release of vasoconstriction mediators through the reactions triggered by the embolus (e.G.Serotonin, endothelin, and platelet-derived growth factors).A randomized controlled trial of 120 patients undergoing cemented total hip arthroplasty with pmma and undergoing transesophageal echocardiography, showed that 93% of cases had visible fat emboli passing through the heart and evidence of pulmonary shunting during the procedure (no patient had symptomatic emboli).Bcis is an important recognized cause of intraoperative mortality and morbidity in patients undergoing cemented hip arthroplasty.The true incidence of cardiac arrest secondary to bcis is unknown, and mortality data are not systematically collected or published.Data from three published large case reviews of operative mortality during cemented total hip arthroplasty suggest the incidence of intraoperative mortality during cemented total hip arthroplasty to be 0.11%.Pressurization technique and over-pressurization have been cited as potential contributory causes of the emboli generating some of the clinical features of bcis.One review article from the usa detailed an interesting clinical case report showing intra-cardiac emboli of pmma cement material; in addition to detailing some of the cardio-pulmonary effects that can occur from leakage or presence into veins adjacent to the pmma injection site.The constituents and circumstances of use of bone void fillers are indeed different from that of pmma/ bone cement.However, since bone void fillers are implanted into cancellous bone with a cancellous venous network, it is theoretically possible that implantation with these devices could cause microscopic cardio-pulmonary embolization via the venous network.The incidence of this has not been quantified or reported in the literature.Thus the incidence of any intra-operative mortality associated with such micro-emboli has also not been quantified or reported in the literature.A literature search via pubmed, performed by bone support, did not yield any results of intra-operative mortality associated with bone void fillers, including cerament.A search of the maude database in the usa did find one reported case of death with a bone void filler manufactured by a different company to bone support.Summary: micro-autopsy results point to a "bone cement implantation syndrome (bcis)" as the cause of death.The circumstances how the incidence occurred are not known due to the lack of medical records.Bcis is most commonly associated with hip arthroplasty surgery, usually occurring at one of the five stages in the surgical procedure: femoral reaming, acetabular or femoral cement implantation, insertion of the prosthesis or joint reduction.Two of these surgical steps were performed during surgery: acetabular cement / bvf implantation and joint reduction.Cerament bone void filler has been on the us market approved by the fda since 2005.Later cerament bone void filler entered the 21 st dec market in 2009, then later its two sister products cerament g and cerament v (having identical calcium sulfate and hydroxyapatite constituents) in 2013 and 2015 respectively.Over cerament's long history on the market, cerament has been implanted in tens of thousands of patients worldwide, without a single intra-operative death or death causally-related to cerament ever being reported (either to bone support or any regulatory authority worldwide); or indeed any reports of such published in the scientific literature.This makes such an occurrence extremely rare.Because of the well-known risk of bcis, the risk is included in the risk assessment for cerament bone void filler (fmeca document id (b)(4)) and the following precautions have been included in the ifu: over pressurization during injection should be avoided as intra-medullar injection with any bone void filler may lead to fat embolization or embolization of cerament bone void filler into the blood stream.Over pressurization of the device may lead to extrusion of the device beyond the site of its intended application and damage the surrounding tissues.Inject carefully under visual inspection or radiographic monitoring to avoid spreading of product outside of the intended injection site.References: donaldson a j et al.Bone cement implantation syndrome.British journal of anaesthesia 102 (1): 12-22 (2009).Doi:10.1093/bja/aen328.Song ws, choi jc, kim th, oh sh, park sr, park bh.Effect of pressurized cement insertion on cardiopulmonary parameters during cemented hip hemiarthroplasty: a randomized prospective study.Hip pelvis.2014 dec;26(4):243-9.Doi: 10.5371/hp.2014.26.4.243.Koessler mj, fabiani r, hamer h, pitto rp.The clinical relevance of embolic events detected by transesophageal echocardiography during cemented total hip arthroplasty: a randomized clinical trial.Anesth analg.2001 jan;92(1):49-55.Doi: 10.1097/00000539-200101000-00010.Pmid: 11133599.Shridhar p, chen y, khalil r, plakseychuk a, cho sk, tillman b, kumta pn, chun y.A review of pmma bone cement and intra-cardiac embolism.Materials (basel).2016 oct 6;9(10):821.Doi: 10.3390/ma9100821.Pmid: 28773942; pmcid: pmc5456584.

Manufacturer Narrative

Manufacturer batch investigation: review of batch records for mlot0742 including quality release results have been performed.All results from release tests were within limits.The first device from the batch was sold in july 2020.As per the 14th of december 2021, (b)(4) devices of the total batch size of (b)(4) devices have been sold and it is highly likely that the majority of the sold devices have been implanted.No other complaints have been received for the batch.Manufacturer medical investigation: as of today, 4th jan 2022, available medical data is very scarce.Information has been requested, but no medical records or other documentation, have been received from reporting hospital.Therefore, the final medical investigation will be performed once the requested documentation has been received.The letter from fda, dated 21st dec 2021, contained a narrative of the autopsy report: "microscopic autopsy examination concluded the cause of death as: extensive pulmonary micro-emboli of foreign material consistent with cerament bone void filler material.Not fat emboli were identified." the cause of death has been identified, however the circumstances how the incident occurred, are unclear.To evaluate the circumstances, the medical records are needed.The "extensive pulmonary micro-emboli of foreign material" point to a syndrome called "bone cement implantation syndrome (bcis)" background on bone cement implantation syndrome bone cement implantation syndrome (bcis) is an established clinical syndrome which orthopaedic surgeons and anesthetists are aware of, and the importance of various risk stratification and risk mitigating actions in such patients undergoing cemented total hip replacement surgery.Bcis is characterized by a number of clinical features that may include hypoxia, hypotension, cardiac arrhythmias, increased pulmonary vascular resistance (pvr), and cardiac arrest.[1] it is most commonly associated with hip arthroplasty surgery, usually occurring at one of the five stages in the surgical procedure: femoral reaming, acetabular or femoral cement implantation, insertion of the prosthesis or joint reduction.[1] the suggested etiologies of bcis are increase in intramedullary pressure with insertion of bone cement, air embolism, bone marrow embolism or fat embolism, histamine release, complement activation with cement or prosthesis insertion and release of vasoconstriction mediators through the reactions triggered by the embolus (e.G.Serotonin, endothelin, and platelet-derived growth factors).[2] a randomized controlled trial of 120 patients undergoing cemented total hip arthroplasty with pmma and undergoing transesophageal echocardiography, showed that 93% of cases had visible fat emboli passing through the heart and evidence of pulmonary shunting during the procedure (no patient had symptomatic emboli).[3] bcis is an important recognized cause of intraoperative mortality and morbidity in patients undergoing cemented hip arthroplasty.The true incidence of cardiac arrest secondary to bcis is unknown, and mortality data are not systematically collected or published.Data from three published large case reviews of operative mortality during cemented total hip arthroplasty suggest the incidence of intraoperative mortality during cemented total hip arthroplasty to be 0.11%.[1] pressurization technique and over-pressurization have been cited as potential contributory causes of the emboli generating some of the clinical features of bcis.One review article from the usa detailed an interesting clinical case report showing intra-cardiac emboli of pmma cement material; in addition to detailing some of the cardio-pulmonary effects that can occur from leakage or presence into veins adjacent to the pmma injection site.[4] the constituents and circumstances of use of bone void fillers are indeed different from that of pmma/ bone cement.However, since bone void fillers are implanted into cancellous bone with a cancellous venous network, it is theoretically possible that implantation with these devices could cause microscopic cardio-pulmonary embolization via the venous network.The incidence of this has not been quantified or reported in the literature.Thus the incidence of any intra-operative mortality associated with such micro-emboli has also not been quantified or reported in the literature.A literature search via pubmed, performed by bonesupport, did not yield any results of intra-operative mortality associated with bone void fillers, including cerament.A search of the maude database in the usa did find one reported case of death with a bone void filler manufactured by a different company to bonesupport.Summary micro-autopsy results point to a "bone cement implantation syndrome (bcis)" as the cause of death.The circumstances how the incidence occurred are not known due to the lack of medical records.Bcis is most commonly associated with hip arthroplasty surgery, usually occurring at one of the five stages in the surgical procedure: femoral reaming, acetabular or femoral cement implantation, insertion of the prosthesis or joint reduction.Two of these surgical steps were performed during surgery: acetabular cement / bvf implantation and joint reduction.Cerament bone void filler has been on the us market approved by the fda since 2005.Later cerament bone void filler entered the european market in 2009, then later its two sister products cerament g and cerament v (having identical calcium sulfate and hydroxyapatite constituents) in 2013 and 2015 respectively.Over cerament's long history on the market, cerament has been implanted in tens of thousands of patients worldwide, without a single intra-operative death or death causally-related to cerament ever being reported (either to bonesupport or any regulatory authority worldwide); or indeed any reports of such published in the scientific literature.This makes such an occurrence extremely rare.Because of the well-known risk of bcis, the risk is included in the risk assessment for cerament bone void filler (fmeca document id (b)(4)) and the following precautions have been included in the ifu: over pressurization during injection should be avoided as intra-medullar injection with any bone void filler may lead to fat embolization or embolization of cerament bone void filler into the blood stream.Over pressurization of the device may lead to extrusion of the device beyond the site of its intended application and damage the surrounding tissues.Inject carefully under visual inspection or radiographic monitoring to avoid spreading of product outside of the intended injection site.References 1.Donaldson a j et al.Bone cement implantation syndrome.British journal of anaesthesia 102 (1): 12-22 (2009).Doi:10.1093/bja/aen328.2.Song ws, choi jc, kim th, oh sh, park sr, park bh.Effect of pressurized cement insertion on cardiopulmonary parameters during cemented hip hemiarthroplasty: a randomized prospective study.Hip pelvis.2014 dec;26(4):243-9.Doi: 10.5371/hp.2014.26.4.243.3.Koessler mj, fabiani r, hamer h, pitto rp.The clinical relevance of embolic events detected by transesophageal echocardiography during cemented total hip arthroplasty: a randomized clinical trial.Anesth analg.2001 jan;92(1):49-55.Doi: 10.1097/00000539-200101000-00010.Pmid: 11133599.4.Shridhar p, chen y, khalil r, plakseychuk a, cho sk, tillman b, kumta pn, chun y.A review of pmma bone cement and intra-cardiac embolism.Materials (basel).2016 oct 6;9(10):821.Doi: 10.3390/ma9100821.Pmid: 28773942; pmcid: pmc5456584.Update 2022-02-18: further information from hospital was received 2022-01-27.See final investigation, document reference (b)(4), in attachment.

Event Description

According to the reporter the following occurred: patient undergoing hip revision experienced cardiac collapse with death following injection of cerament bone void filler.Microscopic autopsy examination conclude cause of death as extensive pulmonary micro-emboli of foreign material consistent with cerament bone void filler material.No fat emboli were identified.Update 2022-02-18: further information from hospital was received 2022-01-27.See final investigation, document reference (b)(4), in attachment.

• Brand Name: CERAMENT BONE VOID FILLER
• Type of Device: CERAMENT BONE VOID FILLER
• Manufacturer (Section D): BONESUPPORT AB; scheelevägen 19; ideon science park; lund, sweden 22370 ; SW 22370
• Manufacturer (Section G): BONESUPPORT AB; scheelevägen 19; ideon science park; lund, sweden 223 7 0; SW 223 70
• Manufacturer Contact: kerstin sternerup ; scheelevägen 19; ideon science park; lund, sweden 223 7-0 ; SW 223 70
• MDR Report Key: 13153147
• MDR Text Key: 283161298
• Report Number: 3005304945-2022-00001
• Device Sequence Number: 1
• Product Code: MQV
• UDI-Device Identifier: 07350055430066
• UDI-Public: 07350055430066
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: K201535
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Health Professional,User Facility,Distributor
• Reporter Occupation: Risk Manager
• Type of Report: Initial,Followup
• Report Date: 02/18/2022

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Model Number: A0210-11
• Device Catalogue Number: A0210-11
• Device Lot Number: MLOT0742
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: No
• Initial Date Manufacturer Received: 12/08/2021
• Initial Date FDA Received: 01/04/2022
• Supplement Dates Manufacturer Received: 12/08/2021
• Supplement Dates FDA Received: 02/18/2022
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Date Device Manufactured: 06/26/2020
• Is the Device Single Use?: Yes
• Is This a Reprocessed and Reused Single-Use Device?: No
• Type of Device Usage: Initial
• Patient Sequence Number: 1
• Patient Outcome(s): Death
• Patient Age: 66 YR
• Patient Sex: Male