Description of Event or Problem · 1
THIS SERIOUS SPONTANEOUS REPORT WAS REPORTED BY A PHYSICIAN VIA A SALES REP AND CONCERNS A (B)(6) MALE PT (HEIGHT (B)(6), WEIGHT (B)(6)) WHO DIED DUE TO AIR EMBOLISM ON (B)(6) 2009 AFTER REPORTEDLY BEING TREATED WITH QUIXIL, HOWEVER, IT WAS SUBSEQUENTLY CONFIRMED THAT THE PT DID NOT RECEIVE TREATMENT WITH QUIXIL FIBRIN SEALANT OR ITS APPLICATOR. AIR WAS INTRODUCED THROUGH AN UNIDENTIFIED NEEDLE INSERTED INTO THE PT'S KNEE ADJACENT TO THE ARTHROSCOPY PORTAL AND CONNECTED TO AN AIR SUPPLY THROUGH UNSPECIFIED TUBING WHICH WAS NOT PROVIDED WITH THE QUIXIL KIT. THE PT SIGNED TO AGREE TO TAKE PART IN THE STUDY ON (B)(6) 2009 AND WAS ALLOCATED TO THE (B)(6) WITH DEBRIDEMENT ON (B)(6) 2009, TRIAL # (B)(6), HOSP # (B)(6). THE STUDY WAS A NON-OMRIX SPONSORED TRIAL. AN UNSPECIFIED LEGAL PROCEEDING REVEALED A SERIOUS ADVERSE EVENT TO A SURGICAL PT. THE EVENT NARRATIVE IS BASED ON SEVERAL HUNDRED PAGES OF LEGAL DOCUMENTS, INCLUDING THE OPERATING SURGEON'S STATEMENTS, EXPERT OPINIONS AND THE PT'S MEDICAL RECORDS. THE PT WAS UNDERGOING ARTHROSCOPIC AUTOLOGOUS CHONDROCYTE TRANSPLANTATION TO TREAT PERSISTENT KNEE PAIN FROM TRAUMATIC OSTEO-CHONDRAL DEFECT. THE OPERATING SURGEON REPORTEDLY CONNECTED THE CROSS-SEAL PRESSURE REGULATOR TO A PRESSURIZED AIR SOURCE AND APPLIED THE AIR INTO THE RIGHT KNEE JOINT CAPSULE VIA A METALLIC SYRINGE NEEDLE AND A TUBING OF UNSPECIFIED TYPE. THE SURGEON REPORTEDLY APPLIED AIR TO DRY THE CHONDRAL DEFECT SURFACE FROM THE INSUFFLATING SALINE BEFORE THE CHONDRAL GRAFT TRANSPLANTATION. THE PT WENT INTO CARDIAC ARREST AFTER EXPERIENCING SIGNS OF HEMODYNAMIC INSTABILITY DURING THE AIR INFUSION. ALL RESUSCITATION EFFORTS FAILED. THE PT DIED OF AIR EMBOLISM AS DETERMINED BY AN AUTOPSY. THE PT HAD EXPERIENCED MULTIPLE, BILATERAL KNEE INJURIES DURING THE PAST 25 YEARS LEADING TO THE KNEE SURGERY BECAUSE OF HIS EARLIER ACTIVE AND LATER SEDATIVE LIFE STYLES. THE PAIN AND SWELLING IN THE RIGHT KNEE PERSISTED AFTER CONSERVATIVE TREATMENT. TWENTY DAYS BEFORE THE SURGERY, A RADIOLOGY STUDY REVEALED A 2 CM CHONDRAL DEFECT IN THE WEIGHT-BEARING, RIGHT MEDIAL FEMORAL CONDYLE. THE PT THEN CONSENTED TO THE SURGICAL INTERVENTION AS PART OF A CLINICAL STUDY CONDUCTED BY THE OPERATING SURGEON. THE STUDY, WITH NO RELATIONSHIP TO ETHICON OR OMRIX, WAS DESIGNED TO EXAMINE THE EFFECTIVENESS OF USING AUTOLOGOUS CHONDRAL GRAFT TO TREAT TRAUMATIC OR DEGENERATIVE CHONDRAL DEFECTS. THE PT WAS RANDOMIZED TO THE EXPERIMENTAL ARM (AS OPPOSED TO THE CONTROL ARM, IN WHICH CONVENTIONAL TREATMENT WAS CONDUCTED) AND UNDERWENT THE STUDY PROCEDURE. THE PURPOSE OF THE ARTHROSCOPIC SURGERY IN THE RIGHT KNEE CONSTITUTED THE FIRST STAGE OF THE STUDY PROCEDURE WAS FOR CHONDRAL SURFACE DEBRIDEMENT AND TO HARVEST THE PT'S OWN CHONDRAL CELLS. MULTIPLE VIDEO SEGMENTS LATER PROVIDED BY THE HOSP WHERE THE SURGERY WAS BEING PERFORMED SHOWED THE SURGERY AT VARIOUS STAGES INCLUDING MULTIPLE ACTIVE BLEEDING SITES ON THE CONDYLE SURFACE AND BLOOD STREAMING INTO THE INSUFFLATING SALINE. THE VIDEOS ALSO SHOWED A METALLIC NEEDLE INFUSING UNSPECIFIED GAS INTO THE JOINT CAPSULE WHEN THE GAS WAS BUBBLING OUT TO THE EXTERIOR VIA A BLEEDING INCISION PENETRATING THE KNEE JOINT CAPSULE. NONE OF THE SURGICAL INSTRUMENTS (INCLUDING THE METAL SYRINGE NEEDLE) APPEARED TO BE AN OMRIX/ETHICON PRODUCT OR A PART OF AN OMRIX/ETHICON PRODUCT AS SHOWN IN THE VIDEOS. ACCORDING TO A LATER STATEMENT FROM THE OPERATING SURGEON, THE PT'S OXYGEN SATURATION, HEART RATE AND BLOOD PRESSURE DROPPED 55 MIN AFTER THE ANAESTHESIA INDUCTION. THIRTY-FIVE MIN OF CARDIOPULMONARY RESUSCITATION WAS FUTILE. THE PT WAS DECLARED DEAD 60 MIN INTO THE SURGERY. SIGNS OF "SURGICAL EMPHYSEMA" WERE DETECTED IN THE PT'S NECK, CHEST, RETROPERITONEAL SEROSA AND THE MESENTERIES IN AN AUTOPSY CONDUCTED ONE DAY AFTER THE PT'S DEATH. THE CORONER CONCLUDED THAT THE CAUSE OF DEATH WAS AIR (INFUSED INTO THE KNEE JOINT CAPSULE VIA THE NEEDLE) ENTERING THE VENOUS SYSTEM THROUGH DEEP-PENETRATING OSTEOARTHRITIC PSEUDOCYSTS". THE TOTAL VOLUME OF AIR ENTERING THE PT'S CIRCULATION WAS ESTIMATED AT 300 ML. THE OPERATING SURGEON, IN A SUBSEQUENT SUPPLEMENT STATEMENT, INDICATED THAT A CROSS-SEAL PRESSURE REGULATOR WAS USED IN THE SURGERY TO REGULATE THE AIR FLOW INTO THE KNEE JOINT CAPSULE. THE USE OF THE PRESSURE REGULATOR WAS NOT CAPTURED IN ANY OF THE SIX VIDEO SEGMENTS PROVIDED BY THE HOSP. THE DR ALSO CONFIRMED THAT NO QUIXIL BIOLOGICS WERE USED IN THE SURGERY. THE OPERATING SURGEON INDICATED THAT HE MADE THE ADD'L SMALL INCISION PENETRATING THE KNEE CAPSULE (SHOWING BLOODY GAS BUBBLES IN THE VIDEOS) OUT OF THE CONSIDERATION OF AIR EMBOLISM RISK CARRIED WITH INFUSING AIR INTO THE KNEE JOINT CAPSULE. COMPANY PHYSICIAN COMMENT ON (B)(6) 2010: THE AVAILABLE INFO ASSOCIATED WITH THIS CASE CLEARLY INDICATES THAT THE CAUSE OF PT DEATH WAS AIR EMBOLISM. THE AIR ENTRY POINT INTO THE CIRCULATION WAS MOST LIKELY THE DEBRIDED CHONDRAL SURFACE OF THE RIGHT KNEE. NEITHER THE BIOLOGIC COMPONENT NOR THE DEVICE COMPONENT OF THE QUIXIL WAS USED IN THIS PT DURING THE PHASE 1 OF THE AUTOLOGOUS MATRIX INDUCED CHONDROGENESIS (AMIC) ARTHROSCOPIC SURGERY. THEREFORE, NEITHER THE BIOLOGICS NOR THE DEVICE COMPONENTS OF THE QUIXIL WERE RELATED TO THE INTRA-OPERATIVE GAS EMBOLISM AND THE PT DEATH. NO QUIXIL COMPONENT CAUSED OR CONTRIBUTED TO THE REPORTED ADVERSE PT EVENTS. BECAUSE QUIXIL SYSTEM WAS NOT INVOLVED IN THE PROCEDURE AND THE ADVERSE EVENT, "OFF-LABEL USE" AND "DEVICE MISUSE" ARE IRRELEVANT CONCEPTS AND ARE NOT APPLICABLE TO THIS CASE. THE QUIXIL INSTRUCTION FOR USE ((B)(6)) CLEARLY DEFINES THAT THE SPECIALLY DESIGNED APPLICATION DEVICE IS FOR APPLYING THE QUIXIL PRODUCT. THE SPRAYING PRESSURE RANGE AND THE DISTANCE BETWEEN THE APPLICATOR NOZZLE AND THE TISSUE SURFACE ARE ALSO SPECIFIED. ACCORDING TO MUTH ET AL (GAS EMBOLISM, A REVIEW ARTICLE IN THE NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342: 476-482), VENOUS GAS EMBOLISM OCCURS WHEN GAS ENTERS THE SYSTEMIC VENOUS SYSTEM. PHYSICAL PRECONDITIONS FOR THE ENTRY OF GAS INTO THE VENOUS SYSTEM ARE THE INCISING OF NON-COLLAPSED VEINS AND THE PRESENCE OF SUB-ATMOSPHERIC PRESSURE IN THESE VESSELS. NON-COLLAPSING VEINS INCLUDE THE EPIPLOIC VEINS, THE EMISSARY VEINS, AND THE DURAL VENOUS SINUSES. MECHANISM FOR GAS EMBOLISM DEVELOPMENT IN ORTHOPEDIC SURGERIES INCLUDES GAS INSUFFLATION INTO THE VEINS DURING ARTHROSCOPY. IN SOME CASES, AIR MAY ENTER VEINS IN COAGULATED OPERATIVE FIELDS. MULTIPLE SMALL BUT BRISK BLEEDING SITES FROM THE DEBRIDED CHONDRAL SURFACE ARE VISIBLE IN THE VIDEO SEGMENTS 3, 4, AND 6 RECORDED DURING THE SURGERY, SUGGESTING THE INCISING OF SOME NON-COLLAPSING VEINS OR VENOUS SINUS IN THE CHONDRAL TISSUE. VIDEO SEGMENT 5 SHOWS OUTFLOW GAS BUBBLES FROM A BLEEDING INCISION AT THE KNEE, SUGGESTING GAS WITH POSITIVE PRESSURE WAS BEING INFUSED INTO THE KNEE JOINT CAPSULE. BOTH PRECONDITIONS FOR DEVELOPING GAS EMBOLISM WERE APPARENTLY EXISTED AT THE SURGICAL SITE DURING THE ARTHROSCOPIC SURGERY. THE OPERATING SURGEON, ALTHOUGH WAS AWARE OF THE POSSIBILITY OF GAS EMBOLISM DEVELOPMENT IN THE SURGERY AND TOOK MEASURES TO AVOID THE COMPLICATIONS (BY PROVIDING AN OUTLET FOR THE INFUSED AIR), WAS APPARENTLY FAMILIAR WITH THE PATHOGENESIS AND PATHOPHYSIOLOGY OF GAS EMBOLISM. THEREFORE, THE MEASURES TAKEN TO AVOID AIR EMBOLISM WAS PROVED INSUFFICIENT AND INEFFECTIVE. OVERALL, THE QUIXIL SYSTEM (THE BIOLOGICS AND THE APPLICATION DEVICE) WERE NOT USED IN THIS PT AND ARE THEREFORE NOT RELATED TO THE REPORTED EVENTS. "OFF-LABEL USE" AND "MISUSE" OF ANY OF THE QUIXIL COMPONENTS ARE NOT APPLICABLE IN THE MEDICAL REVIEW OF THIS CASE.