NEURAXIAL SAFETY UPDATE (ISO 80369-6 AND CALIFORNIA LAW) ANTONIA ROTH – PRODUCT MANAGER, PAIN CONTROL MARKETING October, 2016

AGENDA Background ISO 80369-6 and California Law Timing Products Affected Questions

Why Are We Here? Wayne Jowett, 18, died after a toxic cancer drug was wrongly injected into his spine at Nottingham's Queen's Medical Centre in 2001. Mayra Cabrera, 30, suffered a heart attack when Bupivacaine, a potent epidural anesthetic, was mistakenly attached to her intravenous drip in 2004. She died after giving birth to her son Zac at Great Western hospital, where she had worked as a nurse. The drug he was given to complete his treatment, Vincristine, is safe if injected into a vein, but highly toxic if given "intrathecally" - into the spine. B. Braun Melsungen AG

Medication Errors During Regional Anesthesia Authors Study design Results Patel et al. 2015 Systematic review Obstetric Neuraxial Drug Administration Errors The review found 29 cases of drug administration errors. There were 14 ampoule errors, 8 syringe swaps, 3 line confusions and 4 infusion errors. Beckers et al. 2012 Inadvertent epidural injection of drugs for intravenous use The authors found that syringe swap and ampoule error and epidural catheter–IV line confusion were common causes of error. Hew et al. 2003 "Syringe swap", "ampoule error", and epidural/intravenous line confusion were the main sources of error in 36/37 cases (97%). B. Braun Melsungen AG

Medication Errors During Regional Anesthesia It is difficult to define the relevant literature, as there is no consensus about the definition of medication errors. A cluster review found that 30 claims alleged administration of the wrong drug; 24 claims that a drug was administered in the wrong dose; 5 claims that a drug was administered in the wrong order; and 2 claims that administration occurred by the wrong route. B. Braun Melsungen AG

Consequences of Medication Errors According to the seminal report ‘To err is human’ by the US-based Institute of Medicine in 2000, adverse events occur in 2.9–3.7% of hospital admissions, with 6.6-13.6% of adverse events leading to death. On the basis of these numbers, the report estimated 44000–98000 deaths per year due to medical errors in US hospitals, with 50% of these adverse events considered to be preventable. [Wacker et al. 2014] A self-reporting survey (Canadian Society of Anesthesiologists) on 687 anesthesiologists reports found four deaths. [Orser et al. 2001] A systematic literature research found a total of 29 cases of errors in obstetric neuraxial drug administration, with 4 deaths. [Patel et al. 2015] Systematic review on administration of Intrathecal chemotherapy: Case reports, clinical studies, and review articles pertaining to Intrathecal medication errors were included in the review. There have been numerous cases of antineoplastic agents intended for administration by the parenteral route being inadvertently given intrathecally. Vincristine has been implicated 31 times (25 deaths), as well as vindesine, asparaginase, bortezomib, daunorubicin, and dactinomycin. This has led to profound toxicity and, commonly, death. [Gilbar 2014] B. Braun Melsungen AG

Consequences of Medication Errors Accidental Intrathecal vincristine administration resulting in progressive ascending radiculomyeloencephalopathy has been repeatedly reported. [Pongudom et al. 2011, Qweider et al. 2007, Dettmeyer et al. 2001] Epidural analgesia can cause severe cardio- and neurotoxicity when inadvertently administered via the intravenous route. Koczmara et al. described a case of Bupivacaine given intravenously, resulting in death. [Koczmara et al. 2007] Other authors have described accidental Intrathecal administration of a large dose of tranexamic acid, also resulting in death. [Yeh et al. 2003] B. Braun Melsungen AG

Possible Reasons for Wrong Route Administration & Misconnections Low Lighting Multiple Devices Multiple Lines Time Pressure Compatible Connectors Compatible Connectors Dis-connections Lack of Tactile Feedback Unintended Use of Tubes Moving Patient Setting B. Braun Melsungen AG http://www.stayconnected.org/resources.html 8

The Challenge Connectivity within the same therapy... but not with other routes IV/ Hypodermic IV/ Hypodermic Limb Cuff Enteral Respiratory Urinary Enteral Respiratory Limb Cuff Neuraxial Neuraxial Urinary B. Braun Melsungen AG StayConnected 9

Who’s Involved? Various Manufacturers, Group Purchasing Organizations, Societies, Foundations, Associations and Institutes B. Braun Melsungen AG

Who’s Involved? B. Braun Melsungen AG

Who’s Involved? B. Braun Melsungen AG

ISO 80369 Series B. Braun Melsungen AG

Status of ISO 80369-6 (NRFit) Standard for small-bore connectors for liquids and gases in healthcare applications Part 6: Connectors for neuraxial applications … PUBLISHED March 15, 2016. B. Braun Melsungen AG

Scope of ISO 80369-6 (NRFit) Specifies requirements for small-bore connectors intended to be used for connections in neuraxial applications. Neuraxial applications involve the use of medical devices intended to administer medications to neuraxial sites, wound infiltration delivery, and other regional anesthesia procedures or to monitor or remove cerebro-spinal fluid for therapeutic or diagnostic purposes. Sites for neuraxial application include… the spine intrathecal or subarachnoid space ventricles of the brain and the epi-, extra, or peri-dural space B. Braun Melsungen AG

Scope of ISO 80369-6 (NRFit) Neuraxial application anesthetics can be administered regionally affecting a large part of the body, such as a limb, and include plexus blocks, such as brachial plexus blocks or single nerve blocks. Also included are continuous infusion of wounds with local anesthetic agents. For the purposes of this standard, local anesthesia injected hypodermically is not considered a neuraxial application. Intended administration includes intrathecal chemotherapy, local anesthetics, radiological contrast agents, antibiotics, analgesics. B. Braun Melsungen AG

Timing for Implementation It is the recommendation of the committees that the content of this publication be adopted for implementation nationally not earlier than 3 years from the date of publication for equipment newly designed and not earlier than 5 years from the date of publication for equipment already in production. IMPORTANT NOTE FOR CALIFORNIA CUSTOMERS:  Starting 2017, California law prohibits health facilities from using an epidural connection that would fit into a connection port other than the type for which it was intended. This means California health facilities should no longer use epidural products with Luer connectors as of Jan. 1, 2017. B. Braun Melsungen AG

California Legislation Assembly Bill No. 444 CHAPTER 198 An act to amend Section 1279.7 of the Health and Safety Code, relating to health facilities. [Approved by Governor August 13, 2015. Filed with Secretary of State August 13, 2015.] legislative counsel’s digest AB 444, Gipson. Health facilities: epidural and enteral feeding connectors. Existing law, as of January 1, 2016, prohibits a health facility, as defined, from using an epidural connector or an enteral feeding connector, that would fit into a connector other than the type it was intended for, unless an emergency or urgent situation exists and the prohibition would impair the ability to provide health care. Existing law also requires a health facility to develop a patient safety plan and, until January 1, 2016, requires that plan to include measures to prevent adverse events associated with misconnecting enteral feeding and epidural lines. Violation of these provisions is a misdemeanor. This bill would make the provisions relating to an epidural connector operative as of January 1, 2017, and would make the provisions relating to an enteral feeding connector operative as of July 1, 2016. The bill would make conforming changes. B. Braun Melsungen AG

California Legislation Assembly Bill No. 444 CHAPTER 198 The people of the State of California do enact as follows: SECTION 1. Section 1279.7 of the Health and Safety Code is amended to read: 1279.7. (a) A health facility, as defined in subdivision (a), (b), (c), or (f) of Section 1250, shall implement a facility-wide hand hygiene program. (b) Commencing January 1, 2017, a health facility, as defined in subdivision (a), (b), (c), or (f) of Section 1250, is prohibited from using an epidural connector that would fit into a connector other than the type it was intended for, unless an emergency or urgent situation exists and the prohibition would impair the ability to provide health care. (c) Commencing January 1, 2016, a health facility, as defined in subdivision (a), (b), (c), or (f) of Section 1250, is prohibited from using an intravenous connector that would fit into a connector other than the type it was intended for, unless an emergency or urgent situation exists and the prohibition would impair the ability to provide health care. B. Braun Melsungen AG

California Legislation Assembly Bill No. 444 CHAPTER 198 The people of the State of California do enact as follows: (d) Commencing July 1, 2016, a health facility, as defined in subdivision (a), (b), (c), or (f) of Section 1250, is prohibited from using an enteral feeding connector that would fit into a connector other than the type it was intended for, unless an emergency or urgent situation exists and the prohibition would impair the ability to provide health care. (e) The Advanced Medical Technology Association shall, on January 1 of each year until the standards are developed, provide the Legislature with a report on the progress of the International Organization for Standardization in developing new design standards for connectors for intravenous, epidural, or enteral applications. (f) A health facility that is required to develop a patient safety plan pursuant to Section 1279.6 shall include in the patient safety plan measures to prevent adverse events associated with misconnecting intravenous, enteral feeding, and epidural lines. This subdivision shall become inoperative as to epidural connectors upon the operative date of subdivision (b), and as to intravenous connectors upon the operative date of subdivision (c). and as to enteral feeding connectors upon the operative date of subdivision (d). B. Braun Melsungen AG

ISO 80369-6 (NRFit) B. Braun Melsungen AG

Examples Examples of devices affected in ISO 80369-6 include: Spinal needles Epidural needles Catheter connectors Loss of resistance syringes Epidural / spinal syringes Epidural pump tubing / extension tubing Filters, Filter Straws, Filter Needles Stopcocks used with Manometers B. Braun Melsungen AG

B. Braun Affected Devices B. Braun Melsungen AG

Epidural Filter Longer, thinner Luer Shorter collar Shorter, thicker Longer collar Longer, thinner Luer Shorter collar Shorter, thicker B. Braun Melsungen AG

Spinal Procedural Slip Syringe Indicates “NRFit slip” Collar No Collar No indication of “NRFit slip” B. Braun Melsungen AG

Glass LOR Lock Syringe Luer No “NRFit” indication Elongated Collar Indicates “NRFit” Luer No “NRFit” indication B. Braun Melsungen AG

No “NRFit Lock” indication 20 mL Dosing Syringe Indicates “NRFit Lock” Yellow plunger Clear plunger No “NRFit Lock” indication B. Braun Melsungen AG

Epidural Needle NRFit Luer Opague stylet hub Translucent stylet hub B. Braun Melsungen AG

Spinal Needle Opague stylet hub Prism to help identify CSF Translucent stylet hub UV bond for better introducer fit Epoxy bond Opague stylet hub No Prism B. Braun Melsungen AG

Spinal Needle w/ introducer Luer needle w/ current luer introducer NRFit needle w/ new luer introducer B. Braun Melsungen AG

B. Braun Products with NRFit - Launching Q4 2016 CATEGORY QUANTITY 17G CONT EPIDURAL TRAYS 5 18G CONT EPIDURAL TRAYS 4 SD EPIDURAL TRAYS 2 EPIDURAL NEEDLE SINGLES (includes two longer lengths) PEDIATRIC EPIDURAL SETS 1 EPIDURAL CATHETER SINGLES CATHETER CONNECTOR SINGLES PLASTIC LOR SYRINGE SINGLES EPIDURAL FILTER SPINOCAN TRAY PENCAN TRAYS SPINOCAN NEEDLE SINGLES (includes two longer lengths) 6 PENCAN NEEDLE SINGLES (includes one longer length) 3 ESPOCAN TRAYS ESPOCAN SETS SYRINGE AND FILTER NEEDLE SETS SYRINGE SINGLES FILTER STRAWS/NEEDLE SINGLES Total Products with NRFit 47 Luer B. Braun Melsungen AG

Information Sources BBraunNRFit.com StayConnected.org CHPSO.com B. Braun Melsungen AG

Questions? B. Braun Melsungen AG