1. Post-vaccination Syncope: Follow-up Survey of Reports to Vaccine Adverse Event Reporting System (VAERS) 44 th National Immunization Conference 04-19-2010 Angela Calugar, MD, MPH Elaine R. Miller, RN, MPH Alison Rue-Cover, BSN, MPH LaTonia Alexander, MS Immunization Safety Office DHQP/NCEZID/CDC 1

2.  Background –Post-vaccination syncope –Recommendations to prevent post-vaccination syncope –VAERS database  Evaluation of post-vaccination syncope reported to VAERS  Conclusions 2 Presentation Outline

3. Post-vaccination Syncope Syncope is a transient loss of consciousness due to decreased perfusion to the brain; diverse etiology Vasovagal reaction –Sudden decrease in blood pressure which deprives the brain of sufficient oxygen causing dizziness (pre-syncope) or a brief loss of consciousness (syncope) –Is the most common cause of syncope (~20 to 35% percent of cases), particularly in patients without apparent cardiac or neurologic disease –Recovery is generally spontaneous –Potential for secondary traumatic injuries from falling 3

4. Features of the Vasovagal Episodes  The episodes are typically recurrent, usually occur when the person is exposed to a specific trigger  Prodrome lasts for at least a few seconds: lightheadedness, nausea, sweating, ringing in the ears (tinnitus), uncomfortable feeling in the heart, weakness and visual disturbances  Consciousness is lost typically when the person is sitting up or standing  If the person tries to sit or stand when they wake up, they may faint again 4

5. Measures to Prevent Vasovagal Reaction and Syncope (Limited Evidence)  Coffee consumption before blood donation had protective effect  Fluid loading, muscle tensing, distraction were observed to be beneficial  Providing more personal attention to an anxious patient  Quickly recognize and reverse mild reaction (prodrome) before the procedure  Obtain information about previous history of vasovagal reaction  Observing a 15-minute waiting period after vaccination 5

6. Recommendations to Prevent Post-vaccination Syncope:  2006 Advisory Committee on Immunization Practices: –“…providers should strongly consider observing patients for 15 minutes after they are vaccinated “ (MMWR 55(No.RR-15): 2006)  2009 Red Book: –“Personnel should be aware of presyncopal manifestations and take appropriate measures to prevent injuries… –Having vaccine recipients sit or lie down for 15 minutes after immunization could avert many syncopal episodes and secondary injuries “ (American Academy of Pediatrics. Active immunization. In: Pickering LK, ed 2009 Red Book) 6

7. Vaccine Adverse Event Reporting System (VAERS)  National post-licensure passive surveillance system for vaccine adverse events (AEs) operated by CDC and FDA  Anyone can report to VAERS, e.g. vaccine administrator, or another healthcare provider, a patient or his/her parent or designated guardian, a manufacturer, etc.  Advantages –Covers US population –Permits monitoring for known AEs –Detects signals for previously unrecognized /rare AEs –Generates hypothesis  Limitations –Underreporting –Stimulated reporting due to media attention and other factors –Incomplete data –Lack of availability of denominator data 7

8. VAERS Published Data on Syncope Following Vaccination VAERS 2000-2005 107 reports of post-vaccination syncope associated with fall and injury including one death and two severe head injuries (Woo EJ, et al. Fatal syncope-related fall after immunization. Archives of Pediatrics and Adolescent Medicine. 159(11):1083, November 2005.) VAERS 2005-2007 63% of the 463 syncope reports were associated with recently recommended adolescent vaccines: Menactra (MCV4), Tetanus, diphtheria and acellular pertussis (Tdap), and Gardasil (HPV). (CDC. MMWR 2008; 57 (No.17) http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5717a2.htm http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5717a2.htm

9. 9 Post-vaccination Syncope: Survey to Evaluate Cases Reported to VAERS between 01/01/2009 and 08/31/2009

10. Survey Objectives  Phone survey of a convenience sample of VAERS cases reported between 01/01/2009 and 08/31/2009 to collect information about post-vaccination syncope: –Visible signs and symptoms before, during, and after the syncope, and health outcomes –Circumstances under which the syncope episode occurred (position the patient was in, onset interval, etc.) –Measures implemented by providers to prevent syncope –Other related descriptive data 10

11. Definitions  “Reporter”: a person who submitted a report to VAERS about post- vaccination syncope  “Case”: a person who experienced post-vaccination syncope and eligible for survey after applying exclusion/inclusion criteria –Only cases with loss of consciousness within 1 hour from immunization were considered for our survey  Serious AEs: –death, life-threatening illness, permanent disability, hospitalization, prolongation of an existing hospitalization  Medical Dictionary for Regulatory Activities (MedDRA) –To code clinical signs and symptoms in VAERS database 11

12. 12 Methods  Identification of VAERS reports –Search in VAERs data base for US primary reports  Submitted between 01/01/2009 to 08/31/2009  MedDRA codes “syncope” or “syncope vasovagal”  Serious and Non-Serious  Onset interval same day of vaccination  Unrestricted by age, gender, and vaccine type  Excluded –Manufacturer reports* –Other reports with incomplete information  Phone survey of a convenience sample of reporters (18 years and older) who submitted cases of syncope (onset within 1 hour of vaccination); interviews conducted in September-November 2009 *Usually are lacking critical identifiable and contact information for the reporter and the vaccine recipient

13. Phone Survey Case Inclusion 13 Initially identified reports, N=381 (adverse event on day “0”, all gender, all ages, all vaccines) Manufacturer reports excluded, N=83 (usually incomplete) Other reports excluded, N=55 (incomplete reports and reports with onset longer than 1hour) Eligible reports, N=243 (called 142 most recently submitted reports; 28 non- responders) Syncope cases included in the survey, N=114 Serious reports, n=3 (3%) Non-serious reports, n=111 (97%)

14. Survey to Evaluate Cases Reported to VAERS between 01/01/2009 and 08/31/2009: Preliminary Results 14

15. Reporters (N=114) and Vaccine Administration Settings*  Reporters of the syncope: –Healthcare providers (n=110) –Parent (n=1) –Patient (n=1) –Other (n=2) * VAERS Cases (N=114) submitted between 01/01/2009 to 08/31/2009 15

16. Distribution of Syncope Cases (N=114) by Gender and Age Gendern%Age range, years Mean age Median age Males2118%10-3516.214 Females9281%2-9117.315 Unknown11%14 16

17. Characteristics of the Syncope Cases (N=114) No.% Previous history of syncope Yes2421% No5649% Unknown3430% Patient had beverage or food intake prior to immunization Yes3430% No2320% Unknown5750% 17

18. Onset Time and Event Distribution by Age Group 18 Syncope Distribution by Age Group

19. Distribution of Syncope Cases by Vaccines Type* 19 Number of patients Vaccines administered alone or in combination *Survey reports to VAERS between 01/01/2009 and 08/31/2009

20. What position was the patient in at the time of the syncope? 20

21. Where did the syncope occur? 21 Location Where Syncope Occurred Number of Patients

22. Was the patient asked by the provider to wait after receiving vaccines? 22

23. Reported Signs and Symptoms Associated with Syncope Episode Did you witness the fainting episode? –Yes- 79 –No -28, –Unknown-7 Reported symptoms in observed cases:  Pale face, n=58  Anxiety, n=38  Nausea, n=29  Sweating, n=23  Vomiting, n=4  Severe inject. site pain, n=4  Tonic clonic movements, n=36 (46% of observed cases) 23

24. Reported Signs and Symptoms Associated with Syncope Episode Did you witness the fainting episode? –Yes- 79 –No -28, –Unknown-7 Reported symptoms in observed cases:  Pale face, n=58  Anxiety, n=38  Nausea, n=29  Sweating, n=23  Vomiting, n=4  Severe inject. site pain, n=4  Tonic clonic movements, n=36 (46% of observed cases) 24

25. Patient Outcomes Syncope Cases*  Recovered completely=72  Fell but was not injured=12  Fell and was injured=31 –Including 3 Serious Reports  Type of injuries: laceration to head, abrasion to face (eyebrow, lip), lacerations to face,abrasion to clavicle, broken noses, blows to the head and neck *Some cases are listed under two categories. Reported to VAERS between 01/01/2009 and 08/31/2009: 25

26. Patient Outcomes: Serious Cases (n=3) 17 year old female had vomiting for a day, followed by nausea for 4 days, and continued feeling sick and weak for 3 weeks. The patient had a prior history of syncope after vaccination with associated tonic clonic movements; was referred to neurologist. 13 year old female syncopized with tonic-clonic movements, described an aura and a brief post-ictal period within 5 min after vaccination. She was standing at the onset and fell backwards hitting her head on the floor. Pt was hospitalized for 1 day in epilepsy unit, EEG and MRI normal. Is followed up by neurologist. 13 year old female walked out of exam room and passed out 5-7 min after injection. Experienced head injury; was evaluated in ER and observed for 23 hours in the hospital. CT negative. 26

27. Waiting policy after Vaccination  Did your office have a policy for patients to wait after all vaccines (at the time this pt fainted)? Yes-44 No-56 Unknown-14  As a result of the syncopal episode, nine providers stated that they changed their policy to institute a waiting period after vaccination. 27

28. Limitations  Convenience sample is not necessarily representative of the total population of post immunization syncope cases  Recall bias: survey was conducted months after the syncope event occurred  VAERS data is subject to underreporting and stimulated over-reporting bias –Potential for underreporting for syncope if cases have been miscoded as anaphylaxis or seizure and these would not have been detected by our search –Potential stimulated over-reporting for syncope cases following HPV4 vaccine because of high media coverage and increased public attention 28

29. Limitations (cont.)  Possible overrepresentation of several categories: –Healthcare Providers accounted for 110/114 reporters; this might be a sign of increased awareness about VAERS in healthcare workers –The predominance of female cases could be a result of higher number of HPV4 vaccine administered in US females; 3-dose series recommendation –High distribution of syncope after HPV4, MCV4, and Tdap vaccines could reflect a recent introduction of these vaccines to the immunization schedule of children and adolescents 29

30. Conclusions  Post-vaccination syncope remains a concern –Secondary injuries with serious outcomes  May affect vaccine acceptance behavior  Current ACIP and AAP recommendations for a 15-minute waiting and observation period following vaccination –Increase awareness among healthcare providers  Healthcare providers consider additional preventive measures –Based on their own observations –Based on medical literature (studies in blood donors and trauma centers’ patients)  Important to recognize pre-syncope signs and symptoms  Refined evidence-based prevention recommendations are needed 30

31. Acknowledgements  Immunization Safety Office –Karen Broder –Maria Cano –Beth Hibbs –Claudia Vellozzi –Oidda Museru –Yenlik Zheteyeva  Immunization Services Division –Robin Curtis –Andrew Kroger 31

32. Disclosure  The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.  CDC investigators wish to disclose they have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters 32

33. Places Where Patient Fainted, Selected Examples  “spent over 15 min in waiting area; fainted after that in the middle of being briefed about the shot  after a brief waiting period fainted while walking to the parking lot  waited ~5 min in the hall, fainted near front door while leaving  waited in exam room 10 min, got up to leave exam room and fainted at the door of the exam room  standing while brother got vaccinated  was waiting with his sister after vaccination, she got dizzy and had to sit in chair, then he fainted. He was standing up when he fainted, father caught him partially” 33

34. Syncope Following Immunization: Increase in Reporting to VAERS* “…increase in post-vaccination syncope and secondary injuries suggests that adherence to the 15-minute post-vaccination observation period and its efficacy in preventing syncope- related injuries should be evaluated systematically. ” (CDC. Syncope after vaccination United States. January 2005-July 2007. MMWR 2008; 57 (No.17) *CDC unpublished data: automated search in VAERS, U.S. primary reports only, unrestricted by age, vaccine, or gender 34

35. Survey Instrument  Questions on the following: –Patient demographics –Immunization setting –Waiting policy for immunizations –Vaccines administered –Patient position during immunization and at the time of syncope –Signs and symptoms associated with syncope –Onset interval –Outcome –Previous history of syncope –Previous food intake –Suggestions for prevention 35

36. demographics AE vax

37. Suggestions from Healthcare Providers on Prevention Measures  Give candy, lollypops after the immunizations  Have the patient lie down for the shot and get up slowly  Have the patient eat prior to immunizations. One office refuses to give vaccinations if the patient hasn’t eaten that day. They remind the pt to eat when they make the appointment reminder call and if the pt still hasn’t eaten, they send them to a fast food restaurant located in their building before they will vaccinate.  Have a room with lounge chairs for patients to wait in after vaccines. Many providers stated they needed to keep exam rooms clear for the next patient so that they would not get behind schedule.  Do not allow teens to drive themselves home. Tell teens prior to their arrival that they have to have a driver take them home after immunizations.  In general, take more time with patients. 37

38. Onset Time From Vaccination to Syncope by Age Group 38

39. VAERS Published Data on Syncope Following Vaccination VAERS 2005-2007  63% of the 463 syncope reports were associated with recently recommended adolescent vaccines: Menactra (MCV4), Tetanus, diphtheria and acellular pertussis (Tdap), and Gardasil (HPV). (CDC. MMWR 2008; 57 (No.17 ) http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5717a2.htm http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5717a2.htm VAERS 2000-2005 107 reports of post-vaccination syncope associated with fall and injury including one death and two severe head injuries ( Woo EJ, et al. Fatal syncope-related fall after immunization. Archives of Pediatrics and Adolescent Medicine. 159(11):1083, November 2005.) VAERS 1990-1995 30% of syncopal episodes that occurred within 15 minute after vaccination were associated with tonic clonic movements. ( Braun MM, Patriarca PA, Ellenberg SS. Syncope after immunization. Arch Pediatr Adolesc Med. 1997:151(3):255-9.)