COCA Conference Call: Syncope as an adverse event following immunization

1. COCA Conference Call:Syncope as an adverse event following immunization Jane Gidudu, MD, MPH Immunization Safety Office CDC

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4. Vasovagal Syncope • Transient loss of postural tone and consciousness with spontaneous recovery • Bradycardia, vasodilatation or hypotension resulting in decreased brain perfusion • Due to abnormal sympathetic reflex • Elicited by a variety of stimuli in settings of fear or emotional distress • Occurs after medical procedures, including vaccinations • Syncope is a transient symptom and not a disease. • coded as “syncope” or “syncope vasovagal” using Medical Dictionary for Regulatory Activities (MedDRA) coding terms

5. General Recommendations on Syncope General Recommendations on Immunization : Advisory Committee on Immunization Practices (ACIP)* “although syncopal episodes are uncommon and severe allergic reactions are rare, vaccine providers should strongly consider observing patients for 15 minutes after they are vaccinated. If syncope develops, patients should be observed until symptoms resolve.” American Academy of Pediatrics, 2006† “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 syncope episodes and secondary injuries.” *MMWR 2006; 55 (No. RR-15) †American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases, 27th ed

6. Vaccine Adverse Event Reporting System (VAERS) • National passive surveillance system • Jointly operated by CDC and FDA since November 1990 • Covering all U.S. licensed vaccines • Receives >20,000 reports per year • Subject to well-described limitations including underreporting and reporting bias

7. Published VAERS Data on Syncope • The most frequently reported adverse event following HPV vaccine included syncope Jan 2006, through Dec. 31, 20081 • Serious injuries with at least one fatality have occurred2 • 89% occurred within 15 minutes3 • VAERS data, 1990-20044 • Total number of reports: 3,168 • 35% were among persons aged 10-18 years • 14% resulted in hospitalization for injury or medical evaluation 1Slade BA, Leidel L, Vellozzi C, et al JAMA 2009;302(7):750-795 2Woo EJ et al. Arch Pediatr Adolesc Med 2005; 159: 1083 3Braun MM et al. Arch Pediatr Adolesc Med 1997; 151: 255-9 4MMWR 2006; 55 (No. RR-15)

8. Syncope Associated with Injuries in VAERS Reports, January 1, 2005–July 31, 2007(n=41*) • Adolescent (11–18 years), n=31 • Females, n=22 (71%) • Males, n=9 (29%) • Syncope onset after vaccination: • 20 (49%) within 5 minutes • 33 (80%) within 15 minutes • Serious† cases, n=10 (24%) *Excludes cases with unknown onset intervals (n=14) †Defined as adverse events provided by the reporter which result in death, life-threatening illness, hospitalization, prolong hospitalization or disability

9. Number of Postvaccination Syncope Episodes Reported to VAERS, by month and year of report – United States, January 1, 2002 – July 31, 2009 Tdap June 29, 2005 HPV June 29, 2006 MCV4 February 10, 2005 2002 2003 2004 2005 2006 2007 2008 2009

10. Vaccines Associated with Syncope Reports in VAERS, 2005 - 2007 *Not mutually exclusive categories

11. Adverse Events* Reported to VAERS,January 1, 2002–July 31, 2009 *Case-patients aged ≥ 5 years ¶ Reports documented up to July 31, 2009 †Defined by FDA as resulting in death, life-threatening illness, hospitalization, prolong hospitalization or disability; according to information provided by the reporter of the adverse event

12. Example of injury related to post-vaccination syncope A 13-year-old girl fainted within 10 minutes of receiving HPV and MCV. She fell backward, hit her head on carpeted floor of the clinic and was admitted to the pediatric intensive care unit because of skull fractures and subarachnoid hemorrhage.

13. VAERS Limitations • Cannot calculate syncope incidence rate based on VAERS data • Underreporting of adverse events • Lack of age or sex specific vaccine doses administered • VAERS MedDRA® coding terms may not reflect diagnosis accurately • Cannot determine if syncope related to vaccine, targeted age group or both

14. Vaccine Safety Datalink Data: Syncope per 1000 Vaccines Visits Following Td, Tdap, Menactra, and Varicella Ages 9-26

15. Conclusions • Since 2005, an increase in VAERS syncope reports among: • Females aged 11–18 years • Nonserious reports • Reports associated with vaccines recommended for adolescents • Similarly in VSD, rates for post vaccination syncope are increasing over time. • We should encourage health care providers to adhere to both the ACIP and AAP recommendations • Although syncope is uncommon, it can have serious yet preventable consequences: CDC recommends • “providers strongly consider observing patients for 15 minutes after they are vaccinated”-ACIP • OR “having vaccine recipients sit or lie down for 15 minutes after immunization” –Red Book could avert many syncope episodes and secondary injuries.”

16. CDC Kimp Walton, MPH Paige Lewis, MPH Julianne Gee, MPH Frank DeStefano, MD, MPH FDA Andrea Sutherland, MD, MSc, MPH Acknowledgements

17. COCA Conference Call:Syncope,Convulsive Syncope, and Traumatic Injury Following Adolescent Vaccines Andrea Sutherland, MD, MSc, MPH FDA

18. Background • High rates of syncope in adolescents • Average age of onset is 13 y/o • Peak prevalence 15-16 year olds • Vasovagal response • Unprecedented number of adolescent vaccines based on ACIP 2005-2006 recommendations (HPV, Tdap, MCV4/MNQ) • Syncope can be associated with convulsive syncope and traumatic injury • Implications for injury prevention guidelines and for school or mass immunization programs

19. Postimmunization Syncope Case Definition • Transient loss of consciousness • Spontaneous, prompt resolution • Presyncopal signs/symptoms (pallor, dizziness, nausea, diaphoresis, visual changes, etc.) • Noted personal or family history of vasovagal syncope • Pain/fear/anxiety (needles) are triggers • Majority occur within 15 minutes after vaccination

20. Risk Factors: 2007 VAERS review described risk factors in 70% (76/109) cases mentioning syncope related traumatic injury occurring within 1 hour after immunization • Personal or family history of vasovagal syncope • Presyncopal signs misunderstood • Fall from high exam table • Patient left alone or unattended • Walking to waiting room • Standing at check out desk making follow-up appointment • “Syncope without warning” • Patient refused to “wait” • Not having eaten or dehydration • In parking lot or driving • Multiple vaccinations administered

21. Postimmunization Syncope Falls Prevented • In 2007 VAERS report review, 53 cases specifically mention a syncope related fall was prevented • 30% specifically describe a family member or health care provider caught the patient • 30% presyncopal signs were recognized and patient assisted to recumbent position and observed • Prevention of syncope related traumatic injury is possible if patient is closely observed, warning signs are recognized, and appropriate intervention is enacted to prevent injury and re-establish perfusions brain

22. Convulsive Syncope:Syncope with seizure-like activity • Convulsive syncope can be associated with prolonged (10-15 seconds) cerebral hypoperfusion • Syncope with tonic spasms, opisthotonos, fist clenching, generalized clonic movements, nystagmus, mydriasis, drooling, urinary incontinence, tongue biting • Convulsive syncope should not be confused with epilepsy • Convulsive syncope is usually transient and benign

23. Conclusion • Postimmunization syncope related traumatic injury continues to occur and remains a potentially preventable vaccine adverse event • Many VAERS reports indicate patients and providers not following current guidelines of 15-20 minutes of observation after vaccination • Convulsive syncope is often misunderstood, need further communication and education • Need education of patients and providers about postimmunization syncope, presyncopal warning signs, and methods to prevent injury

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