Post-vaccination Syncope: Follow-up
Survey of Reports to Vaccine Adverse
Event Reporting System (VAERS)
44th 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
Presentation Outline
 Background
– Post-vaccination syncope
– Recommendations to prevent post-vaccination
syncope
– VAERS database
 Evaluation of post-vaccination syncope reported to
VAERS
 Conclusions
2
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
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
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
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
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
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
Post-vaccination Syncope:
Survey to Evaluate Cases Reported
to VAERS between 01/01/2009 and
08/31/2009
9
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
Definitions
 “Reporter”: a person who submitted a report to VAERS about postvaccination 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
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
12
Phone Survey Case Inclusion
Initially identified reports,
N=381
(adverse event on day “0”, all
gender, all ages, all vaccines)
Other reports excluded,
N=55
Manufacturer reports
excluded, N=83
(incomplete reports and reports
with onset longer than 1hour)
(usually incomplete)
Eligible reports, N=243
(called 142 most recently
submitted reports; 28 nonresponders)
Syncope cases included in the
survey, N=114
Serious reports, n=3 (3%)
Non-serious reports, n=111 (97%)
13
Survey to Evaluate Cases
Reported to VAERS between
01/01/2009 and 08/31/2009:
Preliminary Results
14
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
Distribution of Syncope Cases
(N=114) by Gender and Age
Gender
n
%
Age range,
years
Mean
age
Median age
Males
21
18%
10-35
16.2
14
Females
92
81%
2-91
17.3
15
Unknown
1
1%
14
14
14
16
Characteristics of the Syncope
Cases (N=114)
No.
%
Yes
24
21%
No
56
49%
Unknown
34
30%
Yes
34
30%
No
23
20%
Unknown
57
50%
Previous history of syncope
Patient had beverage or food
intake prior to immunization
17
Onset Time and
Event Distribution by Age Group
Syncope Distribution by Age
Group
Onset Time from Vaccination
to Syncope
45
70
42
40
34
Number of patients
Number of patients
35
12-18
yrs
66
60
30
25
20
15
10
10
50
40
30
10
5
1
1
20-30
min
30-60
min
0
0-5 min 5-15 min
15-20
min
19+
yrs
27
20
6-11
0-5 yrs yrs
3
18
0
1
0-5 yrs
Time in minutes
6-11 yrs
12-18 yrs
19+ yrs
Age groups
18
Number of patients
Distribution of Syncope Cases by
Vaccines Type*
Vaccines administered alone or in combination
*Survey reports to VAERS between 01/01/2009 and 08/31/2009
19
What position was the patient in at the
time of the syncope?
20
Number of Patients
Where did the syncope occur?
Location Where Syncope Occurred
21
Was the patient asked by the provider to
wait after receiving vaccines?
22
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
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
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
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
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
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
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
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
Acknowledgements
 Immunization Safety Office
– Karen Broder
– Maria Cano
– Beth Hibbs
– Claudia Vellozzi
– Oidda Museru
– Yenlik Zheteyeva
 Immunization Services Division
– Robin Curtis
– Andrew Kroger
31
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
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
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 syncoperelated injuries should be
evaluated systematically. ”
(CDC. Syncope after vaccination
United States. January 2005-July
2007. MMWR 2008; 57 (No.17)
900
42
800
41
44
700
600
Included
Serious
VAERS
Reports
500
400
796
730
703
300
Total
VAERS
Reports
200
13
100
*CDC unpublished data: automated
search in VAERS, U.S. primary
reports only, unrestricted by age,
vaccine, or gender
131
0
2006 2007 2008 2009
34
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
demographics
AE
vax
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
Onset Time From Vaccination to
Syncope by Age Group
38
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
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.)