Karen Titus
This is a story about SARS—specifically, how to handle SARS or
suspected SARS specimens in the laboratory.
Ho hum.
That’s not to diminish the harm wrought by the disease, nor
to make light of the threat it poses. Nor is it meant to undermine
the considerable fears it has unleashed among laboratory workers.
But even in the most severely affected site in North America to
date, Toronto, it’s hard to elicit dramatic statements about
the impact SARS specimens have had on lab logistics. And at the
Centers for Disease Control and Prevention, certainly one of the
flash points for information about the disease, matter-of-factness
has been the order of the day. As of late May, laboratory workers
appear to be remarkably safe even in Asia, where SARS has been raging
among health care workers and patients alike.
“Based on our experiences over the last couple of months,
with thousands of specimens in multiple countries, we have yet to
document a laboratory-acquired infection,” says Rob Weyant,
PhD, chief of the laboratory safety branch in CDC’s Office
of Health and Safety, who helped author the CDC’s interim
lab biosafety guidelines for handling and processing SARS-related
specimens. “We believe the risk of acquiring disease via a
laboratory specimen is probably lower than the risk of taking care
of a patient.”
Luck has nothing to do with it. The reasons laboratory workers have
been safe—so far—appear to be rooted in solid adherence
to standard (formerly known as universal) precautions. At the same
time, however, labs face a frightening number of unknowns about
the disease and a crushing amount of information as they continue
to prepare for potential SARS cases.
“It changes on a daily basis. It changes on a minute-to-minute
basis,” says Barbara Robinson-Dunn, PhD, D(ABMM), technical
director of microbiology, William Beaumont Hospital, Royal Oak,
Mich.
“The CDC has sent out an overwhelming amount. Not only that,
but the state health departments send out guidelines, too,”
says Steven Dallas, PhD, D(ABMM), director of microbiology, Presbyterian
Healthcare, Charlotte, NC. “Then the county will give you
information, so you quickly get overwhelmed and say, ‘Which
one of these 30 bulletins should I keep?’ Probably better
too much information than not enough, though.”
At Mount Sinai Hospital in Toronto, the unknowns could hardly
have
been greater when the public health authority sent its directives
in April in response to the unfolding SARS crisis: Two hospitals
would be shut down and two—including Mount Sinai, which had
handled the city’s early SARS cases and was caring for numerous
SARS patients—would be placed on severe restrictions.
“When the restrictions came, they came with virtually no notice,”
recalls Kenneth Pritzker, MD, FRCPC, pathology chief and director
of pathology and laboratory medicine, Mount Sinai, and professor
of laboratory medicine and pathobiology, University of Toronto.
The mandate put a hold on all but essential services at Mount Sinai
and the other restricted hospital; those not performing essential
services were to stay away.
Though one reason for the directive was to limit spread of the virus,
“The primary consideration was that the screening procedures
[to enter the hospital], which were instituted on an instantaneous
basis, were quite elaborate,” says Dr. Pritzker. “And
it was rather important to keep down
the number of people going through those procedures, so we could
get the people performing the essential functions into the hospital
to do their duties.”
The mandate, which also instructed hospital personnel to wear masks,
was issued at 7 PM one evening; by midnight, all the hospitals had
complied. And although the bulk of patients and staff don’t
appear until the start of the 7 AM shift, the impact should not
be underestimated.
“You have to understand the size of the screening magnitude,”
Dr. Pritzker says. The screening process has involved some 30 screeners,
plucked from hospital staff—including laboratorians—working
at three different stations, where arriving employees filled out
epidemiology questionnaires, performed prescribed handwashing, and
had their temperatures taken. “So the drain on our staffing
was very, very substantial,” he says. Separate screening procedures
were set up for visitors and at exits.
The less traffic the better, obviously. But while other departments
were cutting back, the laboratory kept its numbers high. “We
made a decision—and it was a fortunate decision to make—that
all the services that we were providing were essential. We did this
because we really did not know what our volumes were going to be,
or where our specimens were going to be coming from,” says
Dr. Pritzker, noting that in addition to handling specimens from
SARS patients, they continued to provide testing for inpatients
and urgent outpatients, including patients in the hospital’s
high-risk pregnancy unit. “Those kinds of things don’t
wait,” Dr. Pritzker notes. They also knew that as soon as
the crisis passed, they would face a flood of specimens. Only a
small number of lab staff were excused from work during the first
two days—not because of any imminent danger, but in response
to the initial pressures to reduce staff.
“If we were to do anything differently, we wouldn’t
have kept anybody in our services out, even for that 48 hours,”
Dr. Pritzker says. “Every one of our staff would be asked
to be there from the outset and would be put in a redeployable situation.”
For all the “Andromeda Strain” dramatics unfolding,
however, the
laboratory has teetered on the edge of calm.
The most reasonable lab concern—how to handle SARS-related
specimens—has actually been one of the least problematic issues
for Mount Sinai’s laboratory. “The first thing we can
tell you is we’ve been handling the specimens exactly the
way we’ve been handling specimens prior to the SARS crisis,”
says Dr. Pritzker. All the lab’s policies and procedures are
geared toward standard precautions—any specimen coming from
any site is considered potentially infectious. “We try not
to differ for any particular group of patients. So that’s
what we did in terms of the SARS patients,” he says.
The laboratory benefited from other standing procedures. Specimens
from the intensive care and inpatient units are collected by those
working in those units. Since the SARS-affected hospitals were trying
to limit traffic in and out of units with SARS patients, the policy
paid off. “This allowed the specimens to come to us without
difficulties,” Dr. Pritzker says.
Specimens also continued to arrive in the lab via the hospital’s
pneumatic tube system, per usual. Specimens traveling this route
are routinely double-bagged, so if a spill occurs, it is contained
immediately. But that has happened exactly “never,”
says Nancy Hutton, technician, patient services supervisor at Mount
Sinai.
At the same time, because of the tight screening restrictions, the
laboratory had to quickly revamp how it received specimens from
outside the hospital, directing couriers—who were no longer
allowed into the hospital—to specific entry points. “It
might sound trivial, but it certainly was not,” says Dr. Pritzker.
“Every day we receive specimens from as many as 10 sites outside
the hospital. So just getting organized was an effort.” Some
of Mount Sinai’s ambulatory facilities also closed briefly,
but the patients who visited those sites had urgent testing needs
that had to be handled at Mount Sinai’s lab. As if SARS weren’t
a heavy enough load, the region was socked with an ice storm at
the same time. “Fortunately, almost every specimen that was
supposed to arrive here and get processed did so successfully,”
he says.
Such adjustments point to the real problem Mount Sinai’s laboratory
faced—how to look beyond SARS in the midst of the crisis.
As Dr. Pritzker notes, potential disruptions to laboratory services
are not new. Labs have to cope with everything from AIDS to hepatitis
to electricity blackouts. “The key from the laboratory perspective
is to pay very close attention to preventive maintenance and to
drills and procedures so the staff can actually cope with the crises
well, as soon as they come up.
“If we hadn’t been doing this kind of thing for years,
we would have been faced with much greater problems,” he says.
That’s not to say there weren’t SARS-related concerns,
or that such concerns have disappeared entirely. “The anxiety
by the staff was quite considerable,” says Dr. Pritzker. “Appropriately
so, because we had staff within this hospital who were working directly
with the first SARS patients.” The small group of lab workers
who had been excused in the first 48 hours were especially nervous—they
thought they’d been sent home because the workplace wasn’t
safe.
From the outset, Dr. Pritzker and his colleagues, along with the
managerial staff, met those fears head-on. “We had to be out
in the laboratory, talking with groups large and small, outlining
for them, as best we could, what the situation was and letting them
know that under no circumstances would we place them in any known
danger,” Dr. Pritzker says.
It wasn’t easy. Fear swept over many staff when the edict
came down for everyone in the building to wear masks—at the
time, no one knew how SARS might be spread, and the concern was
that anybody could be carrying it. “One of the hardest problems
was trying to explain to the lab staff why they were wearing masks—in
microbiology, pathology, chemistry, wherever—when they had
no patient contact,” says Tony Mazzulli, MD, FRCPC, deputy
chief, microbiology, Mount Sinai.
Dr. Mazzulli and other leaders were inundated with questions from
lab workers, and trying to address them all proved to be one of
their biggest challenges. But doing so helped keep the lab running
smoothly. Many questions were occupational in nature. “Maybe
they had young children or elderly parents at home, and some people
were on forms of immunotherapy for a variety of diseases—and
they all wondered if they’d be safe,” Dr. Mazzulli says.
Talking about safety wasn’t enough—lab leaders took
the extra steps of showing their staff that the safety procedures
were working. For example, lab hoods that are exhausted were checked
again, even though they had recently passed inspection, as was airflow
in the autopsy room. “At the outset we went through all our
procedures to make sure they were, in fact, being done,” says
Dr. Pritzker. “They were actually seen, by our staff, being
done. That was a big part of the reassurance process. And since
this is a fairly large laboratory, this had to be done in many different
corners by people who know their areas well. And this assessment
was done in a matter of hours.”
Throughout the ordeal, it was never clear how far the virus would
spread, nor what, exactly, would be required of staff in responding
to the crisis. “Our people had to make decisions on their
own in order to expedite services, because things were changing
so much,” Dr. Pritzker says. “Fortunately, it all went
very, very smoothly, which indicates that staff on the whole have
been very well trained. They’re capable of handling surprises
and situations where they don’t know all the answers.”
Though Dr. Pritzker sounds justifiably proud of his institution’s
quick response to SARS, he doesn’t hesitate to credit preparations
that occurred far earlier. “All these kinds of things can
only happen if the table has been set a long time back, and as you
conduct practice sessions. The preparation for these things is not
when you have a crisis. The time to do this is when things are calm.”
Most laboratories have not endured the SARS trial by fire
that
MountSinai has, but they’re doing their
best to prepare themselves
for the worst.
At Methodist and Children’s hospitals, Omaha, the microbiology
laboratory—which splits services between the two institutions—underwent
a dry run for SARS specimens in mid-April, reports Nancy Cornish,
MD, director of microbiology. The timing couldn’t have been
better, since two days later they had a suspected SARS case—a
Toronto physician who arrived in the ER with respiratory symptoms
and requesting a mask. “Everything went like clockwork,”
says Dr. Cornish. The lab was notified, the Directigen tests were
done in Methodist’s TB room, and the viral culture specimens
were sent to the public health lab. “Everybody was properly
gowned, wearing the right masks and working in the right room, and
everyone knew what to do,” she says.
The dry run allowed Dr. Cornish and her colleagues to alter several
practices. For example, they decided not to do their direct fluorescent
antibody testing for influenza A, B, and RSV at the Children’s
virology laboratory, which contains a biosafety level two facility.
“With fresh unfixed specimens we wanted a level two with bio
three precautions, and I wanted a negative airflow,” Dr. Cornish
explains. In moving the DFAs over to Methodist, however, they discovered
that doing them under the hoods was too cumbersome; they also wanted
to avoid hauling the needed equipment from Children’s to Methodist.
“We finally decided to go with the Directigen, which is a
rapid test, and use it under the hood,” she says.
Like other laboratorians, Dr. Cornish and her colleagues are trying
to balance the CDC, state, and other guidelines with the nuts and
bolts of their daily operations. “If we were going to err,
we tried to err on the side of doing a little too much. There’s
no such thing as being too safe,” says Dr. Cornish. “But
we also had to be practical, given how our workflow goes.”
Certain specimens are worked up in the TB room—which has a
negative airflow—in a class two biosafety cabinet hood. Workers
handling those specimens wear N95 masks, a solid-front gown, and
gloves and eye protection. “This is for anything that requires
aliquoting or dilution of specimens, uncapping of vacuum tubes,
anything that could produce an aerosol or splash,” says Dr.
Cornish.
The lab also considered how to work up routine specimens from possible
SARS patients. The CDC recommends using standard precautions for
routine serology, chemistry, hematology, and other tests; laboratorians
should wear protective gear, Dr. Cornish says, including gloves,
solid-fronted lab coats, eye protection, and a surgical mask. “If
they’re going to be doing anything with aerosols, then they
would have to do that under a hood,” she says. “Once
it gets loaded into the chemistry analyzers, then we feel it’s
OK—those are closed systems.”
Specimens for microbiologic analysis present their own dilemmas.
The infection control team is supposed to notify the lab of any
suspected or probable SARS cases; in turn, the lab has asked that
specimens in those cases be identified with a hot-pink label reading
“SARS,” which will be placed on the outside of biohazard
bags for everyone to see, as well as on requisition forms.
The labs would work up fresh tissue or fluids under hoods that meet
biosafety level two qualifications, as well as specimens for routine
staining. “So we’d make Gram stains under a hood,”
Dr. Cornish says. “In fact, we’d aliquot the specimen
under the TB hood, because it can be aerosolized. Then once it’s
fixed, it is handled using standard precautions.”
The morgue, surgical pathology room, and TB room are the institutions’
only negative-pressure rooms. “I get a little worried when
I think about someone handling a possible SARS specimen in a class
two hood in the middle of a busy lab where there’s no negative
pressure,” Dr. Cornish says. The TB hood, on the other hand,
is sequestered, away from traffic flow. “It’s probably
the safest hood we have.”
The basic strategy in a possible SARS case, then, is to handle unfixed
fluid and tissue specimens in the TB room. Failing that, the goal
is to move the worker into a negative airflow room and make sure
she or he is wearing an N95 mask. Viral cultures would be sent to
the public health laboratory, which has a full biosafety level three
facility.
“It’s a little confusing, I think, to try to follow
all this,” Dr. Cornish concedes. “But we’re doing
the best we can. And if we have an outbreak situation, well, then
we’d all have to reconvene and discuss how to handle that.”
The CDC’s guidelines, posted on the agency’s
Web site, are the
startingpoint for most discussions about handling
SARS-related specimens. The guidelines have gone through multiple
iterations, evolving as new information becomes available. That,
in turn, creates potential for confusion, the CDC’s Dr. Weyant
acknowledges. “We learn something new about this virus every
week,” he says.
At the same time, he emphasizes that the biosafety level two guidelines
cited in the April 16 interim SARS guidelines are standard practices
in hospital microbiology labs already: no eating, smoking, or drinking
in the laboratory; washing of hands; no mouth pipetting. “These
should already be in place,” he says.
Handling specimens in nonmicrobiology labs gave them pause early
on. “We really wrestled with this,” says the CDC’s
Betty Robertson, PhD, deputy associate director for laboratory science.
The data thus far indicate the virus may be present in blood, though
it’s unclear what the level of viremia might be.
But the matter may be more simple than some labs have feared, Dr.
Weyant says. “We say in the guidelines that blood and urine
specimens can be handled using standard precautions in BSL2 laboratories,
and then we specify the protective equipment that’s needed,
which includes disposable gloves, laboratory coats, eye protection,
and surgical masks or face shields.” The guidelines do not
recommend aliquoting blood and urine in a safety cabinet, he emphasizes.
That particular recommendation is for the area referred to in the
guidelines as “other specimens,” which would “presumably
be from sources where we would expect to find a higher titer of
virus, such as respiratory specimens.”
With blood and urine specimens, adds Dr. Robertson, “We feel
like the risk is minimal.” But, as the guidelines demonstrate
and as many laboratory directors suspect, “We tried to err
on the side of caution,” she says.
The interim guidelines suggest that laboratories turn to “administrative
measures and/or additional personal protective equipment”
if safety equipment recommended in the guidelines is unavailable—a
vague-sounding phrase that’s caused consternation in at least
a few laboratories.
“What we were thinking of,” says Dr. Weyant, “is,
if necessary, limiting
the number of people in the laboratory during a higher-risk procedure”—
for example, centrifuging suspected SARS specimens using an instrument
without safety cups or sealed rotors, with no recourse to a biosafety
cabinet. In such cases, labs could relocate the centrifuge to a
low-
traffic area.
Suspected SARS specimens should be labeled as such, Dr. Weyant says,
clarifying another issue—as some laboratory directors have
noted, standard precautions instruct labs to handle every specimen
similarly, without such labels. “If there is a patient in
the hospital in whom SARS is suspected, there should be good communication
with the lab, so the specimens can be flagged and handled appropriately,”
says Dr. Weyant.
The guidelines are a work in progress. Early versions had more stringent
suggestions for respiratory protection, for example; as the CDC
talked to more laboratorians and gained experience working with
specimens, the guidelines became more flexible, allowing lab managers
to make risk assessment-based decisions.
Dr. Weyant uses the word “flexibility” frequently when
he discusses the guidelines. The authors tried to consider every
possible scenario, he explains, from basic triage laboratories to
sophisticated laboratories. They’ve had to provide guidelines
despite a tremendous lack of data. Laboratory supervisors and safety
officers have to take into account their own situations, equipment,
and procedures. In each case, flexibility was
the watchword.
“These guidelines are designed to help labs perform a risk
assessment,” he says. “They’re meant to give enough
flexibility to do that.”
And they do, says Dr. Robinson-Dunn, of William Beaumont. “You
take what’s in the guidelines and you say, ‘Does this
apply to me? And what
do I need to do? What’s being recommended? And is this feasible
or
not feasible?’”
Adds Jared N. Schwartz, MD, PhD, chair of the CAP Ad Hoc Committee
on Preparedness for National Emergency, “There’s a reason
the CDC calls these ‘guidelines.’”
The focus on SARS may be counterproductive if taken too
far—
a little like someone losing sleep over terrorism, then
failing to fasten his seat belt in the car. As they consider possible
SARS scenarios, labs are discovering that the two best tools at
their disposal are common sense
and experience.
“Our initial thoughts were this: that standard precautions
work for everything so far,” says Presbyterian’s Dr.
Dallas, pointing to TB, hepatitis C and B, and HIV. “We can
prevent all kinds of infectious disease just using the biosafety
level two workplace practices we always do. So unless this really
is the virus from hell, I don’t see why we should change things.”
Other
pathologists weigh in with kindred opinions. Robert Novak, MD, chair
of the CAP Hematology/Clinical Microscopy Resource Committee, suggests
that for blood specimens, no special treatment is required beyond
the standard precautions recommended by CDC. “In terms of
how the laboratory responds to any emerging infection, I think that
standard precautions will be what general diagnostic laboratories
will have to go with until these are shown to be inadequate.”
Anthony Killeen, MD, PhD, who chairs the CAP Chemistry Resource
Committee, says, “Basically, all samples are treated as potentially
infectious. We don’t have any additional precautions for SARS
in chemistry samples.”
Frankly, many laboratorians sound more concerned about non-SARS
cases. “We don’t want to shortchange patients,”
Dr. Dallas says. Possible SARS cases may also be RSV, or the flu
or an adenovirus—in fact, they most likely would be, he says.
“As they say back in school, if you hear hoofbeats, look for
horses. So we want to look for the normal respiratory pathogens
to make sure we get things diagnosed appropriately.”
“These public health concerns, which are on the outside of
our hospital, distract from taking care of the sick people in our
hospital,” he says. “Not that we shouldn’t prepare
for it, but it really does take a lot of our mental energy away
from the acutely ill people we already have in our ICU.”
SARS discussions, however, have enabled laboratories to review basic
procedures and shore up areas that may have been weak. “It
became clear we needed to do a much better job of making sure people
understood the difference between different kinds of masks,”
says Dr. Schwartz, director, Department of Pathology and Laboratory
Medicine at Presbyterian. Not everyone knew, for example, that the
recommended mask was the N95—and that this particular type
must be fitted to the wearer. Likewise, he and his colleagues have
used the situation to remind new and part-time staff of standard
lab procedures, and to make sure they know whom to contact if they
have questions. “We want to make sure every employee has a
comfort level and understands they’re not going to be left
on their own,” Dr. Schwartz says.
Like many others, he sees a potential upside to SARS preparations.
If not SARS, it will be something else, he figures, so taking time
now to prepare for the worst is the only sensible thing to do. Indeed,
few laboratorians limit their SARS discourse to SARS. West Nile
virus, Ebola, bioterrorism, avian influenza, anthrax, and the Norwalk
virus all inspire worried musings—even from those who’ve
been hit hard by SARS.
“Today the urgency is SARS. But tomorrow it’s going
to be something else,” says Dr. Pritzker.
Karen Titus is CAP TODAY contributing editor and co-managing editor.