Benzocaine-containing topical sprays
and methemoglobinemia
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From the October 3, 2002 issue
PROBLEM: Topical anesthetic sprays such as CETACAINE
(benzocaine 14%, tetracaine 2%) and HURRICANE (benzocaine
20%) have been implicated in cases of methemoglobinemia. Because
methemoglobin is a form of hemoglobin that is unable to carry
oxygen, the condition can be life-threatening, causing cyanosis,
confusion, hemodynamic instability, and coma if not recognized
and treated appropriately. The FDA MEDWATCH database contains
about 100 reports of methemoglobinemia related to the use of
benzocaine, the most common topical anesthetic associated with
this reaction.1 However, this is probably only a small fraction
of actual cases experienced in the US. It's well known that
spontaneous reports sent to MEDWATCH severely underestimate
the actual number of occurrences of specific drug-related problems.2
For example, methemoglobinemia has been estimated to occur in
one out of every 7,000 bronchoscopies.3 Given that millions
of doses of topical anesthetics are used each year during endoscopic
procedures and endotracheal intubation, methemoglobinemia is
unlikely to be a rare occurrence.
In reviewing reported cases of methemoglobinemia, clinicians
often used multiple sprays of benzocaine and sprays of longer
duration than recommended. Doses administered during endoscopic
procedures may exceed manufacturer's recommendations for several
reasons. First, unclear package instructions for using the
products may lead to overdoses. In our February 6, 2002 issue,
we mentioned that the directions for use of Cetacaine topical
spray are prone to misinterpretation and could result in patient
harm. One portion of the label states, "Spray in excess
of two seconds is contraindicated," but the directions
state, "To activate spray, press Jetco-Spray Cannula
in any direction with forefinger for approximately one second.
Maximum anesthesia is produced in one minute." This could
be misinterpreted to mean that a continuous spray of up to
one minute is permitted, even desirable, for maximum anesthesia
(Cetylite Industries is clarifying this wording). Another
problem is that clinicians may not be familiar with the significant
absorption of topical anesthetics, so they may not realize
just how much medication they are giving patients when using
the sprays. See our May 15, 2002, edition of the newsletter
for additional information on this problem. Patients also
could self-administer topical anesthetics in doses that exceed
manufacturer's recommendations. Since some products are available
without a prescription (e.g., Hurricane), a patient could,
for example, apply too much spray or gargle too often with
a liquid formulation (or swallow the solution), especially
since the directions for use may be vague (e.g., "apply
a small amount").
SAFE PRACTICE RECOMMENDATION: Alert clinicians and
patients to the proper dosing of topical anesthetics and the
possibility of methemoglobinemia when these products are used.
These drugs should not be used in high doses, especially in
patients who may be predisposed to methemoglobinemia. Predisposing
factors include age (infants under 6 months of age and older
patients with cardiac problems may be sensitive to even low
methemoglobin levels); the status of the area that is being
sprayed (inflamed areas absorb more drug); concomitant use
of other drugs which also have been implicated in causing
methemoglobinemia; and the genetic make-up of the patient
(due to altered hemoglobin, G6PD deficiency, or methemoglobin
reductase enzyme deficiency).4,5 Therefore, patients who may
receive topical anesthetics should be asked about their past
medical history to determine if any of the risk factors are
present.
References:
(1) Ajayi T, Gropper MA. Methemoglobinemia. Pulmonary Perspectives.
2001;18:1-7.
(2) Scott HD, Rosenbaum SE, Waters WJ, Colt AM, Andrews LG,
Juergens JP, et al. Rhode Island physicians' recognition and
reporting of adverse drug reactions. RI Med J. 1987;70:311-6.
(3) Douglas WW, Fairbanks VF. Methemoglobinemia induced by
a topical anesthetic spray (Cetacaine). Chest. 1977;71:587.
(4) Wurdeman RL et al. Benzocaine-induced methemoglobinemia
during an outpatient procedure. Pharmacotherapy. 2000;20:735-38.
(5) http://link.springerny.com/link/service/journals/00464/contents/00/20083/paper/index.html
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