Vital Times 2022 - 102

International governing agencies soon followed
the FDA and discontinued the use of 0.75%
bupivacaine for obstetric anesthesia in the United
Kingdom and Canada. This sparked further
critique internationally given that no cases of
cardiovascular toxicity related to bupivacaine
use had been reported in those countries.
Several international journals published editorials
dismissing the safety concerns over bupivacaine
and insisting that cases of cardiovascular collapse
could be attributed to suboptimal resuscitation
practices or poor procedural technique leading to
intravascular injection.3,4
With definitive proof of bupivacaine's cardiac
toxicity still lacking, the January 1984 issue of
Anesthesiology finally provided conclusive evidence.
A paper titled " Bupivacaine-induced Cardiac
Arrhythmias in Sheep, " written by University of
California, San Francisco Professor Sol Shnider,
MD (1929-1994), and colleagues, revolutionized the
debate. The authors had performed intravenous
injections of lidocaine and bupivacaine at
epidural analgesic doses to gather data on any
potential CNS and cardiac toxicity in sheep. The
animal subjects' pH, pCO2, pO2, base excess,
and serum potassium were measured at frequent
intervals after injection. No significant metabolic
disturbances were seen even during seizure activity,
which was quickly terminated with thiopental.
However, after administration of bupivacaine
at therapeutic and supratherapeutic doses, all
subjects demonstrated serious arrhythmias and/
or EKG changes. Approximately 50% of subjects in
the therapeutic-dose bupivacaine group developed
either atrioventricular block, supraventricular
tachycardia, ST changes, or premature ventricular
contractions after administration. 11% of subjects
in the therapeutic-dose and 80% of subjects in
the supratherapeutic-dose groups developed
ventricular tachycardia. By contrast, no subjects
in the lidocaine group developed a serious
arrhythmia. Overall, the results demonstrated that
" in the absence of marked hypoxia, respiratory or
metabolic acidosis, hyperkalemia, or hypotension,
serious cardiac arrhythmia occurs after
bupivacaine but not lidocaine [administration]. " 5
The work of several Californian anesthesiologists
made possible the discovery of bupivacaine's direct
cardiotoxic effects. Their efforts led to significant
changes in practice and spurred the development of
safer alternative agents, including levobupivacaine
and ropivacaine. More than 40 years later, the
discussions that surrounded this story are still
relevant today. Any medication we use can be
potentially toxic with improper administration or
at supratherapeutic doses. So how do we as a
professional community agree on guidelines to
promote an optimal margin of safety?
5 Kotelko DM, Shnider SM, Dailey PA, et al. Bupivacaine-induced cardiac arrhythmias in sheep. Anesthesiology. 1984;60(1):10-8.
102 | CSA Vital Times

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