Near tripling in US reported lidocaine local anesthetic poisonings/deaths over past decade, analysis reveals

Poisonings and deaths linked to the use of the local anesthetic lidocaine have nearly tripled in the US over the past decade, finds an analysis of National Poison Data System (NPDS) reports, published online in the journal Regional Anesthesia & Pain Medicine.

This increase contrasts with the overall fall in reported poisonings and deaths from other types of local anesthetics over the same period, the analysis shows.

Local anesthetics are widely used for pain control, but carry an inherent risk of systemic toxicity, referred to as LAST, prompting multiple professional societies to issue recommendations in 2010 to manage this.

The researchers wanted to find out what impact these recommendations might have had by comparing the periods 2001–10 and 2010–22. They therefore mined reports submitted to US poisons control centers, the NPDS, from 1983 to 2022.

They assessed the annual number of reports of poisoning and deaths from local anesthesia, grouped by lidocaine and non-lidocaine, from 2001 onwards, when reports on lidocaine were first submitted separately. They also looked at the number of reports of poisoning and deaths from all other substances.

They recorded details of individual cases where these were available: age; gender; type of local anesthetic; delivery method; delivery site (operating room, home, inpatient, outpatient, emergency department, emergency medical services); dose; and other treatments to reverse poisoning.

Between 1983 and 2022, 74 deaths associated with a local anesthetic were reported out of a total of 203,853 local anesthetic poisonings. This compares with a total of 39,913 reports of death out of 79,360,369 reports of poisoning from all causes.

Overall, from 2001 to 2022, 0.1% of reports of lidocaine poisoning resulted in a report of death, compared with 0.01% of reports of non-lidocaine poisoning.

From 2010 onwards, the relative risk of local anesthetic poisoning was 23% lower than that of the preceding decade. But this was primarily driven by an annual 50% reduction in reports of non-lidocaine poisoning from more than 6,000 to fewer than 3,000.

Reports of lidocaine poisoning, on the other hand, rose by more than 50%, from 1,600 in 2016 to 2,500 in 2021.

And the relative risk of death from a local anesthetic more than doubled between 2011 and 2022 compared with the preceding decade, driven by an increase in reports of death associated with lidocaine.

Detailed analysis of 59 individual deaths from all types of poisoning revealed that 32 had been reported before 2010 (average age of 25) and 27 had been reported between 2011 and 2022 (average age 55).

Among the fatalities between 1983 and 2010, lidocaine had been used in two thirds of cases (67%), whereas it had been used in most (82%) fatal cases between 2011 and 2022.

While there was an overall fall in reports of operating room deaths associated with local anesthesia from 47% before 2010 to 15% afterwards, prehospital deaths (emergency medical services or emergency department) rose from 7% to 31%. And reports of death from intravenous lidocaine increased from 3% to 27% of the total.

Almost all cases of lidocaine deaths involved doses that frequently exceeded the recommended upper limit on the package insert, both before and after 2010. These included doses of 2,000 mg—500 mg is the recommended maximum dose—-administered by emergency medical services and in emergency department settings, often by mistake.

The researchers highlight recent case reports suggesting that even small doses of intravenous lidocaine can cause serious side effects in at-risk patients.

To counter the cardiac and neurological effects of lidocaine poisoning, lipid emulsion therapy is recommended, but analysis of the individual cases shows that this was inconsistently used. And in many cases, the patient still died, suggesting it was administered too late. But it may not be enough by itself if the patient has received a very large dose of intravenous lidocaine, suggest the researchers.

The researchers acknowledge some limitations to their findings, including the possibility of under-reporting to the NPDS and incomplete clinical information for all the cases analyzed.

They also suggest that a more appropriate comparator might have been poisonings at health care locations. Between 2001 and 2002, non-lidocaine reports equated to 85% of total poisonings at health care locations, but between 2021 and 2022, they amounted to 31%, suggesting that the reduction in local anesthetic poisonings and deaths might have been underestimated.

“Our findings must be interpreted cautiously, as changes in reported poisonings and deaths may not reflect actual incidence due to the absence of population-level exposure data,” they emphasize.

“However, these findings highlight the need for enhanced administrative guidance on lidocaine use, greater awareness of the risks of high doses of lidocaine, and improved strategies for preventing and managing severe lidocaine-induced toxicity,” they conclude.

Poisonings and deaths linked to the use of the local anesthetic lidocaine have nearly tripled in the US over the past decade, finds an analysis of National Poison Data System (NPDS) reports, published online in the journal Regional Anesthesia & Pain Medicine.

This increase contrasts with the overall fall in reported poisonings and deaths from other types of local anesthetics over the same period, the analysis shows.

Local anesthetics are widely used for pain control, but carry an inherent risk of systemic toxicity, referred to as LAST, prompting multiple professional societies to issue recommendations in 2010 to manage this.

The researchers wanted to find out what impact these recommendations might have had by comparing the periods 2001–10 and 2010–22. They therefore mined reports submitted to US poisons control centers, the NPDS, from 1983 to 2022.

They assessed the annual number of reports of poisoning and deaths from local anesthesia, grouped by lidocaine and non-lidocaine, from 2001 onwards, when reports on lidocaine were first submitted separately. They also looked at the number of reports of poisoning and deaths from all other substances.

They recorded details of individual cases where these were available: age; gender; type of local anesthetic; delivery method; delivery site (operating room, home, inpatient, outpatient, emergency department, emergency medical services); dose; and other treatments to reverse poisoning.

Between 1983 and 2022, 74 deaths associated with a local anesthetic were reported out of a total of 203,853 local anesthetic poisonings. This compares with a total of 39,913 reports of death out of 79,360,369 reports of poisoning from all causes.

Overall, from 2001 to 2022, 0.1% of reports of lidocaine poisoning resulted in a report of death, compared with 0.01% of reports of non-lidocaine poisoning.

From 2010 onwards, the relative risk of local anesthetic poisoning was 23% lower than that of the preceding decade. But this was primarily driven by an annual 50% reduction in reports of non-lidocaine poisoning from more than 6,000 to fewer than 3,000.

Reports of lidocaine poisoning, on the other hand, rose by more than 50%, from 1,600 in 2016 to 2,500 in 2021.

And the relative risk of death from a local anesthetic more than doubled between 2011 and 2022 compared with the preceding decade, driven by an increase in reports of death associated with lidocaine.

Detailed analysis of 59 individual deaths from all types of poisoning revealed that 32 had been reported before 2010 (average age of 25) and 27 had been reported between 2011 and 2022 (average age 55).

Among the fatalities between 1983 and 2010, lidocaine had been used in two thirds of cases (67%), whereas it had been used in most (82%) fatal cases between 2011 and 2022.

While there was an overall fall in reports of operating room deaths associated with local anesthesia from 47% before 2010 to 15% afterwards, prehospital deaths (emergency medical services or emergency department) rose from 7% to 31%. And reports of death from intravenous lidocaine increased from 3% to 27% of the total.

Almost all cases of lidocaine deaths involved doses that frequently exceeded the recommended upper limit on the package insert, both before and after 2010. These included doses of 2,000 mg—500 mg is the recommended maximum dose—-administered by emergency medical services and in emergency department settings, often by mistake.

The researchers highlight recent case reports suggesting that even small doses of intravenous lidocaine can cause serious side effects in at-risk patients.

To counter the cardiac and neurological effects of lidocaine poisoning, lipid emulsion therapy is recommended, but analysis of the individual cases shows that this was inconsistently used. And in many cases, the patient still died, suggesting it was administered too late. But it may not be enough by itself if the patient has received a very large dose of intravenous lidocaine, suggest the researchers.

The researchers acknowledge some limitations to their findings, including the possibility of under-reporting to the NPDS and incomplete clinical information for all the cases analyzed.

They also suggest that a more appropriate comparator might have been poisonings at health care locations. Between 2001 and 2002, non-lidocaine reports equated to 85% of total poisonings at health care locations, but between 2021 and 2022, they amounted to 31%, suggesting that the reduction in local anesthetic poisonings and deaths might have been underestimated.

“Our findings must be interpreted cautiously, as changes in reported poisonings and deaths may not reflect actual incidence due to the absence of population-level exposure data,” they emphasize.

“However, these findings highlight the need for enhanced administrative guidance on lidocaine use, greater awareness of the risks of high doses of lidocaine, and improved strategies for preventing and managing severe lidocaine-induced toxicity,” they conclude.