This month’s medical review is written by Dr. Justin Corcoran, MD. He is a board-certified toxicologist and EM physician. He can be found on Twitter at @J_Corky.
In this case, we have a 53-year-old male who was to undergo anterior cervical discectomy and fusion (ACDF) who unfortunately suffered a cardiac arrest on the table. Despite resuscitative efforts producing return of spontaneous circulation (ROSC) while in the surgery center, he ultimately died at the referral hospital following a subsequent cardiac arrest. It was later discovered that he had died secondary to lidocaine toxicity after the treating anesthesiologist found a bag of lidocaine (variably referred to as 0.4% and 4% in the court documents) and realized it had been infused in place of the volume expander Hespan.
So what is lidocaine toxicity?
Lidocaine is a drug in a class of medications called local anesthetics; in toxicity, they produce a similar constellation of symptoms which is referred to as Local Anesthetic Systemic Toxicity (LAST). LAST is characterized by a combination of potentially severe and life threatening neurologic and cardiac changes; neurologic manifestations include seizure, coma, and respiratory depression while cardiac changes include widening of the QRS complex, subsequent ventricular arrhythmias, and as in this case, cardiogenic shock followed by cardiac arrest. These are not the only effects – classical signs such as perioral numbness, tinnitus, and visual/auditory disturbances occur at lower serum concentrations. These findings are less severe, and are thus not the focus of this review except insofar as they may be an early indicator of worsening toxicity.
Pathophysiology
These symptoms arise as an extension of the primary mechanism of action of local anesthetics, namely, blockade of voltage gated sodium channels. Recall that voltage gated sodium channels are important in nerve conduction, and carry depolarization down the length of a neuron. This is followed by opening of voltage-gated calcium channels in the axon terminal, which results in vesicles releasing neurotransmitters into the synapse. In the case of sensory neurons, blocking voltage gated sodium channels abolishes the action potential and thus the transmission of sensory stimulus.
In typical use, toxicity does not occur, either due to careful IV dosing (such as using low doses of IV lidocaine for pain or as an antiarrhythmic) or because they are injected into soft tissue. Toxicity can occur with inadvertent intravascular injection or with excessive soft tissue infiltration (maximum doses of local anesthetics are published in other resources which are readily available so will not be reproduced here).1 As an extension of the sodium channel blocking activity, local anesthetics have a few other actions in toxic dosing. These include their neurotoxic and cardiotoxic effects. As these drugs are lipophilic, they enter the central nervous system and block voltage gated sodium channels in the brain, producing seizures and coma. Although the initial depression of cortical inhibitory neurons produces seizure, with increasing dosage generalized CNS depression occurs.2
Voltage gated sodium channels are also necessary for normal cardiac electrical function, where they act to carry depolarization throughout the myocardium. Delays in depolarization such as those caused by sodium channel blockade are thus seen on the surface ECG as an increase in the QRS duration. Impairments in sodium channel function can lead to myocardial depression, and arrhythmias induced by sodium channel blockade can be life threatening. It should also be noted that local anesthetics can produce vascular smooth muscle relaxation and thus there is also a vasodilatory component to the shock state that develops.
Treatment
The primary treatment for LAST is lipid emulsion therapy. This has been shown in animal studies to improve survival, although human experience is mostly limited to case series and case reports.3,4 Lipid emulsion is administered as a 20% concentration with a bolus of 1.5mL/kg followed by an infusion of 0.25-0.5mL/kg/min until clinical symptoms resolve or the cumulative dose reaches 12mL/kg.5 Although lipid may be used for neurological abnormalities associated with LAST, the primary indication is for cardiovascular collapse. It should be strongly considered with bradycardia, tachycardia, and hypotension and has a more clear indication in cases of cardiac arrest.5
Treatment is complicated by potential difficulty with recognition of the underlying process; as we can see from the case presented here it was not readily apparent that the cause was local anesthetic systemic toxicity. However, some treatments used in standard ACLS may have a role in treating LAST; due to the cardiodepressant and vasodilatory effects, epinephrine may be used. Additionally, the wide QRS complex with an unknown cause should prompt consideration of treatment with bicarbonate (to empirically treat for a possible sodium channel blocker poisoning). Recognizing that a wide complex tachycardia is due to sodium channel blockade is difficult as the much more likely etiology is ventricular tachycardia. However, bradycardia or normal heart rate with a wide complex is concerning for sodium channel blockade as the primary etiology (other relatively common causes of wide complex bradycardia include hyperkalemia and digoxin/cardioactive steroids). Unfortunately, outside of cocaine, there is very little support for treating local anesthetics with bicarbonate.6,7
For cases of LAST refractory to lipid therapy, it should be noted that case reports exist to support the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO).8,9
Miscellaneous Thoughts
This case provides the opportunity to review a few other miscellaneous points. First, describing drug concentrations as percentages (e.g. 0.4% lidocaine) is prone to error. A better method for describing concentration is mass/volume (e.g. mg/mL). Mass/volume measurements are easier to understand, and easier to use when calculating maximum volumes that can be given to a patient.
Another key point is the difference between the differential for PEA vs wide-complex tachycardia/ventricular tachycardia. It is beyond the scope of this discussion to fully cover this, but RebelEM has a good post here: https://rebelem.com/a-new-pulseless-electrical-activity-algorithm/ . The big take-away from this case is that a wide-complex arrest can be bradycardic, tachycardic, or neither. While wide-complex tachycardic arrest should be treated as though it were ventricular tachycardia, the possibility of sodium channel blockade and/or hyperkalemia should always be in the back of your head. With lower heart rates, the diagnosis is less consistent with ventricular tachycardia and the concern for a tox/metabolic etiology should increase.
Finally, as mentioned previously, LAST can be difficult to diagnose if the local anesthetic administration is not recognized. The combination of neurologic symptoms (primarily seizures and coma) with QRS prolongation (or resulting arrhythmias such as ventricular tachycardia) should raise concern for poisoning with a sodium channel blocker.
Conclusion
Local anesthetic systemic toxicity (LAST) is a potentially life-threatening complication of local anesthetic agents. It should be suspected in patients who present with seizures followed by cardiovascular collapse or ventricular arrhythmias. The primary treatment for LAST is lipid emulsion, although other treatment options exist. Prompt recognition and institution of appropriate therapy is necessary for an optimal outcome.
1. Scott DB. “MAXIMUM RECOMMENDED DOSES” OF LOCAL ANAESTHETIC DRUGS. Br J Anaesth 1989;63(4):373–4.