Why does Sodium Bicarbonate ameliorate the hypotension caused by Drug-induced Cardiac Sodium Channel Block? (and the 100msec QRS toxicity myth)
Last week we discussed the function of the cardiac Na channel and the effect of Na channel blocking drugs (NCBD) which bind to a pore in the Na channel and prolong the activated and/or inactivated confirmations.
This week we are going to discuss the reason Sodium Bicarb ameliorates hypotension caused by NCBDs.
In the 90s, (prior to SSRIs), there were many tricyclic antidepressant (TCA )overdoses(OD) which had a significant mortality. Empirically, it seemed that administration of NaHC03 improved the hypotension. The thought was that increasing the Na ion concentration in the cardiac Na channel unblocked the channel. (We now know that unblocking the channel essentially means pushing the NCBD off the pore and out of the channel. Each NCBD has a different affinity for a pore.)
Initial studies on purkinje fibers bathed in NCBDs demonstrated that the Na channel was unblocked when Na ion concentration was increased. But the studies weren’t reproducible. Which component of the NaHCO3 unblocked the Na channel seemed to depend on the drug causing the block. The Na channel could be unblocked by high Na ion concentration, alkalosis, or a combination of the two. For example, when the Na channel was blocked by flecainide, the combination of high Na ion and alkalosis unblocked the channel. When the Na channel was blocked by disopyramide, alkalosis had no effect, high sodium ion concentration had the most effect on unblocking the Na channel and the combination of alkalosis and hi sodium had a moderate effect. (This was measured by Vmax, which measures how quickly the Na ions moved through the channel). The potent Na channel block caused by cocaine was completely reversed when a pH of 9.0 was attained in the purkinje bath. So, when a patient has a NCBD OD, how do you know which part of Na bicarbonate unblocks the channel?
You don’t. And it doesn’t matter. For some drugs, the Na channel will be unblocked by a high concentration of Na ions, for others, it will be the alkalosis and for still others, it will be a combination of the hi Na ion concentration and the alkalosis. The goal is to give as much NaHCO3 as you can without increasing the serum pH >7.55 which can precipitate alkalemic arrhythmias. If the patient is hypotensive, administer sodium bicarbonate IVP. (Obtain baseline ABG. In an adult, one amp NaHCO3 increases the pH approximately 0.1) This will provide Na ions, alkalosis and their combination.
Remember pH is increased with IVP Na HCO3 (serum alkalinization). With normal kidneys, a Na HCO3 drip alkalinizes the urine (urinary alkalinization) but doesn’t increase serum pH.
There has been much discussion regarding the degree of QRS widening that is prognostic of impending hypotension. A QRS of 100msc has been used as a sign of significant TCA toxicity and even as an indication for serum alkalinization. But this is a misinterpretation of the 1985 NEJM study. (NEJM 1985;313:474-479) This was a poison center study (entrance into study based on HCP call to poison center with TCA ingestion) in which QRS duration was evaluated to see if it correlated with seizures or ventricular dysrhythmias. The groups were divided into group A (QRS < 100msec) which had 13 patients and group B (QRS >100 msec) which had 36 patients. Division into these two groups is the origin of the 100 msec myth. In these 49 patients, patients with a QRS of < 100 msec had no seizures or dysrhythmia, patients with QRS of 100-160msec had a moderate risk of seizures and negligible ventricular dysrhythmias and patients with a QRS >160msce had a high risk of both seizures and dysrhythmia. You can see the issues with study design and small number of patients. Furthermore, much less was known about the cardiac Na channel then as evidenced by the fact that heart rate (HR) was not evaluated. Now we know the HR is as important as the QRS widening (faster HR, greater percentage of time Na channel is in activated and/or inactivated conformation). This study was based on TCAs-there are many NCBDs that are not TCAs and have different pharmacologic activity regarding both seizure potential and degree of cardiac Na channel blockade.
Most poison centers have guidelines regarding the administration of NaHCO3 to alkalinize the serum in NCBD OD. Certainly, hypotension is an indication. IF the patient is not hypotensive and has a HR of 120bpm and a QRS of 120msec, we would recommend serum alkalinization.