Prove It: Is sodium bicarbonate indicated for prolonged cardiac arrest?

Sodium bicarbonate case review: Medic 34 and Engine 3 respond to a report of an unconscious person. The engine arrives first and notifies the responding medic that CPR is in progress.

The medics arrive to find a 68-year-old male lying in a bedroom floor. The patient’s wife said she was out of the house most of the day. When she arrived home, she found her unresponsive husband lying in the bed. He had a heart attack about 10 years ago and had some type of “heart cath” procedure. He takes medications for hypertension, high cholesterol, and an aspirin each day.

The firefighters report they found the man lying unresponsive on the bed. They moved him to the floor and began CPR. They attached the AED, which twice advised that no shock was indicated.

After attaching the ECG monitor, the initial rhythm is asystole. There is easy IV access in the patient’s left arm and Medic Hernandez administers epinephrine. Medic Thompson easily intubates the patient’s trachea on the first attempt, hears bilateral lung sounds, and sees a capnography waveform on the monitor with a reading of 10 mmHg.

Over the next 10 minutes, the patient receives two additional doses of epinephrine. There is no change in the patient’s status. After verifying the engine has been on scene performing CPR for 20 minutes and the patient remains asystolic, the medics discuss terminating the resuscitation attempt. The patient’s wife is comfortable with that decision and the team stops performing CPR.

Later, the medics are conducting an informal debriefing session. One of the firefighters, who also attends paramedic school, asks about giving sodium bicarbonate, stating he was told it was appropriate for prolonged resuscitation attempts. Medic Thompson says he has never seen it work and that is why he didn’t give it.

Sodium bicarbonate study review

Using data from the Resuscitation Outcomes Consortium out-of-hospital cardiac arrest (OHCA) registry, researchers in Canada isolated consecutive cases treated within four metropolitan regions serving 3.3 million people in British Columbia [1]. Each analysis case represented a patient over the age of 17 years who suffered a non-traumatic EMS-treated OHCA. Researchers excluded cases if the patient was 17 years of age or younger, EMS responded but did not treat the patient, patients had valid written or verbal do not attempt resuscitation orders, or for patients declared legally dead at the scene.

Treatment guidelines in British Columbia do not recommend routine sodium bicarbonate administration to all patients suffering from cardiac arrest. However, guidelines permitted bicarb administration in certain conditions, such as suspected hyperkalemia, overdose of tricyclic antidepressants or salicylates, or “prolonged” cardiac arrest, although the interval that defines prolonged is left to the discretion of the individual paramedic. Before sodium bicarbonate administration, treatment guidelines also recommended medics utilize advanced airway control and ensure adequate ventilation.

Researchers classified all qualifying cases into two groups, those who received intravenous sodium bicarbonate and those who did not. The primary outcome variable for the study was survival-to-hospital discharge. The secondary outcome variable was neurological status at discharge, as determined by the modified Rankin scale.

The researchers utilized a complex series of analytical techniques to reduce the uncertainty associated with results from retrospective studies. First, the team performed a series of regression analyses, which allowed mathematical control of variables that could have affected the outcome measures. This strategy permits a researcher to isolate the effects of receiving or not receiving sodium bicarbonate without interference from other variables like patient age, initial EMS-recorded rhythm, bystander CPR, use of an advanced airway, or the length of professional resuscitation, to name a few.

Next, the researchers used a statistical comparison technique called propensity score matching. In this technique, researchers assign each patient a score based on the same potential confounding variables used in the regression analyses. Those scores would permit a fair comparison of two patient groups with almost identical scores who differ only by whether they received sodium bicarbonate, essentially an apples-to-apples comparison.

The final statistical procedure was a sensitivity analysis, which estimates the outcomes if the input variables change. For example, if data was missing for 10% of the cases, it is reasonable to wonder what effect that missing data has on the outcome. Or, one might wonder what effect minor protocol violations would have on the results. A sensitivity analysis can predict those effects and increase the precision of the inferences one can draw from the various statistical analyses.

Sodium bicarbonate study results

An electronic search of the ROC database identified 13,865 patients who met the inclusion criteria over a period of about 10 years. Slightly more than one-third (37.3%) of the patients received a prehospital dose of sodium bicarbonate. The two groups (sodium bicarbonate vs. no sodium bicarbonate) were not different among all potential confounding variables for which the researchers collected data, with the exception of two. Patients receiving sodium bicarbonate generally underwent longer lengths of resuscitation and received higher cumulative doses of epinephrine.

Patients who received sodium bicarbonate at any point during their prehospital resuscitation attempt were less likely to achieve return of spontaneous circulation (38.1% vs. 51.2%), survive to hospital discharge (2.3% vs. 19.8%), or have favorable neurological status at discharge (1.2% vs. 10.6%).

The regression analyses for the complete dataset determined the adjusted odds of surviving to hospital discharge decreased by 52% after receiving sodium bicarbonate. In addition, the adjusted odds of having favorable neurological outcome decreased by 39% after receiving bicarb. The trend in harm associated with bicarb administration persisted despite the amount of epinephrine received, duration of the resuscitation attempt or initial EMS-recorded rhythm.

Statisticians were able to match 5,638 patients based on propensity scores. In this apples-to-apples comparison, sodium bicarbonate administration was associated with a 36% decrease in survival to hospital discharge (adjusted odds) and a 41% decrease in favorable neurological outcome (adjusted odds). The sensitivity analysis demonstrated similar results.

What sodium bicarbonate results mean for you

ACLS guidelines in the early 1970s recommended sodium bicarbonate administration to combat the metabolic acidosis that inevitably developed during prolonged resuscitation attempts [2]. The thought was that correcting acidosis would improve the patient’s response to both endogenous and exogenous catecholamines, which would increase coronary perfusion pressure and improve survival [3]. Although early use of sodium bicarbonate by paramedics was not associated with an increase adverse effects rate [4], the medication did not improve survival-to-hospital admission or survival-to-hospital discharge rates [5].

However, other data suggested that not only does routine sodium bicarbonate administration fail to confer survival benefits to patients suffering cardiac arrest, it may actually create conditions that inhibit return of spontaneous circulation. When sodium bicarbonate is injected into the bloodstream, a series of chemical reactions occur that ultimately results in an increase in carbon dioxide production.

As long as the patient receives adequate assisted ventilation, the extra carbon dioxide is removed and does not become problematic. However, if ventilation is compromised for any reason, the excess carbon dioxide diffuses across the cellular membrane and aggravates intracellular acidosis, which depresses myocardial performance [6]. This could have devastating effects in the period after defibrillation when pacemaker cells are attempting to reestablish normal conduction pathways in the heart [7].

In addition, sodium bicarbonate administration increases blood osmolality (a measure of concentration of particles dissolved in plasma), which has an effect on coronary perfusion pressure and resuscitation success [8]. Increasing blood osmolality draws fluid into the vessels, which increases intravascular volume, preload and right atrial pressure. In addition, increasing osmolarity decreases arterial tone, which decreases aortic diastolic pressure [9]. The combined effect of these hemodynamic changes reduces the pressure gradient in the coronary arteries, which reduces coronary perfusion pressure.

Despite the fact that sodium bicarbonate is not recommended by the American Heart Association for the routine management of cardiac arrest, the medication is still frequently administered in the prehospital environment [10,11]. The 2010 AHA guidelines identify several special circumstances where sodium bicarbonate administration may be beneficial, such as cardiac arrest associated with preexisting metabolic acidosis, hyperkalemia, or tricyclic antidepressant overdose [12].

In addition, medics often consider bicarbonate administration during prolonged resuscitation attempts when patients are not responsive to standard therapies. Although sodium bicarbonate administration during prolonged resuscitation attempts is associated with increased ROSC and improved acid-base balance, it is not associated with increased survival measures [13-15].

It is worth noting that a recent Taiwanese study involving out-of-hospital cardiac arrest was able to demonstrate improved survival to hospital admission following the ED administration of sodium bicarbonate [16]. However in Taiwan, there are very few paramedics and most EMS care is provided by EMT-II level providers, which are roughly equivalent to Advanced EMTs in the United States. Thus, in most cases, there are no medications delivered in the field for cardiac arrest. In that study, physicians administered sodium bicarbonate in about one-third of the cases once the patient arrived in the ED. Patients who received sodium bicarbonate were four times more likely to survive to hospital admission when compared to patients who did not receive bicarb. This association was present in the unadjusted analysis and in propensity-score matched analysis.

While this finding appears encouraging, the devil is always in the details. The majority of patients who received sodium bicarbonate in the emergency department did so only after blood gas analysis, which is not generally available in the prehospital setting. This suggests the medication was not routinely given for prolonged refractory arrest but rather when there was clear evidence of metabolic acidosis.

Additionally, prehospital data was not available for about 92% of the patients, thus researchers could not determine the impact of prehospital variables known to influence survival. However, prehospital data was available for 464 patients. An analysis of that subset found that patients who received sodium bicarbonate were more likely to have a witnessed arrest and to have bystander CPR, two factors that should increase survival in the bicarbonate group.

When the researchers used survival to hospital admission as the outcome measure, the bicarb group did indeed have higher survival. But, when the researchers used 30-day survival, there was no difference between the patients who received sodium bicarbonate and those who did not.

Limitations of the sodium bicarbonate study

Generalization of the results is limited by the retrospective design of the study. Retrospective studies do not permit researchers to control variable that could influence the outcome. In consideration of that limitation, the research team used three different analytical techniques to try to accurately discover the association between sodium bicarbonate administration and survival measures. All three techniques returned similar results, thus lending support to the author’s conclusions.

Another limitation lies in the amount of missing data especially for the secondary outcome variable. Neurological status at discharge was only available for 56% of the patients who survived long enough to be discharged from the hospital. One of the analytical techniques attempted to account for the missing data. Although the results of that analysis are consistent across multiple imputations and consistent with the other techniques, the results represent estimation rather than an absolute.

Sodium bicarbonate study summary

For adult patients suffering an out-of-hospital cardiac arrest, this study suggests an association between prehospital administration of sodium bicarbonate and decreased survival-to-hospital discharge and worsened neurological status at the time of discharge. The study further supports the AHA recommendation against routine administration of bicarbonate for the management of cardiac arrest.

References

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The author has no financial interest, arrangement, or direct affiliation with any corporation that has a direct interest in the subject matter of this presentation, including manufacturer(s) of any products or provider(s) of services mentioned.