Single‐syringe Administration of Diluted Adenosine

Supraventricular tachycardia (SVT) is a potentially life-threatening disease state which accounts for 50,000 emergency department (ED) visits annually.1 SVT encompasses a variety of rhythm disturbances including atrial fibrillation, atrial flutter, sinus tachycardia, atrioventricular nodal reentrant tachycardia, and atrioventricular reciprocating tachycardia.2 The American Heart Association 2015 guidelines for Adult Advanced Cardiac Life Support recommends adenosine in nonhypotensive patients in regular narrow-complex SVT.3 Adenosine is an endogenous purine nucleoside that blocks atrioventricular nodal conduction via the A1 receptors in the cardiac tissue. These in turn act on Gi-cAMP to stimulate potassium channels yielding hyperpolarization of cardiac myocytes thus returning the heart to a normal sinus rhythm (NSR).4 The pharmacokinetic profile of adenosine makes it an ideal agent to treat SVT. With a rapid onset and a half-life less than 10 seconds, cardioversion can be performed quickly with limited adverse effects. Due to these unique kinetics, a large-volume flush of saline is concomitantly administered to ensure adequate delivery to the myocardium. Adenosine is commonly administered as a 6-mg rapid intravenous bolus over 1 to 2 seconds followed by a rapid 20-mL saline flush. If the first dose does not result in termination of SVT to NSR within 1 to 2 minutes, a repeat dose of 12 mg can be given and the dose may be repeated one additional time if required for a total of three doses.5 A decrease in the initial adenosine dose to 3 mg is recommended for administration through a central line. Typically, adenosine is administrated via a two-way stopcock, where drug and a 20-mL saline flush are administered in tandem. This method suffers from physical logistic issues. For example, locating a two-way stopcock may cause a delay in therapy and certain emergency medicine transport services may not stock such a device. This method also requires the nursing staff to precisely coordinate their actions delivering the drug and flush simultaneously.6 An alternative method of combining the drug and the flush in a single syringe may offer higher rates of conversion, lower the need for repeat doses, eliminate the need for a stopcock, and limit peripheral IV extravasations. Combining medication and flush has been popularized by free open-access medical education in recent years. Hayes7 reviewed the benefits, methodology, and available literature in 2012, with an update in 2018. EMcrit.org post from Weingart in 2015 also endorsed a one-syringe method.8 Adenosine is compatible and stable in 0.9% sodium chloride.9 Currently, minimal evidence exists surrounding this method of administration. The objective of this study was to evaluate the administration technique of adenosine delivered as a single-syringe diluted with saline compared to the two-syringe method for conversion of SVT to NSR. This single-center, prospective, observational study was conducted from November, 1, 2016, through February 28, 2018. This was an institutional review board–approved study, with a waiver to consent as the process is standard practice at our institution. Patients above the age of 18 presenting to the ED with stable narrow-complex regular rhythm tachycardia requiring adenosine administration were included. Patients were excluded if systolic blood pressure was below 90 mm Hg, had evidence of poor perfusion, or had a history of bronchospasm. The physician would identify patients with SVT and would inform the pharmacist of his or her preferred adenosine administration method. Selection of administration method was solely up to the provider regardless of admission into the study. The pharmacist would prepare adenosine as either a single-syringe containing both 6 mg of adenosine and 18 mL of 0.9% sodium chloride or two separate syringes of adenosine and 20 mL 0.9% sodium chloride flush. Nursing staff would administer the syringe(s) using the largest IV available. A medical technician would collect a continuous EKG during and immediately after administration of the medication. If conversion to NSR was not achieved, as determined by the physician, the dose of adenosine was increased to 12 mg in both groups and given via the same administration method previously used. A total of three doses could be provided to each patient. The primary endpoint was the percentage of patients with successful conversion of SVT to NSR after the first dose. Secondary endpoints included achievement of NSR up to three doses and adverse effects secondary to the administration techniques. We assumed the efficacy of the single-syringe treatment group (SS) would be at least 80% as effective as the two-syringe method (TS) and set the noninferiority margin to 20%. To achieve a power of 80% with an alpha set at 0.05, it was determined that 75 patients were needed in each group. If no difference was detected between groups, we would be able to reject the null hypothesis. Descriptive statistics were utilized for demographic data, presented as medians and interquartile ranges for continuous data and as percentages for dichotomous and categorical data. A noninferiority test of proportions was utilized to compare the percent of conversion from SVT to NSR between the two methods of administration. The data analysis for this paper was generated using SAS software (Version 9.4) of the SAS System for Unix. Across the study period, a total of 53 patients were enrolled in the study. The median age of patients was relatively similar in both arms, 55 and 58 years old, respectively. The SS arm was predominately female, 62%, while the TS arm was 48% female (Table 1). Successful conversion to NSR with the first dose was higher in the SS arm 73.1% (95% CI = 0.55 to 0.91) to 40.7% (95% CI = 0.21 to 0.61; noninferiority, p = 0.0176). Successful conversion to NSR with up to three doses was also higher in the SS arm 100% (95% CI = 1.0 to 1.0) to 70.4% (95% CI = 0.52 to 0.89; noninferiority, p = 0.0043). One patient in the conventional TS arm suffered extravasation and phlebitis compared to none in the SS arm. This study suffers from several limitations. We were unable to recruit 75 patients in each arm due to time constraints thus limiting the power of the study. Additionally, our noninferiority margin was quite large. As we observed more conversion to NSR in the SS arm, the probability that SS is 20% inferior is low. Although the difference between the groups was stronger than initially assumed, our results should be interpreted as pilot data and referenced for future studies. The location of IV access was not recorded, and more distal lines could potentially confound the rates of NSR conversion. The administration technique for the TS method was not recorded and was not standardized. There could have been a difference in administration success depending on the equipment used: stopcock, single-port IV, two-port IV. We can only draw limited conclusion in regards to safety, as the study was not powered to measure this endpoint and event rates were incredibly low in both groups. We did not exclude patients who may have received additional rate controlling medications prior to adenosine administration. Our patients were not randomized and limits the strength of the study. Most importantly, observational studies can provide erroneous conclusions. As such, our current results merit confirmation in a randomized trial. However, this study represents real-world practices thus lends credit to external validity. There has been provider concern that diluting adenosine prior to administration could reduce the drug’s efficacy. Our results counter this argument and show that the SS method is highly effective with a 73% chance of successful NSR conversion with first dose of adenosine and 100% chance with repeat doses. The differences between the groups were so striking that an ad hoc superiority analysis was performed to determine if only the SS administration method should be recommended. Unfortunately, due to the limited sample size, superiority was not demonstrated. Our results are comparable to those of Choi et al.10 who conducted a similar study comparing a TS method to a SS administration method using only 15 mL of saline to dilute the adenosine. Choi et al. reported no difference in successful termination of paroxysmal SVT, with 80 and 85.7% success rates using the SS and TS method (chi-square test, p = 0.39). While they did not report first-dose success rates, total dose used in each group was similar 10.3 mg SS versus 11 mg TS arm suggesting repeat dosing was common in both groups. Similarly, our cohorts had a decrease in mean total dose of adenosine administered. Our data showed a higher chance of successful conversion to NSR in the SS group with repeated doses of adenosine compared to the TS group, 100% versus 70.4%. These data suggest that regardless of dose the SS method may be a superior technique. Adverse events were limited in each group with no reports of dyspnea, bradycardia, or asystole. In conclusion, the SS administration method is simple and no less effective than the TS method. Physicians should consider using the SS method particularly if no stopcock is available or if only a single-port IV can be used for drug administration. Further randomized control studies should be completed to validate these results.