Background

  • Atrial fibrillation (a-fib) and atrial flutter (a-flutter) with rapid ventricular rate (RVR) are potentially life-threatening arrhythmias that are commonly treated in the emergency department.
  • Diltiazem (a non-dihydropyridine calcium channel blocker) is a first line  medication to treat a-fib/a-flutter with RVR. Hypotension is an adverse-effect of diltiazem and can complicate management of a-fib/a-flutter with RVR. It has been theorized that pretreating patients with calcium before administering diltiazem may prevent hypotension.

Clinical Question

In adult emergency department patients with a-fib or a-flutter with RVR, does pretreatment with intravenous calcium prior to diltiazem decrease the risk of hypotension after diltiazem administration?

Population

  • 217 adults ≥ 18 years presenting to the Emergency Department at a single academic center in Turkey
  • Atrial fibrillation or atrial flutter with RVR (heart rate > 120)
  • Systolic blood pressure (BP) > 90 mmHg

Intervention

  • Group 1: Pretreatment 90 mg IV calcium chloride 
  • Group 2: Pretreatment 180 mg IV calcium chloride
  • Control: Pretreatment IV saline (placebo) 
  • All groups: Diltiazem 0.25 mg/kg IV after completing pretreatment 
    • All groups: Additional diltiazem (0.35 mg/kg IV) given if inadequate rate control within 15 min
      • Adequate rate control defined as heart rate < 100 bpm, decrease in heart rate by >20%, or normal sinus rhythm

Outcomes

  • Primary Outcome: 
    • Change in baseline systolic BP at 5, 10, 15 minutes after diltiazem 
  • Secondary Outcomes: 
    • Change in baseline heart rate at 5, 10, 15 minutes after diltiazem 
    • Need for additional dose of diltiazem (rescue treatment) 
    • Adverse events: hypotension, urticaria, nausea, hypercalcemia

Design

Randomized control trial

Excluded

Excluded

  • Pregnant
  • Hemodynamic instability requiring electrical cardioversion
  • History of sick sinus syndrome, 3rd-degree AV block, or Wolff-Parkinson-White
  • Known or suspected hypercalcemia
  • Allergy to diltiazem
  • Concurrent use of other rate control agents (beta-blockers, amiodarone, digoxin)

Primary Results

Primary outcome:

  • In the 180mg calcium pretreatment group, there was no statistically significant change in mean systolic BP
  • In the placebo and 90mg calcium pretreatment groups, mean systolic BP decreased after diltiazem administration at each measured time point
    • Mean systolic BP was 132 mmHg
    • Placebo group: on average, systolic BP decreased to 
      • 116 mmHg at 5 minutes 
      • 124 mmHg at 10 minutes
      • 117 mmHg at 15 minutes
    • 90mg calcium pretreatment group: on average, systolic BP decreased to 
      • 124 mmHg at 5 minutes
      • 125 mmHg at 10 and 15 minutes
    • The decreases in mean systolic BP reached statistical significance, but may not be clinically significant

Secondary outcomes:

  • Heart rate was lowered significantly in all groups after diltiazem administration (rate control achieved in all groups)
  • No significant differences in rates of adverse effects across groups
  • No significant differences in rates of additional diltiazem needed across groups

Strengths

Overall, this is a well-designed randomized control trial. The methods suggest adequate randomization, blinding and concealment of randomization.

Limitations

  • There is no subgroup analysis based on onset and rhythm
    • Only 12 of the patients had new-onset arrhythmia
    • Only 8 of the patients had a-flutter
  • There is no comparison of mean systolic BP between groups
    • The reader could use the data from Table 3 to do their own calculations comparing differences in systolic BP between each group and may find that these differences are not all statistically significant
  • This study was done at a single academic center, which could limit generalizability of results to other clinical practice settings

Author's Conclusions

  • Administering 180 mg calcium IV prior to diltiazem can effectively prevent drug-induced hypotension in patients with a-fib or a-flutter with RVR over a 15-min timeframe.
  • Administration of calcium does not affect the efficacy of diltiazem in achieving and maintaining heart rate control.
  • The rates of adverse events and need for additional doses of diltiazem were comparable between groups, suggesting that the use of calcium is safe.

Our Conclusions

  • The author’s conclusion that 180 mg of calcium can “prevent drug-induced hypotension” is not supported by their data.
    • 9 patients experienced hypotension and there was no statistically significant difference in this adverse event between the treatment groups.
    • Additionally, a definition of hypotension or what was considered a clinically significant reduction in blood pressure from baseline is not presented.
  • The decreases in blood pressure in the placebo and 90mg calcium groups do not appear to be clinically significant.
    • The lowest post-treatment systolic BP at any time was 116 mmHg, representing a 16 mmHg decrease from baseline– many clinicians would feel comfortable seeing this blood pressure.

Potential Impact To Current Practice

  • Overall, the body of literature analyzing this practice has not been able to show meaningful benefit of pretreatment with calcium before administering diltiazem. 
  • In this study, pretreatment with calcium does not appear to cause harm or increase the need for additional doses of diltiazem, but it does not appear to yield clinically significant benefit.
    • Some may choose to pretreat with calcium because it is a relatively safe intervention with theoretical reward
    • Others may avoid pretreatment with calcium and consider the practice an unnecessary use of resources