Prehospital Pharmacology: Diltiazem

Atrial tachydysrhythmias are the most common sustained cardiac dysrhythmias. Thus, it should come as no surprise that EMS providers in North America will see patients who are symptomatic from these dysrhythmias and their sequelae in their daily practice. One of the most common classes of medications used to manage atrial tachydysrhythmias are calcium channel blockers. This article focuses on diltiazem (trade name Cardizem among others), a widely used calcium channel blocker, and its utility in the prehospital environment. Specific examples are provided from the archives of the Bryn Athyn (PA) Fire Company, where diltiazem was successfully administered to more than a dozen patients in calendar year 2005. This is especially significant, given a transport volume of only 700-800 patients annually.

Case Vignettes
     In July 2005, Bryn Athyn Fire Company responded to a motor vehicle collision with rollover. The sole patient was a 73-year-old male driver of a mid-size passenger vehicle that traveled off a two-lane highway at rush hour and crashed into a wooded area. The patient was found hanging upside down, suspended by his seat belt. He was awake and alert and complained of left wrist pain, but he did not remember the events leading up to the accident.

     The patient was rapidly extricated from his vehicle and a complete trauma assessment was performed in the ambulance. A paucity of traumatic injuries was noted; however, the patient was found to be in rapid atrial fibrillation at a rate of 150 beats per minute, with a blood pressure of 160/120. He denied having a history of cardiac arrhythmia. A 12-lead ECG did not reveal any evidence of acute transmural myocardial infarction. Additional treatment consisted of bilateral large-bore IV access, oxygen, blood glucose testing and full spinal immobilization. Cardizem, 20 mg IV push, was administered by protocol en route to the local trauma center, and the patient's heart rate decreased to 90 beats per minute within 60 seconds. Since the patient denied a history of atrial fibrillation, the crew surmised that the arrhythmia occurred while he was driving, which caused him to develop syncope, veer off the road and crash.

     During the same month, an elderly female nursing home patient with a history of diabetes, hypertension, elevated cholesterol and hypothyroidism complained of chest pressure lasting greater than 12 hours. Initial vital signs included heart rate of 200, respiratory rate of 16 and BP of 100/66. Standard advanced life support measures were implemented, including both 3-lead and 12-lead ECG acquisition, peripheral IV access with 600 cc total fluid bolus, blood glucose testing and nasal oxygen. The paramedic interpreted the rhythm as PSVT, due to the appearance of a regular and extremely rapid, narrow complex tachycardia. After an initial dose of adenosine failed to break the dysrhythmia, the blood pressure by automated cuff dropped to 86/46. Cardizem, 20 mg, was then administered as a slow IV push over five minutes for what became clearly discernable as atrial fibrillation with rapid ventricular response. Within 60 seconds, the patient's heart rate slowed to 126, BP improved to 154/82 and chest discomfort ceased.

Literature Support for prehospital Use
     Prior to the early 1990s, verapamil was the only intravenous calcium channel blocker available for the treatment of atrial tachydysrhythmias. Verapamil was notorious for its negative inotropic effects, particularly the resultant hypotension that was seen most frequently in those patients who were also volume-depleted.

     The intravenous form of diltiazem became available in the U.S. in the early 1990s; however, its use in the prehospital environment was limited until the late 1990s because the drug was initially marketed as a refrigerated medication only. Lyophilized diltiazem has been available for the last eight years or so, and its cost is reasonable compared with other cardiac medications.

     There have been few scientific studies concerning the safety and efficacy of diltiazem in the prehospital environment. As usual, the bulk of information about diltiazem, its safety profile and the presumed utility of the drug in the field comes from emergency department and cardiology research. One of the best prehospital studies appeared in the Annals of Emergency Medicine in 2001 and was authored by noted EMS airway researcher Henry Wang. The conclusion was that intravenous diltiazem was safe, effective and should be considered a standard of care for use in those patients with atrial fibrillation with uncontrolled ventricular response who do not meet criteria for emergent cardioversion.

Indications
     Diltiazem is indicated for the treatment of PSVT and atrial fibrillation or flutter with rapid ventricular response. (ACLS recommends adenosine as the first-line agent for PSVT, and it is usually successful.) The definition of rapid ventricular response for purposes of pharmacologic treatment is greater than 120 beats per minute. The parenteral dose is 0.25 mg/kg given over two minutes. A repeat bolus of diltiazem 10-15 minutes later may be given at 0.35 mg/kg if ventricular response is inadequate. An adequate response is usually considered to be a heart rate less than 120 beats per minute, although true rate control is defined as a rate of 100 or less continuously for a period of one hour.

     In the emergency department, there are two options for maintenance therapy once adequate ventricular response has been achieved. The preferred method is to begin or continue oral dosing with diltiazem or a beta blocker. The patient is then admitted to a monitored (telemetry) bed. Alternatively, a diltiazem drip is begun, which usually commits the patient to an ICU admission. Few EMS systems carry oral cardiac medications other than aspirin, and we are aware of none that carry diltiazem drips. In most systems with transport times of less than 30 minutes, patients can be successfully managed with a single bolus of diltiazem.

Adverse Effects
     Adverse reactions are few and are primarily related to supertherapeutic dosing. These include AV block, bradyarrhythmia, flushing, dizziness and headache. The most common prehospital adverse reaction to be expected is transient bradycardia and AV block due to administration of too large a dose of medication.

     How is this possible if the dosing algorithm is so simple? The answer is in the mathematics. It is well documented that medical professionals do not estimate patient weights very accurately. Typically, overestimating patient weight, combined with rounding up to the nearest whole number in milligrams of medication and then rounding to the nearest 5 mg increment which can most easily be ascertained on the syringe containing the drug, leads to unintentional overdosing of diltiazem. Fortunately, the adverse effects are short-lived and do not require "rescue" with atropine. Paramedics should make note of this fact, since administration of atropine would be contraindicated in a patient whose tachycardia is being managed with diltiazem.

Contraindications
     Contraindications for the use of calcium channel blockers include sick sinus syndrome, heart block, known hypersensitivity to calcium channel blockers and symptomatic hypotension (SBP <90). The latter contraindication deserves special attention because it is relative rather than absolute. A percentage of patients who experience atrial tachydysrhythmias will drop their blood pressure due to the decreased cardiac output that is caused by decreased ventricular filling. This, in turn, is due to the fact that the ventricles do not have adequate time to fill given the rapid heart rate and loss of atrial kick from discordant atrial activity. Once the heart rate is slowed, ventricular filling will improve and most patients will have resolution of their borderline blood pressure within several minutes without the aid of crystalloid infusion.

     The need for electrical cardioversion is another contraindication to using diltiazem; however, cardioversion is rarely necessary. In fact, cardioversion of atrial tachydysrhythmias is only indicated in the emergency setting when the patient is unstable and there is an imminent life threat. This term implies altered mental status, extreme hypotension or severe dyspnea. (Although chest pain is often cited as a definition of "symptomatic tachycardia," we do not believe that this is adequate criteria for cardioversion, since many patients with underlying coronary artery disease who experience a heart rate of 150 bpm will have chest pain due to ischemia.)

     Given the rapidity with which IV access and resuscitation medications can be brought to bear in emergency cardiac care, cardioversion should be used only as a last resort in the EMS setting. Cardioversion is often contraindicated, since patients are not adequately anticoagulated, if at all, which increases chances of dislodging a blood clot in the heart if the dysrhythmia has been present for more than 48 hours.

Logistics of Administration
     Diltiazem will be administered in the prehospital setting most frequently as an intravenous bolus. It is available in both liquid and lyophilized states, although the liquid version requires refrigeration. Both types contain 25 mg to the dose. An average 80-100-kg male patient will require 15-20 mg of the drug to achieve therapeutic effect.

Our Thoughts
     The primary discussion point is whether use of the drug is warranted, given the relative stability of patients with rapid atrial fibrillation. Patients suffering from atrial fibrillation/flutter and PSVT may rarely present in extremis, but most have underlying coronary artery disease and all potentially sustain bouts of coronary ischemia while heart rates are wildly elevated. Thus, it seems intuitive that it is in patients' best interest to have their heart rates controlled as quickly as possible.

     Furthermore, it seems paradoxical not to maintain the capability to treat this dysrhythmia when the majority of medications carried on U.S. ambulances are for ACLS emergencies, despite the fact that none but aspirin and nitroglycerin are used frequently. Notably, Bryn Athyn uses diltiazem at least five times as frequently as adenosine, and none of the administrations have been in error.

     We believe that arguments about whether to initiate ALS treatments in the field are becoming moot, since patient overcrowding situations in U.S. EDs and decreased availability of ambulances due to lopsided supply and demand equations are leading to prolonged times to evaluation for all but those with life-threatening illness or injury. It is our experience in suburban Philadelphia that the average 20-30 minutes from EMS patient contact to actual deposit in a hospital ED stretcher, coupled with the average 30-minute time frame from patient evaluation to procurement and administration of the therapeutic pharmacologic agent, easily justifies use of diltiazem in the field, just as it does other first-line ACLS medications.

Benjamin Zachar, DO, is a third-year resident in emergency medicine at the Albert Einstein Medical Center in Philadelphia. As part of his education, he has assumed responsibility as an assistant medical director in training of Bryn Athyn Fire Company in Montgomery County, PA.

Keith Graham, EMT-P, is a firefighter in the Philadelphia Fire Department, who was also a career firefighter/paramedic at Bryn Athyn Fire Company at the time this article was written.

David Jaslow, MD, MPH, EMT-P, FAAEM, is chief of the Division of EMS, Operational Public Health and Disaster Medicine within the Department of Emergency Medicine at Albert Einstein Medical Center. He is an active firefighter/paramedic, assistant chief for EMS and EMS medical director for Bryn Athyn Fire Company. Dr. Jaslow serves as medical editorial consultant for EMS Magazine.