ORIGINAL CONTRIBUTION r:alcium channel blocker, toxicity
Calcium Channel Blocker Toxicity A retrospective review was conducted of all patients who were reported to a regional poison control center after "overdose" of a calcium channel blocker during a two-year period (1987 and 1988). An analysis of 91 patient cases is presented after excluding allergic reactions, cases involving coingestants, and patients lost to follow-up. Patients who developed any .wmptoms after ingestion were defined as manifesting toxicity. There were 38 cases of verapamil ingestion with toxicity developing in 18 patients. The mean nontoxic dose was 320 rag, whereas the mean toxic ingestion was ,1.2 g. Nine patients became hypotensive, I3 developed conduction ¢ystem abnormalities (sinus node suppression, atrioventricular nodal block, or handle branch block), and 11 manifested arrhythmias. Ten developed neurological symptoms. There were 31 cases of nifedipine ingestion with toxicity developing in seven patients. The mean nontoxic dose was 19 rag, while the mean toxic ingestion was 340 rag. Four patients were hypoten.¢ive, only one developed cardiac conduction abnormalities, and four developed arrhythmias. Three had neurological symptoms. There were 24 cases of dihiazem ingestion with only minor toxicity developing in ,four patients. There was no statistically significant difference in the frequency of hypotension, arrhythmias, or neurological symptoms in patients who overdosed with verapamil as compared with nifedipine (by Fisher's exact test). However, conduction system abnormalities were more common with verapamil ingestion (P < .05). Toxic manifestations after diltiazem overdose were uncommon in our study. Eighteen of the 29 patients who developed toxicity required treatment in excess of gastrointestinal decontamination. Calcium was administered to 14 patients and was helpful in five. /Ramoska EA, Spiller HA, Myers A: Calcium channel blocker toxicity Ann Emerg Med June 1990;19:649-653.]
Edward A Ramoska, MD, FACEP*t Henry A Spiller, RN, MS1: Amy Myers, RPH* Philadelphia, Pennsylvania From the Division of Emergency Medicine, Thomas Jefferson University Hospital;* Department of Emergency Medicine, Methodist Hospital;t and Delaware Valley Regional Poison Control Center,~ Philadelphia, Pennsylvania. Received for publication September 29, 1989. Revision received January 15, 1990. Accepted for publication February 9, 1990. Presented at the Scientific Assembly of the American College of Emergency Physicians in Washington, DC, September 1989. Address for reprints: Edward A Ramoska, MD, FACER Department of Emergency Medicine, Methodist Hospital, 2301 South Broad Street, Philadelphia, Pennsylvania 19148.
INTRODUCTION The group of drugs known collectively as the calcium channel blockers ICCBs) Islow channel-blocking agents or calcium receptor antagonistsl is chemically and pharmacologically diverse. While verapamil, nifedipine, and diltiazem, which were in clinical use during 1987 and 1988, increase coronary blood flow,1 only verapami], a papaverine derivative, and diltiazero, a benzothiazepine, affect atrioventricular nodal conduction. ~ In contrast, nifedipine, a dihydropyridine, has little effect on cardiac conductati0n but is a potent peripheral vasodilator. 3 Verapamil produces less vasodilatation than nifedipine, while diltiazem produces minimal vasodilatati0n.,~ In addition to the above cardiovascular effects, the smooth muscles 0t the lung, gastrointestinal tract, and uterus are also affected by CCBs. 4 The increasing popularity of CCBs as therapeutic agents has led to an increase in overdoses (accidental and intentional). Data collected by the American Association of Poison Control Centers (AAPCC) indicate that the number of ingestions of CCBs has increased by approximately 150% each year since 1984. ,~-9 There were 2,874 exposures involving calcium channel blockers in 1988, with 17 of these resulting in death. This represents more than 25% of the deaths due to overdose of a cardiovascular drug.`) With the exception of a variety of case reports involving principally verapamil, lO-~-~ there are no studies of the frequency or extent of toxicity encountered with the various calcium channel-blocking agents.
19:6June 1990
Annals of Emergency Medicine
649/55
CALCIUM CHANNEL BLOCKERS Ramoska, Spiller & Myers
FIGURE. Age distribution. To examine the toxicity of this class of drugs, we retrospectively examined the records of all patients who were reported to the Delaware Valley Regional Poison Control Center with an ingestion of a calcium channel blocker during the years 1987 and 1988.
METHODS The Delaware Valley Regional Poison Control Center uses the standard AAPCC cooperative poison center report form to record data about all calls received. All forms involving the ingestion of a calcium channel blocker were collected and the following data were abstracted from each form: patient demographics, drug history and dosing, toxic effects and the time that they developed, and any therapeutic interventions attempted and whether they were successful. Serum levels of CCB are not r o u t i n e l y available and were not measured in any of our patients. One h u n d r e d t h i r t y - o n e forms were collected. One nonhuman exposure and one case of an allergic reaction were excluded. T w e n t y - e i g h t cases involved coingestants, either by history or drug screen, and were also excluded so that the effects of pure CCB overdose could be assessed. Ten patients were lost to follow-up. The remaining 91 cases were analyzed. The scheme for classifying medical outcome is the standard one used by the AAPCC. In this system, minor refers to limited symptoms or symptoms not requiring treatment; moderate means more pronounced or prolonged s y m p t o m s , s y m p t o m s that usually require treatment but are not life-threatening and do not result in permanent impairment; and major refers to potentially life-threatening symptoms or symptoms that result in permanent impairment. Statistical significance was determined by Fisher's exact test. RESULTS There were 42 male and 49 female patients. The mean age was 25 years, with a range of 1 to 83 years. The age distribution and reason for ingestion are shown (Figure and Table 1, respectively). There were 38 cases of verapamil ingestion, 31 cases of nifedipine ingestion, and 24 cases of diltiazem ingestion. This totals 93 cases 56/650
24 22
2;
20 m 18--
17
16m u~
~E
14--
12-"6
Calcium Channel Blocker Toxicity A retrospective review was conducted of all patients who were reported to a regional poison control center after "overdose" of a calcium channel blocker during a two-year period (1987 and 1988). An analysis of 91 patient cases is presented after excluding allergic reactions, cases involving coingestants, and patients lost to follow-up. Patients who developed any .wmptoms after ingestion were defined as manifesting toxicity. There were 38 cases of verapamil ingestion with toxicity developing in 18 patients. The mean nontoxic dose was 320 rag, whereas the mean toxic ingestion was ,1.2 g. Nine patients became hypotensive, I3 developed conduction ¢ystem abnormalities (sinus node suppression, atrioventricular nodal block, or handle branch block), and 11 manifested arrhythmias. Ten developed neurological symptoms. There were 31 cases of nifedipine ingestion with toxicity developing in seven patients. The mean nontoxic dose was 19 rag, while the mean toxic ingestion was 340 rag. Four patients were hypoten.¢ive, only one developed cardiac conduction abnormalities, and four developed arrhythmias. Three had neurological symptoms. There were 24 cases of dihiazem ingestion with only minor toxicity developing in ,four patients. There was no statistically significant difference in the frequency of hypotension, arrhythmias, or neurological symptoms in patients who overdosed with verapamil as compared with nifedipine (by Fisher's exact test). However, conduction system abnormalities were more common with verapamil ingestion (P < .05). Toxic manifestations after diltiazem overdose were uncommon in our study. Eighteen of the 29 patients who developed toxicity required treatment in excess of gastrointestinal decontamination. Calcium was administered to 14 patients and was helpful in five. /Ramoska EA, Spiller HA, Myers A: Calcium channel blocker toxicity Ann Emerg Med June 1990;19:649-653.]
Edward A Ramoska, MD, FACEP*t Henry A Spiller, RN, MS1: Amy Myers, RPH* Philadelphia, Pennsylvania From the Division of Emergency Medicine, Thomas Jefferson University Hospital;* Department of Emergency Medicine, Methodist Hospital;t and Delaware Valley Regional Poison Control Center,~ Philadelphia, Pennsylvania. Received for publication September 29, 1989. Revision received January 15, 1990. Accepted for publication February 9, 1990. Presented at the Scientific Assembly of the American College of Emergency Physicians in Washington, DC, September 1989. Address for reprints: Edward A Ramoska, MD, FACER Department of Emergency Medicine, Methodist Hospital, 2301 South Broad Street, Philadelphia, Pennsylvania 19148.
INTRODUCTION The group of drugs known collectively as the calcium channel blockers ICCBs) Islow channel-blocking agents or calcium receptor antagonistsl is chemically and pharmacologically diverse. While verapamil, nifedipine, and diltiazem, which were in clinical use during 1987 and 1988, increase coronary blood flow,1 only verapami], a papaverine derivative, and diltiazero, a benzothiazepine, affect atrioventricular nodal conduction. ~ In contrast, nifedipine, a dihydropyridine, has little effect on cardiac conductati0n but is a potent peripheral vasodilator. 3 Verapamil produces less vasodilatation than nifedipine, while diltiazem produces minimal vasodilatati0n.,~ In addition to the above cardiovascular effects, the smooth muscles 0t the lung, gastrointestinal tract, and uterus are also affected by CCBs. 4 The increasing popularity of CCBs as therapeutic agents has led to an increase in overdoses (accidental and intentional). Data collected by the American Association of Poison Control Centers (AAPCC) indicate that the number of ingestions of CCBs has increased by approximately 150% each year since 1984. ,~-9 There were 2,874 exposures involving calcium channel blockers in 1988, with 17 of these resulting in death. This represents more than 25% of the deaths due to overdose of a cardiovascular drug.`) With the exception of a variety of case reports involving principally verapamil, lO-~-~ there are no studies of the frequency or extent of toxicity encountered with the various calcium channel-blocking agents.
19:6June 1990
Annals of Emergency Medicine
649/55
CALCIUM CHANNEL BLOCKERS Ramoska, Spiller & Myers
FIGURE. Age distribution. To examine the toxicity of this class of drugs, we retrospectively examined the records of all patients who were reported to the Delaware Valley Regional Poison Control Center with an ingestion of a calcium channel blocker during the years 1987 and 1988.
METHODS The Delaware Valley Regional Poison Control Center uses the standard AAPCC cooperative poison center report form to record data about all calls received. All forms involving the ingestion of a calcium channel blocker were collected and the following data were abstracted from each form: patient demographics, drug history and dosing, toxic effects and the time that they developed, and any therapeutic interventions attempted and whether they were successful. Serum levels of CCB are not r o u t i n e l y available and were not measured in any of our patients. One h u n d r e d t h i r t y - o n e forms were collected. One nonhuman exposure and one case of an allergic reaction were excluded. T w e n t y - e i g h t cases involved coingestants, either by history or drug screen, and were also excluded so that the effects of pure CCB overdose could be assessed. Ten patients were lost to follow-up. The remaining 91 cases were analyzed. The scheme for classifying medical outcome is the standard one used by the AAPCC. In this system, minor refers to limited symptoms or symptoms not requiring treatment; moderate means more pronounced or prolonged s y m p t o m s , s y m p t o m s that usually require treatment but are not life-threatening and do not result in permanent impairment; and major refers to potentially life-threatening symptoms or symptoms that result in permanent impairment. Statistical significance was determined by Fisher's exact test. RESULTS There were 42 male and 49 female patients. The mean age was 25 years, with a range of 1 to 83 years. The age distribution and reason for ingestion are shown (Figure and Table 1, respectively). There were 38 cases of verapamil ingestion, 31 cases of nifedipine ingestion, and 24 cases of diltiazem ingestion. This totals 93 cases 56/650
24 22
2;
20 m 18--
17
16m u~
~E
14--
12-"6
