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The risk of seizure recurrence following a first unprovoked seizure: A quantitative review
Abstracts
q A STATEWIDE EARLY DEFIBRILLATION INITIATIVE INCLUDING LAYPERSONS AND OUTCOME REPORTING. Haynes BE, Mendoza A, McNeil M, Schroeder J, Smiley DR. 1991;266:545-7. This article describes California’s development of a comprehensive framework for early defibrillating, including defibrillation by emergency medical technicians (EMTs) and public safety personnel, with a statewide requirement for reporting outcomes and the initial data on patient survival. In California, defibrillation by basic EMTs was first approved in February 1987, and defibrillation by public safety personnel using automated devices only was approved in December 1987. In the first 46 months that defibrillation was authorized, 1487 patients with out-of-hospital cardiac arrests had defibrillatory shocks applied by basic-level rescuers and all outcome data points reported. Most patients receiving shocks had witnessedventricular fibrillation (V fib), and 191 of these patients were discharged from the hospital alive, representing 19% of those with V fib and witnessed cardiac arrest, and 13% of patients who had shock applied. The authors commented that while their data are not meant to validate basic level defibrillation, in 4 years they tripled the number of rescuerstrained in defibrillation from 6000 paramedics and EMTs to more than 15000 laypersons. The authors anticipate more rescuers in the future and hope that survival rates increase. [Juliana Karp, MD] Editor’s Note: Early defibrillation by first responders is of clear benefit (particularly in rural areas) as long as there is active physician medical control and an effective quality assuranceprogram.
0 ACETAMINOPHEN OVERDOSE: A 48-HOUR INTRAVENOUS N-ACETYLCYSTEINE TREATMENT PROTOCOL. Smilkstein MJ, Bronstein AC, Linden C,
Augenstein WL, Kulig KW, Rumack BH. Ann Emerg Med. 1991;20:1094-63. A prospective, multicenter study of the safety and efficacy of a 48-hour IV N-Acetylcysteine (IV NAC) treatment protocol for acute acetaminophen overdose was conducted. Patients were divided into hepatotoxicity risk groups based on initial plasma acetaminophen levels: Group 1 = possible risk, Group 2 = probably risk, and Group 3 = high risk. Groups were further subdivided based on the time that NAC was initiated. One hundred seventy-nine patients with acute acetaminophen overdose and plasma acetaminophen concentration above the treatment nomogram line were treated with the IV NAC protocol: a loading dose of 140 mg/kg followed by 12 doses of 70 mg/kg every 4 hours. Hepatotoxicity was uncommon in all groups treated within 10 hours. When treatment was delayed more than 10 hours, hepatotoxicity was evident in 23 of 85 (27.1 olo)of Group 2 patients and in 16 of 50 (32%) of Group 3 patients. Among Group 3 patients first treated 16 to 24 hours after ingestion, hepatotoxicity occurred in 57.9% (11 of 19). Overall, 2 of 179 enrolled patients died. Adverse reaction resulting from IV NAC occurred in
14.3% of patients; in all instances the reactions were mild, self-limited, and did not require discontinuation of therapy. The authors concluded that the 48-hour IV NAC protocol is a safe and effective antidotal therapy for acetaminophen overdose. Based on available data, 48-hour IV NAC is equal to 72-hour oral and 20-hour IV NAC protocols when started within 10 hours of acetaminophen ingestion. Overall, when treatment is started 10 to 24 hours after overdose, 48-hour IV NAC is as effective as 72-hour oral NAC and more effective than 20-hour IV NAC. The optimum treatment for Group 3 patients receiving their first NAC dose more than 16 hours after overdose remains unclear. [David Magid, MD] Editor’s Note: It is clear that IV NAC is efficacious and is tolerated better by patients when compared with the oral protocol.
0 TREATMENT MATRIPTAN.
OF MIGRAINE
ATTACKS
WITH
SU-
The Subcutaneous Sumatriptan International Study Group. N Engl J Med. 1991;316. Six-hundred and thirty-nine otherwise healthy migraine headache patients were enrolled in a randomized, doubleblind, placebo-controlled study to look at the efficacy of sumatriptan, an agonist of 5-hydroxytryptamine-like receptors that blocks the suspected mechanisms of migraine attack. Patients received either placebo, 6 mg or 8 mg of sumatriptan SQ and were evaluated for response at 60 minutes. Patients who still had headaches received either placebo or sumatriptan in a second blinded injection. Patients who initially received placebo or 8 mg of sumatriptan got placebo in the second dose, while the 6-mg sumatriptan group received either placebo or a second 6-mg dose of the drug. Patients were reevaluated 60 minutes later. Recipients of sumatriptan, regardless of the dose, had significantly more improvement in migraine symptoms when compared to the placebo group (72% to 74% versus 25%) at 60 minutes, and over 90% were symptom-free at 120 minutes. There was no difference between the 6-mg and 8-mg doses and no significant difference in response when a second injection was given. Recurrence rate of migraines was higher in the patients who received sumatriptan (34% to 38% versus 18%). Adverse side-effects, although minor and self-limited, were also more common in the sumatriptan group. Sumatriptan, in a single 6-mg dose, is recommended for rapid, effective treatment of migraine attacks. [Leslie Mime, MD]
0 THE RISK OF SEIZURE RECURRENCE FOLLOWING A FIRST UNPROVOKED SEIZURE: A QUANTITATIVE REVIEW. Berg AT, Shinnar S. Neurology. 1991;
41:965-72. The issue of whether or not to treat a patient following a first unprovoked seizure is widely debated. Estimates of risk of a second seizure range from 23% to 71%. A meta-
The Journal
240 analysis of 16 studies was done and discovered three factors that explain much of this variability: 1) whether only patients with their first seizure were enrolled in a study, 2) retrospective versus prospective study, and 3) the duration of the follow-up period. In prospective studies that include only those patients with a single seizure who were followed for approximately 2 years, there is a 36% risk of recurrent seizures, lower than studies that are not so selective. Partial seizures, abnormal EEGs, and patients with prior neurologic abnormalities predicted an increased chance of recurrence. History of febrile seizureshad a nonsignificant trend toward increased seizures.Prior provoked seizures, history of neonatal seizures, family history of seizures, status epilepticus, sex, and age were not associated with increased incidence of recurrent seizures. The authors note the importance of knowledge of risk of recurrent seizure as well as the risks of antiseizure medication in deciding whether to treat a patient after a first seizure. They do not make formal recommendations but recognize the importance of an individualized decision in each case. [Laurie Vande Krol, MD] Editor’s Note: The risk of anticonvulsant medication is probably not warranted in the setting of a simple, nonfocal seizure with a negative first seizure work-up in the emergency department,
0 SEIZURE CREATININE PARTMENT.
VS. SYNCOPE: MEASURING SERUM KINASE IN THE EMERGENCY DE-
Libman MD, Potvin L, Coupal L, et al. Gen Intern Med. 1991;6:408-12. The evaluation of transient loss of consciousnesscan be frustrating in the ED because of a large differential diagnosis and often vague history. This retrospective study assessesthe clinical utility of serum creatinine kinase (CK) measurements in distinguishing a generalized tonic-clonic seizure from other causesof loss of consciousness. Over a 6-month period, medical personnel were asked to order a CK measurement on bloods drawn from all patients presenting because of transient loss of consciousness. All ED visits during this time period were reviewed, and 96 patients were identified with both a diagnosis suggesting transient loss of consciousness and a serum CK measurement. An investigator blinded to the CK results then classified each patient into 1 of 3 groups: definite or probable seizure (group l), unclear diagnosis (group 2), and those unlikely to have had a seizure (group 3). The mean CK value was significantly higher in the seizure group than in the nonseizure group, 231 .l U/L compared with 70.5 U/L, respectively. The test specificity was 0.98 and the sensitivity 0.43. It was also noted that the difference in mean CK levels between the two groups was strongly associated with the estimated time interval between the event and CK measurement. When the study population was stratified according to this time interval, the test sensitivity increased to 0.80 in those with a time interval greater than 3 hours compared to 0.20 in those measured lessthan 3 hours from the event. The authors conclude that high serum CK values correlate
of Emergency
Medicine
strongly with the presence of seizure. The sensitivity may be improved if the measurement is done more than 3 hours after the event. [Todd Zaayer, MD] Editor’s Note: This is a retrospective study with a highly selected population. It remains to be prospectively determined whether such an investigation would influence patient management more than clinical judgment alone.
0 NARROW
QRS VENTRICULAR
TACHYCARDLA.
Hayes JJ, Stewart RB, Greene L, Bardy GH. Ann Intern Med. 1991;114:460-3. This is a retrospective review of patients referred to an arrythmia service. Of 106 patients with inducible ventricular tachycardia (VT) during electrophysiologic testing, 5 had narrow QRS VT. The definition for narrow QRS VT was QRS of 0.11 seconds or less on the longest duration QRS of a standard electrocardiography. VT was confirmed by use of intracardiac electrodes. The patients with narrow QRS VT when compared to those with wide complex VT tended to be younger (50 versus 61 years) and had higher mean left ventricular ejection fractions (42vo compared with 31%). Of the 5 patients, 4 had right bundle branch block morphology; the remaining 1 had left bundle branch block morphology. Other ECG characteristics used to diagnose VT were examined. Four had QRS morphologic criteria (2 with biphasic Vl, 1 with monophasic Vl, and 1 with QS in V6 and notched S in Vl). Four of 5 had QRS concordance (Vl through V6 are either all positive or all negative). Two of the 5 had ventriculoatrial dissociation. All 5 had a change in the initial QRS vector compared to the sinus rhythm ECG. Retrospective reviews of the individuals’ histories found that one of the patients was given intravenous verapamil for an acute tachycardia and subsequently required electrical cardioversion due to hemodynamic insta[Andrew B. Ziller, MD] bility. Editor’s Note: Though this article was based on patients in an electrophysiologic testing setting, this is additional support for considering adenosine or procainamide in the treatment of hemodynamically stable patients with narrow complex tachycardia and ECG evidence of VT.
Cl LACK OF PROGNOSTIC VALUE OF SYNCOPE IN PATIENTS WITH WOLFF-PARKINSON-WHITE SYNDROME. Auricchio A, Klein H, Trappe HJ, Wen-
zlaff P. Am Co11Cardiol. 1991;17:152-8. Syncope in patients with Wolff-Parkinson-White (WPW) syndrome suggeststhe occurrence of rapid tachyarrhythmias and may be considered a premonitory event heralding possible sudden death. A retrospective study of clinical and electrophysiologic (EP) characteristics of 101 patients was performed to determine the incidence of syncope, the predictability of syncope based on EP findings, and the sensitivity and specificity of syncope as a risk factor for sudden cardiac death in patients with WPW syn-
q A STATEWIDE EARLY DEFIBRILLATION INITIATIVE INCLUDING LAYPERSONS AND OUTCOME REPORTING. Haynes BE, Mendoza A, McNeil M, Schroeder J, Smiley DR. 1991;266:545-7. This article describes California’s development of a comprehensive framework for early defibrillating, including defibrillation by emergency medical technicians (EMTs) and public safety personnel, with a statewide requirement for reporting outcomes and the initial data on patient survival. In California, defibrillation by basic EMTs was first approved in February 1987, and defibrillation by public safety personnel using automated devices only was approved in December 1987. In the first 46 months that defibrillation was authorized, 1487 patients with out-of-hospital cardiac arrests had defibrillatory shocks applied by basic-level rescuers and all outcome data points reported. Most patients receiving shocks had witnessedventricular fibrillation (V fib), and 191 of these patients were discharged from the hospital alive, representing 19% of those with V fib and witnessed cardiac arrest, and 13% of patients who had shock applied. The authors commented that while their data are not meant to validate basic level defibrillation, in 4 years they tripled the number of rescuerstrained in defibrillation from 6000 paramedics and EMTs to more than 15000 laypersons. The authors anticipate more rescuers in the future and hope that survival rates increase. [Juliana Karp, MD] Editor’s Note: Early defibrillation by first responders is of clear benefit (particularly in rural areas) as long as there is active physician medical control and an effective quality assuranceprogram.
0 ACETAMINOPHEN OVERDOSE: A 48-HOUR INTRAVENOUS N-ACETYLCYSTEINE TREATMENT PROTOCOL. Smilkstein MJ, Bronstein AC, Linden C,
Augenstein WL, Kulig KW, Rumack BH. Ann Emerg Med. 1991;20:1094-63. A prospective, multicenter study of the safety and efficacy of a 48-hour IV N-Acetylcysteine (IV NAC) treatment protocol for acute acetaminophen overdose was conducted. Patients were divided into hepatotoxicity risk groups based on initial plasma acetaminophen levels: Group 1 = possible risk, Group 2 = probably risk, and Group 3 = high risk. Groups were further subdivided based on the time that NAC was initiated. One hundred seventy-nine patients with acute acetaminophen overdose and plasma acetaminophen concentration above the treatment nomogram line were treated with the IV NAC protocol: a loading dose of 140 mg/kg followed by 12 doses of 70 mg/kg every 4 hours. Hepatotoxicity was uncommon in all groups treated within 10 hours. When treatment was delayed more than 10 hours, hepatotoxicity was evident in 23 of 85 (27.1 olo)of Group 2 patients and in 16 of 50 (32%) of Group 3 patients. Among Group 3 patients first treated 16 to 24 hours after ingestion, hepatotoxicity occurred in 57.9% (11 of 19). Overall, 2 of 179 enrolled patients died. Adverse reaction resulting from IV NAC occurred in
14.3% of patients; in all instances the reactions were mild, self-limited, and did not require discontinuation of therapy. The authors concluded that the 48-hour IV NAC protocol is a safe and effective antidotal therapy for acetaminophen overdose. Based on available data, 48-hour IV NAC is equal to 72-hour oral and 20-hour IV NAC protocols when started within 10 hours of acetaminophen ingestion. Overall, when treatment is started 10 to 24 hours after overdose, 48-hour IV NAC is as effective as 72-hour oral NAC and more effective than 20-hour IV NAC. The optimum treatment for Group 3 patients receiving their first NAC dose more than 16 hours after overdose remains unclear. [David Magid, MD] Editor’s Note: It is clear that IV NAC is efficacious and is tolerated better by patients when compared with the oral protocol.
0 TREATMENT MATRIPTAN.
OF MIGRAINE
ATTACKS
WITH
SU-
The Subcutaneous Sumatriptan International Study Group. N Engl J Med. 1991;316. Six-hundred and thirty-nine otherwise healthy migraine headache patients were enrolled in a randomized, doubleblind, placebo-controlled study to look at the efficacy of sumatriptan, an agonist of 5-hydroxytryptamine-like receptors that blocks the suspected mechanisms of migraine attack. Patients received either placebo, 6 mg or 8 mg of sumatriptan SQ and were evaluated for response at 60 minutes. Patients who still had headaches received either placebo or sumatriptan in a second blinded injection. Patients who initially received placebo or 8 mg of sumatriptan got placebo in the second dose, while the 6-mg sumatriptan group received either placebo or a second 6-mg dose of the drug. Patients were reevaluated 60 minutes later. Recipients of sumatriptan, regardless of the dose, had significantly more improvement in migraine symptoms when compared to the placebo group (72% to 74% versus 25%) at 60 minutes, and over 90% were symptom-free at 120 minutes. There was no difference between the 6-mg and 8-mg doses and no significant difference in response when a second injection was given. Recurrence rate of migraines was higher in the patients who received sumatriptan (34% to 38% versus 18%). Adverse side-effects, although minor and self-limited, were also more common in the sumatriptan group. Sumatriptan, in a single 6-mg dose, is recommended for rapid, effective treatment of migraine attacks. [Leslie Mime, MD]
0 THE RISK OF SEIZURE RECURRENCE FOLLOWING A FIRST UNPROVOKED SEIZURE: A QUANTITATIVE REVIEW. Berg AT, Shinnar S. Neurology. 1991;
41:965-72. The issue of whether or not to treat a patient following a first unprovoked seizure is widely debated. Estimates of risk of a second seizure range from 23% to 71%. A meta-
The Journal
240 analysis of 16 studies was done and discovered three factors that explain much of this variability: 1) whether only patients with their first seizure were enrolled in a study, 2) retrospective versus prospective study, and 3) the duration of the follow-up period. In prospective studies that include only those patients with a single seizure who were followed for approximately 2 years, there is a 36% risk of recurrent seizures, lower than studies that are not so selective. Partial seizures, abnormal EEGs, and patients with prior neurologic abnormalities predicted an increased chance of recurrence. History of febrile seizureshad a nonsignificant trend toward increased seizures.Prior provoked seizures, history of neonatal seizures, family history of seizures, status epilepticus, sex, and age were not associated with increased incidence of recurrent seizures. The authors note the importance of knowledge of risk of recurrent seizure as well as the risks of antiseizure medication in deciding whether to treat a patient after a first seizure. They do not make formal recommendations but recognize the importance of an individualized decision in each case. [Laurie Vande Krol, MD] Editor’s Note: The risk of anticonvulsant medication is probably not warranted in the setting of a simple, nonfocal seizure with a negative first seizure work-up in the emergency department,
0 SEIZURE CREATININE PARTMENT.
VS. SYNCOPE: MEASURING SERUM KINASE IN THE EMERGENCY DE-
Libman MD, Potvin L, Coupal L, et al. Gen Intern Med. 1991;6:408-12. The evaluation of transient loss of consciousnesscan be frustrating in the ED because of a large differential diagnosis and often vague history. This retrospective study assessesthe clinical utility of serum creatinine kinase (CK) measurements in distinguishing a generalized tonic-clonic seizure from other causesof loss of consciousness. Over a 6-month period, medical personnel were asked to order a CK measurement on bloods drawn from all patients presenting because of transient loss of consciousness. All ED visits during this time period were reviewed, and 96 patients were identified with both a diagnosis suggesting transient loss of consciousness and a serum CK measurement. An investigator blinded to the CK results then classified each patient into 1 of 3 groups: definite or probable seizure (group l), unclear diagnosis (group 2), and those unlikely to have had a seizure (group 3). The mean CK value was significantly higher in the seizure group than in the nonseizure group, 231 .l U/L compared with 70.5 U/L, respectively. The test specificity was 0.98 and the sensitivity 0.43. It was also noted that the difference in mean CK levels between the two groups was strongly associated with the estimated time interval between the event and CK measurement. When the study population was stratified according to this time interval, the test sensitivity increased to 0.80 in those with a time interval greater than 3 hours compared to 0.20 in those measured lessthan 3 hours from the event. The authors conclude that high serum CK values correlate
of Emergency
Medicine
strongly with the presence of seizure. The sensitivity may be improved if the measurement is done more than 3 hours after the event. [Todd Zaayer, MD] Editor’s Note: This is a retrospective study with a highly selected population. It remains to be prospectively determined whether such an investigation would influence patient management more than clinical judgment alone.
0 NARROW
QRS VENTRICULAR
TACHYCARDLA.
Hayes JJ, Stewart RB, Greene L, Bardy GH. Ann Intern Med. 1991;114:460-3. This is a retrospective review of patients referred to an arrythmia service. Of 106 patients with inducible ventricular tachycardia (VT) during electrophysiologic testing, 5 had narrow QRS VT. The definition for narrow QRS VT was QRS of 0.11 seconds or less on the longest duration QRS of a standard electrocardiography. VT was confirmed by use of intracardiac electrodes. The patients with narrow QRS VT when compared to those with wide complex VT tended to be younger (50 versus 61 years) and had higher mean left ventricular ejection fractions (42vo compared with 31%). Of the 5 patients, 4 had right bundle branch block morphology; the remaining 1 had left bundle branch block morphology. Other ECG characteristics used to diagnose VT were examined. Four had QRS morphologic criteria (2 with biphasic Vl, 1 with monophasic Vl, and 1 with QS in V6 and notched S in Vl). Four of 5 had QRS concordance (Vl through V6 are either all positive or all negative). Two of the 5 had ventriculoatrial dissociation. All 5 had a change in the initial QRS vector compared to the sinus rhythm ECG. Retrospective reviews of the individuals’ histories found that one of the patients was given intravenous verapamil for an acute tachycardia and subsequently required electrical cardioversion due to hemodynamic insta[Andrew B. Ziller, MD] bility. Editor’s Note: Though this article was based on patients in an electrophysiologic testing setting, this is additional support for considering adenosine or procainamide in the treatment of hemodynamically stable patients with narrow complex tachycardia and ECG evidence of VT.
Cl LACK OF PROGNOSTIC VALUE OF SYNCOPE IN PATIENTS WITH WOLFF-PARKINSON-WHITE SYNDROME. Auricchio A, Klein H, Trappe HJ, Wen-
zlaff P. Am Co11Cardiol. 1991;17:152-8. Syncope in patients with Wolff-Parkinson-White (WPW) syndrome suggeststhe occurrence of rapid tachyarrhythmias and may be considered a premonitory event heralding possible sudden death. A retrospective study of clinical and electrophysiologic (EP) characteristics of 101 patients was performed to determine the incidence of syncope, the predictability of syncope based on EP findings, and the sensitivity and specificity of syncope as a risk factor for sudden cardiac death in patients with WPW syn-