Vasopressin Similar to Epinephrine in Hospital MIs, but no Clear Evidence of its Superiority

The American Heart Association took some heat with the release of its newest ACLS guidelines because of recommendations that many felt were not adequately supported by the medical literature. Two such recommendations centered on the use of vasopressin and biphasic defibrillation. The use of vasopressin in ACLS was the subject of a study by Ian Stiell and colleagues. In the introduction to the study, they note that some have speculated that non-adrenergic vasoactive drugs may have some advantage over adrenergic varieties because of fewer side effects. They also point out that in experimental models of cardiac arrest, use of vasopressin resulted in increased arterial and coronary perfusion pressures and flows when compared with standard epinephrine doses, and that in two small case series, patients failing treatment with epinephrine survived with vasopressin. Finally, in one prehospital study of 40 patients who did not respond to three countershocks and who were given either epinephrine or vasopressin, the vasopressin-treated patients had a 50 percent increase in the number of admitted patients and a 66 percent increase in patients alive at 24 hours. One study failed to demonstrate a superiority of vasopressin over epinephrine for in-hospital cardiac arrest Unfortunately, in the current comparative study of epinephrine vs. vasopressin in in-hospital cardiac arrests, multiple outcomes were similar, and the superiority of vasopressin over epinephrine could not be established. To be fair, however, we don't know if the dose used was optimal, nor do we know whether giving only vasopressin to one group would have made a difference (both groups received multiple doses of epinephrine after an initial dose of either vasopressin or epinephrine). In any case, the authors “strongly disagree with the decision of the AHA to recommend vasopressin as an alternative therapy to epinephrine.” One final point: this study was published in the Lancet, one of the top three journals in clinical medicine in my opinion. It is clearly prestigious for authors to have their work published in the likes of Lancet and the New England Journal of Medicine. Unfortunately, it is highly unlikely that the physicians who need to see this study most (emergency physicians) will have the opportunity because, I dare say, most don't receive or regularly review the Lancet. Dr. Stiell and colleagues received an extra gold star because their study was published in a prestigious British journal, but how was it intended that the information be disseminated to rank-and-file emergency physicians? Vasopressin vs. Epinephrine for Inhospital Cardiac Arrest: A Randomised Controlled Trial, Stiell IG, et al, Lancet, 2001;358:105 BACKGROUND: Several small experimental and clinical trials have suggested that vasopressin may be more effective than epinephrine for the management of cardiac arrest, and vasopressin has been recommended as an alternative to epinephrine in ACLS guidelines. METHODS: In this trial from the Universities of Ottawa and Western Ontario, 200 adults sustaining in-hospital cardiac arrests (unrelated to injury, exsanguination, surgery, or delivery) with indications for epinephrine administration were randomized to receive a first dose of either IV vasopressin (40 U) or epinephrine (1 mg) during attempted resuscitation. If additional doses were required, epinephrine was administered to both groups at a rate of 1 mg every three to five minutes. Findings provide evidence that the 150J impedance-compensated biphasic truncated exponential waveform AED is more effective than MTE or MDS monophasic AEDs. RESULTS: There were no differences between the groups in arrest characteristics, including the interval from collapse to CPR (under two minutes) or from the onset of CPR to provision of ACLS interventions (just over one minute), or in the types of drugs administered during attempted resuscitation (87% in the vasopressin group and 81% in the epinephrine group required additional epinephrine). There were no differences between the groups in rates of return of a pulse (60% in the vasopressin group and 59% in the epinephrine group), or survival at one hour (39% vs. 35%), 24 hours (26% vs. 24%), or 30 days (13% vs. 14%). There were likewise no differences in the frequency of tachyarrhythmia (10% vs. 8%). CONCLUSIONS: This study failed to demonstrate a superiority of vasopressin over epinephrine for the management of in-hospital cardiac arrest. The Differences between AEDs The following paper is a reanalysis of a prior study trying to determine whether defibrillation waveforms could alter the outcome of defibrillation and ultimately cardiac arrests. The authors point out that biphasic defibrillation is the technique used in implanted defibrillators. It requires smaller and lighter batteries, and battery life is prolonged when biphasic waveform defibrillation is used compared with standard waveforms. The study clearly demonstrated that immediate and intermediate outcomes were better with biphasic defibrillation, but the study was too small to have many of these outcomes reach statistical significance (although the trends are very apparent). Skeptics will focus on the fact that survival to discharge was not improved, although many factors act as determinants of this ultimate outcome. If viewed as the links of a chain, efforts to make each component of ACLS as efficacious as possible would be considered reasonable, with the hope that as each component of care is optimized, overall outcomes also will be improved. To not acknowledge the obvious beneficial trends associated with biphasic defibrillation because outcomes were not changed is expecting too much from just one of the components of ACLS care. As I see it, larger studies are needed to clearly establish if biphasic defibrillation is superior to traditional techniques. And, like the previous study, where was this paper published? In Resuscitation, an Irish journal not likely to be seen by many American emergency physicians. Optimal Response to Cardiac Arrest Study: Defibrillation Waveform Effects, Martens PR, et al, Resuscitation, 2001;49:233 BACKGROUND: The availability of automatic external defibrillators (AEDs) has substantially decreased the intervals from prehospital cardiac arrest to defibrillation. Escalating energy (200–360J) AEDs that deliver either monophasic truncated exponential (MTE) or damped sine (MDS) defibrillation waveforms are most often used, but there is some evidence that successful defibrillation may be more likely with devices that deliver 150J biphasic waveforms, adjusted to patient impedance (ICBTEs). METHODS: The authors of this multinational study supported by Agilent analyzed data from 115 prehospital cardiac arrest patients (exhibiting ventricular fibrillation as the initial rhythm) included in the Optimal Response to Cardiac Arrest (ORCA) trial to compare success rates achieved with biphasic or MTE (Heartstart 3000 or 911) or MDE (Heartstart 2000 or LifePak 200) monophasic waveform AEDs. RESULTS: The rate of defibrillation with a first shock was 96 percent with the ICBTEs, 54 percent with the MTE AEDs, and 77 percent with the MDS AEDs, and corresponding rates of defibrillation with three or fewer shocks were 98 percent, 67 percent, and 77 percent, respectively. The rate of return of spontaneous circulation was 76 percent with the ICBTEs compared with 54 percent for the MTE or MDS AEDs. The rate of survival to hospital admission was 61 percent with the ICBTEs compared with about 50 percent with the MTE or MDS AEDs, and the rate of survival to hospital discharge was 28 percent in the ICBTE group compared with 35 percent and 15 percent in groups resuscitated with the MTE and MDS AEDs, respectively. CONCLUSIONS: These findings provide further evidence that the 150J impedance-compensated biphasic truncated exponential waveform AED is more effective than traditional MTE or MDS monophasic AEDs. Febrile Seizures and Illness In times past, a febrile seizure condemned the young victim to a septic work-up. For decades these children were subjected to all manner of invasive studies trying to find the nasty source of the fever, particularly to exclude meningitis. Being forced to meet the community standard of yesteryear, many of us older emergency physicians routinely performed lumbar punctures on these children despite our better judgment that nothing serious was wrong with the vast majority of them. With time there has evolved a much less aggressive approach to these children because it is clear that most of them are not seriously ill. The following study, which should have been published at least a decade ago, confirms what all of us know from experience — that febrile seizures, particularly in this day and age of H. influenzae and S. pneumoniae immunizations, are rarely associated with serious illness. The paper indicates that the risk of bacteremia was no higher than would be expected in any febrile children, that blood cultures when positive (1.3%) yield just the bug anticipated (S. pneumoniae), and that CSF cultures were always negative. Clearly, the days of the knee-jerk septic work-up for febrile seizures in children six months to five years of age are over. Children with First-Time Simple Febrile Seizures are at Low Risk of Serious Bacterial Illness, Trainor JL, et al, Acad Emerg Med, 2001;8:781 BACKGROUND: Children who present with an apparent simple febrile seizure are often subjected to more rigorous evaluation than equally febrile children presenting without a seizure. METHODS: The authors from Northwestern University in Chicago performed a standardized records review of 455 children aged six months to five years with a first simple febrile seizure. Subjects were identified from among patients who presented to the ED at one of five community hospitals or two pediatric tertiary care facilities from mid-1995 through 1997, and whose discharge diagnosis included the word “seizure.” RESULTS: Blood cultures were positive for S. pneumoniae in four of 315 (1.3%) children undergoing these tests (95% confidence interval [CI] 0.1–2.5%). Three of the four children were treated with antibiotics, and follow-up cultures were negative in all four. Of 171 children having a urine culture, six percent were positive (95% CI 2.4–9.4%). CSF culture was positive in none of 135 children (95% CI 0–2.2%). Stool cultures were performed in only 14 children, and were positive (for Shigella) in two (14%, 95% CI 0–32.6%). The authors note that these rates do not differ substantially from those reported in febrile children without a seizure. CONCLUSIONS: The authors believe that the risk of serious bacterial illness is not increased in children with a simple febrile seizure, and that diagnostic evaluations in these children should be guided by clinical and historical factors rather than the occurrence of the seizure. Their case-finding method may have missed patients who had a serious infection in association with the seizure, however.

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