The goal of therapy for bradycardia or tachycardia is to rapidly identify and treat patients who are hemodynamically unstable or symptomatic due to the arrhythmia. Drugs or, when appropriate, pacing may be used to control unstable or symptomatic bradycardia. Cardioversion or drugs or both may be used to control unstable or symptomatic tachycardia. ACLS providers should closely monitor stable patients pending expert consultation and should be prepared to aggressively treat those with evidence of decompensation.

/pdf/part-8-adult-advanced-cardiovascular-life-support-2010-344vtppnij.pdf

Part 8: Adult Advanced Cardiovascular Life Support 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

Drug-induced hepatotoxicity.

(2003). Hepatotoxicity and Mechanism of Action of Haloalkanes: Carbon Tetrachloride as a Toxicological Model. Critical Reviews in Toxicology: Vol. 33, No. 2, pp. 105-136.

Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model.

https://anestesiar.org/WP/uploads/2011/01/7-neonatos-ERC-2010.pdf

European Resuscitation Council Guidelines for Resuscitation 2010 Section 1. Executive summary.

The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug among young people, particularly those involved in the dance culture. MDMA produces an acute, rapid enhancement in the release of both serotonin (5-HT) and dopamine from nerve endings in the brains of experimental animals. It produces increased locomotor activity and the serotonin behavioral syndrome in rats. Crucially, it produces dose-dependent hyperthermia that is potentially fatal in rodents, primates, and humans. Some recovery of 5-HT stores can be seen within 24 h of MDMA administration. However, cerebral 5-HT concentrations then decline due to specific neurotoxic damage to 5-HT nerve endings in the forebrain. This neurodegeneration, which has been demonstrated both biochemically and histologically, lasts for months in rats and years in primates. In general, other neurotransmitters appear unaffected. In contrast, MDMA produces a selective long-term loss of dopamine nerve endings in mice. Studies on the mechanisms involved in the neurotoxicity in both rats and mice implicate the formation of tissue-damaging free radicals. Increased free radical formation may result from the further breakdown of MDMA metabolic products. Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. There is also some evidence for long-term physiological and psychological changes occurring in human recreational users. However, such evidence is complicated by the lack of knowledge of doses ingested and the fact that many subjects studied are or have been poly-drug users.

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

During the investigational use of oral N-acetylcysteine as an antidote for poisoning with acetaminophen, 11,195 cases of suspected acetaminophen overdose were reported. We describe the outcomes of 2540 patients with acetaminophen ingestions treated with a loading dose of 140 mg of oral N-acetylcysteine per kilogram of body weight, followed four hours later by 70 mg per kilogram given every four hours for an additional 17 doses. Patients were categorized for analysis on the basis of initial plasma acetaminophen concentrations and the interval between ingestion and treatment. Hepatotoxicity developed in 6.1 percent of patients at probable risk when N-acetylcysteine was started within 10 hours of acetaminophen ingestion and in 26.4 percent of such patients when therapy was begun 10 to 24 hours after ingestion. Among patients at high risk who were treated 16 to 24 hours after an acetaminophen overdose, hepatotoxicity developed in 41 percent--a rate lower than that among historical controls. When given within eight hours of acetaminophen ingestion, N-acetylcysteine was protective regardless of the initial plasma acetaminophen concentration. There was no difference in outcome whether N-acetylcysteine was started zero to four or four to eight hours after ingestion, but efficacy decreased with further delay. There were 11 deaths among the 2540 patients (0.43 percent); in the nine fatal cases in which aminotransferase was measured before treatment, values were elevated before N-acetylcysteine was started. No deaths were clearly caused by acetaminophen among patients in whom N-acetylcysteine therapy was begun within 16 hours. We conclude that N-acetylcysteine treatment should be started within eight hours of an acetaminophen overdose, but that treatment is still indicated at least as late as 24 hours after ingestion. On the basis of available data, the 72-hour regimen of oral N-acetylcysteine is as effective as the 20-hour intravenous regimen described previously, and it may be superior when treatment is delayed.

Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985)

Acetaminophen (paracetamol in British literature) is a metabolite of phenacetin which has become increasingly popular as a substitute for salicylates.1 The popularity of acetaminophen has been encouraged by the medical profession because it is allegedly safer than aspirin.2 However, experience in Britain indicates that acute acetaminophen overdosage is both common and significantly more toxic than of salicylates.3-7 Although it is widely used in the United States, only one report describing a single American patient has appeared in the literature.8 This is a puzzling situation. It is axiomatic that if you do not look for something you will not diagnose it. This may provide the answer as there is apparently a general lack of knowledge in the United States concerning the toxicity of acetaminophen. Indeed, one of us (B.H.R.) contacted nine American University poison services in the spring of 1973 and discovered that none had clinical experience or analytical methods in operation. During the past year, however, with a high index of suspicion in Denver, 156 ingestions with four fatalities have been recorded. Because of the nonspecific initial features of acute overdosage, the lack of coma, the delay in onset of jaundice and the rapid fall in detectable plasma levels of acetaminophen, the cause-and-effect relationship may be missed in even a floridly ill or dying patient. Hepatoxicity is the most remarkable feature and the question must be raised as to how many cases of "jaundice of unknown etiology" are actually due to this drug. This review is intended to provide an understanding of the current knowledge of this drug. It should be noted that although toxicity and fatalities have occurred in the adolescent age group, only one death in younger children has been recorded.

Acetaminophen poisoning and toxicity.

Background: The American Association of Poison Control Centers (AAPCC; http://www.aapcc.org ) maintains the National Poison Data System (NPDS). Today, 60 of the nation's 61 US poison centers upload...

/pdf/2006-annual-report-of-the-american-association-of-poison-1pe6dfsmfp.pdf

2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS)

Background: This report is the 25th Annual Report of the American Association of Poison Control Centers (AAPCC; http://www.aapcc.org) National Poison Data System (NPDS). During 2007, 60 of the nati...

2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report.

• Six hundred sixty-two consecutive patients with acetaminophen overdoses were evaluated. Those at risk on the basis of their acetaminophen blood levels, as plotted on the study nomogram, were treated with oral acetylcysteine. Statistically significant differences in severity of hepatic toxicity were observed between patients treated within 16 hours after ingestion and those treated between 16 and 24 hours after ingestion. No deaths occurred among patients treated within 24 hours of ingestion, except for one patient who was an alleged gunshot homicide. Seven percent of patients with plasma acetaminophen levels in the potentially toxic range and treated with acetylcysteine within ten hours of ingestion showed transient SGOT level elevations, whereas 29% of those treated between ten and 16 hours after ingestion and 62% of those treated between 16 and 24 hours after ingestion showed such transient toxicity. No consistent difference in hepatotoxicity could be demonstrated between those patients with a history of chronic alcohol use and those patients with no history of chronic alcohol use. Acute alcohol use resulted in less severe toxic reactions than in those patients without acute alcohol use. (Arch Intern Med141:380-385, 1981)

Barry H. Rumack

Papers

Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985)

Acetaminophen poisoning and toxicity.

2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS)

2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report.

Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment.