Prophylactic Use Of Lidocaine Research Articles

Prophylactic lidocaine for myocardial infarction.

Coronary artery disease is a major public health problem affecting both developed and developing countries. Acute coronary syndromes include unstable angina and myocardial infarction with or without ST-segment elevation (electrocardiogram sector is higher than baseline). Ventricular arrhythmia after myocardial infarction is associated with high risk of mortality. The evidence is out of date, and considerable uncertainty remains about the effects of prophylactic use of lidocaine on all-cause mortality, in particular, in patients with suspected myocardial infarction. To determine the clinical effectiveness and safety of prophylactic lidocaine in preventing death among people with myocardial infarction. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 3), MEDLINE Ovid (1946 to 13 April 2015), EMBASE (1947 to 13 April 2015) and Latin American Caribbean Health Sciences Literature (LILACS) (1986 to 13 April 2015). We also searched Web of Science (1970 to 13 April 2013) and handsearched the reference lists of included papers. We applied no language restriction in the search. We included randomised controlled trials assessing the effects of prophylactic lidocaine for myocardial infarction. We considered all-cause mortality, cardiac mortality and overall survival at 30 days after myocardial infarction as primary outcomes. We performed study selection, risk of bias assessment and data extraction in duplicate. We estimated risk ratios (RRs) for dichotomous outcomes and measured statistical heterogeneity using I(2). We used a random-effects model and conducted trial sequential analysis. We identified 37 randomised controlled trials involving 11,948 participants. These trials compared lidocaine versus placebo or no intervention, disopyramide, mexiletine, tocainide, propafenone, amiodarone, dimethylammonium chloride, aprindine and pirmenol. Overall, trials were underpowered and had high risk of bias. Ninety-seven per cent of trials (36/37) were conducted without an a priori sample size estimation. Ten trials were sponsored by the pharmaceutical industry. Trials were conducted in 17 countries, and intravenous intervention was the most frequent route of administration.In trials involving participants with proven or non-proven acute myocardial infarction, lidocaine versus placebo or no intervention showed no significant differences regarding all-cause mortality (213/5879 (3.62%) vs 199/5848 (3.40%); RR 1.02, 95% CI 0.82 to 1.27; participants = 11727; studies = 18; I(2) = 15%); low-quality evidence), cardiac mortality (69/4184 (1.65%) vs 62/4093 (1.51%); RR 1.03, 95% CI 0.70 to 1.50; participants = 8277; studies = 12; I(2) = 12%; low-quality evidence) and prophylaxis of ventricular fibrillation (76/5128 (1.48%) vs 103/4987 (2.01%); RR 0.78, 95% CI 0.55 to 1.12; participants = 10115; studies = 16; I(2) = 18%; low-quality evidence). In terms of sinus bradycardia, lidocaine effect is imprecise compared with effects of placebo or no intervention (55/1346 (4.08%) vs 49/1203 (4.07%); RR 1.09, 95% CI 0.66 to 1.80; participants = 2549; studies = 8; I(2) = 21%; very low-quality evidence). In trials involving only participants with proven acute myocardial infarction, lidocaine versus placebo or no intervention showed no significant differences in all-cause mortality (148/2747 (5.39%) vs 135/2506 (5.39%); RR 1.01, 95% CI 0.79 to 1.30; participants = 5253; studies = 16; I(2) = 9%; low-quality evidence). No significant differences were noted between lidocaine and any other antiarrhythmic drug in terms of all-cause mortality and ventricular fibrillation. Data on overall survival 30 days after myocardial infarction were not reported. Lidocaine compared with placebo or no intervention increased risk of asystole (35/3393 (1.03%) vs 14/3443 (0.41%); RR 2.32, 95% CI 1.26 to 4.26; participants = 6826; studies = 4; I(2) = 0%; very low-quality evidence) and dizziness/drowsiness (74/1259 (5.88%) vs 16/1274 (1.26%); RR 3.85, 95% CI 2.29 to 6.47; participants = 2533; studies = 6; I(2) = 0%; low-quality evidence). Overall, safety data were poorly reported and adverse events may have been underestimated. Trial sequential analyses suggest that additional trials may not be needed for reliable conclusions to be drawn regarding these outcomes. This Cochrane review found evidence of low quality to suggest that prophylactic lidocaine has very little or no effect on mortality or ventricular fibrillation in people with acute myocardial infarction. The safety profile is unclear. This conclusion is based on randomised controlled trials with high risk of bias. However (disregarding the risk of bias), trial sequential analysis suggests that additional trials may not be needed to disprove an intervention effect of 20% relative risk reduction. Smaller risk reductions might require additional higher trials.

GW24-e2441 SCN5A mutation with lethal ventricular arrhythmias and invalidation of lidocaine in acute myocardial infarction

ObjectivesPatients are at high risk for potentially fatal ventricular tachycardia (VT)/ventricular fibrillation (VF) when suffering from acute myocardial infarction (AMI), due to myocardial ischaemia/reperfusion injury or scar formation. Recently, it...

Confidence Distributions and a Unifying Framework for Meta-Analysis

This article develops a unifying framework, as well as robust meta-analysis approaches, for combining studies from independent sources. The device used in this combination is a confidence distribution (CD), which uses a distribution function, instead of a point (point estimator) or an interval (confidence interval), to estimate a parameter of interest. A CD function contains a wealth of information for inferences, and it is a useful device for combining studies from different sources. The proposed combining framework not only unifies most existing meta-analysis approaches, but also leads to development of new approaches. We illustrate in this article that this combining framework can include both the classical methods of combining p-values and modern model-based meta-analysis approaches. We also develop, under the unifying framework, two new robust meta-analysis approaches, with supporting asymptotic theory. In one approach each study size goes to infinity, and in the other approach the number of studies goes to infinity. Our theoretical development suggests that both these robust meta-analysis approaches have high breakdown points and are highly efficient for normal models. The new methodologies are applied to study-level data from publications on prophylactic use of lidocaine in heart attacks and a treatment of stomach ulcers. The robust methods performed well when data are contaminated and have realistic sample sizes and number of studies.

Prevention of primary ventricular fibrillation in acute myocardial infarction with prophylactic lidocaine

Primary ventricular fibrillation (VF) during an acute myocardial infarction (AMI) occurs with a high incidence and mortality rate with or without thrombolysis. The incidence varies from 2% to 19% depending on the definition of "primary." Primary VF in this study refers to fibrillation occurring in the absence of shock or pulmonary edema. Mortality rate, when primary VF occurs, is 2 to 4 times greater than when it does not. Prevention of VF has been impeded by the publication of the 1996 recommendations of the American Heart Association and American College of Cardiology against the use of prophylactic lidocaine based on meta-analysis studies implying toxicity. This observational study of 4,254 patients with AMI reports the incidence and mortality rates of primary VF over 32 years. Of the 4,254 patients, 4,150 received prophylactic lidocaine, and 104 patients did not receive prophylactic lidocaine due to the 1996 guidelines, after which administration of prophylactic lidocaine was governed by physician choice. The incidence of primary VF was 0.5% among the 4,150 who received prophylactic lidocaine and 10% among the 104 who did not (p <0.0001). Among the 4,150 receiving prophylactic lidocaine, sinoatrial block occurred in 0.5% and complete infranodal atrial ventricular block occurred in 0.2%, all secondary to the site of infarction (concurrent serum lidocaine levels were < 4 microg/ml). Asystole was an agonal rhythm in 4%; these patients had been off lidocaine for 48 hours. Mortality rates were 10.5% in patients without primary VF and 25% in patients with VF (p <0.001). Thus, prophylactic lidocaine markedly decreased the incidence of VF in 4,150 patients with AMI to 0.5% compared with trials before and after thrombolysis (2% to 19%) and with the 104 patients in this study who did not receive prophylactic lidocaine (10%). No lidocaine-induced sinoatrial or atrial ventricular block or asystole occurred.

Perioperative Stroke Prevention

The definitions of commonly used terms are given in Table 1 (1–8). Stroke has been simply defined as any form of cerebral infarction (2), which includes those attributable to hemorrhage. The latter group is more likely to occur as a complication of specific surgical procedures (e.g., carotid endarterectomy) or the use of anticoagulants and is otherwise rare in the perioperative period (3). Hence, much of the information in this review pertains to ischemic cerebral events.

Multicenter randomized trial and a systematic overview of lidocaine in acute myocardial infarction

Background More than 20 randomized trials and 4 meta-analyses have been conducted on the use of prophylactic lidocaine in acute myocardial infarction (MI). The results suggest that lidocaine reduces ventricular fibrillation (VF) but increases mortality rates in acute MI. Methods and Results Patients with ST-elevation MI who were examined <6 hours after symptom onset (n = 903) were randomly assigned to either lidocaine or no lidocaine and to either streptokinase and heparin or heparin alone. Lidocaine was given as 4 boluses of 50 mg each every 2 minutes, then an infusion of 3 mg/min for 12 hours, then 2 mg/min for 36 hours. We compared the incidence of in-hospital death and ventricular arrhythmias. We then performed a meta-analysis of prophylactic lidocaine in acute MI that included these and prior trial results. The rates of VF and death with and without lidocaine were calculated for each trial, then odds ratios (OR) with confidence intervals (CI) were calculated for the risk of these events overall with and without lidocaine. Patients given lidocaine in the randomized study had significantly less VF (2.0% vs 5.7% without lidocaine, P = .004) and a trend toward increased mortality rates (9.7% vs 7.0%, P = .145). Meta-analysis revealed nonsignificant trends toward reduced VF (OR 0.71, 95% CI 0.47 to 1.09) and increased mortality rates (OR 1.12, 95% CI 0.91 to 1.36) with lidocaine. Conclusions Lidocaine reduces VF but may adversely affect mortality rates. The routine use of prophylactic lidocaine in acute MI is not recommended. (Am Heart J 1999;137:792-8.)

Meta-analysis: formulating, evaluating, combining, and reporting.

Meta-analysis involves combining summary information from related but independent studies. The objectives of a meta-analysis include increasing power to detect an overall treatment effect, estimation of the degree of benefit associated with a particular study treatment, assessment of the amount of variability between studies, or identification of study characteristics associated with particularly effective treatments. This article presents a tutorial on meta-analysis intended for anyone with a mathematical statistics background. Search strategies and review methods of the literature are discussed. Emphasis is focused on analytic methods for estimation of the parameters of interest. Three modes of inference are discussed: maximum likelihood; restricted maximum likelihood, and Bayesian. Finally, software for performing inference using restricted maximum likelihood and fully Bayesian methods are demonstrated. Methods are illustrated using two examples: an evaluation of mortality from prophylactic use of lidocaine after a heart attack, and a comparison of length of hospital stay for stroke patients under two different management protocols.

Lidocaine to prevent ventricular fibrillation in the prehospital phase of suspected acute myocardial infarction: The North-Norwegian Lidocaine Intervention Trial

The efficacy of lidocaine to prevent ventricular fibrillation during the prehospital phase of suspected acute myocardial infarction was assessed 3 hours after administration in a randomized controlled trial. A total of 204 patients examined within 6 hours after onset of symptoms were included, and acute myocardial infarction was later confirmed in 63% of these. Lidocaine, administered as a 100 mg intravenous bolus dose followed by a 300 mg intramuscular injection, failed to prevent ventricular fibrillation, which was observed in 2 (2.1%) of 96 patients in the lidocaine group and in 3 (3.0%) of 101 patients in the placebo group ( p = 0.95; odds ratio 0.7, 95% confidence interval 0.4 to 1.3). In addition, sudden cardiac collapse with unknown heart rhythm was observed in three patients who received lidocaine (3.1%) compared with none in the placebo group ( p = 0.23; odds ratio 7.6, 95% confidence interval 2.8 to 22.1). The results of this small study suggest that lidocaine, even when given in a high dose, is ineffective in preventing ventricular fibrillation when administered before hospitalization for suspected acute myocardial infarction. Prophylactic use of lidocaine in this situation may therefore not be warranted or advisable.

Declining incidence of ventricular fibrillation in myocardial infarction. Implications for the prophylactic use of lidocaine.

The purposes of the present investigation were 1) to track the incidence of primary ventricular fibrillation (VF) in the control and lidocaine-treated groups in the randomized control trials (RCTs) of lidocaine prophylaxis against primary VF in acute myocardial infarction, with particular emphasis on the time frame of the randomized trial, and 2) to estimate the number of patients who must receive lidocaine currently to prevent one episode of VF. The following variables from RCTs published between 1969 and 1988 were entered into logistic regression models to predict the percent of patients developing VF: year of publication of the RCT, method of data analysis used in the RCT, route and technique of lidocaine administration, duration of monitoring for VF, and exclusion criteria before randomization (congestive heart failure/cardiogenic shock, ventricular tachycardia/VF, or bradycardia/atrioventricular block). Year of publication was a significant predictor of VF in both the control and lidocaine groups (p less than or equal to 0.002) even after adjusting for other covariates. Based on a univariate logistic regression model with year as the predictor variable, it was estimated that the incidence of primary VF in the control group fell from 4.51% in 1970 to 0.35% in 1990 and from 4.32% down to 0.11% for the lidocaine group over the same time period. Thus, about 400 patients would currently need prophylaxis with lidocaine to prevent one episode of VF. Present estimates of the risk:benefit ratio of lidocaine prophylaxis should consider the low risk of VF in control patients and the large number who need lidocaine prophylaxis to prevent one episode of VF. When added to the previously reported trend toward excess mortality in lidocaine-treated patients, these data argue against the routine prophylactic use of lidocaine in patients with acute myocardial infarction.

Lidocaine in the early phase of acute myocardial infarction: The controversy over prophylactic or selective use

In acute myocardial infarction, lidocaine is considered the drug of choice for the treatment of malignant ventricular arrhythmias. While initially a so-called "selective" treatment strategy prevailed, in which lidocaine was administered only after the onset of certain "warning arrhythmias," the prophylactic use of lidocaine in acute myocardial infarction has been gaining wider usage in intravenous and intramuscular application in recent years. Both therapeutic applications have been found to be problematic of late, which has led to increasingly restrictive use of lidocaine. While in selective treatment forms, the definition and prompt recognition of the so-called warning arrhythmias created especially acute problems, the prophylactic therapeutic use is problematic due to the occurrence of sometimes serious side effects, which is to be expected as the size of the collective being treated increases. Both treatment forms also appear limited by the narrow preventive efficacy of lidocaine against malignant ventricular arrhythmias, especially against ventricular fibrillation. The current therapeutic recommendation for lidocaine in acute myocardial infarction should be limited to patients presenting with very frequent and complex ventricular arrhythmias, especially when these are elicited by an R-on-T phenomenon. Side effects and other therapeutic problems encountered when the therapeutic modality is switched or adjusted can be greatly reduced by careful dosing and selection of the optimal combination substances.

Lidocaine improves survival rate in diabetic rats submitted to acute left coronary artery ligation

This study was designed to evaluate whether the decreased early survival rate of diabetic rats submitted to acute experimental myocardial infarction can be improved by pretreatment with lidocaine. Male Wistar rats (+/- 210 g) were rendered diabetic with i.v. injection of streptozotocin (50 mg/kg), and only those presenting 1 week later a tail-blood glucose value between 250-400 mg/dl were retained in the protocol. Eleven weeks after induction of diabetes, a bolus of lidocaine (2 mg/kg) was administered i.v. about 6 min prior to ligation of the left coronary artery under ether anesthesia in control (n = 54) and diabetic (n = 48) rats; similar studies were conducted in 53 control and 55 diabetic rats without lidocaine pretreatment. Adequate occlusion was confirmed by an elevation of plasma CK-MB levels 4 h later or by a toluidine blue injection technique in rats which died earlier. Rats were followed over 48 h and comparison in the survival rate in each group established with the Fisher's exact test. Early survival rate (measured after 20 min) was significantly decreased in diabetic rats (27% vs 45%; p = 0.04). This was greatly improved by lidocaine pretreatment in diabetic (60% vs 27%; p = 0.0013), but not in control animals (50% vs 45%; p = 0.348). Furthermore, the beneficial effect of prophylactic lidocaine observed early after coronary ligation in diabetic rats was maintained throughout the period of observation (48 h). These data suggest that the prophylactic use of lidocaine is able to reverse the increased incidence of sudden death following experimental myocardial infarction in chronically diabetic rats.

Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction

Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction

Local Anesthetics in Cerebral Ischemia

Local anesthetics are thought to be potentially beneficial in ischemia because they reduce cerebral energy expenditure and may prevent ischemic membrane depolarization. In vitro studies and in vivo studies in models of focal ischemia have indeed shown a benefit from the prophylactic use of lidocaine. Results in global ischemia have been conflicting. The effects of lidocaine may reflect a neurovascular rather than a membrane-stabilizing effect.

Prophylactic Lidocaine in Acute MI

To the Editor.— MacMahon et al 1 recently reported the effect of prophylactic lidocaine in the therapy of acute myocardial infarction, noting that, even today, we do not have enough evidence to support such use of prophylactic lidocaine. In their extensive reference list, the authors' earliest relevant reference is from 1967, in which Gianelly et al 2 suggest the possible use of lidocaine to prevent ventricular arrhythmias in the coronary care unit setting. In the same year, our detailed report in another journal 3 dealt with the prophylactic use of procainamide and certain other intramuscular drugs in patients before admission to the hospital with coronary diagnoses. The primary point of our lengthy report and subsequent commentary 4 was to indicate that it was not possible to recommend any single-drug therapy in the prophylactic treatment of acutely ill coronary patients. Rather, we pointed out that one probably must use a combination

A comparison of paramedic versus basic emergency medical care of patients at high and low risk during acute myocardial infarction

This prospective study compares the outcome of patients with acute myocardial infarction managed by mobile intensive care (paramedic phase) with that of similar patients managed by basic emergency medical care (control phase) in the same community before the introduction of paramedics. All paramedic-transported patients were managed according to a standard chest pain protocol with use of prophylactic lidocaine and, as needed, treatment for sinus bradycardia, hypotension and life-threatening ventricular arrhythmia. There were no specific interventions for supraventricular tachyarrhythmia or hypertension. All patients were treated under similar in-hospital protocols. Percent mortality in patients with hypotension, the highest risk subgroup in the control phase, was significantly lowered with paramedic-level care (69 versus 10%, p = 0.01). Patients with hypertension, a relatively low risk subgroup during the control phase (16% mortality), were also at lower risk during the paramedic phase (10% mortality). In fact, there was no mortality in either study phase for patients with an initial systolic blood pressure greater than 180 mm Hg. During the combined study phases, patients with normotension and tachycardia demonstrated a tendency toward higher percent mortality (33%) than either patients with normotension without tachycardia (10%) or those with hypertension and tachycardia (6%). Although the overall percent mortality was reduced by 24% (from 21 to 16%), this decrease was largely due to the improvement of patients with hypotension. Investigation into the feasibility of prehospital interventions for the high risk patient with acute myocardial infarction normotension and tachycardia appears warranted.

Prophylactic lidocaine in the prehospital patient with chest pain of suspected cardiac origin

The prophylactic use of lidocaine in the patient with cardiac chest pain has been reported to reduce the incidence of sudden death from ventricular dysrhythmias in the hospital setting, but few studies have been done in the early prehospital phase. We conducted a randomized, prospective study comparing the effects of lidocaine versus no lidocaine in stable patients presenting with chest pain to a paramedic system. In a one-year period, 446 patients qualified for the study; 222 received lidocaine and 224 did not. The overall hospital mortality of the two groups was 8.1% and 6.7%, respectively (P = .35). Four patients in each group developed sudden death in the prehospital and emergency department settings with ventricular dysrhythmia as the precipitating rhythm. One hundred twenty-nine (29%) had an acute myocardial infarction. The lidocaine and control group contained 68 and 61 of the patients, respectively, with an overall mortality rate of 14.7% and 13.1% (P = .45). The development of significant dysrhythmias (frequent premature ventricular contractions, ventricular tachycardia, bradycardia, second- and third-degree heart blocks) after initiation into the study was similar in both groups of patients. The use of lidocaine was a factor in decreasing systolic blood pressure (P less than 0.03) but did not appear to be clinically significant. For stable patients presenting with chest pain of suspected cardiac origin, prophylactic lidocaine in the prehospital setting was not effective in preventing life-threatening dysrhythmias, but clinically significant side effects were not noted either.

Prophylactic use of lidocaine to prevent advanced ventricular arrhythmias during pulmonary artery catheterization: Prospective double-blind study

To determine whether prophylactic lidocaine could decrease the incidence of advanced ventricular arrhythmias, 62 patients undergoing 67 pulmonary artery catheterizations were given lidocaine or placebo before and during catheterization. Advanced ventricular arrhythmias occurred in 42 of the 67 catheterizations (63 percent). In 18 of 31 patients receiving lidocaine (58 percent) arrhythmias developed, whereas 24 of 36 patients who received placebo (67 percent) had evidence of arrhythmias. These differences were not significant. However, patients with catheterization times of less than 20 minutes who were treated with lidocaine had less ectopy (25 percent) than patients treated with placebo (68 percent) (p < 0.05). Two patients had sustained ventricular tachycardia and both were receiving placebo. No complications of lidocaine prophylaxis were noted. Prophylactic lidocaine appears to decrease the incidence of mechanically induced arrhythmias in critically ill patients undergoing catheterization that is not prolonged.

Ventricular fibrillation complicating acute myocardial infarction: Reasons against the routine use of lidocaine

Because of recent recommendations that lidocaine be used prophylactically in all coronary care unit (CCU) patients with suspected myocardial infarction (MI), an approach not used in our CCU, we analyzed our experience with ventricular fibrillation (VF) occurring in the setting of an acute MI. The frequency of VF in all patients was 3.2%, in MI patients 5.7%, of primary ventricular fibrillation (PVF) 2.8%, and of complicating ventricular fibrillation (CVF) 6.8%. All patients with PVF were resuscitated immediately. There was an increased in-hospital mortality for patients with VF compared to patients without VF; however, the increased mortality did not seem to result directly from VF. The long-term survival of PVF patients who survived to discharge was excellent (80% at 58 months). The routine use of prophylactic lidocaine would have been of no potential benefit in 96.8% of our patients, subjecting them to extra expense and possible toxicity. Since we have found no compelling evidence that the prophylactic administration of lidocaine can reduce mortality, we do not recommend this therapy for acute MI patients in our CCU.

Prophylactic lidocaine in suspected acute myocardial infarction

The incidence of serious ventricular arrhythmias following acute myocardial infarction is highest during the first few hours after injury, and thereafter declines. Several investigations into the prophylactic use of lidocaine to prevent the development of arrhythmias have shown that lidocaine, given in therapeutic doses, is effective in preventing ventricular fibrillation and in reducing early mortality. Lidocaine was found to be effective when given either by the intravenous or by the intramuscular routes. The recommended dosage is 100 mg given as an intravenous bolus followed by 2 to 4 mg/min as an infusion, which should be given by infusion pump. Another recommendation is to use two 100 mg boluses 20 minutes apart, along with the same infusion. We recommend that lidocaine be started as soon as possible in all patients suspected of having suffered acute myocardial infarction.