Logical approach to lignocaine therapy.

Plasma lignocaine concentrations were measured during and after lignocaine infusions administered for suppressing ventricular dysrhythmias. Twenty-four patients with a primary diagnosis of acute myocardial infarction without gross circulatory disturbance received, after a bolus of lignocaine, either 4 mg/min for 30 minutes, 2 mg/min for two hours, then 1 mg/min thereafter or 1 mg/min throughout. The higher dose regimen produced continous therapeutic levels of lignocaine, which were achieved only after four hours by the lower dose. On the other hand, in patients who had undergone cardiac surgery and who had circulatory and heptic dysfunction the lower dose regimen achieved therapeutic levels early. The plasma half life was longer in the surgical group (P less than 0.02). The higher initial infusion rate is recommended for patients with acute myocardial infarction without gross circulatory impairment.     

On the role of alpha 1-acid glycoprotein in lignocaine accumulation following myocardial infarction.

1 Blood plasma and free lignocaine concentrations have been measured 12 h after beginning a constant infusion of 2 mg/min and again at the end of the infusion (36-72 h) in five patients with myocardial infarction (MI) and compared with five control patients who did not develop objective evidence of MI. 2 In MI patients, total plasma concentration rose significantly between 12 h and the end of infusion. Because of an increase in alpha 1 acid glycoprotein (AAG) plasma binding increased, so that free drug concentration did not change. The rise in whole blood concentration was less than that in plasma as a result of drug redistribution out of red cells due to enhanced binding. 3 In control patients, neither blood nor plasma concentrations changed with time and plasma binding remained constant. Free drug concentrations, however, rose slightly. 4 The concentrations of GX and MEGX remained unchanged in all patients, but the ratio of lignocaine/MEGX concentrations fell in controls but rose in MI patients. 5 Pharmacokinetic modelling suggested that at least some of the rise in blood lignocaine concentration was due to reduced clearance resulting from enhanced plasma binding. 6 We conclude that the rise in AAG following MI is responsible for increased plasma binding and drug redistribution within blood. These changes, together with a reduction in lignocaine clearance, can explain much of the phenomenon of lignocaine accumulation in MI.     

Pharmacokinetics and haemodynamic effects of tocainide in patients with acute myocardial infarction complicated by left ventricular failure.

The pharmacokinetics and haemodynamic effects of tocainide, an orally active structural analogue of lignocaine, were studied in patients with acute myocardial infarction complicated by left ventricular failure. Fourteen patients (mean age 65 years) with acute myocardial infarction complicated by mild left ventricular failure were studied, following a single dose of tocainide (250 mg) by intravenous infusion, over 30 min. Heart rate, systemic arterial pressure, pulmonary artery pressure and cardiac output were monitored. Plasma tocainide levels were estimated by gas chromatography. The mean plasma level of tocainide achieved was 2.95 micrograms/ml (15.37 mmol/l). The mean plasma half-life was 15.6 h. The mean cardiac index was reduced 5 min after completion of the infusion, from 2.24 1 min-1 m-2 (+/- 0.40) to 2.07 1 min-1 m-2 (+/- 0.29) (P less than 0.01). At 90 min the cardiac index had returned to pre-treatment levels. Small changes were seen in the heart rate, arterial blood pressure and the pulmonary artery pressure but these changes were not statistically significant. The pharmacokinetics of tocainide were not significantly altered in patients with acute myocardial infarction complicated by mild left ventricular failure.     

Absorption of oral ciprofloxacin in a patient with cardiogenic shock

Congestive heart failure and cardiogenic shock can alter the absorption process of some drugs. The absorption of ciprofloxacin has been studied in several disease states, but the effect of cardiogenic shock on its absorption is unknown. A 63-year-old man had a large myocardial infarction complicated by cardiogenic shock. When he began taking ciprofloxacin for pneumonia, he had renal and cardiac failure. Ciprofloxacin 500 mg was administered every 24 hours by nasogastric tube. Blood samples were collected 5 minutes prior to the second dose (20 hrs after the initial dose) and then regularly until 11 hours after the dose. Samples were analyzed using high-performance liquid chromatography. The trough concentration 20 hours after the initial dose was 3.7 micrograms/ml, and the serum concentrations after the second dose went from 5.6 to 4.94 micrograms/ml over the 11-hour sampling period. The peak concentration of 5.6 micrograms/ml occurred within 30 minutes after ciprofloxacin administration. It can be concluded from this case study that ciprofloxacin was adequately absorbed in this patient with multiple organ failure.     

Factors affecting free (unbound) lignocaine concentration in suspected acute myocardial infarction.

1. Free plasma lignocaine concentrations were measured for up to 48 h after constant infusion of the drug in 41 subjects with suspected acute myocardial infarction. 2. The free plasma lignocaine clearance at 12 h was significantly and proportionately related to body weight and to the presence of mild (Killip Class II) heart failure, with an 18% reduction in free clearance in the latter condition. 3. The free plasma lignocaine was not related to sex, age or the presence of confirmed acute myocardial infarction, when corrected for the effects of body weight and presence of heart failure. 4. Free plasma lignocaine concentration 1 h after a fixed loading dose were also significantly related to body weight and presence of heart failure but not to sex, age or proven acute myocardial infarction. 5. The data indicate that correction of loading and maintenance infusion for body weight and presence of (even mild) heart failure should somewhat reduce variability in free (and presumably active) plasma lignocaine concentrations but that the free plasma lignocaine concentration at 12 h is most accurately predicted by measuring the free (and to a lesser extent total) plasma lignocaine concentration at 1 h.     

Lignocaine and indocyanine green kinetics in patients following myocardial infarction.

1. Blood clearances of lignocaine and indocyanine green together with indocyanine green half-lives were measured in 17 post-myocardial infarct patients (one patient was studied twice) between 8 h and 36 h after starting intravenous lignocaine infusions for the treatment of cardiac arrhythmias. 2. Mean +/- s.d. values of lignocaine clearance (ml min-1 kg-1) were higher in patients without heart failure (11.8 +/- 2.6, n = 9) than in those with heart failure (7.2 +/- 1.9, n = 9) (P < 0002). 3. Clearances of lignocaine and indocyanine green were not correlated but lignocaine clearance was directly related to the reciprocal of indocyanine green half-life (rs = 0.67, P < 0.01). 4. In eight patients who received both lignocaine and indocyanine green and in a further five patients received only lignocaine and whose lignocaine infusions lasted 24h or more, a 25% rise in lignocaine concentrations was observed between 8-12h and 24-28h. 5. The mean +/- s.d. post-infusion terminal half-life of lignocaine in four patients whose lignocaine infusions lasted 30h or longer was 7.2 +/- 2.1 h. 6. Heart failure was associated with greater changes in lignocaine kinetics than in indocyanine green kinetics. 72% of the variance between observed and predicted lignocaine clearances could be accounted for by multiple linear regression analysis incorporating indocyanine green half-life and the presence or absence of heart failure. Indocyanine green half-life contributed only 17% of the variance indicating that by itself it is of limited value in predicting lignocaine requirements. 7. Lignocaine kinetics during and after prolonged intravenous infusion were not predicted by data obtained after intravenous bolus injection. 8. A lowering of lignocaine dosage may be clinically desirable in the presence of heart failure and if an infusion lasts longer than 24 h.     

Changes in lignocaine disposition during long-term infusion in patients with acute ventricular arrhythmias

Lignocaine disposition was studied in 30 patients with acute ventricular arrhythmias. Serum concentrations of lignocaine, its metabolites Monoethylglycine xylidide (MEGX) and glycine xylidide (GX), and alpha 1-acid glycoprotein (AAG) were analyzed during and after a 48-h lignocaine infusion. AAG concentrations tended to rise in patients with acute myocardial infarction (AMI), leading to binding of the drug in plasma. Lignocaine clearance was estimated at various times during the infusion using a Bayesian parameter estimation program and was found to decline over the course of the infusion. There was a significant reduction in clearance based on estimates obtained at the end of the infusion compared with estimates obtained during the first 0-5 h. Clearance was reduced both in patients who had an AMI and those who did not. Multiple linear regression analysis of the clearance data revealed that these changes could be described by a linear function of time and AAG concentration. These findings suggest that other factors in addition to protein binding changes may influence lignocaine disposition during long-term infusion.     

24例无痛性心肌梗死诊疗分析

目的对无痛性心肌梗死（RMl）患者的临床资料进行统计分析,以期为此病的早期诊断和治疗提供一些实用的建议。方法对在我科进行入院治疗的24例无痛性心肌梗死患者进行回顾性分析。结果 24例RMI患者中,19例患者好转,死亡5例,死亡病例中心脏骤停2例,心源性休克1例,心肌衰竭1例,非心脏疾病1例。结论由于临床症状不明显,所以此病在临床上多有误诊率高、并发症多、死亡率高的特点,因此在临床诊断中应特别关注心肌梗死的不典型症状,以对患者行针对性治疗。     

急性心肌梗死患者空腹血糖水平与近期心血管事件的相关性研究

目的探讨急性心肌梗死患者入院时空腹血糖水平与急性期临床心血管事件发生率之间的关系,为临床实践提供理论依据。方法选取2005年1月至2007年12月急性心肌梗死发病24h之内入本院的138例患者为研究对象,根据入院后第2天空腹血糖水平和既往有无糖尿病史分为2组：糖代谢正常组：血糖≤6.0mmol/L;糖代谢异常组：血糖〉6.0mmol/L或既往确诊糖尿病者,比较2组患者一般临床资料和住院期间心血管事件（充血性心力衰竭、严重心律失常、心源性休克、心源性死亡）的发生情况。结果糖代谢异常组严重心律失常、充血性心衰、心源性休克的发生率显著高于糖代谢正常组（P〈0.05）,心源性死亡两组之间没有统计学意义。结论糖代谢异常的急性心肌梗死患者急性期心血管事件的发生率显著增高;空腹血糖水平是急性心肌梗死患者近期充血性心衰、心源性死亡的主要影响因素;心功能（Killip分级）是急性心肌梗死患者近期心源性休克、严重心律失常。心源性死亡的主要影响因素。     

Biotransformation of furosemide in kidney transplant patients

The disposition of tocainide following an i.v. infusion of tocainide HCl 100 mg was studied in 6 patients with decompensated cirrhosis (ascites) and renal dysfunction. In one patient with active hepatic necrosis the terminal plasma half-life was 57.4, and in the others the half life ranged from 16.0 to 29.0 h. The increase in half-life was correlated with biochemical evidence of renal dysfunction, but not with individual tests of hepatic function. Non-renal clearance of tocainide was similar to values reported previously in healthy subjects and patients with acute myocardial infarction. The apparent volume of distribution of tocainide was increased and the pattern of distribution was abnormal in some patients, as plasma concentrations increased after an initial fall and the elevated concentrations then persisted for several hours. This abnormality appeared to be most marked in patients with the greatest degree of liver dysfunction.     

急性心肌梗死患者急诊介入术中应用IABP的护理

目的 探讨急性心肌梗死（AMI）患者急诊介入术（PCI）中应用主动脉内球囊反搏术（IABP）的护理经验。方法回顾29例发生心源性休克的急性心肌梗死患者PCI中应用IABP纠正休克,维持有效循环落实的护理措施。结果通过合理的监测与综合护理,28例患者术后循环稳定,生命体征平稳,分别在术后1～7天拔出IABP,1例因多脏器衰竭死亡。结论急性心肌梗死心源性休克患者PCI中应用IABP辅助治疗,术中认真落实各项抢救措施和护理措施,是治疗成功的关键所在。     

Beta-adrenergic receptors and catecholamines in acute myocardial infarction

Lymphocyte beta-adrenergic receptor density and plasma catecholamine concentrations were determined in 28 patients with acute myocardial infarction and compared with those in patients with angina pectoris and healthy persons. In patients with acute myocardial infarction beta-adrenergic receptor density was significantly lower (p less than 0.001) and plasma catecholamine levels significantly higher (p less than 0.001) as compared with corresponding values in patients with angina pectoris or healthy persons. beta-adrenergic receptor density in patients with angina pectoris were not significantly different from those in controls. A significant negative correlation between beta-adrenergic receptor density and plasma norepinephrine levels was observed in patients with acute myocardial infarction (r = -0.593; p less than 0.001; r = -0.615; p less than 0.001 respectively). It is suggested that decreased beta-adrenergic receptor density is a consequence of elevated plasma catecholamine levels in patients with acute myocardial infarction. It has been well documented that acute myocardial infarction is associated with enhanced activity of the sympathetic nervous system. Several studies have already been done showing that urinary excretion of catecholamines and plasma catecholamine concentrations are raised in the acute phase of myocardial infarction. Particularly high levels of plasma catecholamines appeared to be related to the severity of clinical course of myocardial infarction and were found in patients with cardiogenic shock, heart failure and arrhythmias. It is of interest that the peak elevation of plasma catecholamines correlated with the extent of myocardial damage as reflected by peak plasma CK activity and also correlated with acute and long-term mortality.(ABSTRACT TRUNCATED AT 250 WORDS)     

主动脉内球囊反搏术在高危急性心肌梗死中的疗效

目的分析和评价高危急性心肌梗死患者在主动脉球囊反搏（IABP）辅助下行经皮冠状动脉治疗（PCI）的临床疗效和安全性。方法回顾性分析51例联合IABP行PCI治疗的急性心肌梗死合并心源性休克患者的临床资料。结果使用IABP后显著改善患者血流动力学及心衰指标,平均动脉压升高,多巴胺用量减少,平均心率下降,尿量增加,脑钠钛水平降低。结论主动脉内球囊反搏术在急性心肌梗死患者中的应用安全、有效,显著降低了急性心肌梗死患者的住院死亡率。     

主动脉内球囊反搏治疗心肌梗死合并心源性休克的价值探讨

目的：探讨主动脉内球囊反搏治疗心肌梗死合并心源性休克的临床价值。方法选取本院收治的80例心肌梗死合并心源性休克患者作为研究对象,随机分为两组,各40例,观察组采用主动脉内球囊反搏,对照组采用急诊心脏介入溶栓治疗,比较两组治疗后的心排血量、平均动脉压变化情况及治疗后出血相关并发症。结果观察组心排血量、平均动脉压显著高于对照组,差异有统计学意义（P＜0.05）,观察组消化道出血、皮下血肿及泌尿道出血的发生率显著低于对照组,差异有统计学意义（P＜0.05）。结论主动脉内球囊扩张能有效提高心肌梗死合并心源性休克患者的心排血量及动脉血压,减少出血相关并发症,值得临床重视。     

Pharmacokinetics and antiarrhythmic efficacy of intravenous ajmaline in ventricular arrhythmia of acute onset

21 patients with acute myocardial infarction and ventricular arrhythmia of Lown class II-IIIB of acute onset received a short infusion of (50 mg/5 min) ajmaline (Gilurytmal). 6 of the patients had normal kidney and liver function (Group 1), 4 patients had acute renal failure and hemodialysis treatment (Group 2), 4 patients had impaired hepatic function (Group 3), 3 patients had cardiogenic shock (Group 4), and 4 patients had been pretreated with phenobarbital for seizures for at least 5 days (Group 5). A distribution half-life of 6 +/- 1 min and an elimination half-life of 95 +/- 6 min was determined in Group 1. The total plasma clearance was significantly lower in patients with impaired liver or cardiac function and significantly higher in Group 5, whereas impaired renal function did not affect total plasma clearance. After short infusion, ventricular arrhythmia of Lown II-IIIB completely disappeared for at least 16 to 36 min (mean: 19 min), which was associated with an ajmaline plasma level of 0.1-0.45 micrograms/ml. Additionally, steady-state plasma levels of ajmaline were determined after continuous infusion of 10-50 mg/h to 16 patients (Group 6) with ventricular arrhythmia of acute onset (Lown class IVA-V). Ventricular arrhythmia completely disappeared or at least changed to lower Lown classes at ajmaline plasma levels of 0.4-2.0 micrograms/ml. The ajmaline plasma protein binding was 76 +/- 9%. Ajmaline had a special affinity to alpha 1-acid glycoprotein.     

经皮冠状动脉成形术(PTCA)治疗急性心肌梗死合并心源性休克30例的疗效观察

目的观察急性心肌梗死合并心源性休克患者行急诊PTCA手术的疗效和其对心功能的影响。方法急性心肌梗死合并心源性休克患者68例,PTCA组30例,溶栓组38例。分析各组患者的临床特征,比较两组患者的住院时间、住院及随访期间不良心血管事件发生率、心功能恢复情况。观察PTCA组年龄、心梗病史、心肌灌注分级、高血压、糖尿病与死亡率的相关性。结果PTCA组较溶栓组血管开通率明显增高,PTCA组住院时间、不良心血管事件发生率、左室射血分数均好于溶栓组。PTCA组患者年龄、心梗病史、心肌灌注分级与死亡率呈正相关。结论PTCA治疗急性心肌梗死合并心源性休克患者是安全、有效的方法。年龄、心梗病史、心肌灌注分级是PTCA手术后患者死亡率的预测因素。     

Tocainide. A review of its pharmacological properties and therapeutic efficacy

Tocainide is an antiarrhythmic drug structurally related to lignocaine with similar electrophysiological, haemodynamic and antiarrhythmic effects. In contrast to lignocaine (lidocaine) it is well absorbed after oral administration and has a plasma half-life of about 15 hours. In several open and controlled therapeutic trials in patients with ventricular arrhythmias, often following a myocardial infarction, tocainide has been relatively effective and usually well tolerated. In treating ventricular ectopic beats and/or ventricular tachycardia tocainide has demonstrated effective suppression in 60 to 70% of patients in both open and controlled studies. It has an acute effect when infused in patients with ventricular arrhythmias complicating myocardial infarction, as well as a prophylactic effect when given orally. The majority of these studies have demonstrated tocainide to be more effective than placebo, but trials against other antiarrhythmic agents are few in number and vary in design. One study combining an infusion of tocainide with oral therapy compared to a bolus injection of lignocaine followed by a constant infusion in patients after myocardial infarction, found the two agents to be of similar efficacy. The most common adverse effects are neurological and gastrointestinal in nature, nausea and dizziness occurring most frequently. Adverse effects resulting in termination of therapy have been reported in about 16% of patients. Aggravation of pre-existing heart failure, increased ventricular arrhythmia, deterioration of conduction disturbances, convulsions, and cases of lupus erythematosus syndrome have occasionally been reported. Thus, tocainide appears to offer a worthwhile addition to the other antiarrhythmic agents available for ventricular arrhythmias. However, its relative place in therapy compared with other antiarrhythmic drugs is not yet clearly established.     

主动脉内球囊反搏联合静脉替罗非班用于急诊冠状动脉介入治疗的临床观察

目的 探讨主动脉内球囊反搏（IABP）联合静脉替罗非班在急性心肌梗死（AMI）合并心源性休克(CS)患者经皮冠状动脉介入(PCI)治疗中的疗效。方法 26例AMI合并CS患者,在IABP及静脉替罗非班支持下行急诊PCI治疗,观察患者手术耐受性、血流动力学、心功能、血栓及出血并发症、病死率等情况。结果 术中除2例因梗死面积过大、泵衰竭死亡外,其余24例均顺利完成冠脉介入治疗并成功实施梗死相关血管（IRA）支架植入术,成功率92.31%,发病至血管再通的平均时间为8.13±2.82h;另外术后3例在监护室因心功能状况恶化死亡,住院期间总死亡率19.23%。未发现下肢动脉栓塞及致命性出血并发症（如颅内出血、内脏出血等）发生。存活病例血流动力学较治疗前有明显改善（P<0.05）;心功能状况较入院时有明显好转（P<0.05）。结论 IABP联合静脉替罗非班用于AMI合并CS患者急诊PCI治疗,可以较大程度地提高患者手术耐受性,改善血流动力学及心功能,减少并发症,降低死亡率。     

The appropriate dosage regime for the transition from intravenous lignocaine to oral tocainide after acute myocardial infarction

Summary To define the appropriate regime for the transition from intravenous lignocaine to oral tocainide after uncomplicated acute myocardial infarction, 43 patients received lignocaine to steady state. Each patient then received a tocainide dosage schedule. Plasma concentration of lignocaine and tocainide was measured frequently until the third peak plasma tocainide level. Tocainide 400 mg 8 hourly starting 4 h before cessation of lignocaine and tocainide 400 mg 4 hourly starting at the end of the infusion produced therapeutic plasma tocainide concentration (3.5–9 mg/l) only after the second dose. Tocainide 600 mg 12 hourly starting 6 h before cessation of lignocaine and tocainide 600 mg 6 hourly starting at the end of the infusion quickly achieved therapeutic plasma tocainide concentration which declined to give subtherapeutic first dose troughs of 2.42 mg/l (±0.28 SEM) and 2.79 mg/l (±0.27 SEM) respectively. Consistently therapeutic plasma tocainide concentrations were achieved by both of these regimes after the second dose. The short plasma halflife of lignocaine which for these regimes was 3.71 h (±0.25 SEM), resulted in subtherapeutic lignocaine concentrations before consistently therapeutic plasma tocainide concentrations had been achieved. On the basis of these results, the 600 mg 6 hourly tocainide dosage schedule was studied with cessation of lignocaine infusion either two or six h after the first tocainide dose. With the former regime only three of 5 patients had therapeutic lignocaine at the subtherapeutic tocainide trough. When lignocaine was discontinued on administration of the second tocainide dose however, therapeutic lignocaine concentration was maintained in all patients until tocainide was rising within the therapeutic range. The latter regime, which we would recommend, was not accompanied by increased side effects. Steady state tocainide was found to be present 12 h after the third tocainide dose allowing continued therapy with tocainide 600 mg 12 hourly.     

Procainamide accumulation kinetics in the immediate postmyocardial infarction period

The rate of change of plasma procainamide concentration during 36 hours of constant-rate intravenous infusion was examined in five acute myocardial infarction patients. It was observed that a steady-state plasma concentration was established in about 16 hours, which is consistent with simulations of plasma concentrations based on pharmacokinetic constants obtained from studies in young healthy volunteers. However, the steady-state level that was attained in these patients was markedly higher than that which the simulations predicted. Thus, on the average, acute myocardial infarction patients have lower total body clearances of procainamide than normal volunteers.