High dose and standard dose adrenaline do not alter survival, compared with placebo, in cardiac arrest.

This trial compared blinded 10 mg aliquots of adrenaline with placebo in 194 cardiac arrest patients treated in hospital using American Heart Association guidelines. In-hospital and out-of-hospital arrests were included. Of the 339 eligible patients a large proportion (145 (45%)) were not randomised and received open 1 mg aliquots of adrenaline. This group is also analysed. Supervising physicians gave significant preference for males, patients with no previous cardiac history and without multiple organ disease to be given open 1 mg adrenaline. Patients in asystole at the time of consideration for entry were preferentially placed in the trial group (114 (69%) vs. 170 (88%)) and patients in ventricular fibrillation were preferentially given open 1 mg adrenaline (31 (21%) vs. 24 (12%) P < 0.03). The most beneficial rhythm changes which led to survival were sinus rhythm and ventricular tachycardia. Analysis of rhythm changes resulting from the dosing showed a significant (P = 0.01) change to a beneficial rhythm with 10 mg adrenaline but not for 1 mg adrenaline or placebo. This was not reflected by an improvement in immediate survival. No significant differences in immediate survival (IS) or hospital discharge (HD) exists between open 1 mg adrenaline (IS 14 (9.7%), HD 3 (2%)) or the 10 mg adrenaline (IS 9 (9.6%), HD 0) vs. placebo (IS 7 (7%), HD 0) trial arms. Patients reaching the point of use of adrenaline have a uniformly poor immediate survival (8.8%) and hospital discharge rate (0.9%). Dosing with 10 mg or 1 mg adrenaline does not influence outcome compared with placebo.

Rhythm changes during resuscitation from ventricular fibrillation.

Defibrillation of patients with primary ventricular fibrillation (VF) results in a variety of rhythm changes. We analysed these changes in rhythm in 200 patients, using the American Heart Association's recommendation of two defibrillations prior to drug therapy. Sixty-three (31.5%) patients were immediate survivors with 38 (19%) being discharged from hospital alive. There was no difference between the age of immediate survivors (66.5 years, S.D. = 11.2) and non-survivors (68.3 years, S.D. = 13.7, P = 0.37). Immediate survivors were significantly more likely to be discharged alive from hospital if they were younger (70.0 years, S.D. 8.5 vs. 62.1 years, S.D. 15.8, P = 0.014). Increasing delays to the initiation of basic life support (CPR) and to defibrillation were associated with significantly less likelihood of cardioversion to sinus rhythm (P < 0.005 and P < 0.002, respectively). Those patients who stayed in VF were not more likely to be defibrillated into asystole or electro-mechanical dissociation. Seventeen percent (34) of patients were defibrillated to sinus rhythm after the first defibrillation and 14% (19) after the second, with similar hospital discharge rates (62% and 58%, respectively). Sixty percent (32) of patients in sinus rhythm, after two defibrillations, were discharged alive, compared to only 4% (6) of those patients not in sinus rhythm after two defibrillations. Our data provide new information on rhythm changes during resuscitation and supports the need for the earliest possible initiation of basic life support and defibrillation to improve survival from cardiac arrest due to ventricular fibrillation.

Catecholamines during cardiopulmonary resuscitation for cardiac arrest.

Serum catecholamines were measured during continued prolonged cardiopulmonary resuscitation and after 10 mg increments of intravenous epinephrine. This was part of an ongoing trial of 10 mg epinephrine versus placebo. Eight patients were in the placebo arm and seven in the epinephrine arm and the rhythms were two ventricular fibrillation, nine asystole and four electromechanical dissociation. Data were analysed by time from onset of the cardiac arrest and samples were analysed for levels of DHPG (dihydroxyphenylglycol) nor-epinephrine, epinephrine, DOPA (dihydroxyphenylalanine) and DOPAC (dihydroxyphenyl acetic acid). There was a significant (P < 0.001) difference between arterial and venous samples of epinephrine but not the other catecholamines. High levels of catecholamines were maintained in all time phases except for nor-epinephrine where significant (P < 0.0003) reduction occurred progressively after 20 min. Non-steady state kinetics were suggested between epinephrine and nor-epinephrine and DHPG and nor-epinephrine for the first 20 min. Very large increases in epinephrine were achieved with administered 10 mg epinephrine and this resulted in high DHPG levels supporting the experimental belief that exogenously administered epinephrine induces myocardial release of nor-epinephrine. This data supports the known effects of CPR on catecholamine release. It provides data on the other neurotransmitter hormones and supports the relationships shown in other animal and human data. It is suggested that supplementation with epinephrine during CPR may be unnecessary and the levels reached may be deleterious. Nor-adrenaline supplementation may be necessary after prolonged CPR.

Prediction of hospital discharge in immediate survivors of ventricular fibrillation or asystole.

Survival from ventricular fibrillation and asystole is influenced by variables measured during resuscitation that affect both immediate survival and discharge from hospital. These variables have been used to develop a formula to calculate an individuals chances of immediate survival and hospital discharge. It has allowed this heterogenous group to be subdivided into groups which can be compared both within and between institutions for the purposes of audit and evaluation of resuscitation protocols. This study evaluates the addition of clinical parameters to the prognostic index. One hundred twelve immediate survivors of ventricular fibrillation or asystole were examined immediately after resuscitation and clinical parameters measured and recorded. At the same time parameters previously described were recorded. The increase in the numbers of survivors improved the reliability (area under the receiver operator curve (ROC) improved from 0.79 to 0.83) of the index for predicting hospital discharge. Addition of the clinical variables of conscious state, respiratory state, blood pressure and pulse rate improved the prognostic index further to an ROC area of 0.86. This ensures that the predictive power of the new index is now highly reliable for predicting hospital discharge after successful resuscitation from ventricular fibrillation and asystole.

Prediction of survival from resuscitation: a prognostic index derived from multivariate logistic model analysis.

Despite advances in resuscitation, the ability to predict survival at cardiac arrests remains unsophisticated. We identified the factors determining outcome of all cardiopulmonary resuscitations performed at our institution over a 4-year period, and used a Cox multivariate regression model to design prognostic indices to assess the probability of successful resuscitation and hospital discharge. Cardiac arrests (710) were studied, and 193 (28%) were successfully resuscitated. The most influential variables, judged by the size and significance of their logistic regression coefficients, were rhythm, resuscitation delay, and age (for successful resuscitation), and rhythm, performance of intubation and defibrillation, defibrillation delay, and age (for survival until discharge). The combination of these in a prognostic index reliably predicted both outcome (area under the receiver operating curve of 0.78), and survival until discharge (area under the curve of 0.80).

Adverse effect of early high-dose adrenaline on outcome of ventricular fibrillation.

Resuscitation for cardiac arrest was monitored over 4 years to examine the effect on survival of a change in the ventricular fibrillation (VF) protocol to include the routine early use of "high-dose" intravenous or transbronchial adrenaline. A significant reduction in the immediate survival of patients with VF was seen when the protocol was changed (22% after the change, 43% before). Prior predictors of poor response were similar in each group, except for the number of witnessed arrests, delay until cardiopulmonary resuscitation, and occurrence of endotracheal intubation, but multiple logistic regression showed the use of adrenaline to be an independent predictor of outcome. Early high-dose adrenaline was associated with a reduction in immediate survival in patients with persistent VF.

Severe hypophosphataemia induced by glucose-insulin-potassium therapy. A case report and proposal for altered protocol.

A case is described where severe hypophosphataemia was induced by a widely used protocol for glucose-insulin-potassium (GIK) infusion. Hypophosphataemia was found to be a universal sequel to the use of this infusion. A new regimen for administering this agent was designed, and shown to lack the potentially serious side effect of phosphate depletion.

Management of familial aortic dissection.

Aortic dissection uncommonly occurs in multiple family members, and this association is most commonly seen in kindreds with Marfan's syndrome. There is increasing evidence that such connective tissue disturbances may not always appear in their complete phenotypic pattern. This report describes two siblings with aortic dissection. It is proposed that this suggests underlying connective tissue disease and warrants investigation of close relatives.

Physical training and fasting serum insulin levels in sedentary men.

The present study examined fasting serum insulin levels in relation to body composition and dietary intake during the initial 4 weeks of a 12-week physical training programme in 26 previously sedentary men. Fasting serum insulin concentrations decreased markedly during the first 4 weeks of training and remained at these reduced levels for the rest of the study. The early fall in serum insulin concentration was significantly correlated with the concomitant decrease in body fat, the increase in lean body weight and the age of the subjects. Body weight and reported dietary intake on the other hand, did not change significantly over this period. These results indicate that the decrease in fasting serum insulin in previously sedentary men with physical training is associated with the concomitant changes in body composition. Increased muscle tissue in particular may contribute to this training-induced decrease in serum insulin.

Isometric exercise following myocardial infarction.

Twenty-six consecutive patients had measurement of ejection fraction by gated blood-pool imaging at rest and during isometric exercise, following recovery from an uncomplicated myocardial infarction. We found there was a highly significant fall in ejection fraction at rest from 56 +/- 3% to 43 +/- 3% during isometric exercise (p less than 0.0001). There was a dramatic fall in ejection fraction during isometric exercise in some patients with a normal resting value. These patients may be a cause for concern. Our preliminary findings suggest these latter patients are at risk for future cardiac events such as, unstable angina, further myocardial infarction and future coronary bypass surgery.

Post-heparin hepatic lipase activity and plasma high density lipoprotein levels in men during physical training.

Plasma post-heparin hepatic lipase (PHHL) activity, plasma lipids, and high density lipoprotein cholesterol (HDL-C) levels, pulse rate at submaximal workload, and body weight were measured in 12 men during the 18 weeks physical training for their first marathon run. Reduced pulse rate at submaximal workload indicated that the men increased their physical fitness during the training period. Plasma HDL-C levels (+27%) and PHHL activity (+29%) also increased significantly after 18 weeks training. These changes were not in accord with the inverse correlation between plasma HDL-C levels and PHHL activity which was observed before training. The results of this study do not support the concept that reduced PHHL activity is mainly responsible for increased levels of plasma HDL-C with training.

Intermittent high intensity physical training and plasma lipoprotein lipid levels in men.

Levels of plasma lipoprotein lipids and anthropometric and physical fitness measurements were followed in 12 normal men over a 16 month period including training for two marathon runs separated by one year. As judged from pulse rate at submaximal work, the physical fitness of the men increased during training for the marathons and also over the whole study. High density lipoprotein (HDL) cholesterol levels which had been raised by training for the first marathon, were at similar levels at peak training prior to the second marathon. Estimated alcohol consumption was significantly higher prior to marathon II compared to the level prior to marathon I but this did not result in increased plasma high density lipoprotein cholesterol levels. The trend towards increased low density lipoprotein (LDL) cholesterol levels early in the study continued until the levels were finally significantly higher than pretraining values. It is possible that plasma high density lipoprotein cholesterol levels in the men reached personal maximum levels after training for the first marathon and were unaffected by an apparent increase in aerobic fitness achieved after training for the second marathon. This study also indicated that the effects of long term training on plasma lipids and lipoproteins may differ from those observed following shorter periods of exercise.

Family history, cigarette smoking and other risk factors in patients with myocardial infarction.

All patients entering a coronary care unit had data collected and stored prospectively on a computer file. Family history and risk factor data have been abstracted for those with confirmed myocardial infarction. These data are compared between those aged less than 50 years and those aged between 50 and 70 years. Cigarette smoking habits are compared with age matched data from the 1976 census population study of cigarette smoking habits. The risk factors of hypercholesteolaemia, obesity, diabetes, hypertension and cigarette smoking greater than 20 per day, do not separate the two age groups although cigarette smoking is more prevalent in the patient groups compared with the census population. Age of fathers' death is not different between the two age groups but death from myocardial infarction, presence of ischaemic heart disease during life in fathers and fewer nonsmokers in the younger age group clearly separate them from older age group patients. This study serves to emphasise that in order to prevent the development of myocardial infarction special attempts sould be made to prevent cigarette smoking in those whose fathers have died of a myocardial infarction or have symptoms of ischaemic heart disease.

Physical training and adipose tissue fatty acid composition in men.

Four months physical training significantly raised the mean proportions (%) of lauric (+0.64), myristic (+0.52), stearic (+2.06) and linoleic (+1.69) acids and lowered the mean proportions of palmitic (-1.46) and oleic (-3.46) acids in adipose tissue of 20 apparently normal men aged 20-55 yr. These changes were dependent on pretraining proportions of the fatty acids. In addition, the decreases in palmitic acid and oleic acid proportions were positively correlated (rho = 0.905, P less than 0.01, tau = 0.758, P less than 0.01). The pattern of significant correlations among adipose tissue fatty acids was altered as a result of training. We suggest that preferential mobilisation of fatty acids from adipose tissue is responsible for the change in adipose tissue fatty acid composition with increased physical training. The significant increase in adipose tissue linoleic acid proportions may be linked with the reduced risk of coronary heart disease which has been previously associated with increased physical activity.

Decreased and continued physical activity and plasma lipoprotein lipids in previously trained men.

Twenty-three moderately active apparently normal men aged 20-55 participated in a 4-month stamina training programme ending in a marathon run. Fourteen men decreased their training levels and 5 men continued training at the same level in the subsequent 2 months. Fasting lipoprotein lipid concentrations, anthropometric data, performance on a bicycle ergometer, reported values for alcohol consumption, smoking and weekly distance run were recorded at each phase of the study. Both groups of men showed significantly increased levels of plasma triglycerides (TG) and very low density lipoprotein triglycerides (VLDL-TG) during the detraining and continued training period. At the same time, plasma total cholesterol (TC), low density lipoprotein cholesterol (LDC-C) and very low density lipoprotein cholesterol (VLDL-C) increased significantly only in men who decreased their level of training. However, final mean values for plasma lipids and lipoproteins did not significantly differ between the 2 groups of men. It is concluded that levels of plasma lipids and lipoproteins, excepting VLDL-C, do not return to pretraining values during 2 months of detraining.

Physical activity and plasma lipoprotein lipid concentrations in men.

Twenty-three apparently normal untrained men aged 20--55 participated in a 4-month self-regulated training programme ending in a marathon run. Fasting plasma and lipoprotein lipid concentrations, adipose tissue lipoprotein lipase activity, anthropometric data, alcohol consumption, smoking habits, weekly mileage run and performance on a bicycle ergometer were recorded before and after the training period. Training induced an increase in high density lipoprotein cholesterol (HDL-C) concentration which was not directly related to concomitant decreases in mean very low density lipoprotein cholesterol (VLDL-C) concentration or mean total skinfold thickness. The degree of the changes in VLDL lipids and HDL-C levels were related to pretraining values, and changes in HDL-C and VLDL triglycerides (VLDL-TG) were also associated. Initial total skinfold thickness correlated inversely with the change in VLDL-TG levels during training. The pretaining concentration of VLDL-C was related to the corresponding value for HDL-C after training. The magnitude of exercise-induced changes in VLDL-C and HDL-C levels are more related to pre-training levels than to changes in measured exercise parameters, indices of obesity or adipose tissue lipoprotein lipase activity. However, the level of adiposity of subjects at the beginning of the study influenced the response of VLDL-TG levels to increased physical activity. The data suggest that VLDL contributes to the increase in HDL-C levels with exercise but is not the major source of the increment.

Sudden death of a young man during a sponsored jogging event.

A case of sudden unexpected death in an apparently fit and healthy young man is reported. Autopsy showed severe atherosclerotic heart disease. There was a family history of a disorder of lipid metabolism.