Cardiotoxicity of local anaesthetic agents.
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Anesthetics, Local↗
Biomedical subjects
S Reiz
Publications and source records attributed to S Reiz.
Isoflurane--a study of its adrenoceptor interaction in the isolated rat parotid gland.
Adrenergic receptor interaction with isoflurane was studied in an in vitro rat parotid gland model in which beta-adrenoceptor agonists evoke amylase release and alpha-adrenoceptor agonists induce potassium secretion from parotid cells. The amylase secretory studies were performed using a batch-incubation technique, and potassium efflux was evaluated using 86Rb+ as a probe for K+. Isoflurane was dissolved in a fat emulsion, which of its own had no secretory effect. Isoflurane induced a dose-dependent amylase release that was unaffected by beta-adrenergic blockade with propranolol and metoprolol. Isoflurane also induced a significant efflux of 86Rb+ that could not be inhibited by the alpha-adrenoceptor antagonist, phentolamine. Dinitrophenol, an uncoupler of oxidative phosphorylation, had no effect on the isoflurane-induced enzyme release, indicating that amylase secretion occurred by passive leakage. It is suggested that isoflurane has no direct action on alpha- or beta-adrenoceptors. Isoflurane, however, induces potent cellular events that might be due to an unspecific effect on the cell membrane, thereby causing changes in membrane permeability.
2,4-Dinitrophenol↗
The double mask--a new local scavenging system for anaesthetic gases and volatile agents.
The double mask, a new concept for local scavenging of anaesthetic gases escaping around face masks and from endotracheal tubes, is described. The system consists of a flexible silicone mask into which the anaesthetic gas mixture is led through a flow distributor which is necessary for adequate scavenging. A rigid transparent polysulphone shell surrounds the inner mask, and escaping gas is evacuated via the 3-4 mm slot between the two masks by a fan, centrally located outside the operating-room. With this system, the anaesthetist's exposure to nitrous oxide during mask anaesthesia was reduced from 145 +/- 29 to 15 +/- 3 ppm (mean +/- s.e. mean, P less than 0.001) and to halothane from 2.9 +/- 1.1 to 0.5 +/- 0.1 ppm (mean +/- s.e. mean, P less than 0.05), as measured in 32 patients aged 1-74 years. The double-mask system provided safe and adequate mask anaesthesia, as judged from inspired concentrations of anaesthetic and fresh gases and transcutaneous and blood gases in 24 patients. The noise level was low with a mean value under regular operating-room conditions around 45 dB(A) in the low frequency range. It is concluded that using the scavenging conditions provided by the system, the Swedish limits for anaesthesiologists' gas exposure could be reduced to the levels recommended by the US National Institute of Occupational Safety and Health (25 ppm for nitrous oxide and 0.5 ppm for halothane).
Adolescent↗
Differential depressant and electrophysiologic cardiotoxicity of local anesthetics: an experimental study with special reference to lidocaine and bupivacaine.
In 15 pigs lidocaine and bupivacaine were injected into the left anterior descending (LAD) coronary artery to investigate the cardiotoxic effects of these drugs. Anesthesia was maintained by a continuous intravenous pentobarbital infusion and ventilation was controlled. Aortic, pulmonary arterial, right atrial, and left ventricular pressures, a standard 12 lead ECG, cardiac output, and great cardiac venous blood flow were recorded. The local anesthetics were administered at body temperature over approximately 10 sec in a random, crossover fashion at the following equipotent anesthetic doses: bupivacaine, 0.25, 0.5, 1, 2, and 4 mg; lidocaine, 1, 2, 4, 8, and 16 mg. The hemodynamic effects were short-lived, peaking about 5 sec after drug infusion. At the highest dose, both drugs decreased left ventricular dP/dT by 28% (P less than 0.001) and aortic blood pressure by 12% (lidocaine) and 8% (bupivacaine) (P less than 0.001 and P less than 0.01). Heart rate, cardiac output, and coronary venous blood flow did not change. Thus, the cardiodepressant ratio between the two drugs was comparable with their local anesthetic the two drugs was comparable with their local anesthetic potency ratio (bupivacaine/lidocaine, 4:1). Seven animals died in ventricular fibrillation within 1 min after 4 mg bupivacaine dose. All animals given 16 mg lidocaine survived. Ventricular fibrillation was preceded by progressive widening of the QRS complexes recorded over the area perfused by the LAD. The ECG changes after 16 mg lidocaine were of the same magnitude as those recorded after 1 mg bupivacaine. In five of the surviving animals 32 and 64 mg lidocaine were injected intracoronarily after termination of the crossover study.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Coronary haemodynamic effects of surgery during enflurane-nitrous oxide anaesthesia in patients with ischaemic heart disease.
The systemic and coronary haemodynamic effects of 1.5 MAC enflurane-nitrous oxide anaesthesia and abdominal surgery were investigated in nine patients with ischaemic heart disease. Anaesthesia decreased systemic blood pressure (-56%) by a combination of cardiodepression and peripheral vasodilation. A marked fall in myocardial oxygen extraction suggested a moderate coronary vasodilation. Surgery markedly increased the circulating levels of adrenaline and noradrenaline, manifested by increases in blood pressure (+76%) and systemic vascular resistance (+83%). Pulmonary capillary wedge pressure increased by 70% without any change in cardiac or stroke volume index, suggesting that the patients were performing at the horizontal part of their left ventricular function curve. Despite the marked rise in coronary perfusion pressure and a 62% increase in myocardial oxygen demand, coronary blood flow remained unaltered. This could be due either to coronary vasoconstriction overriding the normal coronary autoregulation or to an increase in coronary back pressure opposing the diastolic aortic pressure. When coronary blood flow could not increase to meet the demand for oxygen, the myocardium had to extract more oxygen to ensure appropriate oxygenation, demonstrating interference with coronary autoregulation. Surgery markedly increased myocardial extraction of adrenaline and noradrenaline. We could not find any relationship between myocardial adrenaline extraction and heart rate response to surgery or between myocardial noradrenaline extraction and changes in coronary blood flow, calculated coronary vascular resistance, incidence of myocardial ischaemia or cardiac dysrhythmias.
Abdomen↗
Circulatory shock following intravenous propoxyphene poisoning. An experimental study of cardiac function and metabolism in pentobarbital-anesthetized pigs.
The effects of continuously administered intravenous propoxyphene chloride (15 mg X min-1) on ECG, systemic, pulmonary and coronary circulations and myocardial oxygenation were investigated in eight pentobarbital-anesthetized pigs. Circulatory shock, defined as a systolic blood pressure below 60 mmHg (8.0 kPa) and a cardiac output of approximately 2.0 l X min-1 X m-2, occurred after 675 to 2025 mg propoxyphene chloride. At the time when shock occurred plasma concentrations of propoxyphene ranged from 9.6 to 15.3 micrograms X ml-1 which is within the range of the lethal concentration observed in man. Statistically significant decreases were observed for the following variables: maximum rate of rise of left ventricular pressure dP/dt (-90%), mean arterial pressure (-73%), heart rate (-46%), cardiac index (-58%), stroke volume index (-22%), left ventricular stroke work index (-85%), right ventricular stroke work index (-63%) and systemic vascular resistance (-50%). Mean pulmonary arteriolar occlusion pressure increased (+42%), whereas mean right atrial pressure and pulmonary vascular resistance remained unchanged. The arteriovenous oxygen difference increased (+53%) and total body oxygen consumption decreased (-35%). The following coronary variables decreased: coronary sinus blood flow (-57%), coronary vascular resistance (-65%), myocardial oxygen consumption (-68%), myocardial oxygen extraction (-26%) and myocardial lactate extraction (-28%). Prolongation of the ECG PQ and QRS intervals were recorded shortly before shock appeared, and all animals were in sinus rhythm till the last minute before death. The results indicate that intravenously administered propoxyphene besides being a powerful negative inotropic and chronotropic agent, is also a potent systemic and coronary vasodilator.
Anesthesia, General↗
Effects of isoflurane on vascular tone and circulatory autoregulation in the feline small intestine.
The vascular response in autoperfused small intestine was studied in ten cats during basal chloralose anaesthesia and controlled ventilation with either air, nitrous oxide/oxygen (70/30) or 0.7% end-tidal concentration of isoflurane + nitrous oxide/oxygen (70/30). Intestinal blood flow was measured by the optical drop recording technique, and intestinal perfusion pressure was kept constant at either 100, 75 or 50 mmHg (13.30, 9.98 or 6.65 kPa). At perfusion pressures of 100 and 75 mmHg (13.30 and 9.98 kPa), intestinal blood flow was significantly increased and intestinal vascular resistance decreased during isoflurane- + nitrous oxide/oxygen anaesthesia, compared with nitrous oxide/oxygen or air. According to the equation of closed loop gain (Gf), autoregulation was active in the pressure range 100-75 mmHg (13.30-9.98 kPa). In the pressure range 75-50 mmHg (9.98-6.65 kPa), the autoregulatory capacity was attenuated during air or nitrous oxide/oxygen and absent during isoflurane + nitrous oxide/oxygen. The vasodilator responses and the autoregulatory pattern were not changed by post-ganglionic intestinal denervation. The intestinal vasodilator effect of isoflurane was further investigated in the denervated intestine, perfused at systemic arterial pressure by local intra-arterial administration of isoflurane dissolved in a fat emulsion. A dose-dependent vasodilator response was hereby observed.
Anesthesia, General↗
The effects of cardiac pacing on central hemodynamics in experimental propoxyphene-induced cardiac failure.
Coronary sinus pacing was evaluated in 10 pigs during propoxyphene-induced cardiac failure. From baseline, propoxyphene chloride 15 mg . min-1 was infused until circulatory shock developed. Cardiac pacing was evaluated at different dose levels expressed as % of the shock dose of propoxyphene: at intoxication levels below 50% of the shock dose, cardiac pacing improved cardiac performance. At dose levels above 50% of the shock dose cardiac performance deteriorated further during pacing. The results are consistent with a severe negative inotropic effect of propoxyphene in overdose.
Animals↗
The effects of dopamine on central hemodynamics and myocardial metabolism in experimental propoxyphene-induced shock.
The hemodynamic and cardiometabolic effects of dopamine were evaluated in propoxyphene-induced circulatory shock in eight pentobarbital anesthetized pigs. Circulatory shock was induced by an infusion of propoxyphene chloride 15 mg . min-1 i.v. At shock, i.e. CI less than or equal to 2.0 l . min-1 . m-2 and/or MAP less than or equal to 60 mmHg, dopamine was infused at 10, 20, 40, 80 and 160 micrograms . kg-1 . min-1 with an interval between increments of 8 min. After 30 min at 160 micrograms . kg-1 . min-1, the infusion rate was reversibly decreased. The propoxyphene infusion of 15 mg . min-1 was continued throughout the study. Dopamine improved the circulation in seven animals; one animal died in refractory shock during dopamine infusion. Dopamine infusion at shock level resulted in an increase of the following variables (% of baseline value): MAP (69%), HR (109%), CI (138%) and SVI (129%). Normalisation was seen in MRAP (120%) and in MPAOP (100%). A profound decrease in systemic vascular resistance was unchanged. Increases were seen in left and right ventricular stroke work index, to 88% and 176% of baseline, respectively. Left ventricular dP/dt increased (170%). In the coronary circulation myocardial blood flow increased (133%) as did myocardial oxygen consumption (65%) concomitant with a decrease in myocardial oxygen uptake (41%), but coronary vascular resistance progressively decreased (38%). The myocardial propoxyphene extraction changed from +54% to -86% during peak dopamine infusion. In conclusion, dopamine reversed cardiac failure in propoxyphene overdose by a marked positive inotropic stimulation restoring contractility. A marked positive chronotropic stimulation maintained a sufficient cardiac index and a normal blood pressure in spite of a profound vasodilatation which was unresponsive to dopamine.
Animals↗
The effects of naloxone on central hemodynamics and myocardial metabolism in experimental propoxyphene-induced circulatory shock.
The courses of the hemodynamic and cardiometabolic effects of naloxone were evaluated in propoxyphene-induced shock in eight pentobarbital-anesthetized pigs. Circulatory shock was induced by an infusion of propoxyphene chloride 15 mg . min-1 i.v. At shock, i.e. MAP less than 60 mmHg and/or CI less than 2.0 l . min-1 . m-2, naloxone was administered at 0.75, 1.5 and 3.0 mg . kg-1 with an interval between increments of 8 min. The propoxyphene infusion of 15 mg . min-1 was continued throughout the study. Following the injection of naloxone 0.75 mg . kg-1, increases were observed (% of baseline value) in MAP (41%), i.e. deficit to baseline 59%, HR (66%), CI (67%) and SVI (108%), whereas MPAP and MPAOP were unchanged. dP/dt increased (34%). In the coronary circulation naloxone initiated the following changes: CSF increased (69%) as did MVO2 (48%) with unchanged MO2-extraction, but CVR decreased further (36%). The maximum effects of naloxone were registered 2-3 min after 0.75 mg . kg-1. Following 1.5 and 3.0 mg . kg-1, no changes in hemodynamics were observed other than those caused by progressing propoxyphene intoxication.
Animals↗
Cardiac pacing and central hemodynamics in experimental propoxyphene induced shock.
Coronary sinus pacing was evaluated in 10 pigs with propoxyphene induced cardiac failure. During the early phase of intoxication cardiac pacing improved cardiac function slightly but significantly worsened it in severely intoxicated animals. The results are consistent with marked negative inotropic action of propoxyphene in overdose.
Animals↗
Regional coronary hemodynamics during isoflurane-nitrous oxide anesthesia in patients with ischemic heart disease.
The effects of 1.5 MAC isoflurane-nitrous oxide anesthesia on central hemodynamics, regional coronary blood flow, myocardial oxygenation, and lactate balance were investigated in 13 patients with coronary artery disease. Mean arterial pressure was reduced 45% mainly because of systemic vasodilation. Great cardiac venous flow (GCVF) decreased, whereas total coronary sinus blood flow (CSF) was unchanged. Total coronary resistance and resistance in the area drained by the GCVF decreased as did myocardial oxygen extraction, demonstrating coronary vasodilation. The GCVF/CSF ratio did not decrease despite the reduction in resistance to left ventricular ejection. Seven patients had ECG and metabolic indications of myocardial ischemia (lactate extraction reduced from 22 +/- 5% to 7 +/- 3%, P less than 0.02 for the group). Changes in GCVF and oxygen consumption in the corresponding area correlated closely (r = 0.943). However, the regression line was shifted to the left and three patients, who became ischemic, had an increase in GCVF despite unchanged or decreased myocardial oxygen demand. It is concluded that isoflurane may cause coronary blood flow redistribution with regional myocardial ischemia in patients with coronary artery disease.
Aged↗
A new method for clinical assessment of the negative inotropic action of anaesthetics--with special reference to isoflurane and its effect on myocardial oxygenation.
A new method for maintaining the peripheral determinants of myocardial oxygen demand constant is described. Intravenously administered phenylephrine and nitroglycerin were used to control afterload and preload. Heart rate was kept constant with atrial pacing. The method was used to establish the in vivo negative inotropic effect of 1% end-tidal isoflurane in eight patients with ischaemic heart disease during positive pressure ventilation (IPPV). Stroke volume measured during steady-state isoflurane anaesthesia and IPPV with preload, afterload, and heart rate kept constant was 23% below awake control. The decrease in myocardial oxygen consumption was 22% and correlated well (r = 0.891) with the fall in left ventricular performance (stroke volume).
Anesthetics↗
Acute propoxyphene self-poisoning in 222 consecutive patients.
The course of severe propoxyphene self-poisoning in 222 consecutive patients is presented. On admission, 73% of the patients had neurological symptoms, 10% had convulsions, 45% were in respiratory failure, and impaired circulation was present in 48%. A mortality rate of 8% was observed. Twelve patients arrived in asystole of whom six were resuscitated without sequelae. The overdose was accidental in 13 patients, one of whom died. Early medical intensive care was found mandatory for a good prognosis. Before discharge from the ICU we recommend an observation-period free of cardiovascular symptoms for 24 h.
Accidents↗
Effects of enflurane on coronary haemodynamics in patients with ischaemic heart disease.
The effects of enflurane with and without nitrous oxide on coronary haemodynamics and myocardial oxygenation were investigated in 11 patients with generalised atherosclerotic disease. Enflurane decreased systemic blood pressure (-50%) mainly by systemic vasodilation (SVR -41%) and to a lesser degree by impairment of cardiac performance (CO -27%). A change from 1MAC enflurane-nitrogen-oxygen (70/30) to 1MAC enflurane-nitrous oxide-oxygen (70/30) decreased blood pressure and cardiac output further (-16% and -14%). Enflurane-nitrogen-oxygen decreased coronary blood flow (-29%) and perfusion pressure (-47%). Coronary vascular resistance fell (-20%) along with decreases in myocardial oxygen consumption and extraction (-40% and -16%). Regional coronary blood flow measurements in four of the patients revealed maldistribution of blood flow. During enflurane-nitrous oxide-oxygen, myocardial oxygen consumption and extraction decreased further (-29% and -12%) without change in coronary blood flow or resistance. Myocardial ischaemia was observed in four patients during enflurane-nitrogen. During enflurane-nitrous oxide, ischaemia disappeared in two of the previously ischaemic patients and appeared in two not previously ischaemic. The regional blood flow maldistribution was abolished with nitrous oxide. It is concluded that enflurane is a powerful coronary vasodilator and in this respect slightly less potent than isoflurane. Enflurane may induce myocardial ischaemia by redistributing coronary blood flow and/or by producing hypotension. Nitrous oxide added to enflurane depresses cardiac function and augments the coronary vasodilatory effect of enflurane to a level at which coronary blood flow becomes totally pressure dependent.
Aged↗
Severe acute drug overdose treated in ICU.
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Acute Disease↗
Haemodynamic, electrocardiographic and cardiometabolic changes after overdose of propoxyphene. An experimental study in pentobarbitone-anaesthetized pigs.
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Anesthesia↗
Postoperative pain relief and regional techniques.
The methods of providing postoperative analgesia by regional anaesthetic techniques with local anaesthetics are outlined. For the use of epidural analgesia, the techniques of inserting an epidural catheter at any level of the spine must be familiar. The block should be regional, restricted to the area of pain and effective at all times after its institution with a minimum of side effects. Bupivacaine is at present the best local anaesthetic and can be administered either as intermittent injections with an interval of 1-2 hours or as a continuous infusion. A dose regimen for thoracic, abdominal, perineal and lower extremity pain is presented. Side effects of the epidural technique and ways to treat and avoid them are discussed. The intercostal nerve block for post-thoracotomy and upper abdominal pain is described with special reference to the recent development of the continuous technique with bupivacaine and the cryoanalgesia technique.
Analgesia↗