Antegrade selective cerebral perfusion in operations on the proximal thoracic aorta.

BACKGROUND: To determine the factors that influence hospital death and neurologic complications after surgery on the thoracic aorta using circulatory arrest and antegrade selective cerebral perfusion. METHODS: From May 1989 through April 1997, 106 patients underwent surgery on the thoracic aorta using circulatory arrest and antegrade selective cerebral perfusion. Mean age was 64.0 +/- 11.5 years. Unilateral antegrade cerebral perfusion was used in 37 patients (35%), bihemispheric antegrade cerebral perfusion in 69 patients (65%). Mean antegrade cerebral perfusion time was 50.5 +/- 20.5 minutes. Indication for surgery was atherosclerotic aneurysm in 60 (56.5%) patients, postdissection aneurysm in 26 (24.4%), acute type A dissection in 16 (15.1%), other in 4 (4.0%). RESULTS: Hospital mortality was 8.5% (n = 9; 70% CL: 5.8%-11.2%). Independent predictors of hospital mortality were rethoracotomy (odds ratio 5.7, p = 0.02), postoperative temporary (odds ratio 17.3, p = 0.02) or permanent (odds ratio 7.5, p = 0.03) neurologic dysfunction, postoperative dialysis (odds ratio 9.9, p = 0.008). Bilateral antegrade selective cerebral perfusion had a favorable impact on hospital mortality (odds ratio 0.08, p = 0.007). Temporary neurologic dysfunction occurred in 3.8% of patients (n = 4; 70% CL: 2.0%-5.6%); preoperative hemodynamic instability (odds ratio 14.8, p = 0.05) and perioperative technical problems (odds ratio 22.2, p = 0.033) were independent determinants of temporary neurologic dysfunction. Permanent central neurologic damage occurred in 5.4% of patients (n = 6; 70% CL: 3.2%-7.6%). Preoperative hemodynamic instability (odds ratio 18.9, p = 0.009) and approach through a left thoracotomy (odds ratio 9.4, p = 0.031) were significant predictors of permanent neurologic damage. CONCLUSIONS: Hospital mortality is affected significantly by the choice of technique used for antegrade cerebral perfusion. The incidence of both temporary and permanent postoperative central neurologic damage is influenced by preoperative hemodynamic instability. Duration of cerebral perfusion had no influence on the postoperative neurologic outcome.

A randomized multicenter double-blind comparison of urapidil and ketanserin in hypertensive patients after coronary artery surgery.

OBJECTIVES: To compare the hemodynamic responses, safety, and efficacy of urapidil and ketanserin in hypertensive patients after coronary artery surgery. DESIGN: Randomized double-blind study. SETTING: Multi-institutional. PARTICIPANTS: One hundred twenty-two patients undergoing elective coronary artery surgery. INTERVENTIONS: When hypertension (defined as mean arterial pressure > 85 mmHg) developed within the first 2 hours after arrival in the intensive care unit, patients received urapidil (n = 62) or ketanserin (n = 60) to reach a mean arterial pressure between 65 and 75 mmHg. Urapidil was administered by repeated bolus injections (25 to 125 mg) followed by a continuous infusion of maximally 50 micrograms/kg/min. Ketanserin was administered by repeated bolus injections (10 to 50 mg) followed by a continuous infusion of maximally 4.0 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: A complete hemodynamic profile was determined at baseline and at 30 and 60 minutes after start of study medication. In the urapidil group, mean arterial pressure (+/-SD) decreased significantly from 100.6 +/- 12.4 mmHg at baseline to 74.6 +/- 12.1 mmHg at 30 minutes and 73.5 +/- 13.8 mmHg at 60 minutes. In the ketanserin group, mean arterial pressure decreased significantly from 98.7 +/- 10.7 mmHg at baseline to 83.5 +/- 16.8 mmHg at 30 minutes and 83.1 +/- 15.3 mmHg at 60 minutes. Between the groups, there was a significant difference in the degree of lowering mean arterial pressure at 30 and 60 minutes. Heart rate increased significantly by 5.8 +/- 12.7 (30 minutes) and 8.6 +/- 16.5 (60 minutes) beats/min in the ketanserin group. In the urapidil group, no changes in heart rate occurred. Cardiac output increased to the same extent (0.7 L/min) in both groups. Within and between the groups, there were no relevant changes in pulmonary filling pressures. The number of patients not responding adequately to the study medication (mean arterial pressure > 85 mmHg after 30 minutes despite the maximum doses of study medication) was comparable in both groups (9 [U] v 13 [K]). Adverse events attributable to the study medication occurred to a similar degree in both groups. In the patients treated with urapidil, a significantly higher incidence (32.3%) of hypotension (mean arterial pressure < or = 65 mmHg for more than 10 minutes) occurred after 60 minutes of continuous infusion. CONCLUSIONS: In contrast to ketanserin, urapidil did not increase heart rate. Urapidil was more effective in lowering arterial blood pressure than ketanserin. However, one third of the patients treated with urapidil developed hypotension after 60 minutes of continuous infusion.

The myth of the second prophylactic antibiotic dose in aortoiliac reconstructions.

OBJECTIVES: To determine whether a prophylactic second dose of antibiotics is justified when severe blood loss and/or prolonged operation time occurs during aortoiliac reconstructions. METHODS: We measured the cefuroxime concentration in venous blood serum and subcutaneous fat tissue of 30 patients who underwent elective aortoiliac reconstruction after a single intravenous dose of 1500 mg cefuroxime. RESULTS: The mean blood loss was 1912 ml (range 200-7000). The mean operation time was 212 min (range 70-330). The cefuroxime concentration in blood serum 30 min after the gift varied from 53.7-561.6 mg/l and during closure of the abdominal incision from 13.2-90.0 mg/l. Taking the minimum inhibitory concentration for Staphylococcus species as 1.0 mg/l, we found an adequate prophylactic serum cefuroxime concentration in all patients. There was a statistically significant correlation between serum cefuroxime concentration and blood loss (p = 0.01) and operation time (p = 0.0001). CONCLUSIONS: Although serum concentration of cefuroxime is greatly influenced by blood loss and operation time, a second dose of cefuroxime in aortoiliac reconstructions is not necessary if the operation is completed within 5.5 h and if perioperative blood loss does not exceed 7000 ml.

[Effective preoperative studies in outpatient anesthesiology]. / Doelmatig preoperatief onderzoek in de polikliniek Anesthesiologie.

OBJECTIVE: To determine the effect of preoperative patient evaluation by the anaesthesist instead of the surgeon on the requests for additional specialist consultation and investigation and on the costs involved. SETTING: St. Antonius Hospital, Nieuwegein, the Netherlands. DESIGN: Descriptive. METHODS: From June 1993 to June 1995 (2 years), 20,000 patients were evaluated preoperatively by an anaesthesiologist in the outpatient clinic, additional investigations and consultations were requested only when indicated. The data were compared with the routine minimum package of additional requests advised by the Health Council of the Netherlands. The costs were calculated. RESULTS: During the 2-year period there were 19 requests for additional laboratory investigations, ECG or chest X-ray. Consultations of a cardiologist, pulmonologist or internist were required in 137 patients (< 1.4%). Of these patients 67% required further treatment. Elimination of routine consultations and investigations led to a decrease in preoperative hospital admissions. This resulted in savings of approximately 1,300,000 Dutch guilders. CONCLUSIONS: Preoperative outpatient anaesthetic evaluation reduces the number of investigations and consultations and can result in a significant decrease in costs.

Effect of antagonizing residual neuromuscular block by neostigmine and atropine on postoperative vomiting.

Eighty patients undergoing outpatient surgery under general anaesthesia were allocated randomly to two groups: in group A residual neuromuscular block was antagonized with a mixture of neostigmine 1.5 mg and atropine 0.5 mg; in group B spontaneous recovery was allowed. The patients were assessed after operation in hospital and 24 h after discharge. We found a significant difference (P < 0.05) in requirements for antiemetic therapy with a smaller need in the group which received neostigmine (in group A four of 40 patients received an antiemetic compared with 12 in group B). There was no significant difference in frequency of nausea or vomiting between the two groups. The incidence of postoperative nausea was 14 in group A and 18 in group B and the number of patients with postoperative vomiting was 10 in group A and 15 in group B.

High pressure liquid chromatographic analysis of the serum concentration of cefuroxime after an intravenous bolus injection of cefuroxime in patients with a coronary artery bypass grafting.

A simple reversed-phase high pressure liquid chromatographic method was developed for the determination of cefuroxime in the serum of patients undergoing coronary artery bypass grafting. The serum was cleaned up with a 3.3% solution of perchloric acid in water. Cefalexine was used as an internal standard. Detection was made by a UV multi-wavelength detector. The optimum wavelength for cefuroxime is 275 nm. The absolute recovery of this method was 90.9%; the limit of quantification was 0.7 mg/l. This analytical method was used in a study to investigate the cefuroxime serum concentration--time curves in 26 patients undergoing coronary artery bypass grafting. It was found that one single dose is sufficient to obtain effective serum concentrations.

Intoxication with beta-sympathicolytics.

Based on the review of available literature, this article states the possible clinical problems with beta-blocker intoxication. Some 26% of severe cases of intoxication will die. This fact stimulated the attempt, using animal experiments, to gain an insight into the pathophysiological profile of this intoxication. The results of these animal experiments led to the following conclusion: toxic doses of beta-blockers result in a dose-dependent decrease of myocardial contractility. This negative inotropic effect is not related to the antagonizing effects of the beta-blocker at the beta-adrenergic receptor level, nor to the additional properties of this group of drugs, but is influenced by a combination of other factors. These include (1) a direct negative inotropic effect on the myocardium, probably caused by a calcium dependent mechanism; (2) a decrease in serum calcium concentration, probably caused by a decreased parathormone production; (3) a centrally mediated hypotensive action. Toxic doses of beta-blockers do not only affect the myocardium and the haemodynamic system, they can also lead to respiratory arrest. This arrest is caused by the direct effect of these drugs on the central nervous system and can, in itself, be the cause of death. Such results lead to the following therapeutic advice: patients with severe beta-blocker intoxication must be admitted to an Intensive Care Unit, as early initiation of ventilation, as well as administration of beta-antagonist can be essential; the drop in serum calcium concentration must be corrected; drugs which can improve myocardial contractility, other than via the beta-adrenergic receptor, such as phosphodiesterase inhibitors and glucagon, should be administered.

Central origin of respiratory arrest in beta-blocker intoxication in rats.

Propranolol HCl (7.5 mg X kg-1), timolol maleate (7.0 mg X kg-1), and sotalol HCl (10 mg X kg-1) were administered intracerebroventricularly (icv) to spontaneously breathing (SB) rats. The respiratory rate declined until the rats all died from respiratory arrest. Artificial ventilation resulted in survival of the rats for a 3-hr observation period. Intravenous (iv) administration of the same doses of the three beta blockers to SB rats did not result in either respiratory depression or death. Except for a decrease in heart rate (HR) the hemodynamic and respiratory parameters remained almost constant during the 3-hr observation period after iv administration to SB rats. After icv administration to SB as well as to ventilated rats no significant differences could be observed in the initial decrease in HR in comparison with iv administration. In SB rats at the end of the experiments a further decrease in HR was observed which might be ascribed to hypoxia since it did not occur in ventilated rats. After icv administration of each drug to the ventilated rats, mean arterial blood pressure showed a significantly greater decrease at the end of the 3-hr observation period than after iv administration. Plasma concentrations of the three drugs were determined just before death after icv administration in SB rats. In the other two groups they were measured at mean survival time and at the end of the experimental period. The plasma concentrations showed that the route of administration rather than the concentration of the beta blocker in plasma determines the occurrence of respiratory arrest. It was concluded that an overdose of propranolol, timolol, or sotalol can cause a centrally mediated respiratory arrest. Furthermore, a central mechanism appears to be implicated in the decrease in blood pressure.

Calcium interferes with the cardiodepressive effects of beta-blocker overdose in isolated rat hearts.

Propranolol, timolol and sotalol were compared with respect to their cardiotoxic properties in isolated, spontaneously beating rat hearts. Propranolol and timolol induced a dose-dependent decrease in myocardial contractility. A high dose of sotalol had only modest negative inotropic effects. Similar reductions in myocardial contractility were observed in isolated, ventricle-stimulated rat hearts. These observations were similar to those in a previous study in which spontaneously beating and ventricle-stimulated reserpinized rat hearts were investigated. Spontaneously beating rat hearts were perfused with a high-, a normal- and a low-Ca++ medium, each with and without propranolol, timolol and sotalol. Addition of each beta-blocker to a normal-Ca++ medium induced a decrease of myocardial contractility and of heart rate and an increase of AV-conduction time when compared with the drug-free medium. In a high-Ca++ medium containing the same concentration of each beta-blocker, a less pronounced decrease of myocardial contractility was observed. Heart rate decreased and AV-conduction time increased to the same extent as after perfusion with the drug containing normal-Ca++ medium. With respect to the corresponding drug-free medium perfusion with a low-Ca++ medium with each beta-blocker enhanced the decline in myocardial contractility, most pronounced in propranolol and timolol containing media. For propranolol and sotalol the decrease in heart rate and increase in AV-conduction time were similar to the results after administration of the same beta-blocker in a high- and a normal-Ca++ perfusion media. Timolol caused an electromechanical dissociation. It was concluded that in beta-blocker intoxication the negative-inotropic phenomena cannot be explained by an action of the drugs on the beta-receptor since the results in reserpinized and non-reserpinized rat hearts were similar. Other effects have to be responsible for the observed cardiotoxic phenomena. The present results indicate that these phenomena can be influenced by Ca++ and or can be attributed to differences in lipophilicity.

Respiratory arrest as main determinant of toxicity due to overdose with different beta-blockers in rats.

Propranolol, timolol and sotalol were compared regarding their toxicological effects on the cardiovascular and respiratory system. Each drug was administered intravenously to anaesthetized spontaneously breathing and artificially ventilated rats. After the start of infusion in spontaneously breathing rats each drug induced an expected decrease in arterial blood pressure and heart rate. An increase in PQ, QRS and QT interval was observed. From 5/8 of the survival time onwards these changes were accentuated. PaO2, pH and respiratory rate decreased and PaCO2 increased. The rats died as a result of respiratory arrest. Artificial ventilation of rats infused with the same doses increased the survival time significantly. The total doses administered before the animals died as a result of cardiovascular failure were significantly higher for each drug. The initial decreases in arterial blood pressure and heart rate were similar to those in spontaneously breathing rats. Thereafter, significantly smaller decreases were observed. The increases in PQ, QRS and QT interval were significantly less than in spontaneously breathing rats. Blood gases remained unchanged except for a decrease in pH in case of timolol.

Cardiorespiratory depression and haemolysis due to thioridazine overdose in the rat.

The cardiovascular and respiratory effects of an intravenous overdose of thioridazine (125 mg kg-1 h-1) were examined in either spontaneously breathing or artificially ventilated urethane-anaesthetized rats. In both groups PO2, heart rate and mean arterial pressure decreased and atrioventricular and intraventricular conduction time, as well as QT time, increased similarly. PCO2 and pH did not differ significantly except in spontaneously breathing rats where a severe acidosis occurred at the end of the experiments. Haemolysis was suspected. The same dose was administered intravenously to artificially ventilated rats. Plasma concentrations of the drug and its main metabolites, haematocrit and free plasma Hb were determined in separate groups. A severe haemolysis was observed. Thioridazine administered in the same doses intragastrically, intraduodenally or intraperitoneally resulted in lower plasma values than after intravenous administration and there was no haemolysis. Much higher oral doses produced haemolysis at 36 h, at which time plasma concentrations were not higher than those recorded after administration via the other non-intravenous routes. It is probable that the observed changes in cardiovascular and respiratory parameters are partly the result of haemolysis following thioridazine administration.

Different toxicological profiles for various beta-blocking agents on cardiac function in isolated rat hearts.

Propranolol, timolol and sotalol were compared regarding their cardiotoxic properties in isolated, perfused and catecholamine depleted rat hearts. Catecholamine depletion was performed in order to exclude interference of the drugs with beta-adrenergic receptors. The results demonstrate that both in spontaneously beating and atrial- stimulated hearts propranolol (3 - 30 micrograms/ml) and timolol (30 - 300 micrograms/ml) induced a dose dependent decrease in myocardial contractility, stimulus formation and stimulus conduction. Lacking local anesthetic properties as evidenced by effects on coronary flow and threshold voltage in the heart it can be deduced that the negative inotropic effect and an impaired stimulus conduction due to timolol can neither attributed to beta-adrenoceptor antagonism nor membrane stabilising activity. In addition, both propranolol (5 micrograms/ml) and timolol (200 micrograms/ml) reduced myocardial contractility to the same extent in ventricular-paced hearts. Therefore, a direct myocardial depressive effect rather than an indirect effect due to a reduced heart rate must be responsible for the negative inotropy. The hydrophilic beta-blocker sotalol demonstrated a slight cardiodepressant activity either in the spontaneously beating and atrial-stimulated hearts (30 - 300 micrograms/ml) or ventricular-paced hearts (300 micrograms/ml). It is concluded that the toxicological profile of various beta-blocking drugs might be determined by an yet unknown pharmacological property apart from beta-adrenoceptor blockade or membrane stabilising activity. Furthermore, the degree of lipophilicity of the drug might be an important determinant for the cardiotoxic profile of this class of drugs.