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Biomedical subjects

M Hynynen

Publications and source records attributed to M Hynynen.

At least 37 records · Page 2Linked to original sources

A survey of the ASA physical status classification: significant variation in allocation among Finnish anaesthesiologists.

BACKGROUND: The American Society of Anesthesiologists' (ASA) Classification of Physical Health is a widely used grading system for preoperative health of the surgical patient. In previous studies conducted in North America and Great Britain, considerable variation in the ASA classification allocation has been reported. We hypothesised that in smaller and culturally more homogeneous countries there might be less variation in the ASA classification. METHODS: A postal questionnaire depicting 10 hypothetical patient cases was sent to 249 randomly selected members of the Finnish Society of Anaesthesiologists. Responses of anaesthesiologists working in university teaching and non-teaching hospitals were compared, as well as the answers of specialists and non-specialists. RESULTS: Responses were received from 108 anaesthesiologists (response rate 43%). There was marked variation in the classification of all the 10 cases: 1 case was classified to all five possible grades (ASA grades I-V). In 2 cases, there was significant variation between anaesthesiologists working in university teaching and non-teaching hospitals. There was no difference in the grading between specialist and non-specialist anaesthesiologists. CONCLUSION: In a small and culturally homogeneous country, like Finland, there exists similar wide variation in the ASA classification as has been previously reported from larger and culturally more heterogeneous countries. The significant variation should always be considered when using this classification in clinical or scientific work.

Adult↗

Cardiopulmonary bypass-induced changes in plasma concentrations of propofol and in auditory evoked potentials.

Unbound, rather than total, plasma concentrations may be related to the anaesthetic action of propofol. Therefore, we measured plasma concentrations of propofol and recorded Nb wave latencies of auditory evoked potentials (AEP) during continuous infusion of propofol in 15 patients undergoing coronary artery bypass grafting (CABG) surgery. After induction of anaesthesia with fentanyl, propofol was infused continuously at a rate of 10 mg kg-1 h-1 for 20 min, and then the rate was reduced to 3 mg kg-1 h-1. Administration of heparin before cardiopulmonary bypass (CPB) did not affect total or unbound propofol concentration. Initiation of CPB decreased mean total propofol concentration from 2.6 to 1.7 micrograms ml-1 (P < 0.01). Simultaneously, mean unbound propofol concentration remained at 0.06 micrograms ml-1 because of a slight increase in the mean free fraction of plasma propofol (from 2.3 to 3.5%; P > 0.05). During hypothermic CPB, mean total propofol concentration increased to concentrations measured before bypass (to 2.1 micrograms ml-1; P > 0.05 vs value before CPB) and the mean unbound propofol concentration was at its highest (0.07 microgram ml-1; P < 0.05 vs value before heparin). After CPB and administration of protamine, the mean total propofol concentration remained lowered (1.7 micrograms ml-1; P < 0.05 vs value before heparin) and the mean unbound propofol concentration returned to the level measured before heparin (P < 0.001 vs value during hypothermia). The latency of the Nb wave from recordings of AEP increased after induction of anaesthesia, reached its maximum during hypothermia and was prolonged during the subsequent phases of the study. The latency of the Nb wave did not correlate with total or unbound propofol concentration. We conclude that the changes in total and unbound concentrations of plasma propofol were not parallel in patients undergoing CABG. During CPB or at any other time during the CABG procedure, the unbound propofol concentration did not decrease and Nb wave latency was prolonged compared with baseline values measured after induction of anaesthesia before the start of CPB.

Adult↗

Effect of diltiazem on midazolam and alfentanil disposition in patients undergoing coronary artery bypass grafting.

BACKGROUND: Midazolam and alfentanil are desirable anesthetic adjuncts for cardiac anesthesia. They are metabolized by cytochrome P450 3A (CYP3A) enzymes. These isozymes are inhibited by concurrent medications, including the calcium channel antagonist diltiazem, which may have an effect on recovery from anesthesia. METHODS: Thirty patients having coronary artery bypass grafting were randomly assigned to receive either diltiazem (60 mg orally 2 h before induction of anesthesia and an infusion of 0.1 mg.kg-1.h-1 started at induction and continued for 23 h) or placebo in a double-blind study. Anesthesia was induced with 0.1 mg/kg midazolam, 50 micrograms/kg alfentanil, and 20 to 80 mg propofol and maintained with infusions of 1 microgram.kg-1.min-1 of both midazolam and alfentanil supplemented with isoflurane. Plasma midazolam and alfentanil concentrations and areas under the plasma concentration-time curves were determined. The terminal half-life and the time for the drug plasma level to decrease 50% after cessation of the infusion (t50) were calculated for midazolam and alfentanil. Separation from mechanical ventilation and tracheal extubation were performed according to the study protocol. RESULTS: Diltiazem increased the mean concentration-time curves (from end of anesthesia until 23 h) of midazolam by 24% (P < 0.05) and that of alfentanil by 40% (P < 0.05). The mean half-life of midazolam was 43% (P < 0.05) and that of alfentanil was 50% (P < 0.05) longer in patients receiving diltiazem. The mean t50 of alfentanil was 40% longer (P < 0.05) in patients receiving diltiazem, but the change in the mean t50 of midazolam (25%) was not statistically significant. In patients receiving diltiazem, tracheal extubation was performed on average 2.5 h later (P = 0.054) than in those receiving placebo. CONCLUSIONS: Diltiazem slows elimination of midazolam and alfentanil and may delay tracheal extubation after large doses of these anesthetic adjuncts. CYP3A-mediated drug interactions should be considered as confounders when recovery from anesthesia with midazolam and alfentanil infusions is assessed.

Adjuvants, Anesthesia↗

Recall of awareness during cardiac anaesthesia: influence of feedback information to the anaesthesiologist.

We interviewed 303 cardiac surgery patients to evaluate the incidence of intraoperative awareness with recall. First, we randomly interviewed 99 patients, of whom four patients (4%) reported awareness and recall. We informed the cardiac anaesthesiologists of the results of these interviews, and we also gave general information regarding means to reduce awareness and recall during general anaesthesia. Thereafter, we interviewed 204 consecutive cardiac surgery patients. Now, three of the patients (1.5%) had intraoperative awareness with recall. The reduction in the incidence from 4% to 1.5% was not significant. However, the doses of principal anaesthetic drugs had increased significantly between the two interview phases, while the dose of pancuronium, the main muscle relaxant used, had decreased significantly. Also, there was a significant increase in the number of anaesthesias where anaesthetic agents had been administered continuously instead of bolus or non-continuous dosing techniques. Between the patients with awareness and recall and those without it, there was no difference in the doses of anaesthetic agents given. The patients with awareness were significantly younger than those not aware. In conclusion, with educational measures and vigilance over the problem, the incidence of intraoperative awareness during cardiac anaesthesia may be reduced. The incidence figure of 1.5% we observed is of the magnitude reported recently by others with modern cardiac anaesthesia techniques.

Adult↗

Pulmonary vascular effects of nitroglycerin and isosorbide dinitrate in patients with end-stage cardiomyopathies.

BACKGROUND: Severe preoperative pulmonary hypertension predicts a poor outcome after heart transplantation and therefore pulmonary vasoreactivity is frequently evaluated in the pretransplantation screening. Among the i.v. organic nitrates used in this evaluation, isosorbide dinitrate and nitroglycerin differ in their pharmacokinetics, and isosorbide dinitrate has been suggested to be more selective in its effects on pulmonary vasculature than nitroglycerin. METHODS: Haemodynamic effects of nitroglycerin and isosorbide dinitrate were compared in 8 patients with end-stage cardiomyopathy. Each patient was given increasing i.v. infusion-doses of the two nitrates in a random order and double-blind and cross-over fashion until the target of at least 25% decrease in mean pulmonary artery pressure was achieved. RESULTS: A total dose of 11 (3-20) (mean, 95% confidence interval) microgram kg-1 of nitroglycerin and that of 87 (12-161) micrograms kg-1 of isosorbide dinitrate were given during the infusions of 20 (14-27) and 28 (18-37) min duration, respectively. With these doses producing similar acute decreases in mean pulmonary artery pressure, both nitroglycerin and isosorbide dinitrate also showed equal effects on pulmonary and systemic vascular resistances as well as on other systemic and right ventricular haemodynamic parameters. CONCLUSION: We conclude that there is no difference between i.v. nitroglycerin and isosorbide dinitrate in their selectivity on the pulmonary vasculature in patients with end-stage cardiomyopathy.

Adult↗

Continuous infusion of nimodipine during coronary artery surgery: haemodynamic and pharmacokinetic study.

A continuous infusion of nimodipine 15 or 30 micrograms kg-1 h-1 was administered from the evening before operation to the second morning after operation to 14 patients undergoing elective coronary artery bypass grafting (CABG) surgery. Nimodipine was tolerated well by all seven patients who received the lower dose. However, of the seven patients who received the higher dose, in two patients the infusion had to be discontinued after induction of anaesthesia and immediately after surgery, respectively, because of excessive vasodilatation and hypotension. At steady state before cardiopulmonary bypass (CPB), total plasma nimodipine concentration was higher than expected on the basis of previous reports in non-surgical subjects. Similarly, mean clearance of nimodipine was lower than predicted, that is 0.53 (range 0.40-0.72) litre kg-1 h-1. Initiation of CPB decreased total plasma nimodipine concentration, but the unbound plasma concentration did not decrease because of the increase observed in the free fraction of nimodipine in plasma. As evaluated in a separate closed extracorporeal circuit, nimodipine was sequestered into the circuit. Addition of stored whole blood to the priming solution attenuated this sequestration. It is concluded that clearance of nimodipine, as assessed before CPB at steady state, was reduced in patients undergoing CABG and receiving a continuous infusion of nimodipine. Using this finding of decreased clearance in designing infusion schemes of nimodipine for cardiac-surgical patients, it should be possible to predict more accurately the desired plasma nimodipine concentration and therefore reduce the possibility of unexpected haemodynamic responses.

Adult↗

Haemodynamic effects of propofol infusion for sedation after coronary artery surgery.

We have compared the haemodynamic effects of a sedative dose of propofol with placebo (vehicle of propofol) in a randomized, double-blind study in 20 patients immediately after coronary artery bypass grafting (CABG). During a continuous infusion of a mixture of fentanyl and pancuronium, each patient was given in a crossover design, a loading dose of propofol 0.5 mg kg-1 and vehicle over 5 min followed by a continuous infusion of propofol 20 micrograms kg-1 min-1 and vehicle, respectively, for 55 min. Administration of propofol caused a significant decrease in mean arterial pressure (mean change from pre-drug values to those during drug infusion: -15.4% vs +1.3% with placebo; P < 0.001), mean pulmonary artery pressure (-6.5% vs +5.8%; P < 0.001), systemic vascular resistance (-13.8% vs -0.6%; P < 0.05), pulmonary vascular resistance (-2.0% vs +9.0%; P < 0.05), cardiac output (-2.4% vs +2.6%; P < 0.05) and pulmonary artery occlusion pressure (-8.0% vs +1.4%; P < 0.05). Propofol did not affect heart rate, but it tended to decrease stroke volume (P = 0.102). These data suggest that, during the recovery phase from CABG surgery, a short-term infusion of a sedative dose of propofol decreases systemic and pulmonary arterial pressure by decreasing systemic and pulmonary vascular resistance, respectively, and cardiac output. The decrease in cardiac output appeared to be caused mainly by a decrease in stroke volume.

Adult↗

Effects of organic nitrate vasodilators on platelet function before and after cardiopulmonary bypass.

Various in vitro, ex vivo and in vivo tests have shown that organic nitrates attenuate platelet function. Because organic nitrates are commonly administered to patients undergoing cardiac surgery, the postoperative bleeding tendency observed in these patients might be strengthened by nitrates. Therefore, we compared the acute effects of nitroglycerin (0.5 micrograms kg-1 min-1) and isosorbide dinitrate (0.5 or 2.5 micrograms kg-1 min-1) with those of placebo on platelet function both before and after cardiopulmonary bypass in 40 patients undergoing coronary artery bypass grafting (CABG). Bleeding time, platelet retention on glass beads, i.e. platelet adhesiveness, and thromboelastograph tracings were used as indicators of platelet function. Although nitroglycerin and isosorbide dinitrate induced significant haemodynamic changes, e.g. decreases in arterial and pulmonary arterial pressure, they had no significant effects on the indices of platelet function. We conclude that, when given in haemodynamically effective doses, neither nitroglycerin nor isosorbide dinitrate have any measurable acute effect on platelet function as evaluated with on-site tests in patients undergoing CABG surgery.

Adult↗

Propofol sequestration within the extracorporeal circuit.

Various drugs administered during cardiac anaesthesia are sequestered in the extracorporeal circuit in vitro, but it is uncertain whether this sequestration phenomenon affects plasma drug concentration in vivo. The present study was undertaken to evaluate (1) in vitro sequestration of propofol in the extracorporeal circuit and (2) whether the change in plasma propofol concentration induced by initiation of cardiopulmonary bypass in vivo can be explained by haemodilution. For the in vitro evaluation, three separate experiments with a closed circuit (membrane oxygenator, reservoir, and tubings) were performed. The pH and PCO2 of the circulating solution (a mixture of Ringer's acetate and whole blood) were maintained within the normal physiological range, and the temperature of the solution was 28 degrees C. The solution was circulated at a flow of 4 L.min-1 and propofol was added to the solution to achieve a concentration of 2 micrograms.ml-1. Serial samples were taken from the circulating solution for measurement of propofol concentration by high performance liquid chromatography. In the in vivo part of the study, 14 patients received a continuous infusion of propofol, and samples for the determination of plasma propofol concentration and blood haematocrit were taken before and five and ten minutes after initiation of cardiopulmonary bypass. In vitro, at 5 and 120 min after addition of propofol into the circulating solution, approximately 65% and 25%, respectively, of the predicted propofol level was measurable in the solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗

Plasma concentration and protein binding of alfentanil during high-dose infusion for cardiac surgery.

We have studied plasma protein binding of alfentanil in 10 patients given a mean total dose of 949 micrograms kg-1 as the principal anaesthetic agent for coronary artery bypass grafting. The mean unbound fraction of plasma alfentanil increased from 0.09 to 0.16 after administration of heparin and to 0.26 after beginning cardiopulmonary bypass (CPB). After CPB until the end of surgery, the unbound fraction decreased to 0.12. These changes in the unbound fraction were associated with significant changes in plasma total and unbound concentrations of alfentanil also. Within the first 1 min of CPB, total alfentanil concentration had decreased by more than the unbound concentration and the decrease observed in the latter disappeared rapidly. From induction of anaesthesia until awakening of the patient, plasma protein binding of alfentanil was related significantly (P = 0.0166) to the serum concentration of orosomucoid (alpha 1-acid glyco-protein).

Aged↗

Successful treatment of ARDS with two doses of synthetic surfactant.

A 50-year-old man with adult respiratory distress syndrome (ARDS) was successfully treated with synthetic surfactant. The therapy rapidly improved the respiratory function; it also increased the release of endogenous surfactant. Synthetic surfactant may thus be of value in the treatment of ARDS.

Drug Combinations↗

Plasma atrial natriuretic factor during cold-induced diuresis.

The purpose of this study was to evaluate the possible contribution of atrial natriuretic factor (ANF) to cold-induced diuresis. Seven healthy men, dressed in shorts, were exposed to a cold environment (+12 degrees C) for 90 min, and also to a thermoneutral environment. Exposure to cold increased urine output and sodium excretion significantly but plasma ANF concentration remained unchanged. The increase in urinary potassium excretion during cold exposure was not significant (P = 0.0636) and plasma renin activity did not change either. Exposure to cold increased mean arterial pressure significantly but it did not affect heart rate. We concluded that acute exposure to the cold environment induced a diuretic response, which was a solute diuresis in its nature. Our results did not give support to the hypothesis that ANF might be involved in the renal response to cold exposure.

Adolescent↗