Death associated with anaesthesia and surgery in Finland in 1986 compared to 1975.

Mortality associated with anaesthesia and surgery in Finland in 1986 was studied using a retrospective method and was compared with the results of a similar study performed in 1975. The total number of procedures was 325,585. 570 patients fulfilled one of the three criteria: 1. The patient died within three days of a procedure needing anaesthesia. 2. The patient died more than three days after a procedure needing anesthesia, but had suffered a cardiac arrest or been resuscitated, or there was a surgical or an anaesthesiological complication contributing to the death. 3. The patient suffered a major handicapping neurological (or other) deficit, which was associated with anaesthesia, or there was a surgical or an anaesthesiological complication possibly contributing to the death or handicap (no patients). The number of consultant anaesthesiologists had more than doubled since 1975. At the same time there was also a significant increase in recovery room and intensive care facilities. Surgery was the main contributing factor in the death of 22 (frequency 0.68/10,000 procedures), and anaesthesia in the death of five (frequency 0.15/10,000 procedures) patients. The role of surgery had decreased to about one third and the role of anaesthesia to less than one tenth as the main cause of death associated with anaesthesia and surgery compared to the year 1975. 95.3% of all the patients died mainly because of co-existing medical or surgical disease.

Allergic reaction to an amide local anesthetic in segmental epidural analgesia.

A very serious case of anaphylactoid reaction to bupivacaine occurred during epidural analgesia. A rise in complement 3 activation products and a decrease in immunoglobulin E were observed, while bupivacaine toxicity was ruled out by normal serum concentration. Severe maternal hypotension, and a sudden decrease in the fetal heart rate were detected clinically. By a cesarean section, a baby girl was delivered, who at the age of 1 year appears normal.

Elimination of and heart rate response to atropine in the elderly are independent of sex.

Sex-related changes in the pharmacokinetics and pharmacodynamics (heart rate) of atropine were studied in female (n = 9) and male (n = 9) elderly patients after a single 0.02 mg/kg i.v. injection of the drug at the beginning of a combination anaesthesia. No significant differences were found between the sexes, which indicates that there are no sex-related alterations in the response to this anticholinergic agent.

Low-dose enflurane as adjunct to high-dose fentanyl in patients undergoing coronary artery surgery: stable hemodynamics and maintained myocardial oxygen balance.

The effects of enflurane (end-tidal concentration 0.7%) on central and coronary hemodynamics and myocardial oxygenation were studied during steady state, high-dose fentanyl anesthesia in ten patients undergoing coronary artery bypass grafting operations. Compared with the response in ten patients receiving the same fentanyl anesthesia (100 micrograms/kg) without enflurane supplementation, enflurane caused a moderate reduction in mean arterial pressure, systemic vascular resistance, and left ventricular stroke work index. No patient showed signs of myocardial ischemia, and mean coronary sinus flow and calculated coronary resistance remained unchanged. Surgical stimulation induced no central or coronary hemodynamic responses in the enflurane-fentanyl group. No coronary hemodynamic changes occurred in the fentanyl group, but a marked increase in arterial pressure and systemic vascular resistance was seen. Myocardial oxygen extraction decreased in the enflurane supplemented group although it increased in the fentanyl group after surgical stimulation. Three fentanyl group patients and one enflurane-fentanyl group patient had a low myocardial lactate extraction as a sign of myocardial ischemia during surgery. We conclude that a 0.7% enflurane supplementation of 100 micrograms/kg fentanyl anesthesia does not endanger myocardial oxygenation and effectively prevents central and coronary hemodynamic responses to skin incision and sternotomy in patients undergoing coronary artery surgery.

Oral temazepam as a premedicant in elderly general surgical patients.

In elderly, general surgical patients, oral temazepam 20 mg given in a soft gelatin capsule proved to be a useful light premedicant when given before spinal anaesthesia. In comparison with placebo, it caused preoperative subjective sedation, prevented an increase in heart rate and decreased serum cortisol, but not serum antidiuretic hormone levels. However, simple devices (linear analogue scale, Maddox wing test, critical flicker fusion apparatus) appeared to be quite ineffective in differentiating the clinical effects of temazepam from those of placebo. Temazepam given in a soft gelatin capsule to patients in the supine position had a reasonably fast gastrointestinal absorption, but its blood-lumbar cerebrospinal fluid penetration rate appeared to be quite slow.

Midazolam as an intravenous induction agent in the elderly: a clinical and pharmacokinetic study.

Midazolam, the first benzodiazepine derivative with water-soluble salts, was studied as an induction agent in general anesthesia for the elderly. In group 1 (n = 14), 5 or 10 mg oral diazepam was used as premedication, but in group 2 (n = 9), both oral (10 mg dixyrazin as a night-time sedative) and intramuscular (0.01 mg/kg atropine + 1 mg/kg meperidine) premedicants were used. Serum concentrations of benzodiazepines were determined using both gas-liquid chromatographic (unchanged midazolam) and radioreceptor assays (binding equivalents of benzodiazepines plus their active metabolites). In general, midazolam, 0.15 mg/kg, intravenously resulted in smooth induction of anesthesia, although the time required for induction was rather long and a sudden but transient decrease in blood pressure was found in a significant number of patients. The course of anesthesia was otherwise satisfactory. A marked amnesic effect was observed, especially when diazepam was used as premedication. The pharmacokinetic parameters based on gas-liquid chromatographic measurements were quite comparable with those in young, healthy persons published earlier. In both groups, the binding equivalents measured with radioreceptor assay (reflecting total benzodiazepine activity) were higher than the levels of unchanged midazolam determined with gas-liquid chromatography. The relatively low dose of 0.15 mg/kg of midazolam needed for anesthetic induction in the elderly indicates not pharmacokinetic, but pharmacodynamic, alterations in older patients. We conclude that midazolam is a new intravenous induction agent for use in the elderly, but careful titration of the dosage according to the response of the patient is required. Diazepam premedication prior to midazolam causes a marked anterograde amnesic effect.

A comparison of the soft gelatin capsule and the tablet form of temazepam.

Pharmacokinetics and pharmacodynamics of the soft gelatin capsule and tablet form of temazepam were compared. In a single blind study, six healthy volunteers, in the supine position, took either a tablet of temazepam 20 mg or a soft gelatin capsule of temazepam 20 mg. Sixty gynaecological in-patients received either a tablet or a soft gelatin capsule of temazepam 20 mg the night before surgery as premedication. Subjective parameters were assessed in the morning. The soft gelatin capsule yielded clearly higher serum concentrations during the first hour after administration. In the pharmacodynamic parameters there were slight but insignificant differences in favour of the capsule form. As a premedicant the capsule resulted in a significantly (P less than 0.01) shorter delay in the onset of sedative action and to an almost significant (P less than 0.05) delay in falling asleep; also an almost significantly (P less than 0.05) longer action of sleep in comparison with the tablet.

Effect of induced hypotension on serum concentrations of atropine after intramuscular administration.

The serum concentrations of atropine after a single intramuscular injection of 0.01 mg/kg were determined by radioimmunoassay in nine general surgical patients during and after a combination anaesthesia and compared with those of 13 neurosurgical patients operated on during induced hypotensive anaesthesia (sodium nitroprusside plus trimetaphan). Surprisingly, comparable serum levels were found in both patient groups. We conclude that this kind of induced hypotension cannot be used as a model of drug absorption in such clinical situations as cardiac failure, haemorrhage or anaphylactic drug reactions.

Tofisopam and midazolam: differences in clinical effects and in changes of CSF monoamine metabolites.

The effect of two repeated oral doses of 100 mg tofisopam 15 mg midazolam and placebo on the concentrations of monoamine metabolites (MHPG, 5-HIAA, HVA) in lumbar CSF were studied in general surgical patients operated on under spinal analgesia (n = 12 in each group). Midazolam, but not tofisopam, improved the quality of sleep the night before surgery. Both active agents reduced preoperative anxiety of the patients, but tofisopam was without subjective sedative action. In the placebo group, in contrast to the active drug groups, there was a slight positive correlation between the MHPG concentration and degree of anxiety before surgery. The only significant difference in the monoamine metabolites in lumbar CSF was found in the concentrations of HVA between tofisopam and placebo treated patients. The lower HVA concentrations suggest that the curious 3,4-benzodiazepine derivative, tofisopam, modifies central dopaminergic activity.

Serum concentrations and urinary excretion of lidocaine and its two desethylated metabolites after spinal anaesthesia using lidocaine or lidocaine with phenylephrine.

In 13 patients undergoing transurethral prostatic resection under spinal anaesthesia with heavy lidocaine or with heavy lidocaine plus phenylephrine hydrochloride, the serum concentrations of lidocaine, monoethylglycinexylidide and glycinexylidide and their renal excretion were measured with a HPLC method. Seven patients were given lidocaine alone 1.25 mg/kg and six lidocaine 1.25 mg/kg mixed with phenylephrine hydrochloride 3 mg. There was no significant difference between the two groups either in the serum levels of lidocaine or in the renal excretion rate of lidocaine and its metabolites. This finding gives support to the opinion that phenylephrine in low doses has no prolonging effect on spinal anaesthesia performed with heavy lidocaine.

Neurosecretory response of hypothalamic-hypophyseal axis to spinal anesthesia, minor gynecological surgery and irradiation.

The effect of spinal anesthesia, dilatation and curettage plus the first intracavitary radiotherapy or only that of intracavitary radiotherapy on growth hormone (HGH = the response of anterior pituitary) and arginine vasopressin (AVP = the response of posterior pituitary) levels was studied in 10 patients suffering from cervical or endometrial uterine cancer. Differing from earlier animal studies, irradiation had no effect on GH or AVP secretion, nor was there any change in the hormone levels following spinal anesthesia and dilatation and curettage. The neurosecretory response of hypothalamic-hypophyseal axis to spinal anesthesia and minor gynecological surgery appears to be minimal.

Flunitrazepam as an induction agent in elderly, poor-risk patients.

Great interindividual variation was found in response to flunitrazepam when the latter was used as an induction agent for general anaesthesia in elderly, poor-risk patients. However, no significant changes in the pharmacokinetics of this nitrobenzodiazepine derivative were found, which suggests that there are pharmacodynamic alterations in response to the drug with advancing age. A sudden but transient drop in blood pressure was found in three out of 12 patients, even although flunitrazepam was given, i.v., in low 0.3-0.5 mg incremental doses. A marked amnesic effect was found. No analgesics were needed in the recovery room (2 h), supporting the evidence that flunitrazepam has an analgesic-sparing effect. Flunitrazepam resulted, in general, in smooth induction of anaesthesia, but a long time was needed for induction.

Death associated with anaesthesia in Finland.

The mortality associated with 338 934 procedures carried out in 1975 in 100 Finnish hospitals is reported. There were 626 deaths (1/541 or 0.18%). Mortality during the procedure was 1/5059 (0.02%). Twelve patients died primarily of anaesthesia during the procedures and 55 patients later (total anaesthetic mortality 1/5059, 0.02%). The frequency of cardiac arrest was 1/3808 (0.03%). Most of the 67 anaesthetic deaths were caused by inadequacy of management of fluid balance (17 patients) or respiratory insufficiency (15 patients). There were 12 deaths from cardiac complications, five each from technical errors and inadequate supervision after operation. The primary disease was responsible for approximately 72% of the reported deaths.

A comparative study of the clinical effects of pentobarbital and diazepam given orally as preoperative medication.

The clinical effects of pentobarbital, 100 mg, and diazepam, 10 mg, given orally as preoperative medications before dental surgery were tested in a double-blind study in 50 adult patients. The concnetrations of pentobarbital and diazepam (plus its three active metabolites) in plasma, measured by gas chromatography, were correlated with their clinical effects as assessed both subjectively and objectively (sedation, apprehension, excitement, dizziness, pre- and post-operative emetic effect, increase or decrease in systolic blood pressure, pulse rate, and ease of venipuncture). No significant difference in the effects of these two agents was observed, nor was there any obvious relationship between the concentration in plasma and clinical effect.

A comparative study on the clinical effects of oxazepam and diazepam: Relationship between plasma level and effect.

The clinical effects of oxazepam and diazepam as oral premedicants were tested in a double-blind study of 60 children and 50 adults. The gas chromatographically measured concentrations of the active unconjugated forms of oxazepam and diazepam in the plasma were correlated to their clinical effects, as assessed both subjectively and objectively (sleep, sedation, apprehension, excitement, dizziness, emetic effect, headache, increase or decrease in systolic blood pressure, increase in pulse rate, venepuncture). No significant difference in the effects of these two benzodiazepine derivatives were observed, nor was there any obvious relationship between the plasma concentration and clinical effect.