Osmo Viinamäki

Effects of dexmedetomidine, a selective α2‐adrenoceptor agonist, on hemodynamic control mechanisms

Dexmedetomidine, a selective α2‐adrenoceptor agonist, was administered to five healthy male volunteers in single intravenous doses of 12.5, 25, 50, and 75 µg as part of a placebo‐controlled study. The drug caused dose‐dependent decreases in systolic and diastolic blood pressure. A small initial hypertensive response was observed after injection of the two highest doses. Heart rate was decreased. The concentration of norepinephrine in plasma was decreased significantly (by up to 92%), and the decrease was dose‐dependent. No significant drug‐induced alterations were observed in plasma renin activity or in the concentrations of atrial natriuretic peptide and arginine vasopressin in plasma. Other drug effects included dose‐dependent impairment of vigilance and stimulation of growth hormone secretion. Plasma Cortisol levels were unaffected. Dexmedetomidine is a potentially useful tool for studies of the physiology and pharmacology of α2‐adrenoceptors in human beings and may have therapeutic applications in clinical conditions in which sedative and sympatholytic effects are considered beneficial, such as premedication for anesthesia and surgery.

Oral premedication with clonidine: effects on stress responses during general anaesthesia

The effect of clonidine (4.5 μg kg‐1) on haemodynamics and hormonal stress responses was evaluated in 21 female patients undergoing breast surgery. The standardized general anaesthesia included diazepam as premedicant, thiopentone, enflurane, N2O, fentanyl and vecuronium. Venous plasma concentrations of noradrenaline, adrenaline, growth hormone, vasopressin, and Cortisol were assayed at various times before, during and after surgery. Clonidine attenuated the sympathoadrenal response; arterial blood pressure and heart rate increases in association with intubation were lower in clonidine‐premedicated patients. Noradrenaline levels were lower throughout and 3 h after surgery in the clonidine group (P<0.05). Adrenaline levels were lower in this group 2 min after intubation (P<0.05). Growth hormone, vasopressin and Cortisol plasma levels were increased at the end of and after surgery, with no differences between the groups. In spite of the effect on sympathoadrenal response, clonidine did not have any significant additive anxiolytic effect. Statistically significant differences were not found as to need for postoperative analgesics.

Plasma Vasopressin during Normal Menstrual Cycle

Plasma vasopressin concentrations were measured on days 5-7, 11-13, 15-17 and 21-23 of the normal menstrual cycle in 14 healthy women. The four determinations of vasopressin concentrations did not differ significantly. Plasma vasopressin showed, however, a tendency to increase on days 11-13, when the peak concentration of serum estradiol occurs. After the ovulation a decreasing tendency was seen. There was no significant correlation between circulating vasopressin and 17 beta-estradiol studied in four stages of the menstrual cycle.

Effect of thermal stress on serum prolactin, cortisol and plasma arginine vasopressin concentration in the pregnant and non-pregnant state

The thermal responses of serum prolactin, cortisol and plasma arginine vasopressin were studied on pregnant and non-pregnant women. Group I consisted of 15 healthy non-pregnant women, group II of 23 women 13-14 weeks pregnant and group III of 23 women 36-37 weeks pregnant. Blood samples were taken before the stress (21-23 degrees C), at the end of a 20 min stay in a heat chamber (70 degrees C, 15% relative humidity) and 20 min and 45 min after the stress (21-23 degrees C). The rectal temperature increased 0.3-0.4 degrees C. Serum concentration of prolactin increased from the pre-stress level by 82% in group I (NS), by 25% in group II (P less than 0.05) by the end of the stress but declined steadily in group III by 12% till the end of the recovery period (P less than 0.001). The cortisol concentration increased only in group II during the recovery period (54-72%, P less than 0.05). In this group the subjects who felt discomfort after the stress had higher cortisol levels already before the stress. Arginine vasopressin levels increased significantly only in group I by 17% (P less than 0.05) and there were no differences in the proportional changes between the groups. The response of prolactin to thermal stress seems to be abolished at late pregnancy while the responses of cortisol and arginine vasopressin are not influenced by pregnancy.

Enalaprilat in acute intractable heart failure after myocardial infarction: a prospective, consecutive sample, before-after trial.

ObjectiveTo evaluate the acute effects of intravenous enalaprilat infusion in critically ill patients with intractable heart failure after acute myocardial infarction. DesignProspective, consecutive sample, before-after trial. SettingMedical intensive care unit in a university hospital. PatientsEight consecutive patients with intractable acute heart failure after acute myocardial infarction. All study patients continued receiving inotropic, vasodilating, and diuretic medication at a constant rate. Six patients received steady intermittent mandatory ventilation and two patients were on a continuous positive airway pressure mask during the investigation, all with constant positive end-expiratory pressure. Heart failure was defined as intractable if the pulmonary artery occlusion pressure remained >20 mm Hg despite this conventional therapy. InterventionsEnalaprilat was infused at a rate of 1 mg/hr until the pulmonary artery occlusion pressure decreased by ≥20%. Measurements and Main ResultsCentral hemodynamics, oxygenation, and hormonal regulation (plasma renin activity, plasma norepinephrine, epinephrine, endothelin, atrial natriuretic peptide, and vasopressin concentrations, serum angiotensin-converting enzyme activity, and serum concentrations of aldosterone) were assessed at baseline before enalaprilat infusion, and repeatedly during 2 hrs after the infusion. The statistical analysis was performed with analysis of variance for repeated measurements. Enalaprilat infusion (median dose 0.3 mg and infusion time 21 mins) caused significant but short-lasting decreases in pulmonary artery occlusion pressure (p= .007), mean arterial pressure (p= .003), mean pulmonary arterial pressure, and rate pressure product. These findings coincided with inhibition of serum angiotensin-converting enzyme activity, an increase in plasma renin activity, and a decrease in plasma endothelin concentrations (p = .041). Enalaprilat had no significant effects on the other hormones studied. Cardiac output and stroke volume index, venous admixture, oxygen extraction ratio, and mixed venous and arterial oxygen saturations remained unchanged. ConclusionsAdding enalaprilat to conventional therapy makes it possible to transiently relieve pulmonary congestion while maintaining cardiac function and systemic oxygenation. The decrease in plasma endothelin concentrations may have further clinical implications, because endothelin is known to have potent vasoconstricting effects on the coronary circulation and it may also contribute to the extension of myocardial infarction. Whether these observed benefits can be maintained with repeated bolus injections or with continuous m-fusion of enalaprilat, remains to be settled. (Crit Care Med 1994; 22:965–973)

Antidiuretic hormone concentrations following midazolam premedication

Midazolam given orally the night before and on the morning of operation had a distinct subjective pre‐operative sedative effect as compared with placebo. Patients receiving midazolam also experienced less apprehension and excitement before surgery, but in relation to quality of sleep, the difference between the two groups was not statistically significant. Antidiuretic hormone (ADH) concentrations were determined just before induction of anaesthesia and were significantly lower in the midazolam group (2.14 pg/ml, SD 0.96) than in the placebo group (3.07 pgjml, SD 1.73). Our results show that midazolam is a useful sedative anxiolytic oral premedicanl, which appears to prevent initiation of a stress reaction before induction of anaesthesia.

Esmolol for treatment of hypertension and tachycardia in patients during and after abdominal aortic surgery

Cardiovascular and hormonal responses to reconstructive abdominal aortic surgery were studied in 20 patients anesthetized with high-dose (75 μg/kg) fentanyl-oxygen anesthesia. The aortic cross-clamping (ACC) increased mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance (SVR), as well as central venous pressure and pulmonary capillary wedge pressure. Hypertension associated with the ACC was treated with esmolol (0.1 to 0.5 mg/kg/min) in 10 patients, and with isoflurane (1 vol%) in 7 of the 10 other patients. Both esmolol and isoflurane decreased MAP, HR, and cardiac index (CI), whereas SVR decreased after isoflurane, and increased after esmolol. After aortic declamping, MAP decreased by 9% in the isoflurane group, and 10% in the esmolol group, but CI improved in both groups. Postoperatively, patients in both groups developed hypertension and tachycardia. Esmolol decreased MAP by 26% and HR by 19%. It also decreased CI, but increased pulmonary vascular resistance. Hypertension after the ACC and postoperatively was associated with increases in plasma vasopressin and catecholamine concentrations. The results suggest that esmolol is useful in treating hypertension and tachycardia associated with ACC and in the postoperative period in patients anesthetized with high-dose fentanyl for abdominal aortic surgery.

Continuous positive airway pressure with and without high-frequency ventilation: hemodynamics, oxygenation, and endocrine response

After 18 h of mechanical ventilation following open heart surgery, central hemodynamics, systemic oxygen delivery (DO2), and oxygen consumption were assessed in ten consecutive patients receiving continuous positive airway pressure (CPAP) therapy. Plasma vasopressin, norepinephrine, and epinephrine levels were analyzed. While maintaining the mean airway pressure, two CPAP methods were studied: a demand CPAP with continuous flow without (CPAP) and one with high-frequency ventilation (CPAP-HFV). The frequency used during CPAP-HFV was 300 cycle/min. The spontaneous ventilatory rate was found to be equal during CPAP and CPAP-HFV. The cardiac and stroke volume indices were slightly higher (p less than .05) during CPAP-HFV, which accounted for the finding that DO2 was also slightly higher (p less than .05) during CPAP-HFV. The epinephrine and norepinephrine levels did not differ, whereas the vasopressin level was somewhat higher during CPAP-HFV, which might indicate a higher level of vigilance. It is concluded that cardiac output was slightly higher during CPAP-HFV compared to that during CPAP. This may be due to an effect of the oscillations on circulation or to differences in the level of vigilance.

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.

Vasopressin and Prolactin as Stress Hormones

The effect of electric stimulation of the uterine cervix on vasopressin and prolactin secretions was investigated in 16 patients with uterine myomas and/or hypermenorrhea. One month after hysterectomy a similar stimulation was induced near the fornix of the vagina. Particularly the first test also seemed to be a considerable psychic stress for the patients. The stimulation did not cause any significant changes in plasma vasopressin and prolactin concentrations.