Farmacovigilancia de los Agonistas Adrenérgicos en pacientes de la unidad de cuidados intensivos del hospital "Dr. Miguel Pérez Carreño"

Se realizó un estudio de tipo prospectivo descriptivo en 84 pacientes en quienes se determinaron las reacciones adversas (RAM´s) tras la administración IV de alguno de los siguientes agonistas adrenérgicos: noradrenalina (0,5 my/kg/min.), adrenalina (0,1my/kg/min), dopamina (3my/kg/min.) y dobutamina (5my/kg/min.). Se utilizó como instrumento de registro de las RAM´s la Hoja Amarilla de CEVIFARE. Se procedió a la identificación de las RAM´s por su tipo, severidad y causalidad. El 83,33% de los pacientes presentaron RAM´s, siendo las más frecuentes: taquicardia (47,61%), palidez (23,80%), hipertensión (11,90%) y arritmias (7,14%). Todas las RAM´s fueron del tipo A, el 50% leves, 40% moderadas y 10% graves. El 100% de las RAM´s analizadas fueron probadas. Aunque los agonistas adrenérgicos estudiados resultaron ser seguros, la adrenalina tiene el riesgo de producir necrosis tisular distal, por lo cual el papel de la Enfermera(o) que practica la farmacovigilancia es prevenir o disminuir la posibilidad de aparición de RAM´s en los pacientes a su cuidado.

A descriptive study was made in 84 patients to determined adverse drugs reactions (DAR) during the IV treatment with some of the following adrenergic agonists: norepinephrine (0,5mu/kg/min), epinephrine (0.1mu/kg/min), dopamine (3mu/kg/min.) and dobutamine (5mu/kg/min). The Yellow Card of CEVIFARE was used as the instrument for registry of the DAR. DAR were analyzed by its type, severity and causality. 83.33% of the patients had DAR, being most frequent: tachycardia (47,61%), pallor (23,80%), hypertension (11,90%) and arrhythmias (7,14%). All the DAR were type A, mild 50%, moderate 40% and serious 10%. 100% of DAR analyzed were proved. Although the adrenergic agonists turned out to be safe, the epinephrine has the risk of producing distal necrosis, thus the Nursing role in practicing pharmacovigilance is to prevent or to diminish the possibility of appearance of DAR in the patients under her care.

Midazolam pharmacodynamics and pharmacokinetics during acute hypovolemia.

This study was designed to test the hypothesis that acute hypovolemia would compromise the compensatory hemodynamic mechanisms to midazolam and decrease its metabolic clearance. Experiments were performed on seven chronically instrumented female beagle dogs. Animals received a single intravenous dose of midazolam, 10 mg/kg, 4 days apart during normovolemic (N) and hypovolemic (H) states in a random sequence. Hypovolemia was achieved by the withdrawal of 26 ml/kg of blood, equivalent to one-third of the calculated blood volume. Midazolam plasma concentrations were determined at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 h after midazolam injection. Elimination half-life (t 1/2 beta) was significantly longer and total clearance was significantly lower during H than during N. Initial distribution half-life, central compartment volume, total volume of distribution, and plasma protein binding were similar in both N and H states. Midazolam caused a significant decrease in systolic blood pressure (SBP) and an increase in heart rate (HR) during N, and produced significant decreases in SBP, diastolic blood pressure (DBP), and mean arterial pressure (MAP) during H. Midazolam led to similar per cent decreases in blood pressure and cardiac output in states N and H; however, the absolute values of blood pressure and cardiac output were significantly (P less than 0.001) lower in the hypovolemic state than in the normovolemic state. These data suggest that the hypotensive effects of midazolam, like those of other intravenous induction agents, could be potentiated by volume depletion.

Computer-assisted continuous infusions of fentanyl during cardiac anesthesia: comparison with a manual method.

The design and implementation of a computer-assisted continuous infusion (CACI) system to rapidly attain and maintain a constant plasma fentanyl concentration (PFC), as well as a CACI system that allowed the anesthesiologist to change the plasma level of fentanyl during cardiac anesthesia, were developed. In 30 patients (three groups of 10 patients each) these two automated methods of fentanyl infusion were compared with a manual fentanyl administration method. There was excellent agreement in the measured/predicted PFC ratios with the CACI stable fentanyl level system (ratio = 0.99, n = 91) and in the CACI variable fentanyl level system (ratio = 1.08, n = 79). The stable fentanyl level group of patients received significantly more (P less than 0.05) fentanyl than did the other groups. The CACI variable fentanyl level group of patients had greater hemodynamic stability, required significantly (P less than 0.05) fewer adjuvant drug interventions and experienced significantly (P less than 0.05) fewer hypotensive and hypertensive episodes than the manual, bolus fentanyl (control) group. These data show that a computer-assisted automated infusion of fentanyl is safe and as good as manual methods. CACI has greater potential as a new method of intravenous anesthesia administration.

Cardiovascular effects of esmolol in anesthetized humans.

We studied the cardiovascular effects of esmolol, a newly synthesized beta-adrenocepter antagonist, in anesthetized humans. Forty patients (four groups of 10 each) with ischemic heart disease and normal ventricular function were anesthetized with diazepam, pancuronium, and N2O in O2. Esmolol was given by continuous infusion in cumulative doses of 1100 micrograms/kg (group 1), 2000 micrograms/kg (group 2), and 2700 micrograms/kg (group 3); a control group received no esmolol. Infusion of esmolol was begun 3 min prior to and ended 4 min after tracheal intubation. All three doses of esmolol significantly (P less than 0.001) attenuated the heart rate responses to intubation. Rate-pressure products were significantly (P less than 0.001) lower in esmolol-treated patients than in controls after intubation, but ST-segment changes compatible with ischemia occurred in one patient in each group. Increases in heart rate were associated with significant increases in plasma norepinephrine levels (r = 0.45, P = 0.02) in the control group, but not in esmolol-treated patients, a demonstration that esmolol antagonizes the beta-adrenergic effects of norepinephrine. The effect of esmolol on heart rate was absent 5 min after cessation of infusion, and plasma levels of esmolol were undetectable in 26 of 30 treated patients 15 min after the termination of esmolol infusion. Esmolol has a rapid onset and short duration of effect. It can be used safely during anesthesia in patients with normal ventricular function to attenuate cardiac response to sympathetic stimulation.

Pituitary responsiveness to LRF in castrated male hamsters exposed to different photoperiodic conditions.

The effect of various doses of LRF on pituitary LH and FSH release was examined in castrated adult male hamsters with different photoperiodic histories. Gonadotropin (Gn) release in response to LRF was independent of whether the animals had been exposed to a photostimulatory (LD 14:10) or a nonstimulatory (LD 6:18) light cycle for 60 days following castration. The lowest dose that caused a significant increase in serum Gns was 10 ng LRF/100 g b.w. for LH and 50 ng LRF/100 g b.w. for FSH. These results indicate that photoperiod, which is well known to exert major effects on the reproductive system of the golden hamster, does not do so by directly altering the responsiveness of the pituitary gland to hypothalamic Gn-releasing factor.

Changing to problem-oriented methods. Implementation in psychiatric institutions.

The so-called problem-oriented methods for organizing and recording clinical information offer many potential benefits to users in psychiatric institutions. Beyond the mechanical aspects of implementation, incorporating a problem-oriented approach into the practices of clinical teams entails conceptual and practical readjustments of considerable magnitude. Based on an 18-month study of eight psychiatric teams with diverse characteristics, the paper discusses rationales and priorities, as well as administrative and educational considerations in the conversion process. Such a process must be studied and understood in setting objectives and channeling resources, if outcomes are to match the expectations.

The interaction of castration and photoperiod in the regulation of hypophyseal and serum gonadotropin levels in male golden hamsters.

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in intact and castrate adult male hamsters maintained on photostimulatory (LD 14:10) and non-photostimulatory (LD 6:18) light:dark cycles to assess the interaction of photic stimuli and gonadal hormones on pituitary gonadotropin release. Immunoreactive serum LH and FSH levels increased 1.6- and 8-fold respectively, within 3 days after photostimulated hamsters were castrated. In contrast, castration failed to alter serum LH concentration and had only a slight, if any, effect on FSH concentration in hamsters exposed to nonstimulatory photoperiods that induced testicular atrophy. In a second experiment, male hamsters previously maintained on LD 14:10 were castrated, transferred with intact animals to LD 6:18, and killed periodically over 60 days. In intact animals, pituitary content and serum levels of LH and FSH declined substantially during exposure to the non-stimulatory LD 6:18 cycle. In castrated animals, serum LH and FSH levels which had increased 2- and 8-fold in response to the castration eventually declined to about the levels found in the intact initial control animals. In contrast to serum gonadotropins, the increased hypophyseal content of LH and FSH following castration was not reduced during exposure to LD 6:18. Exposure to nonstimulatory photoperiods does not alter the increased hypophyseal LH and FSH content observed after castration. However, our results indicate that exposure to short days renders the hypothalamic-hypophyseal neuroendocrine system governing gonadotropin release relatively insensitive to gonadal steroid hormone feedback.