Hemodynamic effects of medetomidine in the dog: a dose titration study

OBJECTIVE: To characterize the hemodynamic effects of medetomidine administered intravenously at doses ranging from 1 to 20 microg/kg, and to determine whether these effects are dose dependent. STUDY DESIGN: Prospective randomized multidose trial. ANIMALS: Twenty-five clinically normal male beagles (5 groups of 5), aged 1 to 4 years and weighing 13.5 +/- 1.7 kg. METHODS: Medetomidine, at a dose of 1, 2, 5, 10, or 20 microg/kg, was administered intravenously at time 0. Heart rate, arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, body temperature, cardiac output, and packed cell volume were measured immediately before and at selected times after medetomidine administration (3, 7, 10, 20, 30, 40, 50, and 60 minutes in all groups, at 90 minutes for the 10 and 20 microg/kg groups, and at 120 minutes for the highest dose). Cardiac index, stroke index, rate-pressure product, systemic vascular resistance index, pulmonary vascular resistance index, and left and right ventricular stroke work indices were calculated. The degree of sedation was subjectively scored by an observer who was blinded to the treatment used. RESULTS: Heart rate, rate-pressure product, cardiac index, and left and right ventricular stroke work indices decreased below baseline values. Central venous pressure and systemic vascular resistance index increased above baseline measurements. Except in the 2 microg/kg group, after an initial and short lasting increase, a prolonged decrease in arterial pressure was observed. CONCLUSIONS: Hemodynamic changes were observed with the intravenous (IV) administration of medetomidine, at any dose. However, the two lowest doses (1 and 2 microg/kg) produced less cardiovascular depression. CLINICAL RELEVANCE: Medetomidine is an alpha-2 adrenoceptor agonist widely used in dogs, producing sedation, analgesia and cardiovascular depression. When using IV medetomidine, a reduction of the recommended dosage (ie, +/-30 to 40 microg/kg) by up to 6 times did not significantly influence the cardiovascular effects.     

Desmopressin for the treatment of nocturnal polyuria in the elderly: a dose titration study

OBJECTIVE: To evaluate the decrease in nocturnal polyuria and the tolerability of three different doses of oral desmopressin in elderly subjects. SUBJECTS AND METHODS: Subjects were included in the study if they; (i) were healthy and free from medication with possible influence on their diuresis or voiding pattern: (ii) had an increased nocturnal frequency (> or = 2 nocturnal voids, as reported in the pre-screening period); and (iii) had a nocturnal urinary output of > or = 0.9 mL/min. Seventeen men and six women (mean age 68.1, SD 4.7 years) met these criteria and were treated with 0.1, 0.2 and 0.4 mg oral desmopressin given at bedtime, each dose taken for one week on three consecutive weeks. RESULTS: The mean (SD) nocturnal diuresis before treatment was 1.6 (0.7) mL/min, which decreased significantly to 1.1 (0.4) mL/min when 0.1 mg desmopressin was given. A dose of 0.2 mg desmopressin resulted in a further small decrease in the nocturnal diuresis to 0.9 (0.4) mL/min, whereas the 0.4 mg dose produced no additional effect. The reduction in nocturnal diuresis occurred almost exclusively in the group with a nocturnal urinary output of > or =1.3 mL/min. After treatment, diuresis returned to pretreatment levels. There was no change in body weight or in ankle circumference during desmopressin treatment and no serious adverse effects were observed. CONCLUSION: Desmopressin reduces nocturnal diuresis in polyuric elderly subjects and this reduction, occurring with doses of 0.1 mg given at bedtime, does not increase in a dose-dependent way.     

The induction, maintenance, and recovery characteristics of spinal versus general anesthesia in elderly patients

The ability of flavonoid compounds to induce the activity of the phase II anticarcinogenic marker enzyme, quinone reductase (QR), has been studied in a wild-type murine hepatoma cell line (Hepalclc7) and in an Ah-receptor-defective mutant of the same cell line (Hepalclc7 bp(r)cl). The results showed that 10 (beta-naphthoflavone, kaempferide, tamarixetin, rhamnetin, quercetin, kaempferol, quercetin-4'-glucoside, isorhamnetin, daidzein and genistein) of the 13 flavonoids tested induced QR activity in the wild-type cells. Only the latter six also showed such activity in the bp(r)cl mutant, which indicates that they induce phase II enzymes directly (monofunctional inducers), whereas the others induce phase 11 enzymes only in cells with an operative Ah receptor system (bifunctional inducers). The metabolism of representatives of monofunctional (quercetin) and bifunctional (tamarixetin and rhamnetin) flavonol inducers were studied in both wild-type and bp(r)cl cells. In all cases, the major metabolites were glucuronides. Quercetin produced identical metabolites in both cell types, whereas one glucuronide of tamarixetin and two glucuronides of rhamnetin were not formed in the mutant cells. This shows that flavonoids can be mono- or bifunctional inducers depending on their chemical structure, and that the glucuronidation pattern of bifunctional inducers is altered by the presence of a functional Ah receptor system.     

Two-level spinal stenosis in minipigs. Hemodynamic effects of exercise

STUDY DESIGN: Twenty-two G?ttingen minipigs were trained to run on a treadmill. Two-level lumbar spinal stenosis was created in 12 pigs, 10 were unoperated control subjects. Blood flow of the spinal cord and nerve roots was determined with microspheres at rest, during exercise, and after exercise. OBJECTIVES: To study the effect of lumbar spinal stenosis and exercise on blood flow of spinal neural tissue. SUMMARY OF BACKGROUND DATA: Neurogenic claudication, the key symptom of lumbar spinal stenosis, may be caused by vascular impairment or mechanical distress of neural tissue during exercise. Experimental compression of the cauda equina causes reversible nerve root edema, stasis, blood flow decrease, and compromised neural function. The vascular pathophysiology of spinal stenosis during exercise has not been studied previously. METHODS: Pigs were trained daily for 3 months. Two-level 25% lumbar spinal stenosis was introduced by placement of stenosing bands around the dural sac. Neurologic function was monitored before surgery by evoked potentials and after surgery by the Tarlov score. Regional blood flow in lumbosacral neural tissue was measured 3 days after chronic catheterization using microspheres at rest, during exercise at 3 km/h for 15 minutes, and at rest 30 minutes after exercise. RESULTS: Blood flow of grey and white matter increased during exercise in both groups, with no differences between groups. slight hyperemia prevailed after exercise in white matter of the stenotic area but not in grey matter. Nerve root blood flow was largely unchanged in control subjects during exercise but was reduced in spinal stenosis at rest, further depressed during exercise, and normalized after exercise. Dural blood flow was elevated throughout. CONCLUSION: The study suggests that exercise-induced impairment of spinal nerve root blood flow plays a role in the pathophysiology of neurogenic claudication.     

Attentional effects of single dose triazolam

1. While the effects of benzodiazepines on human memory have been extensively studied little is known about the effects of these agents on attentional processes. The authors studied the effects of a single dose of triazolam on selective visual-spatial attention using a double blind, placebo controlled design. 2. In each of 2 sessions 12 normal volunteers ingested either 0.25 mg of triazolam or placebo. Attentional performance was evaluated using two versions of the covert orienting paradigm which measured automatic (exogenous) and controlled (endogenous) aspects of attentional orienting, respectively. 3. Triazolam selectively modified performance on automatic orienting to exogenous cues. Specifically, triazolam increased the facilitation of target detection seen at shorter (150 msec) SOA's. This may indicate an increase in facilitation and a reduction in inhibition or a slowing of the time course of the biphasic attentional effect normally resulting from exogenous cuing. 4. These results indicate the importance of using experimental paradigms which effectively dissociate endogenous and exogenous mechanisms of spatial orienting in studies evaluating the effects of pharmacological agents on visual-spatial attention.     

Shivering threshold during spinal anesthesia is reduced in elderly patients

BACKGROUND: Both accidental and perioperative hypothermia are common in the elderly. The elderly are at risk because their responses to hypothermia may be delayed or less efficient than in those of younger subjects. For example, the vasoconstriction threshold during isoflurane anesthesia is approximately 1 degree C less in elderly than younger patients. However, the extent to which other cold defenses are impaired in the elderly remains unclear, especially in those older than 80 yr. Operations suitable for spinal anesthesia provided an opportunity to quantify shivering thresholds in patients of varying ages. Accordingly, the hypothesis that the shivering threshold is reduced as a function of age during spinal anesthesia was tested. METHODS: Twenty-eight ASA Physical Status 1-3 patients undergoing lower extremity orthopedic procedures were studied. Spinal anesthesia was induced without preanesthetic medication, using bupivacaine sufficient to produce a dermatomal level near T9. Electrocardiogram signals were recorded at 10-min intervals. Subsequently, an observer masked to patient age and core temperature identified the onset of sustained electromyographic artifact consistent with shivering. The tympanic membrane temperature triggering shivering identified the threshold. RESULTS: Three patients did not shiver at minimum core temperatures exceeding 36.2 degrees C. Fifteen patients aged < 80 yr (58 +/- 10 yr) shivered at 36.1 +/- 0.6 degrees C; in contrast, ten patients aged > or = 80 yr (89 +/- 7 yr) shivered at a significantly lower mean temperature, 35.2 +/- 0.7 degrees C (P = 0.002). The shivering thresholds in seven of the ten patients older than 80 yr was less than 35.5 degrees C, whereas the threshold equaled or exceeded this value in all younger patients (P = 0.0002). CONCLUSIONS: Age-dependent inhibition of autonomic thermoregulatory control in the elderly might be expected to result in hypothermia. That it usually does not suggests that behavioral regulation (e.g., increasing ambient temperature, dressing warmly) compensates for impaired autonomic control. Elderly patients undergoing spinal anesthesia, however, may be especially at risk of hypothermia because low core temperatures may not trigger protective autonomic responses. Furthermore, hypothermia in the elderly given regional anesthesia may not be perceived by the patient (who typically feels less cold after induction of the block), or by the anesthesiologist (who does not observe shivering). Consequently, temperature monitoring and management usually is indicated in these patients.     

Reevaluation of spinal anesthesia in elderly people--an evaluation of circulatory changes

Appropriate methods of anesthesia for the elderly people are being discussed as the ratio of elderly people in our society increases. During spinal anesthesia, hypotension was frequently observed in patients with hypertension, arteriosclerosis, coronary deficiency, and so on. It is also difficult to pass the needle between degenerated vertebrae. However, general inhaled anesthesia accompanies the respiratory complications and consciousness derangement after surgical operations more frequently than after spinal anesthesia. In this study, circulatory conditions during spinal anesthesia in elderly people (30-91 years old) were analyzed in 109 cases of spinal anesthesia. Hypotension occurred about 10 minutes and 40-60 minutes after injection of anesthetics and was frequent in patients of high aged group, but tachycardia was not observed among them. In addition, their blood pressure in the recovery room could not recover to the level before anesthesia. It is thought that hypotension during spinal anesthesia was induced by the vascular dilatation caused by sympathetic nerve block and the deficiency of reflective venous constriction in upper extremities and abdominal organs. Tachycardia may also produce hypotension. However, the reflexive vasoconstriction and tachycardia are thought to be poor on account of arteriosclerosis and down regulation of beta-receptor in elderly people. Therefore, during spinal anesthesia in the elderly people, the catecholamine released by the surgical stimulation could not increase blood pressure effectively. To prevent hypotension during spinal anesthesia in elderly people, it is advisable to employ the treatment for upregulation of beta-receptor before anesthesia and the administration of alpha . beta-receptor, epinephrine and dopamine for control of blood pressure during spinal anesthesia.     

The use of a GnRH antagonist (Cetrorelix) in a single dose protocol in IVF-embryo transfer: a dose finding study of 3 versus 2 mg

New gonadotrophin-releasing hormone (GnRH) antagonists, which allow suppression of luteinizing hormone (LH) surges, have recently become available. We compared in this study the results of a single administration of 3 versus 2 mg Cetrorelix in 65 patients undergoing ovarian stimulation and in-vitro fertilization (IVF). The GnRH antagonist (Cetrorelix) was non-randomly administered at a dose of 3 mg (34 patients) or 2 mg (32 patients) on day 8 of the stimulation cycle. In the case of slow follicular development, the injection was delayed until oestradiol reached 400 pg/ml. No difference was observed in the decrease in LH and in oestradiol secretion between the 3 and the 2 mg groups, but the LH secretion was suppressed for a shorter time in the 2 mg group. No LH surge was observed in the 3 mg group, while one surge (3%) and one significant rise in LH were observed in the 2 mg group. No significant difference was observed in IVF results in the two groups of patients. This study demonstrates that a single injection of 3 or 2 mg successfully prevents LH surges for at least 3 days in all the patients treated. The LH rises in the 2 mg group led us to choose the 3 mg dose as a safer dose in our single administration protocol.     

Heart rate variability and the prone position under general versus spinal anesthesia

A rare case of amniotic disease with extensive malformations of fetus was described. A data obtained from literature was done with special consideration of etiopathology.     

Atraucan: a new needle for spinal anesthesia

BACKGROUND AND OBJECTIVES: Atraucan 26-gauge spinal needles have a tip designed to make a small linear cut (as opposed to a V-shaped cut) in the dura mater. The cut is shorter than the outside diameter of the needle and is dilated as the needle passes through the dura. The needle is used with a 20-gauge introducer. In vitro, it causes less leakage of cerebrospinal fluid than Quincke 26-gauge or Sprotte 24-gauge needles. This study was designed to test the ease of use and any damage caused to the needle tip during lumbar dural puncture. METHODS: This was a multicenter trial (six centers in five countries) involving 362 patients undergoing spinal anesthesia. A detailed questionnaire was filled in for every patient by the anesthesiologist. All the needles were returned to the factory and examined microscopically for damage. RESULTS: Lumbar dural puncture was successful in all but one patient. Spinal anesthesia was satisfactory for the planned surgery in 97%. Microscopy of the needle tips showed only a minor degree (0.01-0.19 mm) of bending in 14%, and none of the tips had a "hook." Postdural puncture headache (PDPH) occurred in nine patients (2.5%), all but one of whom (a 15-year-old male) were females under 55 years of age. CONCLUSIONS: The Atraucan needle is easy to use and has a high success rate in identifying the subarachnoid space. Lumbar dural puncture causes minimal damage to the tip. The incidence of PDPH is low, but a larger comparative study needs to be performed.     

Urinary excretion and bactericidal activities of a single oral dose of 400 milligrams of fleroxacin versus a single oral dose of 800 milligrams of pefloxacin in healthy volunteers

Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin, N-demethyl-fleroxacin, and N-oxide-fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects' urine not supplemented with broth was used. With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h; against the E. coli strain for which the MIC was 0.5 microgram/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was 16 micrograms/ml) of both antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for Proteus mirabilis of pefloxacin are significantly higher than those of fleroxacin. For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval. The same is true for Enterococcus faecalis. Against Staphylococcus saprophyticus, UBTs were present for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore, it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections; this should be substantiated in comparative clinical trials.     

Complex effects of general anesthesia on sensory processing in the spinal dorsal horn

A chronic animal preparation allowed us to compare activity of the same single, spinal dorsal horn neurons in the physiologically intact, awake, drug-free state and in the anesthetized state. The inhalation anesthetic enflurane produced profound, and at times, opposite effects on spinal dorsal horn neuron responses to non-noxious and noxious receptive field stimulation. Some effects would not have been predicted, based upon current understanding of anesthetics.     

Adverse effects of a single dose of (+)-sotalol in patients with mild stable asthma

The case history of a 25-year-old man suffering from idiopathic alveolar proteinosis is described. The patient showed a prolonged stable mild disease and a distinct suppressive phenotypic profile of BALF lymphocytes. Specifically, a low T4/T8 ratio and a high percentage of CD11b+ T8 lymphocytes was found. Correlations with disease expression are made.     

Changes of NGF in injured spinal cord following treatment with a single large dose of methylprednisolone sodium succinate

Nerve growth factor (NGF) was detected by ABC-ELISA in rat normal spinal cord, spinal cord with mild contusion of 25gcm, and that with mild contusion plus a single intramuscular injection of large dose of methylprednisolone sodium succinate (MPSS) (80 mg/kg). The mean preinjury NGF level in spinal cord was 10.2 +/- 2.8ng/g. Following injury, NGF level in spinal cord began to increase progressively. NGF level in spinal cord without treatment was attenuated to 30.32 +/- 0.32, 89.51 +/- 2.14, 66.02 +/- 1.51, 50.32 +/- 1.23 and 46.23 +/- 1.42ng/g at 4, 7, 14, 21 and 28 days respectively, while in cord spinal with MPSS treatment it was 121.98 +/- 4.05, 119.56 +/- 1.45, 80.39 +/- 1.50, 68.31 +/- 0.77 and 59.86 +/- 0.97 ng/g at 4, 7, 14, 21 and 28 days, respectively. This result suggests that a single large dose of MPSS enhances NGF level in injured spinal cord with a peak at day 4. The implication of this article is that the changes of NGF level in spinal cord are relevant to spinal cord self-recovery.     

Cerebral energy levels during trimethaphan-induced hypotension in the rat: effects of light versus deep halothane anesthesia

Hypotension may be expected to produce less perturbation of metabolism in the brain when cerebral metabolic rate is lowered by deep anesthesia. Male Wistar rats having unilateral carotidartery ligation were exposed to mean arterial pressure (MAP) of 40 torr for 22 min by an intravenous infusion of trimethaphan during anesthesia with halothane, 0.6 or 2 per cent, in oxygen. Cortical tissue metabolite levels on the side of the ligated carotid artery were more abnormal in rats receiving halothane, 0.6 per cent, than in those receiving halothane, 2 per cent. Values at halothane, 0.6 per cent, were adenosine triphosphate (ATP), 1.71 +/- 0.05 (+/-SEM) mumol/g, phosphocreatine (PCr) 1.97 +/- 0.07 mumol/g. and lactate 16.5 +/- 5.1 mumol/g; corresponding values at halothane, 2 per cent, were ATP 2.27 +/- 0.02, PCr 4.02 +/- 0.23, and lactate 4.75 +/- 0.9 mumol/g. ATP and PCr values were significiantly lower (P less than 0.05) and the lactate value was significantly higher with halothane, 0.6 per cent, than with halothane 2 per cent. Cerebral oxygen consumption decreased 47 per cent in rats anesthetized with halothane, 2 per cent. Preservation of cortical metabolite levels in deeply anesthetized animals suggests a protective effect of cerebral metabolic depression.     

Influence of renal failure on the pharmacokinetics and neuromuscular effects of a single dose of rapacuronium bromide

Neurotransmitter transporters are involved in termination of the synaptic neurotransmission and are implicated as the sites of action of antidepressant medicines and illicit drugs. In addition to their function in neurotransmission, neurotransmitter transporters play a key role in neuroregulation and brain development. In this report, the developmental distribution of the "orphan" transporter NTT4, whose substrate has not yet been shown, is described. Immunohistochemical studies have previously shown NTT4 to be specifically and widely localized to the central nervous system. In this report, the distribution of NTT4 in brain areas enriched in glutamatergic and gamma-aminobutyric acid-ergic innervations is further substantiated. NTT4 is detected beginning at E18 in various parts of the rat brain, including the cerebral cortex, fimbria hippocampi, fornix, lateral lemniscus, anterior commissure, and spinal cord. At E18, strong immunoreactivity of NTT4 is observed in the cortical subplate and marginal layers that later develops into the fimbria hippocampi, and at P22, the expression of NTT4 in the hippocampal formation reaches the mature form. The expression of NTT4 in the spinal cord begins at E18 in the ventral white matter. Heavy staining for NTT4 is observed in the substantia nigra since birth and through all time points examined. Transient immunoreactivity is observed in the inferior colliculus, reaching maximal expression at P10, whereas the superior colliculus commences to express NTT4 only after this time point. The globus pallidus is highly stained after birth, and the caudate putamen shows strong staining for NTT4 only at P22. In the adult rat brain, NTT4 is strongly expressed in the olfactory bulb, cerebral cortex, striatum, hippocampus, thalamus, substantia nigra, pontine nucleus, cerebellum, and spinal cord. The developmental distribution of NTT4 suggests involvement in central nervous system maturation.     

The assessment of residual effects of a single dose of diazepam on visually-defined EEG patterns

Patients with medically intractable trigeminal neuralgia characterized by paroxysmal, triggered, trigeminally distributed pain are excellent candidates for neurosurgical intervention, which can not only relieve the pain of trigeminal neuralgia, but also eliminate the unpleasant side effects of medicines used to treat it. The two major neurosurgical choices are percutaneous denervation and microvascular decompression (MVD). Percutaneous denervation is done best when the surgeon has available radiofrequency and glycerol and uses one, the other, or both depending on technical circumstances that pertain to each patient. The percutaneous denervation is less likely than MVD to cause death, stroke, facial weakness, or hearing loss, but more likely to be associated with recurrence or dysesthesias. Patients with multiple sclerosis, medical illness, or who are elderly are much better candidates for percutaneous denervation. For any patient, a number of other factors also must be considered before deciding on a particular procedure. These include response to previous interventions, ability to tolerate carbamazepine, risk tolerance for various complications, preference regarding duration of hospital stay and postoperative recovery, presence of pain outside the trigeminal distribution, and findings on a high resolution magnetic resonance imaging (MRI) scan.