Control of post anaesthetic shivering with nefopam hydrochloride in mildly hypothermic patients after neurosurgery

Postoperative shivering may be prevented by maintaining normothermia intraoperatively or it may be treated using specific drugs. The aim of this study was to compare the efficacy of nefopam hydrochloride (nefopam) to that of clonidine and meperidine in patients undergoing elective neurosurgical procedures. Three groups of patients were included in the study. Patients in group A (60) received i.v., at random, 20 mg of nefopam, 50 mg of meperidine or 150 μg of clonidine in the immediate postoperative period. The incidence of shivering and the time at which shivering ceased were noted, along with central temperature and main haemodynamic changes. Group B (20) received i.v., at random, either 10 mg of nefopam or saline before awakening from anaesthesia. The effects of nefopam on central temperature, oxygen consumption (Vo₂), carbon dioxide production (VcO₂), basal metabolic rate (BMR) and energy expenditure (EE) were investigated. Group C (10) received i.v. 20 mg of nefopam during surgery: cerebrospinal fluid pressure (CSFP), cerebral perfusion pressure (CPP) and electroencephalogram (EEG) were monitored. In group A nefopam stopped shivering in 95% of patients when compared to meperidine and clonidine, which were effective in 32% and 40% of patients respectively. In group B, only 10% of patients receiving nefopam had postoperative shivering, Vo2, VcO2 and EE were significantly lower in patients treated with nefopam than those in the control group. No changes in CSFP, CPP or EEG were observed in group C. In conclusion, nefopam seems to be more effective than clonidine or meperidine in quickly suppressing shivering, without producing significant adverse reactions.     

Effects of systemic clonidine on auditory event-related potentials in squirrel monkeys

Event-related potential (ERP), electroencephalographic (BEG), and behavioral data were collected from squirrel monkeys (Saimiri sciureus) in a 90−10 auditory oddball paradigm. Background or target tones were presented once every 2 s, and responses to the targets were rewarded. ERPs were recorded from epidural electrodes following systemic administration of clonidine (0.1 mg/kg) or a saline placebo. EEG power spectra and behavioral performance were assessed simultaneously as indices of behavioral state. Clonidine significantly decreased the area and increased the latency of a P300-like potential. The amplitudes and areas of the earlier P1, N1, and P2 components and a later slow wave-like potential were not reduced, nor were their latencies altered. Clonidine produced increased EEG power in the alpha range (7.5–12 Hz) and decreased power in the upper beta range (20–40 Hz) but did not affect performance in the oddball task. Because two major effects of clonidine are to substantially reduce activity in the noradrenergic nucleus locus coeruleus (LC) and to reduce norepinephrine (NE) release from axons, the present results support the hypothesis that the LC and its efferent projection system are important in modulating the activity of P300-like potentials.     

可乐定透皮贴剂联合芬太尼静脉自控镇痛用于原发性高血压病人术后镇痛

目的 观察可乐定透皮贴剂联合芬太尼静脉自控镇痛(PCIA)用于原发性高血压(EH)病人术后镇痛的效果.方法 择期全麻下行腹腔镜胆囊切除术病人60例,均合并EH,依据术后镇痛方法的不同,随机均分为三组,肌注哌替啶组(P组)、芬太尼PCIA组(F组)和可乐定透皮贴剂联合芬太尼PCIA组(CF组).使用芬太尼1.0mg稀释至100ml,PCIA均采用负荷量-持续背景量-PCA量模式,背景剂量芬太尼20 μg/h,PCA追加剂量5 μg,锁定时间15 min.记录病人术后镇痛4、8、24、48 h VAS及Ramsay镇静评分,并记录不良反应和处理措施.监测入院时、术后24、48 h血浆内皮素(ET)及降钙素基因相关肽(CGRP)浓度、血糖(Glu),同时记录MAP、HR.结果 镇痛期间F、CF组VAS低于P组(P<0.01),CF组低于F组(P<0.05).Ramsay镇静评分F组高于P组(P<0.01),CF组高于F组(P<0.05),三组均无过度镇静.CF组MAP、HR术后较入院时明显降低(P<0.01),血浆ET、血浆CGRP浓度与入院时比较差异无统计学意义.术后ET、Glu浓度和MAP、HR F组低于P组,CGRP浓度高于P组(P<0.05).术后ET、Glu浓度和MAP、HR P组>F组>CF组;术后CGRP浓度:CF组>F组>P组(P<0.05).不良反应发生率三组差异无统计学意义.结论 对高血压病人,可乐定透皮贴剂增强芬太尼PCIA镇痛作用,使血流动力学更稳定.     

Role of noradrenergic hyperactivity in neonatal opiate abstinence

Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the α2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.     

An evaluation of Tourette Syndrome and medication use in Canada

Self-report data were gathered from a national sample of over 200 Canadian Tourette Syndrome (TS) patients. Information regarding symptom severity both on and off medication was gathered along with an analysis of different medications in use, and patient ratings of effectiveness of those medications. Patients also rated their own mental health. Results indicated that approximately 60% of TS patients take some form of medication for relief from their symptoms. Of these, over 80% reported that symptoms are less severe when medicated. The most commonly prescribed medications in order of popularity are haloperidol, pimozide, clonidine and benztropine mesylate (Cogentin). Patient ratings of effectiveness of these medications places haloperidol first, pimozide second and clonidine third although all were found to be "somewhat" to "very" effective. Of those TS patients on medications, 50% rated their own mental health as good to excellent and 50% rated it as fair to poor.     

Interaction between clonidine and physostigmine in normal rats and in rats after sinoaortic denervation

Summary Clonidine (3–30 g · kg^–1, i.v.) induced a fall in mean arterial pressure in rats after sinoaortic denervation but not in sham-operated animals. Moreover, sinoaortic denervation reduced the bradycardic action of this antihypertensive drug. Pressor and tachycardic response to physostigmine (60 g · kg^–1, i.v.) were greater in denervated than in sham-operated rats. The increase of mean arterial pressure was 26.2 ± 2.2 mm Hg in sham-operated rats (n = 12) and 53.8 ± 2.0 mm Hg in denervated rats (n = 12, P < 0.005).Pretreatment with 3 g · kg^–1 (i. v.) of clonidine did not alter the pressor response to physostigmine (60 g · kg^–1) in either of the two groups; 10 and 30 g · kg^–1 of clonidine reduced the physostigmine-induced increase of mean arterial pressure in sham-operated rats but enhanced the pressor response in denervated animals. Furthermore, an ineffective dose of physostigmine (30 g - kg^–1 i.v.) induced a pressor response after pretreatment with clonidine (10 gg · kg^–1) in denervated rats.Clonidine (10 g · kg^–1) did not affect the pressor effect of 1,1 dimethyl-4-phenylpiperazinium iodide (DMPP: 50 g · kg^–1 i.v.) or phenylephrine (4 g · kg ^–1, i.v.) in either group.The anticholinergic effect of clonidine in sham-operated rats may be explained by an inhibitory action on the release of acetylcholine in several brain structures but the facilitatory effect of clonidine observed in denervated animals is not clear. The results did not suggest a peripheral involvement in this facilitatory effect. Send offprint requests to M. A. Enero at the above address     

Evaluation of the clonidine-suppression test in the diagnosis of pheochromocytoma

Summary In this study we examined the preoperative value of the clonidine-suppression test in 15 patients with surgically proved pheochromocytomas. The result of the clonidine-suppression test was pathological (epinephrine plus norepinephrine above 500 ng/l 3 h after clonidine) in 10 of 15 patients (66%). These patients had relatively large tumors and higher basal norepinephrine plasma levels. Out of the 5 cases without a pathological clonidine test 4 had normal basal plasma catecholamine levels with the result that the clonidine test could not be properly applied and 1 case produced a false negative result. These 5 cases generally had smaller tumors and lower plasma catecholamine levels. Two of these cases had basally raised epinephrine values. The other three cases had either a paradoxical increase or a suspiciously low fall (less than 25%) in norepinephrine within the normal range. We conclude that the clonidine-suppression test is only reliable for the diagnosis of relatively large pheochromocytomas.Abbreviations MIBG metaiodobenzylguanidine - HPLC High-performance liquid chromatography     

Selective impairment of paired associate learning after administration of a centrally-acting adrenergic agonist (clonidine)

Eight normal volunteers had IV infusions of 200 g clonidine (a centrally-acting adrenergic agonist which reduces noradrenaline release), and saline in a double-blind cross-over design. Clonidine reduced subjective estimates of arousal but did not affect performance on the Digit Symbol Substitution Test. Clonidine impaired pairedassociate learning, but it did not affect performance on a number of measures of short and long term memory. The findings suggest either 1) that there is a specific (adrenergic) mechanism involved in the acquisition of novel associations, but not in other types of learning, or 2) that paired associate learning is more vulnerable than other learning tasks to disruption of adrenergic transmission.     

Increase in insulin response to glucose in the rat chronically treated with clonidine

Summary Effect of chronic clonidine treatment on the response to glucose of rat pancreatic B-cells was investigated. Clonidine treatment was carried out for 10 days by dissolving the drug into drinking water at a concentration of 10 g/ml. Control rats were given drug-free tap water. Serum insulin responses to glucose (750 mg/kg, i. v.) of clonidinetreated rats were much smaller than those of control rats. However, after 1 day's withdrawal of clonidine, the rise in the serum insulin level induced by glucose was approximately 2-fold larger in clonidine-treated rats as compared to that in control rats. Since clonidine treatment decreased body weight of the rat by 10%–20% in 10 days, the same experiments were carried out with rats whose body weight loss was made comparable to that of clonidine-treated rats by restricting food for 10 days. Then, some animals of the group thus treated had food-restriction discontinued for 1 day. In both of the above two groups, no increment in glucoseinduced rise in serum insulin level was observed. Islets of Langerhans isolated from clonidine-treated rats showed pronounced insulin releasing capacity in response to glucose. Insulin content per islet of the clonidine-treated rat was slightly larger than that of control rat. These results indicate that the enhancement of serum insulin response to glucose following clonidine treatment is mainly attributable to the hyper-responsiveness developed in the pancreatic B-cells.