Clinical supervision for specialist nurses

Clonidine is a selective alpha 2 adrenergic receptors agonist with a wide spectrum of activity. Except well known hypotensive effect, clonidine stabilizes circulatory system and has sedative, anxiolytic, analgesic, diuretic etc. activities. Clonidine has some appliance during perioperative period. When used in premedication it has a lot of advantages: causes sedation, has anxiolytic properties, reduces secretion of saliva, stabilizes circulatory system, diminishes stress reaction, augments action of anaesthetic and analgesic drugs. When used during the operation, regulates circulatory system, prolongs and amplifies central and peripheral blocks. Clonidine diminishes patients requirement for opioids and local anaesthetics during postoperative and long-term pain therapy.     

Oral clonidine premedication reduces vomiting in children after strabismus surgery

This is a prospective randomized double-blind trial conducted to determine whether preoperative orally administered clonidine causes or potentiates postoperative vomiting in 140 children (3-12 yr) undergoing strabismus surgery. They were all inpatients and classified randomly into four groups (n = 35 each); placebo (control), diazepam 0.4 mg.kg-1, clonidine 2 micrograms.kg-1, and clonidine 4 micrograms.kg-1. These agents were administered 93-112 min (mean; 100 min) before the anticipated time of induction of anaesthesia. All children received inhalational anaesthesia with halothane and nitrous oxide in oxygen. Muscle relaxation in all patients was obtained with vecuronium and residual neuromuscular blockade was antagonized with neostigmine and atropine before tracheal extubation. Diclofenac suppository was prescribed to prevent postoperative pain. No opioids or postoperative antiemetics were administered. All children remained in hospital for two days postoperatively. The incidence and frequency of vomiting were compared in the groups with Kruskall-Wallis Rank test. Clonidine 4 micrograms.kg-1 caused a lower incidence and frequency of vomiting than did placebo and diazepam (incidence and frequency: 11% and 1.37% and 3, and 34% and 2 in clonidine 4 micrograms.kg-1, placebo, and diazepam, respectively; P < 0.05 for clonidine 4 micrograms.kg-1 vs placebo and diazepam). However, low-dose clonidine was ineffective. These data suggest that preanaesthetic medication with clonidine 4 micrograms.kg-1 may be useful for preventing emesis following strabismus surgery. This property of clonidine indicates that it may be superior to other sedative premedicants such as diazepam and midazolam.     

Basic evaluation of post-anal preoperative pulmonary mechanism in heart surgery patients under extracorporeal circulation

Effects of clonidine on blood pressure, heart rate and rectal temperature in conscious rats were examined. Clonidine (0.1-1 mg/kg s.c.) caused a prevailing pressor response and dose-dependently a fall in heart rate and body temperature. The pressor response to clonidine (0.3 mg/kg s.c.) was completely reduced by phentolamine (10 mg/kg s.c.), chlorpromazine (10 mg/kg s.c.) but not by hexamethonium (30 mg/kg i.p.), guanethidine (30 mg/kg s.c.) or reserpine (5 mg/kg s.c. 18 hr + mg/kg i.p. 4 hr prior to clonidine). Conversely, a remarkable potentiation of the pressor response to clonidine was observed after treatment with reserpine. The bradycardia with clonidine (0.3 mg/kg s.c.) was significanlty reduced by phentolamine, chlorpromazine or atropine (5 mg/kg s.c.) but was potentiated by reserpine. The hypothermia with clonidine (0.3 mg/kg s.c.) was not influenced by phentolamine or atropine but was significanlty potentiated by chlorpromazine. From the above results it is suggested that the prevailing pressor response to clonidine in conscious rats is due to a stimulation of peripheral alpha-adrenoceptors, the bradycardia with clonidine is exerted through the sympathetic pathway and the baroceptor-vagal reflex, and that the hypothermia with clonidine is mainly due to the central mechanism.     

Phosphofructokinase interacts with molecular chaperonins GroEL and GroES

OBJECTIVE: The present investigation was designed to provide the first empirical examination of the effects of clonidine, a selective alpha 2-adrenergic agonist, on sexual arousal in women with and without prior sympathetic nervous system [SNS] stimulation by exercise. The purpose was to help elucidate the influence of adrenergic mechanisms on sexual function in women. METHODS: Thirty sexually functional women participated in two experimental sessions in which subjective (self-report) and physiological (vaginal photoplethysmograph) sexual responses to erotic stimuli were measured after either clonidine (0.2 mg) or placebo administration in a randomized, double-blind, crossover protocol. Before viewing the experimental films, 15 subjects engaged in 20 minutes of intense exercise designed to elicit significant SNS activation. RESULTS: Clonidine significantly decreased vaginal pulse amplitude, vaginal blood volume, and subjective sexual responses to the erotic films in subjects who were in a state of heightened (via exercise), but not baseline (no exercise) SNS arousal. CONCLUSIONS: Clonidine can significantly inhibit subjective and physiological sexual arousal in women. These findings have implications for deriving an etiological theory of sexual function in women and for understanding the effects of psychotherapeutic drugs on female sexual function.     

Centrally acting sympathetic inhibitors for therapy of patients with hypertension

The blood pressure is maintained by the tonic vasomotor activity of efferent sympathetic neurons which are tonically regulated by the rostral ventrolateral medulla (RVLM) in the brain. The alpha 2-adrenoceptor agonist such as clonidine, guanabenz and guanfacine, acts on RVLM to decrease sympathetic neuron activity and lower blood pressure. Drug such as alpha-methyldopa, through its metabolite alpha-methylnoradrenaline, acts like clonidine as an alpha 2-adrenoceptor agonist in the brain. Clonidine and allied drugs except for alpha-methyldopa also bind to imidazoline receptors, which is believed to mediate the hypotensive action. The centrally acting antihypertensive drugs are used for treatment of moderate to severe forms of hypertension and are effective in patients with renal failure. The treatment with these drugs induces central nervous system side effect of sedation and drowsiness, which limits the clinical usefulness and are believed to be mediated by central alpha 2-adrenoceptors. The new imidazoline compounds, rilmenidine and moxonidine, which selectively act on imidazoline receptors, may be a useful antihypertensive drug without such central side effects.     

Clonidine and ketanserin both are effective treatment for postanesthetic shivering

BACKGROUND: Although meperidine is an effective treatment of postanesthetic shivering, its mechanism of action remains unknown. Investigation of other drugs might help clarify the mechanisms by which shivering can be controlled. Accordingly, we investigated the efficacy of clonidine, an alpha 2-adrenergic agonist, and ketanserin, a 5-hydroxytryptamine antagonist, in treating postanesthetic shivering. METHODS: First, 54 patients shivering after general anesthesia were allocated randomly to receive an intravenous bolus of saline, 150 micrograms clonidine, or 10 mg ketanserin. A second study explored the dose-dependence of clonidine. Forty shivering patients were given saline or clonidine, 37.5, 75, or 150 micrograms. RESULTS: The duration of shivering was significantly shorter in those given clonidine (2.1 +/- 0.9 min) than in the other two groups and shorter in the ketanserin group (4.3 +/- 0.9 min) than in the saline group (12.0 +/- 1.6 min). Clonidine and ketanserin significantly decreased systolic arterial blood pressure when compared to saline. Core rewarming was significantly slower in the clonidine group. In the second study, 37.5 micrograms clonidine was no more effective than saline. Two minutes after treatment, 150 micrograms obliterated shivering in all patients. Five minutes after treatment, all patients given 75 micrograms had stopped shivering. Systolic arterial pressure and heart rate decreased significantly in patients given 75 and 150 micrograms clonidine. CONCLUSIONS: Clonidine (150 micrograms) and ketanserin (10 mg) both are effective treatment for postanesthetic shivering. The effect of clonidine on shivering is dose-dependent: whereas 37.5 micrograms had no effect, 75 micrograms clonidine stopped shivering within 5 min.     

Oral clonidine premedication reduces minimum alveolar concentration of sevoflurane for tracheal intubation in children

BACKGROUND: Sevoflurane is a useful anesthetic for inhalational induction in children because of its low solubility in blood and relatively nonpungent odor. Clonidine has sedative and anxiolytic properties and reduces the requirement for inhalation agents. Nitrous oxide (N2O) also decreases the requirement of inhaled anesthetics, but the effect is variable. The minimum alveolar concentration for tracheal intubation (MAC(TI)) of sevoflurane was assessed with and without N2O and clonidine premedication. METHODS: Seventy-two patients, aged 3-11 yr, were assigned to one of six groups (n = 12 each). They received one of three preanesthetic medications (two groups for each premedication): placebo (control), 2 microg/kg oral clonidine or 4 microg/kg oral clonidine. In one group of each premedication, anesthesia was induced with sevoflurane in oxygen; in the other group, anesthesia was induced with sevoflurane in the presence of 60% N2O. Each concentration of sevoflurane at which tracheal intubation was attempted was predetermined according to Dixon's up-and-down method and held constant for at least 20 min before the trial RESULTS: The MAC(TI) of sevoflurane in the absence of N2O (mean +/- SEM) was 3.2 +/- 0.2%, 2.5 +/- 0.1%, and 1.9 +/- 0.2% in the control, 2-microg/kg clonidine, and 4-microg/kg clonidine groups, respectively. Nitrous oxide (60%) decreased the MAC(TI) of sevoflurane by 26%, 24%, and 27% in the control, 2-microg/kg clonidine, and 4-microg/kg clonidine groups. CONCLUSIONS: Oral clonidine premedication decreased the MAC(TI) of sevoflurane. Nitrous oxide also decreased the MAC(TI). The combination of clonidine and N2O lessened the MAC(TI) of sevoflurane more than did either drug alone.     

Effects of clonidine on power spectral analysis of heart rate variability in mild essential hypertension

Patients with essential hypertension often show alterations of the autonomic nervous system. We evaluated the sympathetic and parasympathetic drive to the heart in 12 mildly hypertensive patients and 9 healthy subjects by power spectral analysis of heart rate variability. All subjects underwent measurements of RR interval, low (LF) and high frequency (HF) components of heart rate variability, LF/HF ratio and blood pressure in the resting and sitting positions, both before and after oral clonidine (300 microg), a central sympatholytic agent. In the supine position before clonidine, hypertensive patients had higher blood pressure and lower HF values than healthy subjects. Clonidine induced increases in RR interval and HF in both groups, while LF and LF/HF ratio decreased in healthy subjects, but not in hypertensive patients. On assuming the sitting position, both groups showed reductions in RR and HF and increments in LF and LF/HF. In healthy subjects, the response to the postural challenge was unaffected by clonidine. In contrast, hypertensive patients showed no changes in LF and LF/HF ratio, and a significantly lower decrease in HF. These differences were probably due to the existence of two subsets of patients, one exhibiting similar responses to clonidine as healthy subjects, and the other showing no appreciable response to the drug. These results suggest that hypertensive patients have an altered sympatho-vagal balance to the heart, which can be unmasked by clonidine. This phenomenon should be taken into account to achieve a better control of the overall cardiovascular risk of hypertensive patients.     

The effect of alpha2-adrenergic drugs on the activity of neurons in the rat nucleus raphe magnus in vitro

The nucleus raphe magnus (NRM) is an important descending inhibitory system for pain transmission. We tested whether clonidine, an alpha2-adrenergic agonist, and yohimbine, an alpha2-adrenergic antagonist, modulate the activity of NRM neurons using extracellular recording in a rat brainstem slice preparation. Clonidine 1-20 microM increased firing frequencies (FF) in 22 (37%) and decreased FF in 6 (10%) spontaneously active neurons. Correlation between the concentrations of clonidine and FF changes was unremarkable. Eight spontaneously active neurons (13%) showed increases followed by decreases in FF with increasing doses of clonidine. The remaining 24 neurons (40%) showed no change in FF. Yohimbine 1 microM decreased FF in 38 spontaneously active neurons (58%), whereas the remaining 27 neurons (42%) showed no change in FF. In some neurons, yohimbine antagonized the increase or decrease in FF by application of clonidine. In three silent neurons (25%), clonidine (5 or 10 microM) induced firing activity, which stopped or decreased with the increasing doses of clonidine. In the remaining nine neurons (75%), clonidine did not induce firing activity. We conclude that activation and inhibition of alpha2-adrenergic receptors of NRM neurons augments and suppresses output of the descending inhibitory pain pathway. Implications: The nucleus raphe magnus is implicated in descending control of the nociceptive processes. We found that clonidine and yohimbine increased and decreased, respectively, the firing activity of a substantial number of nucleus raphe magnus neurons. Clonidine and may facilitate and yohimbine may reduce the outflow of the descending inhibitory pathway.     

Carcinoma of the vulva in women: clinical and morphopathological problems

1. To investigate the relationship between the autonomic drive to the heart and heart rate variability, as evaluated by power spectral analysis, we studied the effect of clonidine (300 microg), a central sympatholytic agent, on heart rate variability. 2. Six healthy subjects (mean age 31 +/- 3 years) were studied in the supine and the sitting position (15 min each) on two different occasions, respectively, before and after clonidine administration. Using an autoregressive approach, the low frequency (LF) and the high frequency (HF) components of power spectral analysis were measured, and their ratio was calculated. Blood pressure was monitored throughout the study and plasma catecholamines were measured at the end of each period. 3. Before clonidine, assumption of the sitting position induced increases in LF, LF/HF ratio, blood pressure and plasma noradrenaline. Clonidine induced remarkable reductions in the normalized values of the LF component and the LF/HF ratio in both the resting and the sitting position (supine: LF = -68%, LF/HF ratio = -80%; sitting: LF = -23%, LF/HF ratio = -55%) without affecting the central frequencies of LF and HF components. Blood pressure and plasma catecholamines also significantly decreased after clonidine. 4. These results support the hypothesis that the LF component of HRV, expressed in normalized units, is an indicator of the sympathetic control of the heart. In addition, this component seems to be largely of central origin, because it is markedly reduced by the central sympatholytic action of clonidine.     

Antagonism of clonidine injected intracerebroventricularly in different models of salt intake

Clonidine, an alpha 2-adrenergic agonist, injected into the brain inhibits salt intake of animals treated by the diuretic model of sodium depletion. In th present study, we address the question of whether central injection of clonidine also inhibits salt intake in animals deprived of water or in the need-free state. Saline or clonidine (30 nmol) was injected into the anterior third ventricle of 24-h sodium-depleted (furosemide + removal of ambient sodium), of 24-h water-deprived and of normovolemic (need-free state) adult male rats. Clonidine injected intracerebroventricularly (i.c.v.) inhibited the 1.5% NaCl intake for 1209 min by 50 to 90% in every model tested. Therefore, different models of salt intake are inhibited by i.c.v. injection of clonidine. Idazoxan, an alpha 2-adrenergic antagonist, injected i.c.v. at a dose of 160 nmol, inhibited the effect of clonidine only in the furosemide + removal of ambient sodium model of salt intake. This indicates that the antagonism of this effect by idazoxan is dependent on the body fluid/sodium status of the animal.     

Effects of sympathetic inhibition on receptive, proceptive, and rejection behaviors in the female rat

The present investigation was designed to examine the effects of sympathetic nervous system (SNS) inhibition on sexual behavior in ovariectomized, steroid-treated female rats. Clonidine, an alpha2-adrenergic agonist, guanethidine, a postganglionic noradrenergic blocker, and naphazoline, an alpha2-adrenoreceptor agonist were used to inhibit SNS activity. Intraperitoneal injections of either 33 micrograms/ml or 66 micrograms/ml clonidine significantly decreased receptive (lordosis) and proceptive (ear wiggles) behaviors and significantly increased rejection behaviors (vocalization, kicking, boxing). Either 25 mg/ml or 50 mg/ml guanethidine significantly decreased receptive and proceptive behavior and had no significant effect on rejection behaviors. Naphazoline significantly inhibited lordosis behavior at either 5 mg/ml or 10 mg/ml doses, significantly inhibited proceptive behavior at 5 mg/ml, and had no significant effect on rejection behaviors. These findings support the hypothesis that SNS inhibition decreases sexual activity in the female rat.     

Action of clonidine on the baroreceptor pathway and medullary sites mediating vagal bradycardia

In anaesthetized dogs, clonidine (10 mug/kg i.v.) increased the spontaneous firing of the carotid sinus nerve and decreased blood pressure and heart rate. After transection of the spinal cord, clonidine decreased heart rate and this bradycardia was abolished by selective baroreceptor denervation. Clonidine (1 mug/kg) injected into the vertebral artery of anaesthetized dogs, pretreated with a beta-adrenoceptor blocking agent (S 2395: 50 mug/kg i.v.) potentiated the bradycardia induced by stimulation of the carotid sinus nerve but did not change the hypotension and bradycardia produced by stimulation of the nucleus tractus solitarius or of the nucleus ambiguus. In anaesthetized cats with bilateral destruction of nuclei tractus solitarii, clonidine (10 mug/kg i.v.) decreased blood pressure and heart rate. Clonidine (2 mug/kg), injected into the vertebral artery of anaesthetized dogs pretreated with a beta-adrenergic blocking agent (S 2395: 50 mug/kg i.v.) or guanethidine, induced a bradycardia but the discharges of the carotid sinus nerve were not increased. Selective baroreceptor denervation abolished this bradycardia. In conclusion, these experiments provide direct evidence that the central facilitory effect of clonidine on baroreceptor impulses play a role in the bradycardic effect of the drug. This facilitation is likely localized in the nucleus tractus solitarius at the first synapse of baroreceptor fibres. The vagally mediated bradycardia can be explained by an increase in baroreceptor discharges and by the central facilitation of baroreceptor impulses. The site of the hypotensive effect of clonidine did not seem to be localized in the nucleus tractus solitarius.     

Clonidine for major vascular surgery in hypertensive patients: a double-blind, controlled, randomized study

The utility of clonidine for hypertensive patients presenting for major vascular procedures remains debatable. Twenty-one hypertensive patients presenting for aortic surgery were given clonidine (n = 11) or placebo (n = 10) in a double-blind, randomized manner. Clonidine was administered 6 micrograms/kg per os 120 min before induction of anesthesia and 3 micrograms/kg intravenously (i.v.) over 60 min from aortic declamping to skin closure. Anesthesia was induced with alfentanil 20 micrograms/kg, midazolam, and atracurium and maintained with nitrous oxide 70%, an alfentanil infusion (0.25 microgram.kg-1. min-1), and isoflurane. Anesthetic requirements, circulatory variables, interventions, and isoproterenol dose-response curves (pre- and postoperatively) were determined. Plasma concentrations of clonidine, alfentanil, and vasoactive hormones were measured. When the clonidine group was compared with the placebo group, (a) isoflurane, alfentanil, and midazolam requirements were reduced by 38%, 42%, and 41%, respectively (P = 0.04, 0.03, 0.0002, respectively); (b) supplemental circulatory and anesthetic adjustments were reduced by 51% (P = 0.0006); (c) interventions with vasopressors were not significantly increased (placebo: two; clonidine: five); (d) systolic and mean arterial pressures and heart rate were reduced; (e) increases in norepinephrine, epinephrine, and plasma renin activity were suppressed, whereas vasopressin surge was attenuated; and (f) chronotropic response to isoproterenol was unaffected. Clonidine was effective in reducing anesthetic requirements and in improving circulatory stability in hypertensive patients presenting for major vascular procedures.     

Inhibition of alpha1-adrenoceptor-mediated contractions in isolated tail arteries and aorta of the rat by alpha2-adrenoceptor agonists

The effects of alpha2-adrenoceptor agonists, clonidine, tizanidine and UK-14304 on alpha1-adrenoceptor-mediated contractile responses were studied in isolated tail arteries and thoracic aorta of the rat. When applied during sustained contractile responses to almost maximum concentration (10 microM) of phenylephrine, clonidine (0.3 microM to 100 microM) produced concentration-dependent relaxations in both tissues. The maximum relaxation was smaller in tail arteries than in thoracic aorta. Clonidine up to 100 microM failed to relax both tissues precontracted with KCl (60 microM) or U-46619 (1 microM), a thromboxane mimetic. The clonidine-induced relaxation in tail arteries, was reversed by alpha2-adrenoceptor antagonists, yohimbine and idazoxane. Effects of the alpha2-adrenoceptor antagonists were concentration-dependent (0.1 microM to 1 microM), but not in a competitive manner. On the other hand, the relaxation in thoracic aorta was not significantly antagonized by these alpha2-adrenoceptor antagonists. Tizanidine and UK-14304 also relaxed both tail arteries and thoracic aorta precontracted with phenylephrine. The characteristics of the relaxation and their antagonism by yohimbine in both arteries were similar to those induce by clonidine. In tail arteries, NG-nitro-L-arginine, a nitric oxide synthase inhibitor, at a concentration that completely inhibited acetylcholine-induced relaxations did not significantly affect the relaxation induced by clonidine. In contrast, the relaxation of thoracic aorta in response to clonidine was partly reduced in the presence of NG-nitro-L-arginine. These results indicate that the alpha2-adrenoceptor agonists selectively inhibit the contractions induced by phenylephrine in both tissues. Regional differences in the modes of the inhibition by the alpha2-adrenoceptor agonists exist.     

Comparative effects of central administration of naloxone and clonidine on the blood pressure and heart rate response to anterior and posterior hypothalamic stimulation

The purpose of this study was to examine the roles of brain opioid receptors, using the opioid receptor antagonist naloxone, and brain alpha 2 adrenergic and imidazole receptors, using their agonist clonidine, in the hypertension and tachycardia induced by electrical stimulation of the AHA and PHA area. Unanesthetized and unrestrained Wistar rats 300-400 g that had previously had catheters inserted into the lateral cerebral ventricle and femoral artery and electrodes in AHA or PHA areas received intracerebral (ICV) administration of naloxone or clonidine prior to hypothalamic stimulation. AHA and PHA stimulation with current strength from 0.5 to 2.0 mA produced a significant (p < 0.05) and dose dependent increase in BP and heart rate. Naloxone reduced the increase in BP with AHA stimulation at all but the highest stimulation current intensity. Clonidine also blunted the BP increase to AHA stimulation but to a lesser degree than naloxone. The combination of both naloxone and clonidine completely prevented the increase in BP even at high current intensities. Both naloxone and clonidine prevented the increase in heart rate with AHA stimulation. In contrast to AHA stimulation, naloxone did not alter the BP increase produced by PHA stimulation while clonidine prevented the effects of PHA stimulation. Heart rate did not increase with PHA stimulation. These data suggest that (i) the mechanisms involved in the hypertensive response to AHA are different from that of PHA. (ii) the endogenous opioid system is more operative in mediating the BP elevation produced by AHA but not PHA stimulation (iii) activation of the central alpha adrenergic or imidazole receptors can suppress hypertensive response to both AHA and PHA but is more effective for PHA than AHA stimulation.     

Tail pinching-induced hindlimb movements are suppressed by clonidine in spinal cord injured mice.

Experiments in completely spinal cord transected (Tx) cats have provided compelling evidence that clonidine combined with tail stimulation can promote locomotor function recovery. However, clonidine has generally failed to induce locomotor activity in other comparable animal models suggesting the existence of species- or condition-specific effects. This study aimed at investigating the effects of clonidine administered (0.25 or 5.0 mg/kg, i.p.) in mice during tail pinching in early (6-7 days post-Tx) or late (41-42 days post-Tx) paraplegic animals (Th9/10 level). Comparisons were made with the effects induced by 8-OH-DPAT (1.0 mg/kg, i.p.), a 5-HT1A/7 receptor agonist known to display prolocomotor effects. Clonidine with or without tail pinching failed to induce hind limb movements and even suppressed the frequency of spontaneously occurring nonlocomotor (NLM) and locomotor-like movements (LM) whereas tail pinching alone (prior to clonidine administration) increased the frequency of spontaneous movements specifically in late chronic animals. In turn, 8-OH-DPAT clearly induced hind limb movements that remained relatively unchanged during tail pinching. Altogether, the results suggest that the prolocomotor effects of clonidine reported elsewhere must depend upon stimuli or factors that remain to be identified. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of drugs on walking after spinal cord injury

Clonidine, a noradrenergic agonist, and cyproheptadine, a serotonergic antagonist, have each been associated with improved walking in SCI subjects. Baclofen, a GABA agonist, is frequently prescribed for spasticity but its effects on walking have not been well quantified. The objective of this study was to compare the effects of clonidine, cyproheptadine and baclofen on walking in SCI subjects with incomplete injuries. A motorized treadmill was used and harness support provided when necessary. A repeated single-subject design was employed for the twelve subjects. The greatest effects were found in more severely disabled subjects. Cyproheptadine was associated with greatly reduced need for assistance, increases in maximum treadmill speed (MTS) and reduced clonus. Clonidine was associated with increases in MTS and a generally more upright posture. Baclofen was associated with minor changes in walking. In many cases of drug effects, MTS increases and other changes were retained following washout of drugs. The significance and implications of the drug effects and the retention of effects during washout periods are discussed. It is concluded that clonidine and cyproheptadine have different effects but both appear useful for severely disabled SCI subjects. The effects of baclofen on walking after spinal cord injury remains unclear.     

Epidural epinephrine and clonidine: segmental analgesia and effects on different pain modalities

BACKGROUND: It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues. METHODS: Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 microg, in saline; clonidine, 8 microg/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined. RESULTS: Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve. CONCLUSIONS: Epidural epinephrine and clonidine produce segmental hypoalgesia. Clonidine bolus should be administered at a spinal level corresponding to the painful area. Clonidine inhibits temporal summation elicited by repeated electrical stimulation and may therefore attenuate spinal cord hyperexcitability.     

The effect of clonidine on cerebral blood flow velocity, carbon dioxide cerebral vasoreactivity, and response to increased arterial pressure in human volunteers

BACKGROUND: Because patients may be taking clonidine chronically or may be receiving it as a premedication before surgery, the authors investigated its effect on cerebral hemodynamics. METHODS: In nine volunteers, middle cerebral artery mean blood flow velocity (Vm) was measured using transcranial Doppler ultrasonography (TCD). CO2 vasoreactivity was measured before clonidine administration (preclonidine), 90 min after clonidine, 5 microg/kg orally, then following restoration of mean arterial pressure (MAP) to the preclonidine level. In addition, Vm was measured after a phenylephrine-induced 30-mmHg increase in MAP. RESULTS: After clonidine administration, Vm decreased from 62 +/- 9 to 48 +/- 8 cm/s (P < 0.01), and MAP decreased from 86 +/- 10 to 63 +/- 5 mmHg (P < 0.01; mean +/- SD). Clonidine decreased the CO2 vasoreactivity slope from 2.2 +/- 0.4 to 1.2 +/- 0.5 cm x s(-1) x mmHg(-1) (P < 0.05); restoring MAP to the preclonidine level increased the slope to 1.60 +/- 0.5 cm x s(-1) x mmHg(-1), still less than the preclonidine slope (P < 0.05). CO2 vasoreactivity expressed as a percentage change in Vm, decreased after clonidine, 3.5 +/- 0.8 versus 2.4 +/- 0.8 %/mmHg (P < 0.05); this difference disappeared after restoration of MAP, 3.1 +/- 1.2 %/mmHg. With a 30-mmHg increase in MAP, Vm increased by 13% before and after clonidine (P < 0.05). CONCLUSIONS: Clonidine, 5 microg/kg orally, decreases Vm and slightly attenuates cerebral CO2 vasoreactivity, therefore decreased cerebral blood flow and mildly attenuated CO2 vasoreactivity should be anticipated.