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Addition of Clonidine Increases Duration and Magnitude of Vasodilative Effect Induced by Sympathetic Block With Mepivacaine in Dogs
Abstract
The aim of this study is to examine the duration and magnitude of vasodilative effect induced by sympathetic block with the addition of clonidine to mepivacaine.
We measured mean arterial pressure (MAP), heart rate (HR), and right and left brachial artery blood flow (BABF) before and after stellate ganglion block (SGB) in dogs. The experimental protocol was designed as follows: (1) left SGB using 1.0 mL 0.5% mepivacaine (n = 6) and (2) left SGB using the addition of clonidine 0.5 microg to 1.0 mL 0.5% mepivacaine (n = 6).
MAP and HR did not change significantly throughout the study in either group. Left SGB with mepivacaine increased left BABF significantly from 10 minutes through 50 minutes after SGB (baseline, 100%; peak at 10 minutes after SGB, 176% +/- 28%; P <.01). Left SGB with the addition of clonidine to mepivacaine induced a significant increase of left BABF from 10 minutes through 70 minutes after SGB (baseline, 100%; peak at 10 minutes after SGB, 223% +/- 42%; P <.01). The values of left BABF after SGB with the addition of clonidine to mepivacaine were significantly higher than those of SGB with mepivacaine alone from 10 minutes through 80 minutes after SGB (P <.05). Right BABF decreased significantly after SGB throughout the study in both groups.
The addition of clonidine increases both duration and magnitude of the vasodilative effect induced by sympathetic block over that caused by mepivacaine alone.
... SGB increased brachial artery blood flow significantly in dogs. 12 2. Blood flow of the common carotid artery, lingual mucosa, mandibular bone marrow, and masseter muscle increased in rabbit SGB on the side of the block. 13 There is also a report that cervical sympathetic ganglion block increased blood flow, promoted repair of the intestinal epithelium, and improved the barrier function of the intestinal wall in the intestinal mucosa following radiation and burn injury in rats. ...
Unlabelled:
Lumbar sympathetic nerve block (LSNB) improves blood flow in the lower limbs and relieves pain involving the sympathetic afferents. This study examines the use of LSNB, but there are no reports of its use for the purpose of wound healing. Therefore, the authors planned the following study.
Methods:
An ischemic limb ulcer was created on both lower limbs using a rat model (N = 18). The rats were divided into three groups, namely, A, B, and C. Group A received LSNB on one side (N = 6). Group B was sprayed with basic fibroblast growth factor preparation (trafermin/fiblast) on one side (N = 6). Group C was used as a control (N = 6). Lower limb temperature and the ulcer area were measured over time in each group. Furthermore, the correlation between the ulcer temperature and the ulcer area reduction rate was analyzed.
Results:
Group A had higher skin temperature on the LSNB-treated side than on the nontreated side (P = 0.0022 < 0.05). Regarding the correlation between the average temperature and the ulcer area reduction rate, the correlation coefficient was as high as 0.691 in group A.
Conclusions:
In the LSNB group, the skin temperature increased and the ulcer area decreased significantly. Conventionally, LSNB has been used for pain relief purposes, although the authors consider that it will be useful in the treatment of ischemic ulcers and that it is a potential treatment option for future chronic limb ischemia/chronic limb-threatening ischemia cases.
... The literature shows ropivacaine to exhibit lower cardiotoxicity compared to other LAs, 28 while addition of clonidine prolongs the effect of the LA applied in peripheral nerve blocks 29 and prolongs and increases the vasodilative effect of SGBs in dogs. 35,36 Based on the literature, we recommend ropivacaine with addition of clonidine for us-SGB. ...
Background
Evaluating effectiveness of stellate ganglion blockades (SGBs) proves challenging as criteria defining a successful blockade, are controversial. This may be one reason for the scarcity of studies on this topic, thus forcing clinical guidelines to remain conservative in recommending SGBs. Moreover, factors to predict which patients benefit from blockade series, are not yet available.
Objectives
Objectives are to evaluate through a clinical approach SGBs’ effectiveness performed under ultrasound‐guidance (us‐SGB) and to identify factors to predict effectiveness.
Methods
This study retrospectively analyzes 809 us‐SGBs in 105 patients with complex regional pain syndrome (CRPS) and neuropathic pain syndromes (all potentially including sympathetically maintained pain) regarding pain reduction. Volume and type of local anesthetics, magnitude of pain, temperature of the dorsal hands, heart rate, blood pressure, and occurrence of Horner’s syndrome or complications were assessed.
Results
Pain reduction after blockade series was highly significant and showed no significant correlation with either change of temperature, vital signs, or Horner’s syndrome. For patients with neuropathic pain, predictive potential for pain reduction following a series lies within the range of pain reduction after the first blockade. In a literature comparison, incidences of complications (hoarseness 3.9 %, dysphagia 3.4 %, hematoma 0.6 %) were lower than in non‐ultrasound‐guided techniques.
Conclusions
Data indicate that us‐SGBs are safe and effective in reducing sympathetically maintained pain in patients with CRPS and neuropathic pain syndromes. Pain reduction after the first blockade may predict total pain reduction after a blockade series. Other clinical measures seem unsuitable to predict effectiveness.
... All single-shot USGNBs were performed with clonidine 15 µg as an adjuvant to prolong the duration of the action of local anaesthetic and for its vasodilatory properties which was beneficial in this patient. [15] To conclude, if bilateral stellate ganglion block is to be given in a patient it should always be with ultrasound guidance under strict monitoring. Block should be performed by experienced personnel. ...
Medical management along with stellate ganglion block is frequently given to prevent the vasculitis of fingers in patients of systemic lupus erythematosus (SLE). Bilateral stellate ganglion block is rarely given due to the concern of phrenic and recurrent laryngeal nerve palsy. In this article, we describe the management of a recently diagnosed SLE patient presented with progressive gangrene of fingers of both upper limbs. Meticulously planned serial bilateral ultrasound-guided stellate ganglion blocks were successfully given to prevent impending loss of digits with no complications.
... However, the clinical observation shows a significant venous dilation in the blocked limb. In an animal model, Yoshiyuki and Shinsuke (10) showed that stellate ganglion block increased HBF significantly from 10 minutes through 50 minutes after the block. ...
In this study we investigated and quantified the effects of interscalene block (ISB) on humeral arterial blood flow (HBF). Eleven patients scheduled for shoulder arthroscopic surgery under ISB were prospectively studied. A Doppler ultrasound of the humeral artery was performed before, and 30 min after, the ISB. The resistance index and the HBF were measured at the level of the midpoint of the upper arm. The median (interquartile range) of resistance index decreased from 0.98 (0.95-1.00) to 0.81 (0.77-0.91) (P < 0.01). The median HBF increased from 32 (18-46) to 88 (59-98) mL/min (P < 0.01). We conclude that ISB enhances arterial blood flow and decreases arterial resistance.
... In addition, two canine studies have demonstrated that both clonidine and dexmedetomidine will prolong the duration of vasodilation (i.e. sympathetic block) when combined with mepivacaine for stellate ganglionic blockade (Kimura et al. 2001; Tezuka et al. 2004). Clonidine's mechanism of analgesic action in this setting remains controversial with at least one clinical study suggesting that the effects are mediated centrally and not locally at the level of the nerve axon (Mannion et al. 2005). ...
To compare the sensory and motor effects of adding medetomidine to mepivicaine, administered either perineurally or systemically, for radial nerve block in dogs.
Prospective randomized cross-over study.
Six healthy Beagles, aged 18.7 +/- 6.3 months and weighing 10.4 +/- 1.3 kg.
Dogs were anesthetized briefly with sevoflurane on three separate occasions and received each treatment administered in random order: mepivacaine 5 mg kg(-1) perineurally around the radial nerve with saline 0.01 mL kg(-1) intramuscularly (CONTROL); mepivacaine 5 mg kg(-1) and medetomidine 0.01 mg kg(-1) combined, perineurally with saline 0.01 mL kg(-1) intramuscularly (MEDPN); mepivacaine 5 mg kg(-1) perineurally around the radial nerve with medetomidine 0.01 mg kg(-1) intramuscularly (MEDIM). All nerve blocks were performed with the aid of a nerve locator. Motor effects were evaluated based on the ability to bear weight. Sensory effects were evaluated by the response to a graded-electrical stimulus. These were evaluated at 5-minute intervals for the first hour, and at 10-minute intervals thereafter. Mean intervals were calculated as follows: time to motor block onset, duration of motor block, time to peak sensory block, duration of peak sensory block (i.e. period of no response to maximal stimulus intensity), and duration of residual sensory block (i.e. time to return to baseline sensory function). Treatment means were compared using a one-way analysis of variance for repeated measures and, where significant differences were noted, a Student-Newman-Keuls test was applied; p < 0.05 was considered significant.
Medetomidine, administered either systemically or perineurally, significantly prolonged duration of peak motor block, peak sensory block, and residual sensory block compared with CONTROL.
Medetomidine prolonged sensory and motor blockade after radial nerve block with mepivacaine in dogs.
Medetomidine may prove to be a useful adjunct to peripheral nerve blockade with local anesthetics.
... Local anesthetic solutions are used for SGB. It was reported that duration of action and vasodilation were enhanced after SGB by 0.5% mepivacaine combined with clonidine, an agonist of ␣ 2adrenergic receptor 3) . ...
The goal of this study was to compare oral mucosal blood flow and duration of anesthetic action after stellate ganglion block (SGB) using lidocaine, with or without epinephrine, and discuss the effect of epinephrine on SGB. Duration of anesthetic action was defined as elapsed time from finish of injection to recovery of common carotid blood flow (CCBF) to within+/-5% of respective control value. Male Japan White rabbits were anesthetized with isoflurane and mechanically ventilated. Common carotid blood flow and tongue mucosal tissue blood flow (TMBF) were measured with an ultrasound flowmeter and laser Doppler flowmeter, respectively. End-tidal partial pressure of carbon dioxide (ETCO(2)) and hemodynamic variables were continuously monitored, including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP). For SGB, the tip of the needle was placed on the left transverse process of the cervical vertebra, 1-2 mm caudal to the cricoid cartilage. Either 0.1 ml of 1% lidocaine (Group L) or 1% lidocaine containing 10 mug/ml epinephrine (Group LE) was injected for SGB. There were no differences in values at immediately before SGB and at the time when maximal change in CCBF was observed after SGB for ETCO(2), HR, SBP, DBP or MAP in either group. CCBF showed a significant increase in Group L after SGB. In contrast, CCBF only showed a slight increase in Group LE. TMBF showed a significant increase in Group L after SGB, but not in Group LE. No differences in time required for maximal effect were observed between the two groups. In contrast, duration of anesthetic action in Group LE was significantly longer than that in Group L. Addition of epinephrine to local anesthetic solutions is not suitable for SGB, as it may not facilitate an increase in tissue blood flow, which is the primary objective of SGB.
Objective
Sympathetic blocks are invaluable to prevent morbidity from Raynaud’s phenomena (RP). RP may occur in children with rheumatological disorders and causes severe pain, discolouration of digits, gangrene and auto-amputation.
We describe planning and execution of sympathectomy blocks in children of rheumatological disorders presenting with RP.
Methods
With upper limb involvement, ultrasound guided stellate ganglion block (USGB) was given with ropivacaine and clonidine. When all four limbs were involved, intrathecal block with bupivacaine and clonidine was also given.
Results
A total of 68 sympathectomy blocks were performed- 28 bilateral USGB, 2 unilateral USGB and 10 intrathecal injections. Multiple interventions in a single day were frequently required. For safety, all USGB blocks were performed with an ultrasound and strict adherence to local anaesthetic volume was done with peri-procedure monitoring of 2–3 hours. All blocks were performed by an experienced specialist.
All children reported immediate pain relief with prevention of major amputation.
Conclusion
With meticulous planning, monitoring and precautions, sympathectomy of limbs in paediatric rheumatologic disorders with RP can be safely undertaken.
Background and Objectives:: The aim of this study is to compare 0.25% levobupivacaine with 0.25% bupivacaine and 0.125% bupivacaine to examine the duration and magnitude of vasodilative effect induced by sympathetic block.
Methods:: We measured mean arterial pressure (MAP), heart rate (HR), and right and left brachial‐artery blood flow (BABF) before and after cervicothoracic sympathetic block in 24 dogs. The experimental protocol was designed as follows: (1) left cervicothoracic sympathetic block with 1.0 mL of 0.25% levobupivacaine (n = 8), (2) left cervicothoracic sympathetic block with 1.0 mL of 0.25% bupivacaine (n = 8), and (3) left cervicothoracic sympathetic block with 1.0 mL of 0.125% bupivacaine (n = 8).
Results:: MAP and HR did not change significantly throughout the study in either group. Left cervicothoracic sympathetic block with 0.25% levobupivacaine increased left BABF significantly from 5 minutes through 80 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 185 ± 35%; P <.01). Left cervicothoracic sympathetic block with 0.25% bupivacaine increased left BABF significantly from 5 minutes through 100 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 251 ± 47%; P < .01). Left cervicothoracic sympathetic block with 0.125% bupivacaine increased left BABF significantly from 5 minutes through 80 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 155 ± 20%; P < .01).
Conclusions:: 0.25% Levobupivacaine may have a lower potency compared with 0.25% bupivacaine in sympathetic block in dogs.
The purpose of this study is to establish a model of brachial plexus block (BPB) in anesthetized dogs and evaluate changes in the arterial blood flow after BPB. Sixteen anesthetized dogs were enrolled into this study and divided into two groups as follows: M group (1 %mepivacaine 1mL: n=8)and C group (physiological saline solution (PSS 1 mL: n=8). For BPB, a block needle was inserted into the left brachial plexus under ultrasonic imaging, the brachial plexus was identified using a nerve stimulator and the spread of drug solutions was confirmed by indigo carmine under dissection after the study. Changes in the arterial blood flow were evaluated by the median arterial blood flow (MABF) using the ultrasonic blood flowmeter. In group M, left MABF was significantly increased from 30 min to 120 min after BPB, and maximum increase in MABF was 136.7 ±35 %at 60 min after BPB. In group C, changes in left MABF were not observed during the study. In both groups, right MABF was not changed after BPB. Our results suggest that BPB may have a vasodilating effect induced by sympathetic block.
The aim of this study is to compare sympathetic block using 2.0% mepivacaine with surgical sympathectomy using radiofrequency thermocoagulation for the duration and magnitude of the vasodilative effect. Mean arterial pressure (MAP), heart rate (HR), and right and left brachial artery blood flow (BABF) were measured before and after left cervicothracic sympathetic block using 2.0% mepivacaine or surgical sympathectomy in dogs. The experimental protocol was designed as follows: (1) left cervicothoracic sympathetic block using 1.0 ml of 2.0% mepivacaine (n = 8), and surgical sympathectomy using radiofrequency thermocoagulation (n = 8). MAP and HR did not change significantly throughout the study in both groups. Left cervicothracic sympathetic block increased left BABF significantly from 5 min through 80 min after cervicothracic sympathetic block (baseline, 100%: peak at 10 min after the block, 186 ± 40%: P < 0.01). Left surgical sympathectomy increased left BABF significantly from 5 min through 120 min after the sympathectomy (baseline 100%; peak at 60 min after the sympathectomy, 265 ± 59%: P < 0.01). Left BABF in surgical sympathectomy was significantly higher than those in cervicothoracic sympathetic block throughout the study. The values of right BABF decreased significantly compared with the baseline value throughout the study in both groups. In conclusion left cervicothracic sympathetic block using 2.0% mepivacaine induces less duration and magnitude of the vasodilative effect compared with surgical sympathectomy with radiofrequency thermocoagulation.
The aim of this study was to observe the effects of stellate ganglion block (SGB) on hemodynamic changes and intrapulmonary shunt during one-lung ventilation (OLV).
Thirty ASA class I-II patients undergoing elective esophageal surgery were randomly divided into two groups: general anesthesia group (group N, n=15) and general anesthesia combined SGB group (group S, n=15), patients in group S were received left SGB before induction. Radial artery was cannulated for arterial blood pressure (ABP) monitoring and blood sampling and Swan-Ganz catheter was position in the pulmonary artery via right internal jugular vein under local anesthesia. ECG, MAP, HR, CVP, continuous cardiac output (CCO) index and BIS were continuously monitored during anesthesia. General anesthesia was induced with propofol 1.5-2.0 mg/kg, sufentanil 0.4 μg/kg, and Rocuronium 0.6-0.9 mg/kg. Endobronchial occluder was placed blindly after tracheal indubation and the correct position was verified by auscultation and fiberoptic bronchoscopy. The patients were mechanically ventilated. The ventilation conditions were Fio2=100%, VT = 8-10 ml/kg, I: E = 1:2 and respiratory rate was adjusted to maintained PETCO2 at 35-45 mmHg during both two-lung ventilation (TLV) and OLV. Anesthesia was maintained with continuous infusion of propofol 4-10 mg/kg·h, sufentanil 0.2 μg/kg·h, vecuronium o.1 mg/kg·h, BIS was maintained at 45-55. Blood samples were taken from radial artery and S-G catheter for blood gas analysis at following intervals: during spontaneous breathing when the patient was awake (T0), 1 min after tracheal indubation (T1), 1 min after patient was placed in lateral position (T2) and 15 min after it (T3), 1 min after ribs was braced (T4), 30, 60, 120 min during the course of OLV (T5, T6, T7), the two lungs were ventilated again for 30 min (T8) and Qs/Qt was calculated.
SVRI, MAP, HR in group N increased significantly at T1, T2, T4 compared with group S (p < 0.05). Qs/Qt was significantly increased after patient was placed in lateral position and increased further during OLV; the calculated Qs/Qt values were highest at T5· PaO2 was significantly lower after OLV was started and reached the lowest level at T6 then was gradually increasing. There was no significant difference in Qs/Qt and PaO2 at all time points between two groups.
SGB before induction effectively suppress the stress response work as stable blood dynamics and does not affect Qs/Qt and arterial oxygenation during OLV, SGB is a safe technique of anesthesia for general thoracic surgery.
Stellate ganglion block is utilized both as a diagnostic as well as a therapeutic procedure for certain types of chronic neuropathic pain conditions, namely sympathetically mediated and/or sympathetically maintained pain syndrome. There are various techniques available to successfully block this ganglion. This article discusses the techniques used to block the stellate ganglion. However, special emphasis is given to our new oblique approach to successfully block this ganglion. Additionally, our article discusses among others, the anatomy of the ganglion, indications and contraindications for the block, drug selections and complications.
Neurogenic pulmonary edema (NPE) is an acute and serious complication after a central nervous system insult with high mortality. The pronounced activation of sympathetic nervous system and the release of vasoactive substances are necessary prerequisites for the development of NPE. We introduce a hypothesis that stellate ganglion block (SGB) may prevent NPE development on the basis of the inhibition of sympathetic overactivation, reduction of the concentration of norepinephrine and attenuation of baroreflex sensitivity, and improve the outcome by improving cerebral blood flow and pulmonary circulation and maintaining cardiovascular stability. In clinical practice, the guidance technique and close monitoring might guarantee the safety of SGB. If our hypothesis is supported by further experiments, this may open a new doorway for the treatment of NPE.
A sensitive and selective method has been developed for the speciation of chromium in water samples based on cloud point extraction
(CPE) separation and preconcentration and determination by flame atomic absorption spectrometry. In the CPE method, Cr(III)
reacts with acetylacetone yielding a hydrophobic complex, which is entrapped in the Triton X-100 surfactant-rich phase, whereas
Cr(VI) remained in aqueous phase. Thus, separation of Cr(III) and Cr(VI) could be realized. Total chromium was determined
after the reduction of Cr(VI) to Cr(III) by using ascorbic acid as reducing reagent. Under the optimal conditions, the detection
limit of this method for Cr(III) was 0.32 ng mL−1 with an enrichment factor of 35, and the relative standard deviation was 3.4% (c = 100 ng mL−1, n = 7). The method has been applied to the speciation of chromium in natural water samples with satisfactory results.
Background: The goal of interventional management of refractory pediatric complex regional pain syndrome is to facilitate early restoration of function to the affected extremity. These interventions are more complicated in children, as most do not tolerate these procedures without sedation.
Case report: We report the first detailed description of a pediatric patient with complex regional pain syndrome refractory to medical management who had complete resolution of symptoms after brief inpatient rehabilitation involving continuous brachial plexus blockade and a multidisciplinary apaproach.
Conclusion: Repeated interventional therapy for refractory, severe complex regional pain syndrome may not be feasible in children owing to the requirement for deep sedation or general anesthesia. A multidisciplinary apaproach of brief inpatient rehabilitation and continuous blockade via an indwelling pain catheter may provide a safer, more cost-effective means of restoring function in children with advanced disease.
The aim of this study is to examine the duration and magnitude of vasodilating effect induced by sympathetic block with the addition of different concentrations of clonidine to mepivacaine.
In dogs, mean arterial pressure (MAP), heart rate (HR), and right as well as left brachial artery blood flow (BABF) were measured before and after stellate ganglion block (SGB) used as sympathetic block. The experimental protocol was designed as follows: 1) Group 1: left SGB using 0.5% mepivacaine 1 ml (n = 6), 2) Group 2: left SGB using the addition of clonidine 0.5 microgram to 0.5% mepivacaine 1 ml (n = 6), 3) Group 3: left SGB using the addition of clonidine 5 micrograms to 0.5% mepivacaine 1 ml (n = 6).
MAP showed no significant change throughout the study in the groups 1 and 2. In the group 3, MAP was lower than that of the group 1. HR showed no significant change throughout the study in the three groups. Left BABF increased significantly after left SGB in the three groups. The duration of increased BABF in the group 2 was the longest, and that in the group 3 was the shortest among them. Right BABF after left SGB decreased significantly throughout the study in the three groups, and the magnitude of the decrease in BABF in the group 3 was the highest among them.
Sympathetic block with the addition of clonidine to local anesthetics increases both duration and magnitude of its vasodilating effect. However, sympathetic block with the addition of higher doses of clonidine to local anesthetics may induce shorter duration and lower magnitude of vasodilating effect compared with local anesthetics alone.
The aim of this study was to examine the duration of vasodilation induced by sympathetic block with the addition of dexmedetomidine to mepivacaine.
We measured right and left brachial artery blood flow (BABF) before and after stellate ganglion block used as a sympathetic block in dogs. The experimental protocol was designed as follows: (1) left stellate ganglion block using 1.0 mL 0.5% mepivacaine (n = 8), (2) left stellate ganglion block using the addition of dexmedetomidine 0.5 microg to 1.0 mL 0.5% mepivacaine (n = 8), and (3) left stellate ganglion block using the addition of dexmedetomidine 0.5 microg to 1.0 mL physiological saline solution (n = 8).
Left stellate ganglion block with mepivacaine alone increased left BABF significantly from 5 minutes through 50 minutes after the block (baseline, 100%; peak at 10 minutes after SGB, 181 +/- 27%; P <.01). Left stellate ganglion block with the addition of dexmedetomidine to mepivacaine induced a significant increase of left BABF from 5 minutes through 90 minutes after the block (baseline, 100%; peak at 10 minutes after SGB, 174 +/- 36%; P <.01). Left and right BABF did not change significantly after stellate ganglion block with dexmedetomidine only. Right BABF decreased significantly after left stellate ganglion block with mepivacaine alone or the addition of dexmedetomidine to mepivacaine throughout the study.
The addition of dexmedetomidine prolongs the duration of vasodilation induced by stellate ganglion block with mepivacaine used for sympathetic block in dogs.
The aim of this study is to compare 0.2% ropivacaine with 0.125% bupivacaine or 0.25% bupivacaine for the duration and magnitude of the vasodilation effect induced by sympathetic block.
We measured mean arterial pressure, heart rate, and right and left brachial artery blood flow (BABF) before and after cervicothoracic sympathetic block in 24 dogs. The experimental protocol was designed as follows: (1) left cervicothoracic sympathetic block with 1.0 mL 0.2% ropivacaine (n =8), (2) left cervicothoracic sympathetic block with 1.0 mL 0.125% bupivacaine (n=8), and (3) left cervicothoracic sympathetic block with 1.0 mL 0.25% bupivacaine (n=8).
Mean arterial pressure and heart rate did not change significantly throughout the study in either group. Left cervicothoracic sympathetic block with 0.2% ropivacaine increased left BABF significantly from 5 to 100 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 254 +/- 38%; P <.01). Left cervicothoracic sympathetic block with 0.125% bupivacaine increased left BABF significantly from 5 to 80 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 144 +/- 9%; P <.01). Left cervicothoracic sympathetic block with 0.25% bupivacaine increased left BABF significantly from 5 to 100 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 235 +/- 61%; P <.01).
Ropivacaine may be equally potent to bupivacaine at equal concentrations in sympathetic block in dogs.
Repeated lumbar sympathetic blockade (LSB) with local anesthetics is generally used in complex regional pain syndrome (CRPS) of the lower extremities if the initial block has been successful. However, the symptoms of CRPS may inevitably recur in spite of repeated LSB. Clonidine, an alpha2-adrenoceptor agonist, has both anesthetic and analgesic sparing effects, and when added to local anesthetics may enhance peripheral and central neural block due to its local or central analgesic effects. It is reasonable that clonidine has been used in chronic pain conditions such as neuropathic and sympathetically maintained pain. Here we report two cases of CRPS type 1 who got excellent analgesia and alleviation of clinical symptoms after receiving an LSB with lidocaine and clonidine.
The aim of this study is to compare 0.25% levobupivacaine with 0.25% bupivacaine and 0.125% bupivacaine to examine the duration and magnitude of vasodilative effect induced by sympathetic block.
We measured mean arterial pressure (MAP), heart rate (HR), and right and left brachial-artery blood flow (BABF) before and after cervicothoracic sympathetic block in 24 dogs. The experimental protocol was designed as follows: (1) left cervicothoracic sympathetic block with 1.0 mL of 0.25% levobupivacaine (n = 8), (2) left cervicothoracic sympathetic block with 1.0 mL of 0.25% bupivacaine (n = 8), and (3) left cervicothoracic sympathetic block with 1.0 mL of 0.125% bupivacaine (n = 8).
MAP and HR did not change significantly throughout the study in either group. Left cervicothoracic sympathetic block with 0.25% levobupivacaine increased left BABF significantly from 5 minutes through 80 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 185 +/- 35%; P <.01). Left cervicothoracic sympathetic block with 0.25% bupivacaine increased left BABF significantly from 5 minutes through 100 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 251 +/- 47%; P < .01). Left cervicothoracic sympathetic block with 0.125% bupivacaine increased left BABF significantly from 5 minutes through 80 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 155 +/- 20%; P < .01).
0.25% Levobupivacaine may have a lower potency compared with 0.25% bupivacaine in sympathetic block in dogs.
We have assessed the analgesic efficacy and side effects of caudally administered clonidine in a prospective, randomized,
double-blind, placebo-controlled study. We studied 64 adult patients undergoing elective haemorrhoidectomy. Caudal block was
performed in all patients using a mixture of 0.5% bupivacaine 35 mg with 2% lidocaine 140 mg and epinephrine 5 micrograms
ml-1. Patients were allocated randomly to one of two groups. Clonidine 75 micrograms was added in group C and saline 1 ml
in group S. Median time to first analgesic requirements was significantly longer in group C (mean 729 (SD 120) min) than in
group S (276 (131) min) (P = 0.01). Bradycardia occurred in seven patients in group C but did not affect mean arterial pressure.
Background
Clonidine has been added to local anesthetic regimens for various peripheral nerve blocks, resulting in prolonged anesthesia and analgesia. The authors postulated that using clonidine as a component of intravenous regional anesthesia (IVRA) would enhance postoperative analgesia.
Methods
Forty-five patients undergoing ambulatory hand surgery received IVRA with lidocaine, 0.5%, and were assigned randomly and blindly to three groups. The control group received intravenous saline, the intravenous clonidine group received 1 microg/kg clonidine intravenously, and the IVRA clonidine group received 1 microg/kg clonidine as part of the IVRA solution. After their operations, the patients' pain and sedation scores and analgesic use were recorded.
Results
Patients in the IVRA clonidine group had a significantly longer period of subjective comfort when they required no analgesics (median [range]) for 460 min (215-1,440 min), compared with 115 min (14-390 min) for the control group and 125 min (17-295 min) for the intravenous clonidine group (P<0.0001). The patients who received IVRA with clonidine reported significantly lower pain scores 1 and 2 h after tourniquet deflation compared with the other groups, and they required no fentanyl in the postanesthesia care unit. They also required fewer analgesic tablets (325 mg acetaminophen with 30 mg codeine) in the first 24 h (2+/-1, mean +/- SD) compared with the other two groups, 5+/-1 tablets (control) and 4+/-2 tablets (intravenous clonidine) (P<0.0001). No significant postoperative sedation, hypotension, or bradycardia developed in any of the patients.
Conclusion
The addition of 1 microg/kg clonidine to lidocaine, 0.5%, for IVRA in patients undergoing ambulatory hand surgery improves postoperative analgesia without causing significant side effects during the first postoperative day.
Epidurally administered clonidine represents a new approach to postcesarean section pain therapy, yet the appropriate bolus dose and infusion to provide effective pain relief have not been defined. In addition, whether 2-chloroprocaine, a commonly used local anesthetic for intraoperative anesthesia, interferes with clonidine's analgesia, as it does with that of opioids, has not been examined. In this study, using a randomized, blinded design, 63 women received either bupivacaine or 2-chloroprocaine for epidural anesthesia for cesarean section and then received, upon request for analgesia in the recovery room, epidural clonidine 400 micrograms or 800 micrograms bolus, each followed by a 24-h infusion of 40 micrograms/h, or an equivalent volume bolus and infusion of saline. In the bupivacaine group, both clonidine doses produced equivalent analgesia, as determined by pain scores and time to first supplemental intravenous morphine request, and sustained analgesia was produced by clonidine infusion, as measured by need for supplemental morphine. In contrast, 2-chloroprocaine diminished analgesia from 800 micrograms by 21% and abolished analgesia from 400 micrograms clonidine. After 2-chloroprocaine, sustained analgesia from continuous clonidine infusion was present only in the group who had received 800 micrograms clonidine. Clonidine did not alter resolution of residual local anesthetic sensory blockade, as measured by 2- or 4-segment regression following either local anesthetic, but did prolong duration of motor blockade in women receiving bupivacaine. Clonidine produced small decreases in heart rate and blood pressure. One patient received iv fluids for hypotension; one had asymptomatic bradycardia resolving without therapy; and one had mild hypoxemia with snoring during clonidine-induced sedation, responding to supplemental oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of clonidine and epinephrine, administered into the brachial plexus sheath, were evaluated in 60 patients who underwent surgery of the upper limb. All patients received 40 to 50 ml of 0.25% bupivacaine, injected into the brachial plexus sheath, using the supraclavicular technique. The patients were randomly allocated to two groups so that 30 patients received 150 micrograms clonidine hydrochloride (Group I), and 30 received 200 micrograms epinephrine (Group II). The quality and the duration of analgesia were assessed as well as the possible side-effects. The block produced with the addition of clonidine was longer (994.2 +/- 34.2 vs 728.3 +/- 35.8 min) and superior to that with epinephrine (P less than 0.001). No major side-effects were recorded. We conclude that the injection of clonidine into the brachial plexus sheath is an attractive alternative to epinephrine to prolong the duration of analgesia following upper limb surgery under conduction anaesthesia.
The concept that neurotransmitters can modulate their own release through presynaptic inhibitory autoreceptors is well established. The presynaptic inhibitory autoreceptors involved in a negative feedback mechanism that modulates the release of norepinephrine are of the alpha 2-subtype. Stimulation of central alpha 2-adrenoceptors by drugs like clonidine, guanfacine, and guanabenz produces an antihypertensive and bradycardiac effect through a decrease in sympathetic tone. In vascular smooth muscle, the alpha 1-adrenoceptor subtype predominates and mediates vasoconstriction although alpha 2-adrenoceptors mediating vasoconstriction are also present in some vascular beds. Phenylephrine preferentially stimulates alpha 1-adrenoceptors and guanabenz preferentially stimulates alpha 2-adrenoceptors in vascular smooth muscle, whereas norepinephrine is an agonist at both alpha 1- and alpha 2-subtypes. The pressor response to phenylephrine was markedly reduced by prazosin. In contrast, the response to norepinephrine was relatively resistant to blockade, and that to guanabenz, totally resistant to blockade by prazosin. Inhibition of neuronal uptake by cocaine or desipramine and pretreatment of cats with 6-hydroxydopamine increased the effectiveness of prazosin in blocking the pressor responses to norepinephrine, but not to guanabenz or phenylephrine. These results support the proposal that postsynaptic alpha 1-adrenoceptors are preferentially innervated (i.e., within the neuroeffector junction), while the postsynaptic alpha 2-adrenoceptors are in extrasynaptic locations. The subclassification of alpha-adrenoceptors into alpha 1- and alpha 2-subtypes opens the possibility of designing selective drugs to act as agonists or antagonists on these receptor subtypes. These compounds have useful therapeutic applications, and in the case of selective alpha 2-adrenoceptor antagonists, novel potential uses may exist, both at the level of the central nervous system and in the periphery.
Clonidine analgesia was tested on the hyperalgesia induced by intraplantar injection of prostaglandin E2 or carrageenin. The antinociceptive effect of clonidine was dose-dependent and was abolished by local administration of the selective alpha 2-adrenoceptor blocker, yohimbine or of the opioid antagonists naloxone or quaternary nalorphine. St-91, a clonidine analog which does not cross the blood-brain barrier also promoted significant antinociception. Repeated administration of drugs possessing a central mechanism of analgesic action leads to the development of tolerance in this test. Significant analgesic tolerance was observed following repeated (5 days) morphine (8 mg/kg) or high doses of clonidine (0.5 mg/kg). In contrast, no tolerance was detected to the analgesic effect of low doses of clonidine (0.15 mg/kg) or of St-91 (0.5 mg/kg). These results suggest that, in addition to its central analgesic action, clonidine can induce peripheral antinociception by an alpha 2-adrenoceptor-mediated local release of enkephalin-like substances.
A double-blind study was conducted to assess the efficacy and the safety of epidural clonidine combined with bupivacaine for analgesia during labor.
Two groups of pregnant healthy women were allocated randomly to receive either 10 mL 0.125% bupivacaine plain solution (group B, n = 10) or with 75 micrograms clonidine (group B + C, n = 12). Visual analog scale (VAS) scores were measured over 30 minutes after each epidural injection. Patients were monitored with an automated blood pressure device (Dinamap and a pulse oximeter), and fetal heart rate was measured with a cardiotocograph. Plasma clonidine concentrations were measured at birth in mothers and in the umbilical cord by radioimmunoassay.
Visual analog scale scores were significantly lower in patients who received clonidine. Patients required a second epidural injection after 55 +/- 9 minutes in group B and 127 +/- 11 minutes in group B + C (P < .05). Visual analog scale scores were also significantly lower in group B + C than in group B, after the second injection. Decreases in arterial blood pressure were comparable in the two groups, and no patient experienced arterial oxygen desaturation or bradycardia. Fetal heart rate was decreased in group B + C at the time of the second injection. The duration of labor after epidural administration was prolonged in group B + C patients compared to group B (282 +/- 43 minutes and 169 +/- 26 minutes, respectively, P < .05). Apgar scores at 1 and 5 minutes were similar in both groups. Plasma clonidine concentrations were, respectively, 0.31 +/- 0.16 ng/mL 60 minutes after the first injection and 0.62 +/- 0.13 ng/mL at birth in mothers while plasma umbilical cord concentrations were 0.56 +/- 0.12 ng/mL.
The study documents that clonidine improves epidural bupivacaine analgesia during labor and demonstrates transfer of the drug across the placenta. Therefore, a more extensive study is required to determine the incidence of possible side effects of clonidine in neonates.
To determine whether alpha 2-adrenergic agonists inhibit impulse conduction, clonidine and guanfacine were applied to rat sciatic nerve fibers studied in vitro. Clonidine and guanfacine produced concentration-dependent, tonic inhibition of compound action potentials in large, myelinated A alpha fibers. The 50% effective concentration (EC50) of clonidine measured 2.0 +/- 0.8 mM (mean +/- standard deviation); the EC50 of guanfacine measured 1.2 +/- 0.2 mM. Clonidine was also less potent than guanfacine at phasic block of A alpha compound action potentials examined at 10 Hz. Both drugs inhibited tonic impulse conduction in C fibers in a concentration-dependent, reversible fashion, and produced greater inhibition of C fiber than A alpha compound action potentials at all drug concentrations. Again, clonidine appeared to inhibit C fiber compound action potentials (EC50 = 0.45 +/- 0.01 mM) with less potency than guanfacine (EC50 = 0.17 +/- 0.06 mM). We conclude that clonidine and guanfacine, unlike traditional local anesthetics, demonstrate a tendency toward steady-state differential nerve block wherein C fibers are blocked to a greater extent than A alpha fibers.
Twenty patients with chronic pain who previously had obtained analgesia from epidural clonidine and lignocaine agreed to participate in a double-blind crossover study of lumbar epidural clonidine (150 micrograms), lignocaine (40 mg) and the combination of clonidine (150 microgram) and lignocaine (40 mg), all drugs were given in a volume of 3 ml. There were 11 women and 9 men with a mean age 53 years (range: 23-78 years); 9 patients had low back and leg pain, 9 had neuropathic pain, 1 had pelvic pain and 1 Wegner's granulomatosis. Pain intensity and pain relief, as well as sensory and motor blockade, were assessed for 3 h following each injection. The combination was reported as the best pain relief by 12 of the 17 patients who completed all three arms of the study; 4 patients reported that clonidine was the best, 1 patient reported that none of the injections provided any analgesia and no patient reported that lignocaine was the best. SPID analysis revealed a significant difference between the combination and lignocaine (P < 0.05) but no other significant difference. TOTPAR analysis revealed no significant difference between any of the injections. All 3 injections produced evidence of neurological blockade; clonidine produced sensory blockade in 3 patients and motor blockade in 3 patients. Lignocaine produced sensory blockade in 6 patients and motor in 8 patients, while the combination produced evidence of neurological blockade in all 17 patients, sensory in 6 and motor in 11 patients. Overall there was no relationship between neurological blockade and analgesia. The reported side effects appeared to be related to clonidine. These data indicate that in these patients with chronic pain epidural clonidine had a supra-additive effect and behaved more like a co-analgesic than a pure analgesic.
Postoperative analgesia may be prolonged by the addition of clonidine to local anesthetic solutions used for regional anesthesia. The purpose of this study was to test this hypothesis in a clinical trial of patients undergoing podiatric surgery. The study design was prospective, double-blinded, and randomized. Ninety ASA physical status I or II patients scheduled for bunionectomy or hammer toe repair were randomized to receive ankle or metatarsal blocks with plain 1.73% lidocaine (Group L), 1.73% lidocaine with 10 micrograms/mL of clonidine added (Group C10), or 1.73% lidocaine with 20 micrograms/mL clonidine (Group C20). Time from the performance of the block to 1) loss of sensation to pinprick, 2) return of sensation to pinprick, 3) onset of postsurgical pain, and 4) time of first oral pain medication intake were recorded. Beginning at 1 h after the completion of the block, visual analog scale (VAS) and verbal pain scores were recorded every 30 min. Additional postoperative oral pain medication required in the first 9 h after the block was also recorded. Analysis of variance (ANOVA) was used to analyze intergroup differences in the VAS and verbal pain scores, the time to first reported pain, the time to first oral pain medication, and the total amount of oral pain medications required. Repeated-measures ANOVA was used to analyze the VAS and verbal pain scores overall and integrated assessment of pain scores and rescue medication was per-formed. Adverse events were also recorded for each group. There were no differences among the three groups with regard to overall VAS pain scores although Group C10 had significantly better verbal pain scores after the first 3 h (P < 0.05). There was also no difference in time to loss or return of pinprick sensation. Group C10 had a longer time to first reported pain (P < 0.01), a longer time to first oral pain medication (P < 0.01), a lower average total dose of oral pain medication required (P < 0.05), and a lower integrated assessment of pain and medication (P < 0.01) than Group L. More patients in Group C10 reported no pain postoperatively (P < 0.01) and no pain medication taken (P < 0.01) than Group L. Group C20 results suggested no statistically significant improvement over plain lidocaine. One patient in Group C20 experienced significant hypotension postoperatively. pH determinations and chemical analysis by capillary electrophoresis showed no significant change in composition of the solutions when clonidine was mixed with lidocaine and stored at 4 degrees C for 1 wk. Compared to 1.73% lidocaine, combining clonidine (10 micrograms/mL) with lidocaine for local anesthetic block for foot surgery significantly increases the duration and quality of postoperative analgesia.
This study assessed the minimum dose of clonidine required to prolong the duration of both anesthesia and analgesia after axillary brachial plexus blockade. Eighty patients scheduled for elective hand surgery were divided into eight groups in a randomized, double-blind fashion. An axillary brachial plexus block was performed with 40 mL 1% mepivacaine plus 1:200,000 epinephrine. The control group received no clonidine. In the other groups, increasing doses of clonidine (0.1, 0.2, 0.3, 0.4, 0.5, 1, and 1.5 micrograms/kg) were added to the local anesthetic solution. Onset time, duration of anesthesia and analgesia, postoperative pain score, intake of analgesics, and adverse effects were recorded. The eight groups were comparable in terms of onset time, postoperative pain score, and analgesic requirement. The minimum dose of clonidine required to significantly prolong the duration of analgesia and anesthesia was, respectively, 0.1 and 0.5 microgram/kg. No side effects (sedation, drowsiness, bradycardia, arterial hypotension) were reported. We conclude that the dose of clonidine required to prolong significantly the duration of both anesthesia and analgesia after axillary brachial plexus blockade is 0.5 microgram/kg and that, at this dose, clonidine may be used without important reported side effects even in outpatients.
Clonidine, an alpha-2-adrenoreceptor agonist, has been shown to decrease intraocular pressure (IOP) and to have some analgesic and sedative effects when it is used in premedication for ophthalmic surgery. This study was designed to investigate the efficacy of lidocaine-clonidine retrobulbar block for cataract surgery with respect to its effect on IOP, analgesic action, and sedative effects.
Sixty elderly patients (ASA status I and II) were allocated randomly to receive in a prospective double-blind manner retrobulbar block for cataract surgery. Group I (n = 30) received 3-4 mL of 2% lidocaine with 1 mL saline, while group 2 (n = 30), received 3-4 mL of 2% lidocaine with clonidine 2 micrograms/kg.
A large decrease in intraocular pressure from 13.5 +/- 4.6 to 7.7 +/- 3.7 mm Hg (P < .01) and a small but significant reduction of both systolic and diastolic blood pressure were observed 20 minutes alter the retrobulbar block in patients receiving clonidine, while no changes occurred in the control group. The median duration of analgesia and akinesia was greater in the lidocaine-clonidine group (241 +/- 88 minutes and 80 +/- 20 minutes, respectively) as compared with the lidocaine group (128 +/- 24 minutes and 70 +/- 20 minutes, respectively) (P < .01, P < .05). Sedation scores were greater in group 2 from the 10-minute point (P < .01).
Addition of clonidine to lidocaine for retrobulbar block causes a decrease in intraocular pressure, a sedative effect, and an increased duration of analgesia and akinesia, with relatively stable hemodynamic parameters.
Although addition of clonidine to local anesthetics can prolong pain relief after peripheral nerve block, a dose-range effect has not been determined.
Fifty-six outpatients undergoing carpal tunnel release were randomly assigned to receive in a double-blind fashion 45 ml of a mixture containing either 400 mg lidocaine plus saline or 400 mg lidocaine plus 30, 90 or 300 microg clonidine for axillary nerve block. In each group (n = 14), blocks were evaluated at regular time intervals to determine sensory and motor functions in the five nerve regions of the hand and forearm. Also, adequacy of the block for surgery, postoperative pain intensity, and side effects were evaluated.
Compared with saline, each dose of clonidine reduced the onset time of sensory block and extended the field of adequate anesthesia. Ten minutes after injection, 30 microg clonidine was more effective than 90 microg clonidine in producing sensory blockade. Sedation occurred with clonidine 30 and 300 microg. Clonidine reduced the use of supplementary intravenous anesthetic agents for surgery and produced dose-dependent prolongation of analgesia, reaching a mean 770 min (range, 190-1440 min) for the largest dose. Clonidine also produced a dose-dependent decrease in systolic arterial pressure of up to -22.5% (range, -6.0 29.9%) of baseline. With clonidine, 300 microg, three patients had mean arterial pressure of <55 mmHg; four patients had episodes of arterial oxyhemoglobin saturation of <90%, and two others were not discharged because of hypotension.
This study suggests that a small dose of clonidine enhances the quality of the peripheral blocks from lidocaine and limits the classical alpha2-agonist side effects to sedation.
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We evaluated the analgesic efficacy and hemodynamic and respiratory safety of clonidine when added to bupivacaine for caudal blocks in 58 children aged 38 +/- 2 mo (mean +/- SEM). Patients scheduled for ambulatory hernia repair were randomly given a caudal injection (0.75 mL/kg) of either saline placebo (P group), bupivacaine, 0.25% (B group), bupivacaine plus epinephrine 1:200,000 (BE group), bupivacaine plus clonidine 1 microgram/kg (BC1 group), or bupivacaine plus clonidine 2 micrograms/kg (BC2 group). Postoperative measurements included duration of analgesia, hemodynamics, and respiratory monitoring for 6 h. Thereafter, parents assessed their child's analgesic requirements at home every 3 h for 18 h. The duration of analgesia (median [range]) was significantly longer (P < 0.05) in the BC1 and BC2 groups (360 [270-360] min and 360 [355-360] min, respectively) compared with the P (77[45-190]), B (346[105-360]), or BE group (300[75-360]). Similarly, the BC1 and BC2 groups required less additional analgesic within the first 24 h. All groups showed a significant decrease in mean arterial pressure compared with baseline values, but the differences among the groups were not significant. Bradycardia and respiratory depression were not observed. Clonidine 1 and 2 micrograms/kg can be safely added to bupivacaine caudal blockade in small children for ambulatory hernia repair to achieve an increased duration of analgesia compared with bupivacaine alone or bupivacaine plus epinephrine.
Implications:
The addition of clonidine, an antihypertensive drug with analgesic properties, to local anesthetics in caudal blocks prolongs postoperative pain relief and reduces the need for additional pain treatment in children after hernia operation.
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We evaluated the effect of adding clonidine to bupivacaine on postoperative pain control and oxygenation after intercostal nerve blockade (ICB) for thoracotomy, and attempted to distinguish a systemic from a local effect of clonidine. ICB with 2 mg/kg 0.5% bupivacaine was performed in 36 patients undergoing thoracotomy. Patients were randomized to one of three groups: 1) a control group that received bupivacaine with saline for ICB and an IM injection of saline, 2) an IM group that received bupivacaine with saline for ICB and an IM injection of 2 micrograms/kg clonidine, and 3) a block group that received bupivacaine with 2 micrograms/kg clonidine for ICB and an IM injection of saline. Blood gases, visual analog scale (VAS) scores, and analgesic demand were determined hourly for 8 h after arrival in the postoperative care unit (PCU). Patients in the block group had significantly lower VAS scores, higher arterial oxygen tension, and lower analgesic demand for the first 4 h in the PCU, compared with the two other groups. No difference was noted thereafter. We conclude that the addition of clonidine to bupivacaine for ICB leads to a short-term effect enhancing postoperative pain control and improving arterial oxygenation, probably mediated by a direct effect on the nerves.
Implications:
Severe pain after thoracotomy can lead to impaired ventilation. We studied the effect of adding clonidine to bupivacaine for intercostal nerve blockade after thoracotomy. Clonidine administered directly on the nerves enhanced analgesia and improved oxygenation for a short time compared with systemic administration or control.
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We sought to determine whether spinal clonidine 50 microg prolongs the analgesia from the spinal administration of sufentanil 7.5 microg and bupivacaine 2.5 mg early in the first stage of labor. Thirty patients were randomized to receive a 2-mL spinal injection of sufentanil 7.5 microg + bupivacaine 2.5 mg with or without clonidine 50 microg using a combined spinal-epidural (CSE) technique. Pain, nausea, pruritus, sedation, motor block, blood pressure, and heart rate were assessed until the patient requested additional analgesia. Analgesia was significantly prolonged in patients who received spinal sufentanil + bupivacaine + clonidine (197 +/- 70 vs 132 +/- 39 min; P = 0.004). Pain scores and side effects, including motor block, sedation, and hypotension, were similar between groups. Spinal clonidine significantly prolongs labor analgesia from spinal sufentanil and bupivacaine without producing serious adverse side effects.
Implications:
We studied the effects of spinal clonidine administered with spinal sufentanil and bupivacaine on labor analgesia using a combined spinal-epidural technique and conclude that spinal clonidine significantly prolongs labor analgesia from spinal sufentanil and bupivacaine without producing serious adverse effects.
Clonidine has proved to be a clinically useful adjunct in clinical anaesthetic practice as well as in chronic pain therapy because it has both anaesthetic and analgesic-sparing activity. The more selective alpha-2 adrenoceptor agonists, dexmedetomidine and mivazerol, may also have a role in providing haemodynamic stability in patients who are at risk of peri-operative ischaemia. The side-effects of hypotension and bradycardia have limited the routine use of alpha-2 adrenoceptor agonists. Investigations into the molecular pharmacology of alpha-2 adrenoceptors have elucidated their role in the control of wakefulness, blood pressure and antinociception. We discuss the pharmacology of alpha-2 adrenoceptors and their therapeutic role in this review. The alpha-2 adrenoceptor agonists are agonists at imidazoline receptors which are involved in central blood pressure control. Selective imidazoline agonists are now available for clinical use as antihypertensive agents and their pharmacology is discussed.
Clonidine has been added to local anesthetic regimens for various peripheral nerve blocks, resulting in prolonged anesthesia and analgesia. The authors postulated that using clonidine as a component of intravenous regional anesthesia (IVRA) would enhance postoperative analgesia.
Forty-five patients undergoing ambulatory hand surgery received IVRA with lidocaine, 0.5%, and were assigned randomly and blindly to three groups. The control group received intravenous saline, the intravenous clonidine group received 1 microg/kg clonidine intravenously, and the IVRA clonidine group received 1 microg/kg clonidine as part of the IVRA solution. After their operations, the patients' pain and sedation scores and analgesic use were recorded.
Patients in the IVRA clonidine group had a significantly longer period of subjective comfort when they required no analgesics (median [range]) for 460 min (215-1,440 min), compared with 115 min (14-390 min) for the control group and 125 min (17-295 min) for the intravenous clonidine group (P<0.0001). The patients who received IVRA with clonidine reported significantly lower pain scores 1 and 2 h after tourniquet deflation compared with the other groups, and they required no fentanyl in the postanesthesia care unit. They also required fewer analgesic tablets (325 mg acetaminophen with 30 mg codeine) in the first 24 h (2+/-1, mean +/- SD) compared with the other two groups, 5+/-1 tablets (control) and 4+/-2 tablets (intravenous clonidine) (P<0.0001). No significant postoperative sedation, hypotension, or bradycardia developed in any of the patients.
The addition of 1 microg/kg clonidine to lidocaine, 0.5%, for IVRA in patients undergoing ambulatory hand surgery improves postoperative analgesia without causing significant side effects during the first postoperative day.
Despite a large body of clinical evidence in favour of a local anesthetic effect of clonidine, the underlying mechanism has not yet been elucidated. In this study we have used the sucrose-gap method to measure the effects of clonidine on the electrophysiological properties of nonmyelinated nerve fibers in the rabbit vagus nerve. The results showed that clonidine enhanced the hyperpolarizing and reduced the depolarizing afterpotential that follow compound action potentials during electrical activity. We showed that summation of these afterpotentials shifts the membrane potential toward more negative values, thus creating a region of low safety conduction, where the local circuit currents might fail to depolarize the axonal membrane to the threshold value needed to open voltage-dependent Na(+) channels. Yohimbine did not reverse the inhibitory effects of clonidine on impulse propagation, indicating that the observed effects of clonidine relies on mechanisms not mediated by alpha(2)-adrenoceptors.
Epidural clonidine has not been evaluated as a component of patient-controlled epidural analgesia (PCEA) solutions during labor. A randomized, double-blind trial was conducted to investigate the efficacy and side effects of PCEA using bupivacaine and fentanyl, with or without clonidine.
Seventy-five healthy parturients in active labor were assigned to a PCEA solution of 0.0625% bupivacaine and fentanyl 2 microg/mL (4 mL demand bolus, 15 min lockout), with or without clonidine 4.5 microg/mL. The primary outcome measure was parturient rating of analgesia; others assessments included pain scores, drug utilization, supplementation and side effects.
Thirty-one parturients received clonidine (group BFC) and 38 received control solution (group BF). Eight (6 group BF, 2 group BFC, P = .28) failed to achieve satisfactory epidural analgesia. There was a trend for parturient ratings of pain relief to be higher in group BFC, with significantly more reporting excellent first-stage analgesia (81% v. 57%, P<.05). Pain scores were similar. Clonidine (median dose, 28 microg/h) reduced total bupivacaine and fentanyl use (P<.01), and reduced supplementation (P<.01). Maternal blood pressure (BP) and recordings of systolic BP below 100 mm Hg did not differ. Group BFC had higher sedation scores (P<.01), but no one appeared oversedated. Shivering was reduced in group BFC (P<.01).
The addition of clonidine to epidural bupivacaine and fentanyl for PCEA in labor improved analgesia, reduced the supplementation rate, and reduced shivering. Increased sedation and lower BP were not clinically important.
The new long-acting local anesthetic ropivacaine is a chemical congener of bupivacaine and mepivacaine. The admixture of clonidine to local anesthetics in peripheral nerve block has been reported to result in a prolonged block. The aim of the present study was to evaluate the effects of clonidine added to ropivacaine on onset, duration and quality of brachial plexus block.
Patients were randomly allocated into two groups. In group I brachial plexus was performed using 40 ml of ropivacaine 0.75% plus 1 ml of NaCL 0.9%, and in group II brachial plexus was performed using 40 ml of ropivacaine 0.75% plus 1 ml (0.150 mg) of clonidine. Onset of sensory and motor block of radial, ulnar, median and musculocutaneous nerve were recorded. Motor block was evaluated by quantification of muscle force, according to a rating scale from 6 (normal contraction force) to 0 (complete paralysis). Sensory block was evaluated by testing response to a pinprick in the associated innervation areas. Finally, the duration of the sensory block was registered. Data were expressed in mean+/-SD. For statistical analysis a Student t-test was used. A P-value of < or = 0.05 was considered as statistically significant.
The duration of blockade was without significant difference between the groups. Group I: 718+/-90 min; Group II: 727+/-117 min. There was no intergroup difference in sensory and motor onset or in quality of blockade.
The addition of clonidine to ropivacaine 0.75% does not lead to any advantage of block of the brachial plexus when compared with pure ropivacaine 0.75%.
Adding clonidine to weak ropivacaine solutions (<0.2%) could potentially enhance analgesia as well as further reduce the risk for unwanted motor blockade. The aim of the present study was to compare the postoperative pain-relieving quality of a ropivacaine 0.1%-clonidine mixture to that of plain ropivacaine 0.2% following caudal administration in children.
In a prospective, observer-blinded fashion, 40 ASA 1 paediatric patients undergoing subumbilical surgery were randomly allocated to receive a caudal injection of either plain ropivacaine 0.2% (1 ml/kg) (R0.2) or a mixture of ropivacaine 0.1% with clonidine 2 microg/kg (1 ml/kg) (R0.1C). Objective pain scale score and need for supplemental analgesia were used to evaluate analgesia during the first 24 h postoperatively. Residual postoperative sedation was also assessed.
A significantly higher number of patients in the R0.1C group (18/20) could be managed without supplemental analgesia during the first 24 h postoperatively compared to the R0.2 group (11/20) (P=0.034). Both the degree and the duration of postoperative sedation was similar in both groups. No signs of postoperative motor blockade were observed.
The combination of clonidine (2 microg/kg) and ropivacaine 0.1% is associated with an improved quality of postoperative analgesia compared to plain 0.2% ropivacaine. The improved analgesic quality of the clonidine-ropivacaine mixture is achieved without causing any significant degree of postoperative sedation.
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To evaluate the effects of adding small-dose clonidine to 0.75% ropivacaine during peripheral nerve blocks, 30 ASA physical status I and II patients undergoing hallux valgus repair under combined sciatic-femoral nerve block were randomly allocated in a double-blinded fashion to receive block placement with 30 mL of either 0.75% ropivacaine alone (group Ropivacaine, n = 15) or 0.75% ropivacaine plus 1 microg/kg clonidine (group Ropivacaine-Clonidine, n = 15). Hemodynamic variables, oxygen saturation, and levels of sedation, as well as the time required to achieve surgical block and time to first analgesic request, were recorded by a blinded observer. Time to surgical blockade required 10 min in both groups. Patients in the Ropivacaine-Clonidine group were more sedated than patients in the Ropivacaine group only 10 min after block placement. No differences in oxygen saturation and hemodynamic variables, degree of pain measured at first analgesic request, and consumption of postoperative analgesics were observed between the two groups. The mean time from block placement to first request for pain medication was shorter in group Ropivacaine (13.7 h; 25th-75th percentiles: 11. 8-14.5 h) than in group Ropivacaine-Clonidine (16.8 h; 25th-75th percentiles: 13.5-17.8 h) (P = 0.038). We conclude that adding 1 microg/kg clonidine to 0.75% ropivacaine provided a 3-h delay in first request for pain medication after hallux valgus repair, with no clinically relevant side effects.
Implications:
This prospective, randomized, double-blinded study demonstrated that, when providing combined sciatic-femoral nerve block for hallux valgus repair, the addition of 1 microg/kg clonidine to 0.75% ropivacaine prolongs the duration of postoperative analgesia by 3 h, with only a slight and short-lived increase in the degree of sedation and no hemodynamic adverse effects.
Tourniquet pain is often a limiting factor during intravenous regional anesthesia (IVRA). The purpose of this study was to evaluate the efficacy of 1 microg/kg of clonidine added to IVRA-lidocaine in decreasing the onset of severe tourniquet pain.
Upper extremity IVRA was performed in 15 volunteers with a double-cuffed tourniquet on 2 separate occasions at least 1 week apart. IVRA was established with either 40 mL 0.5% lidocaine (IVRA-L) or 40 mL 0.5% lidocaine with 1 microg/kg clonidine (IVRA-Cl). Verbal pain scores (VPS) from 0 to 10 were recorded every 5 minutes. When the VPS reached 6, the distal cuff was inflated, and the proximal cuff was deflated. This was defined as the first tourniquet time (T1). The study was terminated at a VPS of 10, or at 60 minutes, whichever occurred first. The time from distal cuff inflation to deflation was defined as the second tourniquet time (T2). Total tourniquet time (TT) was the sum of T1 and T2.
T1 for IVRA-L (21.6 +/- 3.9) and IVRA-Cl (22.7 +/- 2.7) were not significantly different. T2 and TT were significantly longer (P < .0001; P < .0007, respectively) for IVRA-Cl (33.0 +/- 6.2; 55.6 +/- 6.6) than for IVRA-L (25.5 +/- 4.4; 47.1 +/- 5.2).
This study shows that the addition of 1 microg/kg of clonidine to 40 mL of 0.5% IVRA-L delays the onset time of tourniquet pain in healthy, unsedated volunteers.
Clonidine, an alpha(2)-adrenergic agonist, has been shown to prolong local anesthesia. It appears that clonidine by itself produces conduction block by acting on peripheral nerves. However, whether clonidine-induced conduction block is mediated through alpha(2)-adrenergic receptors remains unclear. The purpose of this study was to see if clonidine's nerve-blocking action was through alpha(2)-adrenergic receptors by examining clonidine's action in the presence of alpha(2)-adrenergic antagonists.
The compound action potentials (CAPs) evoked by electrical stimuli were recorded from the isolated rat sciatic nerve in a recording chamber. Conduction block was examined by analyzing CAPs with regard to peak amplitude and time-to-peak in the presence of clonidine alone or clonidine plus alpha(2)-adrenergic antagonist yohimbine or idazoxan.
Both clonidine and yohimbine produced concentration-dependent, reversible, conduction block. Based on concentration-response relationships, the 50% of effective concentration (EC(50)) were estimated to be 1.61 +/- 0.51 mmol/L (mean +/- SD) for clonidine and 51.4 +/- 27.2 micromol/L for yohimbine. A mixture of equal volumes of 2.07 mmol/L clonidine and 55.6 micromol/L yohimbine produced conduction block to a level close to the mean value between conduction blocks induced by 2.07 mmol/L clonidine alone and 55.6 micromol/L yohimbine alone. Addition of idazoxan, a more specific alpha(2)-adrenergic antagonist than yohimbine, to clonidine was without effect on clonidine-induced conduction block.
The results indicated that the mixture of clonidine and yohimbine, in which either drug inhibited impulse conduction, produced conduction block in an additive manner, and that clonidine-induced conduction block was not reversed by coapplication with a specific alpha(2)-adrenergic antagonist idazoxan. These data suggest that clonidine's effects likely depend on mechanisms not mediated by alpha(2)-adrenergic receptors.