Dec 6(4) pages211-216 “ Comparative evaluation of oral gabapentin versus clonidine as premedication on preoperative sedation and laryngoscopic stress response attenuation for the patients undergoing general anesthesia”. The aim of the study was to compare the BP, HR during laryngoscopy and intubation as well as to evaluate the preoperative sedation status between oral clonidine and oral gabapentine as premedication for patients undergoing major surgery under general anesthesia . It was a prospective, double-blinded, and randomized controlled study; conducted in 100 adult patients of either sex, aged 20-45, of ASA I and II undergoing major surgery of >1 hour duration .They were randomly allocated into groups C and G were pre treated with oral clonidine (200 µg) and gabapentin (800 mg) respectively 2 hours before induction. Preoperative sedation and haemodynamic parameters were monitored .They concluded that oral clonidine is comparable in producing preoperative sedation to oral gabapentin, at the same time oral clonidine is more efficacious in reducing laryngoscopic stress response than oral gabapentin.
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Department of Anesthesiology and Critical Care Medicine, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania They compared the effects of oral clonidine (4 ug/kg) and midazolam (0.5mg/kg) on the preanesthetic sedation and postoperative recovery profile in children during tonsillectomy with or without adenoidectomy. In a double-blinded, double-dummy study design, 134 ASA physical status I-II children aged 4-12 yr were randomized to receive a combination of either clonidine and placebo (Group A), or placebo and midazolam (Group B) at 60-90 min and 30 min, respectively, before the induction of anesthesia Midazolam was superior to c1onidine as oral preanesthetic medication for these patients.
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A. Islam et al(2008) studied the role of oral clonidine and atenolol in controlling tachycardia and hypertension associated with pneumoperitoneum with CO2 during laparoscopic cholecystectomy. Patients were divided equally into three groups, which were Group-I: Oral clonidine(150ìgm), Group-II: oral atenolol(25mg) and Group-III: placebo (vitamin-c tablet), twenty five patients were in each group. The premedication was given 60 to90 min prior to induction. They compared hemodynamic variables at various points- before induction, after intubation, after skin incision, after insufflation, 5 min, 10 min, 15 min, 20 min after insufflations. The mean pulse rate was significantly low in Clonidine premedicated patients at all points except just before induction and just after insufflations. The decline in pulse rate from induction through the surgery was also notably low in the Clonidine group. They didn’t observe significant difference in the systolic, diastolic and mean arterial pressures, though there was a lowering of blood pressure in clonidine group. They noted that anaesthetic and analgesic requirement was less in Clonidine group and the recovery scores were almost similar in all three groups.
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This to certify that this dissertation entitled ”Comparative study of oral atenolol vs. oral clonidine for hypotensive anaesthesia for patients undergoing functional endoscopic sinus surgery under general anaesthesia”, has been prepared by Dr.M.Amarnath, post graduate student in M.D.Anaesthesiology, Madras Medical College, Chennai, done under the guidance and supervision of Prof. Dr.G.Sivarajan, M.D., D.A., Dept. of Anesthesiology at Madras Medical College and Government General Hospital, Chennai in partial fulfillment of the regulations for the award of the degree of M.D.(Anaesthesiology), examination to be held in March 2007.
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The results of the present study are consistent with those of the study conducted by Mayo et al., which included 100 men over 40 years old with urologic surgery under spinal anesthesia in 1998 . They found that the use of 15 mg prophylactic oral Clo- nidine will be effective to prevent shivering after spinal anesthesia. The shivering rate was 4% in the study group and was 44% in the control group . However, Tewari et al. found that 150 mg of oral clonidine was effective to prevent shivering after a neu- raxial block . Dhorgiol et al.  also found that 150 mg oral clonidine was effective in preventing shivering after a subarachnoid block. Furthermore, the results of our study corresponds to the findings by Vanderstappen et al. , who suggested that the incidence and severity of shivering in the study group was significantly lower than that in the control group.
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two doses of oral clonidine premedication were compared in 60 elderly patients, aged 65 to 82 years, who underwent elective ophthalmic surgery under local anaesthesia. Group I (n = 20) received placebo, group II (n = 20) received 150 microgram of clonidine (2 to 2.5microgram/kg) and group III (n~20) received 300 microgram of clonidine (4 to 4.5 I1g/kg) in a randomized, double blind fashion . Decreases in mean arterial blood pressure were more pronounced and occured earlier after 300microgram of clonidine (31.4 +/-12.1%, P<0.001) as compared to 150 microgram of clonidine (18.1 + 10.9% P <0.001) Throughout the study, 6 patients (30%) in group III (300 microgram clonidine treated group), were treated atleast once for hypotension, while no patient in groups I or II required any such treatment (P<0.05). Heart rate decreased significantly 18.5 +/- 8.1% (P<0.001) only after 300 micro gram of clonidine. Clonidine 150 microgram and 300 microgram decreased IOP 32.1 +/- 14.3% (P<0.001) and 47.8 +/- 17.2% (P<0.001) respectively. After 150 micro gram of clonidine, patients were significantly more sedated as compared to those given placebo (pc0.01) but significantly less sedated than after 300 micro gram of clonidine (P<0.01), where sedation persisted more than 6 hours postoperatively. The authors concluded that a dose of 150 micro gram of clonidine given orally 90 to 120 minutes preoperatively to elderly patients managed with local anaesthesia is as effective as a dose of 300 micro gram in decreasing IOP perioperatively without causing excessive haemodynamic depression and sedation.
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Background: Shivering after subarachnoid block has various deleterious effects. Can be prevented and treated by various non pharmacological and pharmacological methods. Both of these act as synergistic to each other. Objective: To compare the efficacy, potency, hemodynamic effects and side effects of oral clonidine and tramadol in geriatric patients under spinal anaesthesia. Methods: A total of 150 patients undergoing TURP under spinal anaesthesia were randomly divided into GC (50) received oral clonidine 150microgram, GT (50) recieved oral tramadol 50mg, GP (50) recieved placebo preoperatively. In the intraoperative and postoperative period, grades and incidence of shivering were noted in all three groups and treated, if required. Results: Severity grades and incidence were low in group C and group T than group P however goup T had higher incidence and grades than group C. Both decreases incidence and grades of shivering and need of rescue doses. However, clonidine is better than tramadol but causes sedation. Conclusion: prophylactic oral clonidine and tramadol are effective in preventing shivering without side effects, with oral clonidine better than tramadol.
group. Patients premedicated with clonidine had more stable haemodynamics than those pre-treated with diazepam Clonidine premedication effectively blunted the cardiovascular response to surgical stress, especially pneumoperitoneum. Compared with the baseline measurements, there was significantly less increase in heart rate and MAP in the clonidine group compared to the diazepam group and it is almost similar to the study done by Shivinder Singh etal 17 .
and respiratory rate were recorded. These values were noted down as the preoperative value (PO). Then the patients were randomly assigned into three groups of 25 patients each. Group I: control group patients received T.Diazepam 0.1mg/kg (rounded off to the nearest 5mg). Group II: clonidine group patients received T. Clonidine (CATAPRES) 5 microgram / kg, rounded off to the nearest 50 microgram (maximum 0.3 mg) in addition to T.Diazepam 0.1mg/kg rounded off to nearest 5 mg. Group III: Atenolol group patients received T.Atenolol 50 mg (TENORMIN) in addition to T. Diazepam 0.1mg/ kg rounded off to nearest 5 mg. All the drugs were given with sips of water about 2 hours prior to induction of anaesthesia . No anticholinergic drug was given either before or at the time of induction of anaesthesia.
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Table 3 shows the heart rate and blood pressure measurements during the induction of anesthesia at 0, 5 and 10 minutes respectively. It is inferred from the table that the heart rate, systolic BP, diastolic BP and the MAP are statistically significantly lower among the clonidine group of patients when compared to the diazepam group at almost all the time intervals during the induction of anesthesia. So it is shown that clonidine seems to be hemodynamically more efficacious than diazepam.
In our study we have used BIS monitor to assess the depth of Anaesthesia. End tidal Isoflurane concentration (Etiso %) was titrated to keep the BIS between “40-60”. We found that the Et iso (% ) concentration was similar between the two groups during intubation, at after prone position, and 15 min after prone position. At 30 min, 1 hr. and 2 hrs. after prone position, the isoflurane concentration to keep the BIS between 40-60 was significantly less in the Dexmedetomidine group compared to clonidine premedication group. This can be explained by, the peak effect of Dexmedetomidine takes 30 min after intravenous administration that is why, the Et iso concentration till 30mins after prone position was similar in both the groups after 30mins there was a significant reduction in Et iso concentration till 2 hrs. Administering the Dexmedetomidine 30 min prior to starting of surgery could have produced significant reduction in Etiso from the beginning but this was not feasible in our study.
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Clonidine inhibits noradrenaline release from the peripheral prejunctional nerve endings and this may lead to bradycardia. Among the different vascular beds the effects of Clonidine on the coronary circulation is important. Clonidine has been documented to release EDRF (Endothelial derived relaxant factor) in coronary arteries and to enhance coronary blood flow induced by endogenous and exogenous adenosines. Intravenous Clonidine causes a transient hypertensive response due to this direct action on the post-synaptic α 2 receptors. However this effect is soon
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Laryngoscopy and endotracheal intubation are powerful stimuli which can increase the sympathetic activity leading to tachycardia, hypertension and dysrrythmias. These haemodynamic changes are associated with the release of catecholamines (cortisol and nor- epinephrine), which are prone to get aggravated with laparoscopy using CO2 pneumoperitoneum concomitantly. Pre-emptive analgesia with Gabapentin and Clonidine blunt the stress response to anaesthetic and surgical stimuli, also reduce the narcotic and anaesthetic doses in peri operative period. This feature makes Clonidine or Gabapentin useful in the anaesthetic management of patients undergoing laparoscopic surgeries. Accordingly this study was designed to compare the pre-emptive analgesia of oral Gabapentin and Clonidine in attenuating the haemodynamic response to intubation and decreasing the post-operative pain in patients undergoing laparoscopic cholecystectomy. Gabapentin belongs to the second generation anticonvulsant drugs. It is an inhibitory neurotransmitter, 1-(amino methyl) cyclohexane acetic acid, a structural analog of GABA. Peak plasma concentration is reached in 2 to 3 hours after oral intake. Gabapentin is eliminated from the systemic circulation as unchanged drug in urine and unabsorbed drug is excreted in faeces. Elimination half life is 5-7 hours in normal renal function.
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Because of its analgesic action in the spinal cord, clonidine was initially given either by the epidural or intrathecal routes. Epidural or intrathecal clonidine is not neurotoxic and thousands of patients have received the drug by these routes without neurological complication. However, because of the large epidural doses that are necessary to obtain long-term analgesia (up to 2-3000 mcg per 24 H for the epidural route!) sedation, hypotension and bradycardia are common. The use of epidural clonidine as the sole analgesic agent is thus not popular, and combination of epidural clonidine with either opioids and / or local anaesthetics is more commonly used for postoperative analgesia. Even here, the dose should be limited to between 10 and 15 mcg/kg/hour to avoid side effects.
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doses of anaesthetic drugs, attenuates the hemodynamic responses to laryngoscopy and intubation, decreases intraoperative lability of blood pressure and heart rate, decreases MAC of volatile agents, provides analgesia and reduces post-operative shivering. Thus preservative free clonidine when injected epidurally (2-10mcg/kg) or in to the sub- arachnoid space (0.3 to 3 mcg/kg) produces dose dependent analgesia and prolongation of regional anaesthesia by acting on the substantia gelatinosa of spinal cord. Injection clonidine 3 mcg/kg administered intravenously inhibits shivering by inhibition of central thermoregulatory control. Oral clonidine attenuates the heart rate and blood pressure that usually follows ketamine administration. It is also used to diagnose phaeochromocytoma where there is lack of suppression of plasma norepinephrine to less than 500 pg/ml, three hours after a oral dose of 0.3mg clonidine. It is also used in the treatment of hypertension and diabetic diarrhoea.
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Sukmindher jit et al conducted a study to compare two α- 2 adrenergic agonists dexmedetomidine and clonidine in epidural anaesthesia. A prospective randomized trial was carried out which included 50 adult female who underwent vaginal hysterectomies. The patients were randomly assigned into two groups as below ropivacaine + dexmedetomidine (RD) and ropivacaine + clonidine (RC). Onset of analgesia, sensory and motor block levels, sedation, duration of analgesia and side effects were observed. Sedation scores were better with dexmedetomidine than clonidine and based on the results it was concluded that dexmedetomidine is a better neuraxial adjuvant than clonidine for providing early onset of sensory analgesia, adequate analgesia and a prolonged post-operative analgesia.
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needle was used for sub-arachnoid placement. 0.5% hyperbaric bupivacaine 10 mg was injected in B group and 0.5% hyperbaric bupivacaine 10 mg + clonidine 75µg was injected in C group. The patients were then turned supine and a wedge placed under the right buttock. The level of sensory blockade was assessed by pin prick and the surgery proceeded after adequate motor and sensory block were achieved. The pulse rate and blood pressure were monitored at an interval of every 2 min till the delivery of the baby and every 5 minutes thereafter. A fall of MAP by 25% from the base line value was considered as hypotension and managed with intravenous fluids, oxygen and Inj. ephedrine in titrated incremental doses.
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General procedure to prepare PVC membrane was as follow: different amounts of ion-pair along with appropriate amounts of PVC, plasticizer and additive were dissolved in tetrahydrofuran (THF), and the solution was mixed well into a glass dish of 2 cm diameter. Then, THF was evaporated slowly until an oily concentrated mixture was obtained. A plastic tube (about 3 mm o.d.) was dipped into the mixture for about 10 s so a transparent membrane of about 0.3 mm in thickness was formed. The tube was then pulled out from the mixture and kept at room temperature for about 5 h. Afterwards, the tube was filled with an internal filling solution (1.0×10 -3 M of Clonidine hydrochloride solution). The electrode was finally conditioned for 20 h by soaking in the same solution [18-23].
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produced by drugs that act on GABA receptors such as midazolam. Clonidine produces sedation by decreasing the sympathetic nervous system activity and the level of arousal. Clonidine lacks the psychotropic quality of benzodiazepines and causes a state of sedation more similar to normal sleepiness, where a patient can be easily aroused. Drugs that activate GABA receptors produce a clouding of consciousness and can cause paradoxical agitation as well as tolerance or dependence. Clonidine is devoid of respiratory depressant action and lacks the negative effects on cognition, memory and behaviour as seen with midazolam. 47
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Patients were not premedicated due to the evaluation of the potential sedation caused by clonidine. Before intrathecal injection, patients underwent standard monitoring (Datex- Ohmeda S/5 (TM) Monitor, Helsinki, Finland), including an electrocardiogram (5 lead), noninvasive blood pressure and pulse oximeter; we also noted baseline vital parameters. We obtained intravenous (IV) access with an 18-gauge IV canula (Novomed Ltd, Dublin, Ireland) and we administered 0.9% sodium chloride solution (250 mL). Spinal anesthe- sia was performed with the patient in the sitting position, using a 25-gauge Quincke needle (Yale TM Spinal Becton Dickinson, Madrid, Spain) with a midline approach at L3-4 interspace. After intrathecal injection, patients were imme- diately placed in the supine position and, when T10 sensory block was achieved, they were placed in the lithotomy posi- tion for the start of the surgical intervention.