Sepideh Vahabi ( Lorestan University of Medical Sciences, Lorestan,Islamic Republic of Iran. )
Mohamad Heidari ( Lorestan University of Medical Sciences, Lorestan,Islamic Republic of Iran. )
Amir Hooman Kazemi ( Lorestan University of Medical Sciences, Lorestan,Islamic Republic of Iran. )
Mehdi Birjandi ( Lorestan University of Medical Sciences, Lorestan,Islamic Republic of Iran. )
Elham Iran-Pour ( Urology and Nephrology Research Center (UNRC), Tehran, Islamic Republic of Iran )
Objective: To assess the effect of oral clonidine as a premedicative drug on 24-hour urine output, urine specific gravity, plasma renin activity as well as serum and urine electrolytes levels.
Methods: This prospective study was carried out on 60 women aged 20-40 years old undergoing repair of cystocoele - rectocoele perineorraphy under general anaesthesia in Asali Hospital in 2004 in Khorramabad, Iran. Subjects were randomly divided into two equal groups of 30 each. Group I and group II received clonidine tablet at the dose of 5mg/kg and placebo tablet, respectively, 90 minutes before induction of general anesthesia. In this study, blood and urine samples were taken for laboratory measurements prior as well as 6 hours after taking the tablets. Differences between the two groups were compared through Mann-Whitney u-test, c² test and t-student test. P-value<0.05 was considered statistically significant.
Results: There were no significant changes before and after receiving tablets in urine and blood Na and K as well as urine specific gravity in group II (P >0.05). Group I had higher urine Na and K level (P=0.001), however, no differences had been shown in blood Na and K level (P>0.05). Urine specific gravity was lower in group I after receiving tablet (P<0.009). A significant increase in 24-hour urine output (P=0.001) and a marked decrease in plasma renin activity was seen in group I (P=0.001).
Conclusion: This study suggests that clonidine is a safe premedicative drug in anaesthesia and does not change the serum electrolytes levels (JPMA 60:570; 2010).
Clonidine, an imidazoline compound,1 is a selective alpha2 adrenoceptor agonist2-4 that is used as a premedicant and valuable adjunct in anaesthesia in recent years. Desirable effects of clonidine in anaesthesia include sedation, analgesia, perioperative haemodynamic stabilization, and diminishing the requirement of other anaesthetic drugs.5 Clonidine may also be used to reduce supine hypertension,4 nocturnal natriuresis,4 withdrawal syndrome from dependence on narcotics, opiate, alcohol and nicotine (smoking), panic disorder, emesis in cancer chemotherapeutic regiment, diabetic diarrhoea5 and cirrhosis.3 Although clonidine affects different organs, its effect on renal system as diuresis is significant. The exact mechanism is not fully understood. However, there are theories on how this drug acts on the renal system.6-12
This study was designed to evaluate the effect of clonidine as a premedicative drug on plasma renin activity, 24-hour urine output, urine specific gravity as well as serum and urine electrolytes levels.
This prospective, randomized, double-blind and placebo-controlled study was carried out on 60 women aged 20-40 years in American Society of Anaesthesiologists (ASA) physical status I, II undergoing repair of cystocoele - rectocoele perineorraphy under general anaesthesia in Asali Hospital Khoramabad, Iran in 2004. Patients with hypertension, cardiovascular, renal and psychotic diseases were excluded from this study. After obtaining the approval from the hospital ethics committee and written informed consents from the patients, they were randomly divided into two equal groups of 30 cases each. Group I and group II received Clonidine tablet at the dose of 5mg/kg and placebo tablet, respectively, with 30cc water 90 minutes before induction of anaesthesia. Foleys catheter was then inserted. General Anaesthesia was induced with sufentanil (2mg/kg) and thiopental (5mg/kg); and tracheal intubation was facilitated with atracurium (0.3mg/kg), followed by oxygen and nitrous oxide (30%, 70%, respectively) in combination with halothane which varied from 0.5% to 1.5%. Patients were monitored for blood pressure (BP), pulse rate (PR), electrocardiogram (ECG) and pulse oximetry. At the end of the operation, residual of neuromuscular block was reversed by neostigmine and atropine. The injected fluid used during the anaesthesia course was crystalloid solution (Nacl 0.3% plus dextrose 3.33%) based on the following formula: Replacement of insensible loss (2 ml/kg/h) plus moderate surgical trauma loss (5 ml/kg/h) plus blood loss (every 1 ml of blood loss with 3 ml of serum) plus urine loss (every 1 ml urine loss with 1 ml of serum). On the first day of the surgery, patients received 2 ml /kg/hour of dextrose 5% - Nacl 0.9% serum. Blood and urine samples were assessed prior as well as 6 hours after taking the tablets for determining Na, K, urine specific gravity and plasma renin activity. Besides, the 24-hour urine output was charted. Data were analyzed by Mann-Whitney u-test, c² test and t-student test. P-value<0.05 was considered statistically significant.
Baseline demographic and background characteristics were similar between groups I and II. There were no significant differences between the two groups regarding BP, PR, ECG and pulse oximetry. There were no significant changes before and after receiving tablets in urine and blood Na and K as well as urine specific gravity in group II (P >0.05) (Table-1). Group I had higher urine Na and K level (P=0.001), however, no differences had been shown in blood Na and K level (P>0.05) (Table-1 and 2).
Urine specific gravity was lower in group I after receiving the tablet (P<0.009) (Table-1). This change was significant compared to group II (Table-2). Significant increase in 24-hour urine output (P=0.001) was seen in group I compared to group II (Table-3).
Significant decrease in plasma renin activity was seen in group I (P=0.001) (Table-3).
In a study by Laisalmi et al in 2001, the effect of clonidine with dose of 4.5 mg/kg and placebo on haemodynamics, neuroendocrine response and parameters were compared in 30 patients undergoing laparoscopic cholecystectomy. Results showed no differences in urine output, urine oxygen tension and anti-diuretic hormone between the groups.13 In another study done by Buchman et al, transdermal clonidine in patients with proximal jejunostomy increased weekly urine volume although it was not significant.14 This is in line with our findings on the increased urine output by clonidine.
Lenaert et al in 2006, concluded that additional administration of clonidine to diuretics in ascitic patients induced diuresis3 which is also compatible with our study.
Poliak et al concluded that clonidine tablet causes decrease in noradrenaline and dopamine level as well as plasma renin activity, but no change in epinephrine level was seen.15
In a study carried out by Mase et al in 1996, intravenous administration of clonidine in awake dogs led to increase in renal prostaglandins and decrease in plasma renin activity that induced hypo-osmotic diuresis.16 Similar findings were observed in our study.
El-Mas and colleagues in 2007 demonstrated that clonidine with dose of 150 microgram/kg per day for 12 weeks in rats increased urine output during 8-hour treatment period. Plasma and urine osmolality and electrolytes were not altered by clonidine17 while in our study, group I had higher urine electrolytes level and lower urine osmolality. This difference may be due to a different dosage of clonidine used in our study (5 microgram /kg).
This study showed that clonidine as a premedicative drug does not decrease blood electrolytes and increases 24-hour urine output and urine Na and K level as well. Moreover, it decreased plasma renin activity and urine specific gravity, thereby requiring appropriate fluid therapy in perioperative period.
This work was supported by grants from Lorestan University of Medical Sciences. The authors would like to thank Dr. Mahnoosh Davoodzade for her contribution to laboratory analysis.
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