|Year : 2007 | Volume
| Issue : 3 | Page : 205-210
Haemodynamic changes during laparoscopic cholccystectomy: Effect of clonidine premedication
Mrinmoy Das1, Manjushree Ray2, Gauri Mukherjee3
1 PG Student, Department of Anaesthesiology, Medical College, Kolkata-73, India
2 MD, MNAMS, Professor & HOD., Department of Anaesthesiology, Medical College, Kolkata-73, India
3 DA, MD, Assistant Professor, Department of Anaesthesiology, Medical College, Kolkata-73, India
|Date of Acceptance||20-Mar-2007|
|Date of Web Publication||20-Mar-2010|
12/1, A. K. Point, 68B, A.P.C. Roy Road, Kolkata-700 009
Source of Support: None, Conflict of Interest: None
Clonidine has been shown to reduce perioperative haemodynamic instability. The aim of the study was to investigate the clinical efficiency of oral clonidine premedication in prevention of haemodynamic response associated with pneumoperitoneum.
Sixty adult patients of ASA physical status I& II, scheduled for elective laparoscopic cholecystectomy were recruited for a prospective randomized, double-blinded comparative study. They were randomly allocated to one of the two groups to receive either oral clonidine 150 gg (Group C) or ranitidine 150 mg (Group P), 90 minute before induction of anaesthesia.
Significant rise in heart rate was observed following pneumoperitoneum in Group P as compared to Group C (99.23±14.02 Vs 81.26±8.40 bpm). Similarly, rise in systolic arterial pressure (143.63±19.60 Vs 119.6±10.06 mm Hg), diastolic arterial pressure (99.23±14.02 Vs 81.26±8.40 mm Hg) and mean arterial pressure (114.13±16.57 Vs 93.83±8.107 mm Hg) was more in Group P following pneumoperitoneum. Nitroglycerine drip was started in 33.3% patients in Group P to control intraoperative hypertension. Incidence of postoperative nausea-vomiting and shivering was also less in Group C.
To conclude, clonidine premedication provides perioperative haemodynamic stability, hence it can be recommended as a routine premedication for laparoscopic procedure.
Keywords: Laparoscopic cholecystectomy; Pneumoperitoneum, Haemodynamic response; Clonidine premedication.
|How to cite this article:|
Das M, Ray M, Mukherjee G. Haemodynamic changes during laparoscopic cholccystectomy: Effect of clonidine premedication. Indian J Anaesth 2007;51:205-10
|How to cite this URL:|
Das M, Ray M, Mukherjee G. Haemodynamic changes during laparoscopic cholccystectomy: Effect of clonidine premedication. Indian J Anaesth [serial online] 2007 [cited 2021 Jul 26];51:205-10. Available from: https://www.ijaweb.org/text.asp?2007/51/3/205/61143
| Introduction|| |
Laparoscopic cholecystectomy has revolutionized gall bladder surgeries and it has now become the "gold standard" of cholelithiasis. It offers many benefits than conventional cholecystectomy, and has been promoted, as a "gentle surgery". However, this procedure is not risk free. In fact it produces significant haemodynamic changes specially in elderly and haemodynamically compromised patients.
Pneumoperitoneum (Pnp) affects several homeostatic systems leading to alteration in acid-base balance, cardiovascular, pulmonary physiology and stress response. The extent of cardiovascular changes associated with pneumoperitoneum include an increase in mean arterial pressure, decrease in cardiac output and increase in systemic vascular resistance which in turn compromise tissue perfusion.
Various pharmacological agents were chosen to prevent haemodynamic changes associated with pneumoperitoneum. Nitroglycerine was used to correct the reduction of cardiac output associated with increased pulmonary occlusion pressure and systemic vascular resistance. 
Aho et al  used á2 adrenergic receptor agonist for prevention of haemodynamic responses associated with laparoscopic surgery. They found that dexmedetomidine effectively reduces the maximum heart rate response after intubation and pneumoperitoneum. Clonidine inhibits the release of catecholamine and vasopressin and thus modulates the haemodynamic changes induced by pneumoperitoneum. 
Considering all these observations, the present study was designed to evaluate the type and extent of haemodynamic changes associated with laparoscopic surgery and also to find out the efficacy of clonidine in prevention of such haemodynamic changes.
| Methods|| |
This randomized prospective study was carried out in 60 adult patients of ASA physical status I and II, scheduled for laparoscopic cholecystectomy. The study was approved by the institutional Ethical Committee and written informed consent was obtained from all the patients before being included in the study. Patients with history of hypertension, ischaemic heart disease, aortic stenosis, left ventricular failure and atrioventricular conduction block were excluded from the study. Patients concomitantly taking clonidine, methyl dopa, beta blocking drugs, benzodiazepines and MAO inhibitors were also excluded from the study.
All patients received diazepam 5mg orally on the night before surgery. They were randomly assigned to one of the two groups to receive either clonidine 150 µg (Group C) or ranitidine 150 mg (Group P) orally 90 minutes before induction of anaesthesia. The observer was totally blind about the groups or medications received by the patients. Group sizes of 30 were determined by power analysis based on standard deviation data from previously published reports.
On arrival in the operation theatre, monitors were attached and baseline parameters such as heart rate, systemic arterial pressure and peripheral oxygen saturation were noted down. Level of sedation (sedation score) was assessed by sedation scale : (1) awake and agitated (2) awake and comfortable (3) asleep but arousable (4) asleep with sluggish response to persistent call or touch and (5) no response to call or touch.
After intravenous cannulation, glycopyrrolate 0.2 mg, was administered intravenously. Patients were induced with sleep dose of thiopentone sodium. Endotracheal intubation was facilitated by succinylcholine 1.5 mg.kg-1 of body weight. Anaesthesia was maintained with 33% oxygen in nitrous oxide, 0.4% halothane and vecuronium bromide 0.1 mg.kg-1. Peroperative analgesia was provided by fentanyl citrate 1.5 ug.kg-1 body weight. The tidal volume (V ) and the ventilatory frequency was adjusted and intermittent positive pressure ventilation (IPPV) was continued by mechanical ventilator to maintain end tidal carbon dioxide between 35-45 mm Hg.
Pneumoperitoneum was created by insufflation of carbondioxide and operation table was tilted about 15° reverse Trendelenburg position. Intra abdominal pressure (IAP) was not allowed to exceed 15 mm Hg throughout the surgical procedure. After pneumoperitoneum, necessary changes in ventilator setting (tidal volume, respiratory rate) were made to maintain normocapnia.
Throughout the procedure, any rise in mean arterial pressure more than 20% from the baseline was treated with nitroglycerine drip.
Systemic arterial pressure including the systolic, diastolic and mean arterial pressure, heart rate, SpO 2 , EtCO 2 and electrocardiography (ECG) with ST segment analysis were recorded at the following points of time : (1) prior to induction (2) three minutes after endotracheal intubation (3) before pneumoperitoneum (4) fifteen minutes after pneumoperitoneum (5) thirty minutes after pneumoperitoneum (6) ten minutes after release of CO 2 and (7) ten minutes after extubation.
At the end of surgery residual neuromuscular block was reversed by appropriate dose of neostigmine and glycopyrrolate intravenously. Trachea was extubated and patients were transferred to recovery room. In the postanaesthesia care unit (PACU) they were monitored for any evidence of complications or adverse events. Degree of sedation and intensity of pain were also assessed by using 10 point visual analogue scale (VAS).
The results obtained in the study are presented in tabulated manner. Statistical analysis was done by students 't' test. Chi square test was performed for nonparametric values and corresponding P was computed. P value <0.05 was considered statistically significant.
| Results|| |
Two patients were withdrawn from the study because the proposed laparoscopic cholecystectomy surgery was converted to open cholecystectomy. Aside from these two patients, 58 patients completed the analysis.
Demographic profile and preoperative vital parameters were compared among the two groups of patients and no significant difference was found [Table 1]& [Table 2]. Mean intra-abdominal pressure was 13.1±1.47 mm Hg in Group P and 12.7±1.15 mm Hg in Group C. Normocapnia was maintained throughout the procedure. EtCO 2 varied from 31.13±3.45 to35.46±5.36 mmHg in Group P and30.66±2.38 to 34.06±3.18 mm Hg in Group C.
Mean pulse rate varied from 81.43±11.21 to 113.17±13.33 bpm in Group P. In Group C it varied from 74.1±8.71 to 93.6±7.93 bpm. Upon statistical comparison in two groups of patients, significant variation was observed throughout the intraoperative period except for the baseline value when no significant difference was observed [Figure 1], [Table 3].
Changes in the blood pressure when compared in the two groups of patients was found to be statistically highly significant excepting the base line values where no significant difference was found [Figure 2], [Figure 3] [Table 4], [Table 5] and [Table 6].
Ten patients (33.3%) in Group P received nitroglycerine infusion (0.5 µg.kg -1.min -1) for treatment of intraoperative hypertension. It was not required in Group C patients, because they remained haemodynamically stable.
Intensity of pain was less in Group C as compared to Group P (VAS 1.9±1.688 Vs 5.214±2.114) during early postoperative period.
Incidence of nausea-vomiting, hypertension, shivering and shoulder pain were 35.70%, 35.70%, 10.7% and 14.3% in the Group P, while only 6.89% patients suffered from nausea vomiting in Group C. Sedation was common in Group C (33.33%). Other complications were not observed in Group C. None of the patient showed any evidence of ischaemia or arrthymia intraoperatively
| Discussion|| |
Pneumoperitoneum during laparoscopy produces significant haemodynamic changes, which can be detrimental especially in elderly and haemodynamically compromised patients. . Various techniques and pharmacological agents have been used to counteract these detrimental effects of pneumoperitoneum.
This double blind prospective study was carried out in 60 adult patients, to evaluate the effect of clonidine premedication in attenuating haemodynamic stress response associated with pneumoperitoneum.
Clonidine, an imidazoline derivative is a selective á2 adrenergic agonist. It is a potent antihypertensive drug. It produces a fall in the heart rate and blood pressure associated with decreased SVR and cardiac output. 150 µg (2.7 µg.kg -1) clonidine was administered orally, 90 minutes before surgery in this series. Dose of clonidine varied from 2 to 5 µg.kg -1 in different studies. Higher dose of clonidine (5 µg.kg -1) is usually required for potentiation of postoperative analgesia by intrathecal morphine. . A small oral dose of clonidine decreased the incidence of perioperative myocardial ischemic episodes without affecting haemodynamic stability.  Aho et al  used 3 µg.kg -1 and 4.5 µg.kg -1 clonidine for suppression of haemodynamic response to pneumoperitoneum. Rise in blood pressure and heart rate was less in both the groups but 4.5 µg.kg -1 clonidine produced greater fall in mean arterial pressure before induction. Joris et al  used very high dose of clonidine (8 µg.kg -1) for reducing the level of catecholamine and vasopressin following pneumoperitoneum. Malek et al  used 150 µg of clonidine as i.v. infusion and intramuscularly while Sung et al  and Yu et al  used 150 µg of oral clonidine as premedication for maintenance of haemodynamic stability during pneumoperitoneum.
Following pneumoperitoneum with carbon dioxide, patients were hyper ventilated to maintain normocapnia. Every effort was made to maintain intra abdominal pressure (IAP) below 14 mm Hg. Mean intra-abdominal pressure was 13.1±1.47 mm Hg in Group P and 12.7±1.15 mm Hg in Group C.
Haemodynamic changes associated with pneumo peritoneum was first recognized in 1947.  Diamant et al  reported 35% decrease in cardiac output in dog with a raised intra abdominal pressure of 40 mm Hg. Ishizaki et al  tried to evaluate the safe intra-abdominal pressure during laparoscopic surgery. They observed significant fall in cardiac output at 16 mm Hg of intra-abdominal pressure. Haemodynamic alterations were not observed at 12 mm Hg of intra-abdominal pressure. Based on all these observations the current recommendation is to monitor intra-abdominal pressure and to keep it as low as possible.
Cunningham et al  and Dorsay et al  assessed the ejection fraction (EF) of left ventricle by trans esophageal echocardiography during pneumoperitoneum. No significant change in ejection fraction was reported up to 15 mm Hg of intra-abdominal pressure. Considering all these facts intra abdominal pressure was kept below 14 mm Hg.
In spite of maintaining normocapnia and keeping intra-abdominal pressure below 14 mm Hg significant rise in heart rate, systolic blood pressure, diastolic blood pressure and mean arterial pressure was noticed in Group P. Rise in systolic, diastolic and mean arterial pressure was more than 20% from the baseline. Slight fall in systolic blood pressure, diastolic blood pressure and mean arterial pressure was noticed following premedication with clonidine. Following intubation and pneumoperitoneum, increase in arterial pressure was noticed but it never crossed the base line value. Hence clonidine premedication was able to achieve haemodynamic stability during pneumoperitoneum.
Similar findings were reported by Aho et al , Joris et al , Malek et al , Sung et al , Yu et al  and Laisalmi et al .
Aho et al  observed that 4.5 µg.kg -1 of clonidine significantly decreased the mean arterial pressure before induction of anaesthesia. So they recommended 3 µg.kg -1 of clonidine for perioperative haemodynamic stability. Joris et al  used higher dose of clonidine for reduction of catecholamine and vasopressin associated with pneumoperitoneum. Clonidine significantly reduced the concentration of catecholamine but not vasopressin and cotisol concentration. Similarly Sung et al  observed haemodynamic stability during pneumoperitoneum with 150 µg oral clonidine. Requirement of isoflurane was also less by 30% in the clonidine group. Esmolol, labetalol and nifedipine were used to control hypertension in control group. Finally Yu et al  recommended the routine use of clonidine premedication in laparoscopic patients.
The adverse effects in the postoperative period were less in the patients who had clonidine premedication in comparison with placebo premedication. There was incidence of shivering in 10.70% patients in the placebo group compared to none in the clonidine group.
This finding corroborates the finding of Nicolaou et al, where they concluded that clonidine inhibits cold thermoregulatory response due to an effect on central integration control and output from the thermoregulatory centers. . Thus he opined that clonidine can be used as an effective agent for inhibition of perioperative shivering which can adversely increase metabolic rate and cardiac work and may also disrupt surgical repair or result in wound dehiscence.
Thirty five percent of patients of the Group P suffered from nausea and / or vomiting, while only 6.89% of the patients receiving clonidine had any such episode. Clonidine increases gastrointestinal motility by decreasing sympathetic outflow and increasing parasympathetic outflow from the central nervous system. Although many workers have reported the antiemetic property of clonidine, the mechanism by which it acts warrants further investigation.
In conclusion, premedication with 150 μg oral clonidine, has been found to be relatively safe as well as effective method that provides stable haemodynamics and protection against stress response triggered by pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. Clonidine also affords an added advantage of reduction in postoperative complications such as nausea-vomiting and shivering.
Hence 150 μg oral clonidine can reasonably be recommended as premedicant for all laparoscopic procedures in otherwise healthy patients. However further study is required to find out its efficacy in patient with compromised cardiovascular system.
| References|| |
|1.||Feig BW, Berger DH, Doughtery TB, et al. Pharmacologic interventions can re-establish baseline haemodynamic parameters during laparoscopy. Surgery 1994; 116 : 733-7. |
|2.||Aho M, Scheinin M, Lehtinen AM, et al. Intramuscularly administered dexmedetomidine attenuates haemodynamic and stress responses to gynaecologic laparoscopy. Anesth Analg 1992; 75 : 932-9. |
|3.||Joris J, Chiche JD, Lamy M. Clonidine reduced haemodynamic changes induced by pneumoperitoneum during laparoscopic cholecystectomy. Br J Anaesth 1995; 74 (suppl) : A124. |
|4.||Dhoste K, Lacoste L, Karayan J, et al. Haemodynamic and ventilatory changes during laparoscopic cholecystectomy in elderly ASA III patients. Can J Anaesth 1996; 43 :783-8. |
|5.||Goyagi T, Nishikawa T. Oral Clonidine premedication causes the quality of postoperative analgesics by intrathecal morphine. Anesth Analg 1996; 82 : 1192-6. |
|6.||Malek KJ, Knor J, Kurzova A, Lopourova M. Adverse haemodynamic changes during laparoscopic cholecystectomy and their possible suppression with clonidine premedication. Comparison with intravenous and intramuscular premedication. Rozhl Chir 1999; 78 : 286-91. |
|7.||Sung CS, Lin SH, Chan KH, Chang WK, Chow LH, Lee TY. Effect of oral clonidine premedication on perioperative haemodynamic response and postoperative analgesic requirement for patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiol Scand 2000; 38 : 23-9. |
|8.||Yu HP, Hseu SS, Yien HW, Teng YH, Chan KH : Oral clonidine premedication preserves heart rate variability for patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiol Scand 2003; 47 : 185-90. |
|9.||Booker WM, French DM, Molano PA. Further studies on the acute effects of intra abdominal pressure. Am J Physiol 1947; 149 : 292-8. |
|10.||Diamant M, Benumot JL, Saidman LJ. Haemodynamics of increased intra-abdominal pressure : interaction with hypovolaemia and halothane anaesthesia. Anesthesiology 1978; 48 : 23-7. |
|11.||Ishizaki Y, Bandae Y, Shimomura K, Abe H, Ohtomo Y, Idezuki Y. Safe intra abdominal pressure of carbon dioxide pneumoperitoneum during laparoscopic surgery. Surgery 1993; 114: 549-54. |
|12.||Cunningham AJ, Turner J, Rosenbaum S, et al. Transoesophageal echocardiographic assessment of haemodynamic function during laparoscopic cholecystectomy. Br J Anaesth 1993; 70 : 621. |
|13.||Dorsay GA, Greene FL, Baysinger CL. Haemodynamic changes during laparoscopic cholecystectomy monitored with trans oesophageal echocardiography. Surg Endosc 1995; 9 : 128. |
|14.||Laisalmi M, Koivusalo AM, Valta P, Tikkanen I, Lindgren L. Clonidine provides opioid-sparing effect, stable haemodynamics and renal integrity during laparoscopic cholecystectomy. Surg Endosc 2001; 15: 1331-5. |
|15.||Nicolaou G, Jonston CE, Bristow GK. Clonidine decrease vasoconstriction and shivering threshold, without affecting the sweating threashold. Can J Anaesth 1997; 44 (Suppl). : 636-44. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]