Thoracic epidural anesthesia for laparoscopic cholecystectomy using either bupivacaine or a mixture of bupivacaine and clonidine: A comparative clinical study.

INTRODUCTION: Traditionally laparoscopic cholecystectomy is done under general anesthesia. But recently there is a growing interest to get it conducted under central neuraxial blockade. We conducted a clinical study comprising bupivacaine alone or a combination of bupivacaine and clonidine (2 μg/kg) in thoracic epidural anesthesia for laparoscopic cholecystectomy (LC). The aim was to attenuate the undesirable hemodynamic changes due to pneumoperitoneum (PNO) and achieve a better qualitative blockade. PATIENTS AND METHODS: After taking approval from Institutional Ethical Committee, 50 adult patients of ASA grade I and II were divided into two groups; group A where bupivacaine was given with 2 μg/kg of clonidine (Cloneon, Neon) and in group B bupivacaine (Anawin, Neon) was given with 1 ml of saline as placebo. Thoracic epidural was given at the T9-T10 or T10-T11 interspace to obtain a block of T4-L2 dermatome. Hemodynamic parameters like heart rate (HR), noninvasive blood pressure (NIBP), respiratory rate (RR), electrocardiogram (ECG), oxygen saturation (SpO2) and arterial pressure of carbon dioxide (PaCO2) were monitored and readings were recorded before and 10 minutes (min.) after the blockade and then at 5 min, 15 min and 30 min after PNO and 15 min after exsufflation.
RESULTS: All the parameters of the patients in group A remained stable but the patients of group B showed an increase in mean arterial pressure (MAP) and HR at 5, 15 and 30 min after PNO and 15 min after exsufflation as compared to Group A. PaCO2, SpO2 and RR values in both the groups were comparable. In group A, two patients complained of shoulder pain while in group B12 patients complained of shoulder pain.
CONCLUSION: Thoracic epidural anesthesia for LC is a satisfactory alternative technique in selected cases. Addition of clonidine (2 μg/kg) to bupivacaine produces better qualitative anesthetic conditions. It prevents hemodynamic perturbations produced by pneumoperitoneum and also decreases the incidence of shoulder pain. Thus we strongly advocate the incorporation of clonidine as an adjuvant in thoracic epidural anesthesia for LC.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Laparoscopic surgery results in many benefits but significant hemodynamic changes are observed during laparoscopy due to PNO. These changes can be attenuated by optimizing preload before pneumoperitoneum and by direct vasodilating drugs viz., α2-adrenergic receptor agonist like clonidine, high doses of opioids and ß-blocking agents. Clonidine given before PNO reduces catecholamine release and decreases hemodynamic changes due to stress response.

Laparoscopic cholecystectomy is usually done under general anesthesia. Thoracic epidural anesthesia has also been used for LC. Epidural clonidine has been used for postoperative analgesia but no literature is available regarding its intraoperative use in LC to decrease the hemodynamic effects of pneumoperitoneum when thoracic epidural was used as sole anesthetic. We used thoracic epidural as sole anesthetic technique in laparoscopic cholecystectomies. To attenuate hemodynamic effects of carbon dioxide insufflation, we used 2 μg/kg of clonidine as an adjuvant in thoracic epidural anesthesia and compared its effects with that of bupivacaine alone.

PATIENTS AND METHODS

After getting approval from the Ethical Committee of the institution, we selected 50 patients of ASA grade I and II of either sex with age between 29 and 55 years and weight ranging between 45 and 70 kg. The exclusion criteria were body weight more than 25% of ideal weight, presence of acute cholecystitis, cardiorespiratory disease with medications, patients with jaundice and common bile duct (CBD) stones, pregnancy, abnormal coagulation profile and unwilling patients.

Thorough preanesthetic checkup was done and informed written consent was taken the day before surgery. Tablet alprazolam 0.25 mg and tablet ranitidine 150 mg were given orally as premedication at night before surgery. The patients were randomly divided into two groups. Group A was given bupivacaine and clonidine and Group B was given bupivacaine and 1 ml of saline. The syringes were prepared by an anesthetist who was unaware of the proceedings. On the day of surgery intravenous (IV) access was established, monitors attached and baseline parameters were recorded. Ringer lactate (15-20 ml/kg) was infused before giving epidural anesthesia. Each patient was placed in sitting position and thoracic epidural was given in T9-T10 or T10-T11 interspace with full aseptic precautions. The Tuohy's (18-G) needle was inserted in paramedian position after local infiltration with 2% lignocaine hydrochloride. Loss of resistance to air technique was used to identify the epidural space and epidural catheter was inserted and advanced 2-3 cm in cephalad direction. After test dose of 3 ml of 2% lignocaine hydrochloride with adrenaline; 15 ml of 0.5% bupivacaine and 2 μg/kg of clonidine were injected through the catheter after placing the patient in the supine position in Group A; and 15 ml of 0.5% bupivacaine and 1 ml of saline were injected in Group B. If required, 5 ml increments of 0.5% bupivacaine were given in the epidural space so as to obtain a block of T4-L2 dermatome. The onset and extent of blockade was assessed by response to pin prick method and hemodynamic parameters were recorded 10 minutes after the blockade. Inj. ondansetron 4 mg and Inj. butorphanol 1 mg IV were given to all patients. After the desired level of analgesia was achieved, the carbon dioxide was insufflated slowly at 2 L/min using low flow setting of insufflator, to achieve an intra-abdominal pressure (IAP) of 10-12 mmHg, in trendelenburg position. When desired level of IAP was achieved, the tilt was changed to head-up and right side-up position.

Throughout the perioperative period HR, NIBP, RR, ECG, SpO2 and PaCO2 were monitored and readings were taken 5 min, 15 min and 30 min after PNO and 15 minutes after exsufflation. All the patients were catheterized and oxygen was administered to all the patients by face mask. When hypotension occurred, it was corrected easily by IV fluids and inj. mephenteramine.

At the end of the study the data was compiled systematically and analyzed using statistical package for social sciences (SPSS) version 15 for Windows. Chi-square test was used to compare the proportional data. Mean differences were compared using students T-test and a P value < 0.05 showed a significant intergroup difference.

RESULTS

The demographic profiles of the patients of both the groups were comparable. SpO2 in both the groups remained within 95%-99%. PaCO2 increased but was comparable in both groups (P > 0.05) and remained within 39-51 mmHg. RR increased and it was comparable in both groups (P > 0.05).

Increase in mean arterial pressure (MAP) and HR was significant (P < 0.05) in control group at 5 min, 15 min and 30 min after pneumoperitoneum and 15 min after exsufflation in comparison to clonidine group. The MAP remained below preoperative levels throughout the surgery in group A. Increase in BP and HR occurred in control group after pneumoperitoneum which in contrast did not occur in clonidine group. Two patients complained of shoulder pain in clonidine group as compared to 12 patients in control group, which responded to IV dose of 25-50 mg of ketamine. Nasogastric tube and endotracheal intubation was not required in any patient in both the groups. No complication related to epidural anesthesia occurred in any patient.

Postoperative nausea and vomiting (PONV) occurred in three patients of control group and two patients of clonidine group. The patients were started oral liquids and mobilized the next day.

DISCUSSION

Laparoscopic cholecystectomy has become an established procedure of choice in the management of symptomatic cholelithiasis; however, it produces hemodynamic changes due to carbon dioxide pneumoperitoneum. Joris et al. documented that peritoneal insufflation of carbon dioxide (CO2) to an intra-abdominal pressure (IAP) >10 mmHg causes decrease in venous return and cardiac output (CO) and increase in MAP, systemic and pulmonary vascular resistance. However, peritoneal insufflation of CO2 to an IAP < 10 mmHg does not produce significant hemodynamic changes in healthy patients. This reduction in CO and venous return can be attenuated by increasing circulating volume before PNO is produced. Preloading with 15-20 ml/kg of ringer lactate and insufflation in supine or 10° head down position and then tilting patients gradually to head-up position after CO2 insufflation, attenuates hemodynamic changes.[1] In this series we had used only 10-12 mmHg. IAP during PNO.

Hayashi and Maze reported that clonidine is a α2 adrenergic agonist. It is highly lipid soluble and hence readily penetrates blood brain barrier. Epidural administration of clonidine (1-4 μg/kg) produces sedation, improves the quality of block and prolongs the postoperative analgesia 2-3 folds. Sedation is one of the most consistent properties of clonidine due to its effect on locus coeruleus and this sedative effect is [Figures 1 and 2] attainable even when given epidurally[2] Bernard et al. reported that analgesia induced by epidural clonidine is mediated by activation of α2-adrenergic receptors on the dorsal horn of the spinal cord. Plasma clonidine concentrations are comparable after intravenous or epidural administration of a similar dose owing to rapid and extensive absorption of the drug from the epidural space. The supraspinal effects after epidural injection of clonidine are mainly due to absorption of the drug into the blood. Analgesic response involves both supra spinal and spinal sites. Hypotension and bradycardia caused by clonidine are centrally mediated by inhibition of sympathetic outflow. In clinically appropriate doses respiratory depression does not occur. Its potency is enhanced synergistically with concomitant administration of opioids.[3]

Figure 1

Epidural catheter is being inserted

Figure 2

The patient is awake and free of pain after LC

Traditionally LC is done under GA. Recently there is a growing interest in the anesthetic management of LC with TEA or subarachnoid block (SAB), hence this study was conducted to assess and compare the hemodynamic effects of TEA with and without epidural clonidine as an adjuvant for LC.

In our study which comprised 25 patients in each group, the demographic characteristics were comparable and statistically insignificant with regard to age, weight, sex and ASA grading, as shown in the Table 1 of demographic data. All patients received TEA at T9-T10 or T10-T11 to attain a block from T4-L2. Only bupivacaine was given epidurally in group B whereas a combination of bupivacaine and clonidine was administered in group A. HR, MAP, RR, ECG, SpO2 and PaCO2 were monitored and readings were taken at the specified intervals as shown in the tables. The first clinically significant change in HR and MAP occurred at 5 min after PNO in group B (as compared to group A) thereafter HR and MAP in group B remained significantly elevated throughout the procedure while in group A, HR and MAP remained below baseline reading throughout the operation and this can be attributed to clonidine. Thus the rise in BP and HR due to absorption of CO2 is alleviated by clonidine. Therefore it can be emphasized that this technique is good for hypertensive and coronary artery disease patients.

Table 1

Demographic data

The magnitude of increase in RR and PaCO2 in both the groups was similar and statistical comparison was insignificant. The consistent increase in PaCO2 after PNO in both groups corroborates the hypothesis of absorption of CO2 from the peritoneal cavity. However, the increase in RR did not match with an increase in PaCO2. Thus it can be inferred that there is a tendency of mild hypercapnia in patients undergoing LC in epidural anesthesia in spite of the fact that there is approximately 25% increase in RR to compensate the rising PaCO2 due to PNO. Tzovaras et al. and Imbelloni et al. compared spinal anesthesia with GA for LC. They reported that LC with low pressure PNO can be safely performed under spinal anesthesia.[45]

The similar results were expressed by Pursnani et al., Kim et al. and Gramatica et al., who conducted LC under epidural anesthesia in COPD patients.[678] Thus it can be assumed that LC can be done under epidural anesthesia even in patients with mild to moderate respiratory insufficiency provided due caution is exercised.

The sedative and analgesic action of clonidine acted synergistically with that of butorphanol and produced a better quality of block thus reducing the incidence of shoulder pain also. Subanesthetic doses of ketamine (0.5 mg/kg) were administered in the patients who complained of shoulder pain. The incidence of shoulder pain is also proportional to the magnitude of IAP. Sarli et al., Sandhu et al., Kar et al. and Sinha et al. have documented that a low IAP reduces the incidence of shoulder pain.[9101112] Yuksek et al. used 25 μg of fentanyl IV to alleviate shoulder pain when LC was done in spinal anesthesia. They also did local washing of right diaphragm with 2% lidocaine in five cases.[13] Van zundert et al. conducted LC under segmental thoracic spinal anesthesia at T-10 level. 1 ml of 0.5% bupivacaine (5 mg/ml) was mixed with 0.5 ml of sufentanil (5 μg/ml). They also noted shoulder pain in two of their patients.[14]

Ghodki et al. gave intrathecal clonidine besides bupivacaine in spinal anesthesia for LC which provided prolonged postoperative analgesia and sedation besides relief of shoulder pain.[15] Rademaker et al. used continuous thoracic epidural for LC and found that metabolic endocrine response was attenuated and postoperative pain was also less.[16] Ciofolo et al. reported that epidural anesthesia per se does not induce any ventilatory depression.[17] Lee et al. reported that epidural anesthesia may be used for LC. However, careful patient recruitment and management of shoulder pain should be considered.[18] Gupta et al. used 10 mm Hg IAP in epidural anesthesia for LC. They used ketamine for shoulder pain in 15 patients. Besides this they instilled 12 ml of 0.25% bupivacaine into the right subdiaphragmatic space in all the patients.[19]

Sung et al., Passi et al., Singh et al., and Joris et al. have used oral or IV clonidine during GA to suppress hemodynamic response of CO2 pneumoperitoneum.[202122] In patients, under epidural anesthesia PaCO2 may increase during LC, which can potentially cause acidosis, and arrhythmias. However, we did not observe any change in heart rhythm in any of the patients of this series.

CONCLUSIONS

Thoracic epidural anesthesia for LC is a satisfactory alternative technique in selected cases. Addition of clonidine (2 μg/kg) to bupivacaine not only produces better qualitative anesthetic conditions but also prolongs the duration of analgesia. It prevents hemodynamic perturbations produced by pneumoperitoneum and also decreases the incidence of shoulder pain. Thus we strongly advocate the incorporation of clonidine as an adjuvant in thoracic epidural anesthesia for LC.