European Journal of Cardiovascular Medicine

General anesthesia is currently the standard technique used for breast surgery. However it has various disadvantages which include, but not limited to, inadequate pain control due to a lack of residual analgesia, higher stress response, higher incidence of nausea and vomiting, and increasing the length of hospitalization.¹ The side-effects and complications of general anesthesia preclude ambulatory surgery for most patients undergoing breast surgery. Regional anaesthesia can attenuate surgical stress response and provide better analgesia with reduction in postoperative opioid consumption.²

Segmental thoracic spinal anesthesia (STSA) is gaining interest. Although the technique is not unknown and the procedure is mainly looked upon as an alternative to general anesthesia (GA), where GA was considered at higher risk of morbidity and mortality due to patients co-morbid conditions³.

There are a number of advantages to deliver the spinal anesthetic directly to the required heights in the body. Firstly, one of the most obvious advantages is that there is no blockade of the lower extremities, i.e. little caudal spread. This means that a significantly larger portion of the body experiences no venal dilation, and may offer a compensatory buffer to adverse changes in blood pressure intra-operatively. This is one of the major risks identified in surgery. Secondly, the dosing of the anesthetic is exceedingly low, given the highly specific block to only certain nerve functions along a section of the cord. Thirdly, the degree of muscle relaxation achievable without central or peripheral respiratory or circulatory depression is superior to that with general anesthesia. In addition, the danger of cardiac arrest is much diminished. Fourthly, the patients have motor control over their legs during the surgery, which in turn means many patients exhibit a high level of satisfaction with the technique and decreased anxiety.⁴

The intrathecal application of clonidine increases the duration of both sensory and motor block, as well as postoperative analgesia. The mechanism of clonidine in spinal anesthesia is reported to be mediated by presynaptic (inhibition of transmitter release) and postsynaptic (enhancing hyper polarization) effects.⁵

The aim of this prospective, randomized study was to evaluate the effects of clonidine in co-administration with bupivacaine during spinal anesthesia, regarding the onset and regression of motor block, sensory block, postoperative analgesia and possible side effects.

The present study was conducted at Chamarajnagar institute of medical sciences, chamarajnagar, Karnataka. This was a prospective comparative study conducted in a tertiary care hospital among the 70 female patients aged 18 and 80 years. To evaluate the analgesic effects of intrathecal clonidine in isobaric bupivacaine for thoracic spinal anaesthesia in patients undergoing breast surgery. The objectives of the study were explained to the patients in easily understandable local language and then informed written consent was obtained from them who fulfill the inclusion and exclusion criteria. Patients aging with ASA class I or II undergoing elective breast surgery (modified radical mastectomy for carcinoma breast, lumpectomy for breast lump/gynaecomastia, and wide local excision for phylloids tumor) and BMI < 35 Kg/m2 were included in this study. The exclusion criteria were pregnant patient, patient with bleeding disorder and cardiovascular disease; presence of infection in the site of block; known allergy to local anesthetic; patients with abnormalities of the spine (kyphosis or scoliosis), and in cases with a change in surgical plan or more than two attempts for performing regional anaesthesia procedure. After arrival in the operating room, an 18G IV cannula was inserted in a peripheral vein and infusion of balanced crystalloid solution was started. Patient’s baseline vital parameters were recorded using pulse oxymeter, ECG and non-invasive blood pressure (NIBP). Patients were placed in sitting position and T5-T6 intervertebral space was identified. Under full aseptic precautions and skin infiltration with (1% lignocaine) local anesthetics, a Quincke’s babcock spinal needle 25G was placed in mid-line/paramedian approach. Correct placement was confirmed by free flow of clear CSF. Then, Group C: 1 ml of 0.5% isobaric bupivacaine (5 mg) mixed with 0.2 ml of clonidine (30 microgram) was injected Group P: 1.2ml of 0.5% isobaric bupivacaine (5 mg) was injected and patients were placed in supine position immediately. After that, clinical examination was done to assess the sensory and motor block along with heart rate, blood pressure, and SpO2. The vital parameters were recorded in regular interval until the end of surgery. The level of sensory block was assessed by pinprick, and motor block was assessed by Epidural scoring scale for arm movements (ESSAM) score for upper limb [hand grip (T1/C8), wrist flexion (C8/C7), and elbow flexion (C6/C5)]15 and modified Bromage scale for lower limb (0 = able to lift extended legs; 1 = just able to flex knees, full ankle movement; 2 = no knee movement, some ankle movement; 3 = complete paralysis).Once the block was considered adequate (minimum block T2–T8), and patients were sedated by 1 mg midazolam intravenously. All patients were given oxygen supplementation at 5 L/min with facemask. Adverse effects were treated accordingly e.g hypotension with ephedrine, bradycardia with atropine as i.v. boluses as required, and nausea or vomiting was treated with Ondansetron 4 mg. After surgery, patients were transferred to the recovery room. The objectives of this study were intraoperative hemodynamic changes, perioperative complications, time of first rescue analgesic, total paracetamol consumption in first 24 hours. Statistical analysis: Collected data were analyzed using SPSS (Statistical Package for Social Sciences) for Windows, version23.0. Qualitative variables were expressed as frequency and percentages. Quantitative data were expressed in mean ± standard deviation. The results were presented using tables and figures.

This study was conducted among the 70 female patients undergoing breast surgery. These 70 patients were randomly allocated in to Bupivacaine group (35 patients) and Clonidine + Bupivacaine group (35 patients). The mean age (mean ± standard deviation) of the total 70 patients was 43.34 ± 16.67. The mean age of Bupivacaine group and Clonidine + Bupivacaine group was found to be 28.20 ± 4.99 and 58.49 ± 8.19 respectively. The reason for the difference in the mean age between the two groups is that the patients undergoing surgery of fibro adenoma and other begin tumour were younger patients and were given only Bupivacaine along with thoracic spinal anaesthesia. The older patients underwent surgery of malignant breast tumours and also modified radical mastectomy among which the time duration of surgery is longer so to reduce the pain, intrathecal clonidine in Bupivacaine with thoracic spinal anaesthesia was given.

Table 1: Age group wise distribution of patients underwent breast surgery (N=70)

Figure 1: Distribution of the patients according to their body mass index (BMI)

Note: Body mass index (BMI) in kg/m². Normal: 18.5 to 22.9. Over weight: 23 to 24.9.  Obesity class 1: 25 to 29.5. Obesity class 2: >30 

Figure 2: Multiple line diagram showing the means of mean arterial pressure (MAP) of Bupivacaine only group and clonidine + Bupivacaine groups among the patients underwent breast surgery

Figure 3: Multiple line diagram showing the means of pulse rate (PR) of Bupivacaine only group and clonidine + Bupivacaine groups among the patients underwent breast surgery

Table 2: Rescue analgesic on patient demand to treat the pain in Bupivacaine only group and Clinidine +Bupivacaine group (N=70)

Table 3: Number of intravenous paracetamol doses (rescue analgesic on patient demand in case of VAS score more than 30mm at rest) required to treat the pain in Bupivacaine only group and Clinidine +Bupivacaine group (N=70)

The intravenous paracetamol doses were given as rescue analgesic on patient demand for both in Bupivacaine only group and Clonidine + Bupivacaine group for relief of pain during the post operative period of first 24 hours.    

For treating the post operative pain, this difference in the requirement of number of intravenous paracetamol doses between the Bupivacaine only group and Clonidine + Bupivacaine group for the treatment of post operative pain was found to statistically significant (p< 0.001). Therefore the intrathecal administration of clonidine in isobaric bupivacaine for thoracic spinal anaesthesia is useful in reducing the post operative pain following the breast surgery. [Table 3]     

Table 4: Assessment of pain intensity using visual analogue scale (VAS) score among the post operative breast surgery patients (N=70)

[Note: Visual analogue scale (VAS) score: 0 to 4 mm is No pain, 5 to 44 mm is Mild pain, 45 to 74 mm is Moderate pain and 75 to 100 mm is severe pain]

This research study was done among the 70 female patients undergoing breast surgery. The total 70 patients were randomly divided in to Bupivacaine group (35 patients) and Clonidine + Bupivacaine group (35 patients). The mean age of Bupivacaine group and Clonidine + Bupivacaine group was found to be 28.20 ± 4.99 and 58.49 ± 8.19 respectively. The reason for the difference in the mean age between the two groups is that the patients undergoing surgery of fibro adenoma and other begin tumour were younger patients and were given only Bupivacaine along with thoracic spinal anaesthesia. Ullah MM et.al²., conducted an observational study among 55 patients completed the study successfully. Modified radical mastectomy, Lumpectomy and Wide local excision were done in 42 (76%), 8 (15%) and 5 (9%) patients, respectively. The mean age of the patients was 50.78±8.98 years.

In our study we found that, after giving anaesthesia block to the patients, the means of mean arterial pressure (MAP) were 81 +7.37 and 82 +8.74 in Bupivacaine only group and Clonidine + Bupivacaine group respectively. It was observed that the means of MAP were decreased in the both the groups of the patients in the initial intra-operative period and the post-operative period and then the means of MAP were returns to the normal MAP as the post-operative time period processes towards 24 hours. According to study conducted by Ullah MM et al.²., there were no significant changes in haemodynamic parameters during the intraoperative period. The frequencies of adverse effects were less and complications also less. Segmental thoracic spinal anaesthesia provides better satisfaction in patients undergoing breast surgery. Case report study conducted by Hobaika A.B.D.S et al.¹⁰ showed that, the thoracic spinal anaesthesia was shown to be a safe and reliable technique in the patients with severe diseases. It allowing a surgical anaesthesia, with tolerable hemodynamic changes and with no manipulation of airways 

In our study, it was observed that the means of pulse rate (PR) were decreased in the both the groups of the patients in the initial intra-operative period and the post-operative period and then the means of pulse rate (PR)  were returns to the normal pulse rate (PR)  as the post-operative time period processes towards 24 hours. A study conducted by Paliwal et al.⁶ showed that, there was no significant difference in hemodynamic parameters (except significantly lower heart rate at 15 min in group TS (P = 0.001) and surgeon satisfaction score between groups and also it showed that, the patient in group segmental thoracic spinal anaesthesia (TS) had significantly higher satisfaction score median 5 (IQR 1) compared to patients in group General anaesthesia (G) median 4 (IQR 3.5) (P = 0.001). Nausea and vomiting were significantly higher in group G compared to group TS (P = 0.01). 

Among the total 35 patients of bupivacaine only group, 25 (71.4%) of them were given first dose rescue analgesic within 1 to 2 hours in the post-operative period Among the total 35 patients in the Clonidine + Bupivacaine group, 16 (45.7%) of them were given first dose of rescue analgesic at the 5 to 6 hours of post operative period. The post operative analgesic effect is longer in the Clonidine + Bupivacaine group because of the analgesic effect of the clonidine which was given along the bupivacaine. [Table 4] Study conducted by Ullah MM et al.² showed that, the mean time for 1st dose of analgesic was 5.8±1.8 hours and total opioid consumption was 76.77±15.7 mg in first 24 hours. Both patient (91%) and surgeon (95%) were highly satisfied with Segmental Thoracic Spinal Anaesthesia technique.

A study conducted by Gecaj-gashi et al.⁵ showed that the mean time of achievement of motor block (Bromage 3) and sensory block at level T9 was statistically significantly (p < 0.001) shorter in the bupivacaine + clonidine (BC) group compared with bupivacaine (B) group. The motor block regression time was not significantly different between the two groups (p = 0.237). The postoperative analgesia requirement was significantly longer in group BC compared with group B (p = 0.001). No neurological deficit, sedation or other significant adverse effects were recorded.  Finding of our study was similar to the study conducted by Gecaj-gashi et al.⁵ that is, the intrathecal application of clonidine in combination with bupivacaine improves the duration and quality of spinal anaesthesia; it also provides longer duration of postoperative analgesia, without significant side effects. In a study conducted by Paliwal et al.⁶, the mean time to rescue analgesia was 33.21 ± 7.48 min in group G as compared to 338.57 ± 40.70 in group TS and opioid consumption was also significantly lower in group TS (70.00 ± 27.38) as compared to group G (366.07 ± 59.40). 

Among the total 35 patients in the Bupivacaine only group, all the 35 patients were given 5 doses of intravenous paracetamol each for the post operative pain relief. So during the 24 hours post operative period, total 175 doses of intravenous paracetamol required for pain relief in patients of the Bupivacaine only group. Among the total 35 patients in the Clonidine + Bupivacaine group, 18 (51.4%) patients were given 2 doses of intravenous paracetamol each and 17 (48.6%) patients taken 3 doses of intravenous paracetamol each for the relief of post operative pain. So during the 24 hours post operative period, total 87 doses of intravenous paracetamol required for pain relief in patients of the Clonidine + Bupivacaine group. Therefore the intrathecal administration of clonidine in isobaric bupivacaine for thoracic spinal anaesthesia is useful in reducing the post operative pain following the breast surgery and this difference between the two groups was found to be statistically significant.   A study by Paliwal et al.⁶ showed that, the quality of postoperative analgesia was better in group thoracic spinal anaesthesia (TSA0. Segmental thoracic spinal anesthesia technique provides better satisfaction with superior postoperative analgesia and fewer complications in patients undergoing breast cancer surgery compared to general anaesthesia (GA).   Spannella, F. et al.⁹ conducted a study among Ninety patients. Additional intravenous paracetamol or weak opioids were required in 23% and 2.2% of patients, respectively. No direct complications of thoracic continuous spinal anaesthesia/analgesia (TCSA) were reported. cardiac, respiratory and surgical complications occurred in 15.6%, 13.3% and 13.3% of patients, respectively. Delirium occurred in 14.4%. Hospital mortality was 5.6%. TCSA may be a valid alternative to general anaesthesia in high-risk older patients undergoing major abdominal surgery.  

After  the  breast surgery, all the patients in the both the groups (Bupivacaine only group and Clonidine + Bupivacaine group) did not experienced any type of pain at the 30 minutes and also at 1 hour of the  post operative period.  At 4 hours of post operative period of breast surgery, Bupivacaine only group, 27 (77.2%) patients experienced moderate pain, where as patients in the Clonidine + Bupivacaine group, 19 (54.3%) experienced mild pain.

At the 12 hours of the post operative period, among the Bupivacaine only group 20 (57.1%) and 15 (42.9%) of the patients experienced moderate and severe pain respectively where as in the Clonidine + Bupivacaine group, all the patients 35 (100%) complains of moderate type of pain. This shows that the intrathecal administration of clonidine in isobaric bupivacaine for thoracic spinal anaesthesia is useful in reducing the post operative pain following the breast surgery.

It was observed that, at the post operative periods 18 hours and 24 hours, the intensity of pain increased among the patients in the Clonidine + Bupivacaine group, it was because of the decrease in the analgesic effect of clonidine over a period of time which was given along with the isobaric bupivacaine for the thoracic spinal anaesthesia among the patients undergoing breast surgery. The post operative pain was treated with rescue analgesia that is intravenous paracetamol infusion.

A study on effectiveness of segmental thoracic spinal anaesthesia in breast surgery conducted by Ullah MM. at.et al.²., found that the duration of analgesia was longer. This is attributed to the residual analgesic effect of local anaesthetic and fentanyl in subarachnoid space. Paliwal et al.⁶, Chandra et al.⁷ have found that the length of stay in the recovery room and in the hospital was less due to less postoperative pain. Van Zundert, A. A. et al.⁸. conducted a study to determine the feasibility  of segmental thoracic spinal anaesthesia for Laparoscopic Cholecystectomy.  This study has shown that segmental spinal anaesthesia can be used successfully and effectively for laparoscopic surgery.

Chauhan et al.¹¹. conducted a study on to determine the effectiveness of thoracic spinal anaesthesia for caesarean section in severe pre-eclampsia. a case of a 35-year-old at 33+5-week period of gestation with severe pre-eclampsia and bullous lesions managed successfully with segmental thoracic spinal anaesthesia. General anaesthesia in this patient could have been risky as the patient was not fasting; airway bullous lesions could not be ruled out and Mallampati grade was III on airway examination. Segmental thoracic spinal anaesthesia can be used successfully and effectively for lower segment caesarean section by experienced anaesthetists. 

A study conducted by Waesberghe J. et al.¹². showed that, the patients who received a regional anaesthesia for a hip fracture had a lower incidence of myocardial infarction and respiratory distress in the postoperativeA study conducted by Daszkiewicz et al.¹³. showed that the thoracic combined spinal-epidural anaesthesia is alterative to general anaesthesia for cholecystectomy in an obese patient with asthma and multiple drug allergies. A retrospective cohort study conducted by Boykov et al.¹⁴. to investigate the safety, feasibility, and patient satisfaction of thoracic SA for spine surgery. Thoracic spinal anaesthesia incorporating adjuvants such as midazolam, clonidine or dexmedetomidine, and dexamethasone demonstrates not only efficient conditions for spine surgery, a favorable safety profile, high patient satisfaction, and intrathecal sedation but also effective opioid-free pain management

The intrathecal administration of clonidine in isobaric bupivacaine for thoracic spinal anaesthesia is useful in reducing the post operative pain following the breast surgery. Financial support and sponsorship: Nil Conflicts of interest: There are no conflicts of interest. Acknowledgements: First and foremost I thank our institution for providing platform and opportunities for conducting this study and also for providing required equipment. I also thank our HOD and other seniors in our department foe guiding me throughout the study and for constant support from topic selection, methods and methodology, proofreading and interpretation of results. I would like to thank statistical team for the analysis of the data. I thank the study subjects for taking part in the study and also thank our surgical colleagues for their support.

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