Application of preemptive parasternal intercostal nerve block in patients undergoing off pump coronary artery bypass grafting:A Double-Blind,Randomised, Controlled Trial

Background: Parasternal intercostal nerve block as superficial block has been increasingly used for postoperative analgesia via performed before sternal suture placement, and has shown that this technique can provide effective postoperative analgesia and facilitate rapid-recovery. However, the impact of preemptive parasternal intercostal nerve block has not been researched for cardiac surgery patients. Methods: Sixty-four patients underwent OPCABG were randomly divided into parasternal intercostal nerve block with ropivacaine ( n = 32) group and parasternal intercostal nerve block with saline ( n = 32) group. Before anaesthesia induction, 20ml of 0.35% Ropivacaine along with 1 mg dexamethasone or saline on each side, total dosage 40 ml, via parasternal intercostal injection. 5ml of 0.35% ropivacaine along with 0.5 mg dexamethasone or saline on each leg, total dosage 10 ml, via peripheral saphenous nerve block. Results: The consumptions of intraoperative sufentanil and vasopressor were significantly lower in ropivacaine group(P0.05). Analgesia was adequate in the ropivacaine group up to 20 h. VAS score in the ropivacaine group significantly was lower compared with the saline group up to 12 h postoperatively(P 0.05). The time of first rescue analgesic, anaesthesia recovery and extubation were significantly less in patients of the ropivacaine group(P0.05). The majority of the ropivacaine group patients did not need rescue dezocine, while the most of the saline group needed dezocine (P <0.05). The hemodynamic variables were stable in all patients. Few cases reported trivial adverse effects. Conclusions: Preemptive parasternal intercostal nerve block provide adequate analgesia for the first 20 h after surgery and reduce intraoperative sufentanil, intraoperative norepinephrine and postoperative dezocine consumption as well as the time of extubation. Trial registration: The study was registered at chictr.org.cn (identifier:


Background
Off pump coronary artery bypass grafting (OPCABG) is one of the major surgical treatments for coronary heart disease. Maintaining the stability of intraoperative hemodynamics and myocardial protection has been one of the hot topics in the field of cardiac anaesthesia.
Adverse perioperative pain stimulates the neuroendocrine system and causes stress, which has adverse effects on the cardiovascular system, respiratory system, and digestive system. (1,2) Effective postoperative pain control may be benefit for early extubation, as well as cost reduction and rapid recovery. (3)(4)(5) In addition, appropriate analgesia can reduce morbidity related pain.
Acute thoracotomy pain is multifactorial in nature. It involves nociceptive and neuropathic mechanisms originating from somatic and visceral afferents. The main source of pain is intercostal nerves. Therefore, a multimodal analgesic approach is recommended.
A large number of studies on epidural anesthesia and thoracic paravertebral nerve block for postoperative analgesia after cardiac surgery have shown that both techniques can provide effective postoperative analgesia and improve postoperative mortality.(4, 6-10) but due to the corresponding complications caused by the deep depth of the needle, especially in the treatment of antiplatelet or anticoagulant, which is usually administered to elderly patients with OPCABG, these techniques are still controversial. (11,12) In order to avoid above of complications, parasternal intercostal nerve block has been suggested as it is a "superficial block", compared to epidural anesthesia and thoracic paravertebral nerve block. Recently, there have been a large number of studies on the efficacy of parasternal nerve block for postoperative pain in cardiac surgery, (13)(14)(15)(16)(17) but the effectiveness of preemptive parasternal nerve block for cardiac surgery has not been reported. It was therefore considered in this study that, parasternal intercostal nerve block could be used not only 4 postoperatively, but also intraoperatively.

2.methods
The randomised controlled trial was approved by the local research ethics committee ( patients with OPCABG surgery were selected, regardless of gender. The inclusion criteria were as follows: Age 45 to 75 years old, weight of 40-90 kg, ASA Ⅱ or Ⅲ, NYHA I ~ Ⅲ, no valvular disease, without Intra-Aortic-Balloon-Pump, and no neuropsychiatric disorder.
Exclusion criteria were as follows: infection of the puncture site; left ventricular ejection fraction <50%; chronic liver or kidney disease; allergy to amide-type anesthetics; Low cardiac output syndrome with inotrope and/or intra-aortic balloon pump support. Other reasons for withdrawn were changing to cardiopulmonary bypass during operation postoperative complications requiring re-operation, requiring intra-aortic balloon pump support intraoperative or postoperative postoperative tracheal intubation again, and sedation for more than 48 h.
After obtaining written informed consent from the 64 participating adults, using the sealed envelope method, 64 participants undergoing OPCABG were randomized into group R or group S and administered with either ropivacaine or saline. Medication administration and data collection were performed in a double-blinded manner, such as one anaesthesiologist prepared the ropivacaine or saline and administered the block, other anaesthesiologist 5 administered anaesthesia and collected the data, the intensive care unit staff gave postoperative care.
The parasternal intercostal block primarily anesthetized the intercostal nerves close to the sternal border and the anterior cutaneous branch of the intercostal nerve. For parasternal intercostal nerve block Patients, 0.35% ropivacaine and 1 mg dexamethasone or 0.9% saline were administered with 20 mL aliquots through injection into the space between the Intrathoracic fascia and T3-T4 anterior intercostal muscle on each side 2-2.5 cm lateral to the sternal edge by ultrasound (Fig.1). The block was administered by an anesthesiologist in a standardized fashion guided by ultrasound before anaesthesia induction. Take care to ensure that no blood was aspirated to avoid intravascular injection resulting in local anesthetic intoxication. In addition, patients were treated with peripheral saphenous nerve block with 0.35% ropivacaine and 0.5 mg dexamethasone or 0.9% saline administered in 5 mL aliquots on each leg, as well as under the guidance of ultrasound (Fig.2).

3.statistical Analysis
Continuous variables were presented as means with standard deviations, and groups were compared by using a 2-sided Student t test with equal variance. The intra-group comparison was performed by repeated measures analysis of variance. χ 2 test (Fisher's exact test) was used to examine the relationship between qualitative variables. The tests were performed using Statistical Analysis System software. The power of the study was 85%, so, in this work the sample size was sufficient in each group. Significance was set to a P-value < 0.05.

Results
Sixty-four patients were randomized (28 ropivacaine and 27 saline). Four patients from the ropivacaine group and five patients from the saline group were withdrawn from the study (Fig. 3). For the ropivacaine group, patients were withdrawn for the following reasons: 2 patients were under postoperative sedation for more than 48 h and 2 patients required intra-aortic balloon pump support. Of the saline patients who were withdrawn, 2 required intra-aortic balloon pump support, 2 were under postoperative sedation for more than 48 h and 1 required additional tracheal intubation due to low oxygen in the blood. Patients' demographics and baseline clinical characteristics were similar between the two groups (Table 1). Patients who received ropivacaine had significantly less dose of sufentanil at the time of skin incision, median sternotomy and total consumption ( Table 2), especially at the time of median sternotomy and total consumption of sufentanil were approximately 50% lower in the ropivacaine group(P<0.001).
Hemodynamic data showed that patients were hemodynamic stable between the two groups. Hemodynamics (heart rate, Mean artery pressure) were no statistically significant differences between the ropivacaine and saline groups (Fig. 4). However, at the time of the dissection of IMA, 5min after reperfusion, closure of sterno and the end of surgery, patients who received ropivacaine had significantly less dose of norepinephrine( P<0.05) ( Table 2 Table 3).
The most of ropivacaine group patients did not need rescue dezocine doses, while the majority of saline group needed dezocine ( P < 0.05) ( Table 3). The time to recover from anaesthesia and extubation were significantly lower in the ropivacaine group ( P<0.05).
Nevertheless, no effect was shown on the length of stay in ICU and hospital after surgery for 8 the ropivacaine group (Table 3).
Postoperative nausea and vomiting occurred in 3 patients in the ropivacaine group, and 4 patients in the saline group and there were no complications related to nerve block in either group.

discussion
Hemodynamic stability is a significant concern in the intraoperative management of OPCABG. In the past, large doses of opioids were used in thoracotomy to inhibit the stress response caused by strong stimuli such as skin incision, saw sternum and chest closure.
However, opioids are associated with side effect such as inhibiting the cardiovascular system, making it unsuitable for maintaining the stability of intraoperative hemodynamics.
Our study demonstrated that ropivacaine with application of the parasternal intercostal nerve block before surgical incision, intraoperative opioid was decreased. There was no difference in hemodynamic parameters between the ropivacaine group and the saline group but norepinephrine consumption was decreased in the ropivacaine group that probably indicates that parasternal nerve block can maintain hemodynamic stability to a certain extent.
In recent years, general anaesthesia combined with regional anaesthesia has become a hot topic. The current regional anaesthesia for thoracotomy encompasses both thoracic Nerve block of local anesthetics for postoperative analgesia in different surgical settings has been studied and has been shown to be effective in reducing postoperative pain.
Although the same method directly used in cardiac surgery has been studied, the results are still controversial (15,21,22). Additionally, studies of continuous local anesthetic injections in patients with sternal trauma also have produced different outcomes for reducing postoperative PCA analgesics, (14,25) The data from our study also confirmed that these studies provide good postoperative analgesia for the parasternal intercostal block. Most of researches on parasternal nerve block for postoperative analgesia were performed after cardiac surgery.
In this study, we adopted the concept of preemptive analgesia through the application of In this study, the time of recovery from anaesthesia and indubation was lower in the ropivacaine group compared with the saline group, which may be related to the reduction of intraoperative sufentanil dose, but there was no difference in ICU monitoring time, and postoperative hospital stay. This was probably due to the intensive care unit has strict criteria for transfer out of the ICU. Apart from parasternal nerve block, recovery of myocardial function, use of postoperative vasoactive drugs and hemodynamic stability are also important factors that influence the time of ICU stay.

Limitations
The outcomes of this study are, however, limited to the short-term effect of parasternal intercostal nerve block. Hence, its long-term effects need to be further studied. In addition, there was no observation in intraoperative and postoperative serological indicators, postoperative hemodynamics indicators, postoperative vasoactive drug use, and changes in myocardial enzymes. These were a limitation of this study that needs to be explored in further studies.

7.conclusion
In conclusion, this study has demonstrated an effective and practical treatment for off pump coronary artery bypass grafting. A parasternal intercostal block results in reduced consumption of opioid, higher hemodynamic stability, less postoperative pain and adjunction analgesia in the general cardiac surgery population.