A Retrospective Study of Coronary Artery Bypass Grafting with Low-Thermal Plasma Dissection Device Compared to Conventional Monopolar Electrosurgery

Introduction: The objective of this study is to compare the effects of conventional monopolar electrosurgery (CMES) and low-thermal plasma kinetic cautery (PKC) on complications such as bleeding, abnormal wound healing, pain, and drainage in patients who underwent on-pump coronary artery bypass grafting (CABG). Methods: This retrospective clinical study included 258 patients undergoing CABG; the patients were randomized to PKC (PEAK PlasmaBlade, n=153) and CMES (n=105) groups. The patients’ clinical data were examined retrospectively for biochemical variables, postoperative drainage, post-surgery erythrocyte suspension transfusion count, surgical site pain examined with visual analogue scale (VAS), and wound healing. Two-sided P-value > 0.05 was considered as statistically significant. Results: The median post-surgery erythrocyte suspension transfusion number was significantly lower with PKC compared to CMES (0 [0-1] vs. 1 [1-4], respectively, P<0.001). Mean postoperative drain output and time until removal of drain tubes were significantly lower with PKC compared to CMES (300±113 vs. 547±192 and 1.95±1.5 vs. 2.44±1.8; P<0.001 and P=0.025, respectively). Mean VAS score for spontaneous and cough-induced pain were significantly lower with PKC compared to CMES (1.98±1.51 vs. 3.94± 2.09 and 3.76±1.46 vs. 5.6±1.92; P<0.001 for both comparisons). Reoperation due to bleeding was significantly higher with CMES compared to PKC (0 vs. 11 [7.2%], P=0.001). Conclusion: Use of PKC during CABG considerably reduces postoperative drainage, need for blood transfusion, reoperation due to bleeding, and postoperative pain. PCK appears to be a good alternative to CMES for CABG.


INTRODUCTION
Ischemic heart disease patients undergoing coronary artery bypass grafting (CABG) have a significantly increased risk of complications such as surgical site infection, abnormal wound healing, and blood loss (complication rates are 3%, 19%, and 10%, respectively) suggesting that major comorbidities such as old age, diabetes, low cardiac output, vascular circulation problems, and use of anticoagulant drugs may compromise outcomes [1,2] . However, surgical technique-related and modifiable factors can minimize these complications. One of them is the choice of device used for cutting tissues and ablation of blood vessels. The standard and commonly used device is the conventional monopolar electrosurgery (CMES) device, which uses continuous-waveform radiofrequency energy delivered by an uninsulated metal electrode to cut tissue by thermal ablation, producing simultaneous hemostasis [3] . CMES device provides an operating temperature in the range of 250 °C to 350 °C [3] . This high temperature results in significant thermal damage, widespread deep tissue necrosis of the incised tissues, and delayed wound healing, and has a potential to injure adjacent structures such as the heart, lung, vagus and phrenic nerves, and grafts such as internal mammary artery or vena saphena magna.
As an alternative to CMES cautery, plasma kinetic coagulation and resection uses radiofrequency energy by utilizing bipolar plasma kinetic technology. Plasma kinetic cautery (PKC) (PEAK PlasmaBlade®, Medtronic Advanced Energy LLC, Portsmouth, United States of America [USA]) is a novel, low-thermal-injury electrosurgical instrument that uses very brief (40 μs) high-frequency pulses of radiofrequency energy to induce electrical plasma hemostasis along the edge of a thin (approximately 12.5 μm), flat, 99.5% insulated electrode [3] . PKC produces an operating temperature between 40 °C and 100 °C with its electrode [3] . The efficacy and reliability of PKC has been shown in human ophthalmologic dissection (retina and other intraocular tissues), bariatric surgery, mastectomy, and urologic surgery where PKC was reported to have similar precision as a scalpel and hemostatic control to CMES [3][4][5][6][7][8][9] .
In recent years, PKC hemostasis and incision has started to be used in a small number of cardiac surgery clinics. However, no study on the efficiency and reliability of PKC in patients undergoing CABG is currently available in the literature.
In this retrospective clinical study, we compared the effects of CMES and PKC on complications such as bleeding, abnormal wound healing, surgical site pain, and drainage in patients who underwent on-pump CABG.

Patient Selection
This is a retrospective observational study that was carried out in accordance with the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the local ethical committee (13.05.2020/143) and all patients provided written informed consent for using of their medical records prior to the planned surgery. Two hundred fifty-eight adult ischemic heart disease patients who underwent on-pump CABG between January 2016 to December 2019 were included in the study. The inclusion criteria were: patients aged between 18 and 80 years and who underwent CABG requiring cardiopulmonary bypass (CPB). Exclusion criteria were: low ejection fraction (EF < 30%), emergency operation, left ventricular aneurysm, reoperation, concomitant procedures (such as valve replacement, carotid endarterectomy, left ventricular aneurysm resection, and others), perioperative myocardial infarct, preoperative diagnosis of chronic renal or hepatic insufficiency, malignancy, systemic inflammatory disease, history of cardiac surgery, lack of consent, and failure to obtain all the patient data necessary for the study.
The patients who underwent CABG with PKC only (n=153) were assigned as the study group while patients who underwent surgery with CMES and blade (n=105) were assigned as the control group. Low-density lipoprotein cholesterol (> 160 mg/dL [4.1 mmol/L]), non-high-density lipoprotein cholesterol (> 190 mg/dL [4.9 mmol/L]), and triglycerides (> 150 mg/dL, nonfasting) were used to determine the presence of hyperlipidemia, and hypertension is defined as a systolic blood pressure ≥ 140 mm Hg or a diastolic blood pressure of ≥ 90 mm Hg.

Biochemical Parameters
Preoperative and postoperative hematologic and biochemical parameters were collected from the patients' records. Complete blood counts were analyzed with an automatic 24-parameter blood count device (Bayer Pentra 80-Siemens Healthcare Diagnostics Products, Marburg, Germany). All the other biochemical parameters were analyzed using fresh plasma with a Siemens BCS measuring device (Siemens Healthcare Diagnostics Products GmbH 2008 Marburg, Germany).

Histopathologic Procedure
All harvested arterial segments were immersed in 10% neutral formalin solution and embedded in paraffin. Sections were cut with a cryostat at 6-μm thickness and were prepared for histochemical studies. These sections were evaluated for luminal endothelial integrity in the left internal mammary artery (LIMA) and in the vaso vasorum.
Also, to represent the cutting edge burnt tissue, thymus tissue was totally excised following median sternotomy in a patient and the thymus tissue was incised full section with both cautery systems, then the cutting edge photographs were taken.

Visual Analogue Scale Pain Score
Visual analogue scale (VAS) pain scores were obtained from the patients' records. The intensity of pain was evaluated after extubation every six hours, for a total of 72 hours (12 times), during the intensive care unit stay and whenever the patient had complaints and need for analgesics. Patients were asked to state their pain intensity during rest and while coughing using VAS. Pain intensity was measured by critical care nurses in a routine workup who were blinded to the protocols and results of the study but were fully trained and familiar with VAS.

Surgical Protocol
All operations were performed by the same surgical team. During surgery, two different cautery systems were used. In the study group, only PKC was used for full-thickness skin incisions, bleeding hemostasis, and preparation of LIMA, which was prepared as a pedicled graft and major saphenous vein (MSV) grafts. For the application of PKC, an ultrasonic scalpel (PEAK PlasmaBlade, Medtronic, Portsmouth, USA) was used. A radiofrequency power source (PULSAR II Generator, Medtronic, Portsmouth, USA) of 160 W at a radiofrequency of 340-450 Hz was used for the supply of electrosurgery and PK3 mode at 340 V2 was applied for tissue resection. The incident power was 160 W during cutting and 80 W for coagulation. In the control group, routine surgery was performed with blade and CMES. For CMES, a monopolar reusable cautery pen (Denizler Med İstanbul, Turkey) was used with Petkot 500S 220V AC 50-Hz energy input (Petas, Ankara, Turkey) for electrosurgical energy. Monopolar mode at 80-110 W was used for cutting. The incident power was 70 W for coagulation and 40 W for tissue cutting.

Cardiopulmonary Bypass Technique
Following median sternotomy, LIMA and MSV grafts were prepared for all patients. After systemic heparin administration, the artery was clipped, wrapped in a papaverine-soaked cloth, and stored under the manubrium sterni until anastomosis. A redundant 1-cm long arterial segment proximal to the clip was cut off and preserved in formalin for laboratory examination. After this, an aorto-two stage cannulation CPB was conducted and an antegrade cardioplegia cannula was placed on the ascending aorta. A roller pump (Jostra HL20, Herrlingen, Germany) was used in all cases. The CPB of each patient consisted of a cardiotomy reservoir, a tubing set, a hollow fiber membrane oxygenator, and a 40 μm arterial line filter. Mild hypothermia was applied with a nasopharyngeal temperature of 32 °C and a non-pulsatile flow of 2.4 l/min/m 2 and a mean arterial pressure of 55-65 mmHg was maintained during the CPB. Hemodilution was achieved with a hematocrit level of 26%. The circuits were primed with a mixture of 500 ml of succinyl gelatine 6 % (Gelofusine IV, B. Braun Medikal Dış Ticaret A.Ş, Esenler, Istanbul, Turkey), 1000 ml of isolyte, 100 ml of mannitol 20 %, NaHCO 3 8.4%, 250 mg of methylprednisolone (Prednol 250, Mustafa Nevzat Inc., Istanbul, Turkey), and 1 g of cefazolin (Cefamezin 1 g, Zentiva Saglık Urünleri San. ve Tic. A.S., Istanbul, Turkey) at room temperature (20 °C) adding up to a total of 1600 ml fluid. Myocardial protection was provided via intermittent (20 min intervals) antegrade cold blood cardioplegia in a standard formula. The cardioplegic solution was initiated at a volume of 1000 ml and repeated in volumes of 500 ml every 20 minutes, reaching a total of 2000-2500 ml, depending on the patient. Patients were weaned off the CPB systematically after completing all vascular anastomosis and ensuring that the entire surgical area was free of any bleeding site. At least two chest tubes (one for mediastina and one for left pleural cavity) were placed in all patients.
Erythrocyte suspension and fresh frozen plasma were given at the anesthesiologist's discretion. Blood transfusion was performed only if the hemoglobin level was < 7 mg/dl, hematocrit value was < 25 %, and if any clinical sign of blood loss existed.

Data Collection
Preoperative and postoperative levels of hemoglobin, hematocrit, neutrophils, platelets, blood urea nitrogen (BUN), creatinine, alanine aminotransferase, C-reactive protein (CRP), and EF (%) were obtained from the electronic database of the hospitals' patient file system. Clinical patient data were collected by reviewing medical and nursing records. Several parameters were determined such as age, body mass index, blood pressure, operative time points, time until drain removal, total volume of drain output, postoperative VAS pain scores, complications, blood transfusion, revision for bleeding, and mortality. Abnormal wound healing included wound dehiscence, sternal dehiscence, surgical site infection, and deep tissue necrosis.

Statistics
Data analyses were carried out using IBM Corp. Released 2017, IBM SPSS Statistics for Windows, Version 25.0, Armonk, NY: IBM Corp. Results were expressed as mean and standard deviation or number and percent. At first, all data were examined by Shapiro-Wilk test to determine whether intraindividual differences were distributed normally. As a normal Gaussian distribution was not found, comparisons of differences between groups were carried out using Mann-Whitney U test for nonparametric data, and χ 2 -test or Fisher's exact test for categorical variables. Data for different time points were compared with related-samples Wilcoxon signed-rank test. Two-sided P-value > 0.05 was considered as statistically significant.

RESULTS
Demographic variables are shown in Table 1, which indicates that the study and control groups were comparable for the presence of risk factors (age, gender, body surface area, systolic/diastolic blood pressure, hypertension, smoking, insulindependent diabetes mellitus, peripheral vascular disease, chronic obstructive lung disease, family history of ischemic heart disease, and EF [%]). There were no statistically significant differences in any of the demographic parameters between the groups except the prevalence of hyperlipidemia. The PKC group showed a significantly higher prevalence of hyperlipidemia compared to the CMES group (P=0.01).
Both  Table 3). The incidence of postoperative complications such as thromboembolic event, atrial fibrillation, sternal and leg incision complication, and mortality were statistically similar in both groups (Table 3). Mean BUN, creatinine, platelet count, white blood cell count, CRP, and aspartate aminotransferase levels were increased compared to baseline levels in both groups, but this difference did not reach statistical significance (P>0.05 for all of the above parameters in two groups) (Figures 1 A to F).
The histopathological changes and the coagulation depths of the surgical procedure in the thymus tissue and LIMA specimens were obtained for qualitative purposes only and, therefore, a statistical comparison could not be carried out. Nonetheless, the depth of the tissue that was affected by coagulation was 1.52 mm with CMES and 1.29 mm with PKC. Endothelial damage of the LIMA was minimal with both devices (Figure 2).

DISCUSSION
The purpose of this study was to evaluate if PKC could reduce bleeding complications and improve the wound-healing process  Mortality, n (%) 2 (1.9) 6 (3.9) 0.298 Comparison of the postoperative complications and VAS score for low-thermal plasma dissection device (PKC) and monopolar electrosurgery (CMES) groups. *P-value is for testing the null hypothesis that population values (ranks sums or proportions) are equal between the two groups. Two-sided Fisher's exact test with a significance level of 5 % SD=standard deviation; VAS=visual analogue scale  reduction in serous drainage was most likely due to successful vascular coagulation with minimal thermal injury with the use of PKC. Akgul et al. [4] reported that the depth of coagulation of the tissue from the cautery system is an important factor for the reduction of bleeding rate and successful hemostasis. These authors reported that the depth of coagulation with PKC was 3.2±1.53 mm and with monopolar electrocautery it was 1.52±1.29 mm in patients with benign prostate hyperplasia, which is a homogenous tissue. This is an important factor to consider during the preparation of both arterial and venous grafts and necessitates the preparation of grafts at a safe distance in patients undergoing on-pump CABG. CABG entails a very large surgical incision site that includes median sternotomy and the entire course of MSV. The current study results show that PKC significantly reduced the incidence of bleeding-related reoperation, postoperative drain output, and time until drain tubes removal, surgical site pain, and need for blood transfusion. Abnormal wound healing was lower with PKC compared to the electrocautery technique, although the difference did not reach statistical significance and the wound healing process with PKC was better than the electrocautery technique from the perspective of the surgeon.
Although there are previously studies concerning PKC and CABG patients and data from surgeries with similar large surgical incision sites, such as abdominoplasty or mastectomy, have been reported, there are no studies comparing the use of PKC and CMES in post-CABG complications [3,[10][11][12] . To the best of our knowledge, this is the first study to report a comparison of the use of PKC and CMES in post-CABG complications.
In cardiac surgery, the large incision site requires the use of extensive cauterization and other instruments, such as vascular clips, sutures, and others, to reduce bleeding. Even with meticulous surgical technique, patients may have high amount of bleeding and drainage (hemorrhagic, serohemorrhagic, and serous, in due course, respectively) compared to other surgeries because of preoperative use of anticoagulant or antiplatelet therapy, intraoperative heparin administration, and postoperative hemodynamic distribution. Therefore, the best option is to manage coagulation concurrent with performing tissue incision. Although, CMES has been used safely during CABG for decades, PKC is a novel surgical instrument that provides minimal tissue injury, similar precision as a scalpel, and similar hemostatic control as CMES. Electrocautery generates high thermal energy, which can result in deep and wide coagulation of tissue and lysis of subcutaneous fatty tissue. These events are likely to be less with PKC, making PKC an attractive alternative. There are several studies showing better coagulation results in different surgery modalities. Dogan et al. [11] reported that PKC could reduce the drainage amount and duration compared to electrocautery in mastectomy patients. Ruidiaz et al. [10] reported that PKC generated 25.6% lower serous drain output compared to scalpel and traditional electrosurgery in abdominoplasty. Similar to these recent reports in the literature, the current study also demonstrated a statically significant decrease in drainage amount and time until drain tubes removal with PKC. The observed in the current study that the PKC group showed clinical signs of successful coagulation including reduced drainage volume and need for erythrocyte transfusion. However, in our opinion, this finding should be supported further with clinical or clinical simulation studies before advising clinicians on this difference in depth between PKC and CMES. Moreover, safety should be confirmed with histopathological examination of the arterial grafts especially during the preparation of LIMA grafts.
Although the current study has some limitations, it is important because it sheds light on the advantages of PKC over CMES.

Limitations
There are limitations in this study that should be considered when interpreting the data. First, the patients received some anticoagulant and antiplatelet therapy prior to the surgery; however, it was impossible to discontinue these medications because of the presence of ischemic heart disease that resulted in bleeding and prolongation of the postoperative drainage. In our opinion, this was not a significant limitation of the study because every patient had the same clinical conditions. Second, although the differences in wound healing and complications did not reach statistical significance, based on the surgeon's knowledge and experience, many differences were noted during the healing process of the wound. The current study method and statistical analysis were not designed to evaluate the healing process, but the observations made have initiated a new study plan to confirm the findings. Third, the data can be affected by the limited number of patients recruited from a single center. Fourth, the technique of the surgeon who carried out these surgeries may also have an effect on the study outcomes. Therefore, a multicenter randomized controlled study design with different surgeons and surgical techniques as well as large numbers of patients are needed to support our findings and in order to gain wider acceptance of the use of PKC in CABG.

CONCLUSION
The low-thermal PKC appears to be effective and safe in performing dissection and hemostasis during CABG with its considerable reduced postoperative drainage, need for blood transfusion, reoperation, and postoperative pain. At the end of the procedure, PKC provides a better surgical outcome with minimal bleeding and reduced incidence of blood transfusion. The low thermal effect is a persuasive advantage of this technique for preparing grafts in a more reliable environment, especially for grafts as LIMA. The final conclusion of the study may be that PCK appears to be a good alternative to CMES for CABG.