The use of prophylactic intra-aortic balloon pump in high-risk patients undergoing coronary artery bypass grafting.

OBJECTIVE: Intra-aortic balloon pump (IABP) is one of the most commonly used mechanical circulatory assist devices for high-risk patients undergoing cardiac surgery. In an effort to validate previously reported clinical outcomes, we describe the preoperative characteristics and outcomes of patients who underwent prophylactic IABP in high-risk patients undergoing coronary artery bypass grafting (CABG).
DESIGN: A prospective observational study.
METHODS: From 2005 to 2017, 471 patients underwent either isolated or combined CABG at our institution. Of those, 393 patients underwent isolated CABG and were included for the analysis. Eighty-five patients (22%) were considered high-risk and underwent prophylactic IABP, with subsequent review of surgical morbidity and mortality rates.
RESULTS: The 30-day postoperative mortality (prophylactic IABP group vs non prophylactic IABP group: 0% vs 1.6%, p = 0.589) and major adverse cardiac or cerebrovascular events (5.9% vs 3.3%, p = 0.333) were not significantly different between the two groups. Prolonged mechanical ventilation (>72 hours) (12.5% vs 4.2%, p = 0.014) occurred more frequently in the prophylactic IABP group.
CONCLUSIONS: No IABP-related complications were noted, emphasizing that the use of prophylactic IABP in high-risk patients undergoing CABG is an acceptable option.

Introduction

Patients with ischemic heart disease, particularly those requiring coronary artery bypass grafting (CABG), pose a major challenge for anesthesiologists and cardiothoracic surgeons, emphasizing the need for risk stratification and prophylactic measures to reduce postoperative morbidity and mortality. Cardiopulmonary bypass (CPB) and aortic cross-clamping or off-pump coronary artery bypass (OPCAB) grafting are the most commonly utilized approaches during CABG, but are highly dependent on the patient’s condition, the proficiency level of the surgeon and staff, as well as institutional policy.

Nihonkai General Hospital is a community hospital in the coastal area of Yamagata Prefecture, covering a population of 300,000 people across multiple mountainous terrains. Due to the lack of physician-follow up, shortage of doctors, and the challenging geography many high-risk patients, including emergent cases, often present to our institution. However, as a general community hospital, subspecialized providers–such as cardiac anesthesiologists–are unavailable, making preoperative and prophylactic interventions critical amongst patients undergoing intensive procedures.

At present, intra-aortic balloon pump (IABP) is the most commonly used device for circulatory assistance in cardiac surgery and preoperative prophylactic IABP has been shown to improve outcomes in high-risk patients [1, 2]. In an effort to validate prior studies on the benefits of postoperative clinical outcomes, we conducted a prospective observational study of preoperative prophylactic IABP in high-risk patients undergoing CABG with the aim of describing subsequent morbidity and mortality rates.

Patients and methods

Nihonkai General Hospital institutional ethical review board approved the research protocol prior to initiation of this study, and written consent was obtained from all subjects.

This was a single-center, prospective observational study conducted at Nihonkai General Hospital, and involved 471 unique patients from December 2005 to December 2017 who underwent isolated or combined CABG. Of those, 393 patients underwent isolated CABG and were included for the analysis. Prior to all CABGs, a multidisciplinary team of cardiothoracic surgeons, cardiologists, nurses, and medical technicians met to discuss the indication for preoperative and prophylactic IABP in high-risk patients. High-risk patients were those with hemodynamically stable and meeting two or more of the following criteria: 1) New York Heart Association (NYHA) Functional Class III or IV; 2) left ventricular ejection fraction (LVEF) less than 40% (evaluated by preoperative echocardiography with modified Simpson methods); 3) left-ventricular end-diastolic internal diameter >65mm; 4) left main stenosis >50%; 5) diffuse coronary artery disease, defined as the requirement for three or more distal anastomoses; and 6) refractory unstable angina. Patients with contraindications to IABP, defined as severe peripheral vascular disease, aortic regurgitation, dissection, or aneurysm, were excluded from this study.

Of the 393 unique patients who presented for CABG, 85 (22%) were considered high-risk by the aforementioned definitions and underwent prophylactic IABP (. Baseline characteristics and intraoperative data were collected and are detailed in We conducted a cardiac operative risk assessment using European system for cardiac operative risk evaluation (EuroSCORE II), a validated risk prediction model. Acute kidney injury (AKI) was defined by increased serum creatinine (SCr) to 0.3 mg/dl/48h or more, increased SCr by 1.5 times or more, or decreased urine output to 0.5ml/kg or less during 6 hours [3, 4].

All high-risk patients had prophylactic IABP. IABP was inserted in the catheterization lab the day prior to CABG, with continuous intraprocedural IABP, and postoperatively as clinically indicated; patients were monitored in the ICU pre- and post-operatively. Non-high-risk patients received IABP if clinically indicated based on hemodynamic instability pre- or intra-operatively. All patients who received a prophylactic IABP entered the ICU and were waiting.

Placement of IABP was through percutaneous puncture of the femoral artery, with subsequent introduction of an 8-French balloon catheter with a guide wire through an arterial sheath. The IABP balloon was selected according to the height of the patients and then connected to a CS300TM (Getinge AB, Gothenburg, Sweden). Positioning was confirmed immediately with chest angiography. Use of an IABP was discontinued when hemodynamic stability was restored.

IABP weaning was dependent on stabilization of circulatory dynamics. Weaning was done when diuresis was present and there was warm in peripheral sensation. However, there was no numerical target.

All non-urgent patients underwent extensive cardiac rehabilitation prior to surgery. Even patients that were admitted into the emergency room underwent cardiac rehabilitation if surgical intervention was not urgent. Additionally, we treated dental conditions, glycemic imbalances, and co-morbid treatable diseases such as carotid artery stenosis prior to cardiac surgery. Extensive rehabilitation had been especially applied for patients whose activities of daily living (ADL) were limited due to treatment for heart failure after hospitalization. Rehabilitation aims for patients to be as close to the original ADL as possible. As a first goal, we place importance on standing (out-of-bed exercise) [5]. Extensive rehabilitation is not applied to patients with a high risk for preoperative load, such as cases with LMT lesions, symptom cases, and unstable circulation. Additionally, patients who developed symptoms during extensive rehabilitation underwent surgery immediately. The procedures and the distribution were the same in both groups. It had been uniform throughout the study time. There were 10 surgeons during the observation period, 5 of which were staff surgeons and 5 resident surgeons. There were 7 surgeons in prophylactic IABP group(4 staff surgeons and 3 resident surgeons) and 10 surgeons in no prophylactic IABP group. According to the policy of the first staff surgeon, the procedures are consistently the same and the first surgeon (the one that performed the surgery) is currently involved in the treatment as staff. The guidelines for the application of prophylactic IABP, the choice of Off pump / On Pump, and the type of graft used are consistent for all patients. A CPB circuit was used when deemed necessary during the preoperative assessment. It primarily included criteria such as a large left ventricle and low cardiac function. Additionally, on-pump CABG was scheduled following a comprehensive risk assessment, which included the location and quality of target vessels, and accounted for technically challenging cases. If complete revascularization was feasible, OPCAB was scheduled. Conversion to CPB was considered if there was any evidence of hemodynamic instability, such as ventricular arrhythmia, hypotension (systolic pressure ≤ 80 mmHg), and cardiac arrest during OPCAB procedures. The OPCAB is performed after a median sternotomy. The heart was displaced using a posterior pericardial stitch, gauze, and a tissue stabilizer (Octopus Evolution tissue stabilizer and Octopus Evolution AS tissue stabilizer; Medtronic Corporation, Minneapolis, MN, USA). Body position changes and gravity support (Trendelenburg, right and left table rotations) were carried during surgery. A CO2 blower mister device was used in situations where a bloodless field was not achieved after proximal target vessel occlusion. An intracoronary shunt (Phycon coronary minishunt; Fuji systems, Tokyo, Japan) was used during grafting. On pump isolated CABG was performed utilizing the same techniques. All on pump CABG was performed while the heart was beating. Grafting was always performed from the left internal mammary artery to the left anterior descending coronary artery, followed by grafting of the circumflex coronary artery and right coronary artery using a radial artery or a saphenous vein. The bilateral internal mammary was used in the non-touch aorta technique and ascending aortic sclerosis or calcification was assessed based on pre-operative findings from imaging examinations and intra-operative palpation. The quality of the anastomosis was assessed post-graft utilizing a transit-time flow probe (VeriQ System and TTFM probes; Medistim ASA, Oslo, Norway).

The primary endpoint was postoperative 30-day mortality (death occurring within 30 days after surgery). Secondary endpoints included major postoperative complications, such as low cardiac output syndrome, myocardial infarction, bleeding requiring surgical intervention, stroke, postoperative atrial fibrillation, mediastinitis, intubation time longer than 72 hours, ICU stay longer than 7 days, and postoperative length of stay longer than 30 days. Occurrence of any short runs of atrial fibrillation more than 30 seconds during the hospital stay was considered to represent an occurrence atrial fibrillation. Major adverse cardiac and cerebrovascular events (MACCE) included death, acute myocardial infarction, cerebrovascular event, or further revascularization by percutaneous coronary intervention or CABG. The neurologic event was defined as an endpoint when symptoms appeared and could be corroborated using computed tomography (CT) and magnetic resonance imaging (MRI). The final diagnosis was performed by a neurosurgeon and it was considered a neurologic event if diagnosed. If there were no visual findings, the transient ischemic attack was not included.

Statistical analysis

Continuous variables were expressed as the mean and standard deviations or the median and interquartile ranges, and categorical variables were shown as frequencies or percentages. Continuous data were analyzed using the Independent Student’s t-test or Mann-Whitney U-test. Categorical variables were analyzed by Chi-Squares and Fischer’s exact test. The in-hospital survival rates and MACCE-free rates after surgery between two groups were determined by Kaplan-Meier survival curves and compared by the log-rank test. Analyses were conducted with JMP software, version 10 (SAS Institute Japan, Tokyo, Japan).

Results

A total of 393 consecutive patients were included in this study, with 85 patients (group A, 22%) considered high-risk and placed in the prophylactic IABP group and 308 patients (group B, 78%) considered non-high risk patients not allocated to prophylactic IABP. The preoperative clinical data are listed in . There were no significant differences in age, gender, body mass index, comorbidities and insulin use between both groups. In patients in the group A, preoperative low ejection fraction (group A versus group B: 50 ± 18 vs 54 ± 14%, p<0.0001), emergency operation (19 [22.4%] vs 24[7.8%], respectively; p = 0.001), NYHA III/IV functional class (30 [35.3%] vs 74 [24.1%], respectively; p = 0.051, left main coronary stenosis (45 [53%] vs 105 [37%], respectively; p = 0.009), and the current smoker (21 [24.6%] vs 29 [9.4%], respectively; p = 0.003) were more frequent. For recent AMI, the progress of all members was confirmed and the results were listed in Table 1. A recent AMI was defined as being diagnosed with AMI when hospitalized. There were no differences between the two groups (12 [14.1%] vs 31 [10.1%], respectively; p = 0.326). Our policy is that if there is a time allowance for those who have surgical indications for carotid artery lesions, they will be treated first, but in this study there were no such patients. As a treatment for stenotic lesion of the carotid artery and its treatment, none of the patients in this patient group underwent a surgical operation (including stent insertion). Nine patients had pointed stenosis of the carotid artery before surgery and all were consulted for neurosurgery at this hospital. Additionally, single photon emission computed tomography was performed. It was decided that there was little need for preoperative surgical treatment.

Table 1

Baseline patient characteristics, preoperative data.

Characteristic	Total (n = 393)	Prophylactic IABP (n = 85)	No prophylactic IABP (n = 308)	p-value (prophylactic IABP vs. non-prophylactic)
Age, y				0.252
Mean ± SD	69 ±10	70 ± 10	68 ± 9
Median (IQR)	70 [63, 75.5]	69 [63, 78]	70 [63, 75]
Male, %	86.1	87.1	85.7	0.861
Height, cm				0.621
Mean ± SD	161.2 ± 8.6	162.1 ± 8.6	161.6 ± 8.4
Median (IQR)	162.00 [156.20, 167.00]	163.00 [157.38, 167.13]	161.60 [156.00, 167.00]
Weight, kg				0.808
Mean ± SD	61.2 ± 12.7	60.9 ± 12.4	61.3 ± 12.7
Median (IQR)	60.15 [53.00, 69.43]	60.50 [54.00, 69.75]	60.15 [52.85, 69.43]
BMI, kg/ m2,				0.595
Mean ± SD	23 ± 4	23 ± 4	23 ± 4
Median (IQR)	23.44 [20.63, 25.50]	23.75 [20.74, 25.62]	23.39 [20.62, 25.49]
BMI ≥30, %	4.7	2.4	5.4	0.383
OMI, %	50.4	43.5	42.3	0.178
Hypertension,%	80.7	76.2	82	0.273
Hyperlipidemia,%	64.9	59.5	66.4	0.247
Diabetes mellitus,%	47.0	45.2	47.5	0.805
Insulin, %	12.2	4.8	14.2	0.022
Family history,%	16.5	12.9	17.9	0.426
Smoking,%	66.5	69.4	65.6	0.644
Current smoker,%	13.2	24.6	9.4	0.003
Post PCI, %	22.4	19.1	23.4	0.462
PAD, %	7.1	2.4	8.4	0.081
SCr, mg/dl, Mean ± SD	1.0 ± 1.0	0.8 ± 0.3	1.1 ± 1.1	0.172
CRF, %	11	6	12.3	0.116
hemodialysis, %	4.3	1.2	5.2	0.137
Stroke, %	8.4	7.1	8.8	0.825
Recent AMI, %	10.9	14.1	10.1	0.326
NYHA III or IV, %	26.5	35.3	24.1	0.051
LVEF, %				<0.0001
Mean ± SD	55 ± 11	50 ± 18	54 ± 14
Median (IQR)	57.50 [43.00, 67.00]	50.00 [34.00, 66.0]	59.00 [46.00, 68.00]
LMT stenosis, %	40	53	37	0.009
Coronary stenosis ≥50, Mean ± SD	2.5 ± 0.7	2.6 ± 0.7	2.5 ± 0.7	0.101
emergency operation, %	10.9	22.4	7.8	0.001
EuroSCORE II, Mean ± SD	2.0 ± 2.3	2.8 ± 2.9	1.7 ± 2.1	0.0001

SD: Standard Deviation, IQR: Interquartile Range, BMI: Body Mass Index, OMI: Old Myocardial Infarction, PCI: Percutaneous Coronary Intervention, PAD: Peripheral Arterial Disease, SCr: Serum Creatinine, CRF: Chronic Renal Failure, AMI: Acute Myocardial Infarction, NYHA: New York Heart Association, LVEF: Left Ventricular Ejection Fraction, LMT: Left main coronary trunk, EuroSCORE: European system for cardiac operative risk evaluation

Extensive rehabilitation had been performed in 19 (4.8%) patients. There was a significant difference between the prophylactic IABP group that underwent extensive rehabilitation (8 [9.4%] vs 11 [3.6%], respectively; p = 0.041) (Table 2). Seventy-nine percent (15 patients) of the patients started with in-bed exercise and eventually advanced to out-of-bed exercise (63% [5 of 8] vs 91% [10 of 11], respectively; p = 0.262). Reasons for extensive rehabilitation (the reason why ADL decreased) were due to many factors including the onset of heart failure (8 patients), the onset of AMI (6 patients), temporarily use of IABP after hospitalization (3 patients), onset of AMI and heart failure (1 patient), and brain infarction (1 patient). In this study, only one patient underwent surgery with the need to halt extensive rehabilitation (Table 2).

Table 2

Preoperative extensive rehabilitation.

Result	Total (N = 393)	Prophylactic IABP (n = 85)	No prophylactic IABP (n = 308)	p-value (prophylactic IABP vs. non-prophylactic)
Extensive rehabilitation, %	4.8 (19 of 393)	9.4 (8 of 85)	3.6 (11 of 308)	0,041
Rehabilitation period, days				0.065
Mean ± SD	25 ± 13	19 ± 11	30 ± 13
Median (IQR)	23.00 [16.00, 37.00]	19.5 [9.25, 22.75]	36.00 [19.00, 38.00]
In-bed exercises, %	100 (19 of 19)	100 (8 of 8)	100 (11 of 11)	1
Out-of-bed exercise, %	79 (15 of 19)	63 (5 of 8)	91 (10 of 11)	0.262
Exit ICU, %	79 (15 of 19)	63 (5 of 8)	91 (10 of 11)	0.262

SD: Standard Deviation, IQR: Interquartile Range, ICU: Intensive Care Unit, in-bed exercises = Achievement of in-bed exercises, out-of-bed exercise = Achievement of out-of-bed exercise

At the induction of anesthesia and just before the start of surgery, group B tended to have higher blood pressure and less use of catecholamines, and group A had higher cardiac index (Table 3).

Table 3

Clinical outcomes Pre- and Postoperative data with or without prophylactic IABP patients.

Result	Total (N = 393)	Prophylactic IABP (n = 85)	No prophylactic IABP (n = 308)	p-value (comparing prophylactic IABP and non-prophylactic)
Preoperative (at the induction of anesthesia)
shock state—Yes, %	2	1.2	2.3	1
ECMO use, %	0	0	0
Systolic BP—mmHg, Mean (SD)	131 ± 24	125 ± 22	133 ± 25	0.113
Mean BP—mmHg, Mean (SD)	88 ± 15	82 ± 13	89 ± 15	0.0001
CI L/min/m2	2.5 ± 0.7	2.8 ± 0.7	2.4 ± 0.7	0.008
Catecholamines; n/ total (%)	10.4	31.8	4.6	<0.0001
Dosage (μg/kg/min)—mean SD
Dopamine	0.15 ± 0.77	0.33 ± 0.78	0.10 ± 0.77	0.018
Dobutamine	0.10 ± 0.53	0.27 ± 0.76	0.05 ± 0.43	0.0005
Norepinephrine	0.0004 ± 0.0064	0 ± 0	0.0005 ± 0.0072	0.529
Epinephrine	0 ± 0	0 ± 0	0 ± 0
CI (at the start of operation) L/min/m2	2.5 ± 0.6	2.7 ± 0.7	2.4 ± 0.6	0.0006
Postoperative (before admission in ICU)
shock state—Yes, %	0.51	0	0.65	0.459
ECMO use, %	0.51	0	0.65	0.459
Systolic BP—mmHg, Mean (SD)	101 ± 16	99 ± 14	102 ± 17	0.113
Mean BP—mmHg, Mean (SD)	67 ± 10	64 ± 10	67 ± 11	0.031
CI L/min/m2	2.8 ± 0.7	2.9 ± 0.8	2.8 ± 0.7	0.551
Catecholamines; n/ total (%)	98.2	98.8	98.1	1
Dosage (μg/kg/min)—mean SD
Dopamine	2.16 ± 1.36	2.16 ± 1.09	2.16 ± 1.42	0.989
Dobutamine	0.34 ± 0.98	0.39 ± 0.92	0.34 ± 1.00	0.655
Norepinephrine	0.04 ± 0.43	0.08 ± 0.66	0.03 ± 0.34	0.344
Epinephrine	0 ± 0	0 ± 0	0 ± 0

ECMO: Extracorporeal membrane oxygenation, BP: blood pressure, SD: Standard Deviation, CI: Cardiac index, ICU: Intensive Care Unit

Intra and postoperative results are shown in . There were no significant differences in the operation time, using cardiopulmonary bypass, pump time, converted to on-pump CABG, reoperation for bleeding, required transfusion of red blood cells, leg wound problems, leg wound infection, occurrence of mediastinitis and neurologic events. There was a 93% postoperative follow-up rate over an average of 42.5 months (± 42.6). The follow-up results after discharge were confirmed on the medical records of our hospital, related hospitals, or via telephone. The mean number of distal anastomoses were few in group B patients (2.8 ± 1.1 vs 2.3 ± 1.0; p<0.0001). Post-operative occurrence of AKI between the two groups (3 [3.6%] vs 6 [2.1%], respectively; p = 0.326). However, patients without prophylactic IABP required more dialysis following cardiac surgery (0 of 3 [0%] vs 6 of 7 [86%], respectively; p = 0.033). Only one patient (without prophylactic IABP) with end-stage renal disease requiring maintenance hemodialysis therapy initiated chronic dialysis following cardiac surgery. The duration of mechanical ventilation (1.4 ± 1.4 vs 1.1 ± 1.6 days; p = 0.127), the length of ICU stay (4.2 ± 4.4 vs 4.9 ± 2.3 days; p = 0.181) and the length of hospital stay (25 ± 18 vs 22 ± 15 days; p = 0.095) were no difference between the two groups (“ICU stay” was not counted as ICU admission stay during the preoperative period.), yet significantly difference was diagnosed with the prolonged ventilation>72 hours (11 [12.5%] vs 13 [4.2%], respectively; p = 0.014).

IABP was removed postoperatively after extubation if the patient was hemodynamically stable. No IABP-related complications were reported and there were no instances of IABP-related mortality. Forty-four patients in the non-high-risk group (14%) required IABP support perioperatively, but are not included in the original high-risk prophylactic IABP group.

Overall inpatient surgical mortality was 1.3% (5/393) secondary to postoperative low cardiac output syndrome (n = 3), sepsis (n = 1), and multiple organ failure (n = 1). Mortality in the prophylactic IABP group was 0% (0/85).

Overall 30-day mortality was 0% versus 1.0% in the prophylactic IABP group. Major adverse cardiac or cerebrovascular events (MACCE) occurred in 3.8% overall (including after discharge), with a 5.9% MACCE in the prophylactic IABP group. There were no significant difference in 30 days mortality (group A vs group B = 0 [0%] vs 3 [1%], respectively; p = 1.0) as well as in-hospital deaths (0 [0%] vs 5 [1.6%], respectively; p = 0.589). The 12-months survival curves in the 85 high-risk patients who received prophylactic IABP compared to the 308 non-high risk patients who did not receive prophylactic IABP were similar (p = 0.846) (Fig 2). The postoperative MACCE free rates (1 year) was 69% (group A) vs 69%(groupB) (p = 0.970) (Fig 3).

Fig 2

Kaplan-Meier curves for freedom from overall survival of 393 patients with isolated CABG in our institution: 85 patients with prophylactic IABP group and 308 patients with non-prophylactic IABP patients.

Fig 3

Kaplan-Meier curves for MACCE-free rates of 393 patients with isolated CABG in our institution: 85 patients with prophylactic IABP group and 308 patients with non-prophylactic IABP patients.

Discussion

Currently, the consensus on the benefit of prophylactic IABP is not so widespread. Some papers were reported the Prophylactic IABP insertion in high-risk patients undergoing cardiothoracic surgery has been shown to reduce postoperative mortality [2, 6–8]. Dyub et al. reported that patients who received prophylactic IABP preoperatively had a mortality benefit with an odds ratio (OR) of 0.41 (95% CI 0.21–0.82; p = 0.01) [6]. Multiple studies reported the benefit of prophylactic IABP [1,2, 6–8], but it had not been established as the gold standard for high-risk CABG. One of the reasons was complications. Patients undergoing IABP insertion, however, have been considered at higher risk for rebleeding, and prolonged ventilation, as well as at increased risk of reintubation, tracheostomy, dialysis, and prolonged ICU stay [9, 10]. Yet, when patients are properly evaluated preoperatively for possible contraindications to IABP (such as peripheral vascular disease) and strict postoperative surveillance is maintained, the risk of IABP-related complication can be minimized. In our studies, the success rate of IABP placement was 100% in cases where IABP placement was planned. For all IABP placements, we utilized a percutaneous approach, advancing through the femoral artery. Prior to surgery, we performed CT imaging to ensure there were no problems with the access of the patient.

Nevertheless, while the conclusion of previous studies points towards a benefit with preoperative IABP, the results have been controversial due to lack of both prophylactic IABP insertion criteria and lack of definition of what constitutes a high-risk patient. In our study, we aimed to avoid these limitations by using the definition of a high-risk patient as illustrated by Ding et al [11]. Furthermore, the criteria for IABP insertion in our study cohort was strictly prophylactic, rather than therapeutic such as in low cardiac output syndrome, similar to the methods utilized by Shi et al [12].

Although we were unable to determine the advantages of using prophylactic IABP, some papers report good results.A recent meta-analysis (MTA) reported that prophylactic IABP use reduced mortality and MACCE in high-risk CABG patients [13]. Poirier et al showed that hospital death following preoperative IABP was 2.5%, compared to 12.6% in the control (non-IABP) group. Moreover, from the observational study, the hospital death following preoperative IABP use was 7.6%, compared to 2.4% in the non-use group [14]. In our report, the hospital death in the preoperative IABP group was 0%, compared to 1.6% in the non-use group; there were no differences between the two groups. The significance of IABP is inconsistent based on findings from different studies. In our studies, the preoperative IABP group was a high-risk group; therefore, the use of preoperative IABP may have had an advantage in improving the survival rate. However, future studies are warranted to definitively elucidate the significance of IABP on patient outcomes. Jiayang et al showed that preoperative prophylactic IABP reduced the incidence of CABG-associated AKI[15]. Our results also showed that postoperative dialysis was significantly less in the prophylactic IABP group (0 of 3 [0%] vs 6 of 7 [86%], respectively; p = 0.033). The utility of prophylactic IABP is still open for further study, but early studies indicate that postoperative results may be improved. However, further research is warranted to demonstrate the beneficial effects of prophylactic IABP use.

Our study illustrates the advantages of prophylactic IABP are manifold, including ease of safe placement through fluoroscopy-guidance, improved circulation support at the induction of anesthesia, and circulatory support in the setting of possible postoperative low cardiac output syndrome. Nevertheless, this study reported that no survival advantage was found in the prophylactic application of an IABP in hemodynamically stable we had not experienced IABP-related complications.

Compared to average values, we observed better outcomes in regard to 30-day mortality (group A vs group B = 0 [0%] vs 3 [1%]) and in-hospital deaths (0 [0%] vs 5 [1.6%]). First, a multidisciplinary team of cardiologists, cardiac surgeons, nurses, rehabilitation staff, and medical engineers met to outline a detailed treatment plan for patients, which helped avoid pre-operative risks and increase survival rates. Second, preoperative extensive rehabilitation might have been something related to prevent occurring perioperative complication, Third, post-operatively, we continued hospitalization and monitored patient progress using a coronary angiogram and echocardiography. There was a tendency for postoperative hospitalization days to be prolonged, but patients were fully rehabilitated and discharged in a stable state.

Compared to a study conducted by Poirier et al [14], we found that our prophylactic IABP group tended to have longer ICU stay times (MTA vs. our results: mean 1–4 days vs 4.3 days). However, in their study, Poirier et al stated that “it is important to note that the rate of IABP cross-over (IABP installed during or after cardiac surgery) varied from 13% to 100%”, which is a drastic fluctuation. On the other hand, the timing of IABP removal drastically varies from one study to another; Poirier suggests that these inconsistencies are due to the lack of data on the optimal duration for IABP use. At our institution, IABP removal was performed following hemodynamic stability, which resulted in longer IABP placement periods (IABP cross-over). This seemed to be the cause of the prolonged ICU length-of-stay in the prophylactic IABP group in our studies compared to the recently published MTA. Similarly, for prolonged intubation times post-surgery, heart failure was controlled, circulation was stabilized, and then intubation was performed. The need to control heart failure and stabilize circulation was more prevalent in the high risk group, which could justify the prolonged intubation times following surgery. These are the treatment strategies employed by our institution, which seemed to yield results that contradict findings from recently published studies on IABP. One of the reasons for the low incidence of neurologic events was extensive screening prior to surgery utilizing head and neck CT, MRI and carotid artery echocardiography. Cases deemed necessary might receive treatment for cerebrovascular disease prior to cardiac surgery. We also used epiaortic echocardiography during surgery when it was deemed necessary. In patients with atrial fibrillation, we administered heparin following surgery. Additionally, defibrillation after onset of atrial fibrillation was performed immediately. Although there is no known correlation between our treatment approach and the incidence of neurological events, the occurrence of neurologic events was not evident in this study.

We acknowledge the limitations of this study, such as the lack of a randomized control trial to allow for fixed evaluation of prophylactic IABP during CABG, the limited generalizability secondary to being conducted at a single center, as well as its small cohort size. The nonrandomized design might have affected our results, owing to unmeasured confounds, procedural bias, or detection bias. However, we believe that our study allows a real-life evaluation of prophylactic IABP, particularly its importance at the level of a community hospital, such as ours. We used the definition of high-risk patient based on Ding et al’s report. That was the definition at the time of OPCAB, and that definition may not be applicable to our patient selection in this study. The use of preoperative IABP may involve circulatory dynamics during anesthesia induction, during the weaning of cardiopulmonary bypass, and management immediately after weaning. It may also be involved in stabilizing the circulatory dynamics of patients in the acute phase after surgery. However, these are all speculations and could not be stipulated from this study.

This study has several limitations. First, the number of patients was relatively small. Second, the study was performed at a single center; therefore, the results might not be generalizable to other centers in different situations. The nonrandomized design might have affected our results, owing to unmeasured confounds, procedural bias, or detection bias.

Conclusion

Given the lack of IABP-related complications in this study cohort, our prospective observational study shows that prophylactic IABP in the high-risk patient undergoing CABG is an acceptable option.

Observation data.

(XLSX)

Click here for additional data file.

27 Aug 2019

PONE-D-19-19063

The use of prophylactic intra-aortic balloon pump in high-risk patients undergoing Coronary Artery Bypass Grafting

PLOS ONE

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Reviewer #1: The article presents a prospective observational analysis of 99 patients (group A; 21%) at “high-risk” (out of 471) having undergone from Decembre 2005 to December 2017 either isolated or combined CABG with prophylactic IABP compared to others (Group B 79%, 372 pts). All patients with contraindications to IABP were excluded from the study. The “high risk” criteria the patient should have a stable hemodynamics with 2 criteria out of 6 (NYHA III or IV; LVEF<40%; LVEDD>65mm; LM stenosis >50%; a diffuse CAD defined as more than three distal or more anastomosis and refractory unstable angina.

IABP were inserted the day before operation in CathLab from femoral artery and with a subsequent pre and postoperatively ICU monitoring.

Primary endpoint: 30D mortality

Secondary endpoint: major postoperative complications (LCO, postoperative MI; bleeding; stroke; postoperative AF; IOT>72hh; ICU stay >7dd; total postoperative days >30 dd and MACCE.

Forty seven pts in Group B required IABP postoperatively.

Mean follow up was 32 months.

The two groups were significantly different for LVEF, NYHA class, LM disease; emergent operation and number of stenosis but similar for age, sex, BMI and other comorbidities. Hemodialysis and current smoker were higher in Group B.

The results show similar intraoperative results (time, conversion, postop bleeding, transfusion and strokes).

In the postoperative results Group A had a longer mechanical ventilation and ICU stay.

No complications are reported for the support of IABP.

Overall impatient mortality was 2.1% (2% in group A) (30d 2% Group A vs 1.4% Group B) and no differences in terms of death and MACCE were found.

In the discussion section the authors explain their clinical results and their strategies:

- a multidisciplinary team of cardiologists, cardiac surgeons, nurses, rehabilitation staff, and medical engineers met to outline a detailed treatment plan for patients

- all non-urgent patients underwent extensive cardiac rehabilitation prior to surgery, even patients that were admitted into the emergency room

- all patients underwent treated dental conditions, glycemic imbalances, and co-morbid treatable diseases such as carotid artery stenosis prior to cardiac surgery.

- post-operatively a prolonged hospitalization were used to monitor patient’s progress using a coronary angiogram and echocardiography.

-

The authors, in the end, stated that prophylactic IABP in the high-risk patient undergoing CABG is an acceptable option

Even if the article is interesting, the results are unremarkable and is a hot topic, in my opinion some issues must be solved and more details must be added.

- Patients selection is the key of this article and in my opinion the authors must evaluate just isolated CABG and not combinated ones. Furthermore is not clear the types of operations in each group.

- Surgical description is very poor and there is no mention about conduits and surgical techniques.

- In my opinion the evaluation of the “high risk” patients is not correct in this population. The use of the definition of Ding et al could be useful only in OPCABG because includes technical aspects of off pump surgery, beyond the clinical features, that is inconsistent during ONCABG. Less than 50% of patients underwent OPCABG in your population.

- Your clinical strategy leads to a strict preoperative selection and preparation of patients and even if it is probably very far from my clinical practice I would like to better understand it. So from the first access to the hospital how long do you take for the “exstensive rehabilitation” and which are your endpoints? this strategy also adapt to patients with left main stenosis? You didn’t clarify how many AMI (recent of previous) was present in your population. Probably another interesting evaluation could be made on your strategy for carotid stenosis treatment: how many patients received a surgical or endovascular treatment of the carotid arteries in your population and how long before?

- What about postoperative AKI?

- There is no mention about conduction and completeness of FU.

- In my opinion an actuarial survival estimated by KM analysis has very little sense in a period of observation of 30 days. It should be made on the first year at least.

- The topic is hot and the consensus on the benefit of prophylactic IABP is not so widespread. So in my opinion could be important to emphasize the open question in the discussion section and the references must be enlarged. Furthermore the recent article from Rampersad et al is not a RCT but a metaanalysis.

- The tables are very difficult to read, please reorganize and simplify

Reviewer #2: Thank you for your paper.

It is a very interesting field because IABP seems has to be abandoned by cardiological guidelines but still it has been use consistently in cardiac surgery

As you underlined the cohort of patients in not very wide and is not possible to be definitive on the prophylactic IABP with this numbers

Where do you allocate the patient in the preoperative period? has to be at least an HDU. Has this time counted in the ICU admission stay? In my institution we insert the IABP after the induction in OR.

It seems that the method you have used to detect high risk patients is not working properly since there is a consistent use in not high risk group.

Plus is very interesting that the high risk LVEF, despite is significantly different from the other group, is 49%.

The last consideration is on the weaning time. Have you got any standard parameter to consider to asses the possibility to wean? Do you you use levosimendan?

**********

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28 Sep 2019

Date: September 26, 2019

Andrea Ballotta

Academic Editor

PLOS ONE

Dear Dr. Andrea:

We appreciate the reviewer’s insightful comments on our manuscript entitled, “The use of prophylactic intra-aortic balloon pump in high-risk patients undergoing Coronary Artery Bypass Grafting”. We have revised the manuscript to address the reviewers’ concerns and have included our responses to the reviewers’ comments below.

Thank you for your consideration. I look forward to hearing from you again.

Sincerely,

Ken Nakamura, MD

Division of Cardiovascular Surgery,

Nihonkai General Hospital, 30 Akihochou,

Sakata, 998-8501, Japan.

Tel: +81-23-628-5342

Fax: +81-23-628-5345

E-mail: ken.nakamura622@gmail.com

Reviewer #1

1 Comment: Patients selection is the key of this article and in my opinion the authors must evaluate just isolated CABG and not combinated ones. Furthermore is not clear the types of operations in each group.

Response:

We thank the reviewer for these insightful comments. In accordance with this comment, we evaluated isolated CABG, rather than combined ones. All the obtained values were listed in tables 1, 3, and 4. Three hundred ninety-three patients were included in the isolated CABG group. All statistical analyses were repeated. All applicable locations and numbers have been changed. We added the following sentence to the Patients and Methods section: “at Nihonkai General Hospital, and involved 471 unique patients from December 2005 to December 2017 who underwent isolated or combined CABG. Of those, 393 patients underwent isolated CABG and were included for the analysis.” (Page 5; line 51)

2 Comment: Surgical description is very poor and there is no mention about conduits and surgical techniques.

Response:

Thank you for your comment. In accordance with this comment, we have expanded our Patients and Methods section to include the following, “A CPB circuit was used when deemed necessary during the preoperative assessment. It primarily included criteria such as a large left ventricle and low cardiac function. Additionally, on-pump CABG was scheduled following a comprehensive risk assessment, which included the location and quality of target vessels, and accounted for technically challenging cases. If complete revascularization was feasible, OPCAB was scheduled. Conversion to CPB was considered if there was any evidence of hemodynamic instability, such as ventricular arrhythmia, hypotension (systolic pressure ≤ 80 mmHg), and cardiac arrest during OPCAB procedures. The OPCAB is performed after a median sternotomy. The heart was displaced using a posterior pericardial stitch, gauze, and a tissue stabilizer (Octopus Evolution tissue stabilizer and Octopus Evolution AS tissue stabilizer; Medtronic Corporation, Minneapolis, MN, USA). Body position changes and gravity support (Trendelenburg, right and left table rotations) were carried during surgery. A CO2 blower mister device was used in situations where a bloodless field was not achieved after proximal target vessel occlusion. An intracoronary shunt (Phycon coronary minishunt; Fuji systems, Tokyo, Japan) was used during grafting. On pump isolated CABG was performed utilizing the same techniques. All on pump CABG was performed while the heart was beating. Grafting was always performed from the left internal mammary artery to the left anterior descending coronary artery, followed by grafting of the circumflex coronary artery and right coronary artery using a radial artery or a saphenous vein. The bilateral internal mammary was used in the non-touch aorta technique and ascending aortic sclerosis or calcification was assessed based on pre-operative findings from imaging examinations and intra-operative palpation. The quality of the anastomosis was assessed post-graft utilizing a transit-time flow probe (VeriQ System and TTFM probes; Medistim ASA, Oslo, Norway).” (Page 9; line 102).

3 Comment: In my opinion the evaluation of the “high risk” patients is not correct in this population. The use of the definition of Ding et al could be useful only in OPCABG because includes technical aspects of off pump surgery, beyond the clinical features, that is inconsistent during ONCABG. Less than 50% of patients underwent OPCABG in your population.

Response: Thank you for your insightful comment. As stated, the definition outlined by Ding et al. was the definition at the time of OPCAB, and may not be applicable to our patient selection in this study. I will add it to the Limitation as follows “We used the definition of high-risk patient based on Ding et al’s report. That was the definition at the time of OPCAB, and that definition may not be applicable to our patient selection in this study.” (Page 19; line 298)

There was no conclusion that the use of IABP was effective with On Pump CABG, and I thought there were some opinions that it was not necessary. We added the following sentence in the Discussion section: “The use of preoperative IABP may involve circulatory dynamics during anesthesia induction, during the weaning of cardiopulmonary bypass, and management immediately after weaning. It may also be involved in stabilizing the circulatory dynamics of patients in the acute phase after surgery. However, these are all speculations and could not be stipulated from this study.”

(Page 19; line 300).

4 Comment: Your clinical strategy leads to a strict preoperative selection and preparation of patients and even if it is probably very far from my clinical practice I would like to better understand it. So from the first access to the hospital how long do you take for the “exstensive rehabilitation” and which are your endpoints? this strategy also adapt to patients with left main stenosis? You didn’t clarify how many AMI (recent of previous) was present in your population. Probably another interesting evaluation could be made on your strategy for carotid stenosis treatment: how many patients received a surgical or endovascular treatment of the carotid arteries in your population and how long before?

Response: We thank the reviewer for these comments. “Extensive rehabilitation” was performed especially for patients whose activities of daily living (ADL) were limited due to treatment for heart failure after hospitalization. Rehabilitation aims to be as close to the original ADL as possible. As a first goal, we place importance on standing (out-of-bed exercise). The result of this as an endpoint has been listed in table 2 (new table). Extensive rehabilitation is not applied to patients with high a risk for preoperative load, such as cases with LMT lesions, symptomatic cases, and unstable circulation. Additionally, patients who developed symptoms during extensive rehabilitation underwent surgery immediately. In our study, only one patient required surgery after halting extensive rehabilitation. Table 2 describes the patient’s rehabilitation period, whether they were able to stand, and whether they were able to move to the ward. Additionally, we have added a paragraph on the completion rate and a justification for rehabilitation (rehabilitation indication) to the manuscript as follows: “All non-urgent patients underwent extensive cardiac rehabilitation prior to surgery. Even patients that were admitted into the emergency room underwent cardiac rehabilitation if surgical intervention was not urgent. Additionally, we treated dental conditions, glycemic imbalances, and co-morbid treatable diseases such as carotid artery stenosis prior to cardiac surgery. Extensive rehabilitation had been especially applied for patients whose activities of daily living (ADL) were limited due to treatment for heart failure after hospitalization. Rehabilitation aims for patients to be as close to the original ADL as possible. As a first goal, we place importance on standing (out-of-bed exercise)〔5〕. Extensive rehabilitation is not applied to patients with a high risk for preoperative load, such as cases with LMT lesions, symptom cases, and unstable circulation. Additionally, patients who developed symptoms during extensive rehabilitation underwent surgery immediately.” (Page 7; line 85) and “Extensive rehabilitation had been performed in 19 (4.8%) patients. There was a significant difference between the prophylactic IABP group that underwent extensive rehabilitation (8 [9.4%] vs 11 [3.6%], respectively; p=0.041) (table 2). Seventy-nine percent (15 patients) of the patients started with in-bed exercise and eventually advanced to out-of-bed exercise (63% [5 of 8] vs 91% [10 of 11], respectively; p=0.262). Reasons for extensive rehabilitation (the reason why ADL decreased) were due to many factors including the onset of heart failure (8 patients), the onset of AMI (6 patients), temporarily use of IABP after hospitalization (3 patients), onset of AMI and heart failure (1 patient), and brain infarction (1 patient). In this study, only one patient underwent surgery with the need to halt extensive rehabilitation (table 2).” (Page 12; line 177).

5. Hodgson CL, Stiller K, Needham DM, Tipping CJ, Harrold M, Baldwin CE et al. Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults. Crit Care 2014;18:658. doi: 10.1186/s13054-014-0658-y.

We changed the sentence “all non-urgent patients underwent extensive cardiac rehabilitation prior to surgery. Even patients that were admitted into the emergency room underwent cardiac rehabilitation if surgical intervention was not urgent. Additionally, we treated dental conditions, glycemic imbalances, and co-morbid treatable diseases such as carotid artery stenosis prior to cardiac surgery.” to “preoperative extensive rehabilitation might have been something related to prevent occurring perioperative complication,” (Page 17; line 264).

For recent AMI, the progress of all members was confirmed, and the results were listed in table 1. A recent AMI was defined as being diagnosed with AMI when hospitalized. As a treatment for stenotic lesion of the carotid artery, none of the patients in this patient group underwent a surgical operation (including stent insertion). Nine patients had stenosis of the carotid artery before surgery and were consulted for neurosurgery department at this hospital. Single photon emission computed tomography was performed. It was decided that there was little need for surgical treatment. Our policy is that if there is a time allowance for those who have surgical indications for carotid artery lesions, they will be treated first, but in this study there were no such patients.

We added the following paragraph: “For recent AMI, the progress of all members was confirmed and the results were listed in table 1. A recent AMI was defined as being diagnosed with AMI when hospitalized. There were no differences between the two groups (12 [14.1%] vs 31 [10.1%], respectively; p=0.326). Our policy is that if there is a time allowance for those who have surgical indications for carotid artery lesions, they will be treated first, but in this study there were no such patients. As a treatment for stenotic lesion of the carotid artery and its treatment, none of the patients in this patient group underwent a surgical operation (including stent insertion). Nine patients had pointed stenosis of the carotid artery before surgery and all were consulted for neurosurgery at this hospital. Additionally, single photon emission computed tomography was performed. It was decided that there was little need for preoperative surgical treatment.”

(Page 11; line 158).

5 Comment: What about postoperative AKI?

Response: Thank you for your comments. We added post-operative occurrence of AKI, whether dialysis was required, serum Creatinine just before surgery, and max Creatinine after surgery in tables 1 and 4. Only one patient (without prophylactic IABP) with end-stage renal disease requiring maintenance hemodialysis therapy was initiated chronic dialysis following cardiac surgery.

We added the following sentence in the Patients and Methods section: “Acute kidney injury (AKI ) was defined by increased serum creatinine (SCr) to 0.3 mg/dl/48h or more, increased SCr by 1.5 times or more, or decreased urine output to 0.5ml/kg or less during 6 hours〔3, 4〕.” (Page 6; line 68)

“There were no differences in the post-operative occurrence of AKI between the two groups (3 [3.6%] vs 6 [2.1%], respectively; p=0.326). However, patients without prophylactic IABP required more dialysis following cardiac surgery (0 of 3 [0%] vs 6 of 7 [86%], respectively; p=0.033). Only one patient (without prophylactic IABP) with end-stage renal disease requiring maintenance hemodialysis therapy initiated chronic dialysis following cardiac surgery.” (Results section:Page 13; line 187)

3. Kellum JA, Bellomo R, Ronco C, Mehta R, Clark W, Levin NW. The 3rd International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI). Int J Artif Organs. 2005;28:441-4.

4. Creatinine Kinetics and the Definition of Acute Kidney Injury. Sushrut SW, Joseph VB. J Am Soc Nephrol: 2009;20: 672–679.

6 Comment: There is no mention about conduction and completeness of FU.

Response: We thank the reviewer for their comments. The follow-up results after discharge were confirmed on the medical records of this hospital, related hospitals, or via telephone. In accordance with the reviewer’s comment, we have added a new sentence as follows: “There was a 93% postoperative follow-up rate over an average of 42.5 months (± 42.6). The follow-up results after discharge were confirmed on the medical records of our hospital, related hospitals, or via telephone.” (Page 12; line 183)

7 Comment: In my opinion an actuarial survival estimated by KM analysis has very little sense in a period of observation of 30 days. It should be made on the first year at least.

Response: Thank you for your suggestion. In agreement with the reviewer, we have incorporated the suggestion into our paper. We examined the one-year survival rate between the two groups and included one-year outcomes in Figure 2. We added a new sentence in the Results section as follows, “The 12-months survival curves in the 85 high-risk patients who received prophylactic IABP compared to the 308 non-high risk patients who did not receive prophylactic IABP were similar (p=0.846) (Fig 2).” (Page 14; line 208)

8 Comment: The topic is hot and the consensus on the benefit of prophylactic IABP is not so widespread. So in my opinion could be important to emphasize the open question in the discussion section and the references must be enlarged. Furthermore the recent article from Rampersad et al is not a RCT but a metaanalysis.

Response: We appreciate these insightful comments. We apologize for the incorrect description. We have corrected the statement in the Discussion section as follows: “A recent meta-analysis (MTA) reported that prophylactic IABP use reduced mortality and MACCE in high-risk CABG patients〔10〕” (Page 7; line 9)

In agreement with reviewer #1, the consensus of prophylactic IABP is not so widespread and may need further consideration in the future. In this study, we could mention that the use of prophylactic IABP did not cause major complications and the patients’ mortality rates were not high. As proposed, the discussion was edited to address the inconsistencies on the beneficial effects of IABP. Additionally, a reference was added.

We added a new sentence in the Discussion section as follows: “Currently, the consensus on the benefit of prophylactic IABP is not so widespread.” (Page 14; line 215), “Multiple studies reported the benefit of prophylactic IABP [1,2, 6-8], but it had not been established as the gold standard for high-risk CABG. One of the reasons was complications.” (Page 14; line 219), “Although we were unable to determine the advantages of using prophylactic IABP, some papers report good results.” (Page 15; line 237) and “Jiayang et al showed that preoperative prophylactic IABP reduced the incidence of CABG-associated AKI〔15〕. Our results also showed that postoperative dialysis was significantly less in the prophylactic IABP group (0 of 3 [0%] vs 6 of 7 [86%], respectively; p=0.033). The utility of prophylactic IABP is still open for further study, but early studies indicate that postoperative results may be improved. However, further research is warranted to demonstrate the beneficial effects of prophylactic IABP use.” (Page 16; line 248)

15. Wang J, Yu W, Gao M, Gu C, and Yu Y. Preoperative Prophylactic Intraaortic Balloon Pump Reduces the Incidence of Postoperative Acute Kidney Injury and Short-Term Death of High-Risk Patients Undergoing Coronary Artery Bypass Grafting: A Meta-Analysis of 17 Studies. Ann Thorac Surg 2016;101:2007–19

9 Comment: The tables are very difficult to read, please reorganize and simplify

Response: Thank you for your suggestion. In accordance with the reviewer’s comment, the tables have been reorganized.

Reviewer #2

1 Comment: It is a very interesting field because IABP seems has to be abandoned by cardiological guidelines but still it has been use consistently in cardiac surgery. As you underlined the cohort of patients in not very wide and is not possible to be definitive on the prophylactic IABP with this numbers

Where do you allocate the patient in the preoperative period? Has to be at least an HDU. Has this time counted in the ICU admission stay? In my institution we insert the IABP after the induction in OR.

Response: Thank you for your insightful comments. All patients who received a prophylactic IABP entered the ICU and were waiting. “ICU stay” was not counted as ICU admission stay during the preoperative period.

We have added a new sentence as follows: “All patients who received a prophylactic IABP entered the ICU and were waiting.” (Page 6; line 75) “ICU stay” was not counted as ICU admission stay during the preoperative period.” (Page 13; line 194)

2 Comment: It seems that the method you have used to detect high risk patients is not working properly since there is a consistent use in not high risk group.

Plus is very interesting that the high risk LVEF, despite is significantly different from the other group, is 49%.

The last consideration is on the weaning time. Have you got any standard parameter to consider to asses the possibility to wean? Do you you use levosimendan?

Response: Thank you for your insightful comments. The patient selection was pointed out by reviewer #1. In order to make the selection as appropriate as possible, we have re-examined only with isolated CABG, except for combined CABG. All of these values were listed in tables 1, 3, and 4. Three hundred ninety-three patients were included in the isolated CABG group. All statistical analyses were repeated. All applicable locations and numbers have been changed. We added the sentence in the Patients and Methods section to the following. “at Nihonkai General Hospital, and involved 471 unique patients from December 2005 to December 2017 who underwent isolated or combined CABG. Of those, 393 patients underwent isolated CABG and were included for the analysis.” (Page 5; line 51)

IABP weaning was dependent on stabilization of circulatory dynamics. Weaning was performed when diuresis was present and there was warm in peripheral sensation. However, there was no numerical target. Also our facility did not use levosimendan as an aid to weaning.

We have added a new sentence as follows: “IABP weaning was dependent on stabilization of circulatory dynamics. Weaning was done when diuresis was present and there was warm in peripheral sensation. However, there was no numerical target.” (Page 7; line 82)

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

10 Oct 2019

The use of prophylactic intra-aortic balloon pump in high-risk patients undergoing Coronary Artery Bypass Grafting

PONE-D-19-19063R1

Dear Dr. Nakmaura,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Andrea Ballotta

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you again for your efforts, i deem your paper suitable for publication.

Reviewers' comments:

21 Oct 2019

PONE-D-19-19063R1

The use of prophylactic intra-aortic balloon pump in high-risk patients undergoing Coronary Artery Bypass Grafting

Dear Dr. Nakmaura:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Table 4

Clinical outcomes and complications with or without prophylactic IABP patients.

Result	Total (N = 393)	Prophylactic IABP (n = 85)	No prophylactic IABP (n = 308)	p-value (prophylactic IABP vs. non-prophylactic)
Follow up, %	93	93	94	0.808
Observation period, months				0.037
Mean ± SD	42.5 ± 42.6	33.9 ± 34.1	44.9 ± 44.6
Median (IQR)	27 [5, 73]	23 [5.5, 51]	28 [5, 82]
Operation time, min, Median (IQR)	258.00 [210.00, 313.00]	256.00 [206.50, 304.00]	259.50 [211.25, 314.00]	0.466
Off-Pump CABG	56.7	50.6	58.4	0.217
Pump time, min, Median (IQR)	118.00 [96.00, 148.00]	109.00 [93.00, 144.00]	120.00 [101.00, 149.75]	0.217
converted to on-pump CABG, %	2.8	2.4	2.9	1.000
Postoperative Max SCr, mg/dl, Mean ± SD	2.3 ± 9.7	1.0 ± 0.4	2.9 ± 11.8	0.383
AKI, %	2.4	3.6	2.1	0.423
required Dialysis, %	60	0.0	86	0.033
reoperation for bleeding, %	1.3	1.2	1.3	1.000
Distal anastomoses				<0.001
Mean ± SD	2.5 ± 1.0	2.8 ± 1.0	2.4 ± 0.9
Median (IQR)	2.00 [2.00, 3.00]	3.00 [2.00, 3.00]	2.00 [2.00, 3.00]
required transfusion of red blood cells, %	59	68.2	57	0.062
Leg wound problems, %	0.7	0.0	1	1.000
Leg wound infection, %	0.3	0.0	0.3	1.000
Neurologic events, %	0	0	0	-
Duration of IABP support, days				0.040
Mean ± SD	2 ± 1.6	1.8 ± 1.2	2.4 ± 2.1
Median (IQR)	1.50 [1.00,2.00]	1.00 [1.00,2.00]	2.00 [1.00,3.00]
Duration of mechanical ventilation (post operative days)				0.127
Mean ± SD	1.2 ± 1.6	1.4 ± 1.4	1.1 ± 1.6
Median (IQR)	1.00 [1.00, 1.00]	1.00 [1.00, 1.00]	1.00 [1.00, 1.00]
Prolonged ventilation >72 hours, %	6.1	12.5	4.2	0.014
Reintubation, %	1.4	0	1.8	0.590
ICU stay (post operative days)				0.181
Mean ± SD	4.3 ± 4.0	4.2 ± 4.4	4.9 ± 2.3
Median (IQR)	3.00 [3.00, 4.00]	4.00 [3.00, 6.00]	3.00 [3.00, 4.00]
ICU stay longer than 7 days, %	6.6	11.4	5.3	0.071
Length of hospital stay.days				0.095
Mean ± SD	23 ± 16	25 ± 18	22 ± 15
Median (IQR)	19.00 [16.00, 24.00]	20.00 [17.00, 25.00]	19.00 [16.00, 23.00]
postoperative length of stay longer than 30 days, %	12.8	14.8	12.3	0.573
Post operative atrial fibrillation,%	11.9	13.4	11.4	0.699
Mediastinitis, %	1.6	1.2	1.7	1.000
30 days mortatlity, %	0.8	0.0	1	1.000
In-hospital deaths, %	1.3	0.0	1.6	0.589
MACCE, %	3.8	5.9	3.3	0.333

IQR: Interquartile Range, SD: Standard Deviation, CABG: Coronary Artery Bypass Grafting, SCr: Serum Creatinine, ICU: Intensive Care Unit, MACCE: Major Adverse Cardiac and Cerebrovascular Events