Preemptive deep parasternal intercostal plane block for perioperative analgesia in coronary artery bypass grafting with sternotomy: a randomized, observer-blind, controlled study

Abstract

Objective

The precise characteristics of deep parasternal intercostal plane block (DPIP), which is useful for providing analgesia during open heart surgery, have not yet been thoroughly elucidated. In this study, we aimed to establish the efficacy, define the cutaneous sensory block area, and determine the duration of preemptive DPIP block at the T3-4 or T4-5 intercostal spaces in patients undergoing coronary artery bypass grafting (CABG) via sternotomy.

Design

A prospective, single-blind, randomized controlled trial.

Setting

Patients were randomly divided into three cohorts, each containing thirty patients.

Participants

Ninety patients who underwent elective CABG via sternotomy were included in this study.

Interventions

The T3-4 and T4-5 groups received a preoperative single-shot DPIP block at the respective intercostal spaces. The principal objective of the study was to ascertain the optimal dosage of sufentanil administered during surgical procedures involving either a DPIP block or its absence, and to conduct a comparative analysis thereof across distinct injection sites, specifically T3-4 and T4-5. Secondary factors considered were the dosage of postoperative analgesics, the extent of sensory block on the skin, pain levels after extubation, time of recovery from anesthesia (time to extubation), duration of the block, and the occurrence of nausea and vomiting.

Measurements & Main Results

Preemptive DPIP block significantly reduced intraoperative sufentanil requirement compared to the control group (T3-4:0.38 ± 0.1, T4-5:0.32 ± 0.10, vs. Control:0.88 ± 0.3 μg/kg/h, p < 0.001). It also resulted in decreased analgesic consumption and numeric rating scale scores on the day of surgery (p < 0.01 compared to the control group). The DPIP block provided accurate anesthetic coverage of the dermatomes in the sternal region and reduced the time to extubation and postoperative nausea. However, the injection point (either via the T3-4 intercostal or the T4-5 intercostal) did not affect the efficacy. Preoperative DPIP block failed to provide adequate analgesia beyond 24 h post-surgery.

Conclusion

Preemptive bilateral DPIP block provided effective analgesia in patients undergoing CABG during surgery and in the early postoperative period. The analgesic effects of the DPIP block in the T3-4 and T4-5 intercostal spaces were comparable.

Keywords:

• Anesthetized dermatomes
• coronary artery bypass grafting
• deep parasternal intercostal plane block
• perioperative analgesia

1. Introduction

Coronary artery bypass grafting (CABG) commonly employs a median sternotomy, a procedure associated with considerable discomfort. Inadequate pain management during the perioperative phase may induce neurohormonal responses impacting cardiovascular stability, elevating oxygen consumption, and potentially leading to myocardial ischemia in patients undergoing CABG [1,2]. While opioids have conventionally served as the principal means of pain alleviation in CABG, their well-documented adverse effects, including respiratory depression, diminished gastrointestinal function, and postoperative delirium, underscore the need for alternative approaches [3,4]. The advent of fast-track surgery in cardiac care has spurred interest in exploring ultrasound-guided regional anesthesia methods, such as chest wall block, as viable alternatives to opioids for pain management throughout the surgical process [5].

Deep parasternal intercostal plane block (DPIP) constitutes an innovative ultrasound-guided method wherein local anesthetics (LA) are administered into the fascial layer positioned between the inner intercostal muscle (IIM) and transversus thoracic muscle (TTM) [6]. This technique has demonstrated efficacy in blocking the anterior cutaneous branches of the thoracic intercostal nerves (Th2-6) through a singular intercostal site injection [7]. The duration of the block’s effect spans from approximately 280 min to 12 h, as evidenced by diverse studies [8,9]. The familiarity with the operational intricacies and the visual challenges inherent in the intermuscular plane between the internal intercostal muscle and the transverse thoracic muscle may impact the efficacy of the block. Despite exhibiting promising outcomes in terms of analgesia during cardiac surgery with sternotomy in both adult and pediatric populations [9,10], there remains a need to elucidate the sensory attributes, site of administration, and duration of this relatively recent block when employed in CABG.

The extent of coverage provided by the facial plane block demonstrates variability, contingent upon the chosen injection site. Research supports the T4-5 intercostal space as the recommended site for DPIP injection [11,12]. Furthermore, other studies underscore the superior spread of locally administered LA in the T4-5 intercostal space, as evidenced by ultrasound-guided assessments, when compared to the T3-4 intercostal space [13]. Nevertheless, a direct comparative analysis of sensory blockade between these two intercostal injections within individual patients is lacking. Additionally, challenges arise in consistently visualizing facets of the plane at a singular fixed intercostal space. When undertaking this block in patients undergoing CABG, the judicious selection of an intercostal space becomes paramount for optimal ultrasound visualization, ensuring efficacious analgesia while mitigating inadvertent damage to the internal thoracic artery (ITA), which resides within the same anatomical plane as this block. With the exception of the T4-5 intercostal space, the feasibility of opting for the T3-4 intercostal space for a safe and effective blockade remains uncertain without unequivocal ultrasound clarity.

The suggested PIP blockade proposed by Bloc et al. represents a plausible approach aimed at sustaining hemodynamic equilibrium and mitigating the proinflammatory response subsequent to CABG surgery [14]. Nevertheless, the harvesting of the ITA during CABG introduces a compromise to the anatomical domain of the DPIP, encompassing innervated anterior cutaneous branches originating from T2 to T6 intercostal nerves [15]. This compromise raises the potential concern that it may adversely impact the effectiveness of preemptive DPIP blockade in providing postoperative analgesia. Furthermore, a contentious aspect persists regarding whether a preemptive single-shot DPIP blockade yields adequate relief for extended periods of postoperative pain subsequent to cardiac surgery [16,17].

In response to these concerns, a randomized controlled trial was designed and implemented. The hypothesis put forth is that the preemptive bilateral single-shot DPIP block, administered under ultrasound guidance from the intercostal spaces T3-4 or T4-5, consistently results in increased efficacy in mitigating opioid consumption for pain management during CABG surgery, as opposed to cases devoid of such intervention.

2. Materials and methods

2.1. Design and patients

This study adopted a single-blind, randomized controlled trial design and was conducted at the First Affiliated Hospital of Sun Yat-sen University. Ethical approval was obtained (Approval [2019]386) and the study was registered in the Chinese Clinical Trial Registry (ChiCTR2000030079) in February 2020. Patient enrollment took place from March 2020 to March 2021, and the study adhered to the principles outlined in the Declaration of Helsinki with approval from the ethics committee.

The study included patients aged ≥ 18 years who were scheduled for elective CABG via sternotomy and voluntarily agreed to participate. Exclusion criteria were individuals who had previously undergone secondary cardiac surgery with sternotomy, those with cognitive impairment, those allergic to local anesthetics or contraindicated to nerve block, patients with opioid dependency or chronic pain, individuals with impaired left ventricular (LV) systolic function before the operation (LV ejection fraction [EF] < 50%) as determined by ultrasound, or those who required mechanical circulatory support (IABP or ECMO).

All patients provided written informed consent and the study findings were reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines.

2.2. Randomization and blinding

Upon commencement of the surgical procedure at the predetermined time, a comprehensive reassessment of the mental and hemodynamic conditions of the patients was undertaken. Individuals exhibiting indications of anxiety, depression, tachycardia, arrhythmia, or hypertension were deemed unsuitable for the conscious administration of the DPIP block and were consequently excluded from the study. Systematic ultrasound examinations were conducted on the anterior thoracic wall, with any indeterminate abnormalities identified in the ultrasound images at intercostal levels T3-4 or T4-5 being excluded from the study.

Subsequently, a randomization procedure was executed, allocating patients into three groups (1:1:1) in a randomized manner as outlined in the study protocol: the T3-4 group, where the DPIP block was administered between the third and fourth ribs; the T4-5 group, entailing the administration of the DPIP block between the fourth and fifth ribs; and the control group (referred to as the C group), where conventional anesthesia protocols without regional techniques were employed. The randomization was facilitated through a random number table generated using SPSS Statistics 22 software, and allocation was concealed within sealed opaque envelopes. The necessary copyright license for SPSS Statistics 22 has been obtained for utilization in this study.

Professionally trained healthcare personnel, who were kept uninformed about the group assignment, conducted evaluations encompassing outcomes, cutaneous sensory block assessments, perioperative analgesics, hemodynamic parameters, and numeric rating scale (NRS) scores at specified research intervals. However, as the administration of the DPIP block occurred in conscious individuals, the patients were cognizant of their group affiliation and were not subject to blinding with respect to the group allocation.

2.3. Intervention

On the day preceding the surgical intervention and during the immediate preoperative period, no pharmacological interventions were administered. Upon admission to the operating room on the morning of the surgery, patients underwent surveillance in accordance with established protocols for cardiac surgical procedures. Subsequently, the DPIP block was executed on individuals in the supine position, employing real-time ultrasonography facilitated by a high-frequency linear transducer (SonoSite Edge II, Fujifilm SonoSite, Washington, USA or Philips EPIQ 7 C, Koninklijke Philips N.V.) under the supervision of one of two proficient anesthesiologists. The single-shot DPIP block was then implemented following the transverse approach described by Sepolvere [18].

For the DPIP block execution, the ultrasound probe was positioned proximate to the sternum in a transverse alignment, parallel to the corresponding rib. The ultrasound depiction (Figure 1) exhibited the IIM and the TTM above the pleura. The ITA was also visualized between the IIM and TTM, with confirmation of its presence through color flow Doppler. A 22-gauge, 80 mm peripheral nerve block needle (Stimuplex A, B. Braun Melsungen AG) was introduced via an in-plane technique, exercising caution to avoid vascular structures, and advanced laterally to the central chest area to access the target region between the IIM and TTM. Accurate needle placement was verified by injecting normal saline (< 3 ml) under real-time ultrasound guidance, with successful injection leading to a downward displacement of the pleura or fluid diffusion above the TTM. Subsequently, 20 mL of 0.4% ropivacaine (a local anesthetic) was bilaterally administered. In the T4-5 subgroup, the local anesthetic was introduced into the fourth intercostal space, while in the T3-4 subgroup, it was injected into the third intercostal space. The block initiation occurred unilaterally, followed by the contralateral side, employing an identical technique. Patients in C group did not receive any regional blocks. In instances where the ultrasound failed to clearly visualize the target structures and landmark vessels, participants were excluded from the study and received conventional anesthesia and pain management interventions. A wound dressing was uniformly applied on the designated area for all participants before evaluating their degree of reduced sensation.

Figure 1. A. Ultrasonographic image of DPIP block. B. Triangle icons indicate the needle track. Local anesthetics were spread in the layer between IIM and TTM. DPIP block – Transversus thoracic muscle plane block. IIM – internal intercostal muscle. Transversus thoracic muscle – TTM.

Twenty minutes post the DPIP block procedure, employing methodologies described in a prior study [19], the extent of sensory blockade in the skin was appraised through two modalities: the application of a cold metal object (4 °C) on the sternum, 2 cm to the left of the sternum, and 2 cm to the right of the sternum. The scope of analgesic efficacy was gauged utilizing von Frey filaments at the same three locations. Temperature and mechanical sensation coverage were distinctly demarcated on the skin and documented.

2.4. Anesthesia and postoperative pain management

The surgical procedures involved in this study adhered to conventional monitoring protocols, encompassing a range of diagnostic assessments and quantifications. These procedures included the implementation of an electrocardiogram, pulse oximetry, non-invasive and invasive blood pressure monitoring, central venous pressure monitoring, transesophageal echocardiography (TEE), as well as the utilization of the Vigileo & Flotrac system (Edwards Lifesciences LLC) and end-tidal carbon dioxide measurement. Anesthesia management was overseen by a supervising anesthesiologist who was unaware of the allocation group. General anesthesia was induced through the administration of etomidate (0.2 mg/kg), sufentanil (0.6–1.0 μg/kg), and cisatracurium (0.2 mg/kg). Following tracheal intubation, a TEE probe was positioned, and a central venous catheter was introduced via the right internal jugular vein.

Anesthetic maintenance during the surgical procedure involved the utilization of inhaled sevoflurane at a concentration of 1% in a gas mixture comprising 50% oxygen and air. Additionally, intravenous administration of propofol (utilizing a plasma-site target-controlled infusion based on the Marsh model) and sufentanil (administered through an effect-site target-controlled infusion according to the Geps model) was employed, facilitated by a target-controlled injection system (Primea Infusion System; Fresenius Kabi, Hamburg, Germany). Cisatracurium was intermittently administered to induce appropriate muscular relaxation. The depth of anesthesia was monitored and adjusted in accordance with the Narcotrend stages (MonitorTechnik, Germany, version 4.0) ranging from D1 to E1.

In instances where Narcotrend stages exceeded D1, propofol was incrementally increased at a rate of 0.5 µg/mL every 30 s until the desired level of anesthesia was attained. Inadequate analgesia was defined as an increase in heart rate (HR) and/or systolic blood pressure (SBP) by more than 20% from baseline, under a proper depth of anesthesia. Hypertension and/or tachycardia were initially managed through a stepwise increase in sufentanil at 0.2 ng/mL intervals. If hemodynamic stability remained unattained with an effect-site sufentanil concentration up to 1.0 ng/mL, nicardipine was introduced.

Hypotension, defined as a mean arterial pressure below 65 mmHg, was managed through the administration of norepinephrine or additional fluid infusion. Bradycardia, defined as HR < 50 bpm, was treated with atropine. The maximum recorded values for HR (bpm), SBP (mmHg), MBP (mmHg), and sufentanil effect-site concentration (ng/mL) were documented during specific surgical phases, namely, skin incision, sternotomy, and sternal closure. Furthermore, the incidence of patients requiring nicardipine, norepinephrine, and atropine during the operative procedure was meticulously recorded.

Following the completion of the surgical procedure, intravenous administration of selective serotonin 3 receptor (5-HT3) antagonists, specifically palonosetron (0.25 mg), in conjunction with dexamethasone (10 mg), was undertaken for the purpose of mitigating postoperative nausea and vomiting.

Following surgery, patients were transferred to the cardiovascular intensive care unit (ICU), where extubation procedures adhered to established ICU management protocols. The duration from the moment of admission to the ICU to the cessation of anesthesia-related intubation was designated as the extubation time. Patients who experienced delayed extubation (> 12 h) were excluded from the study.

All patients were administered intravenous patient-controlled analgesia (PCA) as part of the postoperative pain management protocol. The initiation of the PCA regimen involved the administration of hydromorphone (0.5 mg) upon closure of the skin incision, with subsequent adherence to the prescribed protocol: 0.2 mg bolus doses, a 10-minute lockout interval, and a maximum allowable dosage of 1.0 mg per hour. Following extubation, patients were encouraged to engage the PCA system if the NRS score at rest exceeded 3, thereby adversely impacting sleep quality. Supplementary to the PCA, patients were provided with 0.1 g of tramadol as a rescue analgesic in instances where the PCA failed to effectively alleviate pain. Notably, no alternative analgesics, inclusive of non-opioid options such as paracetamol and atypical analgesics, were utilized in the course of this study.

The NRS was employed for the evaluation of pain intensity in each individual while at rest and during coughing throughout extubation at specified time points, namely, immediately postoperatively (0 h), at 6 h, and 12 h on the day of surgery (POD0), followed by assessments at 24 h intervals for the initial three postoperative days (POD1, POD2, POD3), and subsequently on POD7. Pain scores were recorded on a scale ranging from 0 (indicating an absence of pain) to 10 (representing the most intense pain imaginable).

Postoperative opioid administration, total rescue analgesia during the following three days, and postoperative nausea and vomiting during the two postoperative days were also recorded for each patient.

2.5. Primary and secondary outcomes

The principal objective of the study was to ascertain the administered dosage of sufentanil during surgical procedures involving the utilization of the DPIP block and its comparison with procedures not involving the block, while additionally assessing variations across distinct injection sites (T3-4 and T4-5). Secondary considerations encompassed the evaluation of the scope of sensory block on the cutaneous layer, the quantity of postoperative analgesics administered, pain levels subsequent to extubation, the duration required for recovery from anesthesia (time to extubation), the temporal extent of the block, and the incidence of nausea and vomiting. Safety outcomes included the assessment of potential complications such as injury to the internal mammary artery (IMA), pneumothorax, and intoxication arising from local anesthetic agents.

2.6. Sample size and statistical analysis

The primary outcome, the intraoperative administration of sufentanil, was used to determine the sample size. Three pairwise comparisons among the three groups were included in the main analysis. The Hochberg technique [20] was applied to adjust for multiplicity, while maintaining a family wise error rate of 0.05. Based on our preliminary pilot study, the mean and standard deviation (SD) of the consumptions were 0.71 ± 0.1 μg/kg/h in C group, 0.40 ± 0.1 μg/kg/h in the T3-4 group and 0.32 ± 0.1 μg/kg/h in the T4-5 group.

To evaluate the anticipated minimum inter-group variance in the dispensation of 0.08 g/kg/h, with an SD of 0.1 as the normative parameter, a bilateral test was conducted at a significance threshold of 0.05. This analysis factored in an anticipated attrition rate of 10%, necessitating a sample size of 30 patients per group. The determination of the requisite sample size was performed using PASS 15 (PASS software by NCSS, LLC) for which the appropriate copyright license has been duly acquired.

The modified intention-to-treat (mITT) population, which consisted of all eligible, randomly assigned patients, except for those who required mechanical ventilation longer than 12 h following surgery, was used for the primary analysis. Continuous variables were summarized as mean (±SD) or median (interquartile range [IQR]), as appropriate. Categorical variables are presented as percentages (%).

The primary outcome was analyzed using an analysis of covariance (ANCOVA), including age as a covariate. To control the familywise error rate of 0.05, hierarchical and Hochberg procedures were performed. If there were differences between the three groups, additional pairwise comparisons were conducted with the p-value adjusted using the Hochberg technique. Between-group differences and adjusted confidence intervals were also calculated. The Kruskal–Wallis test and Mann–Whitney U test were used if the normality assumption for ANCOVA was violated, with confidence intervals of the difference in medians between groups estimated using Hodges–Lehmann’s method.

Except for the intercostal block count, continuous secondary outcomes were assessed in a manner similar to the primary result. Using student’s t-test, the number of intercostals with diminished cooling sense and mechanical discomfort was examined. Logistic regression and chi-squared tests were used to evaluate binary secondary outcomes. All secondary outcome analyses included between-group differences and 95% confidence intervals. Analysis of secondary outcomes should be considered exploratory as multiplicity was not considered. The analyses were conducted using IBM SPSS Statistics 22 (IBM, Armonk, New York, USA). All P values were two-tailed, and p < 0.05 was considered significant.

3. Results

For the purpose of this inquiry, a comprehensive screening process was conducted involving a cohort of 97 patients (refer to Figure 2). Prior to randomization in the operating room, seven patients were deemed ineligible for inclusion in the study. Among these, six were excluded due to challenges in accurately identifying TTM or ITA in ultrasound images at intercostal levels T3-4 or T4-5. Additionally, one patient exhibited heightened anxiety and reluctance to undergo the DPIP block while awake. Subsequently, the remaining 90 participants were subjected to random assignment into one of three distinct study groups. However, owing to delayed extubation, one participant each from the T3-4 and T4-5 groups, along with two from the control (C) group, were excluded from the analysis. Consequently, the final dataset for analysis comprised 86 patients. It is noteworthy that the baseline characteristics exhibited homogeneity across all three study groups, as detailed in Table 1.

Figure 2. Patient enrollment and study flowchart. POCD – postoperative cognitive dysfunction.

Table 1. Patient demographic and surgical characteristics.

	Total (N = 86)	C group (n = 28)	T3-4 group (n = 29)	T4-5 group (n = 29)	P-value
Patients characteristics
Age, year	59.66 ± 8.7	59.50 ± 7.8	61.28 ± 7.5	58.21 ± 10.6	0.41
Female, n (%)	23(26.7)	9(32)	8(28)	6(21)	0.62
Height, cm	162.81 ± 8.3	161.07 ± 8.3	162.14 ± 9.2	165.17 ± 6.9	0.15
Weight, kg	62.48 ± 10.5	61.00 ± 10.6	60.95 ± 10.4	65.43 ± 8.9	0.18
Hypertension, n (%)	58(67.4)	18(64.3)	19(65.5)	21(72.4)	0.78
Diabetes mellitus, n (%)	30(34.9)	11(39.9)	9(31.0)	10(34.5)	0.81
Operation related time
Operation time, min	404.21 ± 89.6	399.89 ± 79.8	420.45 ± 99.0	401.79 ± 89.2	0.44
Aortic cross-clamping time, min	83.74 ± 30.2	76.04 ± 33.4	94.31 ± 26.0	80.62 ± 28.8	0.06
CPB time, min	168.30 ± 56.7	160.75 ± 62.6	181.41 ± 51.3	162.48 ± 55.4	0.31

Data are expressed as mean ± standard deviation or number (%). P values were calculated using student t-test for means and Chi-square test for proportions. CPB, cardiopulmonary bypass.

The total administration of intraoperative sufentanil was significantly lower in the DPIP groups (T3-4:0.38 ± 0.1, T4-5:0.32 ± 0.1, respectively) than in the C group (0.88 ± 0.3). The mean difference between the C group and T3-4 group was 0.50 µg/kg/h (97.5% CI, 0.39 to 0.61; p < 0.001), and between C group and T4-5 group it was 0.56 µg/kg/h (98.4% CI, 0.44 to 0.68; p < 0.001). No significant differences were observed between the two DPIP groups (p = 0.23) (Table 2).

Table 2. Primary and secondary outcomes.

	C group (n = 28)	T3-4 group (n = 29)	T4-5 group (n = 29)	P-value	C vs T3-4		C vs T4-5		T3-4 vs T4-5
					Difference (95% CI)	P-value	Difference (95% CI)	P-value	Difference (95% CI)	P-value
Primary outcome^a
Intraoperative sulfentanil, μg/kg/h	0.88 ± 0.3	0.38 ± 0.1	0.32 ± 0.1	<0.001	0.50(0.39, 0.61)	<0.001	0.56(0.44, 0.68)	<0.001	0.06(−0.04, 0.16)	0.23
Secondary outcome^b
Skin incision
Maximum sulfentanil Ce, ng/ml	0.7 (0.43-0.98)	0.3 (0.25-0.35)	0.3 (0.23-0.38)	<0.001	0.50(0.40, 0.50)	<0.001	0.40(0.40, 0.50)	<0.001	0.00(−0.10, 0.00)	0.83
ΔSBP, mmHg	9.26 ± 21.0	−3.59 ± 16.1	−7.24 ± 13.1	<0.01	13.24(4.25, 22.24)	<0.01	16.26(7.28, 25.24)	<0.01	3.02(−5.96, 11.99)	0.51
ΔMAP, mmHg	8.50 ± 13.5	−0.72 ± 11.8	−4.31 ± 10.9	<0.001	9.41(2.99, 15.83)	<0.01	12.68(6.27, 19.09)	<0.001	3.27(−3.14, 9.68)	0.31
ΔHR, bpm	−0.75 ± 12.1	−6.52 ± 9.5	−6.69 ± 7.7	0.04	6.05(0.84, 11.27)	0.02	5.73(0.53, 10.94)	0.03	−0.32(−5.53, 4.89)	0.90
Sternotomy
Maximum sulfentanil Ce, ng/ml	0.7 (0.43-0.98)	0.3 (0.15-0.45)	0.3 (0.25-0.35)	<0.001	0.40(0.30, 0.50)	<0.001	0.40(0.30, 0.50)	<0.001	0.00(−0.10, 0.00)	0.81
ΔSBP, mmHg	13.79 ± 19.4	−2.21 ± 12.6	−5.62 ± 24.5	<0.01	15.98(5.62, 26.33)	<0.01	19.42(9.08, 29.76)	<0.001	3.44(−6.90, 13.78)	0.51
ΔMAP, mmHg	12.55 ± 2.5	0.17 ± 1.6	1.07 ± 1.8	<0.001	12.55(6.96, 18.13)	<0.001	11.33(5.76, 16.91)	<0.001	−1.22(−6.79, 4.36)	0.67
ΔHR, bpm	3.61 ± 15.9	−7.41 ± 11.0	−5.10 ± 8.5	<0.01	11.21(4.91, 17.51)	<0.01	8.58(2.29, 14.87)	<0.01	−2.62(−8.92, 3.66)	0.41
Sternal closure
Maximum sulfentanil Ce, ng/ml	0.6 (0.43-0.78)	0.3 (0.23-0.38)	0.3 (0.23-0.38)	<0.001	0.30(0.30, 0.40)	<0.001	0.30(0.20, 0.30)	<0.001	0.00(−0.10, 0.00)	0.76
ΔSBP, mmHg	15.36 ± 18.0	0.31 ± 15.9	0.48 ± 13.4	<0.001	15.17(6.75, 23.59)	<0.01	14.79(6.38, 23.20)	<0.01	−0.38(−8.79, 8.03)	0.93
ΔMAP, mmHg	13.46 ± 13.4	2.79 ± 12.3	0.83 ± 11.5	<0.001	10.76(4.15, 17.37)	<0.01	12.57(5.97, 19.17)	<0.001	1.81(−4.79, 8.41)	0.59
ΔHR, bpm	13.43 ± 12.1	3.07 ± 10.4	6.48 ± 12.4	<0.01	10.50(4.31, 16.69)	<0.01	6.84(0.67, 13.02)	0.03	−3.66(−9.83, 2.52)	0.24
Extubation time (h)	4.52 ± 1.7	3.08 ± 1.2	3.32 ± 2.2	<0.01	1.45(0.55, 2.35)	<0.01	1.18(0.29, 2.08)	0.01	−0.27(−1.17, 0.63)	0.55
Nausea, n (%)	15 (53.6)	6 (20.7)	5 (17.2)	<0.01	32.43(8.69, 56.18)	<0.01	36.92(13.75, 60.10)	<0.01	4.49(−16.53, 25.50)	0.68
Vomiting, n (%)	8 (28.6)	2 (6.9)	1 (3.4)	0.013	21.67(2.57, 40.78)	0.04	25.12(7.12, 43.13)	0.01	3.45(−7.92, 14.81)	0.552
Postoperative hydromor­phone dosage
POD 0, mg^c	1.32 ± 0.5	0.70 ± 0.4	0.66 ± 0.4	<0.001	0.62(0.39, 0.85)	<0.001	0.66(0.43, 0.88)	<0.001	0.04(−0.19, 0.27)	0.75
POD 1, mg^c	2.24 ± 0.3	2.14 ± 0.3	2.09 ± 0.5	0.29
POD 2, mg^c	2.11 ± 0.3	2.25 ± 0.4	2.08 ± 0.3	0.13
POD 3, mg^c	1.96 ± 0.3	1.89 ± 0.3	1.81 ± 0.3	0.17
Nicardipine require­ment, n (%)	15 (53.6)	1 (3.4)	5 (17.2)	<0.001	50.80(30.74, 70.87)	<0.001	36.16(13.21, 59.12)	<0.01	−14.64(−31.17,1.90)	0.08
Norepine­phrine require­ment, n (%)^c	21 (75.0)	23 (79.3)	18 (62.1)	0.58
Total tramadol, g^c	0.061 ± 0.09	0.062 ± 0.11	0.066 ± 0.08	0.98

^aPrimary outcome was Intraoperative sulfentanil. Pairwise comparisons were conducted with the use of analysis of covariate model (ANCOVA), with age as the covariate. The reported P-value and confidence intervals were adjusted for multiple between-group comparisons using Hochberg method.

^bFor the secondary outcomes, the widths of these intervals were not corrected for multiple comparisons and should not be used to infer definitive clinical effects.

^cUnder the type 1 error–control procedure, hypothesis testing for pairwise comparison was not conducted.

Data are expressed as mean ± standard deviation, median (interquartile range) or number (%). Ce, effect-site concentration. HR, heart rate. bpm, beat per minute. MAP, mean artery pressure. POD, postoperative day.

In the context of sustained depth of anesthesia (as indicated by Narcotrend stages D1-E1), the highest TCI dosage of sufentanil necessary during the phases of skin incision, sternotomy, and sternum closure demonstrated comparable outcomes between the two groups subjected to DPIP interventions. Patients in both DPIP groups exhibited a greater likelihood of maintaining hemodynamic stability with reduced sufentanil dosages when compared with those without preemptive DPIP block. Within C group, more than half of the patients required the administration of nicardipine (53.6% versus T3-4: 3.4% and T4-5: 17.2%), whereas the incidence of patients receiving norepinephrine remained consistent across all three groups, with no instances requiring atropine (Table 2).

The average hydromorphone dosage administered on the POD0 was notably lower in both DPIP groups compared to that in the C group (T3-4: 0.70 ± 0.4 mg, T4-5: 0.66 ± 0.4 mg, C group: 1.32 ± 0.5 mg, respectively). However, 24 h postoperatively, no statistically significant differences were observed in the pain medication dosage, including PCA hydromorphone or rescue tramadol, administered over the subsequent three postoperative days—POD1, POD2, and POD3, regardless of the utilization of DPIP (Table 2).

The confirmation of the sensory block area within the parasternal region was undertaken through the implementation of cooling and pinprick assessments conducted 20 min after the bilateral administration of a single-shot DPIP. The outcomes of these examinations revealed a similar dermatomal distribution of DPIP within the T3-4 and T4-5 groups. Notably, beyond the established cutaneous block spanning T2-6, a singular DPIP injection extended the cutaneous block, involving a T1 block in 80% of the participants and a T7 block in 40% of the participants in both groups during the cooling test. However, von Frey tests exposed a confined range of three intercostal blockages proximal to the injection site in both groups (Figure 3). It is noteworthy that sensory test results within the C group exhibited no discernible changes within the same temporal interval (data not presented).

Figure 3. Percentage of cold hypoesthesia (A) and mechanical pain hypoesthesia (B) at different levels of the sternum. C. The number of intercostal blocks within the sternum and parasternal region.

Note: Panels A and B show the percentage of cold hypoesthesia and mechanical pain hypoesthesia at different sternal levels, respectively. Panel C shows the number of intercostal blocks within the sternal and parasternal regions. Pairwise comparisons using logistic regression (Panels A and B) or Student’s t-test (Panel C) provided no evidence of differences between the two block groups.

The NRS assessments, both at rest and during coughing, exhibited a noteworthy reduction in scores within the T3-4 and T4-5 groups in comparison to the C group immediately and 6 h post extubation (p < 0.01, for all comparisons with the C group). Nevertheless, statistical analyses revealed no significant differences among the groups at subsequent time intervals for Panels A and B, as depicted in Figure 4.

Figure 4. NRS score when resting(A) and coughing(B) assessed immediately after extubation, 6 h after extubation, 12 h after extubation, POD 1, POD 2 and POD 3.

NRS, Numeric rating scale; POD, Postoperative day.

*P < 0.05: The NRS score at rest (Panel A) or during coughing (Panel B) was significantly lower in the two block groups than in the C group immediately and 6 hours after extubation.

No statistically significant differences were observed among the groups at any subsequent time point (both Panels A and B).

The scores are presented as mean (plot) and standard deviation (error bar).

The occurrence of postoperative nausea and vomiting exhibited a noteworthy reduction in the DPIP groups as compared to the C group, and the difference was statistically significant (p < 0.05) (Table 2). Furthermore, the time required for extubation in both DPIP groups displayed a significant reduction exceeding one hour in comparison to the C group (p < 0.01). Throughout the seven-day follow-up period, the absence of major adverse events, including but not limited to IMA injury, pneumothorax, or local anesthesia intoxication, was evident.

4. Discussion

The findings of this study provided clarity that the preemptive administration of bilateral single-shot DPIP block significantly mitigated sternotomy-related pain and diminished the need for opioid analgesics throughout the course of and immediately following CABG surgery. Notably, the effectiveness of DPIP was determined to be unrelated to the specific injection site, whether administered between intercostal spaces T3-4 or T4-5. Nevertheless, it is noteworthy that the preoperative implementation of the DPIP block did not confer sustained pain relief beyond the initial 24-h postoperative period.

The effective management of pain during cardiac surgery involving sternotomy poses a significant challenge. Traditionally, opioid-based regimens have been prominently utilized, a preference substantiated by studies affirming their efficacy in preserving perioperative hemodynamic stability [21]. Nevertheless, the evolution of enhanced recovery strategies subsequent to cardiac surgery has prompted a paradigm shift towards the adoption of regional anesthesia techniques as integral components of a comprehensive pain control strategy [22]. The primary objective is to optimize pain management while concurrently reducing dependence on opioids. Several ultrasound-guided fascial plane chest wall blocks, including the erector spinae plane block (ESPB), pectoserratus plane block, and serratus anterior plane block, have been proposed as viable alternatives. However, it has been observed that these blocks offer limited pain relief in the sternal region [23].

The application of the PIP block technique, encompassing both superficial parasternal intercostal plane block (SPIP) and DPIP, for the purpose of blocking the anterior branches of intercostal nerves, has garnered increasing attention in the field of cardiac surgery involving sternotomy. Numerous studies have demonstrated that the administration of bilateral single-shot DPIP blocks, as an integral component of multimodal analgesia, effectively mitigates sternotomy pain levels for a duration of 24 h subsequent to open cardiac surgery [9,17,24–26]. Our research specifically focuses on the utilization of preoperative DPIP to proficiently diminish nociceptive stimulation originating from surgical interventions, thereby conferring the advantage of facilitating the maintenance of hemodynamic stability throughout the entirety of surgery, as compared to conventional opioid-based regimens. The favorable results of a preemptive fascial plane block on perioperative hemodynamic management in our study is similar to the results of the SPIP study conducted by Bloc et al. [14]. The incorporation of preemptive DPIP resulted in a noteworthy reduction exceeding 50% in opioid dosage during CABG surgery, culminating in well-established advantages such as expedited extubation time and a diminished incidence of postoperative nausea and vomiting.

In this investigation, we conducted a comprehensive evaluation of the specific anesthetic coverage of dermatomes situated on the anterior chest wall in conscious preoperative patients. The study by Fujii et al. utilizing cadavers has substantiated that a singular administration of local anesthetic spans the anterior intercostal spaces from T2 to T6, aligning with the established comprehension of the coverage area associated with DPIP anesthesia [9]. Our sensory cooling assessments demonstrated an extension of the blocked dermatomes beyond the prescribed T2-6 levels, encompassing a range spanning four to five levels. Furthermore, this extension manifested more prominently in the cranial direction (upper to T1) as opposed to the caudal direction (lower to T7) at the sternum for both injection groups, consistent with the outcomes of a recent anatomical study conducted by Harbell et al. [27]. Their study, which involved the administration of a DPIP block at the T3-4 intercostal level, showcased a spread that reached four levels above and below the injection site, effectively staining the intercostal nerves. The outcomes of our study furnish precise and meticulous insights into the analgesic effects of DPIP in the context of anterior thoracic surgeries.

Nevertheless, in the assessment of sensory blocks utilizing von Frey tests, their effectiveness was confined to three levels during the examination. This observation may be attributed to two potential factors. Initially, it is conceivable that the commencement period required for regulating mechanical pain might exceed that for achieving a cessation of cold sensation [28]. Secondly, investigations have indicated the selective blockade of unmyelinated C-fibers, responsible for temperature sensation, by ropivacaine applied to nerves, as opposed to myelinated fibers of A-delta nociceptors accountable for pinprick-induced pain [29,30]. Additionally, an examination of the outcomes following sufentanil administration during surgical interventions revealed that, notwithstanding the alleviation of sternotomy pain intensity through a single injection of DPIP, residual pain endured. Consequently, similar to other thoracic wall blocks, DPIP should be considered as a supplementary component of multimodal analgesia rather than a standalone anesthetic technique. Its role lies in providing opioid-sparing effects rather than complete elimination of opioid usage [31].

The ITA is situated within the DPIP, adjacent to the sternum, positioned between the IIM and TTM. It manifests a slender muscular layer with hypoechogenicity in specific patient cases [32]. Given its primary utilization as the conduit vessel for CABG, impairment of the ITA could impede the success of grafting vessels [18]. Consequently, it is imperative to prioritize the clarity of ultrasound visualization when establishing the pre-CABG placement of the DPIP, particularly in the selection of the intercostal site for injection.

Historically, the T4-5 intercostal space has been the preferred choice for injection in prior studies. However, the results of our study indicate that in instances where visualizing the TTM becomes challenging at the T4-5 intercostal spaces, the alternative use of the T3-4 intercostal spaces can yield analogous analgesic efficacy and anesthetic coverage of dermatomes on the anterior chest wall. Given the inherent difficulty in visualizing the TTM in both intercostal sites during CABG, contemplation of a more superficial SPIP block is warranted.

Although the preemptive DPIP block demonstrated commendable intraoperative analgesic efficacy, the results of our study revealed its inadequacy in influencing postoperative analgesia. Comparable pain scores and analgesic consumption were observed among the three groups, irrespective of the administration of blocks, during the latter part of the surgical day. These findings are consistent with those reported in existing literature, indicating that the majority of single-administration fascial plane blocks afford relief from pain for an approximate duration of 12 h [11]. Nevertheless, certain studies have documented extended analgesic effects surpassing 24 h, specifically in the context of preemptive single-administration bilateral DPIP blocks [10]. Hence, in order to augment the management of postoperative pain through the implementation of the DPIP block, it is imperative to conduct a more thorough examination of the ideal timing for administering DPIP (preoperative or postoperative), as well as the effectiveness of local anesthetic adjuncts or catheterization for sustained analgesic outcomes. Further investigation in these areas is warranted to refine and advance the understanding of optimizing postoperative pain control through DPIP block.

This study has several limitations, notably, the comparatively small sample size, which might be insufficient for the identification of potential adverse events linked to the DPIP block, including infections, hematoma, pneumothorax, and LA toxicity.

In contrast to alternative thoracic wall blocks, the PIP block presents several merits, notably its feasibility during general anesthesia with the patient in a supine position, streamlining any necessary manipulations. Nevertheless, our study aimed to scrutinize the specific anesthetic coverage of dermatomes on the anterior chest wall, opting to administer the block to conscious patients preoperatively, a choice that may attenuate the potential advantages of this block. Incorporating objective real-time nociception monitoring tools, such as the Nociception Level Index (NLI), into the DPIP block may enhance the evaluation of blockade efficacy and function as a reference for intraoperative opioid consumption in anesthetized patients, as recently documented in preemptive ESPB [33].

While chest wall blocks typically exhibit superior efficacy in mitigating superficial pain compared to sympathectomy [34], these methodologies contribute to the modulation of the inflammatory response induced by surgical stimulation. In the current study, the postoperative proinflammatory response was not scrutinized, given its thorough exploration in prior research conducted by Bloc et al. [14]. Subsequent research endeavors need to substantiate the potential enhancement of recovery and mitigation of the inflammatory state subsequent to cardiac surgery through preemptive DPIP.

This study is subject to several supplementary limitations. Notably, the subset of participants recruited for the study, specifically those undergoing CABG, constituted a demographic characterized by the most severe acute postoperative pain. This circumstance may restrict the applicability of the discerned advantages to individuals experiencing moderate or less intense pain. Furthermore, the absence of a placebo injection in the C group stemmed from the collective refusal of patients and surgeons. Additionally, the discernibly superior efficacy exhibited in the group subjected to the block compared to the non-block group presented potential impediments to maintaining physician blinding. Lastly, in the management of postoperative pain, the absence of baseline analgesia was notable, with opioids being the exclusive analgesic agents employed. Non-opioid alternatives were precluded in this study due to the unavailability of acetaminophen at our medical facility. Nonetheless, the integration of a multimodal analgesia strategy through the implementation of a well-established ERAS protocol holds promise for optimizing the opioid effects of the DPIP block in the context of postoperative cardiac pain management.

5. Conclusions

Optimal analgesic management during CABG with sternotomy was successfully attained through the implementation of a preemptive bilateral single-shot DPIP block. Patients subjected to this intervention manifested a sustained and uniform hemodynamic profile throughout the entirety of the surgical procedure, demonstrated expedited emergence from anesthesia, and exhibited a reduced incidence of postoperative nausea and vomiting. Upon comparing the administration of the DPIP block at the T3-4 and T4-5 intercostal spaces, no statistically significant differences emerged with respect to total opioid consumption and sensory anesthesia within the anterior chest wall regions. These findings underscore the need for precise ultrasound guidance in the selection of injection sites, mitigating potential adverse consequences.

Authors contributions

Yu Chen and Qi Li conceived the idea and conceptualised the study. Yi Liao, Ying-yuan Li, Mingying Zhan and Gai-jiao Liu collected the data. Yi Liao, Xiao-e Wang and Qi Li analysed the data. Yu Chen and Qi Li drafted the manuscript, then Qi Li and Li Xiao reviewed the manuscript. All authors read and approved the final draft.

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

I confirm that I read the Editorial Policy pages. This study was approved by the Ethics Committee of The First Affiliated Hospital of Sun Yat-sen University(approval number: [2019]386). This study was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all the participants.

Acknowledgements

We would like to acknowledge the hard and dedicated work of all the staff who implemented the intervention and evaluation components of the study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data used to support the findings of this study are available from the corresponding author upon request.