Comparison of Analgesic Efficacy of Intrathecal Morphine and Ultrasound-Guided Bilateral Erector Spinae Plane Block in Patients Undergoing Open Heart Surgery with Midline Sternotomy: An Open Label Randomized Control Trial

ABSTRACT

Background and Aims:

Intrathecal morphine (ITM) and erector spinae plane block (ESPB) decrease postoperative pain in standard cardiac surgery. In this study, we compared the analgesic efficacy of ITM and B/L ESPB in patients undergoing open heart surgeries.

Methods:

After approval from the institutional ethics committee and written informed consent from patients scheduled for open heart surgeries, they were randomized into two groups: Group ITM patients received ITM (5 mcg/kg), whereas Group ESPB patients received bilateral ESP block (0.3 mL/kg of 0.5% ropivacaine on either side). The primary outcome was to compare postoperative fentanyl consumption during the first 24 hours of ICU stay after extubation. Secondary outcomes were postoperative VAS at rest and on cough during the first 24 hours, pre- and postoperative pulmonary function, and number of rescue analgesics. Quantitative variables were presented as mean (SD) or median (IQR). Categorical variables were expressed as numbers or percentages. Spirometry variables were compared over time between the groups using Friedman test.

Results:

The ITM group had significantly less median fentanyl consumption compared to the ESPB group during the first 24 hours postoperative period [0 (0–75) μg vs. 234 (160–336) μg (95% CI, 171.65, 255.38); P < 0.001]. The VAS score at rest and during cough was significantly better in the ITM group. FEV1 and FVC reduced postoperatively in both groups with significantly better values in the ITM group.

Conclusion:

ITM administered prior to induction provides superior postoperative analgesia compared to bilateral ESPB in patients undergoing open-heart surgery. It significantly reduces opioid requirements, improves patient satisfaction, and enhances postoperative pulmonary function.

INTRODUCTION

Cardiac surgical patients often experience moderate to severe pain, peaking on the day of surgery.[1] Inadequate pain control can trigger sympathetic responses like tachycardia and increased oxygen demand, while impairing breathing and coughing, leading to hypoxemia, atelectasis, infections, and prolonged hospitalization.[2]

Postoperative analgesia typically relies on systemic opioids with NSAIDs and paracetamol. However, opioids may cause respiratory depression, sedation, nausea, and delayed recovery, while NSAIDs can result in renal impairment and coagulation dysfunction.[3,4] In line with Enhanced Recovery After Surgery (ERAS) protocols, regional anesthesia techniques are increasingly used in cardiac surgery as they provide effective analgesia with fewer systemic side effects.[5,6]

Intrathecal morphine (ITM), used historically in low doses, provides prolonged analgesia with relatively fewer side effects.[7,8] More recently, ultrasound-guided erector spinae plane block (ESPB) has gained attention, producing extensive thoracic analgesia by blocking dorsal and ventral rami.[9] Both ITM and ESPB are effective, yet they have not been directly compared in cardiac surgery patients.

This study aims to evaluate and compare the analgesic efficacy and safety of ITM versus bilateral ESPB in open-heart surgery. The primary objective was to assess postoperative fentanyl consumption during the first 24 hours of ICU stay after extubation. Secondary objectives included comparing postoperative VAS scores at rest and on cough, time to extubation, pre- and postoperative pulmonary function, need for rescue analgesics, patient satisfaction, and side effects associated with each technique.

METHODS

This single-center, randomized control trial was conducted in a tertiary health care institute, from May 2022 to September 2023, after obtaining Institutional Ethics Committee approval and registration with Clinical Trial Registry – India (CTRI/2022/04/042171). After getting informed written consent from the patients, 102 patients between the ages of 18 and 70 years, belonging to American Society of Anesthesiologists (ASA) PS II-IV scheduled for elective cardiac valve replacement/repair surgery/atrial septal defect (ASD)/ventricular septal defect (VSD) closure cases with midline sternotomy, were included. We have complied with all ethical guidelines established by the 2013 Helsinki Declaration.

Exclusion criteria were an emergency surgery, patients who refused to participate in the study, allergy to study drugs, cognitive deficits making them inefficient for use of IV Patient-Controlled Analgesia (PCA) pump, any contraindications for spinal and fascial plane block, inability to understand the pain scale or to perform a spirometry, any type of chronic painful condition, left ventricular ejection fraction (LVEF) <40%, preoperative cardiac support (IV inotropes and/or vasoconstrictors), morbid obesity, liver and renal dysfunction, and opium dependence.

All patients underwent a preprocedural evaluation and were informed how to use the PCA pump (CADD-Legacy^® PCA, Model 6300, Smith Medical ASD, Inc., St. Paul, MN 55112, USA). All patients received instructions on how to properly use a handheld spirometer (Contac Handheld SP10 Spirometer, China). Preoperative pulmonary function tests (PFTs) such as forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the FEV1/FVC ratio were assessed and recorded. The Visual Analog Scale (VAS), ranging from 0, indicating no pain, to 10, representing the worst imaginable pain, was explained to each patient, and their baseline pain levels were recorded.

Using a computer-generated random number table, patients were randomly allocated to either group ESP (n = 51) or group intrathecal morphine ITM (n = 51). Allocation concealment was done using sequentially numbered coded sealed opaque envelopes. The envelopes opened just after the patient entered the operating room.

Preinduction, patients belonging to the ESPB group received USG-guided bilateral single-shot ESP block at T5 level with 0.3 mL/kg of 0.5% ropivacaine on either side, with the help of a high-frequency (8–13 MHz) linear probe (LOGIQe, GE Healthcare, Chicago, United States).

For patients in the ITM group, after local infiltration with 2% lidocaine, a 27-gauge spinal needle was inserted at the L3–L4 or L4–L5 interspace under sterile conditions. 5 mcg/kg of morphine was injected into CSF, upon free return of clear cerebrospinal fluid.

Standard ASA monitoring was applied in all patients. An 18G intravenous cannula and left radial arterial line were secured. The intraoperative anesthetic technique was standardized. Induction was with IV midazolam (1 mg), fentanyl (5 mcg/kg), propofol (1 mg/kg), and rocuronium (0.6 mg/kg). The airway was secured with an appropriately sized endotracheal tube, and anesthesia was maintained with inhaled isoflurane.

Any increase in heart rate (HR) or blood pressure (BP) by more than 15% of baseline during surgery was treated with additional fentanyl 1 mcg/kg. All procedures were performed by two senior cardiac surgeons via midline sternotomy. After IV heparin (4 mg/kg), cardiopulmonary bypass (CPB) was initiated when activated clotting time exceeded 480 seconds. During CPB, anesthesia and muscle relaxation were maintained with isoflurane, propofol, and rocuronium boluses, targeting BIS values of 40–60.

At the end of surgery, patients were shifted to the ICU intubated. Extubation followed the institutional protocol, and extubation time was recorded (defined as time from ICU admission until extubation). Paracetamol 1 g IV every 6 hours was administered to all participants. After extubation, VAS scores were assessed. Postoperative analgesia was provided with IV PCA fentanyl (0.5 mcg/kg). If VAS exceeded 4 at rest or on demand, patients received another fentanyl bolus after a 30-min lockout. If pain persisted despite two boluses, ketorolac 30 mg in 100 mL normal saline was administered as rescue analgesia. Patients requiring prolonged ventilation (>6 hours) were excluded.

Preoperative data were collected from medical records. The primary outcome was postoperative fentanyl consumption during the first 24 hours of ICU stay after extubation, recorded from PCA pump data. Secondary outcomes included VAS scores (at extubation, 2, 6, 12, and 24 h postextubation, both at rest and on cough), extubation time, number of PCA boluses, rescue analgesic requirements, and nonsurgical complications (pruritus, vomiting, pneumothorax, hematoma, or local anesthetic toxicity). Pulmonary function testing (PFT) was performed at 24 and 48 hours in the sitting position. Patient satisfaction was assessed at 48 hours using a four-point Likert scale (1 = excellent, 2 = good, 3 = fair, 4 = poor).

Sample size calculation was based on pilot data, where the mean (SD) fentanyl consumption in the intrathecal morphine (ITM) group was 150 (75) mcg. For ESPB to be considered equally effective, postoperative fentanyl use was assumed within 30% (105–195 mcg; SD 85) of ITM. A sample of 102 patients (51 per group) was needed to provide 80% power at a 5% significance level.

Data were compiled using Microsoft Excel. Normality was tested with the Kolmogorov–Smirnov one-sample test. Normally distributed quantitative variables were expressed as mean ± SD, while non-normally distributed and ordinal variables were expressed as median (range). Categorical data were presented as absolute numbers or percentages. Comparisons were performed using Student’s t-test for continuous variables and χ² test for categorical variables. Mann–Whitney U test was used for ordinal and non-normally distributed variables. Spirometry outcomes were compared over time between groups using the Friedman test. A P value < 0.05 was considered statistically significant.

RESULTS

Total one hundred and twelve patients were assessed for eligibility. Ten patients (six patients were not meeting inclusion criteria and four patients refused to participate) were excluded from the study. The remaining 102 patients were enrolled and randomized into group ESPB (n = 51) and group ITM (n = 51). There was no loss to follow-up, and data from all the patients randomized were analyzed [Figure 1].

Figure 1.

CONSORT flow diagram

The patients and surgical characteristics are presented in Table 1. There were no significant differences between the ITM and ESPB groups regarding patient characteristics (age, weight, gender and height, BMI, ASA physical status), duration of surgical time, and the type of surgical repair.

Table 1.

Patient and surgical characteristics

	Group ESPB (n=51)	Group ITM (n=51)	95% CI	P
Age (in years)*	41.86 (12.87)	40.76 (14.34)	(–4.25,6.45)	0.685
Sex (Male: Female)ᵠ	26:25	25:26		0.843
Weight (in kgs)*	54.80 (12.48)	52.83 (11.81)	(–2.80,6.74)	0.416
Height (in cm)*	164.18 (8.21)	160.86 (7.96)	(0.14,6.50)	0.041
BMI (in kg/m2)†	19.6 (17.5-22.3)	19.9 (17.1-22.9)	(–1.88,1.43)	0.647
ASA-PS (III: IV)ᵠ	11:40	11:40		1.00
Duration of surgery (in mins)*	311.76 (42.55)	308.43 (45.22)	(–13.91,20.58)	0.702
Type of surgeryᵠ
Valve replacement	40	40		1.00
CHD (ASD/VSD closure)	11	11

Data are reported as mean±SD*, median (Interquartile range, 25^th to 75^th percentile)^†, number of patients^ᵠ. BMI: Body Mass Index, ASA-PS: American Society of Anesthesiologists - Physical Status, CHD: Congenital Heart Disease, ASD: Atrial Septal Defect, VSD: Ventricular Septal Defect, CI: Confidence interval

The ITM group had significantly less median fentanyl consumption compared to ESPB group during the first 24 hours postoperative [Table 2]. The number of PCA bolus doses attempted was also significantly less in the ITM group than in the ESPB group [0 (0–3) vs. 12 (8–16); median difference 12 (95%CI: 8.64, 13.82); P < 0.001] [Table 2]. The VAS trends for postoperative pain during rest and coughing are shown in Figure 2. At every recorded time point, patients in the ITM group showed significantly lower VAS values than those in the ESP group, both during rest and during coughing. Preoperative PFT variables were comparable between groups; FEV1 and FVC reduced postoperatively in both the groups with the significantly better values in the ITM group than in the ESPB group. In general, ITM group PFT was better preserved [Figure 3]. In the ITM group, the median patient satisfaction score was 2 (2–2), compared to the ESPB group, which was grade 3 (3–3), with the median difference of 1 (95%CI: 0.82, 1.21) and a P value of < 0.001.

Table 2.

Intraoperative and postoperative data

	Group ESPB (n=51)	Group ITM (n=51)	Median difference (95% CI)	P
Intraoperative fentanyl consumption (in mcg)	350 (300-400)	330 (300-350)	20 (0.21,1.03)	0.003
Time to extubation (in minutes)	150 (60-220)	120 (50-200)	30 (–19.07,51.8)	0.321
Total fentanyl consumed 24 h postoperatively	234 (160-336)	0.00 (0.00-75)	234 (171.65,255.38)	<0.001
Number of PCA Bolus doses attempted	12 (8-16)	0 (0-3)	12 (8.64,13.82)	<0.001
Number of rescue analgesia doses required	0 (0-1)	0 (0-0)	0 (0.13,0.49)	<0.001
Patient satisfaction score	3 (3-3)	2 (2-2)	1 (0.82,1.21)	<0.001

Data are reported as median (Interquartile range). VAS: Visual Analog Scale, PCA: Patient Controlled Analgesia, CI: Confidence interval

Figure 2.

(a) VAS score at rest and (b) VAS score on cough

Figure 3.

(a) FVC between groups, (b) FEV1 between groups, and (c) FEV1/FVC ratio between groups

Two patients in the ESPB and five patients in the ITM group had PONV, while six patients in the ITM group had pruritus in our study which were managed medically. None of them had side effects like drowsiness and respiratory depression.

DISCUSSION

Our study demonstrates that low-dose ITM offers superior postoperative analgesia in patients undergoing cardiac surgery, as reflected by significantly reduced fentanyl consumption within the first 24 hours postoperatively. Furthermore, ITM use was associated with lower VAS scores at rest and during coughing, fewer PCA bolus attempts, reduced need for rescue analgesics, and better preservation of PFT compared to bilateral ESPB.

One of the biggest challenges in cardiac surgery with sternotomy is postoperative pain management. It has been found that the conventional opioid-based analgesic regimen lengthens recovery and has a number of unfavourable effects.[10,11] Recently, use of regional analgesic techniques for optimal pain control in cardiac surgery has been advocated by the multiple expert group who support the implementation of the fast-track approach in cardiac surgery.[12,13,14]

Our primary outcome total fentanyl consumption in the first 24 hours postextubation was markedly lower in the ITM group, with a median use of 0 μg versus 234 μg in the ESPB group (P < 0.001). Dos Santos et al.[8] demonstrated significantly reduced opioid requirements in morphine group, particularly at 18 h, 24 h, and 36 h postoperatively. Similar to our result, Elgendy[7] found that with 7 μ/kg ITM administration in patients undergoing aortic valve replacement surgery, the cumulative fentanyl consumption during the first 24 hours after extubation was significantly reduced by 35% in the ITM group (951 μg/first 24 hours) as compared to the control group (1463.6 μg/first 24 hours) (P < 0.001), although they use higher doses of ITM compared to us. Dhawan et al.[15] reported similar findings in minimally invasive cardiac surgery, where ITM markedly reduced the need for systemic opioids. The mechanism behind this lies in ITM’s ability to directly modulate nociceptive transmission at the spinal cord level, offering prolonged analgesia with minimal systemic effects.

The ITM group had significantly lower VAS scores after extubation both at rest and during coughing, underscoring the importance of effective analgesia in the immediate postoperative period. Adequate pain control facilitates deep breathing and effective coughing, essential for preventing atelectasis and reducing the risk of pulmonary complications. Dos Santos et al.[8] observed significantly less VAS scores at 12, 18, 24, and 36 hours after surgery in the morphine group both at rest and when coughing compared to the control group (P < 0.05). Mehta et al.[16] in their study found VAS scores at rest and during coughing at time intervals of 6, 12, 24, and 36 hours postoperatively showed significantly better results in the ITM group. Kang et al.[17] in a comparative study between bilateral ESP block and ITM in laparoscopic hepatectomy concluded that patients who received ITM had lower postoperative pain scores compared to ESPB; their results are in agreement with our study. While ESPB is valued for its safety and ease of administration, particularly under ultrasound guidance, our results suggest it may be less effective than ITM for sternotomy-related pain. Although studies such as that by Macaire et al.[2] have reported benefits of ESPB within ERAS protocols, the block may offer limited dermatomal spread and inconsistent visceral analgesia—factors especially pertinent in median sternotomy.

Postoperative spirometry data revealed a decline in PFT in both groups, a common finding after cardiac surgery. However, patients in the ITM group maintained significantly better FEV1 and FVC values. This likely reflects better analgesia, allowing for more effective respiratory efforts. Our results are consistent with those of Jacobshon et al.,[14] who found improved PFT in the ITM group compared to placebo. In a retrospective cohort study, Ellenberger et al.[18] assessed 1543 elective CABG patients; they demonstrated remarkable decreased occurrence of PPCs in patients with ITM of 8.1% versus 12.8% in patients with IVA (odds ratio, 0.6; 95% CI: 0.40, 0.89; P = 0.012). In contrast, Dos Santos et al.[8] reported no significant difference between ITM and placebo, indicating that factors such as study design and patient selection may influence outcomes. Nevertheless, our findings support the view that optimal analgesia positively impacts postoperative pulmonary mechanics.

No significant difference was observed in the time to extubation between the two groups in our study. However, Elgendy et al.[7] reported significantly shorter extubation times in the ITM group when compared to placebo. This discrepancy could be attributed to the differences in comparator groups—our study compared ITM with ESPB, both active interventions, rather than with a placebo.

Importantly, patient satisfaction scores favored the ITM group. Fewer PCA bolus attempts and reduced need for rescue analgesia underscore the effectiveness and reliability of a single ITM dose administered preinduction. These results are clinically significant, especially where continuous regional blocks may not be feasible.

Despite these advantages, ITM is not without its limitations. Potential complications such as delayed respiratory depression, pruritus, and urinary retention must be considered. In our study, few patients complain these side effect. Importantly, none of the patients experienced serious adverse effects such as respiratory depression, excessive sedation, or block-related complications, findings consistent with those of Santos et al.[8]

Randomization and allocation concealment were strictly followed throughout the study, thereby avoiding the selection bias. Two different interventions were compared, rather than comparing the intervention with the placebo group. These are all the strengths of our study. We had some limitations like a single-center study; single-shot ESP block was given rather than a continuous infusion which would have prolonged the analgesia, and also, effectiveness of blocks was not assessed in the operation theater with the loss of sensation technique before the surgery.

In conclusion, low-dose ITM administered prior to induction provides superior postoperative analgesia compared to bilateral ESPB in patients undergoing open-heart surgery. It significantly reduces opioid requirements, improves patient satisfaction, and enhances postoperative pulmonary function. ITM should be considered an effective and practical component of multimodal analgesia strategies in cardiac surgical patients.

Author contributions

VK: Design, data acquisition, manuscript preparation. RK: Concept, data analysis, manuscript review. SM: Concept, literature search, data analysis, statistical analysis, manuscript editing. AC: Literature search, statistical analysis, manuscript review. MK: Manuscript preparation, manuscript editing. SC: Design, data acquisition. AS: Concept, literature search, data analysis, manuscript editing.

Ethical approval and CTRI registration

The Institutional Ethics Committee approved the study (IEC Reg No. AIIMS/IEC/2022/4022) and registered with Clinical Trial Registry – India (CTRI Reg. No. CTRI/2022/04/042171). After getting informed written consent from the patients, 102 patients between the age of 18 to 70 years, belonging to ASA PS II/III/IV scheduled for elective cardiac valve replacement/repair surgery/ASD/VSD closure cases with midline sternotomy. As we realised that we will not be able to cover the sample size in the given period, we revised our inclusion criteria and title and requisition regarding the same was sent to Institutional Ethics Committee which got approved (IEC Reg no: AIIMS/IEC/2022/5092, Dated 05/08/2022: approved by Dr. Praveen Sharma). These changes were updated with the Clinical Trial Registry – India.

Data availability statement

Data shall be shared after approval as per the authors’ Institution policy.

Conflict of interest

Nil.

Funding Statement

Nil.