Efficacy and Safety of Ultrasound-Guided Erector Spinae Plane Block at Different Injection Depths for Percutaneous Kyphoplasty: A Randomized Controlled Trial

Abstract

Objective

To compare the analgesic efficacy and safety of deep, superficial and combined deep-superficial erector spinae plane block (ESPB) combined with subanesthetic-dose esketamine in patients undergoing percutaneous kyphoplasty (PKP).

Patients and Methods

A total of 120 elderly patients with osteoporotic vertebral compression fractures and undergoing elective PKP were randomly divided into three groups (n=40 each): a deep ESPB group (D), a superficial ESPB group (S) and a combined deep-superficial ESPB group (C). All patients received intravenous esketamine (0.125 mg/kg) preoperatively. We recorded intraoperative and postoperative Visual Analogue Scale (VAS) scores, hemodynamic parameters, the onset time for sensory block, rescue analgesia requirements and adverse reactions.

Results

The combined group exhibited significantly lower cumulative intraoperative pain (AUC: 0–4), fewer administrations of rescue analgesia, and more stable hemodynamics than the two single-depth groups (P<0.01 for all). Differences in postoperative analgesia were only observed at 6 hours, with no significant differences at 12 and 24 hours. No significant difference was found between the three groups in terms of the incidence of adverse reactions.

Conclusion

Combined deep and superficial ESPB combined with subanesthetic-dose esketamine provides superior intraoperative analgesia and hemodynamic stability for patients with PKP, with a safety profile that is similar to single-depth blocks.

Introduction

With the intensification of global population aging, the incidence of osteoporotic vertebral compression fracture (OVCF) is increasing annually and has become a serious public health problem that threatens the health of the elderly.1 Percutaneous kyphoplasty (PKP), as a minimally invasive form of surgery for the treatment of OVCF, can quickly relieve pain, restore vertebral stability, and significantly improve the quality of life of patients by combining balloon dilation to reduce the vertebral body and the injection of bone cement.2 However, PKP-related procedures, such as puncture caused by the working cannula, pedicle dilation, and reaction to bone cement polymerization, can cause severe pain. Insufficient analgesia not only reduces patient comfort but may also induce adverse events such as severe blood pressure fluctuations and myocardial ischemia. In particular, elderly patients are often afflicted by multiple comorbidities that carry higher risks.3 Therefore, optimizing the perioperative analgesic regimen for PKP is crucial to improving patient prognosis.4

Ultrasound-guided erector spinae plane block (ESPB) was first reported in 20165 and is now used widely for perioperative analgesia in thoracic, abdominal, and spinal surgeries due to the fact that this technique is simple to perform, safe, and exhibits a wide analgesic range.6 In this technique, local anesthetics are injected into the fascial plane around the erector spinae muscle. These drugs can diffuse along the costotransverse foramina and paravertebral space to block the anterior and posterior branches of the spinal nerves and the sinuvertebral nerves, thereby achieving multi-segment analgesia.7 However, there is still some controversy regarding the effects of injection depth in ESPB on analgesic efficacy. Specifically, deep block (between the erector spinae muscle and the transverse process) can act directly on the paravertebral plexus, resulting in a more significant block of pain around the bone and pedicle while a superficial block (between the erector spinae muscle and rhomboid muscle) can easily block the posterior branches of spinal nerves innervating soft tissues in the back, with better analgesic effects during the puncture stage.8,9 In clinical practice, a block performed at a single depth often fails to effectively cover different types of pain stimuli throughout the PKP procedure, thus leading to an unbalanced analgesic effect.

As a highly selective antagonist for the N-methyl-D-aspartate (NMDA) receptor, esketamine exerts central analgesic, anti-hyperalgesic, and sedative effects, with minimal impact on respiratory and circulatory systems.10 Previous studies have shown that when a sub-anesthetic dose of esketamine is combined with regional block, there are multiple synergistic effects, including an enhancement in the analgesic effect, prolongation of the block duration, and a reduction in both opioid dosage and adverse reactions.11,12 Previous studies have evaluated the efficacy of esketamine combined with local anesthesia for PKP. However, no systematic studies have compared the effects of different ESPB injection depths combined with esketamine in this patient population. In this randomized controlled trial, all groups received the same dose of esketamine preoperatively to provide a uniform baseline analgesic effect, thus allowing us to identify differences in efficacy that were attributable to different ESPB techniques.

In this randomized controlled trial, we compared the analgesic efficacy and safety of deep, superficial, and combined deep and superficial ESPB. We aimed to identify an optimal block regimen and provide evidence-based reference guidelines for perioperative analgesia in PKP.

Materials and Methods

Ethical Approval

This study was approved by the Ethics Committee of the Fourth Affiliated Hospital of Anhui Medical University (approval number: KYXM-202502-002) and registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2500099539) with complete supervision procedures. The study protocol was conducted in accordance with the principles of the Declaration of Helsinki to protect the privacy and data security of subjects. Written informed consent was obtained from all participants.

Study Design

This was a single-center, three-group, parallel, randomized and controlled trial. We enrolled a total of 120 patients who underwent elective PKP in the Fourth Affiliated Hospital of Anhui Medical University between April 2025 and December 2025. Eligible patients were randomly divided into Group D (the deep block group), Group S (the superficial block group), and Group C (the combined deep and superficial block group) at a ratio of 1:1:1 using a random number table. The random sequence was generated by an anesthesiologist who was not involved in the trial using SPSS version 25.0 software. Grouping information was sealed in sequentially numbered opaque envelopes. Prior to surgery, an independent research coordinator opened the envelopes and revealed the groupings only to the anesthesiologist performing the block. Due to the different injection depths required, the anesthesiologist performing the block could not be blinded to group allocation. However, all other parties – including the patients, the surgeons, and the outcome assessors (postoperative pain evaluators) – were blinded to group assignment throughout the study period. Therefore, this trial is best described as a patient‑ and assessor‑blinded study.

Patient Recruitment

Inclusion Criteria

The inclusion criteria were as follows: (1) aged 60–90 years, with an ASA physical status classification of I to III; (2) diagnosed with OVCF by imaging examinations (X-ray, MRI) and scheduled for single-segment PKP; (3) normal cognitive function and able to accurately express pain intensity; (4) normal coagulation function and no history of allergy to local anesthetics; and (5) voluntarily participated in this study and signed the informed consent form.

Exclusion Criteria

The exclusion criteria were as follows: (1) skin infection or damage at the puncture site; (2) severe hematological disease or coagulation dysfunction; (3) severe insufficiency of vital organ function (NYHA class IV heart failure, Child-Pugh class C liver function or renal failure requiring dialysis); (4) the use of opioids or analgesic and sedative drugs within the previous 14 days; (5) mental illness, peripheral neuropathy, or an inability to communicate normally; (6) pregnant or lactating women; and (7) vascular malformation or anatomical abnormality in the puncture path.

Withdrawal Criteria

The withdrawal criteria were as follows: (1) poor block effect (sensory block degree < grade 2) requiring replacement of the anesthesia method; (2) the occurrence of severe adverse reactions (such as local anesthetic toxicity, severe allergic reaction, or persistent hypotension) making it impossible to continue the trial; (3) active withdrawal or loss to follow-up; (4) the occurrence of severe intraoperative complications (such as nerve compression due to the leakage of bone cement or massive hemorrhage due to vascular injury) requiring emergency treatment.

Intervention Measures

Preoperative Preparation

All patients were required to fast for 8 hours and strictly abstain from drinking for two hours before surgery. For diabetic patients, the fasting time was adjusted appropriately. After entering the operating room, an intravenous access was established, and routine monitoring of blood pressure (BP), MAP, HR, SpO₂, and ECG was performed. The patient was placed in the prone position and given oxygen inhalation via a face mask (oxygen flow rate: 3 L/min). Ten minutes before anesthesia, all three groups received a slow intravenous injection of a subanesthetic dose of esketamine hydrochloride injection (Jiangsu Hengrui Pharmaceutical Co., Ltd., National Medicine Approval Number: H20193336) at 0.125 mg/kg, with an injection time > 1 minute. The patient’s respiratory rate, state of consciousness, and the occurrence of hallucinations and other adverse reactions were closely observed.

Ultrasound-Guided ESPB Operation

All block operations were performed by the same anesthesiologist with more than five years of experience in ultrasound-guided block. Surgery involved a MicroTurbo HFL38x portable color two-dimensional ultrasound instrument (Sonosite, USA) equipped with a low-frequency convex array probe (2–5 MHz). Figure 1 provides a schematic diagram showing the ultrasound-guided ESPB operation and the anatomical block mechanism.

Figure 1.

(A) The combination of deep and superficial ESPB (marked by the green and blue areas) was capable of interrupting both the proximal and distal branches of the spinal dorsal ramus. (B) Schematic of ultrasound-guided ESPB. The blue area represents the injection zone for the superficial erector spinae plane block, while the green area represents the injection zone for the deep erector spinae plane block.

Abbreviations: SP, Spinous process; TP, Transverse process; ESM, Erector spinae muscle.

Localization and Disinfection

The target segment was the vertebra above the lesion vertebra. The ultrasound probe was placed parallel to the long axis of the spine at 2–4 cm beside the spinous process. Sagittal scanning was performed to identify anatomical structures such as the trapezius muscle, rhomboid muscle, erector spinae muscle, and transverse process (the transverse process was considered the key bony landmark), and the puncture point was marked. The skin was routinely disinfected with 1% povidone-iodine, a sterile towel with an appropriate hole was placed over the surgical area, and the ultrasound probe was covered with a sterile protective sleeve and coated with sterile coupling gel.

Puncture and Injection

We adopted the in-plane puncture technique, with the needle inserted from the lateral side to the medial side of the probe:

Group D

The needle tip was punctured to the deep surface of the erector spinae muscle (between the erector spinae muscle and the vertebral transverse process). Following negative aspiration for blood and air, 2 mL of normal saline was injected to confirm the position of the needle tip (indicated by the spreading hypoechoic area under ultrasound), followed by the slow injection of 20 mL of 0.33% Ropivacaine Hydrochloride Injection (AstraZeneca AB, Sweden, National Medicine Approval No. H20140763). This concentration was based on pre-experimental results to balance analgesic efficacy and safety.

Group S

The needle tip was punctured to the superficial surface of the erector spinae muscle (between the erector spinae muscle and rhomboid muscle). The remaining operations were the same as those in Group D, with 20 mL of 0.33% ropivacaine injected.

Group C

The needle tip was first placed on the deep surface of the erector spinae muscle to inject 10 mL of 0.33% ropivacaine. Then, the needle tip was adjusted to the superficial surface of the erector spinae muscle to inject the remaining 10 mL. Diffusion of the drug solution was continuously monitored by ultrasound during the injection process.

Evaluation of Block Efficacy

The patient was observed for 30 minutes following completion of the block. The sensory block effect was evaluated using the pinprick method, which was divided into four grades: Grade 0 (no block, normal sensation), Grade 1 (reduced sensation, reduced pinprick pain), Grade 2 (loss of sensation, no pinprick pain), and Grade 3 (loss of both motor and sensory function). Grade 2 or above was considered an effective block, and surgery could be commenced. If the block effect was Grade 1, we injected esketamine (0.05 mg/kg) intravenously as preemptive analgesia. If the block effect was Grade 0, the block was considered failed, and the patient was withdrawn from the trial.

Intraoperative and Postoperative Management

All surgeries were performed by the same experienced orthopedic surgeon. If a patient’s VAS score exceeded 4 points during surgery, esketamine (0.05 mg/kg) was intravenously injected as rescue analgesia. If the BP increased by more than 20% of the baseline value, urapidil (5 mg) was injected intravenously to control blood pressure. If the HR exceeded 100 beats/min, esmolol (10 mg) was injected intravenously. No postoperative analgesia was used for any of the three groups post-surgery. Patients were transferred back to the ward, and routine vital sign monitoring was performed for 24 hours after surgery. Parecoxib sodium (40 mg) was injected intravenously if the VAS score exceeded 4 points after surgery.

Outcome Measures

Primary Outcome Measures

• (1)VAS scores at the following time points: before anesthesia (T0), during soft tissue puncture with the PKP working cannula (T1), following insertion of the cannula into the pedicle (T2), during balloon dilation (T3), and following the injection of bone cement (T4).
• (2)Area under the curve for intraoperative VAS scores (AUC0-4), calculated using the trapezoidal method and reflecting the cumulative degree of pain throughout the operation.

Secondary Outcome Measures

• (1)Hemodynamic indices (MAP, HR) at each intraoperative time point (T0-T4).
• (2)Static (quiet supine position) and dynamic (30°turning over, one forceful cough) VAS scores at 6, 12, and 24 hours after surgery.
• (3)Onset time for sensory block (time from local anesthetic injection to achieving Grade 2 sensory block).
• (4)The number of intraoperative administrations of rescue analgesia (the number of times esketamine was required).
• (5)The incidence of adverse reactions: including hypotension, nausea and vomiting, hypoxemia (SpO₂ < 90% lasting > 1 min), local anesthetic toxicity, nerve injury (persistent sensory/motor abnormalities 24 hours after surgery), and hematoma at the puncture site.

Statistical Analysis

SPSS version 25.0 statistical software was used for data analysis. Measurement data that conformed to a normal distribution are expressed as mean ± standard deviation. Inter-group comparison was performed by one-way analysis of variance (ANOVA). Repeated measurement data were analyzed by repeated measures ANOVA. If the sphericity assumption was not met, then we adopted Greenhouse-Geisser correction, and Bonferroni correction was used for post-hoc multiple comparisons. Measurement data that did not conform to the normal distribution are expressed as median (interquartile range) [M (Q1, Q3)]. Inter-group differences were tested by the Kruskal–Wallis H-test, and pairwise comparisons were performed using the Mann–Whitney U-test. Count data are expressed as number (percentage) [n (%)]. Inter-group comparison was performed using the chi-squared test or Fisher’s exact probability method. P < 0.05 was considered statistically significant.

Sample Size Calculation

This study was a three-group, parallel, randomized and controlled trial. Intraoperative VAS score was used as the primary outcome measure. According to pre-experiments and previous relevant literature,13 the minimal clinically important difference (MCID) for VAS score was determined to be 1.5, with a standard deviation of 2.0. We applied a two-sided α of 0.05 and a power of 90%. The sample size was calculated using G*power version 3.1.9.7 software. Each group required 36 cases to complete the study, with a total of 108 cases in three groups. Considering a 10% dropout rate, 120 subjects needed to be recruited; these subjects were randomly assigned to the three groups at a ratio of 1:1:1, with 40 cases in each group.

Results

Patient Data at Baseline

A total of 123 subjects were initially enrolled in this study; however, one patient developed a severe allergic reaction, and two patients underwent a change of anesthesia method due to poor block effect. The remaining 120 patients were divided into three groups, each featuring 40 cases. All patients completed the surgery and the 24-hour postoperative follow-up period, and no cases dropped out (Figure 2). There were no statistically significant differences between the three groups in terms of baseline, including age, gender ratio, ASA classification, BMI, and operation duration (all P > 0.05), indicating good comparability (Table 1). Figure 2 provides a CONSORT flow diagram showing the patient recruitment and grouping process (Figure 2).

Figure 2.

CONSORT diagram for patient recruitment.

Table 1.

Comparison of Baseline Data Between Groups C, D and S

Variables	C	D	S	X2/Z/F	P
Age (years)	75.88±5.234	74.68±6.265	75.30±6.458	0.399	0.672
Duration of surgery (minutes)	24.60±1.646	24.45±1.724	24.40±1.429	0.168	0.845
Sex				0.251	0.882
Male	11 (27.5)	10 (25)	12 (30)
Female	29 (72.5)	30 (75)	28 (70)
ASA classification				0.267	0.875
II	11 (27.5)	10 (25)	9 (22.5)
III	29 (72.5)	30 (75)	31 (77.5)
BMI (kg/m2)	20.07 (18.83, 22.54)	19.67 (18.80, 22.59)	20.65 (19.60, 22.61)	1.269	0.53

Primary Outcome Measures: Intraoperative VAS Scores and AUC0-4

There was no significant difference in VAS scores between the three groups at T0 (P > 0.05). At T1 (the soft tissue puncture stage), the VAS score for Group D was significantly higher than that of Group S and Group C (all P < 0.01); there was no significant difference between Group S and Group C (P > 0.05). From T2 to T4 (from cannula insertion into the pedicle to the injection of bone cement), the VAS score for Group S was significantly higher than that for Group D and Group C (all P < 0.01); there was no significant difference between Group D and Group C (P > 0.05). Figure 3 shows a heatmap of P-values for inter-group differences in intraoperative VAS scores at key surgical time points. The overall comparison of intraoperative VAS score AUC0-4 between the three groups revealed a statistically significant difference (F = 156.832, P < 0.01); pairwise comparisons further revealed that the intraoperative VAS score AUC0-4 for Group C (4.200 ± 1.087) was significantly lower than Group D (7.113 ± 1.011) and Group S (7.938 ± 0.826) (all P < 0.01); there was no significant difference between Group D and Group S (P=0.068) (Table 2). Figure 4 shows a comparison of the AUC for intraoperative VAS scores (AUC0-4) among the three groups.

Figure 3.

Heatmap showing P-values reflecting intergroup differences in intraoperative VAS scores at key surgical time points.

Table 2.

Comparison of Intraoperative VAS Scores at Each Time Point Between the Three Groups [M (Q1, Q3), Scores]

Moment	C	D	S	C vs D P value	C vs S P value	D vs S P value
T0	2.00 (2.00, 3.00)	2.00 (2.00, 3.00)	2.00 (2.00, 3.00)	0.350	0.424	0.913
T1	0.00 (0.00, 1.00)	3.00 (3.00, 4.00)	0.00 (0.00, 1.00)	<0.01*	0.755	<0.01*
T2	1.00 (0.00, 1.00)	1.00 (0.00, 1.00)	2.00 (2.00, 3.00)	0.909	<0.01*	<0.01*
T3	1.00 (1.00, 2.00)	1.00 (1.00, 2.00)	3.00 (3.00, 4.00)	0.983	<0.01*	<0.01*
T4	2.00 (1.00, 3.00)	2.00 (1.50, 3.00)	4.00 (4.00, 4.50)	0.801	<0.01*	<0.01*

Note: *Based on pairwise comparison after Bonferroni correction P < 0.05.

Figure 4.

AUC area under the intraoperative VAS curve at different time points. **** indicates statistical differences between the two groups (P < 0.001), ns indicates no significant difference between the two groups (P > 0.05). Based on pairwise comparison of Bonferroni corrected data.

Postoperative VAS Scores

At six hours post-surgery, the static VAS score for Group S was significantly higher than that for Group D and Group C (all P < 0.05). The dynamic VAS score for Group C was significantly lower than that for Group S (P < 0.05). At 12 hours post-surgery, there were no significant differences in the static and dynamic VAS scores between the three groups (P > 0.05). At 24 hours post-surgery, the static and dynamic VAS scores for the three groups all decreased to below 1 point, with no significant inter-group differences (P > 0.05) (Table 3).

Table 3.

Comparison of VAS Scores at Different Time Points After Surgery Between the Three Groups [M (Q1, Q3), Scores]

VAS	C	D	S	C vs D P value	C vs S P value	D vs S P value
Resting state
6 h postoperatively	1.00 (0.00, 1.00)	1.00 (0.00, 1.00)	1.00 (1.00, 1.50)	0.614	0.001*	0.008*
12 h postoperatively	1.00 (0.00, 1.00)	1.00 (0.00, 1.00)	1.00 (0.00, 1.00)	0.967	0.492	0.550
24 h postoperatively	0.00 (0.00, 0.00)	0.00 (0.00, 0.00)	0.00 (0.00, 0.00)	1	0.238	0.238
Active state
6 h postoperatively	2.00 (1.00, 2.00)	2.00 (1.50, 2.00)	2.00 (2.00, 2.00)	0.183	0.007*	0.178
12 h postoperatively	1.00 (1.00, 2.00)	1.00 (1.00, 2.00)	1.00 (1.00, 2.00)	0.562	0.372	0.655
24 h postoperatively	0.00 (0.00, 0.00)	0.00 (0.00, 0.00)	0.00 (0.00, 1.00)	0.513	0.056	0.200

Note: *Based on pairwise comparison after Bonferroni correction P < 0.05.

Secondary Outcome Measures

Onset Time for Sensory Block, the Number of Intraoperative Rescue Analgesia Administrations, and the Incidence of Adverse Reactions

The onset time for sensory block in Group C and Group S was significantly shorter than that in Group D (P < 0.01); there was no significant difference between Group C and Group S (P > 0.05). The number of intraoperative administrations of rescue analgesia in Group C was significantly lower than that in Group D and Group S (P < 0.01); furthermore, the number of rescue administrations in Group D was significantly lower than that in Group S (P < 0.01). There was one case of hypoxemia in Group C, one case in Group D, and one case of hypoxemia plus one case of nausea and vomiting in Group S. None of the patients experienced pneumothorax, dyspnea, or other adverse reactions. There was no statistically significant difference in the incidence of adverse reactions when compared across the three groups (P > 0.05) (Table 4). However, it should be noted that sample size was calculated based on pain outcome; consequently, the study was underpowered to detect differences in rare adverse events such as local anesthetic toxicity, permanent nerve injury, or pneumothorax.

Table 4.

Comparison of Onset Time for Sensory Block, the Number of intraoperative administrations of Rescue Analgesia, and the Incidence of Adverse Reactions Between the Three Groups [M (Q1, Q3)/n (%)]

Group	C	D	S	C vs D P value	C vs S P value	D vs S P value
The Onset Time of Sensory Block	4.00 (3.00, 4.00)	14.50 (14.00, 15.50)	3.00 (3.00, 4.00)	< 0.01*	0.022	< 0.01*
Frequency of Rescue Analgesia During Operation	0.00 (0.00, 1.00)	2.00 (2.00, 2.00)	3.00 (3.00, 4.00)	< 0.01*	<0.01*	< 0.01*
Adverse Effects Rate	1(2.5%)	1(2.5%)	2(5%)	1.000	1.000	1.000

Note: *Based on the pairwise comparison after Bonferroni correction P < 0.05.

Intraoperative Hemodynamic Indices

There was no significant difference between the three groups at T0 with regard to MAP and HR (P > 0.05). At T1, the MAP and HR of Group D were significantly higher than those of Group C and Group S (P < 0.01). At T2, the MAP of Group S was significantly higher than that of Group D (P < 0.05), and the HR of Group S was significantly higher than that of Group C and Group D (P < 0.01). From T3 to T4, the MAP and HR of Group S were significantly higher than those of Group C and Group D (P < 0.05). The dynamic changes of MAP and HR at each intraoperative time point in the three groups are shown in Figures 5 and 6, respectively. Hemodynamic indices for the three groups fluctuated within the normal range, with no persistent hypotension or tachycardia (Table 5).

Figure 5.

Mean arterial pressure over time in each of the three groups.

Figure 6.

Heart rate over time in each of the three groups.

Table 5.

Comparison of Intraoperative Hemodynamic Indices at Each Time Point Between the Three Groups (Mean ± SD)

Vital Signs	C	D	S	C vs D P value	95% CI	C vs S P value	95% CI	D vs S P value	95% CI
MAP (mmHg)
T0	111.48±10.15	108.84±9.19	108.76±9.42	0.228	[−1.677, 6.944]	0.218	[−1.642, 7.075]	0.968	[−4.061, 4.228]
T1	106.33±11.31	116.65±8.26	102.06±8.40	<0.01*	[−14.731, −5.902]	0.059	[−0.159, 8.709]	<0.01*	[10.884, 18.229]
T2	106.45±9.41	106.63±7.32	110.98±8.15	0.926	[−3.929, 3.579]	0.024	[−8.445, −0.605]	0.014*	[−7.800, −0.900]
T3	107.28±9.84	105.37±7.47	115.90±7.37	0.329	[−1.971, 5.805]	<0.01*	[−12.486, −4.747]	<0.01*	[−13.838, −7.229]
T4	109.31±9.35	107.87±6.80	120.00±7.59	0.433	[−2.197, 5.080]	<0.01*	[−14.482, −6.901]	<0.01*	[−15.340, −8.927]
HR (times/minute)
T0	82.85±8.72	80.38±9.10	83.60±9.90	0.218	[−1.493, 6.443]	0.72	[−4.904, 3.404]	0.133	[−7.459, 1.009]
T1	79.68±10.10	88.00±12.44	77.55±9.82	0.002*	[−13.369, −3.281]	0.343	[−2.307, 6.557]	<0.01*	[−5.461, 15.439]
T2	79.70±9.73	79.98±9.06	86.48±8.20	0.896	[−4.459, 3.909]	0.001*	[−10.780, −2.770]	0.001*	[−10.346, −2.654]
T3	80.28±10.45	80.08±8.20	91.23±8.81	0.924	[−3.981, 4.381]	<0.01*	[−15.252, −6.648]	<0.01*	[−14.939, −7.361]
T4	81.08±11.14	80.55±8.58	93.90±8.70	0.814	[−3.901, 4.951]	<0.01*	[−17.274, −8.376]	<0.01*	[−17.197, −9.503]

Note: *Based on pairwise comparison after Bonferroni correction P < 0.05.

Discussion

By comparing the analgesic efficacy and safety of ESPB at different injection depths combined with esketamine in PKP, our analysis first confirmed that the combined deep and superficial ESPB strategy (Group C) provided more balanced and sustained analgesia during the perioperative period of PKP. This combined strategy exhibited the lowest cumulative intraoperative pain level (AUC0-4), the least demand for rescue analgesia, and did not increase the incidence of adverse reactions. These findings suggest that the application of a hierarchical block strategy that targets the pain characteristics of PKP surgery has clear clinical advantages.

Differences in Analgesic Efficacy and the Mechanisms of ESPB at Different Injection Depths

The sources of pain during PKP exhibit obvious stage and multi-structure participation characteristics. The working cannula puncture and soft tissue separation stage predominantly involve the back skin, muscles, and fascial structures, and pain signals are mainly mediated by the posterior branches of the spinal nerves. In contrast, the pedicle dilation, balloon dilation, and bone cement injection stages predominantly stimulate the vertebral periosteum, paravertebral tissues, and sinuvertebral nerves; pain conduction relies more on the anterior branches of the spinal nerves and sympathetic nerve fibers.14 This pattern of pain means that a block in a single anatomical plane cannot adequately address these pain stimuli throughout surgery.15,16 In a previous paper, Kline proposed that the application of modified combined deep and superficial ESPB could optimize block efficacy, and shared his opioid-free anesthesia regimen for spinal surgery.17 In the present study, we found that superficial ESPB (Group S) significantly reduced the VAS score at T1 (the soft tissue puncture stage) but provided insufficient analgesia from T2 to T4, thus suggesting that local anesthetics predominantly act on the posterior branches of the spinal nerves, with limited diffusion to the paravertebral space. Previous imaging studies have also confirmed that when injected superficially, local anesthetics are mostly confined to the superficial fascial layer of the erector spinae muscle and cannot enter the costotransverse foramen area in a stable manner.18 In contrast, our current findings revealed that deep ESPB (Group D) exhibited better analgesic effects during the deep operation stage (T2-T4) but relatively insufficient analgesia during the initial puncture stage; this may be related to its limited ability to cover the superficial sensory nerves. Combined deep and superficial block (Group C) achieved synergistic block of different neural pathways by administering drugs to both the superficial and deep layers of the erector spinae muscle: superficial injection blocks the posterior branches of spinal nerves and back soft tissue sensation, while deep injection diffuses to the paravertebral space through the costotransverse foramen to block the anterior branches of spinal nerves and sinuvertebral nerves, thus forming comprehensive coverage of multi-source pain during PKP. A previous MRI study by Sørenstua et al confirmed that the combination of deep and superficial injection allowed local anesthetics to diffuse to both the superficial fascial layer and paravertebral space, significantly expanding the analgesic range.19 This mechanism is most likely to be responsible for why Group C maintained low VAS scores at all key operation stages and had significantly better cumulative intraoperative pain levels than the single-depth block groups. Notably, although the combined group achieved the best overall analgesic effect, the deep block group showed comparable analgesic efficacy to the combined group during key surgical stages (T2-T4) despite receiving the same total volume of local anesthetic. This suggests that 10 mL of 0.33% ropivacaine in the deep layer may be insufficient to achieve optimal anesthesia, and that increasing the volume of local anesthetic in the deep layer may further improve the analgesic effect of the combined strategy.

Synergistic Analgesic Effect of Esketamine and ESPB

Esketamine can inhibit the formation of central sensitization and hyperalgesia by antagonizing NMDA receptors, and can also exert certain sedative and anti-anxiety effects.20 Previous studies have shown that low-dose esketamine can enhance the analgesic intensity and duration of regional block, improve the quality of postoperative recovery, and reduce the demand for opioids.21 In this study, all three groups received a subanesthetic dose of esketamine as a baseline adjuvant analgesic. This regimen was chosen based on previous evidence showing that esketamine can enhance the effect of regional blocks and reduce opioid requirements. While our results demonstrate that the combination of esketamine with all three ESPB strategies is effective and safe for PKP, our study design did not allow us to quantify the specific synergistic effect between esketamine and ESPB. Future studies, including a control group without esketamine, would be needed to address this question.

Most PKP patients are elderly and often exhibit a range of comorbidities such as hypertension and coronary heart disease. The excitation of sympathetic nerves caused by intraoperative pain can significantly increase the risk of cardiovascular events.22 The Guidelines for Perioperative Anesthesia Management of Elderly Patients emphasize that intraoperative hemodynamic stability should be maintained in elderly patients (blood pressure fluctuation not exceeding ±20% of the baseline value) to reduce the risk of myocardial ischemia and stroke.23 In 2023, Ma et al conducted a randomized controlled trial on elderly patients undergoing general anesthesia for gastrointestinal tumors. Analysis revealed that low-dose esketamine can reduce the incidence of postoperative neurocognitive dysfunction (PND), improve intraoperative hemodynamic and BIS value fluctuations, reduce the incidence of cardiovascular adverse events and intraoperative opioid consumption, and alleviate postoperative pain.24 This is consistent with the safety characteristics of esketamine observed in this study; we found that the combination of a sub-anesthetic dose of esketamine with ESPB achieved a satisfactory analgesic effect but also avoided obvious neurological or hemodynamic complications in elderly OVCF patients. In this study, Group C exhibited the smallest fluctuations in MAP and HR during the key pain stimulation stages, thus suggesting that the sufficient analgesia provided by this technique helped to inhibit the stress response. Compared with simple sedation or general anesthesia, the combination of ESPB with low-dose esketamine achieved effective analgesia while maintaining spontaneous breathing without tracheal intubation, thus reducing complications related to airway management. These findings are in line with the perioperative management goals of “minimally invasive, safe, and rapid recovery” for elderly patients and the concept of Enhanced Recovery After Surgery (ERAS). It is worth noting that there was no significant difference between the three groups in terms of the incidence of common adverse reactions (hypoxemia, nausea and vomiting). However, larger multi-center studies with longer follow-up periods are now needed to fully evaluate the long-term safety and the risk of rare complications of these regimens.

Advantages and Limitations

There are several advantages to our present study: (1) we adopted a randomized, patient- and assessor-blinded design to provide strict control over baseline data and operational bias; (2) we focused on the dual characteristics of intraoperative pain in PKP, the effects of blocks at different depths were compared in a targeted manner, and our conclusions are more clinically relevant; (3) we comprehensively evaluated the whole-course analgesic effect by analyzing indicators such as the AUC0-4 rather than scores at single timepoints, thus increasing the reliability of our results; and (4) this is the first randomized controlled trial to systematically compare the efficacy of deep, superficial, and combined ESPB when combined with a standardized subanesthetic dose of esketamine in PKP patients.

However, this study also has certain limitations that need to be considered. First, this trial was conducted in a single center with a limited sample size; thus, there was a possibility for selection bias, and our results need to be verified by multi-center and large-sample trials. Second, the follow-up time was only 24 hours after surgery, and the analgesic effect at 72 hours post-surgery and its impact on patient recovery time (such as hospital stay and time to get out of bed) were not evaluated. Third, MRI or ultrasound scanning was not used to monitor the diffusion range of local anesthetics in the body; thus, the impact of different injection depths on drug distribution could not be quantified. Additionally, only 2 patients with ineffective blockade (sensory block degree < grade 2) were excluded before the final analysis, with 1 patient in Group D and 1 patient in Group S. Given the small number of excluded patients and their balanced distribution across groups, this exclusion is unlikely to have a significant impact on the overall study results. However, we acknowledge that this per-protocol analysis approach may theoretically introduce slight selection bias. This is a common methodological limitation in regional anesthesia randomized controlled trials, as patients with failed blocks require conversion to alternative anesthesia regimens, which would introduce significant confounding factors and compromise the comparability of study groups. Future studies should further expand the sample size, extend the follow-up time, and utilize imaging technology to evaluate the diffusion characteristics of local anesthetics, thus providing a more accurate and evidence-based basis for the combined block regimen.

Clinical Application Value

OVCF patients are predominantly elderly people with multiple comorbidities; consequently, these patients have significant safety requirements when considering anesthesia. In this study, we confirmed that the combination of ultrasound-guided deep and superficial ESPB with an esketamine regimen was clinically advantageous for several reasons: (1) a comprehensive and balanced analgesic effect, covering pain stimuli throughout the PKP procedure; (2) fast onset (average onset time of approximately four minutes) and a low rescue analgesia rate; (3) stable hemodynamics, few adverse reactions, and high safety levels; and (4) simple operation; ultrasound-guided visualized puncture can reduce the risk of complications, and is easy to promote clinically. This regimen is especially suitable for elderly OVCF patients (ASA class II to III) and can effectively reduce opioid dosage, reduce the risk of adverse reactions such as postoperative nausea and vomiting and respiratory depression, thus conforming to the concept of ERAS, and exhibiting important clinical significance for improving the quality of perioperative analgesia in elderly OVCF patients.

Conclusion

In conclusion, combined deep and superficial ESPB combined with a subanesthetic dose of esketamine provides superior intraoperative analgesia, reduces requirements for rescue analgesia and improves hemodynamic stability when compared with single-depth blocks in patients undergoing PKP. Benefit is most pronounced during the intraoperative period, with limited differences observed during the early postoperative period. All three regimens had a similar incidence of common adverse reactions. This combined strategy may be a useful option for perioperative analgesia in elderly patients undergoing PKP.

Funding Statement

Xiaoqiong Xia’s 2023 Clinical Medicine Discipline Construction Project.

Data Sharing Statement

Data available upon reasonable request from the corresponding author, Xiaoqiong Xia.

Disclosure

The authors report no conflicts of interest in this work.