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Perineural dexamethasone enhances analgesic duration of erector spinae plane block in total hip arthroplasty: A randomized quadruple-blind controlled trial
, Paweł Pietraszekb, Tomasz Puratc, Grzegorz Kowalskia, Aleksander Mularskid, Przemyslaw Daroszewskie, Malgorzata Reysnera,
⁎Corresponding author: Malgorzata Reysner. mreysner@ump.edu.pl
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Received: ,
Accepted: ,
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Abstract
Total hip arthroplasty (THA) is associated with significant postoperative pain, which can impair early mobilization and recovery. Erector spinae plane block (ESPB) has emerged as a promising regional anesthesia technique for lower limb surgeries. However, the duration of single-shot ESPB is limited. This study aimed to assess the effect of perineural dexamethasone as an adjunct to ropivacaine in prolonging analgesia and reducing opioid requirements in patients undergoing THA.
In this randomized, quadruple-blinded, controlled trial, 60 patients aged ≥65 years scheduled for elective THA under spinal anesthesia were assigned to receive ultrasound-guided ESPB with either 20 mL of 0.2 % ropivacaine plus 2 mL saline (control group) or 20 mL of 0.2 % ropivacaine plus 4 mg perineural dexamethasone (dexamethasone group). The primary outcome was time to first rescue opioid analgesia. Secondary outcomes included total opioid consumption, Numerical Rating Scale (NRS) pain scores, motor strength, nerve safety, and blood glucose levels over 48 h postoperatively.
The dexamethasone group showed a significantly prolonged time to first opioid use (16.0 ± 1.3 vs. 8.9 ± 1.7 h; p < 0.0001) and reduced opioid consumption (3.5 ± 4.8 vs. 19.2 ± 12.2 MME; p < 0.0001). NRS scores were consistently lower beyond the 4-h time point. No motor deficits, nerve injuries, or hyperglycemia were observed.
Perineural dexamethasone significantly enhances the analgesic efficacy of ESPB in THA without compromising safety. This simple adjunct offers substantial benefit in postoperative pain control and opioid reduction.
1 Introduction
Total hip arthroplasty (THA) is among the most frequently performed orthopedic procedures worldwide, particularly in the elderly population suffering from advanced osteoarthritis and degenerative joint disease.1 Although the surgical outcomes are generally favorable, postoperative pain remains a significant concern.2 Adequate perioperative analgesia is critical not only for enhancing patient comfort but also for promoting early mobilization, reducing hospital stay, and minimizing opioid-related adverse events—core components of enhanced recovery after surgery (ERAS) protocols.3
Regional anesthesia techniques, including neuraxial blocks and peripheral nerve blocks, have increasingly been employed to improve postoperative pain control while reducing systemic opioid requirements.4 Among these, the erector spinae plane block (ESPB) has emerged as a promising modality. Initially introduced for thoracic analgesia, the ESPB has been adapted to the lumbar region and shown to be effective in providing analgesia for hip and lower limb surgeries.5 ESPB offers several theoretical advantages, including ease of administration, minimal risk of motor block, and a favorable safety profile compared to more invasive nerve blocks.6
However, the duration of single-shot ESPB is often limited, necessitating supplemental analgesia within the first 12–16 h postoperatively.7 Various adjuncts have been proposed to prolong the efficacy of local anesthetics in regional blocks.8 Among these, perineural dexamethasone has gained attention for its analgesia-prolonging properties when co-administered with local anesthetics.9 Its mechanisms are thought to involve anti-inflammatory effects, reduced perineural absorption, and modulation of nociceptive signaling.10 Despite its growing popularity, evidence regarding the effectiveness of perineural dexamethasone specifically in lumbar ESPB for THA remains sparse.
To address this gap, we conducted a randomized, quadruple-blind, controlled clinical trial to evaluate whether the addition of 4 mg of perineural dexamethasone to ropivacaine enhances the duration and quality of postoperative analgesia in patients undergoing THA under spinal anesthesia.11 We hypothesized that dexamethasone would significantly delay the time to first rescue opioid administration, reduce total opioid consumption, and improve patient-reported pain scores, without compromising motor function or increasing adverse effects.
2 Methods
2.1 Study design and setting
This was a randomized, quadruple-blinded, clinical trial conducted at the Poznań University of Medical Sciences, Poland. The study aimed to evaluate the efficacy of perineural dexamethasone as an adjuvant to ultrasound-guided erector spinae plane block (ESPB) in prolonging postoperative analgesia following total hip arthroplasty (THA). The trial was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Ethical approval was granted by the Bioethics Committee at Poznań University of Medical Sciences on October 5, 2023 (Approval No. 541/2023). The trial was officially registered on ClinicalTrials.gov on January 20, 2025, under the identifier NCT06789042.
2.2 Participants
A total of 60 adult patients scheduled for elective unilateral total hip arthroplasty were enrolled between February and July 2025. Eligible participants were aged ≥65 years and ≤100 years, able to provide informed consent, and capable of reliably reporting symptoms. Exclusion criteria included cognitive impairment, language barriers preventing valid consent, and contraindications to regional anesthesia or any of the study medications.
2.3 Randomization and blinding
Participants were randomly assigned in a 1:1 ratio to one of two parallel treatment arms: the control group (0.2 % ropivacaine + saline) or the dexamethasone group (0.2 % ropivacaine + 4 mg dexamethasone). Randomization was performed using a computer-generated randomization sequence created with block sizes of four to ensure balanced group allocation throughout the enrollment period. The sequence was generated by a study coordinator who was not involved in participant enrollment, clinical care, or outcome assessment.
To maintain allocation concealment, the group assignments were placed into sequentially numbered, opaque, sealed envelopes (SNOSE). These envelopes were opened only after the participant had been enrolled and consented to participate in the study. A designated unblinded anesthetic nurse, who was not involved in the ESPB administration or postoperative evaluations, prepared the study solutions in identical 22 mL syringes labeled with only the participant study ID.
The trial implemented quadruple blinding, in which the participants, anesthesiologists performing the ESPB, surgeons, and perioperative staff, and all outcome assessors were blinded to the treatment allocation. The prepared injectate (ropivacaine with either saline or dexamethasone) was visually indistinguishable in appearance, volume, and viscosity, thus maintaining blinding integrity. Throughout the trial, no unblinding occurred, and blinding was preserved until after the final data collection was completed and the database was locked.
2.4 Interventions
All patients undergoing total hip arthroplasty received spinal anesthesia as the primary anesthetic technique. Spinal anesthesia was performed in the sitting position using a 27G Quincke needle, with the intrathecal administration of 4 mL of 0.5 % ropivacaine. After the spinal block was completed, patients were immediately positioned in the lateral decubitus position, with the operative side facing upward. This position was maintained for the subsequent regional block, without repositioning the patient.
While in the lateral position, an ultrasound-guided erector spinae plane block (ESPB) was performed at the L3 lumbar level under strict aseptic conditions by anesthesiologists experienced in regional anesthesia. A high-frequency linear ultrasound transducer was used to identify the transverse process and the overlying erector spinae muscle. An echogenic 22-gauge, 80-mm needle was inserted using an in-plane approach until the tip reached the fascial plane between the erector spinae muscle and the transverse process.
In the control group, patients received 20 mL of 0.2 % ropivacaine mixed with 2 mL of 0.9 % normal saline, for a total volume of 22 mL. In the dexamethasone group, patients received 20 mL of 0.2 % ropivacaine combined with 4 mg of dexamethasone, also yielding a total injectate volume of 22 mL. All solutions were prepared immediately before administration by an anesthetic nurse who was not involved in patient care, block performance, or outcome assessment. Identical syringes were used for both groups to maintain the blinding of care providers and outcome assessors.
Correct needle placement and adequate spread of the injectate were confirmed using real-time ultrasound imaging in all cases. The ESPB was performed approximately 30–45 min before the start of surgery, allowing sufficient time for the onset of analgesia before the surgical incision.
2.5 Outcome measures
The primary outcome of the study was the time to first rescue opioid analgesia, defined as the duration in hours from the completion of surgery to the moment the patient first required administration of an opioid analgesic due to inadequate pain control. This parameter was measured within the first 48 h postoperatively. It was used as a direct indicator of the efficacy and duration of the erector spinae plane block (ESPB) with or without the addition of dexamethasone.
Secondary outcomes encompassed a comprehensive set of clinical variables aimed at evaluating analgesic quality, neuromuscular function, neurological safety, and metabolic response.
Total opioid consumption was recorded over the first 48 h after surgery. It was expressed in morphine milligram equivalents (MME), allowing for standardized comparison between patients and groups regardless of the specific opioid used.
Postoperative pain intensity was systematically evaluated using the Numerical Rating Scale (NRS), ranging from 0 (no pain) to 10 (worst imaginable pain). NRS scores were collected at predefined intervals: 4, 8, 12, 24, and 48 h following surgery. These time points were selected to capture both the early and sustained analgesic effects of the ESPB and to assess the potential impact of perineural dexamethasone on pain trajectories.
Muscle strength was assessed by evaluating quadriceps motor function, specifically knee extension and hip adduction, using the Medical Research Council (MRC) scale, which ranges from 0 (no movement) to 5 (normal strength). This assessment was performed at 4, 8, 12, 24, and 48 h postoperatively to monitor for any motor impairment potentially associated with the block or the addition of dexamethasone.
Neurological integrity was evaluated using a predefined nerve damage scoring system ranging from N0 to N4. This included categories for no neurological deficit (N0), minor sensory paresthesia (N1), complete sensory anesthesia (N2), complete motor deficit with or without sensory changes (N3), and features suggestive of complex regional pain syndrome (N4). Nerve function was assessed at 12, 24, and 48 h after surgery to identify any delayed or evolving complications related to the nerve block.
Additionally, blood glucose levels were measured at 12, 24, and 48 h postoperatively to monitor for systemic effects of perineural dexamethasone, particularly given its known potential to induce transient hyperglycemia.
All outcome assessments were conducted by trained clinical personnel who were blinded to the group assignments in order to minimize bias. Pain evaluations, motor assessments, and glucose measurements were performed at predefined postoperative time points—specifically at 4, 8, 12, 24, and 48 h—according to the standardized protocol. To ensure reproducibility, the same team of assessors used validated clinical instruments and followed uniform procedures across all patients and time points.
2.6 Sample size calculation
The sample size determination was based on the study's primary endpoint, which was the time to first rescue opioid analgesia within 48 h postoperatively. Preliminary estimations were informed by a pilot study conducted before the main trial. The pilot study involved a small cohort of elderly patients undergoing Total Hip Arthroplasty, who received single-shot L3-ESPB under analogous anesthetic conditions. These pilot participants were not included in the final analysis cohort but were used solely for methodological planning purposes. These sources suggested that the addition of dexamethasone to a regional block would result in a clinically significant prolongation of analgesia, with an expected mean difference of approximately 6.5 h between the intervention and control groups.
Assuming a standard deviation (SD) of 2.5 h in both groups, a two-tailed independent samples t-test was planned to detect this difference. Using conventional parameters for statistical significance (α = 0.05) and desired power (1 – β = 0.95), the minimum number of subjects required to detect a 6.5-h difference with adequate precision was calculated to be 26 patients per group (total n = 52).
To ensure adequate statistical power in the event of protocol deviations or participant withdrawal, a 10–15 % margin was added to accommodate potential dropouts, incomplete data sets, or violations of normality assumptions. Therefore, the final target sample size was set at 30 participants per group, totaling 60 patients. This adjustment provided a conservative buffer while still maintaining statistical integrity, and ultimately, all 60 participants completed the trial without loss to follow-up.
The sample size was calculated using the standard formula for comparing two independent means and confirmed using G∗Power software (version 3.1, Heinrich Heine University, Düsseldorf, Germany) to ensure accuracy of power estimation and effect size assumptions.
2.7 Statistical analysis
All statistical analyses were conducted using GraphPad Prism, version 10.5.0 (GraphPad Software, San Diego, CA, USA) and performed using intention-to-treat (ITT) principles. Data were analyzed to evaluate differences between the control group (ropivacaine + saline) and the intervention group (ropivacaine + dexamethasone) across primary and secondary endpoints.
Continuous variables, such as time to first rescue analgesia, opioid consumption, pain scores (NRS), and blood glucose levels, were first assessed for normality using the Shapiro–Wilk test. Normally distributed variables were compared using independent samples Student's t-tests, while non-normally distributed variables were analyzed with the Mann–Whitney U test. Categorical variables, including the need for rescue opioids and nerve damage incidence, were compared using Chi-square or Fisher's exact tests, as appropriate. Statistical significance was defined as p < 0.05 for all tests. Effect sizes were reported as mean differences with 95 % confidence intervals (CI).
3 Results
3.1 Participant flow and recruitment
A total of 73 patients were assessed for eligibility between February and July 2025 at the Wiktor Dega Orthopaedic and Rehabilitation Clinical Hospital. Of these, 11 patients were excluded: 6 did not meet the inclusion criteria, and 5 declined to participate. Sixty-two patients were enrolled and randomized in a 1:1 ratio into the study arms.
Thirty patients were allocated to the control group (0.2 % ropivacaine + saline), and all 30 received the allocated intervention. Thirty-two patients were assigned to the dexamethasone group (0.2 % ropivacaine + 4 mg dexamethasone); however, one patient did not receive the intervention due to intraoperative hemodynamic instability requiring urgent management. Another patient from the dexamethasone group withdrew consent postoperatively, resulting in one case of loss to follow-up.
Consequently, 30 patients per group were included in the final analysis. The full participant flow is summarized in the CONSORT diagram (Fig. 1).
3.2 Baseline characteristics
Baseline demographic and clinical characteristics were comparable between groups (Table 1). The mean age was 70.5 ± 3.3 years in the control group and 70.97 ± 2.9 years in the dexamethasone group (p = 0.560). Gender distribution (F/M), ASA class, body mass index, and surgery duration did not differ significantly between the groups, confirming adequate randomization and group comparability.
| Control | DEX | p | |
| ASA | |||
| II | 9 | 6 | 0.5520 |
| III | 21 | 24 | |
| Age (years) | 70.5 ± 3.3 | 70.97 ± 2.9 | 0.5604 |
| 70.0 [68.0–73.0] | 70.0 [69.0–73.3] | ||
| F/M | 17/13 | 16/14 | >0.9999 |
| BMI | 29.4 ± 2.6 | 30.0 ± 2.9 | 0.3752 |
| 29.0 [27.75–31.0] | 29.5 [28.0–32.0] | ||
| Time of surgery | 78.5 ± 7.2 | 77.3 ± 7.2 | 0.5092 |
3.3 Primary outcome
The time to first rescue opioid analgesia was significantly prolonged in the dexamethasone group relative to the control group. Patients receiving perineural dexamethasone required opioids after a mean of 16.0 ± 1.3 h, whereas those in the control group required opioids after 8.9 ± 1.7 h (p < 0.0001), yielding a mean difference of 7.0 h (95 % CI: 6.0 to 8.0). This result is graphically presented in Fig. 2 and Table 2.
| Outcome | Control | DEX | p | Mean difference with 95 % Cl |
| Time to first rescue analgesia (hours) | 8.9 ± 1.7 | 16.0 ± 1.3 | <0.0001 | 7.0 (6.0–8.0) |
| Total Opioid Consumption (MME) | 19.2 ± 12.2 | 3.5 ± 4.8 | <0.0001 | −20.0 (−20.0 to −15.0) |
| Need for opioids (yes/no) | 23/7 | 12/18 | 0.0082 | N/A |
| NRS | ||||
| 4h | 1.4 ± 0.6 | 1.4 ± 0.8 | >0.9999 | 1.0 (−0.36 to 0.36) |
| 8h | 3.0 ± 0.9 | 1.7 ± 1.1 | <0.0001 | 1.3 (0.78–1.82) |
| 12h | 2.5 ± 0.7 | 1.6 ± 0.6 | <0.0001 | 0.87 (0.54–1.19) |
| 24h | 2.4 ± 0.6 | 1.5 ± 0.5 | <0.0001 | 0.93 (0.66–1.21) |
| Quadriceps muscle strength - knee extension | ||||
| 4h | 5 | 5 | N/A | N/A |
| 8h | 5 | 5 | N/A | N/A |
| 12h | 5 | 5 | N/A | N/A |
| 24h | 5 | 5 | N/A | N/A |
| Quadriceps muscle strength - hip adduction | ||||
| 4h | 5 | 5 | N/A | N/A |
| 8h | 5 | 5 | N/A | N/A |
| 12h | 5 | 5 | N/A | N/A |
| 24h | 5 | 5 | N/A | N/A |
| Nerve damage | ||||
| 12h | 0 | 0 | N/A | N/A |
| 24h | 0 | 0 | N/A | N/A |
| 48h | 0 | 0 | N/A | N/A |
| Blood glucose (mg/dl) | ||||
| 12h | 120.9 ± 13.9 | 120.1 ± 15.1 | 0.8179 | 0.87 (−6.64 to 8.37) |
| 24h | 121.4 ± 19.7 | 118.2 ± 15.6 | 0.4930 | 3.17 (−6.03 to 12.36) |
| 48h | 116.5 ± 14.0 | 116.8 ± 17.4 | 0.9286 | −0.37 (−8.53 to 7.80) |
3.4 Secondary outcomes
3.4.1 Opioid consumption
Total postoperative opioid consumption over 48 h was significantly lower in the dexamethasone group (3.5 ± 4.8 MME) compared to the control group (19.2 ± 12.2 MME), p < 0.0001. The absolute mean reduction was –20.0 MME (95 % CI: 20.0 to −15.0). Additionally, only 12 patients (40 %) in the dexamethasone group required any opioid analgesia, compared to 23 patients (77 %) in the control group (p = 0.0082). These findings are depicted in Fig. 3.
3.4.2 Pain intensity (NRS Scores)
Pain scores evaluated by the Numerical Rating Scale (NRS) at 4, 8, 12, and 24 h demonstrated statistically and clinically significant reductions in the dexamethasone group starting from the 8-h time point onward. While there was no difference at 4 h (mean NRS: 1.4 in both groups, p > 0.999), the dexamethasone group reported significantly lower scores at 8 h (1.7 ± 1.1 vs. 3.0 ± 0.9; p < 0.0001), 12 h (1.6 ± 0.6 vs. 2.5 ± 0.7; p < 0.0001), and 24 h (1.5 ± 0.5 vs. 2.4 ± 0.6; p < 0.0001). Pain trajectories are presented in Fig. 4, confirming sustained analgesic benefit i the dexamethasone group.
3.4.3 Quadriceps muscle Strength
Muscle strength, assessed via the Medical Research Council (MRC) scale for both knee extension and hip adduction, remained normal (score 5/5) across all postoperative time points (4, 8, 12, and 24 h) in both groups. No transient or persistent motor deficits were observed.
3.4.4 Neurological Safety
There were no cases of nerve injury reported in either group at 12, 24, or 48 h postoperatively. All patients scored N0 (no nerve damage) on the predefined nerve injury scale, confirming the neurological safety of ESPB with and without dexamethasone.
3.5 Blood glucose levels
Postoperative blood glucose levels at 12, 24, and 48 h were similar between groups and remained within normal physiological limits. No statistically significant differences were detected at any time point. At 12h: 120.9 ± 13.9 (control) vs. 120.1 ± 15.1 (DEX); p = 0.8179, 24h: 121.4 ± 19.7 vs. 118.2 ± 15.6; p = 0.4930, 48h: 116.5 ± 14.0 vs. 116.8 ± 17.4; p = 0.9286. These findings suggest no systemic glycemic impact from the use of 4 mg perineural dexamethasone in this elderly population.
4 Discussion
This randomized, quadruple-blinded, controlled trial demonstrated that the addition of 4 mg perineural dexamethasone to ropivacaine for erector spinae plane block (ESPB) in patients undergoing total hip arthroplasty (THA) significantly prolonged postoperative analgesia, reduced opioid consumption, and improved pain control without compromising motor function or neurological safety.
The primary outcome, time to first rescue opioid analgesia, was markedly extended in the dexamethasone group, with a mean prolongation of approximately 7 h. This result is consistent with the analgesia-prolonging effects of dexamethasone observed in previous studies involving peripheral nerve blocks such as interscalene, femoral, and sciatic blocks.9,12,13 Dexamethasone likely exerts its effect through a combination of anti-inflammatory, vasoconstrictive, and genomic modulation of nociceptive pathways, resulting in delayed nociceptor sensitization and prolonged local anesthetic action.14,15 Our findings extend this evidence base to the ESPB, a relatively novel fascial plane block whose pharmacodynamics may differ from traditional nerve blocks.
In addition to delayed opioid rescue, patients receiving dexamethasone required significantly lower cumulative opioid doses in the first 48 h postoperatively. Notably, 60 % of these patients required no opioid analgesia at all. This opioid-sparing effect is not only clinically meaningful in the context of enhanced recovery after surgery (ERAS) protocols but also carries public health relevance given the global concerns around postoperative opioid use and dependency.3,16–18 The marked reduction in opioid requirement observed in this study surpasses reductions reported in some previous studies.19–21 It may reflect the combination of adequate neuraxial (spinal) anesthesia with a robust peripheral adjuvant strategy.8,22
Pain intensity scores on the Numerical Rating Scale were consistently and significantly lower in the dexamethasone group at all time points beyond the immediate 4-h postoperative period. This suggests that while spinal anesthesia may provide adequate early analgesia, the addition of dexamethasone to ESPB offers sustained pain relief during the critical intermediate and late postoperative windows.9,19–21 These findings support the integration of perineural dexamethasone into multimodal analgesic strategies for THA, particularly in older adults.23–25
Significantly, the addition of dexamethasone was not associated with any detectable adverse effects. Muscle strength, assessed through MRC grading of quadriceps function, remained intact in all participants, and no sensory or motor deficits were identified. Furthermore, no signs of nerve injury or complex regional pain syndrome were observed at any assessment point. These safety data are reassuring and align with previous reports indicating a low incidence of neurotoxicity with perineural dexamethasone at doses of 4–10 mg.23–27
Given the known potential of corticosteroids to elevate blood glucose levels, particularly in elderly or diabetic patients, we also monitored glycemic responses postoperatively.26,28,29 No significant differences in blood glucose were observed between groups, and values remained within normal ranges. This suggests that 4 mg of perineural dexamethasone, when used in a single-shot fascial plane block, does not produce clinically relevant hyperglycemia in surgical patients.30
This study's strengths include its rigorous quadruple-blind design, standardized protocol execution, and comprehensive outcome assessment by blinded, trained evaluators. Additionally, the use of intention-to-treat analysis, low attrition, and adherence to CONSORT standards bolster the validity of our findings.
However, some limitations must be acknowledged. First, while the study was powered to detect differences in analgesia duration, it may not have been sufficiently powered to detect rare adverse events such as nerve injury or steroid-related complications. Second, the generalizability of our results is limited to older adults undergoing elective THA under spinal anesthesia in a high-resource setting. The effect of dexamethasone in ESPB under general anesthesia, in bilateral surgery, or in different patient populations (e.g., diabetic, obese) remains to be determined. Finally, we used a fixed dose of 4 mg dexamethasone; future studies could explore dose–response relationships to identify the optimal concentration that balances efficacy and safety.
5 Conclusion
The addition of perineural dexamethasone to ESPB significantly enhances postoperative analgesia following total hip arthroplasty, reduces opioid consumption, and improves pain outcomes without compromising motor or neurological safety. This simple, low-cost, and safe intervention has important implications for perioperative pain management and may serve as a valuable component of multimodal analgesic regimens in orthopedic surgery.
Guardian/patient consent
Written informed consent was obtained from all participants prior to study enrollment. All patients were capable of understanding the nature, objectives, and potential risks of the study and were provided with ample time to ask questions before signing the consent form. In the case of participants with limited literacy or minor language barriers, a legally authorized representative or guardian provided consent on their behalf in accordance with ethical guidelines. The consent process was supervised and documented by a qualified member of the research team not involved in data analysis.
Ethics statement
This clinical trial was conducted in full accordance with the ethical principles outlined in the Declaration of Helsinki and Good Clinical Practice guidelines. Ethical approval for the study was obtained from the Bioethics Committee at the Poznań University of Medical Sciences (Approval No. 541/2023), granted on October 5, 2023. The study was registered prospectively on ClinicalTrials.gov (NCT06789042) prior to patient enrollment. All procedures involving human participants were reviewed and approved by the institutional ethics board before commencement.
CRediT author contributions
Tomasz Reysner (TR): Conceptualization, Methodology, Formal analysis, Investigation, Writing – Original Draft, Visualization, Writing – Review & Editing.
Paweł Pietraszek (PP): Methodology, Data curation, Investigation, Writing – Review & Editing.
Tomasz Purat (TP): Investigation, Resources, Project administration, Data Curation.
Grzegorz Kowalski (GK): Methodology, Validation, Writing – Review & Editing.
Aleksander Mularski (AM): Methodology, Resources, Writing – Review & Editing.
Przemysław Daroszewski (PD): Funding acquisition, Visualization, Writing – Review & Editing.
Małgorzata Reysner (MR): Methodology, Project administration, Writing – Review & Editing, Supervision, Correspondence.
Financial support and sponsorship
Poznan University of Medical Sciences, Poland, supported this study. No external funding or sponsorship was received.
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