A Comparative study of preemptive agents alleviating postoperative spinal surgery pain

 Good management of preoperative pain is correlated with better recovery outcomes [5,6]. Reports showed that postoperative, multi-origin pain was stated in the majority of patients who had spinal surgery. Notably, postoperative pain increased in patients with preexisting chronic pain [7]. Usually, those with preexisting chronic pain undertake conventional analgesics or narcotics alongside the long-standing consumption of analgesics. This amends pain perception in these patients, thereby complicating pain management [8-11]. Furthermore, effective postoperative pain management promotes early mobilization as well as expedites hospital discharge {8}. Nowadays, efforts are targeted towards satisfying postoperative pain following microscopic surgical intervention.

Effective postoperative pain alleviation promotes postoperative recovery. Faster pain alleviation will encourage early ambulation, shorten hospital stays, and can prevent the initiation of chronic pain. To achieve this, multimodal analgesia use leads to an accumulative analgesic effect, which causes fewer to no side effects compared to single drug usage [12-15].

Epidural and foraminal steroid injections are a standard treatment modality for patients with degenerative disc disease with lower back pain and radiating leg pain. Steroid treatment was first introduced in 1922 and is still an indispensable part of the non-surgical management for various spine-related problems. The cardinal goal of steroid injections is to reduce pain; to decrease the inflammatory process by targeting the nerve root [16,17]. Steroids reduce postoperative pain by suppressing pain mediators and inflammatory chemicals such as prostaglandins, bradykinin, and histamine [18]. Interestingly, intraoperative epidural steroids are applied as pain-alleviating agents during lumbar spine surgery. We previously reported that adjunct use of perioperative magnesium sulphate in patients with degenerative spine disease could significantly improve the pain score [19]. This study compared the effects of perioperative, preemptive agents, the epidural steroids versus the magnesium sulphate, to effectively relieve postoperative pain following conventional microscopic spinal surgeries.

MATERIALS AND METHODS

Ethics

Patient medical data from May 2019 till June 2020 were obtained from the King Hussein Medical Center (KHMC) database and reviewed in a comparative analysis. This study was approved by the Royal Medical Services Institutional ethics committee (40/10/2020). As this study was a comparative analysis, the requirement for consent was waived.

Patients

Eighty-three patients were eligible for this study. Patients were selected based on inclusion criteria of having one level of degenerative lumbar disease (canal stenosis, foraminal stenosis, or disc herniation), had a moderate or very severe lower preoperative back pain with or without radicular pain (visual analogue scale (VAS) between 4 - 10) in the lower back or leg, and had persistent pain more than six weeks despite the use of other conservative treatment options (physical therapy, medication, etc.). We excluded patients with acute deficits, spinal instrumentations, spinal tumors surgery, and those who did not attend the follow-up.

Inclusion/ exclusion criteria

Inclusion criteria:

1) One level of degenerative lumbar spine disease.

2) Persistent pain more than 6-weeks

3) A minimum follow-up of 4-weeks.

4) Patient underwent surgery.

Exclusion criteria were:

1)      Inadequate documentation of follow up.

2)      Oncology cases scheme.

3)      The presence of severe systemic disease( heart disease, thromboembolism, bleeding tendency, renal malfunction)

4)      Age 18

5)      Patients with acute deficits, spinal instrumentations.

6)      Patients allergic to any of the agents used in the study.

7)      Patients who had hyper-magnesaemia.

8)      Patients were opioid dependent.

Study Design

Patients were randomly allocated into three groups by the main surgeon. In group I, patients received intravenous magnesium sulphate before and during surgery. In group II, patients received intraoperative epidural steroids, and in group III, patients underwent surgery, but received neither of the two agents (control group). Patient demographics were collected in terms of sex, age, duration of symptoms, medical history, and social history. Fifty-nine patients were included in the final stage as 24-patientes were excluded. Patients randomly allocated into these three groups; of those, 21 patients (group I) received intravenous magnesium sulphate (50 mg/kg) for 15 mins and after induction and once general anesthesia was administered, magnesium sulphate treatment was continued intravenously at a rate of 15 mg/kg/hour for the duration of the surgery. Twenty patients received methylprednisolone acetate (group II) via an intraoperative epidural and transforaminal steroid injections. The surgeon introduced 40 mg per level of methylprednisolone acetate around the nerve root on the symptomatic side. Finally, 18-patients (group III) did not receive either agent introduced in the prior groups but were given a regular postoperative pain killer ( not given for the other groups). Intraoperative standard monitoring of pulse oximeter usage, electrocardiography recording, noninvasive blood pressure device application, and temperature monitoring was carried out for all groups. In addition, end-tidal carbon dioxide measurement inspired oxygen concentration, and the use of low oxygen concentration with disconnected ventilator alarms was monitored. If changes were observed to the systolic arterial pressure (below 90 mm Hg) or if the mean arterial pressure was reduced to >20 % from baseline, ephedrine (5 mg) was administered if the heart rate decreased to <45 beats/min, atropine (0.5 mg) was infused intravenously.

Independent reviewers collected all data, including side effects, and patient details, during hospital follow-ups to minimize bias. All patients underwent microscopic spine surgery by one neurosurgeon (Al. R) with the same surgical technique. The surgeon was completely aware of each patient/group allocation. After surgery, all patients were evaluated for specific outcome measurements. VAS values for lower back pain were collected pre-operatively and at 24 hours, one and two weeks after the initial surgery. An assistant team that was blinded to the treatment administered to each patient collected postoperative data of mean arterial pressure (MAP), respiratory rate (RR), SpO2, nausea/vomiting, itching, adverse effects, complications of anesthesia, and surgical complications. Those responsible for the follow-up and analysis of the data were blinded to the respective experimental groups.                                    

Surgical technique

The microsurgical procedure was performed in a standardized manner, surgical steps were as follows. Patient under general endotracheal anesthesia placed in prone position on Wilson frame, the diseased level is marked with X-ray control.

 The region is draped in a sterile fashion, then a vertical midline incision over the appropriate interspace marked using anatomical landmarks and fluoroscopy, subsequently, skin incised and the subcutaneous tissues are dissected , with sub periosteal dissection done down to the specified level to expose the spinous process and the lamina bilaterally. Fluoroscopy is used to reconfirm the level. Bilateral flavectomy performed in addition to bilateral foraminotomy. When dealing with herniated lumbar disc, inter-laminar approach was used preserving the lamina as possible, the exposed nerve root was retracted medially or laterally, depending on the position of the disc and through a transverse annulotomy, all the loose disc material is removed, the disc space washed with normal saline to remove out any remaining free fragments. Facets were left undisturbed. The operating microscope was used in all the cases.

Statistical analysis

To compare clinical outcomes across the different periods, we conducted an unpaired Student's t-test to compare the following three scenarios: pre-operation vs. 24-hours post-operation, pre-operation vs. one-week follow-up, and pre-operation vs. two-week follow-up. Data are presented as mean ± standard deviation (SD) if not otherwise indicated. Clinical and outcome parameters of all patients were summarized descriptively. A Pearson's chi-square test was applied to check for significance in nominal variables. For the comparison of dependent variables, the nonparametric Wilcoxon-test was used. The significance level was set at p < 0.05.

RESULTS

The study population included 33 men and 26 women who met the inclusion/exclusion criteria, and the male-to-female ratio was 1.27:1. The patient ages were between 28 and 58 years, with a median age of 45.38 ±10.68 years. There were no significant differences between the three groups recruited for the analysis in terms of mean age, the extent of the operation, gender, weight, mean operative duration, or mean follow-up duration (Table 1).

The preoperative VAS values recorded for back or leg pain in patients across the three groups had no reportable differences (Table II, III). We identified a substantial decrease in VAS scores of lower back pain (Table II) and reported differences in terms of leg pain scores (Table III). The lumbar spine levels involved were L2–L3, L3–4, L4–5, and L5–S1 (Figure 1). Two patients had uncontrolled bleeding during surgery; however, this was unrelated to the agents administered. Overall, there were no reported technical difficulties in the surgical procedure and no major surgery-related complications. We observed no significant difference in hemodynamic variables (mean arterial pressure and heart rate) during the intra- or early- postoperative period. Three patients in group I and two patients in Group III developed hypotension, and two patients in group I and one patient in Group II experienced bradycardia during surgery. As such, ephedrine and atropine were administered in each event, and in all cases, arterial pressure and heart rate were normalized. There were no statistical differences related to nausea/vomiting or dizziness between the groups (Table IV). During the follow-up at three months, three patients had a disc re-herniation and underwent a redo discectomy. No patient had postoperative complications. Further, no patient developed postoperative or other complications related to steroid application or magnesium infusions.

Table I: Demographic features of study population   

Table II: Average VAS pain scores of low back pain. Values are presented as medians and SD. Group I, Mg group; Group II, intraoperative epidural steroids group; Group III , control group. *P<0.05

  Table III: The average visual analogue scale (VAS) of leg pain

   Table IV: Postoperative clinical observations

Figure 1: level wise procedure performed

Figure 2:  Pain scores on VAS, for all groups. Values plotted on mean values.

DISCUSSION

One of the main active chemicals introduced in anesthesia as a smooth muscle relaxant is magnesium sulphate. Magnesium sulphate competitively blocks intracellular calcium channels, decreases excitation by preventing acetylcholine release leading to impeded smooth muscle contractility. We have used magnesium sulphate as an adjunct drug for perioperative analgesia due to its properties as an N-Methyl-d-aspartate (NMDA) receptor antagonist and calcium channel blocker [20-23]. We reported that perioperative intravenous magnesium sulphate infusion during conventional spine surgery in patients with degenerative spine disease under general anesthesia reduced postoperative pain without any notable complications [19]. Also, we conducted another study analyzing the efficacy of intraoperative steroid infusion (study still under review). Whereas, this study compared both drugs, the magnesium sulphate and the intraoperative epidural steroids effectiveness under the same comparable clinical subjects in terms of immediate and short-term postoperative pain (at 24 hrs., one and two weeks postoperatively )alleviation after microscopic spinal surgery for degenerative spinal disease.

In our comparative study, no significant differences were found in terms of age, weight, gender, or operation duration between the three groups (Table I). Regarding the average VAS values for lower back pain, no statistical differences were found in preoperative pain (Table II). Similar findings were observed after 24 -hours between the three groups. On the other hand, we noticed a significant drop-in group I between preoperative and 24-hrs. Postoperatively (Figure 2). According to our observations at 24-hrs., the average VAS values for leg pain showed a significant reduction across all groups (Table III). This observation was also reported after one and two weeks postoperatively. These findings may be due to nerve root decompression in all groups. After the first postoperative week, the second group that received an intraoperative epidural and foraminal methylprednisolone showed a significant drop in pain scores among all groups; this was also observed after two weeks. We also reported these similar observations, which indicates that intravenous magnesium sulphate reduced immediate postoperative pain compared to intraoperative epidural and foraminal steroids. As a result, we show that intraoperative epidural and foraminal steroids in microscopic spine surgery are a good alternative due to their long-lasting reduction of postoperative pain. This observation may be explained by the immediate and short-term effects of magnesium sulphate compared to steroids that have a delayed, prolonged action.

Although the management of early postoperative pain is still a current issue. In the future, we believe that the number of effective and reliable drugs for initial postoperative pain will continue to evolve, with a focus on innovative methods. Nevertheless, there is still a noticeable lack of documentation for the consequence and the analgesic regimes' adverse side effects. This study encountered some limitations. The relatively small sample size and the short follow-up periods might limit the comparability and understanding of long-term outcomes. Of note, analgesics taken by patients at home were not evaluated. Socio-economic variables that might affect the study results were not incorporated in this study

CONCLUSION

   Therefore, our findings highlight the importance of a comprehensive preemptive analgesic agents' program, which should include a standard epidural or intravenous agent and incorporate a multimodal analgesia regimen as described. This study showed that the adjunct use of intravenous magnesium sulphate in microscopic spine surgery results in short term pain alleviation and limited duration. The intraoperative foraminal and epidural steroid injections could significantly reduce postoperative pain. Based on our primary results, we advise the use of both agents as the results of similar regimens in postoperative pain control are promising. These improvements lead to a significant decrease in days off from working and the need or reduction in the use of pain-killer medications. Therefore, we considered spinal surgery per se to pose as an adjunct pain reliever to improve the multifactorial methodology in pain management.

Future work:

We need a prospective, randomized, controlled, double-blind study and larger populations. To combined both agents and to introduce more agents

Acknowledgments: None.

Conflicts of interest: The author certify that he has no affiliation with or any direct or indirect involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript.

Funding: Authors disclose no external funding sources.

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