TREATMENT MODALITIES OF COMPLEX REGIONAL PAIN SYNDROME AFTER HAND SURGERY A SYSTEMATIC REVIEW AND META-ANALYSIS STUDY

DISCUSSION

The treatment for CRPS is mainly dealt symptomatically with a combination of physical/occupational therapies, psychological therapy, neuropathic pain medications, anti-inflammatories and interventional procedures.³⁷

Karri et al., ¹⁸ published a systematic study in 2021 that focuses on CRPS in children and explores neuromodulation, a well-known therapy option for adults, for pediatric patients. In the pediatric population, the key aims of CRPS therapy are pain reduction and improvement in all areas of functioning to enhance the patient's life quality. Intensive physical treatment is used in conjunction with cognitive-behavioral therapy. Pediatric patients may be assessed for neuromodulation procedures like spinal cord stimulation (SCS) in addition to dorsal root ganglion stimulus (DRG) devices, among other therapies under the standard of care approach. ¹⁹

A total of 12 studies were included showing complicated regional pain syndrome treatment modalities following hand surgery. Among included 12 studies 6 were retrospective and 6 were RCT. A total of 633 cases were included with male\female was 214\387, mean age 50.015 years.

In comparison with the systematic review of Tran et al., ²⁰ in which the search criteria turned in 41 RCTs, each with an average of 31.7 participants. In 70.7 percent and 19.5 percent of RCTs, respectively, blinded evaluation and sample size rationale were given, the best treatment results were with bisphosphonate treatment.

Another research by Eraghi et al. ²¹ was done at Rasoul Akram Hospital in Tehran, Iran, from August 2016 to September 2017. It was a double-blind, randomized controlled experiment. CONSORT (Consolidated Standards of Reporting Trials) criteria were followed by the authors. A total of 179 individuals were investigated, with each fracture being analyzed separately. There was no variance in gender between patients with CRPS and non-CRPS patients. Patients with CRPS had a substantially greater average age (P=0.008).

Symptomatic management for CRPS involves a mix of physical/occupational treatments, psychosocial counseling, neuropathic pain medicines, anti-inflammatories, and surgical intervention. ²² The efficacy of many of the drugs used to treat CRPS is predicated on their efficacy in treating neuropathic pain. The number of medications that have undergone CRPS trials is small, and the data is presented in this review. This review also covers the results of neuromodulation trials including spinal cord stimulating (SCS) and dorsal root ganglion (DRG) stimulus. Many of the treatment methods for CRPS have insufficient evidence to support their usefulness, and further study is needed. ²³

In the current metanalysis; there were several methods of treatments in included studies vitamin C, Spinal cord stimulation, graded motor imagery (GMI), Ketamine, Aspirin, steroids, mirror therapy, sympathetic ganglion block, Immunoglobulin, bisphosphonate, Gabapentin, and Thoracic Sympathectomy.

On the other hand; Duong et al., ²⁴ in which There were 41 RCTs found using the original criteria. Five of them were eliminated because they mentioned non-anesthesia providers (such as acupuncturists) or utilized procedures that were not widely used (e.g., Low-level laser treatment, TMS stimulation, and manual lymphatic drainage). Another experiment was eliminated because the data from the placebo group was not analyzed. 14 RCTs looked into pharmacologic therapies, four looked into neuraxial blocks, and three looked into spinal cord/dorsal root ganglion stimulation. Eight and six research, respectively, looked at intravenous/peripheral sympathetic blocks and adjuvant therapy.

In research by Eraghi et al.,²¹ a total of 103 patients with unilateral, extra-articular distal radius fractures took part in the research for 14 months. Fifty-one individuals were given aspirin and the other fifty-two were given placebos.

In a Cochrane review of Smart et al.,²⁵ 18 randomized controlled trials (RCTs) on physiotherapy-based therapies (n=739) were investigated. The majority of the studies looked at were of 'poor' quality or had a 'high' risk of bias. Despite these flaws, the Cochrane review identified two medicines with the greatest available evidence that might help CRPS I patients improve their pain and function. Graded motor imagery (GMI) and mirror therapy are two extremely comparable treatments.

In terms of the afflicted side, we discovered that the affected side was right in 48 cases and left in 36 cases, with a mean illness duration of 30.3 months.

In comparison with the study of Bean et al., ²⁶ which reported that the majority of the patients were women, and most of them had upper-limb problems. The average illness duration was 62.75 (24.3) days. 

In another retrospective study by Massimo et al., ²⁷ in which the average age at CRPS-I identification was 57.1 ± 12.9 years, with a higher percentage of females (122, 62.9%) and no difference in average age at detection between men and females (P = 0.28). The median duration of the disorder was four months (IQR= 2–6). The lower extremity (foot) was more often afflicted than the upper limb (hand), with 119 patients (61.3%) having foot disease and 75 having hand illness (38.7 percent). Thirteen patients (6.7%) had previously been diagnosed with CRPS-I, which had more typically included another location (10 cases).

In addition to the above findings, the current review reported that the disease subtype was warm (237), cold (52), NA (21) as regard localization was Upper limb in (158) cases and Lower limb in (119) cases, as regard Predisposing event was either due to distal radius fractures, wrist fracture, other surgery, carpal tunnel surgical intervention, cervical spine, extra-articular distal radius fractures, Ischemic cerebral infarction, Hemorrhagic cerebral infarction, Traumatic brain injury, Carpal tunnel syndrome surgery, In this research, crushing injuries were the most prevalent kind of injury, followed by clean-cut injuries, traction injuries, and gunshot injuries.

Jankovic, ²⁸ was conducted and reported that the average age of CRPS patients is 36 to 46 years old, with women accounting for 60% to 80% of cases. A fracture (16 percent–46 percent), strain or sprain (10 percent–29 percent), post-surgery (3 percent–24 percent), and contusion or crush damage (8 percent–18 percent) are the most common causes. Pain, edema, and autonomic malfunction, like changes in temperature or color in the affected limbs, motor impairment, and psychological disorders, such as depression, are common clinical characteristics of CRPS. Sidawy, ²⁹ CRPS spreads in three phases, according to the study. Early on, CRPS usually affects just one limb, causing discomfort, mild edema, and a rise in skin temperature. CRPS has the potential to spread from one limb to the other. In its latter stages, CRPS may affect the whole body as well as the four extremities, causing extreme pain, edema, cold and cyanotic limbs, joint rigidity, and muscle and bone atrophy.

In the current metanalysis; we found that adverse event showed in 127 cases mostly with Ketamine and bisphosphonate and was in form of stomach upset in 47 cases, respiratory depression in 9 cases, Headache in 10 cases, moderate hypocalcemia in 1 case, acute phase reaction in 48 cases, acute anterior uveitis in 1 case, dizziness in 3 cases, drowsiness in2 cases, tinnitus in 2 cases and pin tract infections in 4 cases. Moreover; 12 studies were included 6 studies showed adverse events with highly significant heterogeneity p-value <0.0001.

Bisphosphonates are extensively utilized in the treatment of CRPS, according to data from several modest RCTs that have shown considerable benefits. ³⁰. Bisphosphonates are thought to have a role in controlling inflammatory mediators, as well as the proliferation and migration of bone marrow cells, while the specific mechanism is unknown²². Young et al., 19 compared the use of three 60 mg intravenous pamidronate infusions to oral prednisolone in 21 post-stroke CRPS patients and showed that pamidronate was equally as efficacious for pain management.

Chevreau et al., ³² published a meta-analysis in which four RCTs with a total of 181 patients found that bisphosphonates significantly reduced pain in patients with CRPS-1 when compared to placebo, confirming the effectiveness and safety of bisphosphonates in the management of CRPS.

In addition to the above findings, 10 studies showed responders with a high event in bisphosphonate then in Ketamine study with highly significant heterogeneity among included studies p-value  0.0005.

The meta-analysis results of Zhao et al., ³³ revealed that in comparison to the self-controlled baseline, the Ketamine therapy resulted in a lower average pain score (p <0.000001). However, between-study heterogeneity has statistical significance. The occurrence rate for immediate pain alleviation was 69 percent (95 percent confidence interval (CI) 53 percent, 84 percent). The pain alleviation event rate was 58 percent at the 1–3-month follow-ups (95 percent CI 41 percent, 75 percent). The currently available research on ketamine infusion for CRPS was evaluated, and meta-analyses were undertaken to assess ketamine infusion's effectiveness in the treating of CRPS. Their results showed that ketamine infusion may give clinically efficient pain-relieving for less than three months in the short term.

Bisphosphonates have also been studied in two further RCTs for CRPS. Varenna et al., ³⁴ found that a ten-day intravenous infusion (100 mg qid every third day) of neridronate, an amino-bisphosphonate chemically identical to alendronate and pamidronate, resulted in decreased pain ratings at 20 and 40 days when compared to placebo. Moreover, at day 40, the neridronate group had a higher percentage of patients with a pain reduction of ≥ 50% (73.2 percent vs 32.5 percent, respectively; P = 0.0003), lower edema, less pain with passive motion, and a lower incidence of both allodynia (15 percent vs 50 percent; P < 0.0001) and hyperalgesia (12.5 percent vs 61.1 percent; P = 0.0027) than the placebo group. Young et al. ³¹ In the second research, hemiplegic stroke patients with CRPS were compared to a two-week tapering course of oral prednisolone vs six-day intravenous pamidronate (60 mg TID every other day) regimen. These researchers discovered that prednisolone reduced wrist circumference more than palmidronate did at one, two, and four weeks, while palmidronate reduced pain ratings more at one and two weeks.

Finally, we found that 6 studies comparing Average baseline pain score pre and post-treatment show highly significant heterogeneity p-value <0.0001

Fischer et al. ³⁵ randomized 56 CRPS patients to a five-day regimen of intravenous magnesium (70 mg.kg^-1 over four hours each day) or saline in 2013. At one, three, six, and twelve weeks following the commencement of therapy, no intergroup variations in Impaired Level Sum Scores or pain (11-point BOX scale) were identified. Van der Plas et al., ³⁶ looked at the advantages of injectable magnesium in individuals with CRPS-related dystonia. The subjects were given either injectable magnesium (escalating daily dosages of 1,000 to 2,000 mg) or saline for three weeks. They received the other medication after a one-week washout period; no intergroup variations in dystonia were identified. However, these findings should be taken with care since van der Plas et al., ³⁶ abruptly ended the experiment (after enrolling only 22 out of a planned 40 patients) due to recruiting difficulties.

CONCLUSION

In conclusion, although there has yet to be good therapy for CRPS, years of study have taught us a lot about the disorder, and our knowledge of it is still growing. A CRPS population is varied, with various subgroups presenting different clinical and biochemical traits, resulting in a wide range of therapeutic responses. Furthermore, in comparison to CRPS type I, the evidentiary foundation for CRPS type II is limited. As a result, further research is required to determine which patient subgroups might benefit the most from presently available treatments. Because of the syndrome's complexity, focusing on a single mechanism is unlikely to be beneficial. Combination therapy, like with other chronic disorders, maybe the future of CRPS management, and research into this will be required.