Platelet-Rich Plasma: Optimal Use in Surgical Wounds

Reference: Trull-Ahuir C, Sala D, Chismol-Abad J, Vila-Caballer M, Lisón JF. Efficacy of platelet-rich plasma as an adjuvant to surgical carpal ligament release: a prospective, randomized controlled clinical trial. Sci Rep. 2020;10(1):2085. doi:10.1038/s41598-020-59113-0

Rationale: Surgical decompression of the median nerve, an established procedure for those with severe carpal tunnel syndrome (CTS), may be complicated by discomfort, delayed healing or return to work, or reduced hand function and grip strength. Platelet-rich plasma merits study as an adjunct to alleviate these complications of CTS surgery.

Objective: Conduct a triple-blind RCT comparing grip strength, time off work, and scale scores for validated comfort, function, and wound assessment up to 6 weeks after CTS surgery for those receiving one intra-incisional dose of PRP during surgery with those receiving a similar dose of PPP.

Methods: A triple-blind RCT consistent with the Declaration of Helsinki was conducted in a university hospital surgery clinic in Spain from June 2018 to November 2018 and published according to consolidated standards for reporting trials. After power analysis indicated at least 42 patients were needed to support statistical significance (α P  <.05) of hand grip strength differences, 50 patients (age range, 18–65 years) with clinically and electromyographically confirmed CTS were computer-randomized to receive intraoperative incision irrigation with either PRP (n = 25) or PPP (n = 25). Treatment assignment was concealed from patients and all staff involved in their care. Those previously treated with surgery or corticosteroids, or those with vascular metabolic, hand, or endocrine pathology, neoplastic disorders, osteoporosis, pregnancy, hemophilia, and those requiring anticoagulant therapy were excluded from participation. Carpal tunnel syndrome was graded using a standardized neurophysiologic scale⁶ as “extreme” (no median nerve motor or sensory response), “severe” (no sensory response, abnormal distal motor response latency), “moderate” (abnormal sensory nerve conduction velocity and abnormal distal motor response latency), or “mild” (abnormal sensory nerve conduction velocity with normal distal motor response latency). Activated platelets were obtained from an upper-arm venous blood sample of 27 mL from each patient following manufacturer instructions in a standardized activated platelet separation kit. These samples were centrifuged using standardized procedures, and aliquots of  0.5 ml each of PRP and PPP were laboratory-tested for quality control and platelet counts. Blind-labeled 3-ml aliquots of PRP or PPP, according to random treatment assignment, were then injected via catheter into the same patient’s CTS closed incision after surgical release of the patient’s carpal ligament (before the incision was covered with a moisture-retentive film dressing). All patients engaged in the same standardized rehabilitation protocol. All outcomes were recorded by 2 trained observers blinded to treatment allocation before and 6 weeks after CTS surgery. Hand grip strength (HGS), the primary outcome, was measured by the seated patient in standardized position pressing a CAMRY hydraulic hand dynamometer as hard as possible for 3 seconds to 5 seconds, with strong verbal encouragement. Valid, reliable secondary outcome measures included the Wong-Baker Faces Scale (0–10) for patient-reported pain, CTS severity and function using 5-point Likert scales pre-surgery and post-surgery, and post-surgical wound status and days off from work.

Results: Pain, severity of CTS symptoms, and functional status improved similarly from baseline to 6 weeks after surgery for both PRP and PPP groups (P <.001), with similar wound assessment scores and no complications reported at the 6-week follow-up. Hand grip strength at 6 weeks post CTS surgery was not restored to normal levels for PPP-treated patients but was in the PRP-treated patients, who returned to work an average of 2 weeks earlier than those treated with PPP. Sample sizes were insufficient for time off of work to reach statistical significance. No outcome was significantly correlated with the platelet count in the PRP dose (mean, 3.1 x 10⁹) or PPP dose (mean, 9.7 x 10⁷).

Authors’ Conclusions: This study supports feasibility of using PRP as an adjunct to CTS surgery to promote earlier return of hand grip strength. Conditions of use and benefits of PRP therapy merit further study. 

Reference: Gohar MM, Ali RF, Ismail KA, Ismail TA, Nosair NA. Assessment of the effect of platelet rich plasma on the healing of operated sacrococcygeal pilonidal sinus by lay-open technique: a randomized clinical trial. BMC Surg. 2020;20(1):212. doi:10.1186/s12893-020-00865-x

Rationale: Excision and second intention healing of pilonidal sinus disease (PSD) results in less likely recurrence than other interventions but has drawbacks of prolonged healing with frequent dressing changes and infection risk. Platelet-rich plasma has been reported to accelerate chronic wound healing and may be useful in healing PSD excision wounds.

Objective: Conduct an open-label RCT comparing healing of PSD wounds with a volume of 35 cc or less treated using lay-open excisions (ie, excision and healing by granulation) with or without PRP injected into the excision 4 days and 12 days after the sinus was surgically excised.

Methods: After appropriate institutional review board approval, and with written informed patient consent, patients admitted to Kafr El Shiekh University Hospital in Egypt for surgical PSD excision between December 2018 and December 2019 were randomly assigned to receive either standard of care with 0.1 mL PRP/cm² injected into the lay-open excision area (n = 50) or without PRP (control, n = 50). All patients received standard of care and consisted of surgical site disinfection with 10% povidone iodine and 1 dose of third-generation cephalosporin, administered 30 minutes before surgical excision opening of the sinus to heal by second intention. After methylene blue dye was injected through the sinus openings, an elliptical incision circumscribed the sinus orifice, extending to the deep fascia and excising the PSD tissue en-block. After achieving hemostasis, the excision volume was measured by recording the amount of normal saline required to fill it. To assure volumes were comparable at baseline, wound cavities of up to 35 cc were included in the study. All wounds received twice-daily irrigation with normal saline and disinfection with 10% povidone iodine before being packed with cotton gauze. All patients received postoperative infection prophylaxis with daily intramuscular ceftriaxone for 3 days and 500 mg of paracetamol orally 3 times daily to manage pain without interfering with platelet function. Postoperative wound evaluation was performed during regularly scheduled clinic outpatient visits on postoperative days 4, 6, 9, 12, 17, 22, and 27, then weekly on days 35, 42, and 50 until complete healing occurred. On days 4 and 12 following excision, the PRP group received 0.1 cc of PRP, obtained using standardized methods from autogenous venous blood, injected 13 mm deep into the wound using an insulin needle over a course of less than 30 seconds. The remaining 3.9 mL of PRP was used to fill the wound, which then was covered with a latex dressing for 24 hours to retain the PRP. The primary outcome (wound volume reduction) and secondary outcome (postoperative pain duration) were measured on postoperative days 4, 12, 30, and 50. Incidence of SSI, duration of paracetamol use, and time to return to work also were recorded. Quantitative outcomes were analyzed using the student’s t-test, and categorical results were analyzed using the χ² test, all with P less than .05 considered statistically significant.

Results: On enrollment, both groups were comparable on pain, discharge, and number of sinus pits (range, 3–5). All 50 patients in each group completed the study and were included in the analysis. Patients treated with PRP experienced shorter pain duration and time to return to work as well as earlier comfort in both sitting and toilet sitting than control patients (P <.001). Wound volumes were similar during the first 10 postoperative days; from day 15 to day 45 after surgery, wound volumes were lower for the PRP-treated group (P <.001). Mean time to complete healing was 45 days for those treated with PRP and 57 days for those receiving standard of care without PRP (P <.001). Patients treated with PRP experienced 3 SSIs compared with 10 SSIs for control patients (P <.01). Among those with an SSI, healing was delayed in 3 control patients and 1 patient who received PRP (P =.3).

Authors’ Conclusions: Injecting PRP into lay-open pilonidal sinus excisions resulted in faster healing with less postoperative pain, fewer complications, and earlier return to work compared with control patients who did not receive PRP.

These two studies^4,5 highlight the potential of PRP to improve surgical wound healing and infection rates. The ideal parameters of PRP administration remain to be determined, including depth and route, timing, dose, vehicle, frequency, and interval of use for administering PRP to optimize healing effects on all chronic and acute wounds. Platelet-rich plasma may be a useful tool in surgical wound care, but a single intraoperative dose does not appear to have a prolonged effect on wound healing.^3,4 Additionally, use of PRP does not preclude the need for thoughtful diagnosis and treatment of the original cause of a chronic wound. Rather, topical and/or injected PRP may be a valuable adjunct to standard of care, such as offloading for diabetic foot ulcers and compression for venous ulcers.^1,2 Studies exploring the ideal parameters of PRP administration require blinded treatment and outcome observations to rule out placebo effects as well as use of rigorous controls to identify the PRP mechanism of action. The pilonidal sinus excision study results⁵ would have been more compelling if control patients had received identical treatment with the PPP fraction of the venous blood applied similarly to the excision site with wound professionals and patients blinded to the treatment group. Earlier return of grip strength in patients whose CTS sites were irrigated with PRP as compared with PPP⁴ suggests the merit of using PRP to reduce scarring or other inflammatory sequelae of surgical procedures, including the possibility of adding it to interventions designed to reduce incidence or severity of adhesions following abdominal surgery. Optimizing the usefulness of PRP in surgical practice will require rigorously controlled clinical studies to define effective dosage, administration, and timing with careful, blinded outcomes monitoring to map the boundaries of efficacy and mechanisms of action.