CASE REPORT

The Use of Oral Proteolytic Enzymes
in the Post-Lipoplasty Patient 

By John Eric Lomax, MD

 

Three common problems in the post-lipoplasty patient are bruising, edema, and discomfort. Changes in technology, technique, and post-operative care are all directed at reducing one or all of these problems.^1,2 The majority of changes that have occurred in lipoplasty have come about as an attempt to reduce either the cause or the effect of the aspira­tion of adipose tissue on surrounding structures. The damage to the surrounding structures is what results in bruising, edema, and discomfort. Vitamins, trace elements, and other dietary supplements have been used by many physicians to help reduce post-lipoplasty morbidity.³ These regimens are usually based on personal experience, anecdotal patient reports, or studies done on the effect of dietary supplementa­tion in the treatment of athletic injuries.⁴ There has been very little data in the plastic surgery literature during the past 20 years to direct us in how we might use dietary supplements to help our patients recover from lipoplasty. I would like to report on three patients who saw a reduction in post-lipoplasty morbidity when tak­ing a specific dietary supplement.⁵ These three patients prompted a double-blind clinical research study and the results of the initial phase of this study will also be reported.

In the three case report patients, all underwent lipoplasty of both flanks and the abdomen in two separate procedures. The procedure was performed using a modified tumescent technique and IV sedation. The patients were required to wear the appropriate compression garments for two weeks. After surgery, each patient also received six ultrasound treat­ments to the area of lipoplasty. The only medications taken were oral analgesics containing acetaminophen and hydrocodone. Two patients had the abdominal lipoplasty done first and then the flanks. The other patient had the flanks done first. A minimum of ten weeks separated the two procedures. All patients received a protease-based dietary supplement following the second procedure. The patients were evaluated for post-lipoplasty bruising, edema, and dis­comfort beginning on the day of surgery and continuing for 4 days. Bruising and edema were evaluated by the surgeon on a scale of O to 5, and the patients evaluated their discomfort on a scale of O to 5. All patients were seen on the third, tenth, and twentieth-day post-lipoplasty by the surgeon.

Patient number one was a 35-year-old white male who underwent a 400 cc aspiration of the right and left flanks. On Day 3 he was noted to have significant bruising of the flanks with the migration of the ecchymosis to the genitalia. Pitting edema was noted throughout the area of ecchymosis. The patient was unable to rest without analgesia. Day 10 there were minimal changes in the ecchymosis and edema. The discomfort level was diminishing. Day 20 there was minimal yellowing of the skin. The edema and discomfort had resolved. Twelve weeks later the patient underwent a 475 cc aspiration of the lower abdomen with the protease-based dietary supplement added to the normal post-operative management. On Day 10, he showed complete reso­lution of bruising, and edema had almost completely resolved. On Day 20, he showed complete reso­lution of all symptoms. The dis­comfort was present only on the first night after surgery and no analgesia was required after the first post-surgical day.

Patient number two was a 39-year-old female who underwent a 900 cc aspiration of the lower abdomen. On Day 3 and Day 10, she had 4+ bruising, edema, and discomfort. The bruising and edema were localized to the areas of aspiration. Analgesics were required for nearly three weeks following the procedure. Day 20 revealed some mild yellowing of the skin and edema was still palpable in the tissue. The discomfort was minimal but still present. Ten weeks later the same patient underwent a 1,700 cc aspiration of the flanks. Again the protease-based dietary supplement was added to post­operative management. Day 3 revealed moderated bruising and edema with a severe discomfort level. Day 10 saw a complete resolution of bruising. The edema and pain levels were unchanged. Day 20 showed complete resolution of pain and only minimal edema on deep palpation.

Patient number three was a 38-year-old white female who had a 1,000 cc aspiration of the lower abdomen. Day 3 revealed significant bruising and ecchymosis with associated edema and discomfort. Day 10 showed a reduction in bruis­ing and edema to moderate levels but the discomfort level was unchanged. Day 20 revealed some residual bruising, edema, and complete resolution of the discomfort. Twelve weeks later she underwent an 1,150 cc aspiration of the flanks with the dietary supplement added to the post-lipoplasty protocol. Day 3 showed low to moderate bruising and edema. The discom­fort had fully resolved. Day 20 had resolution of bruising, dis­comfort, and only edema on deep palpation.

The three patients prompted the development of a double-blind study to determine if the decrease in post-lipoplasty morbidity was reproducible on a regular basis. Twenty-five patients underwent a total of 41 proce­dures. These ranged from a submental lipoplasty to bilateral lower leg lipoplasty (see Table 1). The volume of aspirate ranged from 50 cc to 2,500 cc (Table 2). The post-lipoplasty management of the patient remained as described in the case reports with one exception. All patients received a post-lipoplasty oral supplement. Twenty-three procedures received the oral enzyme compound after lipoplasty and 18 procedures received a placebo. All patients were placed in compression garments and all patients received post­lipoplasty ultrasound therapy, as in the case studies.

The results of the double-blind study demonstrate a significant decrease in the post-lipoplasty morbidity of the study participants who received oral enzyme compounds. The most common complaints seen in the recovery period after lipoplasty include ecchymosis, edema, and pain. Each of the patients was evaluated for these three features and each was graded on a scale of O to 5 (Tables 3, 4, 5). The evalua­tions were done by the surgeon on the third, tenth, and twentieth day post-lipoplasty. The group that received the enzyme supplement underwent 23 procedures. The aver­age volume of aspirate was 1,039 cc. The average age of the patients was 44 years. The placebo group under­went 18 procedures with an average aspirate of 910 cc. The average age for this group of patients was 44.5 years. All procedures in both groups were performed by the same surgeon to minimize any variations in technique.

The first feature evaluated was ecchymosis or the amount of bruising seen. In the placebo group (Table 6) 16 of the 18 procedures or 89 percent resulted in ecchymosis which cov­ered the entire surgical area at Day 3. In 15 of the procedures this persisted to Day 10. In the supplement group (Table 7) 5 of the 23 procedures or 22 percent resulted in significant ecchymosis and in only 1 of 23 patients did this persist until day 10. The supplement group demonstrated less significant ecchymosis which resolved more rapidly than did the placebo group.

The second feature evaluated was edema. In the placebo group 14 of the 18 procedures or 78 percent developed significant post-lipoplasty edema. In eight of these procedures notable edema persisted until Day 10, and 10 procedures had demonstrable edema at Day 20. The supplement group had significant edema in four of 23 or 17 percent of procedures. Four procedures resulted in mild edema which persisted for 10 days and one procedure resulted in demonstrable edema at the 20th day. The supplement group had fewer procedures which produced significant edema and it resolved in a shorter period of time.

Pain was the last feature evaluated in each group. The placebo group procedures resulted in significant pain in 10 of 18, or 56 percent of lipoplasties at Day 3. Five procedures were continuing to produce pain on Day 10 and 3 procedures produced persistent pain until Day 20. The supplement group procedures resulted in significant pain in 3 of 23, or 13 percent of cases. Seven procedures resulted in pain on Day 10. All patients had resolution of their pain by Day 20. The supplement group had a lower incidence and shorter duration of pain when compared to the placebo group.

Protease dietary supplements have been available as an over-the-counter nutritional supplement for more than 30 years. The rationale for the use of protease enzymes can be found in a large body of scientific data. Despite what is commonly taught, evidence exists to support the intestinal absorption of hydrolytic enzymes.^6,7,8,9 Up to 40 percent of enzymes may be absorbed functionally intact.¹⁰ If macromolecules such as enzymes are absorbed functionally intact, then is there any evidence to support the use of enzymes in the post-surgical period? Data has been collected on both trauma¹¹ and surgically created¹² hematomas which would indicate a benefit from taking proteolytic enzymes. Studies have also shown how enzymes can impact on inflammation by reducing its severity and duration.¹³ Clinical data also exists to demonstrate the absorption and efficacy in the treatment of post-surgical bleeding, swelling, and pain by oral enzyme compounds.^14,15 The problem with past studies was that there was not a good standard to compare one injury with another. With lipoplasty the mechanism of injury is controlled and thus other variables such as age, gender, location, and volume of aspirate could be accommodated in a broad double blind study.

The results of this clinical study indicate a role for oral dietary enzyme supplements in the treatment of post-lipoplasty patients. The mechanism by which this occurs is not clearly understood. There are four primary pathways to suggest how oral enzyme supplements may act as biological response modifiers. The first mechanism of action is thought to be by increasing the activity of macrophage.¹⁶ The level of activity may be increased several fold resulting in increased clearance of tissue debris by the macrophage. Oral enzyme supple­ments may also act by altering the normal fibrinolytic path­ways.¹⁷ This may also be enhanced by improvements in the microcirculation brought about by the response to oral hydrolytic enzymes.¹⁸ With improvements in microcirculation the body is better able to clear tissue debris and the products of hemolysis and fibrinolysis. The improvement in microcircu­lation should also enhance the delivery of substrate needed for tissue repair. Oral enzyme preparations may also stimulate macrophage to release tumor necrosing factor, interleukin 1-B and interleukin 6.¹⁹ These compounds and other cytokines play an important role in the inflammatory response and the breakdown of various cells. Oral enzyme preparations are also believed to work by altering the complement cascade and by reducing adherence of cellular and tissue debris to healthy tissue.²⁰ This allows for more rapid clearance of these unwanted by-products of surgery. The oral enzyme supple­ment used in this study is a combination of several proteolytic enzymes. The method of action of the supplement is probably a combination of all these pathways. The key feature of enzymes used in this fashion is that they stimulate and enhance normal responses within the body and do not block or inhibit function like pharmaceuticals such as steroids do.