Injection lipolysis: clinical practice

Maria Shirshakova , Ph.D., dermatovenerologist, cosmetologist, head of the cosmetology department at the Expert Clinik (Russia)

Definition and legalization of the method

By definition, “lipolysis” is the process of breaking down fats into their constituent fatty acids by the action of lipase. The procedure for injection lipolysis (chemical ablation of adipose tissue, adipolypolysis, intralipotherapy, lipodissolve) is the introduction directly into adipose tissue of a medicinal mixture of biodetergents based on phosphatidylcholine and sodium deoxycholate in order to reduce subcutaneous fat. According to a number of experts, the procedure occupies an intermediate position between non-invasive methods of body correction and surgical intervention (liposuction and abdominoplasty).

Despite the high popularity of the method, the situation in the world with the legalization of injection lipolysis is very paradoxical. Thus, in the USA, injection lipolysis is widespread in clinics and medical centers, but there is not a single ready-made form of biodetergents officially approved for use. Doctors independently prepare prescriptions for “cocktails” based on phosphatidylcholine, sodium deoxycholate, often in combination with L-carnitine, buflomedil, caffeine and plant extracts, to prepare prescription drugs in a pharmacy and then administer the finished medicinal mixture to the patient. Thus, in the USA, injectable lipolysis procedures are in practice carried out using medicinal mixtures that are not approved by the Food and Drug Administration (FDA) and are not officially approved.

The situation in Europe is somewhat milder, since a number of European manufacturers have modern laboratories for the production of mesotherapy products, equipped in accordance with international GMP standards. It is traditionally believed that Spanish manufacturers have succeeded more than others in this area. However, in most cases, drugs produced in Europe are registered as injectable medical products or cosmetic lotions for external use.

In addition to the problem of legal use of the method, there is also the problem of using injection lipolysis for non-officially approved indications, often using so-called mesotherapeutic lipolytic cocktails prepared independently ex tempero, which in some cases leads to the development of serious complications and discrediting the procedure.

Thus, injection lipolysis procedures are carried out almost all over the world, the results obtained are discussed by doctors and patients on forums on the Internet and on the pages of printed publications. In order to generalize the accumulated experience, assess the effectiveness and risks of adverse events after injection lipolysis, and develop recommendations for the use of this method in clinical practice, scientific societies are created, interesting publications by doctors about its high effectiveness appear, doses are adjusted, and long-term results of the procedure are monitored. For example, currently in the USA and in 50 other centers around the world, under the auspices of the FDA, Kythera Biopharmaceuticals (USA) is conducting a study of the pharmacodynamics and pharmacokinetics of the drug for injection lipolysis ATX-101, as well as a histological assessment of tissues that have been administered a mixture of biodetergents. Kythera Biopharmaceuticals conducted a preclinical and clinical evaluation of the ATX-101 submental fat reduction program. Two randomized, double-blind, placebo-controlled international studies found that ATX-101 was well tolerated and demonstrated statistically significant effectiveness in reducing submental fat, as rated by both clinicians and patients. The company's specialists also conducted four initial stages of clinical studies (pharmacokinetic, histological, lipid determination and tolerability) to determine the safety of injection lipolysis (separate results of these studies were published in 2009).

Pharmacological aspects of injection lipolysis

Most formulations intended for injectable chemical ablation of adipose tissue contain phosphatidylcholine and sodium deoxycholate.

Phosphatidylcholines

Phosphatidylcholines are chemical substances from the group of phospholipids, whose molecules in their structure resemble triglyceride molecules. Unlike triglyceride molecules, instead of one of the fatty acids, phospholipid molecules contain a phosphoric acid ester with various ionic or nonionic substituents and, therefore, are no longer a high-calorie source of energy for the body. And again, unlike triglycerides, which create fat reserves in the body, phospholipids and, in particular, phosphatidylcholines, having surface-active properties, are the main structural components of all cell membranes of the body.

The use of phosphatidylcholines in combination with other biodetergents leads to a more intense stimulation of the fat utilization process, creating favorable conditions for the accelerated restoration of carbohydrate reserves and a more vigorous restoration of metabolism in the body.

Phosphatidylcholine, whose molecule contains two polyunsaturated fatty acids, has the greatest pharmacological activity. It is this molecule that is capable of maximally stabilizing structures and increasing the microviscosity of cell membranes. The sources of this phosphotidylcholine are mainly soybeans. The phosphatidylcholine molecule from other sources (for example, from egg yolk) contains only one polyunsaturated fatty acid, which significantly affects its structure-forming properties.

There are several biochemical mechanisms of action of phosphatidylcholine drugs on body cells:

• removal of excess cholesterol from cell membranes;
• exchange with more “refractory” membrane lipids;
• replacement of damaged, for example oxidized, lipids;
• restoration of mechanical damage to cell membranes;
• displacement of toxic substances from membranes;
• participation in the transportation of fats, cholesterol and fat-soluble vitamins through the bloodstream;
• increasing the availability of triglycerides to triglyceride lipase;
• participation as ready-made “building blocks” of membranes of dividing and growing cells;
• antioxidant activity;
• a source of biologically active substances (phosphorus, choline, polyunsaturated fatty acids) involved in the mechanism of lipid and carbohydrate metabolism;
• regulation of surfactant formation in the alveoli of the lungs;
• inhibition of platelet aggregation.

All of the listed biochemical mechanisms for correcting lipid balance are implemented both individually and in complex, causing relatively slow but steadily accumulating positive changes in metabolism, as well as in the activity of the vascular and nervous systems of the body.

In medicine, phosphatidylcholine is widely used in complex therapy of the following conditions:

• hepatitis (acute and chronic), toxic hepatitis, drug and alcoholic liver damage (alcoholic hepatitis), poisoning;
• fatty liver – fatty hepatosis of various origins (caused by diabetes mellitus, chronic infections);
• liver dysfunction in somatic diseases;
• liver cirrhosis;
• necrosis of liver cells, liver failure, hepatic coma and precoma (in the form of an injection solution);
• as pre- and postoperative treatment, especially during operations in the hepatobiliary zone, for example cholecystectomy (in the form of an injection solution);
• hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia;
• diseases of the cardiovascular system: coronary heart disease, angina pectoris, conditions after myocardial infarction and stroke, cerebral and peripheral circulation disorders, hypertension, vascular atherosclerosis, diabetic angiopathy; for the prevention of thromboembolism before surgery, the prevention and treatment of fat embolism (in the form of an injection solution);
• diseases of the digestive system (chronic pancreatitis, peptic ulcer of the stomach and duodenum, etc.);
• toxicosis of pregnancy (edema, proteinuria and hypertensive disorders);
• radiation sickness (radiation syndrome);
• psoriasis, atopic dermatitis, diffuse neurodermatitis, eczema, as well as for the prevention of premature aging.

It should be noted that phosphatidylcholine is insoluble in water, and to create its injectable form, an emulsifier is needed, for which most manufacturers of injection lipolysis formulations use sodium deoxycholate. With the combined presence of phosphatidylcholine and sodium deoxycholate in an aqueous medium, liposome-deoxycholate micelles are formed, and non-covalent binding of these molecules is also possible, which leads to increased bioavailability of the active ingredients. Thus, phosphatidylcholine acts as a unique system - a carrier of sodium deoxycholate molecules.

Sodium deoxycholate

Sodium deoxycholate (deoxycholic acid) belongs to the group of secondary bile acids that are synthesized by the microflora of the large intestine. The pharmacological action of sodium deoxycholate is based on the fact that it changes the composition of the bile acid pool in the body, thereby reducing the content of potentially toxic compounds. In addition, the drug promotes the dissolution of cholesterol gallstones, reduces the amount of cholesterol, and quantitatively and qualitatively changes the composition of bile.

Recent studies show that it is sodium deoxycholate that is responsible for the lysis of adipocyte membranes in cell culture. It causes disorganization of cell membranes, cell lysis, that is, in fact, induces chemical destruction of adipose tissue.

When assessing the local tolerance of injection lipolysis, one should also remember the physicochemical parameters of the administered drug mixture. It has been shown that the use of iso-osmolar solutions of biodetergents with a physiological pH value is the most justified, since it allows minimizing pain and tissue inflammation at the injection site. Due to the presence of phosphatidylcholine, a physiological pH level is maintained (about 7.0).

Adding other components to the finished forms, for example, 0.5% organic silicon, 2% lidocaine, saline solution, etc., can lead to destabilization of the emulsion, disruption of its physiological pH level, and the development of drug incompatibility, which may be negative will affect the results of treatment. Thus, the instructions for the drug “Lipostabil” clearly indicate that in cases where dissolution is recommended, only sugar solutions (glucose, levulose, invertase) or the patient’s own blood are used in a 1:1 ratio. Other solvents should not be used.

However, some proprietary methods involve the use of “hypo-osmolar” mixtures for intralipotherapy. In this case, cocktails independently prepared by a doctor are used based on phosphotidylcholine, sodium deoxycholate, water for injection and a number of other components. Our own clinical experience shows that the introduction of such “cocktails” into adipose tissue is characterized by low clinical effectiveness and poor tolerability: injections are painful, significant swelling and hyperemia develops after the procedure, and post-injection infiltrates persist for several weeks.

Injection lipolysis: clinical practice

Indications

In most countries of the world, the indication for injection lipolysis is the presence of local fat deposits, including on the anterior abdominal wall, iliac crest and sacrum, fat pads on the lateral surfaces of the body, thighs, buttocks, riding breeches, knees, pre-axillary areas, in the area of the menopausal hump, as well as the double chin.

One of the indications is also the correction of insufficient results of liposuction, especially when it is necessary to smooth out the skin texture. In this case, injections of biodetergents are carried out no earlier than three months after the operation. In our opinion, this indication is one of the most successful, since the resulting reduction of small portions of subcutaneous fat leads to a significant improvement in the results of surgical intervention.

Despite the fact that in the literature there are descriptions of cases of successful correction of lipomas, our clinical experience shows the low effectiveness of injection lipolysis procedures for the treatment of large (more than 5 cm) lipomas. However, small diffuse lipomas that do not have a connective tissue membrane significantly decreased after the third procedure.

The effectiveness of injection lipolysis programs depends on the condition of subcutaneous fat. The results are more striking if injections are performed into the so-called soft fat, that is, in those areas where there is no pronounced swelling and tissue fibrosis. It seems to us that the areas most successfully amenable to correction are the areas of the upper and middle third of the anterior abdominal wall, the lateral ridges on the torso, the pre-axillary areas, as well as the double chin and menopausal hump. The effectiveness of procedures in the back area, in the lower third of the anterior abdominal wall, and on the inner thighs is somewhat lower.

The greatest problems arise when correcting the “breeches” area and the inner surface of the knee - here the failure rate, according to our observations, ranges from 30 to 50%. To increase the effectiveness of correction in these areas, patients should be recommended a hypocaloric diet (with a daily calorie restriction of up to 1,200–1,500 kcal), and also combine injection lipolysis with hardware and other methods of cosmetological correction of local fat deposits.

Dangerous correction zones include the inner surface of the shoulder and the inner area of the so-called children's cheeks. When performing injections in these areas, we received extensive hematomas, widespread swelling and significant tissue infiltration for 2–3 weeks. Also, in our opinion, it is dangerous to perform injections in places where infraorbital fat accumulates (due to the high risk of developing necrosis and hematomas in this area).

Contraindications

Procedures are not carried out:

• patients with a complicated history of allergies, allergies to soy products and/or intolerance to any components of the drugs;
• persons under 18 years of age;
• pregnant and lactating women;
• patients with autoimmune diseases (including autoimmune thyroiditis), rheumatoid arthritis, collagenosis, endocrinopathy, cancer, liver and kidney diseases, chronic infectious diseases;
• patients with diabetes, microangiopathy, peripheral circulatory disorders, arterial hypertension and other cardiovascular diseases, antiphospholipid syndrome, blood diseases, psoriasis, eczema, inflammatory and infectious skin diseases, multiple nevi in the area of drug administration, a tendency to form keloid and hypertrophic scars, psychosomatic disorders in the stage of decompensation.

Regarding issues of drug interactions, injection lipolysis procedures are not recommended during therapy with anticoagulants, antiplatelet agents, prednisolone drugs, and non-steroidal anti-inflammatory drugs.

Based on my own clinical experience, I would like to note that relative contraindications to injection lipolysis procedures are smoking and addiction to alcohol. Smoking patients often experience microangiopathies and peripheral circulatory disorders, and those who drink find it difficult to control their diet.

Examination and interview of the patient

During the preliminary examination, the doctor must carefully examine the condition of the patient’s skin and subcutaneous fat and his general health. You should find out whether the patient has recently had symptoms of herpes, atopic dermatitis, or psoriasis. In order to prevent exacerbation, patients with recurrent herpes should be prescribed antiviral drugs of the acyclovir group on the day of the procedure and then according to the generally accepted regimen. If there are active manifestations of herpes or exacerbation of skin diseases, the procedure should be postponed until recovery or stable remission.

During the examination, it is necessary to assess the thickness of the fat fold using plyometry, perform anthropometric measurements (waist, hip, etc.), and assess the body mass index. Injection lipolysis procedures are performed for patients with normal or slightly overweight if they have “fat traps” that cannot be corrected with training or diet (BMI < 30). Experience shows that the procedures are useless for those patients who refuse to change their diet or increase the level of physical activity, expecting to passively get rid of extra pounds.

It should also be noted that for cellulite, one cannot count on the effectiveness of monotherapy using the injection lipolysis method. It is necessary to gradually build a patient management scheme taking into account the pathogenetic features of the development of lipodystrophy, primarily as a pathology of the vascular bed and connective tissue.

Method of performing the procedure

Since injection lipolysis procedures are quite painful, the first stage is topical anesthesia with creams containing lidocaine. Anesthetic drugs are applied according to instructions, usually for 30–40 minutes with occlusion. After this, the skin at the injection sites is treated with an aqueous solution of chlorhexidine.

The most important factor in the effectiveness and safety of procedures is the depth of injections. It must be remembered that injections of phosphatidylcholine and sodium deoxycholate should be carried out strictly into the subcutaneous fat, since the introduction of such a mixture into the muscles or skin can lead to the formation of extensive hematomas and necrosis, regardless of the concentration of these compounds.

For injections, needles or blunt-tipped cannulas of 27 or 30 G are used. The needle (or cannula) is inserted strictly perpendicular to the surface of the skin to a depth of 10–13 mm in all areas, with the exception of the submental and the projection area of the seventh cervical vertebra C7 (menopausal hump), where the insertion depth is 6–8 mm. You can remove the needle or cannula from the tissue only after completely stopping the administration of the drug.

The issue of dosage and frequency of administration of a mixture of biodetergents is still being discussed. According to some authors, each time it is necessary to administer 0.2–0.3 ml of a mixture of phosphatidylcholine/sodium deoxycholate every 0.5–1.0 cm, sometimes 0.05–0.1 ml every 0.5 cm, that is, to achieve diffuse infiltration of subcutaneous fat using low doses of drugs. Our experience of working with more than 80 patients from Russia shows that the technique of single administration of large doses of a lipolytic mixture with a significant distance between injection points (0.3–0.5 ml every 1.5–2.0 cm) is justified. As a rule, from 6 to 50 ml of lipolytic solution is administered per procedure, depending on the concentration of phosphatidylcholine and sodium deoxycholate.

Approximate doses of the drug to treat one area:

• double chin – from 6 to 10–15 ml;
• knees – 5–10 ml;
• “breeches” – 10–15 ml;
• menopausal hump – 10–15 ml;
• stomach – 20–50 ml;
• “fat traps” in the area of the iliac crest and sacrum – 10–15 (maximum 20) ml;
• preaxillary zones – 5–10 ml in total;
• in the area of lipomas, xanthelasma – 1–5 ml.

The dose of the drug is always selected individually, taking into account the clinical picture, assessment of treatment tolerability and the results of previous procedures. In one session, no more than 2–3 zones are treated, while the total dose of the administered lipolytic mixture should not exceed 50–100 ml, which in terms of phosphatidylcholine is 1.25–2.5 g and is fully consistent with the opinion of a number of foreign experts. If the intervention is supposed to be carried out over a large area, then during the first procedure in order to assess the tolerability of treatment, it is not recommended to use more than 20–30 ml of the drug. After the injections, the skin is re-treated with a chlorhexidine solution, and then a fairly active massage is performed in the injection area to evenly distribute the lipolytic mixture throughout the subcutaneous fat. After the procedure, the patient should be under medical supervision for some time to monitor the development of possible complications in the early post-procedure period (15 to 30 minutes).

The optimal interval between procedures is 3–4 weeks, provided that the injections are performed in the same area. Since the effect of injection lipolysis is prolonged over time (inflammation, necrosis of fat cells, tissue regeneration and fibrosis), before performing the next procedure it is advisable to wait for complete regression of inflammatory phenomena and a good clinical response to the previous procedure. The course includes from 3 to 5 procedures; in rare cases, up to 8–10 procedures may be needed.

Post-procedure management

After the procedure, the doctor should warn the patient about the need to consume approximately 1.5–2 liters of fluid daily, which is necessary to activate drainage processes and detoxification. The daily calorie content of food should not exceed 1,200–1,500 kcal, with the inclusion of antioxidants, sources of microelements, polyunsaturated fatty acids in the diet, as well as a sharp reduction in the consumption of carbohydrates and refractory fats.

The patient should also be warned that it is not recommended to wear tight clothing that squeezes and rubs the injection sites. However, when correcting the hips, torso and submental area, it may be recommended to wear compression garments.

Skin care in the injection area in the first 3–7 days after the procedure includes the use of external therapy with anti-edematous, anti-inflammatory and angioprotective effects, and in case of pronounced inflammation (developed hyperemia, pain, swelling, increased local tissue temperature), cold wraps should be recommended, cryotherapy, cubic microcurrents. In case of emergency, it is permissible to take non-steroidal anti-inflammatory drugs and/or analgesics.

In order to improve the excretion of lipolysis products, patients are recommended to use hepatoprotectors, enzyme preparations, and means to improve blood microcirculation; it is also justified to prescribe hardware lymphatic drainage procedures (LPG), carboxytherapy or ozone therapy. Subsequently, you can use traditional anti-cellulite creams and gels containing nicotinic acid and caffeine, and carry out mud wraps.

During the week after the procedure, you must avoid visiting the solarium, bathhouse, sauna, or gym.

If complications occur - high temperature (more than 37.8 ° C), throbbing pain at the injection sites, severe asymmetry, long-term persistent swelling and redness of the tissues - the patient must immediately (!) consult a doctor.

Adverse reactions and complications

An analysis of the literature data convincingly indicates a low percentage of complications after injection lipolysis. Thus, Chubati R. and Duncan D., summarizing the experience of many doctors, note that side effects and complications are observed on average in 12% of cases. The most typical of these are transient hyperpigmentation and persistent soreness for 2 weeks.

Persistent hyperpigmentation is extremely rare and is usually caused by the deposition of hemosiderin under the skin due to the formation of extensive hematomas. Such pigmentation usually does not cause significant discomfort, since it resolves on its own within 3 months.

Analyzing the works of Salti D., we can come to the conclusion that there is a higher incidence of complications when using a solution for injection that includes deoxycholate alone. The author conducted a comparative study of the safety of using lipolytic solutions consisting only of sodium deoxycholate and consisting of a mixture of phosphatidylcholine/sodium deoxycholate. Thus, upon palpation of subcutaneous fat after injections of a mixture of biodetergents, slightly painful nodes measuring 4–5 mm were detected for 1 month. When the same patients underwent ultrasound dermoecho scanning, changes in subcutaneous fat tissue were observed within 2 months. As for monotherapy with sodium deoxycholate, such injections were more painful and were less well tolerated by patients. After the procedure, large (8–10 mm in diameter) nodes formed in the subcutaneous fat tissue, which were also identified on an ultrasound scanogram.

Systemic negative effects included abdominal pain, nausea, vomiting, and hypersalivation. All reactions were dose-dependent and, both intravenously and orally, were observed at single doses of phosphatidylcholine exceeding 2.5 g. We also observed a single case of overdose on a combination drug containing phosphatidylcholine / sodium deoxycholate, which manifested itself in the appearance of patients experience nausea, vomiting, weakness and a sharp drop in blood pressure 1.5–2 hours after the procedure.

When performing injection lipolysis, the recommended doses of phosphatidylcholine should not be exceeded (no more than 2.5 g!), since an overdose may result in a large amount of fatty acids entering the bloodstream, which is inevitably fraught with sterosis and fat embolism. Thus, according to Matarasso A. et al., the use of large amounts of phosphatidylcholine leads to the development of myocardial infarction in laboratory animals.

In connection with the above, we believe that before and after injection lipolysis (after two hours, a day, 2-4-6-8 weeks and 6 months) it is necessary to conduct laboratory monitoring of the blood condition. This will allow you to evaluate changes in the lipid profile, the amount of circulating fatty acids and triglycerides, other biochemical parameters of the blood, as well as liver and kidney functions.

It should be remembered that one of the degradation products of phosphatidylcholine, lysophosphatidylcholine, promotes liver cholestasis and can cause intravascular hemolysis. Therefore, for patients who have undergone injection lipolysis, if there is an appropriate clinical picture, it is recommended to perform an ultrasound of the liver.

In Russia and Ukraine, there are no studies assessing the effectiveness and safety of such procedures yet. According to the majority of Russian experts, the most common adverse events are swelling, tissue infiltration, hematomas and petechiae, pain for 2 weeks after injections of phosphatidylcholine/sodium deoxycholate.

Recently, several incidental cases of the development of adverse events after injection lipolysis have been described in the literature. Thus, during the correction of a double chin, one patient developed severe swelling, which within a few minutes spread to the neck and was accompanied by a feeling of lack of air. After stopping the swelling and relieving the symptoms of suffocation (prednisolone 90 mg IM, diphenhydramine 1.0 ml IM, furosemide 40 mg once a day and Panangin 1 tablet 3 times a day), pain in the injection area persisted for about a month and was most pronounced upon palpation of the neck area. Analysis of the situation showed an error in the injection technique: too deep injections with a moderately pronounced subcutaneous fat layer led to the penetration of a mixture of biodetergents into the platysmal muscle.

The same publication described the development of the symptom of jaundice, with staining of the skin and sclera, on the third day after the injection lipolysis procedure in the abdomen, lower back and double chin. During the initial examination, the patient hid her existing diseases (chronic hepatitis B and C and HIV infection) and even her pregnancy. Only adequate therapy for existing diseases, prescribed by a therapist and an infectious disease specialist, made it possible to quickly stop an attack of jaundice. (The patient gave birth to a healthy baby at term.)

Summarizing the data on the safety of biodetergent injections, it should be noted that the objective reasons for the development of complications are most often inadequate injection technique, the introduction of too large a volume of lipolytic mixture, non-compliance with the permitted injection depth, as well as too short a distance between the points of drug administration. Therefore, practicing doctors need to remember that, despite its simplicity, this method needs to be carefully mastered, since in inept hands it can be ineffective at best, and at worst be accompanied by the development of side effects and complications.

Of course, when carrying out procedures, it is necessary to strictly observe the basic principles of asepsis and antisepsis, which will help to avoid infection (including mycobacteria), dermatitis, and chronic skin ulcerations.

Expected reactions observed immediately after the procedure include swelling, redness, bruising, itching and burning of tissue (the latter manifestations are associated with the histamine liberatory activity of phosphatidylcholine). Isolated cases of persistent itching or burning sensation may be due to hypersensitivity to the components of the injection mixture, most often to the preservative - benzyl alcohol. If a patient develops such phenomena, detoxification and antihistamine therapy is recommended.

Immediately after the injection or, more often, the next day, most patients develop moderate pain in the injection area, which intensifies with movement. As a rule, this reaction is a consequence of local inflammation in the subcutaneous adipose tissue and is self-limiting.

First published: Les Nouvelles Esthetiques Ukraine, No. 4 (80), 2013