Lipodissolve Victory in Nebraska: Proposed Legislative Bill in Competitive Effort to Ban Lipodissolve Fails

Lipodissolve wins Nebraska ruling from a commercially backed conspiracy to ban the treatment.

The Nebraska Legislative notified physicians on February 27, 2008, that a bill pushed by Dr Joel Schlessinger to be raised in the Nebraska Legislative against Lipodissolve was ‘indefinitely phoned’. Dr Joel Schlessinger, an Omaha Nebraska based dermatologist and general cosmetic surgeon, is a sponsored researcher with Kythera Pharmaceuticals for a new, competing Lipodissolve-drug. The drug known as ATX-101 (Sodium Deoxycholate for Injection) is backed with a $40 million investment for Stage II FDA studies. On acquiring for FDA studies, Dr Schlessinger along with other researchers for the company, began campaigns against Lipodissolve. These campaigns were created to prepare the pre-marketing efforts for a new drug.  Sodium Deoxycholate is a solvent used in phosphatidylcholine during the compounding process to create an injectable out of soy-granulas, and is a normal ingredient in phosphatidylcholine for more than 50 years.

In a nationwide campaign against Lipodissolve lead by Dr Joel Schlessinger of Nebraska, [1,2,3] in effort to clear the market for a new drug in FDA phase II development, repeatedly pushed a legislative bill to be introduced to ban the treatment. The consistent efforts to ban Lipodissolve was presented to State Senator, Rich Pahls of Omaha. The bill proposed that doctors would be prohibited from administering certain substances aimed at dissolving fat under a bill introduced in the Nebraska Legislature. The bill would affect Lipodissolve and other treatments administered by injection, as well as medical spas. The bill says the substances could not be administered for dissolving fat unless as part of clinical testing approved by the U.S. Food and Drug Administration.

Ron Schroeder, an aide to Pahls, said in a media announcement that the senator introduced Legislative Bill 713 because of repeated concerns raised by Dr. Joel Schlessinger. Opposition to the bill was raised by independent medical practitioners,  Lipodissolve founders, and medical consultants, and by numerous local senators, and representatives of the State’s Medical Board. In the process of communication, Lipodissolve founders were contacted by Senator Joel Johnson’s office to state that bill 713 (LB 73) was “killed” in the hearing and failed to create a ban on Lipodissolve treatments.

Paid ‘defamation’ campaigns

Dr Joel Schlessinger has been the initiator of many months of targeted, intentional, and negative nationwide media attention against Lipodissolve via public websites, privately paid press releases,  anonymous forum posts (revealing the doctors ip address), and excessive sensational warning letters to State Senators,  State Medical Boards, and the FDA. The warning letters have emphasized on the ‘lack of safety’ from Lipodissolve, with the only argument and evidence presented as swelling, bruising and tenderness.
Dr Schlessinger has claimed in media reports that unsufficient research fail to show whether Lipodissolve is safe and effective although numerous clinical data and reports exist, including University studies (to see a list of some publish studies in English, select the link). In a collecting effort feedback over a period of several months indicate Dr Schlessinger’s efforts to defame Lipodissolve in the media originate from a desire for personal monetary gain. Dr Schlessinger encourage liposuction surgery as a ‘safe’ treatment for patients, although studies propose the procedure has a high death rate. The FDA website quotes a study showing that deaths associated with lipo could be as high as between 20 and 100 per 100,000 procedures. Death from car accidents is only 16 per 100,000 crashes. Superwet liposuction has a reported death rate of 1/1000 while mega-liposuction has a staggering death rate of 1/100 patients. Although there is a substantial safety issue with liposuction surgery, there has been no efforts to stop or ban the treatment as liposuction is an individual choice by patients. An estimated 300,000 Lipodissolve procedures were performed in the United States in 2007, with high safety reports and no reported cases of deaths or serious, life threatening side-effects. There are, however, reports of a small handful of cases with minor side-effects from Lipodissolve, including unsual side-effects such as hives. More serious reports although extremely few in number, involve elevated deoxycholate use leading to skin breakdown and skin grafting.

It is noteworthy to emphasize that Lipodissolve criticism originate from a pharmaceutical corporation (Kythera Biopharmaceuticals) with a new product in the pipeline, that does exactly what Lipodssolve is achieving today.

Dr Schlessinger: paid researcher for new Lipodissolve drug

Dr Schlessinger has been recruiting patients for and conducting trials on the new Kythera Pharmaceutical product that imitates Lipodissolve. The doctor has served as a consultant for numerous other pharmaceutical and medical corporations [4].  Schlessingers criticism of Lipodissolve is emerging with perfect timing for early marketing of Kythera Pharmaceuticals new product, following the completion of their Phase I trials, and the company’s entry into Phase II trials with new investment funding behind it.

In the ASCDAS 2007 Annual Meeting on November 29, 2007, Dr Schlessinger gave a presentation called “Mesotherapy – Lipodissolve controversy” which was sponsored by an “unrestricted educational grant” provided by Kythera Biopharmaceuticals. The company has sponsored various other published studies [5, 6]. It is noteworthy to mention that members of the ASCDAS (for whom Dr Schlessinger served briefly as a former president) oppose the doctor’s views, and many are avid supporters of Lipodissolve injections and use the treatment on regular basis on patients.

Founders respond to sham criticism

Lipodissolve founders respond to the criticism: “The doctor’s behaviour has been shocking and deplorable. There is room for everyone in this market. Our interest by introducing Lipodissolve has been more from a medical perspective than commercial. The doctor has shown complete violation of ethical medical conduct. It is sad that a physician with such high credentials and a former president representing a medical society put his name in disrepute, in a sham pretense of caring for patient safety.”

“Dr Schlessinger suggest in letters to State Medical Boards and to the press, that his private studies reveal “bruising, pain, swelling, bloating,” in six patient cases where “Lipodissolve” was administered. But is bruising, pain, swelling and bloating signs of extreme danger from a treatment that it must be banned? These are normal side-effects from many cosmetic procedures today. The doctor has singled out Lipodissolve based on false intentions and false representation of the treatment. Since the doctor has never been certified in Lipodissolve from authorized sources, how does he know the exact and accurate protocols for his studies? It would be more to claim the doctor has never come across signs of bruising, swelling and bloating on his own surgical patients.”
“A common and known risk from cosmetic surgery is death, yet Dr Schlessinger has made no efforts to campaigning against cosmetic surgery and protecting his patients from the known potential risks. In addition, over 15% of plastic surgery patients have reported being fully dissatisfied with their treatments. This is a higher percentage than the non-responder cases from Lipodissolve where 8% is the average. In recent statistics on rated cosmetic treatments, liposuction surgery received a mere 53% satisfaction rate.”

To view Dr Joel Schlessinger’s name as a participating commercial benefactor on behalf of a pharmaceutical company, please view this link.

Dr Schlessinger cause millions in losses

The effect of Dr Joel Schlessinger’s actions have caused substantial financial losses to medical clinics across the country, estimated to total several million dollars per month and at least $230 million a year.

The founders say: “What has happened is such a shame, because Lipodissolve is a good procedure and was developed for patients, first and foremost, to offer a milder treatment option. Now many may be mislead by the propaganda and go for unecessary risky procedures. Lipodissolve offer an excellent solution for post-surgical corrections, but with the false notions spread by Dr Schlessinger and his ilk, many patients may not seek the help they can have from bad surgery. Lipodssolve is an excellent treatment for the right candidate, and is naturally no more a miracle than any other medical treatment but has its limitations. In the past year the demand for Lipodissolve escalated due to high patient demand, causing pseudo-versions of the treatment to appear everywhere. This has been easy since Lipodissolve is a simple treatment with low risks.”

Lipodissolve has often been compared with Botox®. The same controversy surrounded Botox® in early stages of introduction, without the power of the internet reaching the public in a larger scale. But Botox® eventually survived its worse critics: plastic surgeons. Today, Botox® is the most popular nonsurgical treatment of all. Turf protection was the main cause for Botox® propaganda in the past, and the same cause is the target for Lipodissolve propaganda.

FDA approved studies by ASAPS

In a positive development amongst the intentional efforts to distract patients and give them unecessary fears about Lipodissolve, Dr Leroy Young of the New Trends Taskforce with the American Society of Aesthetic Plastic Surgery (ASAPS) is conducting an FDA approved trial on phosphatidylcholine injections. Dr Young says, “It would be good if this turns out to work, but if it doesn’t work and all these people are wasting their money we need to say that too.” Some sceptics believe the ASAPS study aims to find ways to discredit Lipodissolve further, as the ASAPS has been a long-standing opponent against Lipodissolve.  The ASAPS research team has been offered to be introduced with the right protocols correlated to highest safety data, and access to high quality pharmaceuticals for their research efforts, but the group has rejected to respond to all offers.

We too want facts to be known and hope these studies will be based on accurate protocols and medications contained in actual Lipodissolve, and not imitation procedures.

Reference:
1. Omaha World-Herald: Fat-dissolving procedure targeted for regulation
January 23, 2008
2. Schlessinger, Joe: Lipodissolve, is it safe?
September 24, 2007 (privately paid newswire by the doctor)

3. Will Lipodissolve continue to be popular?
December 12, 2007  (privately paid newswire by the doctor)

4.  Fat-Dissolving Injections: Too Good to Be True?. NPR by Alison Audrey, April 17, 2009. (Schlessinger continues his critique)

5. Dr. Schlessinger is a researcher and advisor for connetics corporation; Galderma laboratories, lP; medicis
Pharmaceutical corporation; obagi medical Products; and Stiefel laboratories, Inc. Dr Schlessinger has received financial sponsorship from Kythera Pharmaceuticals.

6. Lipomas treated with subcutaneous deoxycholate injections
(Dr A Rotunda; Am Acad of Derm;Oct 17, 2005)

7. Detergent Effects of Sodium Deoxycholate Are a Major Feature of an Injectable Phosphatidylcholine Formulation Used for Localized Fat Dissolution
(Dr A Rotunda; Dermatol Surg 2004;30:1001-1008)

8. Dr Joel Schlessinger is named as one of the sponsored researchers on behalf of Kythera Pharmaceuticals for ATX-101 (Sodium Deoxycholate for Injection) Phase 2 Study for the Treatment of Superficial Lipomas

Other financially sponsored researchers on behalf of Kythera Pharmaceuticlas include:

Gary D. Monheit, M.D.
Birmingham, Alabama

Stacy R. Smith
San Diego, California

Steven Grekin, D.O.
Warren, Michigan

David J. Goldberg, M.D.
Westwood, New Jersey

Neil S. Sadick, M.D.,
New York, NY

Michael H. Gold, M.D.
Nashville, Tennessee

IMCAS 2009 Topics Summary

The most important developments at this year’s IMCAS medical congress in Europe that are emerging for 2009:

This year’s IMCAS was, compared to many other events, one congress that was well worth visiting. There are many new developments emerging in the field of aesthetic medicine which we would like to briefly describe below.

1. Development of aesthetic medicine in the face of the financial crisis.
There are clear indications that some smaller firms are already being massively hit by the effects of the current crisis. On the whole, however, a further increase in the volume of aesthetics treatments is expected. It would interest me to know whether my colleagues are already observing any impact on their patient numbers. I would welcome brief communications from different countries on this point.

2. Development of new botulin toxins.
Things are happening on the botox market. It is expected that several suppliers will be offering Botox in future. The new product from Mentor with the product name PurTox was presented. Unfortunately, Mentor has not been able to provide hard evidence for any clear advantages, e.g. longer shelf life, through studies. But there are almost certain to be changes on the price front.

3. Filler treatments of the face and body with hyaluronic acid.
Especially for the facial area, there are numerous new studies covering periods of 1 to 2 years. In the filler sector, a massive increase in the market is anticipated. It was noticeable that the majority of exhibitors came from this field. As users, we can expect many of the firms to try and place their products on the European market in the coming months.

4. Fractioned lasers.
Here, CO2 lasers seem to be becoming increasingly established as the standard. A seminar on side-effects made it very clearly that sound training in this area is essential.

5. Development of collagen stimulators.
As well as a slight increase in volume, collagen stimulators, e.g. ß-HCG, also bring about an improvement in the skin structure. It remains to be seen how this sector will develop in future. Some encouraging initial activities are already in progress.

6. Ultrasound and radio frequency therapy.
Numerous ultrasound and radio frequency devices for treating cellulite and reducing fatty tissue are a clear indication of the demand from the market, though so far there have been no genuinely convincing studies in this area. Of interest is the development of a fractioned radio frequency for the facial area.

7 . New methods for administering hyaluronic acid.
In principle, the administration of hyaluronic acid over a large area of the face by means of compressed air is a highly interesting method; however, the before & after pictures and the down time were not wholly convincing.

8. Lipodissolve, Mesotherapy and Injection lipolysis.
There were once again a very large number of papers on injection lipolysis at this year’s event. One negative aspect was that they were spread over the whole period of the congress and occurred in several different topic areas. The lectures were very well attended and showed the continuing interest in this therapy. It was also noticeable that the critical voices of former years are almost not present due to the many available clinical studies and published results especially on Lipodissolve which still brings a high interest from the medical community.

Liposuction surgery: Pathophysiology and Complications

Dr Jeffrey Klein: Chapter 6

Clinical Biostatistics of Safety

Cosmetic surgical procedures must be judged in three dimensions: (1) patient safety (does the procedure expose the patient to any unnecessary risks?), (2) ethical propriety (is the procedure truly in the patientÕs best interest, or would the patient be better served without the procedure?), and (3) aesthetic results (are surgical outcomes beneficial to the patient?). Patient safety has precedence over the other two and all other considerations.

How can a surgeon objectively decide when a cosmetic surgical procedure is safe and when it is not? Risk-benefit analysis is one of the surgeonÕs most basic and recurring activities. A comparison between two methods to prevent perioperative deep venous thromboses is a straightforward example of comparing the risks and benefits of alternative procedures. When considering drug safety, however, the analysis and decisions are not the simple ÒyesÓ or ÒnoÓ results of comparing two alternatives. Drug safety is a more subtle assessment and involves a toxicologic dose-response analysis.

What is safety? Dictionary definitions of safety, such as Òthe state of being safeÓ or Òfreedom from injury,Ó have little clinical usefulness. The clinical distinction between safe and unsafe is cloudy, with no definite boundary line. In medicine and surgery the concept of safety is most appropriately defined in terms of probability and statistics.

Dose-Response Phenomenon

Tumescent liposuction has two potential sources of danger: too much lidocaine and excessive liposuction. The more lidocaine or the more liposuction, the greater is the danger. Either situation can be represented mathematically by doseresponse function (see later discussion).

What is a safe amount of lidocaine? A surgeonÕs administration of more than 85 mg/kg body weight of lidocaine on numerous occasions without Òserious complicationsÓ does not prove this is a safe practice. Which of the following local lidocaine doses is ethically preferable: 90 mg/kg for a single surgery, at a risk of one death in 1000 surgeries, or 45 mg/kg for each of two liposuction procedures, each performed 1 month apart, at a risk of one death in 100,000 surgeries for each procedure?

What is a safe amount of liposuction? Although a single anecdotal report can easily disprove the safety of a procedure, it requires a much greater sample size to prove safety. A surgeonÕs removal of more than 5 L of supranatant fat by liposuction on numerous occasions does not prove the safety of this procedure. Which of the following is safer: a single megaliposuction of 9 L of fat, at a risk of one death in 1000 surgeries, or three liposuction procedures, each removing 3 L of fat and performed at 1-month intervals, at a risk of one death in 100,000 surgeries for each procedure?

In cosmetic surgery, especially liposuction surgery, questions about safety often are not determined by scientific method. The philosophic and conceptual aspects of safety are a challenging part of biostatistics. For example, when determining the maximum safe dose of lidocaine with tumescent liposuction, the surgeon might simply treat a few patients whose mg/kg doses of tumescent lidocaine were not predetermined, then do linear regression on mg/kg lidocaine dose versus serum lidocaine concentration. Such an approach gives the illusion of science, but it is no more helpful than a Òclinical guess.Ó

Experimental Toxicology

The experimental design of a scientific study of toxicity using experimental animals is distinctly different from a clinical study of toxicity in human subjects. It is instructive to have a conceptual understanding of experimental toxicology using animals before discussing clinical toxicology in humans.

Observational linear regression merely provides an estimate of safe tumescent lidocaine dose. Any estimate with a large but unknown standard deviation (or variance) is of minimal clinical utility when it involves potentially lethal doses of a drug used for cosmetic surgery. The smaller the standard deviation of the estimate of a parameterÕs numeric value, the greater is the accuracy of the estimate. Predictions based on observational linear regression are much less accurate than experimental linear regression.

Experimental linear regression provides more accurate results by giving the same mg/kg dose of lidocaine to a large number of experimental animals (e.g., mice) and provides good estimates with small variance. For example, a specified dose, d</i><span style=”font-style: normal;”><sub>i (mg/kg), results in a fatality with a probability, p</i><span style=”font-style: normal;”><sub>i. Thus, if 10 mice are given a subcutaneous dose (d</i><span style=”font-style: normal;”><sub>i) of lidocaine and observe n</i><span style=”font-style: normal;”><sub>i lethal outcomes, n</i><span style=”font-style: normal;”><sub>i/10 is an estimate of the true p</i><span style=”font-style: normal;”><sub>i that d</i><span style=”font-style: normal;”><sub>i will cause a death. The more mice that are given the same d</i><span style=”font-style: normal;”><sub>i, the more accurate (smaller standard deviation) will be the estimate of p</i><span style=”font-style: normal;”><sub>i. If 1000 mice are given the same d</i><span style=”font-style: normal;”><sub>i, the frequency of death as N</i><span style=”font-style: normal;”><sub>i/1000 is a more accurate estimate of p</i><span style=”font-style: normal;”><sub>i than the first estimate, n</i><span style=”font-style: normal;”><sub>i/10.

The conceptual framework of animal toxicology is important for an appreciation of clinical situations involving patients. A typical toxicologic study might use mice to determine the probability that any chosen dose will produce a toxic reaction. Suppose P(d) is the probability of toxic reaction T occurring at dose d (mg/kg) of lidocaine, where 0²</span><i>P(d)²1 by definition. Although we cannot ever know the true probability that d will cause a toxic reaction, we can obtain an estimate of P(d) by counting the frequency p(d) = n/100, where n is the number of toxic reactions that occur when 100 mice are given dose d.

If we select 10 different doses (d</i><span style=”font-style: normal;”><sub>1, d</i><span style=”font-style: normal;”><sub>2, d</i><span style=”font-style: normal;”><sub>3 . . . , d</i><span style=”font-style: normal;”><sub>10) of lidocaine and estimate the probability of a toxic reaction p(d</i><span style=”font-style: normal;”><sub>i) at each dose, a plot of the graph of p(d</i><span style=”font-style: normal;”><sub>i) will be a sigmoid, S-shaped curve (Figure 6-1).

For example, if we define T as a peak serum lidocaine level of 6 μg/ml or greater, the graph of p(d) will help us estimate the chance that any given dose will result in a serum lidocaine concentration greater than 6 μg/ml. This graph allows us to derive a quantitative definition of safety in terms of potentially toxic serum levels. Thus we might define safe to mean that less than one mouse in 100 will have a serum lidocaine concentration greater than 6 μg/ml.

Similarly, if we want to study the probability that any given dose of lidocaine will kill a mouse, we can repeat the previous study by defining T as death. In this case we might define safe dose as the dose expected to yield less than one death per 100 mice. The graph of p(d) is also used to estimate the median lethal dose (LD<sub>50) for lidocaine in mice, which is the minimum dose that has a 50% probability (p = 0.5) of killing a mouse.

Human Toxicology

When researching lidocaine toxicity among humans, any study design using experimental linear regression is unlikely to find many volunteers. Because toxicity experiments using humans are unacceptable, we must glean as much information as possible by simply observing the real world.

When studying human toxicology, epidemiologic methods provide an ethical way of obtaining reasonably accurate data on dose-response phenomena. When studying a drug that might cure a fatal disease, we can ethically consider a drug dose with a 1 in 10 chance of lethal toxicity. In this setting a clinical study involving a relatively small number of patients is reasonable. In cosmetic surgical procedures, however, ethical tolerance for lethal toxicity is much lower. This is where moral philosophy interfaces with cosmetic surgery. How much of a risk of fatal toxicity are we willing to accept? Which of the following thresholds represent an acceptable probability that a given total dose of lidocaine will result in a patientÕs death?

1 in 10 patients

1 in 100 patients

1 in 1000 patients

1 in 10,000 patients

1 in 100,000 patients

1 in 1 million patients

After agreeing on the level of acceptable risk, we can then discuss whether or not a given surgical procedure is Òsafe.Ó

Toxicity Estimates. Without human experiments, we cannot generate enough experimental data to construct a sigmoid dose-response curve. Nevertheless, by understanding the principles behind the curve, we can better understand how safety is defined quantitatively. The clinical approach to lidocaine toxicity in humans is based more on pragmatism and art than on precise science.

In the experimental animal study the likelihood of toxicity was estimated by calculating the frequency n/100. In this case, the experimenter specified the denominator as 100 mice, then determined the number n by giving dose d to each of 100 mice.

In humans, typically the numerator is specified as n = 1, and the denominator is determined by epidemiologic observation. For example, suppose I have never observed a patient with a potentially toxic serum lidocaine concentration of 6 μg/ml. Then, after giving a patient 60 mg/kg, I find that the patientÕs serum lidocaine concentration is 6 μg/ml. In my experience with tumescent lidocaine, I have given 60 mg/kg or more to about 300 patients. The 1 in 300 is a rough estimate of the incidence of lidocaine toxicity at a dose of 60 mg/kg.

At present in the United States, it is virtually impossible to conduct epidemiologic studies of iatrogenic disasters (see Chapter 5). Not revealing such data is systematically built into the U.S. legal system, and peer review often makes it illegal to comment publicly about another surgeonÕs complications. The only clinical solution is an expertÕs best estimate.

The following estimates of liposuction-related surgical mortality are based on my subjective experiences as a physician with training in epidemiology and biostatistics (Table 6-1). Objective epidemiologic data would show that the true risk of death is less for the tumescent technique totally by local anesthesia but greater for the superwet technique (see Chapter 9).

The true tumescent technique for liposuction uses no intravenous (IV) fluids, with supranatant volumes of fat less than 4 L and less than 4% of the patientÕs weight. Let us make the hypothetic supposition that one unreported death has been associated with tumescent liposuction (as a result of a pulmonary embolism). Considering the number of patients worldwide who have had true tumescent liposuction, 1:500,000 is probably a conservative estimate of mortality.

The superwet technique for liposuction uses systemic anesthesia, significant IV fluid infusions, and a 50% smaller volume of subcutaneous infiltration. The mere exposure to prolonged use of general anesthesia or IV sedation/analgesia has an estimated mortality rate of 1:10,000 to 1:20,000 in healthy ASA (American Society of Anesthesiologists) class I patients. A recent survey of surgeons who use the superwet technique reported that the risk of death associated with liposuction under systemic anesthesia is 1:5000.1 Among surgeons who limit volumes of supranatant fat to less than 4 L and do not use IV infusions, the mortality should be significantly less than 1:10,000.

The extreme superwet technique for liposuction is significantly more dangerous than the true tumescent technique totally by local anesthesia. It exposes the patient to excessive volumes of liposuction (supranatant fat exceeding 4 L), excessive number of areas liposuctioned in a single day, routine infusion of multiple liters of IV fluids, use of bupivacaine instead of lidocaine, surgery of excessive duration, excessive number of ancillary surgical procedures, and excessive amounts of anesthetic agents. I estimate that approximately 100 deaths have been associated with the extreme superwet technique or with ultrasonic liposuction.

Megaliposuction combines all the high-risk factors for liposuction and inflicts them on a single, usually naive and unsuspecting patient. Its value and safety have never been established. It is an experimental procedure without ethical oversight by a human studies research committee or an institutional review board. Megaliposuction exposes patients to the greatest risks of liposuction syndromes, which involve pulmonary embolism and pulmonary edema.

Liposuction volume limits

What is the LD<sub>50 for liposuction? The volume limits of safe liposuction must be defined, but it is simplistic to measure the degree of surgical risk based solely on the volume of aspirated supranatant fat. Which is more dangerous: removing 3 L of fat from a 50-kg woman or 6 L from a 100-kg woman, where each patient has the same lean body mass?

Several factors help to determine the amount of liposuction that can be safely performed in a single day of surgery (Box 6-1). Despite the lack of a well-defined threshold for safety, subjective criteria can be defined for liposuction safety. I feel more secure about safety when my patient is alert and conversing during surgery. When the patient is alert and smiling and can walk out of the surgicenter 30 minutes after liposuction, I have some confidence that the surgery has not been too aggressive. When a patient can return to work within 1 or 2 days after surgery, I am confident that I have not treated too many areas or removed too much fat.

The total volume of supranatant fat is not the only determinant of safety, but it does correlate with the length of postoperative recovery and the risk of complications. The following definitions of liposuction volumes of supranatant fat facilitate communication among surgeons:

1. Small-volume liposuction: less than 100 ml. Small-volume liposuction with tumescent local anesthesia is probably as safe as any minor dermatologic surgery. The risk from small-volume liposuction is comparable to removing an equivalent volume of fat by the excision of multiple lipomas.

2. Medium-volume liposuction: 100 to 1500 ml. With traditional liposuction, aspiration of more than 1500 ml of ÒstuffÓ was widely regarded as an indication for an autologous blood transfusion. With current tumescent liposuction, blood loss with medium-volume liposuction should be insignificant. Surgeons with limited experience should not remove more than 1500 ml of fat in a single day.

3. Large-volume liposuction: 1500 to 4000 ml. Large-volume liposuction was revolutionized with the widespread recognition of the profound hemostasis provided by tumescent vasoconstriction. A patientÕs ease of recovery is inversely related to the volume of aspirated fat. In my practice, liposuction of more than 3000 ml in a single day is uncommon; liposuction of more than 4000 ml is extremely rare. The belief that Òdo-it-all-at-onceÓ surgery will minimize recovery time is a fallacy. Patients who have had liposuction of 2000 ml of supranatant fat require approximately 25% of the recovery time needed by patients with liposuction of 4000 ml.

4. Extremely large-volume liposuction: 4000 to 7000 ml. Removing more than 4 L of supranatant fat in 1 day is relatively unsafe; it is safer to divide the procedure and perform it on 2 different days separated by several weeks or months. Extremely large-volume liposuction has been appropriately described as Òbeyond the paleÓ; it is Òbeyond boundsÓ and beyond the pale of safety. Surgeons who assert that extremely large-volume liposuction is safe because many other surgeons boast of doing it are instruments of the consensus gentium fallacy (see Chapter 7).

5. Megaliposuction: (more than 7000 ml). Megaliposuction is ÒlicentiousÓ in the sense of disregarding commonly accepted rules, deviating freely from correctness, and overstepping customary limits.

lidocaine dose limits

To verify that 55 mg/kg yields safe peak serum lidocaine concentrations, a researcher would have to repeat the study in a large number of volunteers. This requirement makes such an achievement unrealistic even if the effort is shared by multiple researchers. If we accept a conservative estimate for a maximum safe tumescent lidocaine dose, however, a large study is probably unnecessary. Again, we can obtain considerable information from simple clinical observations.

Two fatalities have occurred in patients who inadvertently received 105 mg/kg of lidocaine, as well as excessive IV fluids. In each case the coroner diagnosed pulmonary edema and lidocaine toxicity. Therefore any estimate of the maximum safe dose of tumescent lidocaine will be significantly less than 100 mg/kg.

One surgeon (who shall remain anonymous) gave lidocaine doses of 70 to 90 mg/kg to more than 10 patients and reported that 30% experienced nausea or vomiting. Clearly this range of tumescent lidocaine is associated with an unacceptably high incidence of clinical toxicity.

I now recommend lidocaine doses of 50 mg/kg or less, with a strict maximum of 55 mg/kg. I have measured the peak serum lidocaine concentration in approximately 20 patients after tumescent lidocaine doses in the range of 55 to 65 mg/kg. All patients had peak serum concentrations of less than 3.5 μg/ml. In addition, we have treated more than 400 patients with doses of approximately 55 mg/kg without clinical toxicity.

In one patient, 60 mg/kg of tumescent lidocaine with liposuction was associated with an episode of clinical toxicity (nausea and disorientation). Serum lidocaine concentration approximately 12 hours after infiltration was 6.1 μg/ml. In this case a probable lidocaine drug interaction with sertraline (Zoloft) may have been mediated by competitive inhibition of the hepatic microsomal enzyme cytochrome P450 3A4 (CYP3A4). Because serum lidocaine levels greater than 6.0 μg/ml are considered potentially toxic, we must assume that a safe maximum lidocaine dosage is less than 60 mg/kg.

Another patient had three serial tumescent liposuction procedures over 1 year. At the first and second surgery the patient received 58.3 and 49.7 mg/kg of lidocaine, respectively, without incident. At the third surgery, however, the lidocaine dose of 55.3 mg/kg produced a 3-hour episode of disorientation, confusion, short-term memory loss, and ataxia. The patient was taken to an emergency room, and the serum lidocaine concentration was 5.0 μg/ml. Interestingly, the day before surgery, the patient had completed a 10-day course of the antibiotic clarithromycin (Biaxin), which inhibits CYP3A4.

Based on these experiences, I would recommend that lidocaine doses be minimized and, again, should never intentionally exceed 50 mg/kg. Furthermore, drugs that interfere with CYP3A4 should be discontinued 1 or 2 weeks before surgery (see Chapter 18).

Finally, the maximum safe dose of tumescent lidocaine should be determined with serial measurements of blood concentration when there is no concurrent liposuction. Sequential serum lidocaine concentrations measured in the same patient after equal tumescent lidocaine doses are approximately 20% lower with liposuction than without liposuction. Because some disruption might prevent completion of liposuction after infiltration of lidocaine, the surgeon would not want to give a relatively high dose of tumescent lidocaine and then be obligated to do liposuction in order to avoid lidocaine toxicity.

To reiterate, my current estimate for a safe maximum tumescent lidocaine concentration is 50 mg/kg. Greater dosages, as high as 55 mg/kg, should be avoided.

summary

One case report is often sufficient to prove a procedure is unsafe. An anecdotal report of 100 cases without complications, however, is insufficient to prove a procedure is safe. A huge sample size is necessary to prove safety.

When is it reasonable to be enthusiastic about a new procedure? If a new procedure has advantages in terms of increased safety and improved clinical results, a cautious test of the new technique is warranted. When tumescent liposuction was first introduced, the advantages in safety were the elimination of significant surgical bleeding and the elimination of risks of general anesthesia. Surgeons were correct to withhold judgment, however, until the tumescent doses of lidocaine were shown to be safe based on extensive clinical experience.

When is it reasonable to be skeptical about a new procedure? Clearly, if a procedure offers no cosmetic advantages over an existing technique and is potentially more dangerous, skepticism is in order. The mere absence of unfavorable reports does not prove safety. For example, internal ultrasonic liposuction has yet to be proved safe. The dismal European experience with ultrasonic-assisted liposuction (UAL) should be a warning not to jump on the U.S. media bandwagon that has promoted UAL (see Chapter 29).

Reference

1. Glazer FM, de Jong RH: Fatal outcomes from liposuction: census survey of cosmetic surgeons, Plast Reconstr Surg 105: 436-446, 2000.

Figure 6-1 Estimating median lethal dose (LD<sub>50), the minimal dose that can be expected to kill approximately 50% of treated individuals. In other words, LD<sub>50 is minimum dose that has a 50% chance, or a probability p = 0.5, of killing a mouse. In this graph, half the mice can be expected to have a fatal reaction to a dose equivalent to d</i><span style=”font-style: normal;”><sub>6. Thus LD<sub>50 = d</i><span style=”font-style: normal;”><sub>6. Analogously, minimal dose that can be expected to kill 10% of mice is d</i><span style=”font-style: normal;”><sub>2.

BOX 6-1 Factors in Determining Safety of Liposuction

Number of areas treated

Volume of supranatant fat removed

Percent of body fat removed

Ratio of body weight to the weight of fat removed

Dosage (mg/kg) of lidocaine

Volume of intravascular fluid infused

Duration of surgical procedure

TABLE 6-1 Estimates of Liposuction-related Mortality Rates

Technique*

Mortality Estimate

True tumescent

1:500,000

Superwet

1:5000

Extreme superwet

1:1000

Megaliposuction

1:100

*See text for descriptions.