Self-funded TLA Research Makes an Impact

Dr-Jeffrey-Klein

Jeffrey A. Klein, MD – Inventor of Tumescent Lidocaine Anesthesia

Tumescent lidocaine anesthesia (TLA) was developed 30 years ago to allow successful liposuction procedures totally using local anesthesia. In decades since, Jeffrey A. Klein, MD, has expanded his knowledge of TLA so that it could potentially be used for other surgical procedures and to deliver new treatments for painful conditions.

“The more experience my colleagues and I got doing liposuction, the more we became aware that in tumescent liposuction there were virtually no surgical site infections or blood clots after surgery,” Dr. Klein said. “That is one of the big advantages of tumescent anesthesia, and it could allow us to do many surgical procedures under local anesthesia that used to be done under general anesthesia.”

Dr. Klein shared his experience with TLA Sunday when he presented the Eugene J. Van Scott Award for Innovative Therapy of the Skin and Phillip Frost Leadership Lecture, “Tumescent Drug Delivery: Lidocaine and Beyond.”

In an interview before his lecture, Dr. Klein, a dermatologist from San Juan Capistrano, California, reflected on his years of self-funded research into TLA, and looked ahead at some of its potential uses, from treating severe battlefield injuries to relieving the chronic pain of shingles.

When lidocaine was first used as a local anesthetic for liposuction in the mid-1980s, there were concerns about its potential toxicity, he said.

“But with tumescent anesthesia, the lidocaine and epinephrine are very diluted, which increases the amount of lidocaine that can be used fourfold, and it also increases the volume of local anesthetic 22-fold,” Dr. Klein said.

The medical literature in the 1980s said that peak levels of concentration of lidocaine occurred in two hours or less after injection. But as Dr. Klein tested blood levels in that time period after injection, he found the lidocaine concentration was negligible. Consequently, liposuction surgeons, including Dr. Klein, were confident there would be no toxicity as they gradually increased their dosages while carefully monitoring patients.

“Then one day, I asked a patient if I could get blood levels from him hourly for seven hours. When I got the results, the hourly blood levels were going higher and higher,” Dr. Klein said. “That told me that I didn’t know what I was doing, and neither did anybody else. I decided I had to start measuring blood levels over 36 hours. With this new data, I was able to determine that the peak lidocaine level occurs at 12 hours, not two hours.

“With that data, I could predict what the peak level would be at any given dosage. The data suggested that a conservative, but rough, estimate of the maximum safe dosage was 35 mg/kg. I published a paper in Dermatologic Surgery and Oncology that showed that 35 mg/kg was a reasonable estimate. That became an influential observation.”

Dr. Klein did research on the side as he continued his dermatology practice during the 1990s and early 2000s, and he began to think about the greater potential of TLA, especially because tumescent lidocaine seemed to reduce the risk of surgical site infections.

“I started thinking that maybe we could take this technique and apply it to general surgery or orthopedic hip replacement or even cardiac surgery,” he said. “I also wondered ‘What would happen if I were to add an antibiotic to the tumescent lidocaine solution and then inject it under the skin?’”

To test this idea, Dr. Klein carried out an independently funded pharmacokinetic clinical study reviewed by the Western Institutional Review Board.

“As it turns out, compared to intravenous drug delivery, tumescent antibiotic delivery gives sky-high subcutaneous tissue concentrations of antibiotic — much higher than what could be achieved with intravenous delivery,” he said.

As the antibiotics are slowly absorbed into the blood from under the skin, the concentration of antibiotic in the serum resembles a slow, constant IV infusion, Dr. Klein said.

“The science behind the rate of absorption of these drugs and lidocaine gives rise to the question of what other drugs could be delivered by tumescent anesthesia,” he said. “Theoretically, it could be amazing. For example, tumescent delivery of lidocaine anesthesia eliminates the pain in that area 100 percent almost immediately. If there is a traumatic wound, you can eliminate the pain and, using an antibiotic, you can prevent wound infection — all at once.

“I am hoping to get the military excited about this. If a soldier in the field is injured by an explosion or a bullet or a burn, one could use this drug delivery technique to help that soldier every step of the way.”

Dr. Klein also has experimented with using tumescent drug delivery to treat patients in pain from shingles.

“With tumescent drug delivery, you can take a tumescent lidocaine solution and put an antiviral drug in there — acyclovir — and inject that under the skin. The tumescent local anesthesia immediately relieves the patient of pain for 12-18 hours,” he said. “I have only treated a few patients this way, but they have all responded nicely.

“I am not an academic, and my research is not funded by anybody but me. This is totally investigator-initiated and investigator-financed research. I just enjoy doing my little research projects more than playing golf. I do this in my spare time at the kitchen table with my laptop open, in between conversations and interactions with my wife and kids.”

This article was reproduced from The AAD 2016 Annual Meeting News 

Tumescent.Org is Dedicated to Information About Tumescent Anesthesia.

Tumescent.Org is an informational website intended to provide information about Tumescent Local Anesthesia (TLA) including history of local anesthesia, books and articles on local anesthesia, current applications, as well as recent and on-going research.

Tumescent Drug Delivery: Lidocaine & Beyond

Tumescent lidocaine anesthesia (TLA) was developed 30 years ago to allow successful liposuction procedures totally using local anesthesia. In decades since, Jeffrey A. Klein, MD, has expanded his knowledge of TLA so that it could potentially be used for other surgical procedures and to deliver new treatments for painful conditions.
Dr. Klein shared his experience with TLA Sunday when he presented the Eugene J. Van Scott Award for Innovative Therapy of the Skin and Phillip Frost Leadership Lecture, “Tumescent Drug Delivery: Lidocaine and Beyond.”
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Download the PDF version of Dr. Klein's presentation at the AAD

Estimated Maximal Safe Dosages of Tumescent Lidocaine

maximal-safe-dosage-lidocaine
Download Article PDF

Jeffrey A. Klein, MD, MPH,*† and Daniel R. Jeske, PhD†

BACKGROUND: Tumescent lidocaine anesthesia consists of subcutaneous injection of relatively large volumes (up to 4 L or more) of dilute lidocaine (≤1 g/L) and epinephrine (≤1 mg/L). Although tumescent lidocaine anesthesia is used for an increasing variety of surgical procedures, the maximum safe dosage is unknown. Our primary aim in this study was to measure serum lidocaine concentrations after subcutaneous administration of tumescent lidocaine with and without liposuction. Our hypotheses were that even with large doses (i.e., >30 mg/kg), serum lidocaine concentrations would be below levels associated with mild toxicity and that the concentration-time profile would be lower after liposuction than without liposuction.

METHODS: Volunteers participated in 1 to 2 infiltration studies without liposuction and then one study with tumescent liposuction totally by local anesthesia. Serum lidocaine concentrations were measured at 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours after each tumescent lidocaine infiltration. Area under the curve (AUC∞) of the serum lidocaine concentration-time profiles and peak serum lidocaine concentrations (Cmax) were determined with and without liposuction. For any given milligram per kilogram dosage, the probability that Cmax >6 μg/mL, the threshold for mild lidocaine toxicity was estimated using tolerance interval analysis.

RESULTS: In 41 tumescent infiltration procedures among 14 volunteer subjects, tumescent lidocaine dosages ranged from 19.2 to 52 mg/kg. Measured serum lidocaine concentrations were all <6 μg/mL over the 24-hour study period. AUC∞s with liposuction were significantly less than those without liposuction (P = 0.001). The estimated risk of lidocaine toxicity without liposuction at a dose of 28 mg/kg and with liposuction at a dose of 45 mg/kg was ≤1 per 2000.

CONCLUSIONS: Preliminary estimates for maximum safe dosages of tumescent lidocaine are 28 mg/kg without liposuction and 45 mg/kg with liposuction. As a result of delayed systemic absorption, these dosages yield serum lidocaine concentrations below levels associated with mild toxicity and are a nonsignificant risk of harm to patients. (Anesth Analg 2016;122:1350–9)

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TAD Tumescent Antibiotic Delivery - Abdomen

Dr. Jeffrey Klein explains the theoretical concepts relating to tumescent antibiotic delivery and demonstrates the technique using SubQKath cannulas.

Painless Tumecent Infiltration

Jeffrey Klein MD shares his expertise in tumescent lidocaine local anesthesia of the abdomen using a Klein peristaltic pump and Monty infiltration cannulas.

News

.09 Saline Shortage

There is currently a shortage of sterile 0.9% Saline for IV infusion in 1 liter plastic IV bags. This shortage affects surgical procedures that use tumescent local anesthesia. The FDA is working to alleviate this shortage. Learn more here:
FDA updates on saline drug shortage

Articles

FDA 2010 Approved Lidocaine Epinephrine Labeling

Download the FDA approved insert for Lidocaine Hydrochloride and Epinephrine Injection, USP For Infiltration and Nerve Block.
FDA 2010 Approved Lidocaine Epinephrine Labeling

Books

XYLOCAINE – CHEMISTRY, PHARMACOLOGY
AND CLINICAL APPLICATIONS – Lofgren, Lundqvist 

Preface
The scientific and clinical development of Xylocaine has been as remarkable as it has been rapid, Synthesized
only as recently as 1943, it is currently regarded as one of the safest and most reliable of the local anesthetics that are in common use today.

Articles

FDA Lidocaine Analysis Documents

The complete collection of documents containing the data upon which the FDA based its official 7mg/kg maximum recommended dosage for lidocaine with epinephrine for infiltration local anesthesia (obtained under the Freedom of Information Act).
FDA Lidocaine Analysis Documents