Tumescent Lidocaine Maximum Safe mg/kg Dosage
Information source: Klein, Jeffrey A., M.D.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Anesthesia
Intervention: Tumescent Local Anesthesia (lidocaine, epinephrine) (Drug); Liposuction (Procedure)
Phase: Phase 1/Phase 2
Status: Enrolling by invitation
Sponsored by: Klein, Jeffrey A., M.D. Official(s) and/or principal investigator(s): Jeffrey A Klein, MD, Principal Investigator, Affiliation: University of Californiia, Riverside
Summary
This pharmacokinetic clinical trial is a dose ranging study of lidocaine in tumescent local
anesthesia. The goal is to understand the absorption pharmacokinetic of tumescent lidocaine
and to determine an objective (statistical) estimate of the maximum safe mg/kg dosage of
lidocaine in tumescent local anesthesia without liposuction.
Clinical Details
Official title: Tumescent Lidocaine Bioavailability and Absorption Kinetics:Maximum Safe mg/kg Lidocaine Dosage
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Peak or maximum serum lidocaine concentration (Cmax) following a given mg/kg dosage of lidocaine delivered by subcutaneous infiltration of tumescent local anesthesia
Secondary outcome: Cmax following 45mg/kg tumescent lidocaine has a Normal distribution. We define the probability that Cmax exceeds 6 microgram/ml, the toxic threshold for lidocaine as a function of lidocaine dosage.
Detailed description:
Background:
Tumescent local anesthesia (TLA) permits a wide variety of therapeutic surgical procedures
of subcutaneous tissues and skin to be performed totally by local anesthesia ( ).
Infiltration of a sufficient volume of TLA causes the target tissues become temporarily
tumescent, or swollen and firm.
TLA is defined as the subcutaneous infiltration of a large volume of a tumescent local
anesthetic solution (TLAS). The safe use of TLA requires the safe formulation and safe use
of a tumescent local anesthetic solution (TLAS). By definition TLAS contains very dilute
lidocaine (≤ 1 gm/liter = 0. 1%) and epinephrine (≤ 1 mg/liter = 1: 1,000,000) with sodium
bicarbonate (10 milliequivalents/liter) in a physiologic crystalloid solution.
Bicarbonate, an essential ingredient, neutralizes the acid pH of commercial lidocaine and
epinephrine thereby eliminating the intense stinging discomfort which often associated with
the infiltration of commercial local anesthetics. Lidocaine which has been infiltrated for
TLA is referred to as tumescent lidocaine.
The FDA-approved maximum recommended dosage is 7 mg/kg for lidocaine with epinephrine
infiltration local anesthesia. However with TLA much larger mg/kg dosages of lidocaine are
used. The safety and efficacy of TLA is based on the unexpected slow lidocaine absorption
associated with large volumes of very dilute lidocaine and epinephrine when infiltrated into
subcutaneous tissue. Published estimates of a maximum safe mg/kg dosage of tumescent
lidocaine are derived from liposuction patients and have ranged from 35 mg/kg to 55 mg/kg (
) and much higher lidocaine doses without evident toxicity have been reported.
Liposuction, a cosmetic surgical procedure which removes subcutaneous fat, also removes some
tumescent lidocaine thereby reducing lidocaine bioavailability. In contrast, therapeutic
surgeries usually do not remove subcutaneous lidocaine and therefore the bioavailability of
lidocaine is relatively increased as is the peak serum lidocaine concentration (Cmax) and
the risk of lidocaine toxicity. Because TLA is now used for surgical procedures unrelated
to liposuction, it is desirable to have a reliable estimate of the maximum safe dosage of
tumescent lidocaine based on clinical data from subjects not having liposuction.
The goal of the present study is to obtain reliable estimates of the maximum safe mg/kg
dosage of lidocaine after tumescent local anesthesia both with and without subsequent
liposuction. The plan for the present pharmacokinetic study involves the following steps:
1. Show that there is a significant difference between the bioavailability of tumescent
lidocaine with or without liposuction. This will validate the need to determine the
maximum safe mg/kg dosage of tumescent lidocaine without liposuction.
2. Show that the magnitude of the peak serum lidocaine concentration is a linear function
of the mg/kg dosage of tumescent lidocaine, with and without liposuction. This will
support the use of interpolation and extrapolation in the discussion of results.
3. For any specified mg/kg dosage of tumescent lidocaine, estimate the risk that the peak
serum lidocaine concentration will exceed the 6 µg/ml toxic threshold.
Methods:
The protocol and consent forms for this research has been approved by an institutional
review board. All clinical procedures are to be conducted within an accredited ambulatory
surgery center.
Serum lidocaine concentration will be measured by high pressure flame chromatography (HPFC).
Female volunteer subjects will each participate in three procedures. Each procedure
involves the infiltrating of TLA followed by sequential serum samples obtained from a
peripheral vein via plastic catheter at time (T) = 0, 2, 4, 6, 8, 10, 12, 14, 16, 18 and 24
hours to be assayed for lidocaine concentration by HPFC. For each procedure, the mg/kg
dosage of tumescent lidocaine and a corresponding peak or maximum serum lidocaine
concentration (Cmax) are to be recorded.
The areas targeted for infiltration of tumescent local anesthesia (TLA) will vary from
subject to subject and include abdomen, hips, outer thigh, inner thighs and knees, female
breasts, lateral thorax and back. For each subject, the first two investigative procedures
involve an infiltration of TLA without subsequent liposuction; in the third procedure the
subject receive TLA followed by liposuction. Thus each patient serves as her own control.
Liposuction will be initiated one to two hour after completion of the infiltration process.
For each subject the TLA infiltration will be in the same area and sequential infiltrations
are to be separated by at least two weeks. As compensation for participation in the three
clinical studies, each procedure requiring more than 24 hours, the patients will receive
liposuction of the targeted area at no cost.
The total mg/kg dosage of tumescent lidocaine will vary between patients and for different
procedures within the same patient. An individual patient will receive the same mg/kg
dosage of tumescent lidocaine on at least two occasions, once followed by liposuction and at
least once without liposuction. Some patients will receive the same dosage of tumescent
lidocaine for all three procedures. Similarly, in order to explore the effect of varying
the concentrations lidocaine or the concentration of epinephrine within the TLA solution or
to understand the effect of varying the mg/kg dosage of TLA, in some patients these factors
will be varied.
In order to determine if liposuction significantly affects the amount of lidocaine that
enters the systemic circulation, the bioavailability associated of tumescent lidocaine
without and with liposuction will be compared. The statistical significance of the
difference between the area under the curve (AUC) without liposuction and the AUC with
liposuction will be calculated For each procedure, a graph of the sequential serum lidocaine
concentrations C(T) as a function of time (T) will be drawn and each peak serum lidocaine
concentration and time will be recorded both with liposuction and without liposuction.
Confidence intervals will be determined in order to estimate the risk that, for any given
mg/kg dosage, the Cmax will exceed the toxic threshold for lidocaine.
Eligibility
Minimum age: 18 Years.
Maximum age: 72 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Healthy female (ASA class 1 or 2)
- Desires liposuction
- Easily accessible veins
Exclusion Criteria:
- History of Hepatitis C, HIV
- ASA class greater or equal to 3
Locations and Contacts
Capistrano Surgery Center, San Juan Capistrano, California 92675, United States
Additional Information
Starting date: January 2005
Last updated: June 14, 2011
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