Buffer-Demand and pH of Local Anesthetic Solutions Containing Epinephrine

Jong, Rudolph H. de; Cullen, Stuart C.

doi:10.1097/00000542-196311000-00009

Cited by 25 publications

(9 citation statements)

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“…1). The EC 50 for capsaicin activation of TRPV1 was 19.2 Ϯ 0.5 M; consistent with previous findings, 14,30 the Hill coefficient was 2.1 Ϯ 0.1 (Hill four-parameter, nonlinear regression, P Ͻ 0.001), indicating cooperativity between binding sites to open the TRPV1 ionic pore. 31 While activation occurred at higher concentrations than in some previous studies, it is possible that the observed differences in capsaicin sensitivity are attributable to differences in the expression system used (e.g., oocytes vs. HEK293t cells), the TRPV1 isoforms studied (e.g., rat vs. human), or the procedure of drug application (e.g., we used an automated fast-switching perfusion system [see Materials and Methods and Drugs and Chemicals] and standardized drug applications to 10 s, ensuring a plateau # Software available at http://rsb.info.nih.gov/ij.…”

Section: Resultssupporting

confidence: 90%

“…29 In general, pain upon injection of LAs is a wellknown phenomenon and often a source of discomfort for patients undergoing local anesthesia. 49 One possible mechanism may be the low pH of some LA formulations, 50 because TRPV1 is considered the main transducing receptor system for proton-induced excitation of nociceptive sensory neurons. 28,51,52 However, the drug-containing solutions in our study were titrated to a pH of 7.4, and previous studies have suggested that LAs themselves may produce pain upon injection by directly activating TRPV1.…”

Section: Pain Medicinementioning

confidence: 99%

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The Quaternary Lidocaine Derivative, QX-314, Exerts Biphasic Effects on Transient Receptor Potential Vanilloid Subtype 1 Channels In Vitro

Rivera-Acevedo¹,

Pless

Ahern

et al. 2011

Anesthesiology

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Background: Transient receptor potential vanilloid subfamily member 1 (TRPV1) channels are important integrators of noxious stimuli with pronounced expression in nociceptive neurons. The experimental local anesthetic, QX-314, a quaternary (i.e., permanently charged) lidocaine derivative, recently has been shown to interact with and permeate these channels to produce nociceptive and sensory blockade in animals in vivo. However, little is known about the specific interactions between QX-314 and TRPV1 channels. Thus, the authors examined the mechanistic basis by which QX-314 acts on TRPV1 channels. Methods: The authors conducted an in vitro laboratory study in which they expressed TRPV1 and TRPV4 channels in Xenopus laevis oocytes and recorded cation currents with the two-electrode voltage clamp method. They used confocal microscopy for Ca 2ϩ imaging in TRPV1 transient transfected tsA201 cells. Drugs were bath-applied by gravity perfusion. Statistical analyses were performed using Student t test, ANOVA, and post tests as appropriate (P Ͻ 0.05).

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Section: Resultssupporting

confidence: 90%

Section: Pain Medicinementioning

confidence: 99%

The Quaternary Lidocaine Derivative, QX-314, Exerts Biphasic Effects on Transient Receptor Potential Vanilloid Subtype 1 Channels In Vitro

Rivera-Acevedo¹,

Pless

Ahern

et al. 2011

Anesthesiology

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“…Specimens (50 μL) were taken from the open/exposed set at 0, 1, 4, 8, 12, 24, 48, and 72 hours, while specimens from the closed/dark set were taken at 0, 24, and 72 hours. Following measurement of pH each specimen was mixed with 5 mL of 0.1M HClO 4 to stabilize the epinephrine and prevent further degradation 3,8 …”

Section: Methodsmentioning

confidence: 99%

“…Because both lidocaine and epinephrine are unstable and relatively insoluble at physiologic pH, they are commercially stored with citric or hydrochloric acid to lower their pH. Storing these drugs at a pH of 3.5 to 5.0 prevents degradation of light‐sensitive epinephrine to adenochrome 3 . Unfortunately, the acidic pH of local anesthetic agents produces a great deal of patient discomfort during its infiltration.…”

mentioning

confidence: 99%

Buffered Local Anesthetics and Epinephrine Degradation

Murakami

Odland

Ross

1994

The Journal of Dermatologic Surgery and Oncology

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Lidocaine with epinephrine is currently the most common local anesthetic agent used for facial soft tissue surgery. This combination is generally safe and effective in providing complete anesthesia and adequate hemostasis. Because epinephrine is unstable at physiologic pH, the commercial preparation is formulated with a low pH (3.5-5.5). Unfortunately, this acidic pH causes significant pain during infiltration. To reduce pain, clinicians sometimes buffer acidic local anesthetic agents with sodium bicarbonate. However, little is known about the stability of epinephrine when the pH of epinephrine is clinically altered. Using high pressure liquid chromatography (HPLC), epinephrine levels were measured after the addition of sodium bicarbonate. Our results indicate a significant amount of epinephrine degradation occurs in some of these specimens. Recommendations regarding the use of buffered local anesthetic agents are made.

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“…The addition of epinephrine and the necessary preservatives decreases the pH of the solution and, therefore, increases the potential beneficial effect of buffering (13,14,20,21). The literature should be viewed with this in mind, and clinical application and future research tailored accordingly.…”

Section: (3) Error Bars Represent 95% Cismentioning

confidence: 99%

How acidic is the lidocaine we are injecting, and how much bicarbonate should we add?

Frank

Lalonde

2012

Canadian Journal of Plastic Surgery

101

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T he infiltration of local anesthetics can be painful, and some of this pain may be attributed to the acidity of the anesthetic solution (1). In spite of the fact that a Cochrane study recommended buffering lidocaine with bicarbonate to decrease the pain of injection (2), the use of bicarbonate with lidocaine has only been adopted by a minority of practicing surgeons.One of the possible reasons that surgeons do not use buffered lidocaine is that most hospital pharmacies only premix bicarbonate and lidocaine without epinephrine, which is not as useful as buffered solutions containing epinephrine. In addition, there is a lack of knowledge about how exactly one is required to mix bicarbonate with the local anesthetic and what ratio of the mixture is ideal.The present study aimed to measure the pH of commonly used lidocaine-containing anesthetic agents available at our institutions and to validate the proper concentration of bicarbonate that should be added to lidocaine with epinephrine to neutralize its pH. The present article also aims to generate awareness among surgeons about how simple and inexpensive it is to mix bicarbonate with lidocaine to eliminate the acidity-related pain of local anesthetic injection. MethodsCommercially available solutions of 1% and 2% lidocaine, with and without epinephrine 1:100,000 were obtained (AstraZeneca Inc, Canada; Alveda Pharma, Canada). These were collected from various settings throughout a tertiary care institution (Dalhousie University, Halifax, Nova Scotia; Saint John, New Brunswick) to capture the possible effects of prolonged storage, previously opened bottles or improper storage conditions, to simulate true clinical use conditions. A total of 200 samples were collected (50 samples of each solution) from a variety of lots and ranging in expiration dates. Note was made of whether each multiuse vial was factory sealed or had been opened previously. The pH of each sample was measured using a temperaturecompensating pH meter (Model 98128, Hanna Instruments, Canada) with a resolution of 0.01 and a mean (± SD) accuracy ±0.05.To determine the proper concentration of bicarbonate for neutralization, additional samples of 1% lidocaine with 1:100,000 epinephrine were obtained, along with samples of 8.4% sodium bicarbonate (Hospira, Canada). Ten samples of each were collected. Aliquots of sodium bicarbonate (0.5 mL) were added to 20 mL of lidocaine and BaCkGround: The infiltration of local anesthetics can be painful, which is likely due, in part, to their acidity. In spite of a Cochrane study that recommended neutralizing lidocaine with bicarbonate to decrease the pain of injection, not many surgeons have adopted the practice, and there are many 'recipes' for how much bicarbonate one should add. oBJeCtIVe: To determine the acidity of lidocaine and the correct ratio of bicarbonate that should be added to neutralize lidocaine to achieve body pH. Methods: Fifty samples each of commonly used anesthetics (lidocaine 1% and 2%, with and without epinephrine 1:100,000) were obtained and tes...

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Buffer-Demand and pH of Local Anesthetic Solutions Containing Epinephrine

Cited by 25 publications

References 0 publications

The Quaternary Lidocaine Derivative, QX-314, Exerts Biphasic Effects on Transient Receptor Potential Vanilloid Subtype 1 Channels In Vitro

The Quaternary Lidocaine Derivative, QX-314, Exerts Biphasic Effects on Transient Receptor Potential Vanilloid Subtype 1 Channels In Vitro

Buffered Local Anesthetics and Epinephrine Degradation

How acidic is the lidocaine we are injecting, and how much bicarbonate should we add?

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