Storage at Body Temperature Alters Concentration of Vasoconstrictors in Local Anesthetics

Fry, Bill W.; Ciarlone, Alfred E.

doi:10.1177/00220345800590061301

Cited by 8 publications

(5 citation statements)

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“…Adrenochrome formation was confirmed in supernatants from V. cholerae cells in minimal M9 medium. The improved stability of E in M9 medium compared to that in serum-SAPI was due to the shorter incubation time in M9 (24 h in M9 versus 48 h in serum-SAPI) and the lower temperature (30°C in M9 versus 37°C in serum-SAPI) (43).…”

Section: Discussionmentioning

confidence: 98%

Response of Vibrio cholerae to the Catecholamine Hormones Epinephrine and Norepinephrine

et al. 2015

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In Escherichia coli or Salmonella enterica, the stress-associated mammalian hormones epinephrine (E) and norepinephrine (NE) trigger a signaling cascade by interacting with the QseC sensor protein. Here we show that Vibrio cholerae, the causative agent of cholera, exhibits a specific response to E and NE. These catecholates (0.1 mM) enhanced the growth and swimming motility of V. cholerae strain O395 on soft agar in a medium containing calf serum, which simulated the environment within the host. During growth, the hormones were converted to degradation products, including adrenochrome formed by autooxidation with O 2 or superoxide. In E. coli, the QseC sensor kinase, which detects the autoinducer AI-3, also senses E or NE. The genome of V. cholerae O395 comprises an open reading frame coding for a putative protein with 29% identity to E. coli QseC. Quantitative reverse transcriptase PCR (qRT-PCR) experiments revealed increased transcript levels of the qseC-like gene and of pomB, a gene encoding a structural component of the flagellar motor complex, under the influence of E or NE. Phentolamine blocks the response of E. coli QseC to E or NE. A V. cholerae mutant devoid of the qseC-like gene retained the phentolamine-sensitive motility in the presence of E, whereas NE-stimulated motility was no longer inhibited by phentolamine. Our study demonstrates that V. cholerae senses the stress hormones E and NE. A sensor related to the histidine kinase QseC from E. coli is identified and is proposed to participate in the sensing of NE. IMPORTANCEVibrio cholerae is a Gram-negative bacterium that may cause cholera, a severe illness with high mortality due to acute dehydration caused by diarrhea and vomiting. Pathogenic V. cholerae strains possess virulence factors like the cholera toxin (CTX) and the toxin-coregulated pilus (TCP) produced in response to signals provided by the host. In pathogenic enterobacteria, the stressassociated hormones epinephrine (E) and norepinephrine (NE) of the human host act as signal molecules for the production of virulence factors and promote bacterial growth by the sequestration of iron from the host. Here we show that V. cholerae, like some enterobacteria, benefits from these stress hormones and possesses a sensor to recognize them. Stress enhances the susceptibility of a mammalian host to infection by bacteria. The stress-associated mammalian hormones epinephrine (E) and norepinephrine (NE), for example, support the growth (1-3) and motility (4, 5) of the enterobacteria Escherichia coli, Salmonella enterica serovar Typhimurium, and Klebsiella pneumoniae (6), of Pseudomonas aeruginosa (7,8), and of some Vibrio species (9) in a serum-based bacteriostatic medium. As E and NE share structural similarities to the bacterial catechol siderophores-a benzene ring with two adjacent hydroxyl groups-it was suggested that these stress hormones may be involved in the binding and uptake of iron by bacteria, thus promoting growth or motility (1-5). Recently, the mechanism by which catecholamine hormo...

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Section: Discussionmentioning

confidence: 98%

Response of Vibrio cholerae to the Catecholamine Hormones Epinephrine and Norepinephrine

et al. 2015

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“…It is likely that the concentration of this antioxidant determines thermal stability. The 1:10,000 adrenaline which showed a 64% degradation and 30% reduction in biological activity in Grant et al's study contained 1mg/mL of sodium metabisulphate, and the concentration of this antioxidant was even lower in the dental preparations which demonstrate thermal degradation 6–8 .…”

Section: Discussionmentioning

confidence: 95%

“…Thermal degradation of adrenaline, an important drug in the delivery of emergency care, has been demonstrated when exposed to extremes of temperature. Stability testing of drugs sent to the Sudan showed almost no adrenaline activity after storage in temperatures up to 45°C 5 and studies on adrenaline in preparations of local anaesthetic have demonstrated substantial reduction in adrenaline activity at temperatures of 37°‐50°C 6–8 .…”

Section: Introductionmentioning

confidence: 99%

Adrenaline activity is not significantly altered by high ambient temperatures.

Rudland¹,

Annus

1997

Emergency Medicine

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Drugs used in prehospital care are exposed to extremes of temperature, which exceed the manufacturerer's recommended storage conditions, and may result in degradahon of the formulation. Adrenaline, which can be degraded by high temperatures, is a key agent for the effective management of cardiac arrest and acute anaphylaxis in the prehospital setting. We demonstrate that the activity of adrenaline vials carried in St John's ambulances in the Perth metropolitan area during summer months when ambient temperatures can reach 40°C was not significantly altered.

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“…One study examined storage of 2% lidocaine with 1:100,000 epinephrine at 34 to 37°C compared to controls stored at room temperature. The concentration of epinephrine was still 82% of control values stored at room temperature at 2 months, still acceptable to achieve vasoconstrictor activity 4 . The turnover of our syringes is much faster from these warming blocks in our practice, where they are replenished about twice daily.…”

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confidence: 83%

Warmed Local Anesthetic for Dermatologic Surgery

Krathen

Donnelly

2008

Dermatologic Surgery

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The authors have indicated no significant interest with commercial supporters. D ecreasing the amount of pain caused by local anesthetics is a constant goal in dermatologic surgery. Many physicians buffer their anesthetic solutions with sodium bicarbonate to neutralize the pH. However, this causes degradation of the epinephrine and the lidocaine at a much more rapid rate. 1 Therefore, most store this solution in the refrigerator, which allows one to keep it for 2 weeks and still retain the effectiveness of the anesthetic and epinephrine. Other techniques tried to decrease the pain of injection include a slow rate of injection and insertion of the needle into a follicular orifice.Tumescent anesthesia is often warmed before local infiltration for liposuction. This warmed anesthetic has been shown to be much less painful on infiltration. 2 It is unclear how increased temperature decreases pain. Two possibilities have been suggested. 3 Warmed solution may stimulate nerve endings less than cold solution, because nerve fibers are sensitive to cold, or warmed anesthetic may diffuse more rapidly, resulting in a faster onset of anesthesia and therefore inhibition of pain sensation.We have begun using warmed lidocaine with epinephrine for all injections in our practice with the aid of a syringe warmer (Figure 1). This syringe warmer, manufactured by Vista Dental Products (Racine, WI, http://www.vista-dental.com/), has seven slots for 3-cm 3 syringes in a warming block that plugs into a conventional wall outlet. The anesthetic is warmed up to 1301F (product packaging information). Other models are available with larger syringe slots if needed. It takes approximately 20 minutes to warm up when initially plugged in, and each syringe after that point can be warmed in just minutes.All patients have reported decreased pain on injection compared to their referring dermatologist's office or their prior experience in our office. We conducted a small trial with 20 blinded subjects comparing injection of room temperature 1% lidocaine with epinephrine to injection of warmed 1% lidocaine with epinephrine from the syringe warmer. Each subject was injected subcutaneously on the ventral forearm with 0.5 cm 3 over 5 seconds. Injection of the warmed or room temperature solutions was randomized, so 50% of subjects received the warmed solution first and 50% received the room temperature solution first. The first solution was injected into one forearm and the second into the contralateral forearm. Subjects were asked to rate the subjective pain of injection on a scale of 1 to 10, where 10 is the most severe pain imaginable, immediately after each injection. They could not change their response after the second injection. The average (mean) pain rating for the warmed injection was 3.75 of 10 (standard deviation 1.92) and the average (mean) pain rating for the room temperature injection was 5.45 of 10 (standard deviation 1.67). This amounts to an approximately 30% decrease in the subjective pain of injection when using warmed lidocaine with epin...

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Storage at Body Temperature Alters Concentration of Vasoconstrictors in Local Anesthetics

Cited by 8 publications

References 0 publications

Response of Vibrio cholerae to the Catecholamine Hormones Epinephrine and Norepinephrine

Response of Vibrio cholerae to the Catecholamine Hormones Epinephrine and Norepinephrine

Adrenaline activity is not significantly altered by high ambient temperatures.

Warmed Local Anesthetic for Dermatologic Surgery

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