RESUMEN
The introduction of the hollow needle and glass syringe in the middle of the 19th century was one gigantic step in the progress of medicine to the current state of art. However, the needle with the pain it causes, become the source of fear for many patients. Indeed, immunization of millions of people who feared the needle, against the deadly contagious diseases, would not have been possible without the introduction of a jet-injector, the Med-E-Jet (Peace Gun), a pain-free way of delivering immunizing medication.
Asunto(s)
Anestesia Local/tendencias , Anestésicos Locales/administración & dosificación , Diseño de Equipo , Humanos , Inyecciones a Chorro/tendencias , Agujas/efectos adversos , Agujas/estadística & datos numéricosRESUMEN
STUDY OBJECTIVE: To compare efficacy and cost of lidocaine cutaneous anesthesia by two jet injectors to routine needle infiltration for pain relief of intravenous (i.v.) catheterization, hypothesizing that jet injection of lidocaine is less painful than its needle infiltration. DESIGN: Randomized, prospective, controlled trial. SETTING: University hospital outpatient surgical unit. PARTICIPANTS: 75 surgical patients ASA I and II. INTERVENTIONS: Three groups of 25 patients each were given intradermal lidocaine anesthesia via conventional 25-gauge needle/syringe; by MedEJet or Biojector jet injector prior to IV catheterization with an 18-gauge Jelco catheter. MEASUREMENTS AND MAIN RESULTS: Visual analogue pain scores (VAS) (0 = no pain, 10 = intolerable pain) and subjective pain intensity scores (PIS) (0 = not painful, 4 = intolerable pain) at lidocaine application and at i.v. catheterization, were recorded. Cost assessment of each method was made. At local anesthetic application, no pain by proportion of VAS = 0 with MedEJet: 25/25 (confidence interval [CI]: 0.868, 0.999) and Biojector: 24/25 (CI 0.804, 0.991) was noted, but-22 of 25 patients experienced pain with needle administration: (with VAS = 0; 3/25 [CI: 0.044, 0.302]) (posterior probability [PP] > 0.999). The corresponding VAS scores (means +/- SD) were 0.00 +/- 0.00, 0.04 +/- 0.20, and 2.4 +/- 2.23 (p < 0.001). No pain by proportion of PIS = 0 with MedEJet: 25/25 (CI: 0.868, 0.999 and Biojector: 23/25 (0.749, 0.976) was noted, but pain in 20/25 was felt with the needle: 5/25 (CI: 0.090, 0.394) (PP > 0.999). The corresponding PIS scores were 0.00 +/- 0.00, 0.16 +/- 0.55, and 1.24 +/- 1.00 (p < 0.001). At i.v. catheterization, no pain by proportion of VAS = 0 with MedEJet: 22/25 (CI: 0.698, 0.956) or Biojector: 21/25 (CI: 0.651, 0.934) was noted; but pain in 19/25 with needle administration was experienced: 6/25 (CI: 0.116, 0.436) (PP > 0.999). The corresponding scores were 0.12 +/- 0.33, 0.44 +/- 0.20, and 1.64 +/- 1.50 (p < 0.001). No pain by proportion of PIS = 0 with MedEJet: 24/25 (CI: 0.804, 0.991) or Biojector: 24/25 (CI: 0.804, 0.991) was noted, but pain was apparent in 12/25 with needle administration: 13/25 (CI: 0.334, 0.701) (PP > 0.999). The corresponding scores were 0.00 +/- 0.00, 0.00 +/- 0.00, and 0.76 +/- 0.88 (p < 0.001). Cost per application: MedEJet = $0.13; needle/syringe = $0.50; Biojector = $0.94. CONCLUSIONS: Almost completely painless i.v. catheterization was carried out by jet injection of lidocaine, but needle infiltration produced discomfort or pain and did not significantly reduce discomfort or pain at the i.v. needle insertion.
Asunto(s)
Anestésicos Locales/administración & dosificación , Cateterismo/métodos , Inyecciones a Chorro , Lidocaína/administración & dosificación , Dolor/prevención & control , Administración Cutánea , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: The objective of this study was to compare the efficacy of intradermal lidocaine anesthesia by two jet injectors to the routine needle infiltration and to the topical EMLA cream. SUBJECTS AND METHODS: In a randomized, prospective, controlled trial, 100 consenting surgicenter patients in a university hospital setting were divided into four groups (n = 25, each); intradermal lidocaine anesthesia was given either by the conventional 25 g needle/syringe or the Med-E-Jet or Biojector injector or EMLA cream was applied on the skin. Visual analogue pain scores (VAS) or verbal pain intensity scores (PIS) were reported by the patients at lidocaine application and i.v. catheterization. Cost was also assessed. RESULTS: At lidocaine application, no pain was reported, since proportions of VAS = 0 were 25/25 (CI: 0.868, 0.999) with Med-E-Jet; 24/25 (0.804, 0.991) with Biojector; 25/25 (0.868, 0.999) with EMLA; in contrast to pain, 3/25 (0.044, 0.302) with the needle (PP > 0.999). The VAS scores (mean +/- SD) were 0.00 +/- 0.00, 0.04 +/- 0.20, 0.00 +/- 0.00, and 2.4 +/- 2.2 respectively (p < 0.00 1). No pain was reported by proportions of PIS = 0 with Med-E-Jet: 25/25 (CI: 0.868, 0.999); with Biojector: 23/25 (0.749, 0.976); EMLA 25/25 (0,868, 0.999); but pain with the needle: 5/25 (0.090, 0.394) (PP > 0.999). The mean +/- SD PIS scores were 0.00 +/- 0.00, 0.16 +/- 0.55, 0.00 +/- 0.00, and 1.24 +/- 1.00, respectively (p < 0.001). At i.v. catheterization, the proportions of VAS = 0 scores were 22/25 with Med-E-Jet (0.698, 0.956); 21/25 (0.651, 0.934) with Biojector; but some pain with needle: 6/25 (0.116, 0.436) (PP > 0.999). The mean +/- SD VAS scores were: 0.12 +/- 0.33, 0.44 +/- 0.20, and 1.64 +/- 1.50, respectively (p < 0.001). No pain was reported by PIS = 0 scores in 24/25 (0.804, 0.991) with Med-E-Jet; 24/25 (0.804, 0.991) with the Biojector; but pain by zero PIS scores 13/25 (0.334, 0.703) in half of the patients in the needle group (PP > 0.999). The mean +/- SD scores were 0.00 +/- 0.00, 0.00 +/- 0.00, and 0.76 +/- 0.88, respectively (p < 0.001). The EMLA cream was not evaluated because of inadequate duration of application prior to anesthetic induction. Cost/application were: Med-E-Jet = $ 0.13; needle = $ 0.50; Biojector = $ 0.94 and EMLA = $ 3.76. CONCLUSION: Almost completely painless i.v. catheterization by jet injection of lidocaine was accomplished, while needle infiltration produced pain/discomfort and did not significantly reduce it at the i.v. needle insertion.
Asunto(s)
Anestésicos Locales/administración & dosificación , Cateterismo Periférico , Lidocaína/administración & dosificación , Piel/efectos de los fármacos , Administración Cutánea , Anestésicos Combinados/administración & dosificación , Anestésicos Combinados/economía , Anestésicos Combinados/farmacología , Anestésicos Locales/economía , Anestésicos Locales/farmacología , Cateterismo Periférico/economía , Cateterismo Periférico/métodos , Cateterismo Periférico/normas , Costos y Análisis de Costo , Femenino , Humanos , Inyecciones Intradérmicas , Inyecciones a Chorro , Lidocaína/economía , Lidocaína/farmacología , Combinación Lidocaína y Prilocaína , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Prilocaína/administración & dosificación , Prilocaína/economía , Prilocaína/farmacología , Estudios ProspectivosRESUMEN
UNLABELLED: Ketamine and magnesium (Mg2+), well known bronchodilators, have been used to treat patients with status asthmaticus. Both can block the N-methyl-D-aspartic acid (NMDA) receptor. NMDA receptors exist in the airway, and their activation seems to be linked to the release actions of sensory neuropeptides resulting in increased airway tone. We sought to determine whether ketamine relaxes the guinea pig trachea contracted by histamine by blocking the NMDA receptor. Female guinea pigs (250-400 g) were killed with an overdose of pentobarbital. The trachea was removed and cut spirally into strips 3 mm wide and 15 mm long. The strips were mounted in a 10-mL organ bath filled with Tyrode's solution bubbled through with 95% O2/5% CO2 at 37 degrees C. Strip contractions were measured isometrically with a force displacement transducer. We then studied the effect of NMDA receptor antagonists on histamine-induced tracheal contraction. In this protocol, we examined the effect of ketamine, Mg2+, zinc (Zn2+), or MK-801 (a noncompetitive NMDA receptor blocker) on strips contracted by 10(-5) M histamine. After full contraction was attained, ketamine (0.5-1.5 mM), MgSO4 (2-8 mM), ZnCl2(0.2-0.8 mM), or MK-801 (1.5-6 x 10(-5) M) was added, and the strip tension was measured again. We also studied the effect of NMDA on the relaxation by ketamine. After full contraction by 10(-5) M histamine, 0.5-1.5 mM KET was added alone or in combination with 0.1 mM NMDA, and the strip tension was measured again. Finally, we measured the effect of MK-801 on the relaxant effect of ketamine. After full contraction by 10(-5) M histamine, 0.5-2 mM ketamine was added alone or in combination with 0.75 or 1.5 x 10(-5) M MK-801, and the strip tension was measured again. All NMDA receptor antagonists tested reversed the tracheal contraction induced by histamine in a dose-dependent manner. However, neither the agonist NMDA nor the noncompetitive receptor blocker MK-801 affected tracheal relaxation induced by ketamine. We conclude that ketamine relaxes the tracheal smooth muscle contracted by histamine through a mechanism independent of NMDA receptors. The decreased bronchomotor tone induced by ketamine is probably due to interference with a Ca2+-requiring step necessary to maintain the contraction caused by histamine. IMPLICATIONS: Stimulation of the N-methyl-D-aspartic acid (NMDA) receptor in the airway results in airway constriction. The bronchodilator ketamine blocks the NMDA receptor. However, ketamine relaxes the guinea pig trachea contracted by histamine through a mechanism independent of the NMDA receptor.
Asunto(s)
Broncodilatadores/farmacología , Ketamina/farmacología , Relajación Muscular/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/fisiología , Tráquea/fisiología , Animales , Cloruros/farmacología , Maleato de Dizocilpina/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Cobayas , Histamina/farmacología , Técnicas In Vitro , Sulfato de Magnesio/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Tráquea/efectos de los fármacos , Compuestos de Zinc/farmacologíaRESUMEN
The contractile response of smooth muscles to spasmogens can be divided into two components by modifying the extracellular Ca2+ concentration. The phasic component depends on the mobilization of Ca2+ from intracellular stores whereas the tonic component depends, to a large extent, on the influx of extracellular Ca2+. The present study was designed to investigate the effect of ketamine on the tonic response to carbachol or histamine in the guinea pig trachea. Tracheal spirals from female guinea pigs were mounted in organ baths filled with aerated physiological buffer, and their isometric tension was measured. The phasic response to 10(-7) M carbachol or 10(-5) M histamine in Ca(2+)-free, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-containing buffer and the tonic response to each spasmogen after restoring [Ca2+] in the buffer was measured in the absence or presence of ketamine. In the presence of normal physiological buffer, ketamine decreased the contractions induced by carbachol or histamine in a dose-dependent fashion. No measurable phasic response to either carbachol or histamine was obtained in our preparation. Ketamine (5 x 10(-5) M-10(-3) M) reduced the tonic response to 10(-7) M carbachol to 79.5 +/- 2.7-4.3 +/- 0.7% of the response without ketamine. Similarly, ketamine (5 x 10(-4) M-2 x 10(-3) M) decreased the tonic response to 10(-5) M histamine to 80.7 +/- 3.9-23.0 +/- 3.2% of the response in the absence of ketamine. Our findings support the hypothesis that ketamine inhibits the paracrine agent-induced contractions of smooth muscles by interfering with the influx of extracellular Ca2+ or with an intracellular event(s) requiring extracellular Ca2+.
Asunto(s)
Anestésicos Disociativos/farmacología , Broncoconstrictores/farmacología , Carbacol/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Histamina/farmacología , Ketamina/farmacología , Contracción Muscular/efectos de los fármacos , Parasimpaticomiméticos/farmacología , Tráquea/efectos de los fármacos , Animales , Tampones (Química) , Calcio/metabolismo , Quelantes/farmacología , Ácido Egtácico/farmacología , Femenino , Cobayas , Transporte Iónico/efectos de los fármacos , Contracción Isométrica/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/metabolismo , Comunicación Paracrina/efectos de los fármacos , Tráquea/metabolismoRESUMEN
The jet injector route for ketamine was used on 30 children 1-6 years of age undergoing various surgical procedures. A randomly selected dose of 2.5, 3.5, or 6.0 mg/kg of ketamine was given to induce anesthesia. Peak plasma ketamine levels did not follow a simple arithmetic increment related to dose. Dosage based on mg/m2 body surface area or mg/kg body weight provided similar blood levels of ketamine. The beta-phase t1/2 of ketamine in these children was shorter than that found in adults. Considerable individual variability was observed in both the plasma levels to a given dose of jet-injected ketamine and in the beta-phase t1/2. The ketamine beta-t1/2s were not dose related.
Asunto(s)
Anestésicos Intravenosos/farmacocinética , Ketamina/farmacocinética , Envejecimiento/metabolismo , Anestésicos Intravenosos/administración & dosificación , Superficie Corporal , Peso Corporal , Calibración , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Semivida , Humanos , Lactante , Inyecciones a Chorro , Ketamina/administración & dosificación , MasculinoRESUMEN
Endothelins (ETs) are synthesized not only in vascular endothelial cells but also in airway epithelial cells. Increased ET-1 has been demonstrated in bronchial epithelium of asthmatic patients, and, in severe asthma attacks, ET-1 increases in plasma and bronchoalveolar lavage fluid. In this study, we investigated whether ketamine (KET) relaxes ET-induced tracheal contractions. Female guinea pigs were killed with an overdose of pentobarbital. The trachea was removed and cut spirally into two strips that were mounted in an organ bath filled with Krebs-bicarbonate buffer. The response of each strip to 10(-7) M carbachol was taken as 100% contraction to which the response to ET was referred. The contribution of the epithelium to the relaxant effect of KET was studied in denuded tracheae or in the presence of 5 x 10(-5) M indomethacin. ET-1 (3 x 10(-8) M) induced contractions that were 76 +/- 3% of those induced by carbachol. KET reversed the response to ET-1 in a dose-dependent fashion. Similarly, ET-2 (3 x 10(-8) M) induced contractions that were 74 +/- 5% of those induced by carbachol, and KET also reversed this response in a dose-dependent manner. In epithelium-denuded strips, ET-1 induced contractions that were 104 +/- 3% of those induced by carbachol, and KET still reversed this response. The tonic phase of the response to ET-1 was equal (100 +/- 6%) to the response to carbachol, and KET did not affect it significantly. In the presence of ryanodine, KET reduced the ET-1-induced contraction from 67 +/- 2% to 36 +/- 3.%, P < 0.01. In the presence of nicardipine, KET also inhibited the ET-1-induced contraction. We conclude that KET relaxes the tracheal smooth muscle contracted by ETs via a mechanism that is independent of the tracheal epithelium. The relaxant effect of KET on the ET-induced contraction of the trachealis muscle is not dependent upon blockade of 1) sarcolemma influx of Ca2+ through the dihydropyridine Ca2+ channel or 2) the release of intracellular Ca2+ through the ryanodine-sensitive intracellular Ca2+ channel. It is likely that the action of KET relaxing ET-induced tracheal contractions is at some point of the inositol 1,4,5-trisphosphate signaling pathway.
Asunto(s)
Anestésicos Disociativos/farmacología , Endotelina-1/farmacología , Ketamina/farmacología , Tráquea/efectos de los fármacos , Animales , Calcio/metabolismo , Canales de Calcio/efectos de los fármacos , Carbacol/farmacología , Ácido Egtácico/farmacología , Femenino , Cobayas , Técnicas In Vitro , Contracción Muscular/efectos de los fármacos , Nicardipino/farmacología , Tráquea/fisiologíaRESUMEN
Airway epithelial cells and vascular endothelial cells modulate the tone of the underlying smooth muscle by releasing relaxing factors such as prostanoids and nitric oxide (NO). In the present study, we investigated whether the relaxant effect of ketamine depends on any of the epithelium-derived relaxing factors. Tracheae of female guinea pigs were cut spirally into strips (15 x 3 mm) and mounted in water-jacketed organ baths filled with Krebs-bicarbonate buffer aerated with a mixture of 95% O2 and 5% CO2 at 37 degrees C. Changes in the tension of the strips were measured isometrically with a force displacement transducer and recorded with a polygraph. In the first set of experiments, we examined the effect of ketamine on the concentration-response curves for histamine and carbachol in strips in which the epithelium was kept intact and in strips with denuded epithelium. In the second and third set of experiments, we studied the effect of indomethacin, a cyclooxygenase inhibitor, and N-omega-nitro-L-arginine methylester(L-NAME), a NO synthase inhibitor, on the relaxant activity of ketamine on tracheal strips contracted by histamine or carbachol. The following results were obtained: 1. Mechanical denudation of the tracheal epithelium shifted the concentration-response curve for histamine to the left (the 50% effective concentration [EC50] value of histamine decreased from 3.5 +/- 0.02 x 10(-6) M in the intact strips to 0.98 +/- 0.01 x 10(-6) M in denuded strips, P < 0.001). However, removal of the tracheal epithelium did not change the response to carbachol (the EC50 for carbachol was 1.1 +/- 0.02 x 10(-7) M in intact strips versus 0.88 +/- 0.01 x 10(-7) M after epithelial removal, P > 0.05). 2. Ketamine shifted to the right the concentration-response curves for histamine and carbachol in both intact and denuded tracheae. 3. Indomethacin did not alter the relaxant effect of ketamine on the tracheae contracted by either histamine (the concentration that inhibits 50% [IC50] of ketamine = 1.5 +/- 0.01 x 10(-3) M in control strips and 1.3 +/- 0.04 x 10(-3) M in strips pretreated with indomethacin, P > 0.05) or carbachol (the IC50 of ketamine was 2.5 +/- 0.02 x 10(-4) M in control strips and 2.4 +/- 0.01 x 10(-4) M in strips pretreated with indomethacin, P > 0.05). 4. L-NAME did not influence the relaxant effect of ketamine on tracheae contracted by either histamine (the IC50 of ketamine = 1.6 +/- 0.05 x 10(-3) M in control strips and 1.6 +/- 0.05 x 10(-3) M in strips pretreated with L-NAME, P > 0.05) or carbachol (the IC50 of ketamine = 2.6 +/- 0.04 x 10(-4) M in control strips and 2.3 +/- 0.01 x 10(-4) M in trips pretreated with L-NAME, P > 0.05). These results indicate that neither the mechanical removal of the tracheal epithelium nor the blockade of the release of potent mediators from tracheal epithelial cells influence the relaxant effect of ketamine on guinea pig tracheal strips contracted by histamine or carbachol. We conclude that ketamine relaxes the airway smooth muscle by an epithelium-independent mechanism.
Asunto(s)
Resistencia de las Vías Respiratorias/efectos de los fármacos , Anestésicos Disociativos/farmacología , Ketamina/farmacología , Músculo Liso/efectos de los fármacos , Tráquea/efectos de los fármacos , Animales , Ácidos Araquidónicos/fisiología , Carbacol/farmacología , Epitelio/efectos de los fármacos , Femenino , Cobayas , Histamina/farmacología , Técnicas In Vitro , Indometacina/farmacología , Óxido Nítrico/fisiología , Parasimpatolíticos/farmacología , Tráquea/citologíaRESUMEN
PURPOSE: Droperidol (D) is effective in the treatment of patients with status asthmaticus. It has been reported that D inhibits the bronchoconstriction induced by serotonin (5-HT) but not that by histamine (H) or acetylcholine. However, haloperidol, another butyrophenone, is known to interact with and inhibit calmodulin, an intracellular Ca(++)-binding protein which is important in the contraction of smooth muscles. The present study was designed to investigate the effects of D on tracheal contractions induced by 5-HT, H or carbachol (C) and to determine the contribution of alpha-adrenoceptors to the relaxant effect of D in vitro. METHODS: Tracheas of female guinea pigs were cut spirally into strips and mounted in water-jacketed organ baths in Tyrode's solution, aerated with a mixture of 95% O2 and 5% CO2 at 37 degrees C. The changes in isometric tension induced by each spasmogen in the strips were measured with a transducer and a polygraph. RESULTS: We found that D inhibited the tracheal contractions induced by 5-HT, H or C in a concentration-dependent manner. At 1.25 x 10(-6) M D blocked the effect of 10(-4) M 5-HT by 44.1 +/- 4.3% and at 2.5 x 10(-6) M by 63.8 +/- 3.8%. Similarly, at 5.0 x 10(-6) M concentration, D blocked the effect of 10(-5) M H by 27.7 +/- 5.3% and at 10(-5) M by 56.2 +/- 2.6%. Furthermore, 5 x 10(-6) M of D reduced the contractions produced by 10(-7) M C by 37.1 +/- 3.0% and 10(-5) M of D by 76.1 +/- 3.2%. The inhibiting effect of D was strongest on contractions induced by 5-HT. Prazosin (10(-6) M) affected neither 5-HT-induced contractions nor the inhibition by D. CONCLUSION: Our data indicate that D partially blocks the contractile responses not only to 5-HT, an effect which would be mediated through a blockade of the 5-HT receptors, but also to H or C, probably through inhibition of calmodulin. Our data support previous reports indicating that droperidol may be an important therapeutic agent in the treatment of patients with hyperreactive airways.
Asunto(s)
Anestésicos Intravenosos/farmacología , Carbacol/farmacología , Droperidol/farmacología , Histamina/farmacología , Agonistas Muscarínicos/farmacología , Contracción Muscular/efectos de los fármacos , Serotonina/farmacología , Tráquea/efectos de los fármacos , Animales , Femenino , Cobayas , Técnicas In Vitro , Prazosina/farmacología , Tráquea/fisiologíaRESUMEN
The mechanism by which racemic (R(+/-)) ketamine relaxes airway smooth muscle is unclear and there is no information on the differential effects of ketamine and its isomers. In this study, we have examined the spasmolytic effect of R(+/-) ketamine and its isomers S(+) and R(-) ketamine and the role of intracellular calcium and opioid receptors in R(+/-) ketamine-induced relaxation. The tension of isolated guinea pig tracheal strips was measured isometrically with a force displacement transducer and contraction elicited with histamine 10(-5) mol litre-1. In histamine-preconstricted strips, the two ketamine isomers (4.5-18.0 x 10(-4) mol litre-1) produced equipotent relaxation. A subthreshold dose of each isomer of ketamine (10(-4) mol litre-1) which alone did not relax histamine-induced contraction (S(+), P < 0.01; R(+/-), P < 0.01; R(-), P < 0.05) significantly potentiated adrenaline 1.25-5.0 x 10(-9) mol litre-1-induced relaxation (potency: S(+) > R(+/-) > R(-)). Increase in extracellular Ca2+ (1.8-14.4 x 10(-3) mol litre-1) significantly reduced R(+/-) ketamine-induced relaxation. S(-) Bay K 8644, at concentrations up to 2.0 x 10(-6) mol litre-1, partially antagonized R(+/-) ketamine-induced relaxation whereas at 10(-5) mol litre-1 or higher it potentiated the response. Naloxone 1.5-6.0 x 10(-6) mol litre-1 did not affect the relaxation caused by R(+/-) ketamine. We conclude that although both ketamine isomers produced equipotent spasmolytic effects on airway smooth muscle precontracted with histamine, they differed in their ability to potentiate the relaxing effect of adrenaline. S(+) ketamine produced the greatest potentiation. Changes in intracellular Ca2+ level secondary to a reduction in the L-type Ca2+ current may partially mediate the spasmolytic effect of R(+/-) ketamine.
Asunto(s)
Anestésicos Disociativos/farmacología , Ketamina/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Tráquea/efectos de los fármacos , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Animales , Calcio/farmacología , Técnicas de Cultivo , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Epinefrina/farmacología , Femenino , Cobayas , Antagonistas de los Receptores Histamínicos/farmacología , Relajación Muscular/efectos de los fármacos , Músculo Liso/fisiología , Naloxona/farmacologíaRESUMEN
Ketamine (K) i.m. has been widely used for anesthetic induction in small children in the last decades, if mask induction has failed. In many instances, however, physical restraint was required. In order to eliminate the pain of i.m. injection and to prevent the psychological and physical trauma associated with restraint, we evaluated the utility of jet-injection (j.i.) of K for anesthetic induction in a dose-range finding study. Thirty children (age 1-6 years), whose parents gave a valid consent approved by the IRB and were scheduled for minor surgeries, were randomized into 3 equal groups: A/ketamine 6.0 mg/kg j.i., B/ketamine 3.5 mg/kg j.i., C/ketamine 2.5 mg/kg j.i. As a drying agent atropine 20 microg/kg was also given i.v. The onset of full amnesic/sedative effect of K, the scoring of sedation and emotional state, the ease of placement of the i.v. catheter, the speed of recovery by Aldrete scores, and the time for safe discharge were evaluated. Although no demographic differences were observed among the groups the duration of surgery and anesthesia were longer in the B group (41 and 49 min) than in the A or C groups. The onset of sedation was significantly (p < 0.05) faster in group A (174 sec) than in group B (312 sec) or C (303 sec). However, no significant difference was observed in the onset of complete sedation among the groups. The sedation index was the lowest representing the best sedation in group A (4.2) while in group B and C were somewhat higher (4.6 and 4.4). There were no differences in the ease of i.v. cannulation among the groups. Recovery from anesthesia was the slowest in group A, although the differences among the 3 groups did not reach statistical significance. The mean discharge times ranged from 10-13 min with no differences among the groups. Laryngospasm occurred in 4:10 in group A and 1:10 in groups B and C. Evidently the high dose of K, 6.0 mg/kg caused a proneness to laryngospasm. Since no additional benefit was derived from this high dose, the lower doses (3.0 mg/kg) of K may be sufficient for routine use. None of the children experienced unpleasant recall or pain for the injection or the whole procedure. This new route of anesthetic induction with the jet-injector utilizing K may provide pain-free and stress-free induction as compared to its i.m. injection. This technique also prevents transmission of infection and is [correction of and cost] cost effective since simultaneous and/or sequential injection can be given from a single vial of K.
Asunto(s)
Anestesia/métodos , Anestésicos Disociativos/administración & dosificación , Inyecciones a Chorro , Ketamina/administración & dosificación , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Vías de Administración de Medicamentos , Humanos , LactanteRESUMEN
Recent studies indicate that not only inflammatory cells but also neural mechanisms by which tachykinins such as substance P (SP) and neurokinin A (NKA) are released from vagal afferent C-fiber contribute to asthma. Although ketamine (K) has been used in the anesthetic management of asthmatic patients, the mechanism by which K relaxes the airway smooth muscle is still uncertain, and no information exists on any differential effect of K and its isomers. We determined the spasmolytic effect of racemic [R(±)]K and its isomers S(+) K and R(-) K on SP and NKA-induced contraction of tracheal smooth muscle in guinea pigs. Strips of guinea pig trachea were mounted in an organ bath filled with Tyrode's solution at 37°C bubbled with 95% O2/5% CO2. Strip tension was measured isometrically with a force displacement transducer. Strip contraction was elicited with SP 10(-6) M or NKA 5×10(-7) M.R(±), R(-), or S(+) K (4.5-18.0×10(-4)M) was cumulatively administered into the bath. The calculated ED50 values (the concentration that relaxed the contraction by 50%) of R(±), R(-) and S(+) K were 7.6±0.5, 7.8±0.6, and 7.6±0.5 (10(-4)M), respectively, when the contraction was elicited with SP, and 8.0±1.0, 8.2±1.2, and 7.9±1.3 (10(-4)M), respectively, when NKA was used. We concluded that K and its isomers have equipotent spasmolytic effects on airway smooth muscle precontracted with tachykinins.
RESUMEN
In order to assure rapid anesthetic induction in children and to prevent the psychological and physical trauma associated with restraint during mask induction or intramuscular injection, we evaluated the utility of a jet-injector and the effectiveness of midazolam for anesthetic co-induction in a dose-range finding study. Forty children (age: 1-6 yrs), whose parents gave a valid consent approved by the Institutional Review Board (IRB) and who underwent minor surgery, were randomized into four equal groups: A. midazolam 100 micrograms/kg by jet-injection (JI); B. midazolam 150 micrograms/kg JI; C. midazolam 200 micrograms/kg JI; D. midazolam 80 micrograms/kg i.m by conventional syringe-needle. As a drying agent, atropine 20 micrograms/kg JI or i.m. was also added to the midazolam solution. The onset and full sedative effect of midazolam, the scoring of sedation and emotional state, the ease of placement of the intravenous catheter, the speed of recovery by Aldrete-scores and the time for safe discharge were evaluated. No demographic differences were observed among the four groups with similar mean duration of surgery and anesthesia. The mean sedation score was reduced in Group C the most, less in the B, A and D groups. The onset of sedation ranged from 3-5 min in groups A, B or C as compared to 5-9 min in D. Ideal conditions for the start of i.v. catheter were best achieved in group C (8:8) and B (8:10) in contrast to groups A (2:10) and D (0:10). Whereas no i.v. start was difficult in B and C, 6:10 were difficult in D and A. None of the children in the three JI groups (A, B and C) experienced unpleasant recall or pain from the injection during the whole procedure. Response to verbal stimuli recovered in 3 min after the end of anesthesia and the children were discharged 8-9 minutes afterward. None of the children needed a longer than 15-minute interval to reach an Aldrete score of 10. No differences among the groups were observed as to the time of recovery or discharge. This new route of midazolam administration with the jet-injector allows pain-free and stress-free induction of anaesthesia after rapid placement of an intravenous catheter and prevents the transmission of infections.
Asunto(s)
Anestesia General/métodos , Midazolam/administración & dosificación , Preescolar , Relación Dosis-Respuesta a Droga , Vías de Administración de Medicamentos , Femenino , Humanos , Lactante , Inyecciones Intramusculares/métodos , Inyecciones a Chorro , MasculinoRESUMEN
During the inflammatory response, tissues release histamine (H), substance P, serotonin (5-HT), prostaglandins and kinins, agents that mediate manifestations of inflammation such as pain, vasodilation, increased capillary permeability and smooth muscle contraction. In this study we investigated whether racemic (R[+]) ketamine (K) and its isomers are spasmolytic on intestinal smooth muscle contracted by inflammatory mediators, and whether the spasmolytic effect of K is related to changes in calcium influx through the L-type calcium channel or to an interaction of K with opioid receptors. We measured the contractions of guinea-pig ileum mounted in an organ bath containing Tyrode's solution gassed with 95% O2/5% CO2 at 37 degrees C. In the first protocol we determined the effect of K and its isomers on contractions induced by five mediators: 10(-7) M H, 10(-8) M substance P, 10(-8) M neurokinin A, 5 x 10(-9) M bradykinin and 5 x 10(-7) M 5-HT. For each of these mediators, we plotted concentration-response curves for the inhibitory effect of K, and from regression fitting of these curves, we calculated the IC50 concentration of K that inhibited the contraction by 50%). In the second protocol we measured the contraction induced by the calcium ionophore A23187 (5.0 x 10(-6) M), both alone and after 1.8-7.2 x 10(-4) M R(+/-)K. Then we examined how the inhibition caused by R(+/-)K was affected by increases in the concentration of extracellular calcium by adding calcium (1.8-7.2 x 10(-3) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Canales de Calcio/efectos de los fármacos , Calcio/metabolismo , Íleon/efectos de los fármacos , Ketamina/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Animales , Calcimicina/farmacología , Calcio/farmacología , Canales de Calcio/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Cobayas , Íleon/metabolismo , Íleon/fisiología , Técnicas In Vitro , Mediadores de Inflamación/farmacología , Ionóforos/farmacología , Ketamina/análogos & derivados , Masculino , Relajación Muscular/efectos de los fármacos , Naloxona/farmacología , Parasimpatolíticos/farmacologíaRESUMEN
BACKGROUND: As ketamine has local anaesthetic actions and local anaesthetics are known to have anti-inflammatory effects, ketamine could be expected to be an anti-inflammatory agent. Here we sought to determine whether ketamine is indeed anti-inflammatory in chemical peritonitis induced by HCl in rats. METHODS: Peritonitis was elicited by applying 0.02 M HCl on the surface of the cecum or appendix and quantified by measuring the extravasation of intravenously injected Evan's Blue bound to albumin extracted from those tissues. Three experimental sets were performed. In the first set, four groups of 10 rats each received: 1%, 2%, and 4% ketamine and 1% lidocaine. In the same animal, before induction of peritonitis one area was topically pre-treated with 0.9% saline (control site) and another area was topically pre-treated with 1%, 2% or 4% ketamine or 1% lidocaine (experimental site). In the second set, two groups of 10 rats each received: 2% ketamine or 1% lidocaine. Ten min after the induction of peritonitis, the control site was topically treated with 0.9% saline, while the experimental site was treated with 2% ketamine or 1% lidocaine. In the third set 20 rats, divided into two groups, were pre-treated either with 2% S(+)ketamine or 2% R(-)ketamine before the induction of peritonitis instead of the previously employed racemic version of the drug. RESULTS: Treatment of the cecum or appendix areas with ketamine or lidocaine before the induction of peritonitis decreased the extravasation of Evan's Blue-albumin from 5.7 +/- 0.7 micrograms/100 mg tissue to 4.5 +/- 0.8, N.S. with 1% ketamine; from 5.9 +/- 0.8 to 4.1 +/- 0.7, P < 0.01 with 2% ketamine; from 4.8 +/- 0.7 to 3.5 +/- 0.6, P < 0.05 with 4% ketamine and from 5.9 +/- 0.6 to 3.6 +/- 0.8, P < 0.01 with 1% lidocaine. Treatment of the areas of peritonitis with 2% ketamine or 1% lidocaine decreased the extravasation of Evan's Blue-albumin from 5.6 +/- 0.5 micrograms/100 mg tissue to 4.4 +/- 0.6, P < 0.05 and from 6.0 +/- 0.8 to 5.0 +/- 0.7, P < 0.01. Administration of the isomer S(+)ketamine to colonic areas before the induction of peritonitis reduced the extravasation of Evan's Blue-albumin from 6.5 +/- 0.7 micrograms/100 mg tissue to 4.1 +/- 0.6, P < 0.01; while the isomer R(-)ketamine was inactive. CONCLUSIONS: These results indicate that topically applied ketamine inhibited the development of chemical peritonitis. This action of racemic ketamine was due to the isomer S(+)ketamine.
Asunto(s)
Albúminas/antagonistas & inhibidores , Antiinflamatorios no Esteroideos/uso terapéutico , Ketamina/uso terapéutico , Peritonitis/tratamiento farmacológico , Administración Tópica , Albúminas/metabolismo , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Apéndice/efectos de los fármacos , Apéndice/metabolismo , Apéndice/patología , Ciego/efectos de los fármacos , Ciego/metabolismo , Ciego/patología , Azul de Evans , Extravasación de Materiales Terapéuticos y Diagnósticos , Ácido Clorhídrico/efectos adversos , Isomerismo , Ketamina/administración & dosificación , Lidocaína/administración & dosificación , Lidocaína/uso terapéutico , Masculino , Peritoneo/efectos de los fármacos , Peritoneo/metabolismo , Peritoneo/patología , Peritonitis/inducido químicamente , Peritonitis/metabolismo , Peritonitis/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Pipecuronium bromide, a new neuromuscular relaxant with steroidal structure, is devoid of effects on the autonomic nervous system and may be useful in patients where haemodynamic stability is mandatory. However, tracheal intubation may alter this haemodynamic profile. Therefore, we carried out a prospective double-blind study in 30 patients undergoing coronary artery bypass surgery with the purpose (1) of determining if intubation influenced the haemodynamic stability in patients paralyzed with pipecuronium and (2) of comparing plasma catecholamine concentrations after pipecuronium with those after pancuronium. Thirty patients were randomized into two groups receiving either pipecuronium 100 micrograms.kg-1 or pancuronium 150 micrograms.kg-1 after induction of anaesthesia with midazolam and fentanyl. Haemodynamic variables and plasma catecholamines were measured before and after induction, after the muscle relaxant three times and twice after intubation. After anaesthesia induction decreases in heart rate (HR), mean arterial pressure (MAP) and cardiac index (CI) were observed in both groups. These haemodynamic variables were unchanged after pipecuronium whereas after pancuronium HR increased from 53 +/- 11 b.min-1 to 64 +/- 9 b.min-1 after induction (P < 0.05) and CI from 2.5 +/- 0.5 L.min-1 to 3.0 +/- 0.8 L.min-1 (P < 0.05). Furthermore ECG signs of myocardial ischaemia appeared in four patients after pancuronium and the decay of plasma norepinephrine concentration was slower than with pipecuronium. We conclude that pipecuronium given after induction of anaesthesia is free of sympathomimetic or vagolytic activity and does not influence haemodynamic variables for up to ten minutes after tracheal intubation.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Catecolaminas/sangre , Puente de Arteria Coronaria , Frecuencia Cardíaca/efectos de los fármacos , Pancuronio/farmacología , Pipecuronio/farmacología , Anestesia Intravenosa , Método Doble Ciego , Electrocardiografía/efectos de los fármacos , Epinefrina/sangre , Femenino , Humanos , Intubación Intratraqueal , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Norepinefrina/sangre , Pancuronio/administración & dosificación , Pipecuronio/administración & dosificación , Estudios ProspectivosRESUMEN
Narcotic mu-agonists have been shown to increase the common bile duct pressure. With a recently introduced non-invasive ultrasonographic technique, we have demonstrated that morphine caused constriction of the common bile duct. We have now investigated the effect of highly potent, widely used mu-agonists, fentanyl and sufentanil on the diameter of the common bile duct using this technique in a double-blind, randomized study in 17 patients undergoing cholecystectomy. After premedication with midazolam and glycopyrrolate, anesthesia was induced by midazolam, 50 micrograms.kg-1 and thiopental, 3.0-5.0 mg.kg-1. Tracheal intubation was facilitated by succinyl-choline, 1.0 mg.kg-1 and muscle relaxation maintained with vecuronium. Anesthesia was maintained with enflurane or isoflurane and nitrous oxide in oxygen. The diameter of the common bile duct was determined before and at 4 and 8 minutes after the administration of the study drugs. One way analysis of variance and paired t-test were used for statistical analysis. P < 0.05 was considered significant. No significant change in common bile duct diameter was observed after i.v. placebo, nor were there any significant changes after fentanyl or sufentanil administration. Since the baseline common bile duct diameters were not significantly different among the three groups, fentanyl or sufentanil in the doses used had no more effect than a placebo on common bile duct diameter. It is concluded that fentanyl and sufentanil caused no effect on the common bile duct, therefore, these mu-agonists seem to be safe in patients in whom spasm of the common bile ducts should be avoided.
Asunto(s)
Conducto Colédoco/efectos de los fármacos , Fentanilo/farmacología , Sufentanilo/farmacología , Adulto , Conducto Colédoco/diagnóstico por imagen , Método Doble Ciego , Femenino , Humanos , Masculino , UltrasonografíaRESUMEN
Butorphanol and nalbuphine, narcotic agonist-antagonists were shown to cause no increase in biliary pressure in contrast to morphine in dogs or men. A non-invasive, ultrasonographic technique confirmed that morphine caused constriction of the common bile duct while placebo caused no effect. To prove the lack of constrictive effect of butorphanol and nalbuphine on the common bile duct, the changes in its diameter were measured following placebo or the two agonist-antagonists by ultrasonography. In a double-blind, randomized study, 17 patients undergoing open cholecystectomy were evaluated. No morphine or opioids were allowed for 12 hours prior to the study. After premedication with midazolam and glycopyrrolate, anesthesia was induced by midazolam, 50 micrograms.kg-1 and thiopental, 3.0-5.0 mg.kg-1. Tracheal intubation was facilitated by succinylcholine 1.0 mg.kg-1 and muscle relaxation was maintained with vecuronium. Anesthesia was maintained with isoflurane or enflurane and nitrous oxide in oxygen. After imaging the common bile duct by ultrasonography, placebo, nalbuphine 0.3 mg.kg-1 or butorphanol 40 micrograms.kg-1 were injected intravenously. The diameter of the common bile duct was measured before and at 4 and 8 minutes after drug administration. One-way analysis of variance and paired t-test were utilized for statistical analysis. P < 0.05 was considered significant. No significant changes in the common bile duct diameter was observed after placebo administration, nor was any change observed after either nalbuphine or butorphanol as compared to the baseline. The comparison of three groups of patients showed no statistically significant difference.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Butorfanol/farmacología , Conducto Colédoco/efectos de los fármacos , Conducto Colédoco/diagnóstico por imagen , Nalbufina/farmacología , Adulto , Análisis de Varianza , Conducto Colédoco/anatomía & histología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , UltrasonografíaRESUMEN
Although the increase in the common bile duct pressure in response to morphine has been repeatedly reported in experimental animals and humans, this is the first double-blind non-invasive, ultrasonographic study designed to demonstrate constriction of the common bile duct caused by i.v. administration of morphine in surgical patients. In a double-blind, placebo-controlled, randomized study, 12 patients undergoing open cholecystectomy were enrolled. No opioids were allowed for 12 hours prior to the study. After premedication with midazolam and glycopyrrolate, anesthesia was induced by midazolam, 50 micrograms/kg-1 and thiopental, 3.0-5.0 mg/kg-1. Tracheal intubation was facilitated by succinylcholine, 1.0 mg/kg-1 and muscle relaxation was maintained with vecuronium. Anesthesia was maintained with enflurane and nitrous oxide in oxygen. After imaging the common bile duct by ultrasonography, placebo or morphine, 0.2 mg/kg-1 was injected intravenously. The diameter of the common bile duct was measured before and 4 and 8 minutes after the drug. Student t-test was utilized for statistical analysis. P < 0.05 was considered significant. No significant change in common bile duct diameter was observed after placebo administration. Morphine caused a significant reduction in the diameter of the common bile duct. Before morphine, the mean +/- SD diameter was 9.5 +/- 3.3 mm; after morphine at 4 and 8 minutes, 7.2 +/- 2.1 and 5.8 +/- 2.1 mm, respectively. It is concluded that ultrasonography in a double-blind placebo-controlled design has proven to be a valid method for the evaluation of the effect of drugs on the common bile duct.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Colecistectomía , Conducto Colédoco/diagnóstico por imagen , Morfina/efectos adversos , Adulto , Conducto Colédoco/efectos de los fármacos , Constricción Patológica/inducido químicamente , Constricción Patológica/diagnóstico por imagen , Método Doble Ciego , Femenino , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Premedicación , UltrasonografíaRESUMEN
Secobarbital is still widely used as a hypnotic and morphine as an analgesic perioperatively in surgical patients. Their combination is often used as a preanesthetic medication. Although their ventilatory depressant effect is recognized, the resulting blood gas changes have not been studied as yet adequately in a sufficiently large population of healthy volunteers. Therefore this study was undertaken. Thirty healthy volunteers who gave valid written consent were studied. Secobarbital 2.0 mg/kg intravenously caused a significant (P < .05) decrease in arterial oxygen pressure (PaO2), peaking at 10 minutes (n = 10; mean age, 23.4 years). Morphine, 0.2 mg/kg intravenously also caused a significant decrease in PaO2 at 5 minutes (n = 10; mean age, 26.3 years). The combination of the same doses of morphine and secobarbital caused a significantly (P < .01) greater decrease in PaO2 at 5 and 10 minutes than the sole administration of either drug (n = 10; mean age, 23.5 years). Arterial oxygen pressure remained significantly (P < .05) reduced for 30 minutes. Although the PaCO2 increases after secobarbital and morphine did not reach statistical significance, their combination caused a significant (P < .05) increase in PaCO2. Both secobarbital and morphine alone caused significant (P < .05) decrease in pHa at 30 minutes. Their combination caused a significant (P < .01) reduction in pHa from 5 minutes until 60 minutes. In conclusion, both secobarbital and morphine alone caused ventilatory depression. The duration of ventilatory depression was greater with the intravenous combination than with either drug alone.