[effect Of Ropivacaine Combined With Pancuronium On Neuromuscular Transmission And Effectiveness Of Neostigmine And 4-aminopyridine For Blockade Reversal: Experimental Study].

The local anesthetic effects on neuromuscular junction and its influence on blockade produced by nondepolarizing neuromuscular blockers are still under-investigated; however, this interaction has been described in experimental studies and in humans. The aim of this study was to evaluate in vitro the interaction between ropivacaine and pancuronium, the influence on transmission and neuromuscular blockade, and the effectiveness of neostigmine and 4-aminopyridine to reverse the blockade. Rats were divided into groups (n=5) according to the study drug: ropivacaine (5μgmL(-1)); pancuronium (2μg.mL(-1)); ropivacaine+pancuronium. Neostigmine and 4-aminopyridine were used at concentrations of 2μgmL(-1) and 20μgmL(-1), respectively. The effects of ropivacaine on membrane potential and miniature end-plate potential, the amplitude of diaphragm responses before and 60minutes after the addition of ropivacaine (degree of neuromuscular blockade with pancuronium and with the association of pancuronium-ropivacaine), and the effectiveness of neostigmine and 4-aminopyridine on neuromuscular block reversal were evaluated. Ropivacaine did not alter the amplitude of muscle response (the membrane potential), but decreased the frequency and amplitude of the miniature end-plate potential. Pancuronium blockade was potentiated by ropivacaine, and partially and fully reversed by neostigmine and 4-aminopyridine, respectively. Ropivacaine increased the neuromuscular block produced by pancuronium. The complete antagonism with 4-aminopyridine suggests presynaptic action of ropivacaine.

Validation of an HPLC analytical method for determination of pancuronium bromide in pharmaceutical injections

Pancuronium bromide is used with general anesthesia in surgery for muscle relaxation and as an aid to intubation. A high performance liquid chromatographic method was fully validated for the quantitative determination of pancuronium bromide in pharmaceutical injectable solutions. The analytical method was performed on an amino column (Luna 150mm4.6mm, 5m). The mobile phase was composed of acetonitrile:water containing 50mmol L-1 of 1-octane sulfonic acid sodium salt (20:80v/v) with a flow rate of 1.0mL min-1 and ultraviolet (UV) detection at 210nm. The proposed analytical method was compared with that described in the British Pharmacopoeia.

Effects of paralysis with pancuronium bromide on joint mobility in premature infants.

To study the effects of muscle paralysis on joint mobility, we compared eight premature infants treated with pancuronium bromide with a control group. A significant reduction was observed in hip and knee flexion, and in ankle dorsal extension, which tended to resolve in time. We conclude that muscle paralysis reduces the mobility of selected joints; spontaneous activity appears to prevent long-term contractures.

PRESYNAPTIC AND POSTSYNAPTIC MECHANISMS INVOLVED IN TETANIC FADE INDUCED BY PANCURONIUM IN THE ISOLATED RAT MUSCLE

The mechanisms underlying the fade of the tetanic contraction induced by pancuronium were studied in vitro by means of myographical and electrophysiological techniques in the extensor digitorum longus muscle of the rat. Pancuronium (0.5 mu mol/l) induced a complete fade of the tetanic contraction while leaving the twitch unaffected. At the same concentration it decreased the amplitude and increased the tetanic rundown of trains of endplate potentials (e.p.ps) evoked in the frequency of 50 Hz. The electrophysiological changes induced by pancuronium were due to decreases in both quantal sizes and quantal contents of the e.p.ps. The former effect was the result of a postsynaptic competitive action and the latter of a presynaptic inhibitory action of that compound. The decrease in quantal. content affected the e.p.ps starting from the first in the train and became larger during the generation of the sequence of e.p.ps. This intensified their tetanic rundown. It is concluded that the fade of the tetanic contraction induced by pancuronium is due to a summation of pre- and postsynaptic actions and, therefore, not only to an increase in the tetanic rundown of e.p.ps. Possible explanations for the distinct abilities of neuromuscular blockers in affecting tetani and twitches in a differential manner are also discussed.

Pancuronium dose refinement in experimental pigs used in cardiovascular research

To quantify the dose of pancuronium required to obtain moderate neuromuscular blockade as monitored by acceleromyography (NMB(mod) : train-of-four count of ≤2) as a part of a balanced anaesthetic protocol in pigs used in cardiovascular research.

Determination of Vecuronium Bromide in Pharmaceuticals: Development, Validation and Comparative Study of HPLC and CZE Analytical Methods

Vecuronium bromide is a neuromuscular blocking agent used for anesthesia to induce skeletal muscle relaxation. HPLC and CZE analytical methods were developed and validated for the quantitative determination of vecuronium bromide. The HPLC method was achieved on an amino column (Luna 150 x 4.6 mm, 5 mu m) using UV detection at 205 nm. The mobile phase was composed of acetonitrile:water containing 25.0 mmol L(-1) of sodium phosphate monobasic (50:50 v/v), pH 4.6 and flow rate of 1.0 mL min(-1). The CZE method was achieved on an uncoated fused-silica capillary (40.0 cm total length, 31.5 cm effective length and 50 mu m i.d.) using indirect UV detection at 230 nm. The electrolyte comprised 1.0 mmol L(-1) of quinine sulfate dihydrate at pH 3.3 and 8.0% of acetonitrile. The results were used to compare both techniques. No significant differences were observed (p > 0.05).

Intratracheal suctioning in sick preterm infants: prevention of intracranial hypertension and cerebral hypoperfusion by muscle paralysis.

In a prospective nonrandomized study, using each baby as his or her own control, we compared intracranial pressure (anterior fontanel pressure as measured with the Digilab pneumotonometer), cerebral perfusion pressure, BP, heart rate, transcutaneous Po2, and transcutaneous Pco2 before, during, and after endotracheal suctioning, with and without muscle paralysis, in 28 critically ill preterm infants with respiratory distress syndrome. With suctioning, there was a small but significant increase in intracranial pressure in paralyzed patients (from 13.7 [mean] +/- 4.4 mm Hg [SD] to 15.8 +/- 5.2 mm Hg) but a significantly larger (P less than .001) increase when they were not paralyzed (from 12.5 +/- 3.6 to 28.5 +/- 8.3 mm Hg). Suctioning led to a slight increase in BP with (from 45.3 +/- 9.1 to 48.0 +/- 8.7 mm Hg) and without muscle paralysis (from 45.1 +/- 9.4 to 50.0 +/- 11.7 mm Hg); but there was no significant difference between the two groups. The cerebral perfusion pressure in paralyzed infants did not show any significant change before, during, and after suctioning (31.5 +/- 9.1 mm Hg before v 32.0 +/- 8.7 mm Hg during suctioning), but without muscle paralysis cerebral perfusion pressure decreased (P less than .001) from 32.8 +/- 9.7 to 21.3 +/- 13.1 mm Hg. Suctioning induced a slight decrease in mean heart rate and transcutaneous Po2, but pancuronium did not alter these changes. There was no statistical difference in transcutaneous Pco2 before, during, and after suctioning with and without muscle paralysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Paralysis of ventilated newborn babies does not influence resistance of the total respiratory system.

Paralysis with pancuronium bromide is used in newborn infants to facilitate ventilatory support during respiratory failure. Changes in lung mechanics have been attributed to paralysis. The aim of this study was to examine whether or not paralysis per se has an influence on the passive respiratory mechanics, resistance (Rrs) and compliance (Crs) of the respiratory system in newborn infants. In 30 infants with acute respiratory failure, Rrs was measured during paralysis with pancuronium bromide and after stopping pancuronium bromide (group A). Rrs was also measured in an additional 10 ventilated infants in a reversed fashion (group B): Rrs was measured first in nonparalysed infants and then they were paralysed, mainly for diagnostic procedures, and the Rrs measurement repeated. As Rrs is highly dependent on lung volume, several parameters, that depend directly on lung volume were recorded: inspiratory oxygen fraction (FI,O2), arterial oxygen tension/alveolar oxygen tension (a/A) ratio and volume above functional residual capacity (FRC). In group A, the Rrs was not different during (0.236+/-0.09 cmH2O x s x mL(-1)) and after (0.237+/-0.07 cmH2O x s x mL(-1)) paralysis. Also, in group B, Rrs did not change (0.207+/-0.046 versus 0.221+/-0.046 cm x s x mL(-1) without versus with pancuronium bromide). FI,O2, a/A ratio and volume above FRC remained constant during paralysis. These data demonstrate that paralysis does not influence the resistance of the total respiratory system in ventilated term and preterm infants when measured at comparable lung volumes.

Sugammadex versus neostigmina en la reversión de la relajación neuromuscular en neurocirugía. Experimento clínico. Reporte preliminar

Existen grupos quirúrgicos específicos donde es mandatorio el uso de relajantes neuromusculares no despolarizantes, como es el caso de los pacientes llevados a procedimiento de neurocirugía; debido a sus características particulares el rocuronio es una buena alternativa para este tipo de procedimientos, ya sea en bolos o en infusión. Sin embargo la relajación residual y los efectos adversos de los medicamentos para revertir la relajación neuromuscular deben tenerse en cuenta en este grupo de pacientes en particular. El presente trabajo busca comparar la reversión de la relajación de infusiones de rocuronio, con Neostigmina mas Atropina vs la reversión con Sugammadex en pacientes llevados a manejo quirúrgico de lesiones supratentoriales por parte del servicio de neurocirugía de la Fundación Cardioinfantil, evaluando complicaciones durante la administración de los medicamentos y 24 horas posoperatorias, así como los tiempos para extubación y salida de salas de cirugía. Estudio con características de experimento prospectivo, aleatorizado, ciego, controlado. En este documento se realiza un reporte preliminar descriptivo de 14 pacientes reclutados hasta la actualidad.

Differential effects of neuromuscular blockers on twitches and tetani in the isolated rat muscle: a multiple comparison study using simultaneous confidence intervals

In the present work a comparative quantitative evaluation of the differential effects of neuromuscular blockers on twitches and tetani was performed, encompassing: atracurium, cisatracurium, mivacurium, pancuronium, rocuronium and vecuronium. The sciatic nerve-extensor digitorum longus muscle of the rat was used, in vitro. Twitches were evoked at 0.1 Hz and tetani at 50 Hz. The differential effects of the studied compounds on twitches and tetani were statistically compared using simultaneous confidence intervals for the ratios between mean IC(50) for the block of twitches and mean IC(50) for the block of tetani. The results of ratios of mean IC(50) together with their corresponding 95% simultaneous confidence intervals were: vecuronium: 2.5 (1.8-3.5); mivacurium: 3.8 (3.0-4.9); pancuronium: 3.9 (2.0-7.6); rocuronium: 6.1 (3.8-9.9); atracurium: 9.0 (6.4-12.6); cisatracurium: 13.1 (6.0-28.4). Using the criteria that neuromuscular blockers displaying disjunct confidence intervals for the ratios of mean IC(50) differ statistically with regard to differential effects on twitches and tetani, significant differences in ratios of IC(50) were detected in the following cases: vecuronium vs. rocuronium, vs. atracurium and vs. cisatracurium and mivacurium vs: cisatracurium and vs. atracurium. The results show that the magnitude of the differential effects of neuromuscular blockers on twitches and tetani, as evaluated in the present work in the form of ratios of mean IC(50), does not depend on the chemical structure (comparing steroidal and isoquinolinic compounds), but seems to depend on differential pre- and post-synaptic effects of the compounds. It is also suggested that the greater the ability of a compound to block twitches and tetani in a differential manner, the safer is the compound from the clinical anesthesiology viewpoint.

The tof-guard neuromuscular transmission monitor and its use in horses

Quando da utilização de bloqueadores neuromusculares, já foi enfatizado na literatura médica humana, que é de vital imporância a monitoração do bloqueio neuromuscular e que estes agentes nunca devem ser utilizados sem a mesma. O objetivo deste estudo foi o de avaliar o uso do monitor da transmissão neuromuscular TOF-Guard em eqüinos. Para tanto, doze eqüinos foram separados aleatoriamente para receberem como bloqueadores neuromusculares o pancurônio ou o atracúrio. Todos os eqüinos foram pré-medicados com romifidina, induzidos com diazepam e quetamina e mantidos com halotano. Foi administrado o atracúrio ou o pancurônio, seguindo-se a apnéia e início da ventilação mecânica controlada. O tempo entre a administração do relaxante muscular e a obtenção de um bloqueio máximo (T1=0), o retorno do T1 para 25% e da razão do TOF para 0,7 e o tempo do retorno do T1 de 25 para 75% foram mensurados. Concluiu-se que é de grande importância a monitoração do bloqueio neuromuscular quando da utilização de um bloqueador neuromuscular não-despolarizante, uma vez que ela torna o ato anestésico e cirúrgico mais seguro, com a utilização de doses adequadas que inviabilizam a superficialização do bloqueio durante o procedimento cirúrgico. O monitor TOF-Guard mostrou ser uma boa opção para a monitoração do bloqueio neuromuscular em eqüinos.

Evaluation of laryngeal mask as an alternative to endotracheal intubation in cats anesthetized under spontaneous or controlled ventilation

Objective To compare the cardiorespiratory effects and incidence of gastroesophageal reflux with the use of a laryngeal mask airway (LMA) or endotracheal tube (ET) in anesthetized cats during spontaneous (SV) or controlled ventilation (CV).Study design Prospective randomized experimental trial.Animals Thirty-two adult crossbred cats, weighing 2.7 +/- 0.4 kg.Methods the cats were sedated with intramuscular (IM) methotrimeprazine (0.5 mg kg(-1)) and buprenorphine (0.005 mg kg(-1)), followed 30 minutes later by induction of anesthesia with intravenous (IV) thiopental (12.5-20 mg kg(-1)). An ET was used in 16 cats and an LMA in the remaining 16 animals. Anesthesia was maintained with 0.5 minimum alveolar concentration (0.6%) of halothane in oxygen using a Mapleson D breathing system. Cats in both groups were further divided into two equal groups (n = 8), undergoing either SV or CV. Neuromuscular blockade with pancuronium (0.06 mg kg(-1)) was used to facilitate CV. Heart and respiratory rates, direct arterial blood pressure, capnometry (PE'CO2) and arterial blood gases were measured. Gastric reflux and possible aspiration was investigated by intragastric administration of 5 mL of radiographic contrast immediately after induction of anesthesia. Cervical and thoracic radiographs were taken at the end of anesthesia. Data were analyzed using ANOVA followed by Student-Newman-Keuls, Kruskal-Wallis or Friedman test where appropriate.Results Values for PaCO2 and PE'CO2 were higher in spontaneously breathing cats with the LMA when compared with other groups. Values of PaO2 and hemoglobin oxygen saturation did not differ between groups. Gastroesophageal reflux occurred in four of eight and two of eight cats undergoing CV with ET or LMA, respectively. There was no tracheal or pulmonary aspiration in any cases.Conclusions and clinical relevance the use of an LMA may be used as an alternative to endotracheal intubation in anesthetized cats. Although aspiration was not observed, gastric reflux may occur in mechanically ventilated animals.

Use of bispectral index to monitor depth of anesthesia in isoflurane-anesthetized dogs

Objective-To evaluate the correlation between the bispectral index (BIS) and end-tidal isoflurane (ETISO) concentration and compare the use of 3 BIS sensor positions in dogs.Animals-6 adult dogs.Procedures-Mechanically ventilated dogs received pancuronium, and depth of anesthesia was altered by increasing ETISO concentration from 1.5% to 2.3% and 3.0%. The BIS, suppression ratio (relative percentage of isoelectric electroencephalographic waveforms), and signal quality index (SQI) were recorded at each ET, so concentration for each of 3 BIS sensor positions (frontal-occipital, bifrontal, and frontal-temporal positions).Results-The BIS and ETISO concentration were poorly correlated-, regardless of sensor positioning, mean BIS values did not change significantly as ETISO was increased. At 3% isoflurane, regardless of sensor positioning, there was an increase in suppression ratio coincident with BIS < 40 in some dogs, whereas paradoxic increases in BIS (> 60) were recorded in others. Furthermore, at 3.0% isoflurane, the SQI was significantly lower for the bifrontal sensor position (compared with values for the other positions), but low SQI values prevented recording of BIS values from the frontal-occipital sensor position in 2 dogs. Overall, BIS values derived from the 3 sensor positions did not differ.Conclusions and Clinical Relevance-In dogs, BIS values may not reflect changes in depth of isoflurane anesthesia in the absence of noxious stimulation. of the 3 sensor positions, frontal-temporal positioning provided better correlation with changes in depth of anesthesia induced via changes in isoflurane concentrations. However, the sensor placements yielded similar results at SQI values > 50.

Comparison of a sidestream capnograph and a mainstream capnograph in mechanically ventilated dogs

Objective-To compare the ability of a sidestream capnograph and a mainstream capnograph to measure end-tidal CO2 (ETCO2) and provide accurate estimates of Paco(2) in mechanically ventilated dogs.Design-Randomized, double Latin square.Animals-6 healthy adult dogs.Procedure-Anesthesia was induced and neuromuscular blockade achieved by IV administration of pancuronium bromide. Mechanical ventilation was used to induce conditions of standard ventilation, hyperventilation, and hypoventilation. While tidal volume was held constant, changes in minute volume ventilation and Paco(2) were made by changing the respiratory rate. Arterial blood gas analysis was performed and ETCO2 measurements were obtained by use of either a mainstream or a sidestream capnographic analyzer.Results-A linear regression model and bias analysis were used to compare Paco(2) and ETCO2 measurements; ETCO2 measurements obtained by both capnographs correlated well with Paco(2). Compared with Paco(2), mainstream ETCO2 values differed by 3.15 +/- 4.89 mm Hg (mean bias +/- SD), whereas the bias observed with the sidestream ETCO2 system was significantly higher (5.65 +/- 5.57 mm Hg). Regardless of the device used to measure ETCO2, bias increased as Paco(2) exceeded 60 mm Hg.Conclusions and Clinical Relevance-Although the mainstream capnograph was slightly more accurate, both methods of ETCO2 measurement correlated well with Paco(2) and reflected changes in the ventilatory status. However, ETCO2 values > 45 mm Hg may inaccurately reflect the severity of hypoventilation as Paco(2) may be underestimated during conditions of hypercapnia (Paco(2) > 60 mm Hg).