Effect of preoperative ivabradine on hemodynamics during elective off-pump CABG.

Background: Ivabradine is a specific heart rate (HR)-lowering agent which blocks the cardiac pacemaker If channels. It reduces the HR without causing a negative inotropic or lusitropic effect, thus preserving ventricular contractility. The authors hypothesized that its usefulness in lowering HR can be utilized in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. Objective: To study the effects of preoperative ivabradine on hemodynamics (during surgery) in patients undergoing elective OPCAB surgery. Methods: Fifty patients, New York Heart Association (NYHA) class I and II, were randomized into group I (control, n = 25) and group II (ivabradine group, n = 25). In group I, patients received the usual anti-anginal medications in the preoperative period, as per the institutional protocol. In group II, patients received ivabradine 5 mg twice daily for 3 days before surgery, in addition to the usual anti-anginal medications. Anesthesia was induced with fentanyl, thiopentone sodium, and pancuronium bromide as a muscle relaxant and maintained with fentanyl, midazolam, pancuronium bromide, and isoflurane. The hemodynamic parameters [HR and mean arterial pressure (MAP)] and pulmonary artery (PA) catheter-derived data were recorded at the baseline (before induction), 3 min after the induction of anesthesia at 1 min and 3 min after intubation and at 5 min and 30 min after protamine administration. Intraoperatively, hemodynamic data (HR and MAP) were recorded every 10 min, except during distal anastomosis of the coronary arteries when it was recorded every 5 min. Post-operatively, at 24 hours, the levels of troponin T and brain natriuretic peptide (BNP) were measured. This trial's CTRI registration number is CTRI/005858. Results: The HR in group II was lower when compared to group I (range 59.6-72.4 beats/min and 65.8-80.2 beats/min, respectively) throughout the study period. MAP was comparable [range (78.5-87.8 mm Hg) vs. (78.9-88.5 mm Hg) in group II vs. group I, respectively] throughout the study period. Intraoperatively, 5 patients received metoprolol in group I to control the HR, whereas none of the patients in group II required metoprolol. The incidence of preoperative bradycardia (HR <60 beats/min) was higher in group II (20%) vs. group I (8%). There was no difference in both the groups in terms of troponin T and BNP level after 24 hours, time to extubation, requirement of inotropes, incidence of arrhythmias, in-hospital morbidity, and 30-day mortality. Conclusion: Ivabradine can be safely used along with other anti-anginal agents during the preoperative period in patients undergoing OPCAB surgery. It helps to maintain a lower HR during surgery and reduces the need for beta-blockers in the intraoperative period, a desirable and beneficial effect in situations where the use of beta-blockers may be potentially harmful. Further studies are needed to evaluate the beneficial effects of perioperative Ivabradine in patients with moderate-to-severe left ventricular dysfunction.

Deep Tissue Incision Enhances Spinal Dorsal Horn Neuron Activity During Static Isometric Muscle Contraction in Rats.

Translational correlates to pain with activities after deep tissue injury have been rarely studied. We hypothesized that deep tissue incision causes greater activation of nociception-transmitting neurons evoked by muscle contraction. In vivo neuronal activity was recorded in 203 dorsal horn neurons (DHNs) from 97 rats after sham, skin-only, or skin + deep muscle incision. We evaluated DHN responses to static, isometric muscle contractions induced by direct electrical stimulation of the muscle. The effect of pancuronium on DHN response to contractions was also examined. Approximately 50% of DHNs with receptive fields in the hindpaw were excited during muscle contraction. One-second .5- and 1.0-g muscle contractions produced greater DHN activity after skin + deep muscle incision (median [interquartile range], 32 [5-39] impulses, P = .021; and 36 [26-46] impulses, P = .006, respectively) than after sham (6 [0-21] and 15 [8-32] impulses, respectively). Neuromuscular blockade with pancuronium inhibited the muscle contractions and DHN activation during electrical stimulation, demonstrating contraction-induced activation. The greater response of spinal DHNs to static muscle contraction after skin + deep muscle incision may model and inform mechanisms of dynamic pain after surgery. PERSPECTIVE: Completion of various activities is an important milestone for recovery and hospital discharge after surgery. Skin + deep muscle incision caused greater activation of nociception-transmitting DHNs evoked by muscle contraction compared with skin-only incision. This result suggests an important contribution of deep muscle injury to activity-evoked hyperalgesia after surgery.

Association between levobupivacaine and pancuronium. Interference in neuromuscular transmission and blockade in rats

ABSTRACT PURPOSE: To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro. METHODS: Thirty rats were distributed into groups (n = 5) according to the drug used alone or in combination: Group I - levobupivacaine (5 µg.mL-1); Group II - pancuronium (2 µg.mL-1); Group III - pancuronium (2 µg.mL-1) + levobupivacaine (5µg.mL-1). The following parameters were evaluated: 1) amplitude of diaphragmatic response to indirect stimulation, before and 60 minutes after the addition of levobupivacaine and pancuronium alone, and after the addition of levobupivacaine combined with pancuronium; 2) membrane potentials (MP) and miniature endplate potentials (MEPP). RESULTS: Levobupivacaine alone did not alter the amplitude of muscle response and MP. In preparations previoulsy exposed to levobupivacaine, the block with pancuronium was significantly denser (90.2 ± 15.2%), showing a significant difference (p=0.031) in comparison to the block produced by pancuronium alone (48.9% ± 9.8%). There was a decrease in the frequency and amplitude of MEPPs. CONCLUSION: Levobupivacaine potentiated the neuromuscular blockade produced by pancuronium, confirming a presynaptic action by a decrease in miniature endplate potentials.

Effect of ropivacaine combined with pancuronium on neuromuscular transmission and effectiveness of neostigmine and 4-aminopyridine for blockade reversal: experimental study / Efeito da associação ropivacaina-pancurônio na transmissão neuromuscular e eficácia da neostigmine e 4-aminopiridina na reversão do bloqueio: estudo experimental / Efecto de la asociación ropivacaína-pancuronio en la transmisión neuromuscular. Eficacia de la neostigmina y 4-aminopiridina en la reversión del bloqueo. Estudio experimental

BACKGROUND AND OBJECTIVES: 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. METHODS: Rats were divided into groups (n = 5) according to the study drug: ropivacaine (5 µg mL-1); pancuronium (2 µg mL-1); ropivacaine + pancuronium. Neostigmine and 4-aminopyridine were used at concentrations of 2 µg mL-1 and 20 µg mL-1, respectively. The effects of ropivacaine on membrane potential and miniature endplate potential, the amplitude of diaphragm responses before and 60 min 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. RESULTS: Ropivacaine did not alter the amplitude of muscle response (the membrane potential), but decreased the frequency and amplitude of the miniature endplate potential. Pancuronium blockade was potentiated by ropivacaine, and partially and fully reversed by neostigmine and 4-aminopyridine, respectively. CONCLUSIONS: Ropivacaine increased the neuromuscular block produced by pancuronium. The complete antagonism with 4-aminopyridine suggests presynaptic action of ropivacaine. .

JUSTIFICATIVA E OBJETIVOS: Os efeitos dos anestésicos locais na junção neuromuscular e sua influência no bloqueio produzido por bloqueadores neuromusculares não-despolarizantes é ainda alvo de pouca investigação, no entanto esta interação tem sido descrita em trabalhos experimentais e em humanos. O objetivo deste estudo foi avaliar in vitro, a interação da ropivacaína com o pancurônio, a influência na transmissão e bloqueio neuromuscular e a efetividade da neostigmina e 4-aminopiridina na reversão do bloqueio. MÉTODO: Ratos foram distribuídos em grupos (n = 5) de acordo com o fármaco estudado: ropivacaína (5 µg mL-1); pancurônio (2 µg mL-1); ropivacaína + pancurônio. A neostigmina e a 4-aminopiridina foram usadas nas concentrações de 2 µg mL-1 e 20 µg.mL-1, respectivamente. Avaliou-se: 1) efeitos da ropivacaína sobre o potencial de membrana e potenciais de placa terminal em miniatura; 2) a amplitude das respostas do diafragma antes e 60 minutos após a adição da ropivacaína; o grau de bloqueio neuromuscular com o pancurônio e com a associação pancurônio - ropivacaína; 3) a efetividade da neostigmina e 4-aminopiridina na reversão do bloqueio neuromuscular. RESULTADOS: A ropivacaína não alterou a amplitude das respostas musculares, os potenciais de membrana, mas diminuiu a frequência e a amplitude dos potenciais de placa terminal em miniatura. O bloqueio produzido pelo pancurônio foi potencializado pela ropivacaína, e parcial e totalmente revertido pela neostigmina e 4-aminopiridina, respectivamente. CONCLUSÕES: A ropivacaína potencializou o bloqueio neuromuscular produzido pelo pancurônio. O antagonismo completo com a 4-aminopiridina sugere ação pré-sináptica da ropivacaína. .

JUSTIFICACIÓN Y OBJETIVOS: Los efectos de los anestésicos locales en la unión neuromuscular y su influencia en el bloqueo producido por bloqueantes neuromusculares no-despolarizantes todavía son poco investigados, sin embargo, esta interacción ha sido descrita en trabajos experimentales y en seres humanos. El objetivo de este estudio fue evaluar in vitro la interacción de la ropivacaína con el pancuronio, la influencia en la transmisión y bloqueo neuromuscular y la efectividad de la neostigmina y 4-aminopiridina en la reversión del bloqueo. MÉTODO: Unos ratones fueron distribuidos en grupos (n = 5) de acuerdo con el fármaco estudiado: ropivacaína (5 µg/ml-1); pancuronio (2 µg/ml-1); ropivacaína + pancuronio. La neostigmina y la 4-aminopiridina fueron usadas en concentraciones de 2 µg/ml-1 y 20 µg/ml-1, respectivamente. Evaluamos: 1) efectos de la ropivacaína sobre el potencial de membrana y potenciales de placa terminal en miniatura; 2) la amplitud de las respuestas del diafragma antes y 60 min después de la adición de la ropivacaína; el grado de bloqueo neuromuscular con el pancuronio y con la asociación pancuronio-ropivacaína; 3) la efectividad de la neostigmina y 4-aminopiridina en la reversión del bloqueo neuromuscular. RESULTADOS: La ropivacaína no alteró la amplitud de las respuestas musculares, los potenciales de membrana, pero disminuyó la frecuencia y la amplitud de los potenciales de placa terminal en miniatura. El bloqueo producido por el pancuronio fue potenciado por la ropivacaína, y parcial y totalmente revertido por la neostigmina y 4-aminopiridina, respectivamente. CONCLUSIONES: La ropivacaína potenció el bloqueo neuromuscular producido por el pancuronio. El antagonismo completo con la 4-aminopiridina muestra una acción presináptica de la ropivacaína. .

Adenosine A(2A) receptor antagonists are broad facilitators of antinicotinic neuromuscular blockade monitored either with 2 Hz train-of-four or 50 Hz tetanic stimuli.

1. The 2 Hz train-of-four ratio (TOF(ratio)) is used to monitor the degree of patient curarization. Using a rat phrenic nerve-hemidiaphragm preparation, we showed that antinicotinic agents, such as hexamethonium, d-tubocurarine and pancuronium, but not cisatracurium, decreased contractions produced by physiological nerve activity patterns (50 Hz) more efficiently than those caused by 2 Hz trains. Uncertainty about the usefulness of the TOF(ratio) to control safe recovery from curarization prompted us to investigate the muscarinic and adenosine neuromodulation of tetanic (50 Hz) fade induced by antinicotinic agents at concentrations that cause a 25% reduction in the TOF(ratio) (TOF(fade)). 2. Tetanic fade caused by d-tubocurarine (1.1 µmol/L), pancuronium (3 µmol/L) and hexamethonium (5.47 mmol/L) was attenuated by blocking presynaptic inhibitory muscarinic M(2) and adenosine A(1) receptors with methoctramine (1 µmol/L) and 1,3-dipropyl-8-cyclopentylxanthine (2.5 nmol/L), respectively. These compounds enhanced rather than decreased tetanic fade induced by cisatracurium (2.2 µmol/L), but they consistently attenuated cisatracurium-induced TOF(fade). The effect of the M(1) receptor antagonist pirenzepine (10 nmol/L) on fade produced by antinicotinic agents at 50 Hz was opposite to that observed with TOF stimulation. Blockade of adenosine A(2A) receptors with ZM 241385 (10 nmol/L) attenuated TOF(fade) caused by all antinicotinic drugs tested, with the exception of the 'pure' presynaptic nicotinic antagonist hexamethonium. ZM 241385 was the only compound tested in this series that facilitated recovery from tetanic fade produced by cisatracurium. 3. The data suggest that distinct antinicotinic relaxants interfere with fine-tuning neuromuscular adaptations to motor nerve stimulation patterns via activation of presynaptic muscarinic and adenosine receptors. These results support the use of A(2A) receptor antagonists together with atropine to facilitate recovery from antinicotinic neuromuscular blockade.

SUGAMADEX: novos horizontes para a reversão do bloqueio neuromuscular / SUGAMMADEX: new horizons for the reversal of neuromuscular blockade

O sugamadex é uma droga nova e revolucionária desenvolvida como antagonista seletivo dos agentes bloqueadores neuromusculares (ABNM) esteroides (rocurônio > vecurônio ¼ pancurônio). O medicamento é uma y-ciclodextrina modificada e hidrossolúvel que forma um composto estável com o ABNM na razão de 1:1. Ele se liga ao ABNM livre no plasma, criando um gradiente de concentração que desloca o ABNM dos receptores nicotínicos na junção neuromuscular, levando à reversão completa e duradoura do BNM. O sugamadex não se liga às proteínas ou a qualquer outro receptor no organismo, o que lhe confere ótimo perfil de tolerância. O sugamadex pode ser usado na reversão do BNM profundo, promovendo recuperação mais rápida em relação à succinilcolina. Seu emprego pode diminuir a necessidade de monitorização do BNM, a incidência de bloqueio residual e ainda evitar os efeitos adversos causados pelos anticolinesterásicos e anticolinérgicos. Entretanto, também há limitações em relação à utilização 00 sugamadex. Ele impede o uso dos AB- NMs esteroides durante 24 horas, caso seja necessário novo BNM, e pode aumentar o risco do emprego desnecessário e indiscriminado dos ABNMs. Além disso, faltam dados da sua utilização em alguns grupos populacionais e de seu uso em larga escala. Por fim, deve-se considerar também o fator econômico, visto que se trata de uma droga nova e de valor ainda elevado no mercado...

Sugammadex is a novel and unique compaund designed as a selective antaganist ot steroidal neuromuscular blaeking agents (NMBA) (rocuronium>vecuronium¼pancuronium). The drug is a modified water-saluble y-cyclodextrin that forms a stable complex at a 1:1 ratio with the NMBA. It combines with the NMBA creating a concentration gradient favoring the movement ot the NMBA from the nicotine receptors ot the neuromuscular junction leading to the complete and lasting reversal af the neuromuscular blockade (NMB). Sugamadex does not bind to plasma proteins or any other receptors system in the body what provides him a great tolerance profile. Sugamadex can be used in the reversal af deep neuromuscular blockade with a faster recovery time in relation to succinylcholine. Its use can diminish the necessity af monitoring af the NMB, the incidence ot residual blockade and still prevent the adverse effects caused by the antiecholinesterase and anticholinergic drugs. However, there are limitatians regarding the use af Sugammadex. It hinders the use ot the steroidal NMBA during 24 hours if a new NMB must be restablished and it can increase the risk ot unnecessary and indiscriminate use af the NMBA. Mareaver, there is a laek ot data regarding the its use in some population groups and in large scale. Final/y, the economic factor must be also considered, since it is a new drug with a still raised value in market...

Presynaptic facilitatory adenosine A2A receptors mediate fade induced by neuromuscular relaxants that exhibit anticholinesterase activity.

1. Pancuronium, cisatracurium and vecuronium are antinicotinic agents that, in contrast with d-tubocurarine and hexamethonium, exhibit anticholinesterase activity. Pancuronium-, cisatracurium- and vecuronium-induced fade results from blockade of facilitatory nicotinic receptors on motor nerves, but fade produced by such agents also depends on the presynaptic activation of inhibitory muscarinic M2 receptors by acetylcholine released from motor nerve terminals and activation of inhibitory adenosine A1 receptors by adenosine released from motor nerves and muscles. The participation of presynaptic facilitatory A2A receptors in fade caused by pancuronium, cisatracurium and vecuronium has not yet been investigated. In the present study, we determined the effects of ZM241385, an antagonist of presynaptic facilitatory A2A receptors, on fade produced by these neuromuscular relaxants in the rat phrenic nerve-diaphragm (PND) preparation. 2. The muscles were stimulated indirectly at 75±3Hz to induce a sustained tetanizing muscular contraction. The lowest concentration at which each antinicotinic agent produced fade without modifying initial tetanic tension (presynaptic action) was determined. 3. d-Tubocurarine-induced fade occurred only at 55 nmol/L, a concentration that also reduced maximal tetanic tension (post-synaptic action). At 10 nmol/L, ZM 241385 alone did not produce fade, but it did attenuate pancuronium (0.32 µmol/L)-, cisatracurium (0.32 µmol/L)- and vecuronium (0.36 µmol/L)-induced fade. 4. The fade induced by the 'pure' antinicotinic agents d-tubocurarine (55 nmol/L) and hexamethonium (413 µmol/L) was not altered by 10 nmol/L ZM 241385, indicating that presynaptic adenosine A2A receptors play a significant role in the fade produced by antinicotinic agents when such agents have anticholinesterase activity.

Role of 5-HT1A receptors in control of lower urinary tract function in anesthetized rats.

The role of 5-hydroxytryptamine (5-HT) 1A (5-HT1A) receptors in lower urinary tract function was examined in urethane-anesthetized female Sprague-Dawley rats. Bladder pressure and the external urethral sphincter electromyogram (EUS EMG) activity were recorded during continuous-infusion transvesical cystometrograms (TV-CMGs) to allow voiding and during transurethral-CMGs (TU-CMGs) which prevented voiding and allowed recording of isovolumetric bladder contractions. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, decreased volume threshold (VT) for initiating voiding and increased contraction amplitude (CA) during TU-CMGs but decreased CA during TV-CMGs. 8-OH-DPAT prolonged EUS bursting as well as the intrabursting silent periods (SP) during voiding. N-[2-[4-(2-methoxyphenyl)-1- piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamine trihydrochloride (WAY-100635), a 5-HT1A antagonist, increased VT, increased residual volume, markedly decreased voiding efficiency, decreased the amplitude of micturition contractions recorded under isovolumetric conditions, and decreased the SP of EUS bursting. These results indicate that activation of 5-HT1A receptors by endogenous 5-HT lowers the threshold for initiating reflex voiding and promotes voiding function by enhancing the duration of EUS relaxation, which should reduce urethral outlet resistance.

Presynaptic M1, M2, and A1 receptors play roles in tetanic fade induced by pancuronium or cisatracurium.

PURPOSE: We investigated whether presynaptic facilitatory M1 and/or inhibitory M2 muscarinic receptors contributed to pancuronium- and cisatracurium-induced tetanic fade. METHODS: Phrenic nerve-diaphragm muscle preparations of rats were indirectly stimulated with tetanic frequency (75 +/- 3.3 Hz; mean +/- SD). Doses of pancuronium, cisatracurium, hexamethonium, and d-tubocurarine for producing approximately 25% fade were determined. The effects of pirenzepine and methoctramine, blockers of presynaptic M1 and M2 receptors, respectively, on the tetanic fade were investigated. RESULTS: The concentrations required for approximately 25% fade were 413 microM for hexamethonium (26.8 +/- 2.4% 4% fade), 55 nM for d-tubocurarine (28.7 +/- 2.55% fade), 0.32 microM for pancuronium (25.4 +/- 2.2% fade), and 0.32 microM for cisatracurium (24.7 +/- 0.8% fade). Pirenzepine or methoctramine alone did not produce the fade. Methoctramine, 1 microM, attenuated the fade induced by hexamethonium (to 16.0 +/- 2.5% fade), d-tubocurarine (to 6.0 +/- 1.6 fade), pancuronium (to 8.0 +/- 4.0% fade), and cisatracurium (to 11.0 +/- 3.3% fade). 10 nM pirenzepine attenuated only the fades produced by pancuronium (to 5.0 +/- 0.11% fade) and cisatracurium (to 13.3 +/- 5.3% fade). Cisatracurium (0.32 microM) showed antiacetylcholinesterase activity (in plasma, 14.2 +/- 1.6%; 6%; in erythrocyt 17.2 +/- 2.66%) similar to that of pancuronium (0.32 microM). The selective A1 receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 2.5 nM), also attenuated the fades induced by pancuronium and cisatracurium. CONCLUSION: The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine.

Effects of anesthetic induction in patients with diastolic dysfunction.

PURPOSE: To evaluate the effects of anesthetic induction on bi-ventricular function in patients with known preoperative left ventricular (LV) diastolic dysfunction undergoing coronary artery bypass grafting surgery (CABG). METHODS: Fifty patients with diastolic dysfunction undergoing CABG were studied. Preoperative transthoracic echocardiographic (TTE) examination was performed on the day before surgery and transesophageal echocardiography (TEE) assessment was undertaken after induction of anesthesia with sufentanil, midazolam, isoflurane, and pancuronium. Mean arterial pressure (MAP) and heart rate (HR) were recorded. The diameters of the left atrium (LA) and right atrium (RA) and right ventricular (RV) end-diastolic area (EDA), end-systolic area (ESA) and fractional area change (FAC) were obtained from the apical 4-chamber view. The LV EDA, LV ESA and LV FAC were measured from a transgastric midpapillary view. Pulsed wave Doppler of the transmitral flow (TMF) and transtricuspid flow (TTF), pulmonary venous flow (PVF) and hepatic venous flow (HVF) were measured. Mitral (Em, Am) and tricuspid (Et, At) annulus velocities were assessed by tissue Doppler imaging (TDI). Assessment of diastolic dysfunction was graded from normal to severe using a validated score. RESULTS: Following induction of anesthesia, HR decreased (66 +/- 12 vs 55 +/- 9 beats.min(-1), P < 0.0001) while MAP remained unchanged (86.1 +/- 9.0 vs 85.6 +/- 26.5 mmHg, P = 0.94). The diameters of the LA, RA and RV chambers increased, and these increases were associated with opposite changes in LV dimensions. The RV FAC decreased, but the LV FAC remained unchanged. While most Doppler velocities decreased (P < 0.05), a greater reduction in the atrial components of the TMF, TTF and TDI ratios was observed. The LV diastolic function score improved after induction of anesthesia (100% of patients with a score > or = = 3 pre-induction compared to 58% of patients with a score > or = 3 post-induction; P = 0.0004). CONCLUSION: In patients with left ventricular diastolic dysfunction, cardiac dimensions and bi-ventricular filling patterns are significantly altered after induction of general anesthesia. These changes can be explained to some extent by a reduction in venous return with general anesthesia, reduced atrial contractility, and the effect of positive pressure ventilation. Although the LV diastolic function score improved after induction of anesthesia, it is difficult to dissociate this effect from that of altered loading conditions.

[Delayed diagnosis of a postanaesthesia temporomandibular joint dislocation]. / Luxation de l'articulation temporomandibulaire diagnostiquée au décours d'une anesthésie générale.

Temporomandibular joint (TMJ) dislocation during anaesthesia is a rare occurrence. Patients with a history of prior dislocations or TMJ dysfunction, and patients with mandibular retrognathism are at risk of this complication. This is a case report of delayed diagnosis of TMJ dislocation after a general anaesthesia for aortic valvular replacement surgery in a predisposed patient. Considering this unusual presentation, TMJ evaluation should be performed during preoperative anaesthetic assessment. In at-risk patients, one should not worry about TMJ dislocation during intubation but concentrate on glottic exposure. However, afterwards, one should be highly aware of this possible complication in order to detect it early, allowing an immediate simple manual reduction. This manoeuver may be performed with or without sedation by a practitioner, familiar with this way of resetting a dislocated jaw.

Dose-response effect of serum butyrylcholinesterase activity after clinical doses of pancuronium.

INTRODUCTION: Low-dose pancuronium is known to affect serum cholinesterase activity (BChE); however, the dose-response effect of clinical doses of pancuronium on BChE has not been investigated. METHODS: Thirteen ASA I-II patients scheduled for elective surgery requiring muscle relaxation were enrolled in this study. All patients had normal BChE before surgery. Incremental doses of pancuronium (10, 20, 50, and 100 microg/kg) were injected in accordance with surgical needs every 45 min. BChE was measured 3 min after injection by an automatic colorimetric method. RESULTS: BChE decreased significantly in all except one patient in comparison to the baseline (P < 0.05). However all values remained within normal clinical range. A dose of 100 microg/kg yielded significant decrease in comparison to 10 microg/kg but not to other dosages. Linear regression was not significant for the dose-response relationship (P = 0.05). CONCLUSION: After clinical incremental doses of pancuronium, BChE remained within clinical range.

Role of pudendal afferents in voiding efficiency in the rat.

The reciprocal activities of the bladder and external urethral sphincter (EUS) are coordinated by descending projections from the pontine micturition center but are subjected to modulation by peripheral afferent inputs. Transection of the somatic pudendal nerve innervating the striated EUS decreases voiding efficiency and increases residual urine in the rat. The reduction in voiding efficiency was attributed to the lack of phasic bursting activity of the EUS following denervation. However, transection of the pudendal nerve also eliminates somatic sensory feedback that may play a role in voiding. We hypothesized that feedback from pudendal afferents is required for efficient voiding and that the loss of pudendal sensory activity contributes to the observed reduction in voiding efficiency following pudendal nerve transection. Quantitative cystometry in urethane anesthetized female rats following selective transection of pudendal nerve branches, following chemical modulation of urethral afferent activity, and following neuromuscular blockade revealed that pudendal nerve afferents contributed to efficient voiding. Sensory feedback augmented bladder contraction amplitude and duration, thereby increasing the driving force for urine expulsion. Second, sensory feedback was necessary to pattern appropriately the EUS activity into alternating bursts and quiescence during the bladder contraction. These findings demonstrate that the loss of pudendal sensory activity contributes to the reduction in voiding efficiency observed following pudendal nerve transection, and illustrate the importance of urethral sensory feedback in regulating bladder function.

Incidencia de bloqueo neuromuscular residual al ingreso en la unidad de recuperación postanestésica / Incidence of residual neuromuscular block when entering post-anesthesia recovery unit

Introducción: Se denomina bloqueo neuromuscular residual a la condición clínica determinada por la persistencia de los efectos farmacológicos de los bloqueantes neuromusculares no despolarizantes. El objetivo de este estudio fue cuantificar la incidencia de bloqueo neuromuscular residual al ingreso en la unidad de recuperación postanestésica (URPA) tras la administración de atracurio o pancuronio durante el acto anestésico. Pacientes y métodos: Diseño prospectivo observacional, con un muestreo no probabilístico, consecutivo intencional. Se definió bloqueo neuromuscular residual como la presencia de una relación T4/T1 < 0.9 medida en el aductor del pulgar por acelerometría (TOF-GUARD-Organon Teknika). Se estudiaron 140 pacientes sometidos a anestesia general para cirugía programada que habían recibido como BNMND atracurio (n = 125) o pancuronio (n = 15). Resultados: Considerando la definición tradicional (T4/T1 < 0.7), el 13 por ciento de los pacientes (18 de 140) presentó bloqueo neuromuscular residual. Considerando la definición actual (T4/T1 < 0,9), el 49 por ciento de los pacientes (69/140) presentó bloqueo neuromuscular residual. Para ambas definiciones, la incidencia de bloqueo neuromuscular residual al ingreso en la URPA fue significativamente mayor para el pancuronio (53 y 93 por ciento) que para el atracurio (8 y 44 por ciento), respectivamente (p < 0.00005). Se había administrado en quirófano antiacetilcolinesterásicos al 47 por ciento del total de los pacientes observados (66 de 140): 42 por ciento de los pacientes del grupo atracurio (53 de 125) y 87 por ciento del grupo pancuronio (13 de 15). De los 74 pacientes que no recibieron antiacetilcolinesterásicos, 34 (46 por ciento del subgrupo) presentaron bloqueo neuromuscular residual, en tanto que entre los 66 pacientes que sí recibieron la reversión del bloqueo neuromuscular, 35 (53 por ciento del subgrupo) también presentaron bloqueo neuromuscular residual. Estos niveles de incidencia entre los que

Comparación entre el bromuro de pancuronio genérico y el Pavulon®1 / Comparison between generic pancuronium bromide and Pavulon®1

Históricamente se ha planteado el conflicto sobre la eficacia y la seguridad terapéutica entre marcas genéricas y la marca original, lo cual llevó a desarrollar el siguiente estudio. Objetivos: 1) realizar ensayos fisicoquímicos de ampollas que contenían 4 mg/2ml de bromuro de pancuronio, en una marca genérica (G) y en una original (P = Pavulon®), 2) determinar la eficacia y la seguridad terapéutica de ambas drogas, y 3) comparar los resultados entre ambas marcas, tomando como patrón de referencia la marca original. Materiales y métodos: Ensayos fisicoquímicos realizados conforme la Farmacopea Británica 2001 (FB). Eficacia y seguridad terapéutica evaluada mediante un estudio prospectivo, randomizado y doble ciego en cincuenta pacientes ASA I-II a quienes se administró 2 mcg/kg de citrato de fentanilo, 5 mg/kg de tiopental sódico cinco minutos después y 0.1 mg/kg de bromuro de pancuronio. La anestesia se mantuvo con sevoflurano 2 por ciento. Se evaluó el tiempo T1 para alcanzar los valores porcentuales 95,75,25,0 y 25 de recuperación o duración clínica. Comparación: Test de Mann - Whitney, p < 0.05. Resultados: Los ensayos fisicoquímicos para el grupo genérico y el Pavulon® cumplieron con las especificaciones de la FB. En el grupo genérico, los tiempos necesarios para que T1 disminuya hasta 95 y 75 por ciento resultaron respectivamente 33.15 y 48.36 segundos; para que disminuya al 25 por ciento y 0 por ciento, 1.50 Y 2.97 minutos, y la duración clínica fue de 108.99 minutos. En el grupo Pavulon®, el tiempo requerido para T1 = 95 Y 75 por ciento fue de 24.89 y 41.54 segundos respectivamente, mientras que para llegar al 25 y 0 por ciento fueron necesarios 1.34 y 2.71 minutos; la duración clínica en este grupo fue de 111.99 minutos. Conclusiones: Los tiempos evaluados no arrojaron diferencia estadística significativa entre ambas marcas.

Influência da freqüência de estímulos na instalação do bloqueio neuromuscular produzido pelo rocurônio e pancurônio: avaliação pelo método acelerográfico / Influence of stimulation frequency on rocuronium and pancuronium-induced neuromuscular block onset: acceleromyography evaluation

JUSTIFICATIVA E OBJETIVOS: Fatores relacionados ao paciente e ao bloqueador neuromuscular (BNM), assim como outros inerentes à monitorização da função neuromuscular podem influenciar na instalação do bloqueio neuromuscular. O objetivo deste estudo foi avaliar a influência de duas diferentes freqüências de estímulos sobre o tempo de instalação do bloqueio produzido pelo pancurônio e pelo rocurônio. MÉTODO: Foram incluídos no estudo 120 pacientes, estado físico ASA I e II, submetidos a cirurgias eletivas sob anestesia geral, distribuídos aleatoriamente em dois grupos, de acordo com a freqüência de estímulo empregada, para a monitorização do bloqueio neuromuscular: Grupo I - 0,1 Hz (n = 60) e Grupo II - 1 Hz (n = 60). Em cada grupo formaram-se dois subgrupos (n = 30) de acordo com o bloqueador neuromuscular empregado: Subgrupo P (pancurônio) e Subgrupo R (rocurônio). A medicação pré-anestésica consistiu de midazolam (0,1 mg.kg-1) por via muscular, 30 minutos antes da cirurgia. A indução anestésica foi obtida com propofol (2,5 mg.kg-1) precedido de alfentanil (50 'g.kg-1) e seguido de pancurônio ou rocurônio. Os pacientes foram ventilados sob máscara com oxigênio a 100 por cento até a obtenção de redução de 75 por cento ou mais na amplitude da resposta do músculo adutor do polegar, quando foram realizadas as manobras de laringoscopia e intubação traqueal. A função neuromuscular foi monitorizada com aceleromiografia. Foram avaliados: tempo de início de ação do pancurônio e do rocurônio; tempo para instalação do bloqueio total e condições de intubação traqueal. RESULTADOS: Os tempos médios (segundos) para o início de ação e instalação de bloqueio neuromuscular total produzido pelo pancurônio foram: Grupo I (159,33 ± 35,22 e 222 ± 46,56) e Grupo II (77,83 ± 9,52 e 105,96 ± 15,58); para o rocurônio: Grupo I (83 ± 17,25 e 125,33 ± 20,12) e Grupo II (48,96 ± 10,16 e 59,83 ± 10,36) com diferença significativa entre os grupos. As condições de intubação traqueal foram sat...

BACKGROUND AND OBJECTIVES: Factors associated to patients and neuromuscular blockers (NMB), as well as others inherent to neuromuscular function monitoring, may affect neuromuscular block onset. This study aimed at the influence of two different stimulation frequencies on rocuronium and pancuronium-induced neuromuscular block. METHODS: Participated in this study 120 patients, physical status ASA I and II, submitted to elective procedures under general anesthesia, who were randomly allocated in two groups, according to the stimulation frequency employed to monitor neuromuscular block: Group I - 0.1 Hz (n = 60) and Group II - 1 Hz (n = 60). Two subgroups were formed within each group (n = 30), according to the neuromuscular blocker: Subgroup P (pancuronium) and Subgroup R (rocuronium). Patients were premedicated with muscular midazolam (0.1 mg.kg-1), 30 minutes before surgery. Anesthesia was induced with propofol (2.5 mg.kg-1) preceded by alfentanil (50 µg.kg-1) and followed by pancuronium or rocuronium. Patients were ventilated under mask with 100% oxygen until 75% or more decrease in adductor pollicis muscle response, when laryngoscopy and tracheal intubation were performed. Neuromuscular function was monitored by acceleration transducer. The following parameters were evaluated: pancuronium and rocuronium onset time; time for complete block and tracheal intubation conditions. RESULTS: Mean times (seconds) for pancuronium-induced neuromuscular block onset and for complete neuromuscular block were: Group I (159.33 ± 35,22 and 222 ± 46.56) and Group II (77.83 ± 9.52 and 105.96 ± 15.58); rocuronium-induced values were: Group I (83 ± 17.25 and 125.33 ± 20.12) and Group II (48.96 ± 10.16 and 59.83 ± 10.36) with statistical difference between groups. Tracheal intubation conditions were satisfactory...

JUSTIFICATIVA Y OBJETIVOS: Factores relacionados al paciente y al bloqueador neuromuscular (BNM), así como otros inherentes a la monitorización de la función neuromuscular pueden influenciar en la instalación del bloqueo neuromuscular. El objetivo de este estudio fue evaluar la influencia de dos frecuencias diferentes de estímulos sobre el tiempo de instalación del bloqueo producido por el pancuronio y por el rocuronio. MÉTODO: Fueron incluidos en el estudio 120 pacientes, estado físico ASA I y II, sometidos a cirugías electivas bajo anestesia general, distribuidos aleatoriamente en dos grupos, de acuerdo con la frecuencia de estímulo empleada, para la monitorización del bloqueo neuromuscular: Grupo I - 0,1 Hz (n = 60) y Grupo II - 1 Hz (n = 60). En cada grupo se formaron dos subgrupos (n = 30) de acuerdo con el bloqueador neuromuscular empleado: Subgrupo P (pancuronio) y Subgrupo R (rocuronio). La medicación pre-anestésica consistió de midazolam (0,1 mg.kg-1) por vía muscular, 30 minutos antes de la cirugía. La inducción anestésica fue obtenida con propofol (2,5 mg.kg-1) precedido de alfentanil (50 µg.kg-1) y seguido de pancuronio o rocuronio. Los pacientes fueron ventilados bajo máscara con oxígeno a 100% hasta la obtención de reducción de 75% o más en la amplitud de la respuesta del músculo aductor del pulgar, cuando fueron realizadas las maniobras de laringoscopia e intubación traqueal. La función neuromuscular fue monitorizada con aceleromiografia. Fueron evaluados: tiempo de inicio de acción del pancuronio y del rocuronio; tiempo para instalación del bloqueo total y condiciones de intubación traqueal. RESULTADOS: Los tiempos medios (segundos) para el inicio de acción e instalación de bloqueo neuromuscular total producido por el pancuronio fueron: Grupo I (159,33 ± 35,22 y 222 ± 46,56) y Grupo II (77,83 ± 9,52 y 105,96 ± 15,58); para el rocuronio: Grupo I (83 ± 17,25 y 125,33 ± 20,12) y Grupo II (48,96 ± 10,16 y 59,83 ± 10,36) con diferencia...

Pancuronium bromide, a non-depolarizing muscle relaxant which promotes apoptosis of blood lymphocytes in vitro.

BACKGROUND: Several compounds used in anesthesia practice have demonstrated to impair immune function and to influence the process of apoptotic death in T cell population following surgical trauma. We designed this study to test in vitro the impact of neuromuscular blocker, such as pancuronium, at clinically relevant concentration on lymphocyte apoptosis, death factor expression and mitochondrial function. METHODS: Following isolation, lymphocytes were incubated with pancuronium bromide at a clinically relevant concentration (0.136 micro mol l-1) for 3 h at 37 C in a 5% carbon-dioxide-humidified atmosphere and the frequency of apoptotic lymphocytes was then measured. We also investigated crucial steps in the apoptotic process, including Fas/Fas ligand (FasL) phenotype, intracellular expression of the interleukin-1beta-converting enzyme (ICE) p20, mitochondrial membrane potential (DeltaPsim), generation of mitochondrial reactive oxygen species, and glutathione (GSH) levels. Control experiments were performed incubating cells in the complete culture medium added with the dilution medium of the drug without addition of the drug. RESULTS: Expression of Fas, FasL and ICEp20 was six-fold, four-fold, and five-fold increased, respectively, among pancuronium-treated lymphocytes with respect to control cultures (P = 0.0001). The percentage of cells exhibiting either dissipation of mitochondrial membrane potential or increased production of reactive oxygen species was seven-fold increased following exposure to pancuronium compared with untreated lymphocytes (P = 0.0001). These findings were associated with a decrease in GSH level. In addition, the frequency of apoptotic cells was 10-fold greater among lymphocytes cultured in the presence of the drug with respect to control cultures. (P = 0.0001). CONCLUSION: Our data suggest an apoptogenic effect of pancuronium in vitro at clinically relevant concentration on peripheral blood lymphocytes. This could be implicated in the transient immune suppression following a surgical operation.

Potentiation of mivacurium blockade by low dose of pancuronium: a pharmacokinetic study.

BACKGROUND: Mivacurium is potentiated by pancuronium to a much greater extent than other relaxants. In a previous investigation we suggested that this potentiation could be due to the ability of pancuronium to inhibit plasma cholinesterase activity, but we did not measure plasma concentrations of mivacurium. In the current study we performed a pharmacokinetic analysis by measuring the plasma concentration of mivacurium when preceded by administration of a low dose of pancuronium. METHODS: After induction of general anesthesia with propofol and fentanyl and orotracheal intubation, 10 patients (pancuronium-mivacurium group) received 15 microg/kg pancuronium followed 3 min later by 0.1 mg/kg mivacurium, whereas 10 other patients (mivacurium group) received saline followed by 0.13 mg/kg mivacurium 3 min later. Plasma cholinesterase activity was measured before and 3 and 30 min after pancuronium dosing in the pancuronium-mivacurium group and was measured before and after administration of saline in the mivacurium group. Arterial plasma concentrations of mivacurium and its metabolites were measured at 0.5, 1, 1.5, 2, 4, 10, 20, and 30 min after injection. Neuromuscular blockade was assessed by mechanomyography. RESULTS: Plasma cholinesterase activity decreased by 26% in the pancuronium-mivacurium group 3 min after injection of pancuronium (P < 0.01) and returned to baseline values 30 min later; however, no significant variation was observed in the mivacurium group. The clearances of the two most active isomers (Cis-Trans and Trans-Trans) were lower in the pancuronium-mivacurium group (17.6 +/- 5.1, 14.7 +/- 5.3 ml. min-1. kg-1, respectively) than in the mivacurium group (32.4 +/- 20.2, 24.8 +/- 13.5 ml. min-1. kg-1; P < 0.05). CONCLUSIONS: A subparalyzing dose of pancuronium decreased plasma cholinesterase activity and the clearance of the two most active isomers of mivacurium. Pancuronium potentiates mivacurium more than other neuromuscular blocking agents because, in addition to its occupancy of postsynaptic acetylcholine receptors, it slows down the hydrolysis of mivacurium.

Core and thenar skin temperature variation during prolonged abdominal surgery: comparison of two sites of active forced air warming.

BACKGROUND: This study was designed to compare the efficacy of two different sites of active forced air warming, upper body or lower body, to maintain normothermia; and their respective effect on thenar skin temperature in relation to the accelerographic monitoring of neuromuscular blockade during long-lasting abdominal surgery. METHODS: Twenty-six patients were randomised into two groups: upper body, (n=13) and lower body, (n=13), for intraoperative forced air warming. General anaesthesia was induced with thiopentone, sufentanil, and maintained with a mixture of N2O/O2/isoflurane. Pancuronium, 0.1 mg x kg(-1) was used to facilitate tracheal intubation. Reinjection doses of 0.01 mg x kg(-1) were administered once 25% recovery of first twitch height of train-of-four stimulation had occurred, or if surgical relaxation was estimated as inadequate by the surgeon. Thenar skin temperature and core temperature were monitored continuously. RESULTS: A similar trend for core temperature profile was observed in both groups. After an initial mild hypothermia, normothermia was reached progressively. Normothermia was obtained faster with lower body forced air warming than with upper body (2 h versus 3 h), P<0.05. Thenar skin temperature significantly increased during the first 90 min of surgery. This rise was significantly higher in the upper body group at 40 min and 60 min, P=0.03 and P=0.01, respectively. Stabilisation of thenar skin temperature occurred after 2 h without any further significant difference between groups. Muscle relaxant requirements were not significantly different between the groups. CONCLUSION: This study suggests that during long-lasting abdominal surgery, normothermia is maintained after 2-3 h by either upper or lower body active forced air warming. After an initial post-induction mild hypothermia, normothermia was achieved faster with lower body surface warming. Thenar skin temperature trend showed that it remained above 32 degrees C during most of the procedure in both groups.

Effects of non-depolarizing neuromuscular blocking agents on norepinephrine release from human atrial tissue obtained during cardiac surgery.

We have studied the effect of non-depolarizing neuromuscular blocking agents, at concentrations present in serum during anaesthesia, on release of [3H]-norepinephrine ([3H]NE) from superfused atrial appendage obtained during cardiac surgery from 48 patients. Three of the neuromuscular blocking agents (pancuronium, gallamine and rocuronium), which are known to cause an increase in heart rate during anaesthesia, increased stimulation-evoked release of [3H]NE. In contrast, (+)tubocurarine and pipecuronium, neuromuscular blocking agents that do not cause tachycardia, did not affect release of NE. Org 9487 significantly enhanced release while SZ1677 was ineffective, even at concentrations higher than those expected after administration of a 2 x ED95 dose. Atropine enhanced release. These data suggest that the axon terminals of sympathetic nerves in human heart have muscarinic heteroreceptors whose activation by acetylcholine (ACh) released from the vagal nerve reduces release of NE. This action contributes to lowering of heart rate. Therefore, any neuromuscular blocking agent with antimuscarinic actions and capable of increasing the release of NE may produce tachycardia.