The middle ear muscle reflex in the diagnosis of cochlear neuropathy.

Cochlear neuropathy, i.e. the loss of auditory nerve fibers (ANFs) without loss of hair cells, may cause hearing deficits without affecting threshold sensitivity, particularly if the subset of ANFs with high thresholds and low spontaneous rates (SRs) is preferentially lost, as appears to be the case in both aging and noise-damaged cochleas. Because low-SR fibers may also be important drivers of the medial olivocochlear reflex (MOCR) and middle-ear muscle reflex (MEMR), these reflexes might be sensitive metrics of cochlear neuropathy. To test this hypothesis, we measured reflex strength and reflex threshold in mice with noise-induced neuropathy, as documented by confocal analysis of immunostained cochlear whole-mounts. To assay the MOCR, we measured contra-noise modulation of ipsilateral distortion-product otoacoustic emissions (DPOAEs) before and after the administration of curare to block the MEMR or curare + strychnine to also block the MOCR. The modulation of DPOAEs was 1) dominated by the MEMR in anesthetized mice, with a smaller contribution from the MOCR, and 2) significantly attenuated in neuropathic mice, but only when the MEMR was intact. We then measured MEMR growth functions by monitoring contra-noise induced changes in the wideband reflectance of chirps presented to the ipsilateral ear. We found 1) that the changes in wideband reflectance were mediated by the MEMR alone, and 2) that MEMR threshold was elevated and its maximum amplitude was attenuated in neuropathic mice. These data suggest that the MEMR may be valuable in the early detection of cochlear neuropathy.

High gender -specific susceptibility to curare- a neuromuscular blocking agent.

Curare, a selective skeletal muscle relaxant, has been used clinically to reduce shivering and as an anesthetic auxiliary in abdominal surgery. It is also widely used in animal experiments to block neuromuscular junction activity. Effective doses of curare diminish muscle contraction without affecting brain function, but at higher doses it is known to be lethal. However, the exact dose of curare initiating muscle relaxation vs. lethal effect has not been fully characterized in mice. In this study we carefully examined the dose-response for achieving muscle inactivity over lethality in both male and female mice (C57BL6/J). The most striking finding of this study is that female mice were highly susceptible to curare; both the ED50 and LD50 were at least 3-fold lower than male littermates. This study shows that gender-specific differences can be an important factor when administering skeletal muscle relaxants, particularly curare or other analogous agents targeted to the neuromuscular junction.

High gender -specific susceptibility to curare- a neuromuscular blocking agent

Curare, a selective skeletal muscle relaxant, has been used clinically to reduce shivering and as an anesthetic auxiliary in abdominal surgery. It is also widely used in animal experiments to block neuromuscular junction activity. Effective doses of curare diminish muscle contraction without affecting brain function, but at higher doses it is known to be lethal. However, the exact dose of curare initiating muscle relaxation vs. lethal effect has not been fully characterized in mice. In this study we carefully examined the dose-response for achieving muscle inactivity over lethality in both male and female mice (C57BL6/J). The most striking finding of this study is that female mice were highly susceptible to curare; both the EDm and LDm were at least 3-fold lower than male littermates. This study shows that gender-specific differences can be an important factor when administering skeletal muscle relaxants, particularly curare or other analogous agents targeted to the neuromuscular junction.

[Neuromuscular monitoring: methods and machines]. / Uberwachung der neuromuskulären Blockade - Methoden und Geräte.

Muscle relaxing agents are clinically in use for general anaesthesia to optimize the conditions to the endotracheal intubation as well as the surgical conditions. Therefore different musclerelaxants with specific pharmacological characteristics are available. Many factors that depend on the condition of the patient and the used musclerelaxant agent influence the duration of the neuromuscular blockade. Rapid reversal of their effects, particularly in cases of profound blockades, proved to be difficult. In cases of postoperative residual paralysis hypoxic complications because of failure of the ventilation increase the morbidity and mortality of the perioperative period. To avoid these complications in cause of postoperative residual neuromuscular blockade it seems to be necessary to evaluate the status of the muscle function. For the tactile or visual assessment or the objective measurement of stimulation the train-of-four (TOF), double-burst (DBS) or tetanus-stimulation of peripheral nerves like the ulnar nerve may be used. Established methods for the objective monitoring of neuromuscular function is the mechanomyography (MMG), the acceleromyography (AMG), the electromyography (EMG), the kinemyography (KMG) and the phonomyography (PMG). A sufficient recovery of the neuromuscular transmission is reached to a TOF-ratio of 0,9 and should be aimed before the extubation at the end of surgery. No subjective evaluation of the neuromuscular recovery is able to identify residual paralysis above a TOF-ratio of 0,5. Recent studies suggest that objective methods should be used to monitor neuromuscular function to avoid postoperative residual blockades.

Erector spinae muscle changes on magnetic resonance imaging following lumbar surgery through a posterior approach.

STUDY DESIGN: Prospective randomized study of patients undergoing lumbar arthrodesis. OBJECTIVES: To quantify MRI changes of the erector spinae following lumbar surgery through a posterior approach and the possible protection of these muscles during surgery by the use of cholinergic blockade. SUMMARY OF BACKGROUND DATA: It has been shown that lumbar spine surgery through a posterior approach can induce iatrogenic lesions in the erector spinae. We have shown in a previous study that histologic changes on muscular biopsy performed in the multifidus at the end of the surgical procedure were not modified by the use of cholinergic blockade during surgery. METHODS: Twenty patients scheduled to undergo pedicle-screw enhanced L4-L5 arthrodesis were enrolled in this study. Ten patients received curare during anesthesia and 10 patients did not. MRI was obtained the day before the operation and at 6 months of follow-up on the same MR scanner. T1-weighted images were obtained in the axial plane. The 2 slices immediately proximal and distal to the pedicle screw construct on the postoperative MRI were selected. The corresponding slices were selected on the preoperative MRI. Each erector spinae on the 4 slices was surrounded using a mouse-guided tool. The contractile component of the cross-sectional area (CCSA) was calculated from the number of pixels surrounded and the signal intensity of each pixel. RESULTS: There was only slight changes in the erector spinae CCSA proximal to a posterior lumbar arthrodesis. Erector spinae CCSA decreased by 27% distal to the arthrodesis. Curare showed no efficacy in preventing muscle damage. CONCLUSIONS: Erector spinae muscle alterations mainly occur distal to posterior lumbar surgical procedures.

The use of curare during anesthesia to prevent iatrogenic muscle damage caused by lumbar spinal surgery through a posterior approach.

STUDY DESIGN: Prospective randomized study of patients undergoing lumbar arthrodesis. OBJECTIVES: To evaluate the use of curare during anesthesia to limit muscle lesions caused by surgery. SUMMARY OF BACKGROUND DATA: It has been shown that lumbar spine surgery through a posterior approach can induce iatrogenic lesions in the erector spinae. The prevention of these lesions by intraoperative cholinergic blockade has never been evaluated. METHODS: Twenty patients scheduled to undergo pedicle-screw enhanced L4-L5 arthrodesis were enrolled in this study. The average age was 48.9 years. Ten patients received curare during anesthesia and 10 patients did not. Postoperative pain was assessed using a visual analog scale (VAS) and the consumption of morphine by patient-controlled analgesia during the first 24 hours. Intramuscular pressure (IMP) in the multifidus was monitored during the intervention. A biopsy of the multifidus muscle was performed at the end of the intervention for histologic study. Serum activity of the MM iso-enzyme of the creatine phosphokinase (CPK-MM) was measured 24 hours after surgery. RESULTS: The average consumption of morphine and the mean value of the VAS at 24 hours were not statistically different between these 2 groups. The use of a self-retaining retractor during lumbar surgery resulted in a substantial increase in IMP, resulting in histologic muscle lesions and an increase in serum CPK-MM activity. There was no significant difference between the 2 groups of patients. CONCLUSIONS: The use of curare during anesthesia did not limit the muscle damage caused by surgery.

EEG should be performed during induced hypothermia.

Induced hypothermia has improved neurological outcome after cardiac arrest. Even though anoxic insults to the brain often provoke epileptic activity, it is unclear whether EEG monitoring is necessary in these patients. We report the case of a 53-year-old female who suffered cardiac arrest. During induced hypothermia extensive shivering was managed by sedation and curare. After their discontinuation convulsions appeared and status epilepticus was disclosed on EEG recording, and was treated by thiopental infusion for 10 days. The patient recovered slowly and has now regained independent living (CPC 1). In induced hypothermia several factors including the use of curare, may conceal clinical signs of epileptic activity. We therefore suggest a broader use of EEG in these patients.

[A new toy: upswing in curare use in Spanish anesthesia]. / A new toy: la irrupción del curare en la anestesia española (1946).

The introduction of curare for general anesthesia by Harold Griffith in 1942 was one of the most important moments in the development of anesthesiology. However, several years passed before curare came to be used in Spain. We review the early application of curare and the role played by Robert Macintosh, Professor of Anaesthesia at Oxford, in introducing the drug to Spain.

Empleo del curare como cebado del atracurio / Employ of curare how atracurium priming

Veintitrés pacientes ASA I y II a quienes se les practicaría cirugía electiva y además estaba indicado el uso de relajantes musculares no despolarizantes e intubación traqueal, los cuales se anestesiaron con Enflurano (1 CAM espiratotio), fueron asignados aleatoriamente para recibir, bien 250 ug/kg de Atracurio en forma de Bolus ó 50 ug/kg de d'Tubocurarina tres minutos antes de 150 ug/kg de Atracurio. El tiempo necesario para alcanzar un bloqueo del 80 por ciento fue significativamente menor en el grupo cebado con curare (p<0,001), esta droga también potencia el máximo efecto del Atracurio (p<0.01) y acorta el tiempo para lograrlo (p<0.001). El cebado en esta experiencia enlentece los índices de recuperación (no significativamente) y prolonga la duración de su efecto clínico (p<0,01). Se notó una tendencia a mejorar las condiciones para la intubación en este grupo cebado

[Gynecologic laparoscopy with or without curare]. / Coelioscopie gynécologique avec ou sans curare.

OBJECTIVE: To assess physiological changes and operating conditions during general anaesthesia with or without neuromuscular blockade in patients undergoing gynaecologic laparoscopy. STUDY DESIGN: Prospective, randomized, double-blind study. PATIENTS: Fifty non-obese patients, mean age 31 years, randomly allocated into either a group of 25 with curare (AC) or a group of 25 without curare (SC). METHODS: All patients were anaesthetized with propofol (2.5 mg.kg-1), sufentanil (0.4 microgram.kg-1) midazolam (2 mg) and N2O-O2. In addition, those of the AC group were given atracurium 0.25 mg.kg-1 for intubation, followed by additional boluses to maintain twitch height < 10% of the control value. Blood pressure, heart rate, peak airway pressure, end-tidal carbon dioxide pressure were recorded before and during pneumoperitoneum maintained at a pressure of 15 mmHg. Operating conditions were assessed at 10-min intervals, using a four point scale. RESULTS: In both groups, blood pressure and heart rate decreased following induction. The decrease in blood pressure was more important in the SC group at 5 min and before pneumoperitoneum (25 vs 15%); P < 0.05). The time course of PETCO2 and peak airway pressures were similar between groups. Operating conditions were not influenced by the muscle relaxant. CONCLUSIONS: Neuromuscular blockade influences neither most of the clinical haemodynamic and respiratory changes induced by pneumoperitoneum for gynaecologic laparoscopy not the operating conditions.

[Risk of secondary neuromuscular blockade after autotransfusion of blood drawn from the patient following curare administration]. / Risque de curarisation secondaire après autotransfusion de sang prélevé chez un patient curarisé.

A secondary neuromuscular blockade can occur after transfusion of autologous blood withdrawn after injection of muscle relaxants. In this study time course of muscle relaxation after transfusion of blood withdrawn before or after administration of atracurium (A) or vecuronium (V) was assessed. Forty adults undergoing haemorrhagic urologic surgery were included in the study. After induction of general anaesthesia and intubation of the trachea facilitated by local lidocaine, they were divided into 4 groups. In groups A1 and V1 the blood units were withdrawn before injection of atracurium 0.5 mg.kg-1 or vecuronium 0.1 mg.kg-1. In group A2 and V2 the blood units were withdrawn after administration of muscle relaxants. Haematocrit was decreased to 0.30. The last bolus of these muscle relaxant was injected 30 min before the end of surgical procedure. Autologous blood was transfused when train of four (T4R) recovered to 0.80. Electromyographic elicited responses to T4R stimulation were obtained every minute during the 4 first minutes after the beginning of transfusion (T1 to T4), thereafter every minute during the 5 first minutes after the end of transfusion (T5 to T9), and finally every 5 minutes for 10 minutes (T10 and T11). There was a secondary neuromuscular blockade in patients of groups A2 and V2. The intensity of blockade was more important after vecuronium than after atracurium (p < 0.01 from T2 to T11 between groups A2 and V2). In group A2, the T4R had not reached the control level at the end of the procedure (0.78 at T11 vs 0.80 at T0). These data emphasize the importance of withdrawing blood units before administration of muscle relaxants.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct negative chronotropic and inotropic efects of curare on isolated and perfused frog's heart

It has been stated that curare has no direct effect upon the heart because the cardiac muscle is deprived of nicotine receptors. While performing an experimental work, we noticed that when high doses of curare were administered to frogs, a change in cardiac activity occurred. In order to elucidate whether the cardiac effects of curare wee the results of a direct action or a reflex response, we studie the effects of increasing doses of d-tubocurarine on the rate and contractility of 8 isolated and perfused frogs'hearts. After testing the d-tubocurarine effects on the heart rate and contractility, we added either acetylcholine, atropine, atenonol or verapamil in orden to find out whether any change ocurred in the cardiac effects produced byd-tubocurarine. Thirty seven measurements were carriet out and it wasfound that 1) high doses (between 1 and 15 micrograms) of d-tubocurarine produced a highly significant decrease in heart rate an contractility; 2) d-tubocurarine did not avoid the acetycholine effect; 3) atropine, atenonol and verapamil did not interfere with d-tubocurarine effects. We conclude that high doses of d-tubocurarine produce "dosis-dependent" heart rate and contratility reductions. These effects are not mediated by muscarinic receptors beta-1 receptors or the show calcium channels